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When you get what you're really looking for on your plate

Remember China in 2008, when at least six children died after consuming milk that contained melamine, an industrial chemical. In 2011, over 50 people died in Germany from sprouts poisoned with E. coli. This was the world’s deadliest E. coli outbreak and may have originated in a German farm. Another food-related disaster occurred in the USA in 2011 and 2012 with the listeria outbreak in cantaloupe, when 30 people died and 146 were sick. In 2013, a scandal inflamed opinion worldwide when traces of horsemeat were found in burgers in Ireland and Germany.

The global food chain under scrutiny

This news sends shivers down our spines, particularly as it is becoming increasingly difficult in the ‘global village’ to control each element of the food chain. In 2008, national audit institutions gathered experts from the BAG, cantonal laboratories, Swiss universities and the food industry to set up postgraduate courses in “Food Safety Management” that are fully Bologna compliant. The team established the diploma course DAS for graduates wanting to acquire experience in the technical domain, evaluate processes and take the lead in an HACCP team. This ‘Hazard Analysis and Critical Control Points’ concept, a food-specific prevention system, is approved around the world. The CAS certificate course is aimed at people who would like to continue training in a specific topic and update their theoretical knowledge.

The MAS master's course provides specific expertise for leadership in food safety, for example in operational and personnel management, communication with the media, as well as legal, economic and food policies. It offers the perfect training for food safety managers in authorities, product development and quality control in food sectors.

Linking theory and practice

The practically-oriented range of training courses, seminars and workshops has aroused considerable interest on the part of young people. “I would like to stress the importance of continuing professional development as the half-life of knowledge is becoming ever shorter”, says Professor Margareta Neuburger. She has managed the ‘Advanced Studies’ program at Basel University for 20 years and set up 31 postgraduate courses. As she has also supervised a European Life Sciences project over a period of 10 years, she knows just how important education is.

Since 2009, courses in Food Safety Management have firmly established themselves, recruiting some 40 participants every two years. “In doing so we are unifying food safety training in Switzerland, since – independently of the linguistic regions - we are offering just one course a year”, explains microbiologist Rudolf Schmitt, cofounder and lecturer at the HES-SO Valais in Sion. He is both expert and practitioner, bringing knowledge and expertise from microbiology and food safety, and demonstrating to the students how theory and practice can be linked.

The starting signal for the ‘Advanced Studies’ courses MAS, DAS and CAS for 2014-2017 at Basle University will be given on the occasion of an opening ceremony on 2 September 2014, with representatives from the Federal Food Safety and Veterinary Office, the cantonal chemist and Basle University in the Hall of the University of Applied Sciences HES-SO in Sion.


Quality assurance across the whole food chain poses a challenge for the Food Safety Manager. The vocational courses at the HES-SO convey knowledge relating to managerial tasks in food safety and food quality services.
(photo HES-SO)

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posted: 23.07.2014

PhytoBalk – focusing on medicinal plants

Medicinal plants are becoming increasingly popular. Take the gel from the leaves of Aloe Vera and use it to speed the healing of burned or wounded skin, or use the sap in the base of the leaf as a digestive stimulant and a strong laxative. Or think of Echinacea, one of the most popular herbs in America: People like to shorten a common cold and flu or boost their immune system to fight infections with this plant. Look at the bark of the cinchona tree, which contains quinine and is a prescribed treatment for malaria in regions where anti-malarial drugs are not available.

Back to nature

According to the WHO, the World Health Organization, up to 80% of the global population trusts in medicinal plants as a traditional treatment method. But medicinal plants have also aroused enormous interest on the part of the pharmaceutical industry, given the currently observed increasing drug resistance of pathogenic micro-organisms to traditionally administered antibiotics. Plants show huge structural diversity and possess a high number of pharmacologically active functional groups in their molecules, which means that they are less likely to develop resistance. On the other hand, although many active molecules nowadays are produced by chemical synthesis, this process does not function with a lot of products due to their complicated nature, or else the synthetic processes are too expensive and economically disadvantageous.

An excellent source of actual medicinal plants is Europe, with its varied geography and climate, providing a wide range of more than 12,500 vascular plants. The Balkan countries especially seem to be a real treasure chest for the production of biologically active plant extracts, fractions and individual compounds. A specialist in this area is the Bulgarian scientist Dr Kalina Danova. In a research study conducted at the Department of Plant Physiology at Sofia University, she compared the biosynthetic capacity of three Hypericum species characteristic of the Balkan region to produce antioxidant secondary metabolites with a phenolic structure under laboratory conditions. Now at the Institute of Organic Chemistry at the Bulgarian Academy of Sciences, she was the driving scientific force in setting up a project with a Swiss biotechnet partner funded by the Swiss National Science Foundation (SNF) and the Bulgarian Science Directorate at the Ministry of Education, Youth and Science (SD/MEYS). The choice fell on the group of Professor Dr Beat Meier, Head of Phytopharmacy at the Institute of Biotechnology at ZHAW Wädenswil, where the project is led by Dr Evelyn Wolfram, Senior Scientist and Lecturer.

How to exploit synergistic benefits

The PhytoBalk project, starting in 2013 for a duration of three years, aims to investigate whether the cultivation of wild-growing medicinal plants is possible in a laboratory environment with biotechnological processes and to establish a similar profile of equally effective secondary metabolites. Tissue culture initiator Kalina Danova knows about the secret places in nature where the interesting plants grow, collects them sustainably by hand and looks after the whole development of the in vitro cultures. Together with her Bulgarian team she produces extracts, fractions or purified compounds of the biotechnologically derived plant material and is putting the pieces of the puzzle together in the attempt to explain why plants tend to produce one compound or another depending on the environment in which they grow. The ZHAW Wädenswil team then analyses the content of the target compounds of the plant material derived from the different biotechnological optimizations of the wild plant genotypes. Once the diverse activities of the plant material are established, hypotheses are proposed as to which compound or fraction has the highest potential as a future lead for the production of biotechnologically derived phytotherapeuticals. The whole working process involves the investigation of plant species, the preparation of standardized protocols for the ex situ conservation of the investigated species and the biotechnological derivation of the most promising therapeutically active products selected by a wide array of predetermined bioassays. These acquisitions will bring scientifically based new knowledge and also serve as a model for other valuable medicinal plant species that are representative of the flora.

“In this way, valuable raw materials of a standardized quality and with negligible natural variation can be sustainably secured for the pharmaceutical, cosmetic and health food industries”, explains Evelyn Wolfram. The objective is to create, under laboratory conditions, highly productive cell, tissue and organ lines by cultivation. For this purpose, the scientists at ZHAW Wädenswil evaluate the processes using chemical analyses and biological test procedures in order to assess the therapeutic potential for the prevention and treatment of common diseases. In other words, only part of the project is basic research; the main focus is on practice-oriented results and the technology transfer to the medical and pharmaceutical industry. “The combination of both the Swiss and Bulgarian competences provides a higher scientific visibility and a better practical relevance of the research and development results”, concluded Kalina Danova and Evelyn Wolfram and their teams during their status meeting in April 2014 in Wädenswil. “As to the geographical distance and the cultural and financial differences in the cooperation, these represent a challenge and are a valuable enrichment for both parties.”

Information: http://www.lsfm.zhaw.ch/de/science/institute-zentren/ibt-phytopharmazie.html


Inula britannica : Its flowers have been used for the treatment of digestive disorders, bronchitis and inflammation in traditional Chinese medicine.
(Picture Kalina Danova)


ZHAW_Organgenese…
New plant cells (Callus) growing on an explant of inula Britannica.
(Picture Kalina Danova)

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posted: 06.07.2014

Disease cell-models : that's what industry needs

The first TEDD workshop 2014, organized by the HES-SO in Sion, attracted interested experts who expressed their views on the topic of disease cell-models and their use in industry.

For instance, Peter Girling of CELLnTEC Advanced Cell Systems AG in Bern related his experience on how to age skin cells naturally in vitro without the need for acute, artificial chemical treatment in just 2-3 weeks. His precisely designed culture environment maintains the nutrients required for routine metabolism, but reduces or omits ingredients commonly used to protect or extend the lifespan of cells in vitro. peter@cellntec.com

Infectious disease models in human cell cultures involve the adhesion of the pathogen-like Candida albicans to human mucosal cells, and the subsequent inflammatory irritation and infiltration of the host tissues. Bruno Schnyder from the HES-SO Valais in Sion explained how his team established 2D and novel 3D cell systems in order to evaluate the anti-infective potential of biotherapies. bruno.schnyder@hevs.ch

The objective of the study by Martial Geiser at the HES-SO Valais was to monitor the quality of water using human intestinal cells. martial.geiser@hevs.ch

Idiopathic pulmonary fibrosis, or IPF, a chronic, progressive and fatal lung disease that is thought to be provoked by chronic microaspirations of gastric refluxate, was the topic presented by Marcel Felder from ARTORG Berne. He demonstrated how microfluidic flow focusing was a robust and highly reproducible technique for selective cell exposure in intact epithelium. He also reported on the formation of alveolar microinjuries during exposure to physiological reflux. He concluded by affirming that microfluidic flow focusing is a versatile and reliable technique for in vivo-like epithelial wounding. marcel.felder@artorg.unibe.ch

Laura Suter-Dick from the Fachhochschule Nordwestschweiz in Muttenz focused on the development of a 3D microtissue culture for studying liver fibrosis and cirrhosis. This in vitro system will contain functional hepatocytes, Kupffer and stellate cells. Her team evaluates primary rat liver cells with these key cell types, as well as available cell lines of human origin. Firstly, the models need to be carefully characterized in terms of available cell types and activation status. Both rodent and human systems are intended to mimic disease progression and responses to pharmacological intervention. laura.suterdick@fhnw.ch

Pascal Schneider from UNIL Lausanne presented TNF family ligands and receptors that play important roles in several aspects of the immune system, bone homeostasis and development. Agonists and antagonists of TNF family ligands and receptors have proven, or potential, applications, but functional testing of these reagents can sometimes be cumbersome. Cell-based assays that rely on the activation of the apoptotic Fas pathway upon exposure to a ligand allow testing of virtually any agonist or antagonist of the TNF/TNFR family in a single type of assay. Moreover, agonists or antagonists characterized using these assays are extremely likely to display the same activity in the natural endogenous system. pascal.schneider@unil.ch

ScqmRT-PCR is a method for gene expression analysis that allows several marker genes to be amplified in parallel, thus requiring very little starting material. Sarah Wegmüller from HES-SO Valais explained how this is achieved by preamplification of the cDNA for several cycles with all PCR primers of all marker genes at once before a qPCR is performed for all markers individually. An scqmRT-PCR was developed for markers involved in the formation of Advanced Glycated End (AGE) products aimed at identifying the anti-AGE potential of plant extracts on a diabetic skin model. sarah.wegmueller@hevs.ch

Marc Pfeifer of HES-SO Valais reported on click chemistry for cellular microarrays and molecular trafficking studies. Developments of copper-free click chemistry in recent years have led to new possibilities of immobilization of cells for in vitro diagnostics, as well as for the labelling of molecules for dynamic in vivo imaging purposes. Covalent attachment of cyclooctyne-type probes to azides introduced metabolically has been shown to be a viable route to study trafficking of different compounds. Good biocompatibility and rapid kinetics also allow for investigations of subcellular partitioning and internalizations under pharmacological simulation. marc.pfeifer@hevs.ch

Human embryonic stem cells (ESCs) are potential sources of neurons that can be used to develop in vitro engineered tissues for use in basic research or as tools for molecular screening in toxicology. Luc Stoppini from HES-SO Geneva showed how, in 2D cultures, the influences of neighbouring cells and physical polarity are reduced when compared to in vivo conditions. 3D tissue engineering can be used to design a complex biological structure, bridging the gap between classical 2D cell culture and animal tissue. The aim of his work is to develop 3D stable and long-term in vitro culture conditions that may be used as a model for in vitro neurotoxicity testing. luc.stoppini@hes.ge.ch

The workshop concluded with a presentation by Stéphane Demotz from DORPHAN SA at the EPFL Innovation Park, on the development of iminosugar-based pharmacological chaperone compounds for the treatment of mucopolysaccharidoses, severe and rare genetic diseases caused by deficiencies in enzymatic activities responsible for the degradation of glycosaminoglycans. A therapeutic approach involves the rescue of the mutated enzymes by pharmacological chaperone compounds. These molecules, by binding to the mutated enzymes, favour their folding and promote their traffic to the lysosomes where they perform their catabolic functions. DORPHAN is conducting the pre-clinical development of iminosugar-based chaperone compounds for the treatment of type IIIB and IVB mucopolysaccharidoses. The pharmacological features of the compounds are being assessed in enzymatic tests, cell-based assays of the diseases and the blood brain barrier, and in animal studies. The overall goal of this work is the selection of drug candidates for further development towards clinical trials. demotz@dorphan.com

Professor Ursula Graf-Hausner, head of the TEDD competence centre at the Institute of Chemistry and Biological Chemistry ZHAW Wädenswil, draws a positive conclusion of this first TEDD workshop: “We organized the event in the French part of Switzerland to include also local partners in the TEDD network”, she explains. “I am happy to state that the TEDD philosophy of bringing together experts from academia and industry to develop and apply 3D tissue cultures in practice is successful and helps to generate new ideas and network projects.”

www.icbc.zhaw.ch/tedd


Group portrait of the representatives of the TEDD network and the HES-SO with invited speakers. (Picture HES-SO Sion)

More Information: biotechnet

posted: 23.05.2014

The fight against antibiotic resistance

It’s a ticking time bomb: According to the WHO, in the EU, up to 12% of hospital patients acquire an infection during their stay. Estimated 400’000 present with a resistant strain, about 25’000 die every year. The reason for is increasing antimicrobial resistance.

The focus is especially on Gram-negative bacteria such as Escherichia coli or Klebsiella pneumonia, where hitherto unknown resistant mechanisms are emerging and efficient medication is not available. Besides deaths and great suffering, multidrug-resistant bacteria cause also an economic loss of more than € 1.5 billion each year.

From a brilliant idea to a market-ready product

Two young scientists at the Department of Biosystems Science and Engineering of the ETH Basle, Dr Marc Gitzinger and Dr Marcel Tigges, studied the issue and had a sudden brainstorm: why not to switch off bacterial resistance with their proprietary technology enabling multilevel screening for TRIC (Transcription Regulator Inhibitory Compounds) that block the transcription of resistance-enabling genes, thus outwitting bacterial resistance. And it worked! Meanwhile studies have shown the potential of compounds that inhibit the action of the repressor protein implicated in ethionamide resistance, thus stimulating activation of the drug and thereby restoring the activity of the antibiotic for treatment of Mycobacterium tuberculosis.

In order to expand their screening and compound portfolio to nosocomial bacterian strains, the earlier mentioned ‘hospital infections’, the two researchers, founders of their own company BioVersys, are actively engaged in a National Research Consortium for the development of active agents to fight antibiotic resistance. The project, supported by the Commission for Technology and Innovation (CTI), consists of research groups from the Universities of Basel, Bern and Geneva as well as the Universities of Applied Sciences in Muttenz and Wädenswil.

Strong partnerships in the biotechnet

The project is divided into different work packages, and each of the partners contributes its unique strengths and competencies to the joint operations. While BioVersys is responsible for the project management and the biological assays, the Life Sciences group of Professor Daniel Gygax is specialized in bioanalysis and will test the molecules synthesised by the team of Professor Rainer Riedl in Wädenswil with biochemical assays regarding their activity. Besides the chemical synthesis, the team of Rainer Riedl takes also care of the pharmacokinetic analytics. Professor Vincent Perreten at the Institute of Veterinary Bacteriology in Bern and Professor Jacques Schrenzel at the Bacteriological Laboratory of the Hôpitaux Universitaires de Genève look after the genexpression analysis in clinical pathogens. Last not least Professor Manuel Battegay, Head of Infectiology & Hospital hygiene at the Basle University Hospital, and PD Dr Nina Khanna, are the experts to realize infection models and pharmacokinetics.

“The CTI project and the competences within biotechnet allow us to outsource chemical and biological aspects”, comments Dr Marcel Tigges, CSO of BioVersys. “Switzerland is particularly suitable for innovative developments, as we can find here a high level of professionalism and quality awareness, as well as qualified experts on the market.” He expects that within two or three years the research community of this ambitious project will have created a candidate for a clinical molecule, tailored to a new class of therapeutic compounds, so called TRICS, able to switch off bacterial resistance to conventional antibiotics.


In the BioVersys laboratories: from left to right: lab technician Birgit Schellhorn, CEO Marc Gitzinger, CSO Marcel Tigges, and Michel Pieren, leader of the described project.
(photo BioVersys)

More Information: biotechnet

posted: 26.01.2014

Olten Meeting 2013 – Make Changes

The annual Olten Meeting took place on 29 November 2013 under the heading ‘Make Changes - bioinformatics and bioprocess engineering’. Ex-pert speakers from Swiss academia and abroad introduced new and inno-vative concepts in both domains, representatives of science and compa-nies took the opportunity to exchange ideas and to establish new contacts across the border.

Daniel Gygax, President of biotechnet Switzerland, highlighted the chanc-es given by the new partnership of the Swiss Biotech Association and the biotechnet Switzerland linking their R&D and their activities related to the knowledge and technology transfer within the NTN Swiss Biotech™. This National Thematic Network covers all relevant competences across the entire value generation chain from innovation to product development and commercialization. Initial positive reactions include the 16 new memberships, new CTI projects up to CHF 2.8 million and the successful development and internationalization of the TEDD competence centre in Tissue Engineering for Drug Development.

‘Via regia’ to structural information for proteins

Among the speakers were Torsten Schwede, associate professor for structural bioinformatics at the Biozentrum of the University of Basel and the SIB Swiss Institut of Bioinformatics. For him, knowing a protein’s three-dimensional structure is crucial to understanding its biological function at the molecular level. But despite advances in experimental protein structure determination, there is still no experimental structural information available for the majority of protein sequences resulting from large-scale genome sequencing and metagenomics projects. In order to fill this gap, different computational methods for predicting the structure of proteins have been developed. They differ in their computational complexity, the range of proteins that they can be applied to, and also the accuracy and reliability of resulting models. New horizons have been opened by SWISS-MODEL. This server for automated comparative modelling of 3D protein structures provides several levels of user interaction with its web interface.
http://swissmodel.expasy.org

How to accelerate bioprocess development

An interesting approach for accelerating bioprocess development was demonstrated by Christoph Herwig, Professor of Bioprocess Technology at the Vienna University of Technology. According to the Global Biotechnology Market Research Report of April 2013, the global recession tempered the demand for non-essential health products in the last five years. But despite these factors, industry growth is forecast to continue skyrocketing in the next five-year period. Robust and scalable bioprocesses are prerequisites for product safety and economic efficiency in the production of biomolecules in ‘red’ and ‘white’ biotechnology. Furthermore, the optimization of the processes is essential, for instance to compete with biosimilars. The focus is on a “50% / 2x” approach: reduce process development time by 50% and achieve a 2-fold increase in productivity. You can find the full article on www.researchgate.net

Microcapsules for high cell density

The domain of Ian W. Marison, Professor at and Head of the School of Biotechnology at the National Institute for Bioprocessing Research & Training (NIBRT) of the Dublin City University, is Process Analytical Technology for the online monitoring and controlling of high cell density cultures. Microencapsulation offers a unique potential for high cell density, high productivity mammalian cell cultures. The process involves the complete envelopment of a pre-selected core material within defined porous or impermeable membrane using various techniques to realize miniature particles. However, for successful exploitation there is the need for microcapsules of defined size, properties and mechanical stability. With a custom-developed Vibrating-Nozzle Jet, a laminar flow jet break-up technique, Ian Marison and his crew produced alginate beads without any defined core in the size range of 150 µm to 2 mm and a deviation of ± 1.5%. Their capsules – for instance liquid-core microcapsules used for drug recovery – range between 200 µm and 2 mm with a deviation of ± 2.5%. www.nibrt.ie

Break down plastic waste using bacteria

About 280 million tons of petrol-based and yet cheap plastics will be pro-duced worldwide in 2014. The consumption in Switzerland is about 1 mil-lion tons, of which 650,000 tons are incinerated each year. That’s why the idea of developing plastics synthesized by bacteria is receiving growing attention due to rising oil prices and plastic waste being an environmental problem with a global impact. For Manfred Zinn, Professor in Biotechnology, specializing in bioprocess design and biomaterials at the HES-SO Valais in Sion, possible alternatives are polyhydroxyalkanoates (PHA), bacteria-synthesized, intracellularly accumulated polyesters from sugars as well as fatty acids.

“Our idea is to replace traditional carbon substrates – sugars and fatty acids – with cheap, non-food competitive alternatives from Valais”, explains the scientist. He and his colleagues at the Institute of Life Technologies at HES-SO Valais investigate therefore pomace – the residue obtained after pressing and distillation – of native fruits such as apricots, cherries, and grapes. In the case of wine waste especially, promising results were achieved for producing PHA by bacterial fermentation. “PHA is interesting for producing PHA by bacterial fermentation”, comments Manfred Zinn. “Its material properties can be adjusted to produce different products such as adhesives (glue), elastomers (hydrophobic coatings) and thermoplasts (solid products).”

For further information, please contact Dr. Daniel Gygax, Professor of Bioanalytics at the FHNW School of Life Sciences and President of biotechnet.
daniel.gygax@fhnw.ch

Illustrations


Upstream processing suite at the National Institute for Bioprocessing Re-search & Training (NIBRT) in Dublin, showing a completely controlled 150-litre perfusion bioreactor.
(Copyright NIBRT)


Researchers at the Institut für Verfahrenstechnik, Umwelttechnik und Technische Biowissenschaften at the Vienna University of Technology have developed a method of obtaining information much faster than before with the aid of metabolism of micro-organisms which increases productivity.
(Copyright Vienna University of Technology)

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posted: 15.01.2014

TEDD Annual Meeting 2013

On October 22, ZHAW Wädenswil became the Mecca for experts from Tissue Engineering for Drug Development and Substance Testing. The conference room was packed! Network partners from academia and industry familiarized themselves with the latest developments in Neural Tissue Models.

Serving up innovation on a silver plate

An exciting topic – 3D neural tissue as models for drug development – was presented by Professor Ellen Fritsche from the Leibniz Research Institute of Environmental Medicine. “We work on the identification of signalling pathways which contribute to exogenously-induced developmental neurotoxicity or brain aging. Preventive strategies against such adverse effects of compounds or age are investigated.” These research questions circle around a 3D in vitro model which consists of human or rodent neurospheres, clusters of primary neural progenitor cells. “Pathways of interest include the aryl hydrocarbon receptor, thyroid hormone receptor and Nrf2 signalling. Knowledge on toxicity pathways feed into the application of such a system for toxicity testing or drug screening. High content image analysis is established to increase the image-based experimental throughput.”

Dr Karin Sch¨tze, co-founder of CellTool GmbH has developed a compact Raman microscope system for non-destructive early recognition of cell differentiation based on Raman spectroscopy. The BioRam® represents a valuable tool for biomedical applications as it can discriminate tumour cells from non-tumour cells or identify cell types e.g. B-cell and T-cell derived Hodgkin lymphoma, the most common blood cancer. It I also possible to monitor invasion of neural glioblastoma cells into engineered neural tissue. Glioblastoma tumours arise from astrocytes and are usually highly malignant. Raman spectroscopy works with living or fixed 2D- or 3D-cell cultures and - most important - does not require any staining or antibody based markers. It also can discriminate e.g. fibroblasts from stem cells or detects stem cell differentiation much earlier than common methods.

Dr Martin Stelzle from NMI (Naturwissenschaftliches und Medizinisches Institut) Reutlingen presented a technological advance known as the Hepa Chip. Liver damage is one of the most common adverse drug reactions. Since results obtained with animal experiments can only be transferred to the human situation to a limited extent, there is a need for cell-based systems that model human organ function as closely as possible. The Hepa Chip, based on human liver and endothelial cells, is able to do just this. Its special feature is its ability to use human liver cells cultivated in a particular way. “Standard culture vials can only be used to test substances for their cellular effect for a period of between several hours and a few days”, comments Martin Stelzle. “The unique feature and advantage of our biochip is that the cells are actively arranged by electric forces in such a way as to form organ-like structures. As a consequence they are expected to exhibit organ-like function for much longer. Our ultimate goal is to incubate the drugs for several months, which will enable us to test the biotransformation of drugs under even more realistic conditions.”

Exchange of ideas in the greenhouse

A very popular event was "Lunchtime in the ZHAW greenhouse", where network partners from academia and industry presented their latest innovations at interesting exhibition stands.

InSphero explained how 3D neural microtissues for drug development and substance testing are created. Their organotypic neuro models serve for testing for neurotoxicity, disease modelling, modelling the blood brain barrier, studying cell interactions or brain development.

CSEM exhibited novel in vitro models, in particular of biological barriers, made possible by ultrathin porous supports. Electrodes can be integrated to support TEER (transepithelial electrical resistance) to monitor the quality of the cell layer. The supports can be combined with microfluidic networks or miniaturized bioreactors to form bioMEMS components that are optimized for specific applications.

At Cellec, a spin-off of Basel University, the U-CUP perfusion bioreactor is a user-friendly tool for establishing and controlling 3D cell cultures. U-CUP has been specifically designed to be used by any scientist or lab technician working in the life sciences.

In its Expertise Platform Proteases programme, Novartis is focusing on the currently substantial and unmet need for medical treatments for skeletal muscle and tendon-related diseases. The problem is the lack of organotypic in vitro models for efficient physiological screening and characterization of compounds. In a cooperation with ZHAW Wädenswil and the companies RegenHU and WEIDMANN, the Novartis Institutes for BioMedical Research Musculoskeletal are seeking to engineer new in vitro 3D organotypic human skeletal muscle and tendon tissues by means of bioprinting and design new tissue culture devices allowing mechanical and/or electrical stimulation and recording in a reliable and robust system geared toward compound screening.

At the exhibition stand of Credentis, visitors were able to see how Curodont™ Repair provides dentists with a non-invasive option for natural mineralization rather than classical repair of carious lesions. Applied to an early lesion, Curodont Repair forms a scaffold within the lesion so that new hydroxyapatite can form and grow. Ideally, the lesion will mineralize within a few weeks. This effect is observed in a growing number of patients both in clinical studies and daily practice settings.

MucilAir™ comprises premium 3D human airway epithelia reconstituted in vitro with long shelf-life and was presented by Epithelix SàRL in Geneva. It is made from primary human cells isolated from the nasal cavity, trachea and bronchus and then cultured at the air-liquid interface. MucilAir™ mimics the in vivo tissue of the human respiratory epithelium. The focus is on pathologies such as smoking-related diseases, allergic rhinitis, asthma, COPD and cystic fibrosis.

The resounding success of the TEDD Annual Meeting 2013 shows that the TEDD network contributes to new scientific evidence and is a significant contribution to future economic development in this promising domain.

Information:
Professor Dr. Ursula Graf-Hausner
Life Sciences and Facility Management
ZHAW Wädenswil

Phone 0041 58 934 5518
E-mail ursula.graf@zhaw.ch
URL www.icbc.zhaw/tedd

More Information: biotechnet

posted: 22.12.2013

The myth of the antixodiant capacity of coffee

For some years now there have been reports on epidemiological evidence suggesting that a few cups of coffee a day reduce the risk of the development of certain neurological disorders such as Parkinson’s disease, as well as inflammatory and cardiovascular disorders, type 2 diabetes, liver disease and various types of cancers.

The group headed by Professor Chahan Yeretzian at the Zurich University of Applied Sciences in Wädenswil wanted to know for sure. ZHAW Wädenswil is a centre of expertise in the Science and Art of Coffee and boasts highly qualified specialists with experience in coffee.

Knowledge is better than ignorance

The ZHAW team set out to revisit a range of antioxidant assays. They then created a platform composed of three complementary and validated antioxidant assays: Folin-Ciocalteu reagent (FCR) is a mixture of phosphomolybdate and phosphotungstate used for the colorimetric in vitro assay of phenolic and polyphenolic antioxidants. ABTS, or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), is a chemical compound used to observe the reaction kinetics of specific enzymes, while ORAC (Oxygen Radical Absorbance Capacity) is a method of measuring antioxidant capacities in biological samples in vitro. The first two methods are based on electron transfer reactions: the FC assay for total phenols and the ABTS assay which, on oxidation, forms the cationic chromophore ABTS. The third assay, ORAC, is based on hydrogen atom transfer, in which the antioxidant and the substrate fluorescein compete for thermally generated peroxyl radicals after their formation by the decomposition of 2,2’-azobis-2-amidinopropane, dihydrochloride (AAPH).

Routine assessment of coffee brews

“Given the many assays that have been reported for measuring antioxidants, we have focused on identifying a small group of validated assays that can reliably measure the total antioxidant capacity in coffee brews, and the antioxidant capacity of various coffee components that have been associated with potential beneficial health effects”, comments the chemist and coffee specialist. The principal aim of this work has been to develop a platform of antioxidant assays that can be used routinely for the assessment of coffee brews and quality control. “However”, recalls Chahan Yeretzian, “all assays are based on chemical reactions, and it is a big, and not altogether justifiable, step to equate their results with any specific health consequences arising from consumption of the beverage.”

The methods developed by the ZHAW researchers have been chosen to measure different aspects of the antioxidant activity in coffee brews, and thus to produce a more differentiated and complete picture of their antioxidant activities than can be obtained with a single assay. Three assays have been thoroughly validated and are now suitable for routine measurements. While fundamental studies aimed at acquiring a better understanding of the underlying chemical processes of these assays are under way, they are currently also being used within a larger project designed to maximize the antioxidant potential of coffee via specific time-temperature roasting profiles. This research has led to a series of publications, and more are expected as the ZHAW team progresses in their endeavour.

Information:
Professor Chahan Yeretzian
Life Sciences and Facility Management
ZHAW Wädenswil

Phone 0041 58 934 5526
E-mail chahan.yeretzian@zhaw.ch
URL www.icbc.zhaw.ch/coffee

Illustration


Dr Alexia Gloess, project manager of the study, analysing and discussing results with Prof Dr Chahan Yeretzian.

More Information: biotechnet

posted: 19.11.2013

The art of coffee extraction

As the legend says, it all began in Ethiopia, when the goat herder Kaldi prepared a potion made from beans after he observed the dynamic behaviour of his goats after eating them. Sufi mystics in the 15th century enjoyed the stimulating beverage and soon coffee was en vogue in Arabia, India and Europe. But tastes differ: While in Ethiopia one enjoys the ‘buna’ with salt or butter instead of milk and sugar, the ‘kahwa’ is served in Saudi Arabia pre-sweetened and flavoured with cardamom. The ‘Viennese blend’ looks like one espresso shot topped with steamed milk and milk foam, while Italians swear by a caramel-coloured crema layer thick enough to support a spoonful of sugar, and Mexicans will surprise you with their ‘Café de Olla’ with cinnamon sticks.

How to reveal secrets with chemistry

But as Chahan Yeretzian, who created the CAS (Certificate of Advanced Studies) in The Science and Art of Coffee, knows: It is not just about spices, it is about how to extract the coffee. “There are many different ways to prepare coffee depending on the geographic, cultural and social context, as well as on personal preferences”, recalls the Professor at the Zurich University of Applied Sciences (ZHAW) in Wädenswil, “and these affect the flavour, mouthfeel and appearance.” A typical distinction made in Western societies is between a lungo and an espresso. “An espresso is a concentrated extract of 20 to 40 ml, while a lungo is a cup size of up to 250 ml, both brewed by forcing hot water at high pressure through ground coffee.”

As Chahan Yeretzian and his team not only have the knowledge and experience on coffee, but also the infrastructure for roasting, grinding and extraction as well as state-of-the art analytical labs, they have carried out a study on nine different extraction methods. The goal was to develop an “identity card” for each cup of coffee. The coffees were characterized using instrumental and sensory methods. The range of extraction methods included an automatic and a semi-automatic machine, a single-serve capsule system, a percolator and a French press, a Bayreuth coffeemaker and a filter coffee machine.

Studying coffee with scientific precision

When drinking coffee, the first impression is a visual one, followed by the aroma, perceived ortho-nasally. “More than 1000 volatile organic compounds have been identified in the gas phase of coffee”, explains Chahan Yeretzian. “Yet only a fraction is odour-active, and around 20 are key aroma compounds, i.e. relevant for a typical coffee aroma.”

When drinking coffee, the perceived flavour in the mouth is a combination of taste, retro-nasal aroma, texture and temperature. A good espresso flavour consists of a well-balanced acidity with a fruity and roasty note, rounded off by a slight coffee-like bitterness and a thick texture. While most of these attributes can be assessed by a sensory panel, instrumental methods have been applied to measure the acidity, the aroma and the texture. In order to evaluate the influence of the extraction method on acidity, the group measured the titratable acidity. The aroma was measured by gas chromatography and the texture, a further important sensory descriptor for coffee, as the total dissolved solids in the cup. For sustained sensation at the end of a sip, the finish should be a good balance of aroma, acidity and astringency.

But Yeretzian and co-workers have also examined the content of certain ingredients that may affect our metabolism. Indeed, besides the directly sensory impression, drinking coffee may also have implications for our well-being. “The contents of caffeine and chlorogenic acids are said to be important factors for the salubriousness of coffee”, explains the coffee expert. “The caffeine may improve our physical and mental performance, while the chlorogenic acids are a family of powerful antioxidants.”

Making coffee enjoyment comprehensible

As the results show, the extraction efficiency of different coffee components shows great differences between the various extraction techniques. Compounds like caffeine are essentially quantitatively extracted already in a 30 ml cup and diluted when extending to larger cup sizes. By contrast, some chlorogenic acids are less water soluble, and their extraction yield increases as the coffee is extracted with increasing volumes of water. “A higher amount of water, as in the extraction of a lungo, generally leads to higher extraction efficiency for compounds of lower water solubility. A prolonged extraction time and/or a higher extraction temperature further enhanced extraction efficiency”, concludes Chahan Yeretzian. The impact of higher extraction yield at higher temperatures was particularly noticed in Moka coffee, where coffee is extracted at nearly boiling temperature (~100 °C); the other coffees are extracted at around 90 °C. Referring to the flavour of coffee, extraction under pressure (for example espressi) led to a cup dominated by body, acidity and some bitterness, while filter type coffees had lower body and bitterness, but eventually with a hint of sweetness.

The aim of the study was not to find out the best coffee extraction procedure, but to approach the subject from a scientific perspective. With this in mind, it’s been a real success, as Chahan Yeretzian puts it: “To the best of our knowledge, so far no study has comprised such a large number of extraction methods evaluated according to instrumental and sensory aspects.”

This work was published in: A. N. GLOESS, B. SCHÖNBÄCHLER, B. KLOPPROGGE, L. D`AMBROSIO, K. CHATELAIN, A. BONGARTZ, A. STRITTMATTER, M. RAST, C. YERETZIAN.; Eur Food Res Technol 236(4), 607 (2013)

Information:
Professor Chahan Yeretzian
Life Sciences and Facility Management
ZHAW Wädenswil

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posted: 06.11.2013

TEDD represented at the World Medtech Forum Lucerne

Medtech products need to satisfy the highest standards of precision, quality, safety and traceability. The Expert Park at the WMTF focused on process chains in medtech manufacturing. Established specialists in milling, cutting, laser marking, injection molding and coating presented successful solutions for manufacturing medtech products that are competitive in the global markets. One of them was regenHU with its 3D tissue printer for biomedical applications as an attractive magnet for WMTF visitors. Interview with Marc Thurner, CEO of regenHU:

  1. What is the USP of regenHU – the core of your innovation – you presented at the WMTF

    regenHU commercializes 3D tissue printers for biomedical applications, tissue and organ fabrication for regenerative medicine and drug discovery. The unique selling proposition of regenHU’s technology is the capacity to print bioactive components such as cells and signal molecules in combination with a broad range of biomaterials like biopolymers, calcium phosphate and synthetic or natural hydrogels. Having a spatial control of these components and biomaterials allows us to recreate a three-dimensional biological environment that mimics living tissue functionalities (e.g. epidermal skin, bone, lung…tissue models).

  2. 1.The valued added to a medtech product is created by all the factors in production working together. What is unique about your 3D tissue printers in this respect?

    regenHU’s tissue printers offer new opportunities to biomedical product development - material combination that is not possible with state of the art fabrication techniques. 3D tissue printing also provides new business models of how to bring cell based therapies into clinics, for example chair-side manufacturing of biomedical products. The medical industry is moving towards personalized medicine. 3D tissue printing is a promising approach to manufacture patient specific solutions. Patient specific means in terms of geometry but also in the biological composition of the device, providing medical products with better clinical, esthetical and functional outcomes.

  3. 1.Can you say something about the network of partner companies you are working in?

    regenHU is internationally active, deserving world-wide leading universities and R&D departments. Switzerland is an important player in this emerging field. In Switzerland for example, regenHU is an active partner of the TEDD Competence Center for Tissue Engineering and Drug Development, performing research on tissue models for drug discovery. In general, we try to keep a strong relation with our customers, helping them to progress in their scientific work and partnering up when they need an industrial partner to convert science to market. One successful example of such a partnership is regenHU’s spin-off company VIVOS Dental that brings into market a novel bone grafting solution that has been jointly developed with the University of Geneva.


Marc Thurner, CEO of regenHU

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posted: 26.10.2013

International recognition for the TEDD network

To mark the CLINAM 2013 European conference on clinical nanomedicine in Basel, the TEDD network organized a Satellite Session on June 25, at which experts from academia and industry presented the latest developments in 3D tissue models. This article gives a glance behind the scenes.

Active ingredient testing is an essential part of developing new compounds, but it is expensive and frequently not very accurate. The solution is in vitro cell culturing of synthetic tissues of the kind being produced by the TEDD network, which is based at Zurich University of Applied Sciences at Wädenswil (ZHAW).

Synergies within the network

Professor Barbara Rothen-Rutishauser of the Adolphe Merkle Institute in Fribourg is investigating the interaction between artificially produced nanoparticles and biological systems, particularly the lungs. One of her projects focuses on optimizing cell culture models and aerosol deposits and visualizing and identifying nanoparticles using high-resolution stereological tools. The objective is to evaluate the risk associated with inhaled bio-nanomaterials and to develop new drug delivery systems to treat lung problems. Prof. Rothen wanted to investigate the air-blood tissue barrier where oxygen and carbon dioxide are exchanged between respired air and blood. Studies have shown that nanoparticles can overcome this thin barrier and then be distributed in the body via the circulation.

Since no commercial model of this kind of blood barrier was available, the research scientist contacted Marc Thurner through the TEDD network. He is CEO of regenHU Ltd. and – with the assistance of ZHAW – the developer of the BioFactory®. This 3D bioprinter enables researchers to design cells, biomolecules and a range of soft and hard materials in the required 3D composite structures and in this way to imitate bio-mimetic tissue models. The automated and standardized printing processes offer a high throughput, and they produce a tissue whose architecture matches the situation in vivo and is thus eminently suitable for use as an artificial lung model.

Trend towards automation

Cellendes GmbH in Reutlingen, one of the partners in the network, specializes in biomimetic hydrogels for 3D cell cultures. The company has developed the 3D Life hydrogel system, a complete set of reagents for the flexible design of extracellular matrix compositions in 3D cell cultures. The reagents are easy to use and provide complete control over biomolecular modification, producing hydrogels that are compatible with various cell types. The biomimetic versions produce various 3D cell environments, depending on the purpose of the cell culture. The choice of cross-linking agent determines whether the cells decompose the hydrogel locally, creating room for movement in the process. Also involved in the development work were the group led by Professor Ursula Graf-Hausner, a lecturer at ZHAW Wädenswil and the initiator of the TEDD network, and Tecan Group AG, an internationally operating Swiss-based manufacturer of laboratory equipment. Tecan supplied the Freedom EVO® system used to automate the process. It features four workbenches and ensures that liquids are handled accurately and reliably by user-friendly robots.

Innovation at the interfaces

ZHAW Wädenswil is collaborating with InSphero, a company that supplies organ-typical 3D microtissue in a format suitable for drug testing. A project is under way with Balgrist University Hospital to characterize primary human osteosarcoma tissue and use it in drug testing. Prof. Graf-Hausner’s team is also working closely with Prof.Simon Hoerstrup, Head of Regenerative Medicine at Zurich University, to find out what users really need. She, Prof. Hoerstrup, InSphero and Hamilton, the market leader in laboratory robotics, are currently planning to partner on the automated pro-duction of human 3D microtissue for regenerating heart muscle after a heart attack.

http://www.icbc.zhaw.ch/tedd


The 3D Life hydrogel from Cellendes

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posted: 07.09.2013

8th Summer School in Advanced Biotechnology Innsbruck, Austria, September 01 – 05, 2013

Biotechnet Switzerland and the BIRS (Master degree in Biotechnology for Industry and Scientific Research) program of the University of Palermo are continuing their established Summer School in Advance Biotechnology by holding the 8th in the series in Innsbruck, Austria.


MCI Management Center Innsbruck

The Summer School promotes professional contact between all participants and in-spires students and young researchers to pursue careers and research in different fields of biotechnology. The program meets these goals by offering lectures by distinguished speakers from both academia and industry. About 60 students and 40 lecturers from the participating universities – MCI Innsbruck, ZHAW, FHNW, HES-SO Wallis, Universität Tübingen, Technische Universität Berlin and Università degli Studi di Palermo – will meet at the MCI Management Center Innsbruck from September 1 through 5, 2013. The on-site organizer is Professor Christoph Griesbeck, Head of Department & Studies Biotechnology (BSc/MSc).

A number of speakers from Switzerland will be attending. They, and the topics they will be addressing, are (at the time of writing):

  • Environmental biotechnology
  • Drug screening and data mining with speakers including Eric Kübler, FHNW (Syn-thetic biology for the discovery of novel 11b – HSD1 inhibitors) and Beate Sick, ZHAW Winterthur (Visualization and mining of biological data)
  • Proteins
  • Cell biology with Jack Rohrer, ZHAW Wädenswil, (Glycosylation of Biosimilars)
  • Antibotics
  • Cell culture
  • Pharmaceuticals
  • Diagnostics with Armin Zenker, FHNW Muttenz (In vitro/in vivo assays), and Daniel Gygax, FHNW (In vitro diagnostics)
  • Engineering with Uwe Pieles, FHNW (Nanomaterials in medicine)
  • Biomaterials with Manfred Zinn, HES-SO Sion (Novel carbon sources for the bacterial production of sustainable polyhydroxyalkanoate in bacteria).

For further details, please visit:
http://www.biotechnet.mci.edu/home

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posted: 29.07.2013

How a small red fruit becomes a tasty brown bean

Have you ever been walking down a street when you suddenly noticed a complex fragrance that reminded you of toasted bread or popcorn? This irresistible aroma that wafts seductively into your nose is the smell of coffee roasting. It’s a chemical pro-cess by which flavour components are created to augment the taste, acidity and body of this beverage that is enjoyed by millions of people throughout the world. It is probably the most significant and dramatic processing step in a long chain of transformations undergone by coffee beans – a highly complex, heat- and time-dependent process whereby the characteristic organoleptic properties of coffee are generated.

However, what actually happens within the individual beans during these dynamic processes is still a closed book to scientists. At the Zurich University of Applied Sci-ences (ZHAW), Professor Chahan Yeretzian wanted to uncover the secret behind these processes. He thus set up a research group – a center of expertise on The Science and Art of Coffee – and launched the CAS Certificate of Advance Studies, the first continuing education course on coffee at a Swiss university. Thanks to his infrastructure, which includes on-site extraction and roasting facilities, he recently also began to simulate the heat and mass transfer in individual coffee beans during roasting using computational fluid dynamics (CFD). His tool is highly suited to predicting physical fluid flows and heat transfer using computational methods.

For the experimental validation of the numerical model, he placed an individual coffee bean in a cylindrical glass tube and roasted it with a hot air flow. In doing so, he used the identical geometrical 3D configuration and hot air flow conditions as those used in numerical simulations. In a subsequent step, he compared temperature and humidity calculations from models with experimental data measured in the dissertation by Stefan Schenker from Bühler AG Uzwil, the project’s industry partner. Valuable support was also provided by researchers from the Universidad Autónoma del Estado de Morelos in Mexico.

“The model predicts the actual process quite accurately and represents a useful ap-proach to monitor the coffee roasting process in real time”, comments the former re-searcher from Nestlé Nespresso. “It provides valuable information on time-resolved process variables that are otherwise difficult to obtain experimentally, but critical to a better understanding of the coffee roasting process at the individual bean level.” This includes variables such as time-resolved 3D profiles of bean temperature and moisture content, and temperature profiles of the roasting air in the vicinity of the coffee bean. The methodology applied has proven to be a precious tool for predicting coffee bean temperature and its time evolution during roasting. It thus complements and extends current methods for monitoring and evaluating the impact of roasting parameters on the quality of roasted coffee, the world’s most widely traded tropical agricultural commodity.

Fachstelle Analytische und Physikalische Chemie (ZHAW)

More Information: Chahan Yeretzian

posted: 23.07.2013

The Vaccine-Factory in the Box – from vision to reality

Certain inveterate habits seem to be almost indestructible: It’s hard to believe, but the vast majority of currently commercialized seasonal influenza vaccines are – with some exceptions - still based upon embryonated chicken eggs serving as a substrate for virus propagation. Completely new ground is broken by Redbiotec AG. The biopharmaceutical spin-off of the ETH Zurich founded in 2006 and still privately held has developed its proprietary rePAX® technology platform to develop vaccines based on multi-component VLPs. These so called reVLPs™ are produced by co-expression of multiple proteins.

VLPs – spontaneous assembling with the right condition

VLPs or virus-like particles look like a virus and are therefore recognized by the body’s immune system. But they have no core genetic material what makes them non-infectious and unable to replicate. All they contain is either one protein (monomeric) or several proteins (multimeric) from a single strain, serotype or disease. Chimeric VLPs with a defined viral capsid and one or several proteins from different sources or even different diseases are generated in respect to their application. Additionally, enhancing factors for product and/or expression improvement can be co-expressed. The basis of the self-amplifying reVLP™ production is the highly efficient baculovirus vector expression system (BEVS), where VLPs pass – depending on the selected capsid – through a self-assembly and are secreted together with the baculoviruses.

VLPs are ideal candidates for safe vaccines aiming at enveloped and non-enveloped viral targets like RSV (respiratory syncytial virus), the most common cause of bronchiolitis, HCV (hepatitis C virus), Dengue fever, also known as break-bone fever, Influenza, a serious public health problem that causes severe illnesses and deaths for higher risk populations, and HPV (human papilloma virus), the most common sexually transmitted infection. Redbiotec is today the leading company who nearly identically mimicks even complex dangerous viruses with the objective to combat them.

Unbeatable advantages

The benefits are clear: “With the rePAX® technology, cloning, expression and manufacturing of reVLP™ is fast, with an estimation of 3 to 4 months from strain to vaccine, allowing for more rapid vaccine production in response to emerging viruses”, comments Christian Schaub, CEO and co-founder. “The whole process is easily scalable due to the use of disposable production technology.” Based on the single-use concept, he also considers the ‘factory in a box’ as a mobile production unit to rapidly build up a new infrastructure in any part of the world and to start immediately a vaccine production be it in a developing country or in a region where a pandemic outbreak occurs. But the strategy expert has still other trump cards to play: The VLPs can also be used as a kind of biological adjuvant in the cancer therapy (heterologous prime-boost) or for antibody screening. As a result, Redbiotec develops a globally unique competence in three specific business segments where we are still urgently waiting for efficient problem solutions.

www.redibiotec.ch

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posted: 18.06.2013

A close look at the expansion of adult mesenchymal stem cells

Adult stem cells are progenitor cells of other, more specialised cells which can develop many types of specific cells. That makes them very interesting for biopharmaceutical applications like cancer therapy or regenerative medicine.

In order to achieve a higher yield of cells it is necessary to realise a scale-up of the cultivation processes from small (ml systems) to large-volumes (l systems). To do so, the reactor systems have to be characterized from a bioprocessing perspective and appropriate criteria for process transfer have to be defined.

In his bachelor thesis, the biotechnology student Valentin Jossen, scientific assistant in the group of Professor Dieter Eibl and Professor Regine Eibl at the ZHAW Wädenswil, investigated the propagation of human mesenchymal stem cells within a research project financed by Lonza Ltd and the Commission for Technology and Innovation CTI. The challenge was to identify criteria which permit the scale-up of the cell expansion from a stirred spinner flask to a stirred bioreactor at benchtop scale. As he found out, micro-carrier based cultivation processes can be transferred to larger stirred systems which offer a better control of the reproduction conditions than the planar cultivation systems used today. His numerical investigations can minimize the experimental efforts, as it is thus possible to characterize the cultivation system and to estimate previously the shear stress. This makes it possible in the future to determine in advance optimal process conditions.

For his contribution to the development of a technology platform for the scalable manufacturing of therapeutically relevant stem cells, Valentin Jossen received in June 2013 the award of the Schweizerische Gesellschaft der Verfahrens- und Chemieingenieurinnen SGCV (the Swiss society of process and chemical engineers).


Valentin Jossen (second from left)

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posted: 11.06.2013

The TEDD network: Mimicking real tissue with 3D cell culture

When in 1907, the American zoologist Ross Harrison at Johns Hopkins University experimented with a frog’s embryonic nerve tissue and discovered a way to grow cells outside the body, he could hardly imagine that he laid the basis of modern tissue culture technique and the fascinating research on isolated living cells in a controlled environment. But meanwhile we know that 2D cell culture has its limitations, as morphology, proliferation, metabolism and expression profiles of cells grown in 2D systems are not equal to cells in living tissues. That’s why, over the past years, 3D scaffolds have been developed respecting the nanoscale structure of the native extracellular matrix, important for cell culture in a laboratory environment.

A good example is Alvetex®, a highly porous, polystyrene scaffold structure with a uniform and well-defined architecture allowing cells to acquire and maintain their naturel 3D shape and organization during incubation. As the Alvetex® Scaffold technology created by the market leader for fast growing 3D cell cultures, reinnervate, provides more biologically relevant information by overcoming the limitations of monolayer cultures, it’s the perfect candidate to exploit synergies with the Freedom EVO® liquid handling workstation developed by Tecan, leading provider of laboratory instruments, enabling automation of the process.

Both companies joined their technical expertise to perform – with the TEDD network* - a series of experiments at Zurich University of Applied Science (ZHAW), Institute of Chemistry and Biological Chemistry in Wädenswil. There, the process of cell seeding, cell maintenance and cell analysis within Alvetex Scaffolds was automated with the colon carcinoma cell line HCT-116. The results are impressive: The cells seeded with the Tecan platform in Alvetex® Scaffold 96-well plates propagate and show viability comparable to growth in manual 3D culture. The process turns out to be reliable and robust, reducing the variability that is potentially introduced by human intervention, and therewith provides more biologically relevant data.

Regarding viability and DNA content of HCT-116 cells, the CellTiter-Glo Luminescent Cell Viability Assay and Quant-iT PicoGreen dsDNA Assay Kit were used. These are classical viability and proliferation assays for different research areas like toxicity testing, biology and cancer research as well as cell-based screens in target identification and validation of drug discovery. Both assays indicate that cells in Alvetex® Scaffolds 96-well plates handled on an automated Freedom EVO workstation show a satisfactory development. Results can be compared to manual cell culture using Alvetex® and confirm that cells grow and proliferate better in cell cultures mimicking tissue-like architecture.

This sophisticated combination gives biologists in the future the chance to achieve a higher throughput, better predictability and a higher degree of standardization for both basic research and drug discovery.

*The TEDD network connects partners from academia and industry in concrete research projects and knowledge transfer. The created platform actively contributes to the development and application of alternative test methods for routine use in industry.

www.reinnervate.com

www.tecan.com/3Dcellculture

www.project.zhaw.ch/de/science/tedd.html

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posted: 09.06.2013

Sophisticated 3D organomimetic models

Drug developers and advanced regenerative medicine solution providers believe that the next evolutionary step in cell-based models will be to create human tissue-like tissues and organs for drug screening and development as well than for therapeutic applications. The increasing demand for organ transplantation is leading to a shortage of organs and criminal trafficking all over the, world while the R&D costs involved in identifying, developing and marketing new drugs is constantly increasing. Novel tissue and organ bio-printing technologies show substantial promises as a way of addressing these challenges.

regenHU Ltd. , The Swiss company is opening the way

This innovative biomedical company in Villaz-St-Pierre, Switzerland, is part of the CPA Group SA and provides a unique approach to creating biologically relevant tissue models by printing bioactive materials such as cells and signal molecules in a three-dimensional environment that mimics the extracellular matrix. regenHU’s bio printer 3DDiscovery® and BioFactory® are specially designed for biomedical and drug screening purposes. The company provides a Tissue engineering kit: the BioInk®, a proprietary hydrogel for 3DDiscovery® and BioFactory® printers that promote cell growth by providing cell adhesion sites and mimicking the natural extracellular environment, are used to create complex three-dimensional 83D) constructs mimicking natural tissues and organ functions. The applications field of this innovative approach includes the manufacturing of complex organ models for automated tissue-based in vitro assays, drug discovery and drug toxicity assessment, as well as complex in vitro models of human diseases.

The secret of regenHU’s novel tissue manufacturing technology lies in the bioprinting process, which involves building up a tissue equivalent layer by layer. Thus cells, signal molecules and biomaterials such as biopolymers, synthetic or natural hydrogels or calcium phosphates form a highly dynamic network of proteins and signal transduction pathway. As a result, the printed 3D cell-cell and cell-extracellular matrix comes very close to natural human tissue.

From 3D structures to organs

Skin equivalents for compound testing

Another recipe for success is regenHU’s close cooperation with excellent scientific partners. In a joint project with the ZHAW Wädenswil and the Bern University of Applied Sciences, regenHU’s bioprinting know-how was used to fabricate a 3D skin model “on demand” for compound testing that could potentially be used as alternatives to animal models.

Skin for transplantation and therapeutic use

Together with Professor Ernst Reichmann, Head of the Tissue Biology Research Unit at the Department of Surgery and a member of the Zentrum für Klinische Forschung at the University Children’s Hospital, Zurich, regenHU is working on acquiring knowledge of the automated generation of novel dermo-epidermal skin grafts. These complex skin substitutes are produced in an automated process by what is known as the “SkinFactory”. The “SkinFactory” has been designed and engineered by regenHU, for use in both basic research and clinical trials treating severe, full-thickness skin defects.

regenHU will be in the spotlight on 26 June 2013 at the European summit on clinical nanomedicine CLINAM 2013 in Basel during the Satellite Session organized by the Swiss competence centre TEDD.

Information: www.regenhu.com

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posted: 25.05.2013

TEDD: Award for Innovation

Partners of the TEDD network (Tissue Engineering for Drug Development) are innovative minds like Barbara Rothen-Rutishauser, full professor at the Adolphe Merkle Institute for nanoscience of the University of Fribourg, the centre of competence for research in soft nanoscience and materials science. Within a National Research Programme she leads the project ‘Biomedical nanoparticles as immune modulators’ and examines how the therapeutic nanoparticles in the lung affect the immune system. Up to now, current studies to assess the risk of inhalation of foreign substances and newly developed drugs in the lungs are conducted on animals. To get away from these animal experiments, researchers are developing three-dimensional cell models in the laboratory. But to date there is no scientific research validated model of the alveoli, the final branchings of the respiratory tree which act as the primary gas exchange units of the lung.

Together with another member of the TEDD network, Marc Thurner, Barbara Rothen-Rutishauser set up a project to realize a 3D lung tissue of the air-blood barrier with a bio-printer. This 3DDiscovery® instrument, developed by Thurners company regenHU Ltd. is a cost-effective 3D bio-printing platform to explore the potential of 3D tissue engineering through the bio-printing approach. Spatial control of extracellular matrix molecules, cells and morphogens in a three-dimensional scaffold is an innovative approach in order to construct designed organotypic in-vitro models of soft and hard tissues. Thank to this special method of bio-printing, the desired tissue can be printed layer by layer, including different types of cells. The artificial lung model of the alveolar region serves as a platform to study environmental pollutants and effectiveness of new drugs.

For this brainwave the Ypsomed Innovation Fund for Research and Development honoured Barbara Rothen-Rutishauser with this year’s 2nd prize. With these awards Ypsomed Innovation Fund aims to promote innovative activities and supports projects for independent funding of start-ups and existing businesses.

www.regenHU.com

www.am-institute.ch

www.innovationsfonds.ch

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posted: 06.02.2013

Olten Meeting 2012: The potential of drug development

A report from the Office of Health Economics – a UK think tank – has confirmed what is already common knowledge: costs and time expenditure to develop new drugs with therapeutic potential grow at a tremendous rate. In plain language this means that the average cost of developing an approved drug has risen from $199 m in 1970 to more than $1.9 bn today. It’s one of the most complex and difficult undertakings in the pharmaceutical industry. The reasons for this are huge R&D costs, a success rate that has been halved from 1:5 to 1:10, a vast increase in the time spent in clinical trials (up from six years to nearly 14 years) and a significant rise in the cost of capital due to increasing regulatory complexity. But there is also a scientific background that makes the discovery of new therapeutical agents so difficult. It’s the fact that the activity of a drug is the result of different factors such as bioavailability, toxicity and metabolism. At the Olten Meeting 2012, researchers from academia and industry came together and presented their ideas about how they intend to proceed to speed up the development and practical application of new, efficient active substances.

Gisbert Schneider, professor of computer-assisted drug design at the ETH Zurich, allowed a glimpse behind the scenes and explained his computational method for the reaction-based de novo design of drug-like molecules thanks to his DOGS (Design of Genuine Structures) software.

www.modlab.ethz.ch

Dr Marcel Tigges, co-founder and CSO of BIOVERSYS AG, talked about the proprietary technology enabling multi-level screening for TRIC (transcription repressor inhibitor compounds) that block the transcription of resistance-enabling genes, thus switching off bacterial resistance to antibiotics.

www.bioversys.com

Dr Urs Regenass, Senior Director of Oncology at Actelion Pharmaceutical Ltd., pointed out that cancer can only arise and enter a malignant state when cancer cells interact with the microenvironment, the stroma. He concluded that it is therefore necessary, despite the success of so-called targeted therapies with a focus on cancer cells, to also treat the tumour stroma to make therapy more efficacious. As an example he cited Macitentan, a novel dual endothelia receptor antagonist that resulted from a tailored drug discovery process, identified by Actelion and tested in cancer therapy.

www.actelion.ch

Dr Adrian Roth, Global Head of Mechanistic Safety at Pharma Research, Hoffmann-La Roche Ltd, spoke about the issue of assessing drug safety with 3D cell models. It is all about 3D scaffolds – extremely small, but defined nanostructures – that can not only maintain liver function during longer periods, but also provide cues for adhesion and growth of specific cell types in defined patterns for a long time. As these 3D liver systems also include non-parenchymal cells such as stellate and kupffer cells, they allow the study of inflammatory processes relevant for drug-toxicity in vivo.

www.roche-pharma.ch

Dr Tudor Arvinte, Professor at the University of Geneva and Chairman and CEO of Therapeomic Inc. in Basel, argues that formulations of biopharmaceuticals should be designed very early in the development of these substances. He thinks that the investment in a good proof-of-concept that facilitates formulation is minimal compared with the risk that companies are taking in performing human studies with non-optimized formulations. The success of the medical proof-of-concept for phase II and phase III clinical trials and the final market success all depend upon the quality of protein formulation.

Dr Chad Brokopp, working in the Regenerative Medicine Program at University Hospital Zurich, focuses on the Fibroplast Activation Protein (FAP) enzyme. He discovered that the FAP previously observed in cancer and arthritis also contributes to the inflammatory mechanisms of atherosclerosis and to plaque destabilization, the main cause of heart attack and stroke. To solve the problem, he developed a clinical theranostic package and founded his own company, Mabimmune Cardiology AG, to market it.

www.mabimmune.com

You can read the full report in the CHIMIA magazine 1-2/2013.

More Information: biotechnet

posted: 26.01.2013

Soft Materials for Advanced Products

See Flyer SATW Transferkolleg for details.

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posted: 25.12.2012

Tissue Engineering for Drug Development and Substance Testing Annual TEDD meeting at the ZHAW Wädenswil

The annual meeting of the TEDD – Tissue Engineering for Drug Development and Substance Testing – centre of excellence at the ZHAW took place on 23 October 2012. It provided an insight into this platform for human tissue models for drug development and active ingredient testing which, in collaboration with some robust partners, tailors promising technologies to the needs of industry.

The 'travels' of nanoparticles
Dr Peter Wick and his team at Empa St. Gallen are studying the ways in which nanoparticles inveigle their way into our bodies. Their work involves experimenting with human placental tissue donated by mothers at Zurich University Hospital and St. Gallen cantonal hospital who have given their voluntary consent. The scientists introduced into the tissue fluorescent nanoparticles of polystyrene which do not harm the tissue and are easy to identify. The particles measure between 50 nm and half a micrometre. They demonstrated that the tissue was able to hold back particles between 200 and 300 nm in size. Anything smaller than that penetrated the foetal circulation. They are now working on new, 3D multicellular models that will make it possible to provide more efficient screening with the relevant informative value in the longer term and to underpin the development of safe nano applications in medicine.

A 3D skin model
Collaboration between CELLnTEC, Givaudan and the ZHAW is focusing on a 3D human epithelial skin model that will be able to predict the allergenic potential of chemical substances. The model is based on recombinant KeratinoSens™ reporter cells developed by Givaudan. They are integrated into the 3D structure of reconstructed human epidermis obtained using a technique created by CELLnTEC. The substance being tested is applied to the surface, where it penetrates the epidermal 3D structure and acts on the KeratinoSens™ cells. If the substance has sensitising potential, the cells express the reporter gene. The results obtained with the 3D model are analysed and compared with in vivo data and data from KeratinoSens™ cells in 2D culture. The new 3D model means that hydrophobic substances can be applied topically and dose-dependently and their penetration effects can be evaluated.

Tumour microtissue from the freezer
InSphero has just started supplying 3D tumour microtissue that has been cryopreserved at 80°C. The company worked with researchers at the ZHAW to develop a cryopreservation process for microtissue. It is no longer necessary to time tissue purchases to tie in with experiments; the product can now be purchased frozen and the required quantity of plates can simply be taken out of the freezer as needed. Applications for this product are efficacy trials with oncology medicines and studies of the tissue penetration of active ingredients. The cryopreservation process will allow greater flexibility in planning microtissue use in drug development and will also generate additional cost savings.

Skin models from the printer
Marc Thurner, CEO of regenHU AG, and the ZHAW presented his bioprinter devices for organomimetic skin models. The focus here is on scaffolds containing cells that are created layer by layer in extrusion processes and which form the basis of tissue-specific 3D models. The positions in which cells, growth factors and the extracellular matrix are delivered can be controlled exactly. The starting materials include biopolymers, cells, signalling molecules (proteins), hydrogels, collagen, polycaprolactone and polyester. A light-polymerisation process is used to cure the structure. The regenHU BioFactory® produces organ-typical tissues with in vivo-like morphology that reproduce the cells’ in vivo environment far more naturally than is possible in conventional culture plates.

The event in Wädenswil was an opportunity for scientists to find partners interested in joint activities and to think up new projects.

Further information can be found at www.icbc.zhaw.ch/tedd

More Information: Biotechnet

posted: 20.11.2012

Annual report 2011

The annual report 2011 is now available.

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posted: 28.08.2012

Smart bioreactor producing biogas from biowastes

In Switzerland, biowastes have the greatest potential for the production of biogas. But today, the same technology is used whether the material in question is farmyard manure, sludge or waste from food industry. However, specialists agree that the yield could be much better if the procedure was adapted to each individual case. At the ZHAW, Professor Urs Baier and his group of environmental biotechnology are investigating different possibilities in order to optimize the efficiency of the anaerobic fermentation process for different kinds of biomass.

In conventional biogas facilities, a part of the active bacterial mass is washed out with every charging of the bioreactor. As a consequence, the performance of the procedure is reduced and causes long retention times with a big digester volume. In contrast, the membrane bio reactor (MBR) developed within the common project at the ZHAW allows a separation of the methane bacteria and the recycling to the reactor, while the mineralised substances are transferred outward. As a result, the efficiency is increased resulting in more gas, a stable fermentation process and a smaller digester volume. Moreover, the end product is hygienically irreproachable.

Within a project promoted by the Department of the Environment, Transport, Energy and Communications, the Federal Office for Agriculture, AXPO and Swiss Electric Research the ZHAW crew investigates solutions approaches in two anaerobic MBR. Project partners are the Ingenieurbüro HERSENER and the MERITEC GmbH. Their biogas digester in a semi-technical scale runs on a downstream ultrafiltration, a pressure-driven process. The ultrafiltration follows the concept of cross-flow-filtration. The liquid permeates through the membrane. Thanks to the small pore size of the ultrafiltration membrane the organic substances of the biomass are separated from salts and water. The separated, active biomass is redirected into the digester. By doing so, the methane bacteria remain in the digester, but the mineralised substances are transferred outward. The ultrafiltration membrane retains germs, what contributes to a better hygiene in the filtrate. Different from conventional fermentation processes the digestate in the case of the MBR is free of suspended solids. Salts, however, mainly ammonium and potash salts as well as water can be directly used as a liquid fertiliser in agriculture as well as in vegetable growing and horticulture.

As results of the ZHAW researchers show, the MBR procedure can have advantage over the conventional biogas processes, both regarding performance and costs. The MBR system is more effective than the conventional fermentation and the gas and methane yields can be higher for the membrane bioreactor. MBR is a reliable method as to processes and process engineering and allows an economic system operation also for small slurry quantities. These advantages of the MBR indicate that this kind of biogas production could make a considerable contribution to the future generation of power and heat from biogas.

www.umweltbiotech.zhaw.ch


The MBR laboratory facility at the ZHAW. To the right the ultrafiltration (UF), to the left the membrane bio reactor.

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posted: 01.02.2012

TEDD – Platform for Tissue Models

Can a tumour medication act on cancer cells without destroying surrounding tissue? Will my sunscreen really protect my skin and not invade deeper layers of skin? And may I be sure that my antirheumatic ointment does reach the inflamed areas but not affect the epidermis? The demand for safe products has never been as high as today. Nevertheless, drug development and testing still rely on conventional in vitro studies on cells in combination with animal tests, fuelled by REACH, the European Community Regulation on chemicals and their safe use.

An alternative is offered by researchers at the Institute of Chemistry and Biological Chemistry at the ZHAW in Wädenswil. The group of Prof. Dr. Ursula Graf-Hausner, Head of Section of Tissue Engineering and Cell Culture Technology, who has acquired considerable competence in developing organ-like human tissue models showing function and structure of healthy and diseased tissues and organs with surprising physiological characteristics, is now breaking fresh ground: With the help of the Gebert Rüf Foundation, a national Competence Centre for Tissue Engineering for Drug Development (TEDD) was launched at the ZHAW under the aegis of Ursula Graf. A platform is to be generated on which new technologies for drug testing for the pharmaceutical industry and personalised medicine can be developed.

On 21 June 2011, the kick-off meeting gathered the future network partners who cover the entire development and value chain. They encompass basic research like the one carried out at ETH Zurich, medical knowhow from university hospitals like the Department of Biomedicine in Basel, industry related developments made at the CSEM or at the Universities of Applied Sciences like the HSR Rapperswil, suppliers of technical solutions like Delta Robotics, and the end-users from the pharmaceutical industry, biotechnology, medical technology and cosmetics like ACTELION, Roche or Novartis.

An excellent industry partner was found with InSphero AG, a leading supplier of organotypic, biological microtissues for biomimetic drug testing. Their GravityPlus system is the first platform for scaffold-free and automated high-throughput production of 3D microtissues. This technology originates from the hanging-drop method, which allows for gentle, gravity-driven microtissue formation at the liquid-air interface of small medium droplets. By avoiding contact to any foreign material it allows the cells to reform a tissue in a natural manner.

Within the scope of the Gebert-Rüf project, the team of Ursula Graf is analysing different freezing media for the cryo-conservation of microtissues using spheroids from InSphero. In contrast to single cells, microtissues come up against new obstacles during the freezing process due to their 3D structure. The first successful freezing experiments have been carried out and will be further optimised.

Another research topic is the evaluation of different systems for the production of in vitro 3D models. Both methods - with and without scaffolds - are currently investigated and the results will be summarized in a publication. “We want to strengthen the cooperation between basic research, applied research and industry,” states Ursula Graf. “Only with a dynamic transfer of knowledge and technologies we can promote the further development and application of in vitro cell and tissue culture and stimulate the Swiss industry in this promising field of action.”

Several workshops to improve technology transfer and to implement new collaborations will take place during the rest of the year.

Another important get-together will take place at the DECHEMA Symposium 3D Cell Culture at the Zurich Technopark in March 2012. The symposium will present latest technologies and cell culture models for substance testing and the understanding of diseases, safety testing of drugs and industrial applications. Another focus will be the enabling technology devices for 3D cell culture, imaging technologies, systems biology and stem cells.

Tissue Engineering for Drug Development


Tissue model in 3D (HE staining), (ZHWA)

More Information: Biotechnet

posted: 13.12.2011

Mystery tour through the human skin

The skin is not only the outer covering of our body; it’s also our largest organ with a surface area of 1.8 - 2 m2 for an adult. Among its many functions, the most important one is to build a physical barrier to the environment, regulating the passage of water, electrolytes and active agents. The skin of a human being is populated by around 1012 bacteria and provides protection against UV radiation, toxic substances and mechanical attacks. However, it still remains a mystery how the trans-epidermal mass transport of penetrating substances works in detail.

So far, conventional investigation methods for skin penetration consist in chemical analysis of human or animal explants or in tape stripping, by which layers of skin can be removed to analyse applied substances. But now, Dr Christian Adlhart and his team at the Institute of Chemistry and Biological Chemistry of the ZHAW in Wädenswil are breaking fresh ground. The researchers associate Raman imaging and tape stripping to examine the surface distribution and depths profiling of substances penetrated through the skin.

Let’s look at sporting injuries: We apply an analgesic gel, producing immediately a cooling effect thanks to the evaporated alcohol. But a real recovery can only occur when the active ingredients of the pain killer penetrate the callus barrier of the skin. That’s why pharmaceutical additives are added in many cases to accelerate the penetration. “With the aid of Raman microscopy we could track the way the penetration of active agents changes according to the different formulations”, comments Dr Christian Adlhart, head of the Department of Functional Materials and Nanotechnology.

His group also puts in the crosshairs of the sunscreen sector. Advanced sun screens contain a combination of UV filter in order to protect us from harmful influences of the UV radiation as well as from dermal cancer. Moreover, they also retard the ageing process. For this purpose, the pharmaceutical industry utilizes in fact the classical cinnamic acid derivatives, which absorb in the short-wave UV domain and prevent a reddening of the skin, but also particulate sun filters in the nanometer scale to protect from the dangerous long-wave UV radiation. These nanoparticles can only take full effect if they form a homogenous film on the surface without penetrating into the skin. “As our investigations show, there is space for improvement concerning the film formation, as the main part of the particles conglomerates inefficiently in the skin grooves”, explains Dr Franziska Fleischli, scientific collaborator. “But, on the other hand, exactly this effect is required for some cosmetics.”

The measuring procedure developed at the ZHAW attracts interest in the area of working safety for the evaluation of toxic compounds. In order to avoid tests of critical substances on humans, researchers use skin models. Although their structure hardly differs from real skin, their barrier properties are quite different. “This is not amazing, as the skin of mammals also features different barrier properties”, states Christian Adlhart. “However, the thickness of the callus layers, moisture content and lipophilic nature of skin models can be varied until the barrier properties of the skin model will match with real human skin.

For the time being, his team continues to develop the screening technology to clear up open development questions of skin penetration and to adapt their research results on different projects. A co-operation will connect the researchers within the biotechnet with the group of Professor Dr Ursula Graf-Hausner of the Competence Center TEDD (Tissue Engineering for Drug Development), specialized in the development of 3D skin models.


Scientific collaborator, Dr. Franziska Fleischli, in the laboratory of the Institute of Chemistry and Biological Chemistry at the ZHAW Wädenswil

More Information: Biotechnet

posted: 31.10.2011

Good news for prostate cancer diagnosis

About 5800 men fall victim each year to prostate cancer, with 30% the most frequently diagnosed cancer in men and the second leading cause of male cancer-related death. An early diagnosis is therefore advisable. The first choice was up to now the so called PSA test, a blood test that measures levels of a protein called Prostate Specific Antigen. It is manufactured exclusively by the prostate gland. Elevated levels of PSA generally indicate prostate problems. The PSA testing detects prostate cancer with high sensitivity, however it shows poor specificity. “More than 45 million PSA tests are performed annually worldwide and more than seven million are positive with 75% false diagnosis”, states Ralph Schiess, who graduated with a master of science from the University Zurich and studied at the Institute for Systems Biology in Seattle. “That means unnecessary biopsies associated with considerable anxiety, discomfort and complications resulting in high healthcare costs.” He wanted to provide remedy.

While working on his Ph.D. in the group of Professor Ruedi Aebersold, head of the Institute of Molecular Systems Biology at the ETH Zurich, he developed a rational strategy to identify biomarkers. A the very beginning was a mouse model of cancer induced by deleting Pten, the second most frequently mutated tumor suppressor gene, leading among other to uncontrolled cell growth. Together with a group of ETHZ cell biologists headed by Professor Wilhelm Krek, Ralph Schiess investigated the role of the Pten gene during cancer development in the prostate of a mouse. He identified the prostate surface proteins of both healthy mice and those who had developed a prostate cancer because of the inactivated gene. By comparing the healthy mice with those suffering from cancer he determined a pattern of proteins, typical for the mutated version of Pten and of prostate cancer.

To find out whether their findings from mice are also valid for men, Ralph Schiess and the ETHZ team with the help of clinicians from the St. Gallen cantonal hospital and the University Hospital Zurich examined tissue and serum samples of prostate cancer patients and of a control group. By doing so they could identify 39 proteins in men indicating prostate cancer. Out of those 39 candidates they selected the four proteins resulting in the most reliable diagnosis and offering a very high specificity.

The particularly interdisciplinary studies combining basic scientists and clinicians gave rise to an extraordinary biomarker discover technology. “In our common efforts we could realize novel diagnostic tools offering non-invasive diagnostics directly linked to the origin of the disease on molecular level tested in model systems”, explains CEO Ralph Schiess. “The combination of multiple biomarkers captures the complexity of the disease. Thanks to biomarker detection and targeted validation we achieve faster cycles than they are possible with the PSA test and superior results in comparison to competing products under development.” To launch his system on the market, Ralph Schiess founded in 2010 the company ProteoMediX AG as an ETHZ spin-off, together with his colleague Christian Brühlmann, holding a master degree of the University of Zurich in business administration. Co-founders are the systems biologists Ruedi Aebersold, cell biologist Wilhelm Krek and the president of the Swiss Cancer Research Foundation Thomas Cerny.

The ProteoMediX test for the early detection of prostate cancer based on a proprietary protein signature is very promising as it reduces the high number of misdiagnosis, sparing in this way unnecessary biopsies. The cost savings for public health are estimated to 2 billion US $ in the United States only.

In order to make the test applicable to most standard diagnostic platforms, Ralph Schiess he co-operates with Professor Daniel Gygax at the Life Sciences FHNW in Muttenz in a CTI project, supported by the Commission for Technology and Innovation. He is also giving a lecture at the FHNW in Muttenz and will make a speech at the Olten Meeting 2011 of biotechnet on November 23.


control tissue


tumor tissue

More Information: Biotechnet

posted: 18.10.2011

BioTech 2011 at the ZHAW Wädenswil: Chemical Sensors Forum

Biotechnology has a continually growing impact on the chemical industry, on medicine, food and feeding stuff, with a predicted sales increase from today 50 to 300 billion € within the next ten years worldwide. The challenge for the manufacturing base Europe is to tap the full potential with sophisticated bioprocess analytics and sensor technology. On September 1 and 2, the Zurich University of Applied Sciences (ZHAW) in Wädenswil opened its doors at the Campus Gruental to welcome scientists and professionals from both industry and academia to discuss the present state of the art technology as well as latest developments in this field. In the spotlight were three topics: Trends in inline analysis of pH and dissolved oxygen, sensors in the PAT (Process Analytical Technology) framework, and sensors for disposable bioreactors. Just let us single out a few topics among the presentations given.

The all-in-one-sensors

Trend-setting are intelligent sensors which do not show any reaction to mechanical and electrostatic stress, offer signal robustness, longer lifetime and different concepts which means choice. Why does for instance Hamilton Bonaduz AG go for intelligent sensors? “In many cases the problem is not the sensor, but the system”, points out Dr Jörg Pochert, Vice President Laboratory and Sensors. In the world of process analytics, the company is known for its high quality sensors. With their ARC sensor family Hamilton revolutionizes the integration of sensors by rethinking communication between sensor, end users and process control systems “The functionality of a traditional transmitter has been replaced by a microprocessor within the sensor”, explains Jörg Pochert. “ARC sensors bypass the transmitter and communicate directly to the control system. They are available in all standard pH, dissolved oxygen and conductivity formats.” Hamilton sensors deliver well-defined measurements directly to the process control system (PCS), know about their status (identity, quality, validation) and work online.

Fresh ground for disposable bio-manufacturing

Bioprocess development and manufacturing is successful if safe and efficient products of high quality can be produced with consistency. This implies that processes are well characterized. As we come into an area where more and more of the drugs and therapies are manufactured by living cells, process characterization becomes even more critical. “Interestingly enough, bioprocess manufacturing lacks the rigor associated with the computer or auto industry”, states Professor Govind Rao, Director of the Center for Advanced Sensor Technology of the University of Maryland, Baltimore County. “The reason behind is the complexity of living cells, which respond unpredictably to the slightest environmental changes. That’s why sensors monitoring accurately every step of manufacturing play a prominent role.” He was co-founder of the Fluorometrix company which launched the Cellstation™ High Throughput Bioreactor. This new cell cultivation technology allows highly parallel bioprocessing with multiple vessel architecture based on non-invasive monitoring and control of critical process parameters. Key features are deployment of pre-calibrated sensors for disposable bioreactors that confer enormous time and labor advantages over traditional technologies.

“The future demands non-contact, semi-invasive measurements with low-cost light sources and semi-conductor detectors”, Govind Rao gives a foretaste of what is to come. “Optical sensors will replace conventional ones, allow disposable applications. Measurements will be made through glass/plastic in real-time, systems are stand-alone, offering low-cost and simple calibration, without any direct electric contact and they will be more and more miniaturized. Rao notes that it is critical for companies to work together and cross-license technologies so that standard sensor platforms can be used throughout the industry. As an example, he cited the USB consortium that developed USB standards to allow plug and play compatibility for USB devices used with computers. For example, the mini-bioreactors system from Fluorometrix and the SENSOLUX® system from Sartorius share the same core sensor technology, allowing users to compare data from the two systems easily. Otherwise, regulatory agencies are concerned that a fragmented market will result in competing sensors that will have to be individually qualified and add to the already expensive and time consuming process for regulatory approval.

Sensors for disposable bioreactors

Disposable bioreactors are in the ascendant. It’s true that the acceptance of single-use equipment in bio-manufacturing has been slower than expected, but today we state a steady uptake of disposables in production facilities, mainly in the small-to-mid scale. Although it is well-known that the adequate supply of oxygen is the most significant criteria of aerobe cultivations of cells or microorganisms, there is a lack of specific literature regarding oxygen transfer in orbitally shaken, single-use bioreactors. The group of Professor Dieter Eibl, head of bioprocess and cell culture engineering at the Institute of Biotechnology (ZHAW) wanted to provide a remedy. In co-operation with their colleagues at the Hochschule Anhalt and engineers at the PreSens – Precision Sensing GmbH in Regensburg, they used non-invasive optimal oxygen probes to determinate the oxygen mass transfer rate. To this effect, they applied custom-made TubeSpin bioreactors with optical sensor patches from PreSens to measure for the first time dissolved oxygen (DO) in small scale orbitally shaken devices. Special holder devices were designed by PreSens for the TubeSpins to detect the DO and determine the transfer rate using different shaking frequencies, filling volumes and shaking diameters. Data thus obtained are crucial to scale-up processes, starting from cell screening at small scale (several milliliters) to laboratory (several liters) and pilot scale (several tens of hundreds of liters).

As the investigations reveal, both classical start-up methods and the dynamic sulfite method are suitable to measure the transfer rate with single-use oxygen probes. The researchers evaluated their results with statistical-based models and showed good agreement and strong predictive power for each bioreactor. Further research will be carried out to improve the correlation and foreseeability.

Ever-increasing intelligence

“Robust sensors with increased intelligence, integrated functions and made of sophisticated materials are in line with the future trends”, states Dr Caspar Demuth, Head of Centre for Measurement and Sensor Technology at the Institute of Biotechnology (ZHAW). “Our role within the biotechnet is to bend our ear to our industrial partners, to perceive their needs, to offer them advice and the state-of-the-art facilities they require and to help them to develop innovative products for a competitive advantage in the global markets.” The ZHAW projects on sensors for biotechnological applications are good examples of the fruitful collaboration with industry, involving mutual technology transfer. “And as we are also active in education, this co-operation provides access to interesting study topics both for the Bachelor in Biotechnology and the Master in Pharmaceutical Biotechnology”, adds Tobias Merseburger, Director of the Institute of Biotechnology at the ZHAW Wädenswil. “In our study and our research programmes we employ application-oriented strategies in order to stimulate the biotech production location Switzerland.

www.ibt.zhaw.ch/sensortechnik

www.biotech2011.ch

More Information: Biotechnet

posted: 20.09.2011

Hairy roots: the biofactories of the future?

In the laboratories of the ROOTec in Witterswil, most curious incubators are hanging from the ceiling with tufts of white and brownish substance, the so-called hairy roots. They are caused by the Agrobacterium rhizogenes, a Gram negative soil bacterium that infects wounded plants. It transfers a piece of plasmid DNA in the plant genome and stimulates the growth of these so called hairy roots. On an international level, researchers cherish great expectations as these abnormal roots can produce high value phytochemical substances. And they are very easy to culture in artificial media as they do not need any hormones, grow indefinitely and with a high growth rate and offer genetic and biochemical stability. But they are extremely delicate and sensitive, and need a special bioreactor to allow the scaling-up from the laboratory level to the commercial use. Although hairy roots have been investigated since the eighties, the ROOTec team is up to now the only one around the globe, capable of an industrial-scale production.

Its core competency is the ROOTec Mist Bioreactor (RMB), a proprietary development, making it possible to provide every organ culture with the specific requirements regarding gas and nutrient solution for optimal culture conditions. The advantages of ROOTec’s technology are impressive as it makes it possible to exploit the biochemical potential and the properties of the plants without any intrusion into biodiversity or the risk of extinction of wild plants. The phytochemical compounds are manufactured in pharmaceutical quality in a sterile, confined and controlled environment. There is no danger of any contamination and the clonal lines for production are genetically stable. Thanks to the ROOTec technology a rapid set-up of the production process can be realized, quite different from field cultivation and chemical semi or total synthesis.

This cultivation technology gives access to compounds from rare and explored plants. “One out of four pharmaceuticals on the market is based on compounds originally found in plants or is extracted from them”, states Alain D. Meyer, co-founder and CSO of ROOTec. “And there is an increasing interest in nature as a vital source of new, innovative substances with a vast number of applications.” The main markets are the pharmaceutical industry, cosmetics and nutrition supplements. As university studies have found, ginseng can for example help to suppress tumours. As we know about the environmental troubles in Eastern Asia, typically the region of origin of this slow-growing plant, the fabrication in the form of hairy roots would solve a problem. But there is also the ‘Siberian ginseng’ (Rhodiola rosea), of which about 200 to 500 tons are harvested every year, and where a laboratory production in the necessary quantities could ensure the survival of the plant in the long run. The cosmetic industry is an enthusiastic consumer of active substances for anti-ageing, anti-wrinkle compounds, protection of the stem cells in the skin and of alpine herbs who obviously are equipped with an effective ultraviolet protection. “As the cultivation of the fragile hairy roots demands a lot of flair, our chief target is to produce phytochemical compounds with high added value”, comments Alain D. Meyer.

In order to develop further and adapt competences, the ROOTec is co-operating with the Basle University, the Bioprocess and Cell Culture Engineering specialists at the ZHAW Wädenswil, but also with Universities in Germany and France. Master students are making their thesis in the ROOTec laboratories and breathe new life in the labs. But for the time being, the facilities in Witterswil are bursting at their seams: the company should now grow to satisfy the rapidly growing demand of its industrial partners. That means: more infrastructure, more specialized equipment and highly qualified employees. The search is on for the rare pearl, the investor to finance the next step to global business.


rootec 5


rootec 17

ROOTec holds solid intellectual property around its specialized bioreactor technology to produce high-value plant derived compounds, using hairy root cultures.

More Information: Biotechnet

posted: 26.08.2011

Coffee: Power for brain and body

In the 19th century, when the Scottish jurist and philosopher Sir James Macintosh opined with a chuckle that “The powers of a man’s mind are directly proportioned to the quantity of coffee he drinks”, he probably did not realize that there was a grain of truth in his saying. But today we know for sure: The same polyphenols which are to be found in the outer layers of the plants and protect them from oxidation, pests and UV radiation, exert in our favourite drink a beneficial influence on our body and mind. “Coffee is one of the prime sources of antioxidants in our diet”, states Dr. Chahan Yeretzian, Head of Analytics and Analytical Technologies at ZHAW Wädenswil. “Chlorogenic acid, the most abundant polyphenol in coffee, represents a substantial part of coffee antioxidants, a compound that is already present in the green coffee.” He is not the only one to make this amazing statement: As studies at the University of Scranton in Pennsylvania on different foodstuff such as vegetables, fruit, nuts, spices, oil and beverages reveal, coffee is the most important source of antioxidants in the USA. Also their colleagues from the Chia Nan University of Pharmacy and Science in Taiwan found out that water extracts of roasted coffee residues showed a remarkable protective effect on oxidative damage of protein. This is good news, as antioxidants help to protect our body against reactive oxygen species and free radicals, known to be implicated in the development of cancers as well as cardiovascular and neurological diseases.

However, there are differences to be observed: In green coffee the content of chlorogenic acids is higher in C. Robusta than in C. Arabica. Also processes such as roasting and brewing affect the final content in the brew to varying degrees. “It would be favourable to optimize the coffee roasting process in order to maximize the antioxidant content in coffee”, admits the scientist. “But the chemistry behind this process is very complicated and therefore a fascinating research topic.”

To bring light into the darkness, several analytical procedures with different detection systems were developed to identify and quantify phenolic compounds such as liquid chromatography, capillary electrophoresis, voltammetry, amperometric analysis and batch spectrophotometry. A very promising procedure to determine the total polyphenol content in coffee brews turned out to be a semi-automated flow-injection analysis (FIA) with colorimetric detection***. The researchers in Wädenswil based their system on the Folin-Ciocalteu (FC) method and succeeded in expressing the total polyphenol content in terms of gallic acid equivalents. “The advantages are high sensitivity, no need for colorimetric correction of the background colour of the coffee brews, negligible matrix influence and availability of the FC reagent from commercial sources”, states Chahan Yeretzian. “In particular it can be applied directly onto the brew.” On the other hand, the FIA meets the quest for speed, improved reproducibility and higher automation, necessary for industrial use.

The scientists applied their method to two different coffee systems. First they compared the brews of different coffee varieties and could prove that a light roasted Robusta has an approx. 25% higher total polyphenol content than Arabica. Then, an Arabica was roasted with different time-temperature profiles and varying roast degrees. The work revealed that a fast roasted coffee (10 min) respectively one roasted at a higher roast temperature has an approx. 25% higher total polyphenol content compared to slower roasted coffees, irrespective of the roast degree. It’s a satisfying result, but the researcher keeps his feet on the ground: “The coffee roasting process will keep us busy in the coming years”, he predicts. “There are many companies showing a vivid interest in our research.”

In October, the busy scientist could celebrate a special success: The 15 students of his first post-graduate program ‘The Science and Art of Coffee’ received their diploma; another training course will follow in autumn 2011. “It’s important to form highly qualified people as Switzerland is one of the most important places for the coffee industry around the globe”, states Chahan Yeretzian. “Not only were the instant coffee and the capsule system invented here: Swiss coffee machine manufacturers are the leaders in fully automated systems with a growing market, and up to 80% of the world-wide trade with green coffee is unrolled in Switzerland.”

***S. Petrozzi et al., J. of Flow Injection Anal. 28(1), 23-28, 2011

Information: www.icbc.zhaw.ch/coffee


Chahan Yeretzian, Head of Analytics and Analytical Technologies, ZHAW Wädenswil

More Information: Biotechnet

posted: 22.08.2011

Antibiotics: Inactivity is fatal

When Sir Alexander Fleming discovered the antibiotic substance penicillin in 1928, he laid the groundwork for the first efficient treatment of diseases like gangrene, tuberculosis and syphilis. Antibiotics work in two ways: Either as a bactericidal antibiotic, killing bacteria by interfering with the formation of the bacterium’s cell wall, as it’s the case for penicillin, or as a bacteriostatic antibiotic stopping bacteria from multiplying by interfering with bacterial protein production, DNA replication or other aspects of bacterial cellular metabolism. Examples of those bacteriostatic antibiotics are tetracyclines or sulphonamides. But what in the Forties used to be a blessing for the patients, now turns out to be a bane.

The fact is that antibiotics have lost their power as micro-organisms have developed a drug resistance so that they can survive exposure to the treatment. Antimicrobial resistance (AMR) has become a serious problem, now tackled by the World Health Organization (WHO). More and more infections caused by resistant micro-organisms fail to respond to conventional treatment. Most malaria-endemic countries record a growing resistance to earlier generation antimalarial medicines. In the hospital environment, more and more patients are infected by highly resistant bacteria such a methicillin-resistant Staphylococcus aureus. According to WHO registers, each year roughly 25 000 human beings are the victim of AMR in Europe. About 440 000 new cases of multidrug-resistant tuberculosis emerge annually, causing about 150 000 deaths around the world. "The inappropriate and irrational use of antimicrobial medicines provides favorable conditions for resistant micro-organisms to emerge, spread and persist", states Dr. Rainer Riedl, Head of Organic and Medicinal Chemistry at the ZHAW Wädenswil. "The longer an antibiotic has been used, the higher is the probability that it does not work anymore."

Researchers around the globe are exploring new approaches to launch a counter-offensive. At the ZHAW Wädenswil, the specialists for Organic and Medicinal Chemistry joined, two years ago, the BioVersys AG in Basle, an ETHZ start-up in order to abrogate the antibiotics resistances. For this purpose, they conceive with computer-aided design optimized active agents which they synthesize before passing them over to the biologist team at BioVersys for the tests. Their special molecules do not attack the bacteria at the metabolic level, but at their genetic constitution. Thanks to their expert knowledge about the genetics behind bacterial resistance mechanisms they recognize the pathways which are activated once resistant bacterial strains come into contact with an antibiotic. Then the patented compounds of BioVersys interfere with the activation of the bacterial defense program and the original antibiotic can kill the bacteria. That means that they obstruct the possibility for further development of resistances and to open the way for conventional antibiotics. A strategy could consist in combining both compounds in one single preparation.

The antibiotics market is one of the largest in biopharmaceutical therapeutics, with close to 27 billion US $. A successful therapy of bacterial infections, above all those caused by multi-resistant strains, will probably be based on dual-intervention strategies, like the one followed by the partners in this project.

www.icbc.zhaw.ch/organische-chemie

More Information: Biotechnet

posted: 18.08.2011

Student Exchange in Biotechnology: the Lake of Zurich meets the Vltava River

Around ten years ago the Institute of Biotechnology (IBT) at the ZHAW in Wädenswil and the Institute of Chemical Technology (ICT) in Prague initiated the first student exchanges under the scope of their research projects. In June 2011, scientists from both institutions and representatives from industry met in Prague for the 5th Czech-Swiss Symposium (part of the Biotech 2011), and decided to extend these exchanges to Master’s and PhD students.

The Czech-Swiss Symposium, a tri-annual scientific congress, was launched in 1999 by Hans-Peter Meyer from Lonza and Jan Kas from the ICT. At the recent symposium Czech and Swiss referees from academia and private industry presented the latest biotechnological innovations in the pharmaceutical and nutritional fields as well as strategies for sustainable new processes. The Swiss delegation was composed of representatives from SMEs (for example, Atheris Laboratories, Herbonis, ICB-Partners and ROOTec bioactives) and major global enterprises (such as Lonza, Nestlé, Novartis and Roche) as well as from the ETH Zurich and universities of applied sciences active in biotechnet Switzerland.

In order to establish a close link between the biotechnology study programmes in Wädenswil and in Prague, Karin Kovar, the Head of the Bioprocesses Section at the IBT, drew on her personal network. Her activities were supported by Tobias Merseburger, the Director of the IBT, who welcomed the opportunity for Swiss students to gain experience of other cultures and be exposed to different perspectives in a foreign country. The first Swiss students got to know the industrial manufacturing sites and the university research institutions in the Czech Republic in 2002. From this time Czech students have also been able to sample working on a range of applied research projects at the IBT in Switzerland.

In view of the interest shown by the industry, the Commission for Technology and Innovation (CTI) financially supported the Swiss-Czech research cooperation as part of the EUREKA-programme. These projects were also co-financed by Czech research funds. Thanks to them, the IBT now has a leading role in the implementation of a generic technology for highly productive processes with Pichia pastoris on industrial scale. This methylotrophic yeast has become one of the most important expression systems for recombinant protein production and continues to be the focus of scientists at both institutions. Moreover, Petr Hyka, a PhD student from the ICT in Prague, is currently using a flow cytometry method to investigate the influence of heterologous protein production on the physiology of P. pastoris at the IBT in Wädenswil.

Microalgae biotechnology is another field which is central to the Swiss-Czech collaboration. Until recently, the pharmaceutical application of substances derived from microalgae was unsuccessful as it was not possible to collect sufficient quantities of biomass from natural environments. However, in his Bachelor’s thesis at the ZHAW, Silas Hauser demonstrated that more than 160 grams per litre of microalgal biomass can be harvested from conventional stirred tank bioreactors in an efficient and reproducible way, independent of seasonal or geographic conditions. Using this method, raw material can be obtained to produce natural active agents which can be specifically tailored for use. In recognition of his contribution to this innovative research, Silas Hauser was awarded both the tebo implementation prize and the LISTA innovation prize.

The ZHAW sees the collaboration with their Czech colleagues as a win-win situation. “Czech biotechnologists have particular strengths in organic chemistry and basic molecular research”, commented Tobias Merseburger. “At the ZHAW, we are more application-oriented, and highly skilled in the improvement of bioprocesses based on their biological principles.” To extend student exchanges beyond the ERASMUS programme, the IBT is now increasingly turning to programmes offered by IAESTE and Sciex-NMSch. However, consolidating the future exchange of Master’s and PhD students remains at the top of IBT’s and ICT’s agendas.


Professor Karel Melzoch (left), Dean of the Faculty of Food and Biochemical Technology at the ITC in Prague, and Professor Tobias Merseburger, Director of the Institute of Biotechnology at the ZHAW, intend to sign an agreement for the exchange of Masters’ and PhD students from autumn 2011.

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posted: 11.07.2011

A bright future for microalgae: customising their composition

The Japanese are mad about Chlorella: for about 5 million people these freshwater, single-celled green algae are their daily companion as a part of their diet. However, despite the many claimed health benefits, these ‘smallest plants’ have not yet been studied in detail as a beneficial component of Western nutrition or medicine. As microalgae, highly dispersed within natural habitats of microbial consortia, their harvesting is less straightforward compared to traditional plants or seaweed with their fairly compact biomass. Therefore, until recently, microalgal biomass could neither be provided in the quantities and reproducible quality required nor propagated without the use of special photo-bioreactors. Because of the limited supply of suitable material, the research into the application of microalgae in the pharmaceutical, food, feed and cosmetics sectors was restricted. Nowadays, however, state-of-the-art technology permits standardised microalgal biomass and bioactive substances to be produced with customised properties.

“Single-celled algae grow up to 20 times more rapidly than cultivated (medical) plants and, when grown in a bioreactor, their performance is also independent of seasonal and climatic influences. Therefore, microalgae have a much better quality assessment as a source of active substances than biomass from plant cultivation”, comments Professor Karin Kovar, Head of Bioprocess Technology Section at the Zurich University of Applied Sciences, ZHAW. In a pilot project supported by the ZHAW in Wädenswil, Professor Kovar’s team has established a technology platform for the biotechnological production of microalgal biomass as raw material for natural active agents. The starting point was Chlorella as a model organism. As a facultative heterotrophic green microalgae, it could be cultivated in closed bioreactor vessels in the absence of light, under well-controlled, safe and reproducible conditions while using an organic substrate as a source of energy and carbon.

Initially the researchers had to establish strategies for the preparation of pure (axenic) initial cultures as well as for efficiently growing them in conventional stirred bioreactors of stainless steel. They opted for a fedbatch process with exponentially increasing addition of glucose and attained biomass concentrations of more than 160 g l-1 in under 5 days of operation. This concentration of biomass and the related productivities surpass those declared in current scientific journals and related patents by 50 – 100%.

If addition of a highly concentrated glucose solution is controlled to be below the rate of the maximum consumption capability of the microalgae, which means that the cells immediately consume all of the available substrate, biomass growth is also controlled. “Controlling the glucose addition is not only essential to avoid high osmolarity leading to a toxic environment, but also to promote efficient formation of a particular product under optimum conditions”, Christian Meier, a project-leader in microalgal biotechnology at the ZHAW, discloses the core principle of the process control. With their state-of-the-art understanding of microbial physiology, the Wädenswil’s team is able to produce biomass deliberately enriched by specific polyunsaturated fatty acids (PUFA) or the inclusion of organically bound micronutrients. “The latter technology, which is a promising way of enhancing the bioavailability of micronutrients and replacing traditional preparations supplemented with inorganic salts, functions on the principle of selective replacement of a particular element within an organic molecule”, explains Silas Hauser, who specialised on this topic during his Master of Science studies.

The technology developed in Wädenswil opens up new opportunities for the biotechnological manufacturing industry in Switzerland and has been recognised for its innovation and implementation potential with awards given to its developers by the tebo- and Lista-foundations in May 2011. The first project with a Swiss-based SME, which is keen to replace its plant cultivation in Asia with an advanced biotechnological process, and the ZHAW along with other partners from the University of Applied Sciences, Northwestern Switzerland, FHNW, is currently under evaluation by the Innovation Promotion Agency, CTI.


Culture of microalgae on an agar plate

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posted: 08.07.2011

Monitoring bacteria in drinking water

About 5000 people around the globe die every day from drinking contaminated water. Microorganisms are the basic problem for causing infectious diseases. Routinely monitoring the concentrations of harmful bacterial cells for better drinking water quality is therefore a priority for global health. Traditionally, analysis relies on cultivation of microbial cells and their growth to visible colonies on nutrients plates, a time-consuming and not very reliable procedure. Researchers at Eawag are breaking new grounds by making use of flow cytometry, a robust, much faster and more complete detection method for microbial cells in water samples. The enumeration of the total cell number requires not more than a few minutes. A fully automated system is now successfully applied in the central water supply of Zurich.

The technology is already well established in medicine, where flow cytometers can analyze several several thousand particles every second. Some instruments are even able to actively separate and isolate particles having specified properties. “But to make the breakthrough in drinking water analysis in daily practice, there is a need for online or fully automated and faster systems that allow the collection and analysis of large data sets and routine monitoring on a continuous basis”, comments Professor Bernhard Sonnleitner, Head of the Chemical and Biochemical Engineering Group at the ZHAW Wädenswil. For years, the internationally distinguished expert has been studying novel developments of process analytical technology in biotech applications and works closely together with the Eawag group. His approach to the present problem is an online, fully automated and real-time flow injection system coupled with flow cytometry for process monitoring. “The system constructed in our laboratories couples a bioreactor with an interface, consisting of a flow injection analysis (FIA). It includes at least a de-foaming/de-gassing and a dilution unit, and the sample transfer into a flow cytometer”, explains Tobias Broger, completing his MSc degree on the subject. “The realized prototype characterizes microbial populations as distributions on the single-cell level, qualitatively and quantitatively during bioprocesses.” It evaluates data in real-time and tunes operating parameters of FIA accordingly. The analysis of data and the bioprocess control is event-driven, the proprietary software elements are linked in order to communicate. “Our online flow cytometry allows fully automated sampling, staining, incubation and analysis of water, acquires extensive data sets repetitively with high frequency”, Bernhard Sonnleitner sums up the balance.

Meanwhile, the scientists tested the flow cytometry system under controlled laboratory conditions and used it to analyse a large-scale pilot plant biofiltration facility treating filtered and ozonized lake water. “Our goal was to assess the impact of filter operational conditions such as changes in the flow regimes and backwashing on microbial concentration in the effluent and to correlate this data to conventional microbial methods as well as online particle data”, states Frederik Hammes from the EAWAG. It looks like a success: Thanks to the microbial analysis an immediate response can be obtained in the case of dramatic events - as for instance operational troubles in the running process or deliberate contamination. Moreover, it leads to a better understanding of gradual changes like growth in biofilters or distribution systems.

The innovative system was presented at the ‘Leading Edge Technology’, the conference of the ‘International Water Association’ (IWA) in Amsterdam in order to find the necessary industrial partners for further developing the promising laboratory prototype into a marketable product.

http://www.icb.zhwin.ch/engin/index.php

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posted: 28.06.2011

An ‘old’ idea for today’s high-tech nanofibers

When, in the early 1930s, the German Anton Formhals had the brainwave to produce polymer filaments using electrostatic force, his intention was to make silk-like fibers. In the year 2011, researchers of the Institute of Chemistry and Biological Chemistry at the ZHAW Wädenswil utilize the same process. But today they make use of the fact that objects change their characteristics when they shrink down to nano dimensions. For instance, the surface grows massively in relation to the volume and the materials’ properties are shaped by the surface features. An adequate way to exploit these nano-effects are immobilized particles on electrospun nanofibers. The ZHAW team uses them to realize membranes for specific adsorption.

The fact is that membranes for solid-phase extraction (SPE) are applicable for a variety of energy-efficient separation techniques, from the selective removal of estrogenic substances in waste water to the chiral separation of pharmaceutical products. “The separation efficiency of a membrane depends mainly on the specific affinity between the membrane and the target molecule, that means, its molecular recognition and the diffusion of the substrate into the membrane, a factor mainly controlled by the membrane’s surface and porosity”, comments chemist Dr Jürgen Ebert. Together with his colleague Christian Adlhart, Head of Functional Materials and Nanotechnology, he develops synthetic polymers with tailor-made molecular recognition abilities, the so called Molecularly Imprinted Polymers (MIPs). They are able to control the specific affinity for the target molecules. Being similar to specific biological receptors such as enzymes or antibodies, they have a better chemical and physical stability and are easy to produce on a large scale. For their application in filter membranes, the MIP microspheres have to be immobilized. Best suited are membranes of electrospun nanofibers as these membranes are large-pored, an advantage for an efficient access of the filtrate. But specific adsorption can also be achieved by directly imprinting the membrane’s nanofibers during the electrospinning process or by chemical post-modification of the nanofiber’s surface with grafting techniques. “The crux of the matter is in how far the molecular recognition properties of the microspheres are changed within the membrane’s matrix”, explains Dr Christian Adlhart.

In their study, the ZHAW scientists synthesized by precipitation copolymerization of two organic compounds MIP microspheres with 4 – 5 µm in diameter for the molecular recognition of the alkaloid cinchonidine. They immobilized the microspheres by incorporating them into membranes of electrospun polyacrylonitrile (PAN) nanofibers of different diameter. Finally, the molecular recognition capacity of the free microspheres and the ones incorporated in the PAN membrane matrix were quantified by guest-binding experiments.

“With our experiments we can prove that the immobilization of functional microparticles in electrospun nanofiber membranes is a versatile and effective method for a simplified handling of micro- and nanoparticles while keeping their functionality depending on their surface area”, states Jürgen Ebert. Thanks to the microspheres’ synthesis and electrospinning techniques the researchers can scale up the process and are flexible regarding the polymer support and the microspheres’ functionality. “That’s why we expect a broader application of composite nanofiber-microsphere membranes with specific recognition abilities as SPE or filtration material for decontamination and purification purposes in water treatment as well as for food, pharmaceutical or fine chemical products.”

www.icbc.zhaw.ch/nanotechnologie

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posted: 26.05.2011

How Nanoparticles enter the Human Body: ‘Nano-Research’ at Empa

It’s hard to imagine life without nanoparticles! With a diameter of up to 100 nm, like carbon or metallic oxide particles, they are present in our daily life and enter our body almost unhampered. As small as they are, they penetrate the cell membrane and are active at the subcellular level. Their biological effects vary depending on their size, shape, chemical composition, surface texture, aggregation state and surface charge. How this takes place is part of current research, for example at the Empa in St. Gallen.

In a co-operation with Professor Ursula von Mandach, Head of Perinatal Pharmacology at the Department of Obstetrics and Gynecology of the Zurich University Hospital, the team of Dr Peter Wick, Co-head of Materials-Biology Interactions at Empa St. Gallen investigated the barrier capacity of the human placenta. Their aim was to clear up the question whether nanoparticles can affect the fetus by crossing the placental barrier. This organ acts as a barrier between the maternal and the fetal circulation. It helps to bring essential nutrients and oxygen exchange to the fetus and makes sure that the bloodstreams of mother and unborn child do not mix. After birth, the placenta separates from the uterus and is pushed out of the mother’s body. As animal models like mice and rats are not adequate for scientific tests because their placenta has another structure, many women place their placenta at the disposal of research.

In the present project, the scientists chose fluorescently labelled polystyrene beads with diameters of 50, 80, 240 and 500 nm as model particles and added them to the maternal circulation to see if they pass into the fetal circulation. “Polystyrene is the ideal material for this kind of studies”, states Peter Wick. “It is easy to detect and does not cause stress to the surrounding tissue.” As the investigations reveal, the fluorescent polystyrene particles with diameter up to 240 nm are taken up by the placenta and can cross the placental barrier without affecting the viability of the placental explant. However, bigger ones could not cross the placental barrier. “The findings suggest that nanomaterials have the potential for transplacental transfer and underscore the need for further nanotoxicologic studies on this important organ system”, comments Ursula von Mandach. The team of Peter Wick is highly motivated to continue the research work on this subject. “When we understand how the transfer into the human placenta works, we can make use of them as tiny vehicles to transport dugs in the circulatory system of an unborn child for therapeutic purposes”, adds the Empa scientists. The knowledge about these transfer mechanisms could allow the administration of medication-like analgesics or anti-inflammatory drugs for pregnant women without impairment of the health of the unborn child.

www.empa.ch

At the Empa laboratories in St. Gallen, Dr Peter Wick and his crew investigate whether particles of polystyrene (in the picture 500 nm diameter) can cross the placental barrier and affect the fetus. Polystyrene is the ideal material for this purpose as it is easy to detect and does not cause stress to the surrounding tissue.

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posted: 14.02.2011

When biofilms take centre stage

Whether in metalworking companies, in medicine, food industry or the distribution of drinking water: in many domains biofilms are unbidden guests. They enhance corrosion, create energy losses, reduce flow and heat transmission or contaminate water. Biofilms are responsible for billions of Swiss Francs in lost industrial productivity as well as product and capital equipment damage every year around the globe. That’s why this most common form of life of micro-organisms, which shows up in almost every surrounding, is combated in many domains. “This does not always make sense”, says Walter Krebs, professor for biology and microbiology at the ZHAW Zurich University for Applied Sciences in Wädenswil. “Well-controlled biofilms have favourable properties, for instance they can purify water.” The micro-biologist is specialized in the research of biofilms. With his crew at the Institute of Chemistry and Biological Chemistry (ICBC) at the Department of Life Sciences and Facility Management he conducts qualitative and quantitative analyses of biofilms in simple test systems. Possible applications are materials for drinking water pipelines, modified surfaces – e.g. biomedical devices as a new area of competence – as well as the control of measures in order to inhibit the development of biofilms.

It’s a challenging task as we recognize today that biofilms are the preferred mode of growth of microbes in a wide range of habitats. The majority of micro-organisms live in communities and form biofilms, most often located at more or less humid surfaces. Main components of biofilms are - besides the organisms - gel-like mucus made of water and extra-cellular polymeric substances (EPS) like polysaccharides and proteins. “To live in a biofilm has a lot of advantages for its inhabitants in comparison with a planktonic way of life”, points out Walter Krebs. "The EPS matrix assumes different tasks like the adhesion to the surface, the development of cell aggregates, adsorption of nutrients, water storage which means protection from dehydration, higher tolerance in face of toxic substances and a poor biodegradability. "

Biofilms cause a lot of trouble and costs, for instance in medicine (caries and parodontosis, contaminations in intubation tubes, catheter or implants), in heat exchangers where biofilms form an undesired isolation layer, in drinking water supply, air conditioning, where biofilms form an ideal habitat for pathogenic bacteria such as Legionella to live and proliferate, in the paper processing industry or the corrosion of metallic surfaces.

Walter Krebs is not the only one in this domain: Many research groups around the globe are working in the field of biofilms, both in basic and applied research, the combating of harmful biofilms being in the focus of their investigations. At the Wädenswil laboratories the researchers focus on the biofilm formation in drinking water supply, paper machines and in metalworking fluids. “We want to develop inexpensive test systems, easy to use, which enable our industrial partners to put to the proof their products which are expected to hinder the development of biofilm formation.” In an innovative approach the ZHAW scientists combine the already existing methods of cultivation and analytics of biofilms in a way to obtain user-friendly but reliable tests systems. A concrete example of a recent successful development is a method for the analysis and control of biofilms in systems for lubricating coolants in collaboration with Blaser Swisslube AG, supported by the Innovation promotion agency CTI.

www.icbc.zhaw.ch

The laboratory of Walter Krebs, professor for biology and microbiology at the ZHAW Zurich University for Applied Sciences in Wädenswil, is specialized on analysis and control of biofilms and the place to go for companies – especially small and medium ones – looking for problem solutions in this domain.

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posted: 26.07.2010

The Culture Collection of Switzerland (CCOS) – a pioneer achievement in biodiversity

In the last years working with micro-organisms and their metabolites has been on the rise and will play an important role in different domains of science and research in the time to come. In order to maintain the innovation ability and the power to of Swiss biotechnology to compete in global markets, bright minds in the biotech scene had the idea of creating a national collection of biological materials such as bacteria and yeast strains. The Culture Collection of Switzerland (CCOS) – launched as a co-operation supported by the Swiss innovation promotion agency CTI - is located at the ZHAW Zurich University of Applied Sciences in Wädenswil. It unites scientists and industrial partners as well as the Swiss Biotech Association and the Swiss Industrial Biocatalysis Consortium.

Swiss research institutions and industry have at their disposal a lot of strains of micro-organisms, which are not yet catalogued and accessible to a wider public. Nevertheless, these strains represent an interesting basic raw material for research in biotech companies, diagnostics laboratories and universities. The aim of the CCOS project is to transfer the strains in a unique collection, to enter all the data into a database and to make it available for research and development to interested parties. Of central importance are secondary metabolites and enzymes of strains, the potential for new expression systems and reference strains for diagnostics. Currently, about 400 well-characterized strains from donors are included in the CCOS. In the end the collection should offer up to 1500 strains which can then be used as reference strains, for the manufacturing of vaccines and enzyme production or as cultures for process development. Each selected strain will be scrutinized for its purity and accurate identification, numbered and included in a catalogue with its application possibilities. The controls for purity and identity of strains are essential to achieve optimal results and well-defined products as well as to ensure the safety of personnel. The strains are stored in liquid nitrogen at a temperature of -196°C and in addition will be freeze-dried to preserve the biological materials. An effective soft-ware will help to administer the strains and organize their distribution to purchasers all over the world.

As an example of the registered strains let’s have a look at Pseudomonas fluorescens, which shows a bluish fluorescence in ultraviolet light. The special feature of this strain is its ability to protect plant roots from attack by filamentous fungi. The fact of the matter is that the strain produces antifungal active agents suppressing the growth of pathogenic fungi. The strain therefore has the potential of a biological pest control. The donors of this strain are the Lausanne University and the ETH Zurich.

The CCOS has been designed to become a main repository of bacterial and yeast strains in Switzerland to serve Swiss science and industry. The CCOS has applied for membership of the World Federation of Culture Collections (WFCC) in order to benefit from the international co-operation between the individual strains collections. In the future the CCOS will be established as a platform for the distribution, the safe deposit of cultures and their identification and therewith make a contribution to preserve the biodiversity in Switzerland.

Information http://www.ccos.ch

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posted: 23.07.2010

Biotech 2010: Pioneers in single use technology meet in Wädenswil

When, in the year 1998, young American and Swiss researchers brought to market their Wave Bioreactor - in the initial phase a 1 litre-bag - specialists in the biotech scene raised their eyebrows. How should it be possible to cultivate cells in a plastic bag? But much to their surprise: it worked very well! Basically, disposable cell culture systems consist of three major components: a rocker platform, a single-use cell culture bag and an aeration/inflation pump. The rocker platform imparts the wave motion to the liquid inside the pre-sterilized bag and provides the necessary oxygen transfer and mixing for cell growth and productivity.

Very rapidly, Regine and Dieter Eibl, scientists at the Institute of Biotechnology (IBT) at the ZHAW Zurich University of Applied Sciences in Wädenswil saw a chance for these ‘disposables’ for bio-manufacturing. They began to apply single-use technology in their bioprocess and cell cultivation technology groups and their lesson plans , and initiated projects based with biotech companies. One of them is Sartorius Stedim Biotech which took over the successful Wave Biotech AG and now offers comprehensive single-use and re-usable products choices for every process step - small and large scale, upstream and downstream for medium volume range.

Single-use technologies are supposed to have a brilliant future. In contrast to their predecessors made of glass and stainless steel, which need thousands of valves, kilometres of pipe and wire and special plant space with filters and cooling equipment, disposables are easy to build up, do not need expensive cleaning and sterilization. They are flexible for different processes and cost-effective in medium production runs. Today’s bioreactor systems contain up to 2000 litres and get along with low investment costs. Still too little known is the possible impact of chemicals that may migrate into the drug product. As BPSA reveals, we have on one hand extractables, chemicals that migrate from fluid contact materials under exaggerated conditions (e.g. solvent, time, temperature) and represent a ‘worst case’ list of chemicals that could potentially contaminate or interact with the drug product. On the other hand there are leachables, chemicals that can be found in final drug products and typically include some extractables from process equipment as well as from the final container/closures or packaging along with any reaction or degradation products of those extractables and the active drug.

In order to discuss the state-of-the-art of single-use equipment und known constraints - like the questions concerning extractables and leachables- with manufacturers and users Regine and Dieter Eibl organized an international conference at the ZHAW Wädenswil on June 7-8, 2010. The echo was overwhelming: instead of the expected 180 participants more than 300 scientists and people from the industrial sector from all over Europe and the USA met in Wädenswil to discuss matters with specialists of the branch and to find out how to tap the full potential of disposables for bio-manufacturing purposes.

Co-organiser was the German DECHEMA, represented by its executive director Professor Dr. Dieter Sell. He founded in March 2010 the temporary working group ‘Single-Use Technology in Biopharmaceutical Manufacture’, conducted by Professor Dr. Dieter Eibl. The general idea is to promote the application of single-use technology in the German-speaking countries, to eliminate today’s constraints and to standardise the systems by establishing quality standards. To strengthen the position of Switzerland in the domain of single-use development and applications and to promote education and training with single-use devices, an association ‘Single-use Applications’ has to be founded. It will cooperate as an independent sub-association within the biotechnet Switzerland with the DECHEMA group as well as with institutions being active in this domain on an international level such as DIN, BPSA and ISPE.

Also an important point is education and training as industry needs skilled personnel, familiar with the handling of disposables, in order to make use of this technology. For this purpose the association ‘Single-Use Applications’ is founded as an independent sector of biotechnet Switzerland. Further participants are DECHEMA, the German Society for Chemical Engineering and Biotechnology, the German Institute of Standardization DIN, the Bio-Process Systems Alliance (BPSA) as well as the International Society for Pharmaceutical Engineering (ISPE). “Our goal is to provide with our competence centre in Wädenswil a basis for a network in Switzerland which helps the single-use technologies - with activities all over Europe - to make its breakthrough”, explains Dieter Eibl. Switzerland is in a good position to initiate this process as the country boasts a very high density of biotech firms and research institutions in the world. They have been working on disposables for about 12 years and are supported therein by the Innovation promotion agency CTI and the biotechnet Switzerland. “There is a wide range of possible applications from bio-pharmaceutical companies and personalized medicine to cosmetics and the food industry”, concludes the ZHAW professor and invites interested people to join him and his colleagues: “The association is open to all comers who like to participate in developing the use of single-use technology in bio-manufacturing.”

Information: www.ibt.zhaw.ch / dieter.eibl@zhaw.ch


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posted: 01.07.2010

3D skin models – for rapid evaluation of safety and efficacy

It was quite a revolution when the first human skin models came onto the market in the 1990s, intended for the treatment of burns and diabetic foot ulcer as well as for in vitro testing. Since then, human-reconstructed skin models have made considerable progress. They are three-dimensional and most of them can recreate the multilayered, multi-cell-type qualities of human skin. As the response of their tissue is more predictive than the conventional monolayer response, they have become increasingly important. Today, the development of new skin model products is focusing more and more on skin toxicity or skin corrosion testing as a response to the requirements of the pharmaceutical and cosmetics industry. On the one hand there is a need to improve the quality of non-regulatory testing with truly predictive efficacy models, on the other hand it is essential to reduce the cost of toxicity assays and other regulatory tests without impairing reliability.

The right address for skin models is the University of Applied Sciences Wädenswil (ZHAW), where Professor Ursula Graf-Hausner and her team of tissue engineering specialists have been working on epithelia models since 2007. To help us understand their research, let’s take a look at the human skin. It consists of two important layers, the epidermis and the dermis. The latter, also known as the corium, is about 2 to 4 mm thick and makes up 90% of the skin’s thickness. It supports the skin and provides energy and nutrition to the epidermis. The dermis is made up of a network of collagen fibres with integrated fibroblasts, which build up and degrade the surrounding matrix. The epidermis is the outer layer of the skin and acts as the body’s major barrier against a hostile environment.

Working within a Swiss BioteCHnet project the Wädenswil scientists realize their human skin models by preparing an animal collagen matrix in which human fibroblasts act as the dermal part. The epidermis is built up with either gingival or epidermal keratinocytes, depending on the type of epithelium. To form the typical epidermis layers, the cell layer on the top has to come into contact with air. After an incubation period of about 14 to 20 days, the model is ready for efficacy tests. Biologist Ursula Graf’s research group conduct their analytical testing using a state-of-the-art infrastructure that features cutting techniques such as cryo and paraffin cut, microscopy and stainings and immunohistological colouring. Moreover they are able to quantify specific target proteins and expression patterns using techniques such as ELISA or PCR. In keeping with the spirit of the Swiss BioteCHnet network, the Wädenswil scientists collaborated with their colleagues at the University of Applied Sciences Valais (HES-SO-Valais) who are a perfect complement for them. Working with Professor Sergio Schmid’s molecular biology group, a high throughput RT-qPCR approach was chosen to measure the expression level of relevant genes. This so called single-channel quantitative multiplex reverse transcriptase PCR (scqmRT-PCR) technology is ideal for robust and simultaneous quantitation of a large number of genes. Analysing the transcript expression level in human skin models provides important fundamental information about the effects of skin care products.

The cosmetic industry’s idea of using AGEs (Advanced Glycation Endproducts) as active agents for skin care products provides an ideal opportunity to demonstrate the excellent results of the project and the efficiency of the skin models. Here glycation is understood to mean the reaction of sugars with lysine side chains of proteins. Since this renders the proteins inactive, glycation results in tissue damage in the long term. AGEs, the result of a chain of chemical reactions that follow on from an initial glycation reaction, affect nearly every type of cell and molecule in the human body. Researchers are currently investigating whether it is possible to use AGEs as cosmetic substances to stimulate and intensify tanning mechanisms in the human skin. They think that one or more active agents from the AGE group or their precursors could increase melanin synthesis. They also want to explore the possibility of developing a hair dye that uses at least one AGE-group compound to stimulate melanin synthesis in hair roots and to store melanin in hair. In the course of their research they also discovered that AGE-group compounds provide outstanding protection and care for human skin.

With a surface of about 2 m2 in the adult, the human skin is the body’s biggest organ. It has many vitally important functions, including procuring and repelling thermal, mechanical, chemical and biological stimuli, and as such plays an important role in regulating human metabolism. Three-dimensional skin structures of the type elaborated by Ursula Graf’s team are an important aid in the development of new, fascinating wound healing and skin-care products and help to ensure that these can be tested rapidly in a safe environment that does not involve the use of animal-derived ingredients.

URL: www.icbc.zhaw.ch


Within the Swiss BioteCHnet project researchers from Wädenswil and Sion realized human skin models by preparing an animal collagen matrix in which human fibroblasts act as the dermal part.

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posted: 23.06.2010

Annual report 2009

The annual report 2009 is now available.

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posted: 07.06.2010

Clearing the ground for drugs with fewer side effects

The event is still fresh in mind: In the 90’s the antiallergenic drug Seldane (terfenadine) was in wide use. But what the patients didn’t know: A toxic effect had slipped the attention of the developers. The active agent could obstruct the so called hERG channels on the surface of the heart muscle cells and therewith hamper the heart muscle to contract. Severe cardiac arrhythmias happened, some of them with fatal consequences. Since then, the pharmaceutical industry has continually been elaborating better standards for toxicological studies, tries to find out the interactions between active agent molecules and functions, to better understand adverse reactions and to choose molecules which do not cause negative effects. If they find evidence of a binding to the hERG channel, the development is stopped or expensive animal experiments are performed in order to clarify the risk of cardiac arrhythmia. The question was how to reduce the compound attrition of active agent molecules with better in-vitro tests and inclusion of structural information in drug discovery of small molecules. The result would be more pharmaceutically efficient drugs, faster development times, safer drugs and a quicker ‘time-to-market’.

In order to increase the understanding of the molecular interaction of drug molecules with the hERG channel and how this blockade affects the function of this important ion channel, scientists of the biotechnet and F. Hoffmann-La Roche Ltd. teamed up to generate protein in a quality and quantity useful for biophysical methods. Of course, the information of the 3D structure of the hERG channel, unknown to date, represents the ultimate goal of this long term project as this could allow prediction of the interactions between active agent molecules and the channel and enable reduction of the binding (‘anti-target’) using drug design methods. Their first effort was the expression and purification of the hERG channel. Their research was based on the knowledge acquired within the NCCR (National Centre of Competence in Research) ‘Structural Biology’, which for the first time was carried out in a project supported by the innovation promotion agency CTI to fill in the gaps with the competencies from the biotechnet.

While Roche contributed its expertise in cloning, expression and analytics, the Zurich University of Applied Sciences (ZHAW) Wädenswil contributed to cloning, expression and in high density cultivation, the Zurich University helped with the purification and crystallization of the protein. The biotechnet was at hand for scientific advice and project administration.

The project partners pursued four principal goals: First they aimed at an efficient heterologous expression of hERG in adequate eukaryotic systems, which they judge to be better suited than E. coli. Eukaryotic systems offer crucial advantages for the manufacturing of membrane proteins as they produce protein with good yield and functionality. A second step in the project was the extraction, purification and stabilisation of the protein. Function tests had to be established as well as the high grade purification of the protein with special methods that include working with a diverse set of detergents. Finally, the usability of the protein for biophysical methods as well as crystallization for the X-ray crystallographic determination of the structure of the hERG channel was evaluated.

“The co-operation as well as the organization, the composition of the working groups and the project progress were optimal and I was impressed by the high motivation of all researchers involved”, comments PD Dr Michael Hennig, Vice Director at Roche. There’s a lot at stake for the industrial partner, as the success of the project aims to optimize the discovery process with a reduction of the attrition rate in lead finding and shorter development times, fewer animal experiments and an enhanced product safety. Professor Daniel Gygax, President of biotechnet concludes: “The unique combination of technologies realized within this project and provided by academic institutions and industry in a joint effort enabled a significant progress of the project.”

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posted: 07.04.2010

ZHAW Wädenswil – soon the prime address for filtration problems?

Filtration and separation are the ideal ways of removing troublesome or even toxic substances from a liquid. This can concern industrial processes from paint and varnish, electronics, grinding and polishing to electroplating and optics, health care like pharmaceuticals, biotechnology as well as beverage and food industry or in a general sense water processing. Very common means are on the one hand membrane filters, thin and highly porous materials which let liquids or gases pass, but retain particles at the surface. On the other hand depth filter sheets are used which have a high capacity to absorb pollutants, serve for the filtration of bigger particles, but also for germ reducing and sterile filtration. Besides the purely mechanical retention of particles, there are electrostatic forces which exert an influence on the filtration impact. Certain filters are doped by cationizing agents with a positive electric potential which causes the adsorption of microorganisms and negatively charged endotoxins – heat-stable components of the bacteria’s cell membrane.

„Among other things there are charges at the surface of the used filter aid or membranes that cause the undesirable loss of flavour and active substances, which frequently occurs in production processes or leads to coagulation in the fractionation of blood plasma“, declares Dr. Jürgen Ebert, lecturer at the Institute of Chemistry and Biological Chemistry at the Zurich University of Applied Sciences (ZHAW). „We would often like to specifically remove a repugnant taste, pyrogens and special compounds from a product without affecting the other ingredients.“ But this is not an easy thing to do as we only have a quite empirical knowledge about the characteristics of the filter aid, limited mainly to technical parameters like the permeability or the particle and pore dimensions. For the chemist, who was responsible in industry for the development and the fabrication of depth filter sheets, there is no doubt: Only with a systematic acquisition of crucial data can we establish a basis which gives industrial partners the possibility to rapidly select the convenient filter aid for a specific task and to obtain an optimal filtration. The economic aspect is vital, as the correct solution means a better filtration performance, a reduced loss of active agents and a higher yield.

Suitable instruments for the characterization of organic and inorganic filter aid are measurements of the zeta potential, gas adsorption as well as analysis with the Scanning Electron Microscope (SEM). The zeta potential is a measurement of the surface charge of a particle and correlates with the magnitude of the repulsion or attraction between particles. Its measurement brings detailed insight into the dispersion mechanism and is the key to electrostatic dispersion control. The measurement of zeta potential is an extremely important parameter across a wide range of industries including brewing, ceramics, pharmaceuticals, medicine, mineral processing and water treatment. It gives information about adsorption phenomena or the dispersing mechanism and allows making use of certain material properties in a more efficient way.

In a first step, a student characterized inorganic and organic filter aid in depth filter sheets, supported by the industrial partner Filtrox AG. In summer 2009, Dr. Ebert started a systematic study on inorganic kieselguhr and perlites with the aid of Schneider Umwelttechnik AG, a raw material supplier. This cooperation was established within the pilot project Innovation cheque for SME launched by the Innovation promotion agency CTI. The team of Dr. Ebert also works together with the BTG Instruments GmbH, producer of zeta potential systems and global market leader for cost-effective ways of improving the productivity of the pulp and paper industry.

„The collaboration between the University of Applied Sciences, the raw material supplier and the systems developer serves as an example“, notes the scientist. „On one side the project benefits from the competences of all partners, on the other side we are sure that the propagation and the commercialization of the results takes place through different distribution channels.“ The ambitious goal of Dr. Jürgen Ebert is to make available for all industrial partners the know-how concerning the solid-liquid separation and the analytical infrastructure of the institute for application-specific questions of filtration processes. Building-up these competences in Wädenswil could soon make the ZHAW the prime address in Switzerland for filtration and separation technologies.

Information
www.icbc.zhaw.ch
juergen.ebert@zhaw.ch

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posted: 01.03.2010

Malignant brain tumours: how to detect and treat them

When Edward Moore ‘Ted’ Kennedy, Senator from Massachusetts, died in his home in Hyannis Port on August 25, 2009, we suddenly had to remember how aggressive the most frequent brain tumor, Glioblastoma multiforme (GBM) is. In the United States, about 60% of the estimated 17’000 primary brain tumours diagnosed are gliomas. And the chances for healing are small; only modest advancements in the treatment have been made in the past 25 years.

An innovative way of treating brain tumour is being pursued by neurosurgeons, cell biologists at the Zurich University of Applied Sciences (ZHAW), physicists at the University of Applied Sciences Northwestern Switzerland (FHNW) and the surgical division of Leica Microsystems AG in a research co-operation. Generally, malignant gliomas are surgically resected and patients are treated by a combinatory radio- and chemotherapy. Nevertheless, survival rates remain very low. The use of 5-aminolevulinic acid (ALA) is a promising approach to achieving better clinical results due to the ability of ALA to be metabolized into the fluorescent product protoporphyrin IX. “PplX accumulates in tumour cells and can be visualized during the operation by a special microscope with a fluorescence filter. It also can be irradiated with visible light for photoactivation. This leads to the generation of reactive oxygen species and therefore the induction of cell apoptosis”, explains Professor Vera Luginbühl, head of the pharmaceutical technology group at the ZHAW. She has been working together with Dr Martin Hefti, neuro surgeon at the University Hospital Schleswig Holstein, for a few years and establishes cell culture models to evaluate in vitro effects of ALA on human glioblastoma cells. In 2007, the research group received the Synthes Award for the in-vitro studies of effects of the 5-aminolevulinic acid on five different glioblastoma cell lines. Aim of the new project is the development of an imaging system, integrated in the surgeon’s microscope, which quantifies the fluorescence intensity, visualizes the results cartographically and offers the possibility of superimposing this view with a ‘live’ microscope image. By this means, the surgeon obtains a rational decision support, which increases precision and sensitivity and helps to avoid interpretation mistakes. “The new method not only improves the clinical results substantially, but – thanks to a better treatment method – the hospital can realize considerable cost savings.” For the industrial partner the measuring system offers a good chance of consolidating his or her leading market position and opens promising perspectives on a future application in the photodynamic therapy (PDT).

The group of Pharmaceutical Technology of Vera Luginbühl deals with research, development and production of pharmaceuticals, the evaluation of production processes, the formulation of active ingredients as well as registration and quality management in production. In April 2008, the group merged with their colleagues in cell biology in order to make use of synergies in a more efficient way. Their competences now comprise the drug formulation development, dissolution, development of controlled release systems (drug delivery systems), micro-encapsulation, biocompatibility testing, bioactivity testing of growth factors, drug analysis and in-vitro cell culture models.

And important activity is continuing education for interested companies, e.g. for marketing departments, regulatory affairs personnel, field staff etc. The courses for the Novartis Learning Center and Aprentas provide training in drug design, formulation, selection of excipients, manufacturing and dosage form characterization.

www.pharmazietechnik.ch

Protoporphyrin IX enrichment in human glioma cells. Confocal laser scanning microscopy, magnification 600x.

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posted: 15.02.2010

Sophisticated simulation for bioreactors

Computational Fluid Dynamics (CFD) is an advanced technique to calculate complex flow patterns in fluid mechanics - the physics of liquids and gases - with numerical simulation. CFD software helps engineers, for instance, to compute the flow around a turbine blade or to optimize the aero- and hydro-dynamics of transportations without being compelled to test the design with expensive prototypes.

This state-of-the art engineering modelling using 2D and 3D flow simulation is the ideal tool for researchers at the Zurich University of Applied Sciences in Wädenswil. The group of Professor Dieter Eibl at the Institute of Life Sciences and Facility Management works on Biochemical Engineering and Cell Cultivations Techniques. In its focus are complex aspects of the cultivation of microorganisms and plant, animal as well as human cell and tissue cultures from t-flasks up to 100 litre scale. This interdisciplinary approach of the comprehension of biology, biochemistry, molecular biology, fluid dynamics, engineering and thermodynamics forms a successful basis for numerous co-operations with industrial partners. One example is the qualification, further development and validation of bioreactor systems. Bioreactors have to meet high requirements concerning homogenization and dispersion, which means that mixing time and power input have to be adjusted carefully. In particular animal cell cultures have to be mixed and aerated very gently. On the basis of CFD simulation the Wädenswil scientists can gain an insight into flow characteristics and the forces which impact on the single cells. They are in a position to optimize existing bioreactors, develop new efficient systems and can scale up facilities from the laboratory to the industrial production scale.

Large reactor volumes and disposable bioreactors with new mixing concepts are a challenge for the scientists who have to ensure controlled cultivation conditions and optimized scale-up and scale-down strategies. In a master thesis a researcher examined the application of CFD to calculate the mixing time and the oxygen transfer in a stirred bioreactor. In large reactors we observe inhomogeneities which cause an undersupply of the cells with nutrients or an accumulation of metabolic products. If you have an aerobic cultivation of cells you need sufficient oxygen which has to be guaranteed continuously. With a high cell density the mass transfer from the gas to the liquid phase can constrain the reaction. While in microbial fermenters usually the power input is increased in order to obtain a better mixing and a more intensive mass transfer, the cultivation of animal cells is more difficult. In contrast to plant cells with an inner cell membrane and an outer cell wall, animal cells only have a cell membrane as outer barrier. Unlike micro organisms and yeasts, the cell membrane of animal cells is less stable, not at the least because of their larger diameter and the corresponding surface-volume ratio. They react more sensitively to mechanical stress and force impact, for instance shearforces. If their cell membrane is damaged, they cease their biologic activity and die off. That’s why homogenization and gas supply have to be performed as gently as possible.

Up to now, the design and the characterization of bioreactors have been made mainly based on physical laws and empirical correlations, assuming that the mixing is excellent. By way of contrast, CFD generates locally and temporally resolved data. “With numeric fluid dynamics we obtain parameters, which we generally cannot capture by experiments or, if so, only with a considerable expenditure”, comments Professor Dieter Eibl. “CFD is therefore the ideal instrument to predict the flow pattern and location- and time-dependent gradients of temperature, pressure, velocity and shear stress.” As CFD parameter studies can be made with less costs than experimental tests, the simulation method progressively finds its way into the development and optimisation of processes.

In order to deepen their knowledge even more, the ZHAW scientists complement their existing infrastructure on the one hand with Particle Image Velocimetry (PIV), a contact-free optical method for measuring the flow velocity, on the other hand with shadowgraphy for the 2D measurement of the velocity and the particle size distribution of particles, drops and gas bubbles.

More Information: Biotechnet

posted: 08.02.2010

Juiceliner: From the vineyard right into the barrel

„Wine is among the beverages the most useful, among the medicines the most pleasant and among foodstuff the most delicious”, confessed Plutarch (50 – 125). But before the precious nectar can ripen in the oak vats, it is subject to hostile attacks of quite dangerous enemies. When it is time for the grape harvest, the winegrowers do their best to let the grapes enjoy the late summer rays of sunshine for as long as possible. But the riper the grapes get, the more vulnerable they are. Mildews and insects like wasps may injure the berry skin so heavily that the juice can seep out. That is the grapes’ Achilles heel: Immediately micro organisms colonize the delicious source of sweetness and reproduce beyond all measure. “This time frame between the vintage and the beginning fermentation is very risky from an oenological point of view”, comments Professor Tilo Hühn, director of the Centre for beverages and flavor research at the Zurich University of Applied Chemistry (ZHAW) in Wädenswil. “Uncontrolled enzymatic activities and the propagation of undesired micro organisms affect the quality of the grape juice.” Once the wine yeast Saccharomyces cerevisiae has transformed the must into wine, the danger is warded off.

In order to shorten the time slot between the harvest and the processing of the grapes, Tilo Hühn has developed together with ERO Gerätebau GmbH, specialized in machines for viniculture since the 1970s, and Westfalia Food Tec, world-wide leader in mechanical separation systems, the Juiceliner. This sophisticated and unique grape harvester - with a juice extraction device integrated - extracts the juice from the grapes immediately after they are harvested, right in the vineyard. A first prototype took hits path successfully through German vineyards in 2005, one year later in Chile and in the year 2007 in France. “The Juiceliner offers the possibility to close the sensitive gap in the grape processing chain”, says Tilo Hühn. “It allows harvesting, juice extraction and must pre-clarification in a continuous process directly in the vineyard, leaving grape peelings, seeds and leafstalk as a natural fertilizer.” The Juiceliner relocates the work normally taking place in the wine cellar onto the place of harvesting, cutting down working time. Already a few minutes after picking them, the grapes are pressed, the Juiceliner has the automatically running enzymatic reactions of the squeezed grapes down pat. Micro biological processes are reduced to a minimum, which guarantees best quality. Tests show that the juice and the resulting young wines are of a quality comparable to conventional processing methods.

“It would now be nice to integrate a cooling system in order to further reduce the micro biological activity”, announces Tilo Hühn his future plans. And possibilities have still to be found to bring down the price. “Granted, acquisition costs of 400’000 Euro are a bit close to the bone, but the harvesting quality is really outstanding and the Juiceliner can be in action for a 2 hour cycle 20 hours a day. No vintager would agree to do so.”

The prospects are good for the Juiceliner: Due to the change in climate the vintage begins earlier than in former times, and the warm and humid weather is favors grape rottenness. From all over the world wine-growing estates are showing interest in the new hard-working member of staff in the vineyard, especially service supply agencies and co-operatives of growers.

www.beverages.ch

More Information: Biotechnet

posted: 03.10.2009

The mystic world of coffee

No, we are definitely no coffee planters. But we were the first ones to have the flash of genius of making soluble coffee; we invented those funny multicoloured capsules with coffee portions now known all over the world and we are the leading producers of fully automatic coffee machines. "Nearly 70% of the global green coffee trade goes through Swiss hands", says Chahan Yeretzian, professor at the Zurich University of Applied Chemistry (ZHAW) in Wädenswil and leader of the analytical chemistry group. With 6 years of international experience in academic teaching and research and 11 years of leadership experience within the global Nestlé R&D network he is an internationally recognized specialist in the science of coffee. His main interest at the ZHAW - where he moved in 2008 - is the development and application of mass spectrometry based on online analytics to unravel the mysteries of coffee.

In 2008, mass spectrometry allowed him to realize a powerful predictive tool for coffee sensory profiles. By applying a novel chemometric strategy, Chahan Yeretzian and his crew could accurately predict sensory profiles of espresso coffees of different cup sizes and flavor profiles based on Proton Transfer Reaction-Mass Spectrometry (PTR-MS). Correlation was conducted according to a knowledge-based standardization of sensory and instrumental data. "Our key to success was a procedure removing the information of absolute intensities leading to data sets essentially containing only quality information, i.e. sensory profiles and instrumental data”, the chemist explains. "Thereafter correlation could be completed according to well-known procedures of principle component regression (PCR)." The developed robust and reproducible model was derived from 11 different espresso coffees and validated using 8 additional ones. It applies to espresso coffee as well as to Lungo.

PTR-MS was also the basis for an experiment in coffee roasting. With this technology the coffee expert wanted to explore the impact of the time-temperature profile on the formation kinetics of volatile organic compounds. For this purpose, green coffee was roasted in a laboratory scale fluidized bed roaster to a fixed end point (dark roast) using different roasting temperatures (isothermal roasting) - 228ºC, 238ºC, 248ºC and 258ºC.The formation kinetics of selected ion masses were monitored on-line by PTR-MS. Strong differences in the formation kinetics of compounds underlying the ion masses were observed, as a function of roasting temperature. The results of this study were presented at the 4th International Proton Transfer Reaction-Mass Spectrometry conference in Austria in February 2009.

Although Switzerland is at the fore in science of coffee, there is a lack of trained people in this domain. With the help of the already existing know-how at the ZHAW and his personal relation network Chahan Yeretzian has created a new course, elaborated with the Swiss Chapter of the Specialty Coffee Association of Europe (SCAE), starting October 16, 2009, and resulting in a Certificate of Advanced Studies (CAS). On 26 days university graduates and experts with professional experience in the coffee business give an insight into the science of coffee and the whole value-added chain. Special topics are cultivation, technology, chemistry, sensor technology, preparation of beverages, trade and marketing as well as social and ethical aspects. Moreover the course gives the participants the chance to make contacts and to enlarge their relationships within the Swiss branch of coffee.

www.icbc.zhaw.ch/coffee

More Information: Biotechnet

posted: 15.09.2009

Sophisticated bio reactor for implant development Explanations for video ‘BioReaktor’

Biological implants for the reconstruction of hard and soft tissue are the favorite playground of Professor Ursula Graf-Hausner, group leader of the Tissue Engineering group at the Zurich University of Applied Sciences. In order to study the interactions between biomaterials and human fibroblasts, the researchers have developed - in a project financed by the CTI, the innovation promotion agency -, a bioreactor for mechanical stimulation. A kind of little sponge made from resorbable biomaterial serves as a scaffold for the buildup of soft tissue. It is made of collagen, a structural protein of the conjunctive tissue present in humans and animals. Its fibers are extremely ductile and have tensile strength. The cell biologists colonize (pipette) the collagen matrix with human fibroblasts under conditions imitating the mechanical stress in a closed soft tissue wound. The bioreactor has six experimental chambers, adapted to the pressure and the shearing forces of wound tissue. The performed in vitro tests allow the evaluation of the behavior of the cells and the tissue generation under conditions coming very close to those in a living organism, which helps to further advance the development of tissue replacement.

Download reactor movie

www.icb.zhaw.ch

More Information: Biotechnet

posted: 19.08.2009

Annual report 2008

The annual report 2008 is now available in the download-section.

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posted: 19.07.2009

Bridging the gap between research and market needs

Membrane proteins give researchers quite a headache: their production is extremely difficult and costly. But for institutions like the NCCR Structural Biology (National Center of Competence in Research) they are important as target structures in the development of new active substances. Partners from the Swiss Biotechnet therefore joined the NCCR in order to realize innovative methods for the expression, production, cleaning and management – solubility, stability and functionality - of membrane proteins.

The focus of attention was an important human ion channel, called hERG (human ether-a-go-go-related gene). Very clean and milligram quantities of protein are required for the crystallization and subsequent structure determination of hERG in order to improve the knowledge about the interaction of substances with this potassium channel. Inhibition of hERG with potential agents may point to possible serious side effects like cardiac arrhythmia of a future medicament. Within the project the hERG protein had to be produced, characterized, purified and made available in large quantities. That is why in a first step an efficient expression system was identified and so a recombinant protein made available in adequate quality and quantity for protein crystallization and the examination of protein-ligand interactions with biophysical methods.

This challenge required the linking of the best heads available. Under the umbrella of the Biotechnet Switzerland which was responsible for the overall project, the Fachhochschule Nordwestschweiz (FHNW) in Muttenz was responsible for the project coordination. The contribution of the Zürcher Hochschule für Angewandte Wissenschaften (ZHAW) in Wädenswil was the cloning, expression and production of recombinant proteins in yeast, insect and mammalian cells as well as wave technology. The Hoffmann-La Roche AG Basel - experienced in human membrane proteins - provided cloning, expression and analytics, while the NCCR located at the University of Zürich looked for the cleaning of the proteins and the crystallization. The NCCR team, well versed in the preparation and characterization of membrane proteins, managed also the structure elucidation of the bacterial membrane proteins.

The competitive advantage for the Roche company is obvious: “This is certainly a very challenging project with high risk to deliver”, comments Dr Michael Hennig, Vice Director and Head of Discovery Technologies at Roche Basel. “The CTI brings together excellent Swiss academic groups and the interest of the industry to share expertise, resources and risks. It would be great if we could contribute with this project to a better understanding of hERG system in order to discover safer drug molecules.”

For Dr Daniel Gygax, President of the Swiss Biotechnet, this cooperation in the domain of the ‘production of bio-molecules’ is a showpiece for the bridge-building between the Swiss National Science Foundation (SNF) and the innovation promotion agency CTI, linking the competences of both the Swiss Biotechnet and the NCCR. “The newly developed technologies represent a breakthrough in the production of membrane proteins.”

Illustration:

Infection of Sf9 cells with virus of hERG(1-870)-GFP-His, Expression of hERG protein and association with the membranes is evident

More Information: Biotechnet

posted: 21.05.2009

Stopping fire blight’s hide-and-seek tricks!

Fire blight takes no prisoners when attacking flowers and shoots of apple and pear trees, and many garden and forest plants. After infecting plants, the pathogenic bacterium, Erwinia amylovora, rapidly spreads throughout plants causing a burnt appearance and can lead to the death of a tree in one or two years. Flowers fail to give fruit, green shoots turn black and branches die.

The cause of this devastating disease survives Jack Frost by hibernating inside diseased cankers on woody branches and reactivates in the spring as temperatures increase. Diseased plants ooze a sticky sweet sap that can fall like rain in an orchard. This attracts insects, especially bees that spread the disease like wildfire to other plants, and can be spread long-distance by gusty wind and rain.

Fire blight is the major economic threat to apple/pear production in Switzerland, and worldwide. Conservative estimates in Switzerland are that fire blight monitoring and sanitation alone have cost over 80 million CHF since 1989. This doesn’t begin to consider the loss of valuable landscape and ecological cornerstone old-growth trees (Hochstamm) or wild plants like Sorbus and Hawthorn.

“Just as in medicine, rapid diagnosis of fire blight is the key to effective implementation of control measures; and this also can improve Swiss trade in fruit plant material”, says Brion Duffy, plant pathologist at the National Competence Center for Fire Blight ACW. In a CTI project, supported by the Innovation Promotion Agency, his research group cooperated with the diagnostic company BIOREBA AG in Reinach/BL in realizing a simple market-ready diagnostic tool for rapid and sensitive diagnosis of fire blight in the laboratory and field. In this partnership, novel antibodies that are specific for Erwinia amylovora werde put on an AgriStrip, just like a pregnancy test. BIOREBA was the first company worldwide to produce and commercialize ELISA reagents for plant virus diagnostics, and in this project they have expanded to bacterial diseases. “In our collaboration with Dr. Duffy we wanted to adapt the existing and successful method to fire blight by developing and validating novel antibodies against the full biodiversity of strains of the fire blight pathogen Erwinia amylovora, with unlimited production capacity and standardised quality”, explains Walter Bitterlin, virologist and Director of BIOREBA.

This innovative AgriStrip test is based on lateral flow immunochromatography for cheap and routine disease diagnosis that is simple to use, putting more power into the hands of plant inspectors and fruit growers. A clever use of the AgriStrip test is integrating it with disease forecasting models in order to aid grower decision making, enabling them to optimise the timing of expensive control products for when and where the pathogen is present, thus reducing fruit-production costs and environmental impact. ACW and BIOREBA are now working on improving the sensitivity of their test to detect very low levels of pathogen cells.

Global demand is high for such a simple diagnostic tool to reduce costs for nation-wide monitoring, to improve use of control products by integration with forecasting models, prevent importation of infected plant material, and provide an affordable tool to routinely monitor pathogen spread. The range of potential customers is wide. “Responsible persons in agriculture who wish a quick diagnosis so they can rapidly take effective measures, maybe consultants, producers of field or greenhouse cultures, inspectors or – in the case of fire blight – services of plant protection”, says Walter Bitterlin. He is very satisfied with the cooperation between ACW and BIOREBA which is illustrating the synergy of public and private institutions in efficiently producing and validating a market-ready product for practical application. The new AgriStrip will be brought on the global market in January 2009.

More Information: Biotechnet

posted: 12.01.2009

Olten Meeting – A contact forum for biotech

The annual Olten Meeting organized by biotechnet switzerland and the Swiss Biotech Association is a place for biotech specialists from the universities and Empa to meet up with people from the private sector to network and initiate joint projects. A look at the presentations given at the event on 19 November 2008.

Up to now, cell-culture technicians have believed that it would be impossible to record the expression of a target protein inside a reactor because the expressed protein would have to undergo extensive processing before it could be quantified. This is now set to change thanks to a new measurement technology developed by Professor Bernhard Sonnleitner and his team.

Fluorescing reporter molecules

Sonnleitner, a lecturer in biochemical engineering at Zurich University of Applied Sciences (ZHAW) in Wädenswil, modified optical measurement probes of the kind used to determine the turbidity of a cell suspension to make them into fluorescence probes. These can measure the fluorescence of reporter molecules inside the reactor – i.e. in situ – completely automatically, non-invasively and in real time. This method is based on Green Fluorescent Protein (GFP) from a jellyfish, which is expressed as a fusion protein at the same time as the target protein in, for example, cells of Pichia pastoris, a methylotropic species of yeast. The researchers stimulate GFP-expressing cells with blue light and the cells in turn emit longer-wave green light. The fluorescence is transmitted to a detector using a fibre-optic receptor probe.

In this project, which is being supported by the federal innovation promotion agency CTI, the scientists in Wädenswil are also working with their industrial partner Aquasant to investigate whether they can record other fluorescent proteins and expand the measurement method to include strains other than the conventional model organism P. pastoris. Sonnleitner is confident. "This measuring technique provides quantitative information about protein expression during the process and could therefore develop into a useful platform technology which would permit better control of upstream and downstream processes."

Focusing on molecular structure

Structure-based drug discovery is the main focus of the activities being pursued by Dr Michael Hennig, Vice-Director of Pharmaceutical Research at Hoffmann-La Roche Ltd. This involves exposing crystallized proteins to synchrotron light and determining their atomic structure from the resulting refraction pattern. The ideal tool for this is the Swiss Light Source, the synchrotron source operated by the Paul Scherrer Institute, which has a Pilatus detector capable of providing data in seconds. Knowledge of the structure of compounds makes it easier to characterize the results of high-throughput screening (HTS) and hence to select a promising lead compound. Optimization of the lead compound involves improving its binding to the target protein and its molecular properties. In this way, structural knowledge helps to optimize the active substances in existing medicinal products and to develop new active substances.

One example is the protein DPP-IV which cleaves and thus inactivates GLPS1 (glucon-like peptide), thus preventing blood glucose from normalizing. If this peptidase – dipeptidyl peptidase IV, to give it its full name – can be inhibited, it should be possible to achieve higher concentrations of GLP1 in diabetic patients and thus to lower their blood glucose levels. "Elucidation of the structure of the target molecule helped to accelerate the identification of molecules that inhibit DPP-IV and to broaden the basis of this work," is how Michael Hennig sums up the situation. "This enabled us to optimize substances that were very different in structural terms and ultimately to test them in the clinical setting."

Aromatase inhibitors to treat breast cancer

Professor Ajay S. Bhatnagar, former head of endocrine research at what was Ciba-Geigy and is now Novartis, is working on the impact of laboratory developments on patients' lives. His special field is aromatase inhibitors in the therapy of breast cancer. Aromatase plays a critical role in oestrogen synthesis, and the enzyme is therefore regarded by experts as a good target for selective inhibition. It was on this basis that the drug Letrozol was developed, in the expectation that maximum suppression of oestrogen would lead to maximum suppression of the tumour. The first and second-generation aromatase inhibitors were not satisfactory because they were not selective enough, but the third-generation compounds are now inhibiting oestrogen production effectively, reducing circulating oestrogens by more than 95% in some cases without affecting other steroid signalling pathways. Modern aromatase inhibitors combine a low rate of side effects with high selectivity and efficiency, and this prevents the hormone-sensitive tumour from growing. "The extent to which aromatase is inhibited determines the clinical success of treatment," Ajay Bhatnagar explains. "This is why the development of aromatase inhibitors represents a paradigm shift compared with the previous therapeutic standard with antioestrogens."

Antibodies armed with active substances

Dario Neri, Professor of Biomacromolecules at the Institute of Pharmaceutical Sciences at ETH Zurich, is working on the binding and catalytic properties of proteins as a new approach to cancer therapy. One of the main focuses of his work is monoclonal antibodies as tumour killers. "Cancer cells form new blood vessels in a process known as angiogenesis, and this supplies the tumour with oxygen and nutrients via the circulation," Neri explains. "What we need to do is stop this process which is vital for the tumour's survival, and this will stop its growth." His team is therefore loading active substances into monoclonal antibodies. The antibodies make straight for the blood vessels that supply the tumour and destroy them. No harm is done to blood vessels that are not associated with the tumour.

Neri and his team are producing their first successful results with three monoclonal antibodies that are being tested clinically in the therapy of kidney and pancreatic cancer. Dario Neri won the SWISS BRIDGE Award in October 2008 for his work. The award is conferred on scientists pursuing outstanding research in the fight against cancer.

Individual structures made from titanium

The annual incidence of craniocerebral trauma is around 8,000 per million inhabitants. If malformations, bone degeneration and the removal of tumours are added to this figure, the need for individual implants becomes clear. Researchers at the Institute of Medical and Analytical Technology (IMA) at the University of Applied Sciences of Northwest Switzerland (FHNW) in Muttenz are tackling the problem using layer-building processes similar to the rapid prototyping method that has been used in technical applications for over 20 years. They derive three-dimensional data sets from the computed tomograms of a patient, for example, and use the data to produce anatomical models. The overriding considerations here are biocompatibility and biofunctionality. The success of integrating a titanium implant into the bone depends on its surface topography and surface chemistry. A rough surface on the implant ensures that it will be anchored well in the bone and thus have excellent biomechanical stability. This is why the team at the IMA is modifying the surfaces of patient-specific implants by sandblasting, spark anodization, electropolishing, anodization or etching so that they can be used in trials. Implant materials used for clinical applications have to be capable of dealing with considerable mechanical stress, so their structural properties are systematically investigated using metallographic structural analysis and dynamic mechanical testing under simulated real-life conditions. A technique known as Selective Laser Melting is used particularly for implants required in surgery of the mouth, jaw and face.

The advantages of the method over established manufacturing methods are obvious. Medical rapid prototyping provides flexibility, enables complex implants with an internal structure to be created, is fast, and enables individual pieces to be produced without tools straight from CAD or medical imaging data. It is also economical, ideal for small numbers of parts since it involves no programming or tooling costs, and also makes efficient use of expensive materials. "Work is still at the research stage," comments Professor Michael de Wild from the IMA. He believes that custom-made implants have a bright future. "Market studies are forecasting double-digit growth rates!"

More Information: Biotechnet

posted: 11.01.2009

Cells’ repair service for disc regeneration

Who has never experienced it? You bend down to pick something up from the floor and you suddenly feel like a sword has stabbed you in the back! You are not alone: Four out of five people suffer from low back pain at some time in their lives. It’s the most common condition prompting visits to physicians after the common cold. Although low-back pain is a common, though benign, self-limiting disorder it can persist in about 5-10% of individuals. The lumbar intervertebral disc (the pillow-like cartilage cushion between the vertebrae) undergoes dramatic changes with age and therefore has become the prime suspect for specific persistent low-back pain. After failure of non-operative treatment, today’s most frequent surgical treatment aims at treating the symptoms of persistent back pain by removing the intervertebral disc and replacing it by bone (spinal fusion). “However, there must be more target-oriented, timely and minimally invasive ways of eliminating pain other than fusing two vertebrae and eliminating spinal motion” says Prof. Boos, Head of Spinal Surgery at the University Hospital Balgrist, Zürich. For a successful and long-term regenerative therapy, we have to strike the evil at its root and become active at the biological level.

Thanks to new knowledge in molecular biology, cell biology and material sciences, innovative strategies are currently being developed. They include biomaterials, cells and growth factors in order to regenerate the human intervertebral discs. Although the biological repair of the affected tissue by cell-based tissue replacements has been successfully applied to bone and cartilage and the therapy looks very promising, its application on the human disc is in a very early stage. Today, cell cultivation is a labour-intensive procedure, requiring many hours of repetitive routine work. The results often depend on the skills of an individual and are poorly repeatable by other lab technicians. The call for automating the whole cultivation process including cell growth, harvest, reseeding and analysis is evident. In order to improve the consistency of the process and reduce laboratory costs we need automated and standardized cell propagation equipment.

A well-known ‘incubator’ for fresh ideas in cell cultivation is the crew of Professor Ursula Graf-Hausner at the Zurich University of Applied Science in Wädenswil. She initiated a project supported by the CTI, the Swiss Innovation Promotion Agency. Partners are Tecan Schweiz AG Männedorf, a leading global supplier of solutions for the biopharma, forensic and diagnostic industries, the University Hospital Balgrist with its famous Centre for Spinal Surgery as well as the recently founded Spine Research Group at the Competence Centre for Applied Biotechnology and Molecular Medicine at the University of Zurich. Their goal is to develop an automated liquid handling robot with advanced cell culture characterization devices, based on an automated liquid handling robotic system by Tecan, for the propagation of primary cells for creating tissue. “Our model cells are for the isolation and automatic proliferation of intervertebral disc cells”, explains Ursula Graf, member of the biotechnet. “The clinical applications for these cells are approved and manual baseline culturing processes are already established within our consortium. Moreover, there is a strong demand for non-fusion therapies for painful intervertebral degeneration.” Special emphasis is placed on repeatability, robustness and data traceability. For Tecan the project is very promising. “An automated high-throughput system will make it easier for research laboratories in industry and academia to robustly cultivate primary cells from various tissues and to study the effect of various compounds in an efficient, standardized and safe manner”, says Dr. Roland Durner, Marketing Manager at Tecan.

All over the world scientists are investigating new biological treatment strategies to routinely cure disc degeneration, but realistically a practicable solution might not be available in the near future. However, the new findings gained from this research and development efforts are moving closer towards efficient therapies. Professor Boos is convinced that “this project will bring us a major leap forward in our attempt to replace or regenerate a painful intervertebral disc by biological means. This will be a major breakthrough in applied musculo-skeletal basic research which will help thousands of back patients!”

Cellerity Corning flasks 24 Septum Piercing

Cellerity, vollautomatisches Hochdurchsatzsystem für Zellwachstum und die Arbeit mit Zellkulturen

More Information: Biotechnet

posted: 05.12.2008

Fungi – the welcome intruders

When they cover our bread with a white fur, cause us a painful sore throat or are on the rampage in historical murals we could wish them to hell. But watch out! Microorganisms populate this blue planet far longer than we do, in fact about 3.8 billion years, and by the way: they also prove to be very useful. Think of the panoply of the fungus Penicillium roqueforti that gives Stilton its savoury taste, or the complex microbiological process they are involved in Port wine that goes with it. Living organisms like fungus are the best decomposer, for instance of wood, where they can perform miracles.

Around the globe, the availability of precious and durable wood for building materials is declining. It’s true that in Switzerland 65% of our forest stand consists in Norway spruce (Picea abies) and European silver fir (Abies alba). But unfortunately their low natural durability limits their use as an outdoor construction material. In order to improve wood properties and make it more usable, its modification with chemical substances or by resin impregnation has become a challenging research topic. But there is another sticking point as these wood species cannot be impregnated with wood treatment products. To solve the problem scientists had the brainwave to improve wood permeability by using biological agents, a process termed ‘bioincising’.

Within the scope of a study financed by the ‘Fonds zur Förderung der Wald- und Holzforschung FFWH’ Francis Schwarze from the Empa Wood Laboratory investigated how to optimise the permeability in heartwood by introducing the white rot fungus Physisporinus vitreous. “The fungus preferentially degrades the pit membranes of bordered pits in the heartwood of conifers under controlled conditions and could therefore enhance the permeability of the wood without inducing significant strength losses”, explains Francis Schwarze, who is also Professor for Forest Pathology at the Albert-Ludwig University in Freiburg and specialized in wood decomposition in living trees by fungi. “With this approach, several processes for wood modification and finishing could be significantly improved.” The study was a success and proved the feasibility under laboratory conditions, because the hyphae – i.e. the vermicelli like cells of the fungus – penetrate the wood actively, in contrast to other inactive substances.

Given these promising results, other players in this domain showed interest. Soon a common project was initiated under the direction of Francis Schwarze and Mark Schubert with the help of the CTI, the Innovation Promotion Agency and financed mainly by Ciba Specialty Chemicals Inc. The objective of this biotechnet enterprise is to optimise the assimilation and distribution capacity of the wood as well as the penetration depth of impregnating and finishing agents. While Empa offers its scientific know-how on wood decomposition, the Institute of Life Technologies of the University of Applied Sciences in Sion places its experience in fermentation and fungus solutions at the disposal of the project partners. From the industrial side participate industrial partners such as Bois RIL SA in Palézieux, specialist for wood impregnation, Böhme AG, producers of wood protection and finishing products, and the fungicidal producers ISP AG with headquarters in Wayne/USA. There’s a lot at stake for the project partners, as points out Francis Schwarze: “If we can realize the up-scaling from the sterile and controlled laboratory conditions to the industrial level, it would be possible to fit out Norway spruce and European silver fir with the hardness of oak and the same durability like teak wood, enabling a much better economic and ecological use of wood as renewable resource.”

The CTI project was presented by Dr Pierre-Henri Dubuis of the Institute of Life Technologies in Sion in his conference ‘Bioincising of resinous wood with the basidiomycete Physyporinus vitreous’ at the Third International Summer School in Advanced Biotechnology at Palermo in August 2008.

Fig. 1. Heartwood specimens of Picea abies (top) and Abies alba (bottom) impregnated with the bluish dye Neolan Glaucin E-A after six weeks incubation with Physisporinus vitreus. Numbers refer to radial and tangential uptake of water in kg m-3; arrows to the direction of hyphal colonization. (Picture Empa)

Fig. 2. After twelve weeks, most bordered pits showed partial to complete dissolution of pit membranes, so that both apertures of pit of pit pairs were occasionally exposed (arrow). Reproduced from Schwarze et al. (2006). (Picture Empa)

More Information: Biotechnet

posted: 01.12.2008

Olten Meeting on 19th of November 2008

biotechnet switzerland and Swiss Biotech Association are glad to invite you to the annual Olten Meeting on November 19th in Olten. The event guarantees for interesting contacts with possible partners for future projects. Stimulating and fascinating discussions are provided by the topics of the lectures.

The lecturers are: Prof. Daniel Gygax, president of biotechnet switzerland, Prof. Bernhard Sonnleitner from the department of chemistry and biological chemistry at ZHAW, Prof Michael Hennig, vice director Pharma Research Basel, Prof. Elmar Heinzle, University of the Saarland, Prof Ajay S. Bhatnager, CEO World Wide Services Group Ltd., Muttenz, Prof. Dario Neri, Institute of Pharmacy at ETH Zurich, Prof. Michael de Wild, School for Life Sciences, and Nic Alexakis, executive Swiss Biotech Association. The program starts at 9 a.m., participation is free of charge.

Registration by Fax +41 34 426 43 91 or by e-mail to franz.baumberger@bfh.ch. Details

More Information: Biotech Today

posted: 17.11.2008

Fewer costs due to miniaturized CAS system

Computer Aided Surgery (CAS) is the basis of minimal invasive surgery, guiding the surgeon safely through all operation steps. Since today’s CAS systems are still suffering from teething problems and lack precision in many applications, Bruno Knobel developed a miniaturized, handheld tracking system for CAS. To solve the technical problems, Knobel asked the CTI, the innovation promotion agency, for support to make a feasibility study and found an ideal backing at the Institute for Medical and Analytical technology at the School of Life Sciences at the FHNW in Muttenz.

With help of Professor Erik Schokommodau and his crew, two functional prototypes have been realized, which obtain a precision ten times better than with classical systems. The systems will allow surgeons to substantially shorten the time between diagnosis and surgical treatment. The scientific task for the future will be the optics development and the chip realisation. At the School of Life Sciences at the FHNW in Muttenz, the team of Prof. Erik Schkommodau will find the specialists in software and camera systems under the same roof. Details here and here.

More Information: Biotech Today

posted: 17.11.2008

Knowledge Management for Biotech People

Information and networking can contribute considerably to the success of an enterprise when used in an intelligent an effective way. With this idea in mind, the Institute of Applied Simulation at the ZHAW in Wädenswil created the website www.xbiotech.ch. The job marketplace with its matching tool offers companies a smart way to find people on a European level who have the competencies, experiences and soft skill that are required for a job.

The literature portal facilitates SME orders for publication with its comfortable research possibilities and direct order services. The resource sharing is a platform which helps companies to make better use of existing synergies and resources, e.g. for expensive equipment biotech companies often need but generally cannot afford. Finally, the technology transfer site gives access to two databases, to the Swiss Technology Transfer Association (swiTT) and to the Enterprise Europe Network Switzerland. Details see here and here.

More Information: Biotech Today

posted: 17.11.2008

Medtech Award 2008

In vitro studies under biomechanical stimulation with an innovative bioreactor system lead to a successful network project which was nominated for the Medtech Award 2008 and won the prize for interdisciplinary R&E of Zurich University of Applied Sciences ZHAW in September ( ursula.graf(at)zhaw.ch).

More Information: Biotech Today

posted: 17.11.2008

Better patient care – fewer costs

Computers have long since made their arrival in the operating theatre and into surgical practice, improving patient care and evaluating risks. Computer Aided Surgery (CAS) is today the basis of minimal invasive surgery, guiding the surgeon safely through all operation steps. But in spite of the high tech involved, these CAS systems are still suffering from teething problems. Their key elements – the navigation systems – lack precision in many applications. A serious problem is that the markers are often hidden by the user. The systems are rather bulky, complex to install, not ergonomic and much too expensive.

For years Bruno Knobel worked on the design and construction of optical tracking systems. One day, he decided to put his experience to use in the development of a miniaturized, handheld 3D tracking system for CAS and, in spring 2007, to start up in a company – the Naviswiss AG - for the sale of his products. He asked the CTI, the innovation promotion agency for support to make a feasibility study and then searched for an adequate partner to solve the technical problems.

The ideal backing was offered at the Institute for Medical and Analytical technology, one of the four institutes the School of Life Sciences in Muttenz is composed of. Professor Erik Schkommodau and his crew are well up in smart implants, visual analytics, personalized therapeutic systems, image based diagnostics and planning. In an interdisciplinary collaboration with the physicians of the Kantonsspital Bruderholzspital and the Universitätsspital Basle they tackled the CAS job. First they asked the clinic users for their requirements and defined their demands. With two industrial cameras they designed a system, developed special markers visible from the tracking systems and the medical imaging. Especially the marker development is a demanding task concerning sterilization and geometry. “But we had the chance to find within the biotechnet materials specialists who advised us to use ceramics”, Erik Schkommodau says. “As laser writing failed, we developed a special procedure to structure the material and succeeded.” The results are markers 15 mm in diameter with a smart system of coordinates. “We obtain a precision ten times better than with classical systems.” As to the software installed, the searcher integrated a marker recognition programme. Photogrammetric modules serve for the calibration and the transformation from 2D to 3D. The integration of the medical data, however, will make up part of another project. Also a task for the future will be the optics development and the chip realization. The partner for this step will be found within the institutes of the Muttenz University of Applied Sciences. “That’s our advantage”, says Erik Schkommodau. “Here we find specialists in software and camera systems development, important for medical applications, under the same roof.”

The first part of the project was closed in June 2008; two functional prototypes have been realized and the results obtained up to now look very promising. The system will allow surgeons to substantially shorten the time between diagnosis and surgical treatment, simplifying the individual steps of the surgery treatment and providing quality management. A priority application may be dental implant surgery, as the combination of the miniaturized and hand-held system with visual and x-ray imaging techniques will considerably reduce the number of individual working steps. The patient will enjoy a shorter waiting period, the medical insurance scheme the reduction in costs.

www.fhnw.ch/lifesciences/ima

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posted: 15.09.2008

Knowledge Management for Biotech People

Information and networking can contribute considerably to the success of an enterprise when used in an intelligent and effective way. With this idea in mind the Institute of Applied Simulation (Institut für Angewandte Simulation) at the ZHAW in Wädenswil created the website www.xbiotech.ch. It was developed by the crew of Professor Marcel Burkhard within a CTI project with the help of the Innovation Promotion Agency. Four fields of particular interest assist small and medium enterprises (SMEs) to obtain and manage useful information.

You’re looking for a technician in your laboratory, a consultant or a managing director for your company? The job marketplace with its matching tool is at hand. A clever algorithm compares the competence of the job seeker with the job profile of the job offer on a European level. The matching not only takes into account the education, language skills and diplomas, but also experience and soft skills like the ability to work in a team, an independent working method and others.

The literature portal facilitates SMEs orders for publications with its comfortable research possibilities and direct order services. Due to high order quantities you enjoy reasonable prices. A central administration prevents double orders within the same company.

The resource sharing is a platform which helps companies to make better use of existing synergies and resources. Especially biotech companies often need expensive equipment they generally cannot afford. They therefore depend on second-hand apparatus or free capacities of other companies. These, on the other hand, are happy to rent out devices they do not need for the time being in order to reduce costs.

Finally, the technology transfer site gives you access to two databases:

  • swiTT: The Swiss Technology Transfer Association is active in the transfer of technology from institutes of public research and education, university hospitals and other non-profit organizations to the private economy.
  • The Enterprise Europe Network Switzerland (ex Innovation Relay Center). It supports SMEs operating in Europe and beyond, develops their innovative potential, gets them involved in EU policy-making activities directed to the entrepreneurship support by collecting and conveying feedback from SMEs to the Commission. The network offers entrepreneurs the broadest range of one-stop shop service which will give opportunities to develop and internationalize their entrepreneurial activities.

Two examples of concrete results of the www.xbiotech.ch are The Swiss Industrial Biotechnology Platform, founded by the Swiss Biotech Association (SBA), and supported by the Swiss Chemical Industry Association (SGCI) and the Swiss Industrial Biocatalysis Consortium (SIBC).

The Antibody Platform, used as an information and informal networking opportunity for start-ups and pharmaceutical companies who have biopharmaceuticals in research pipelines which are based on antibodies.

Today the life science industry represents a global business. The access to the best talents, the adequate partners in academia and industry is therefore the key to success. With the CTI project www.xbiotech.ch, the Swiss Biotech Association (SBA) and the Young European Biotech Network YEBN have taken the initiative to face this challenge.

Information: www.xbiotech.ch

More Information: Roland Gassmann

posted: 13.09.2008

Eve’s temptation – the comeback of a ‚cider apple’

The fresh and juicy fruit was hanging on the tree of wisdom – too big a temptation for Eve who could not resist, with all the consequences we know. Let’s face it: we aren’t even sure whether it was an apple. But if so, it surely came from the Uttwiler Spätlauber, an old apple tree, very popular in times when long shelf life was an important argument. For decades, this robust, spherical apple with little acidity had disappeared from the market stalls. But now what was once classified as a ‘cider apple’ celebrates its comeback as an ingredient of high-tech cosmetics thanks to a group of researchers at Mibelle AG Biochemistry.

The scientists wanted to take advantage of the excellent storability and thus longevity potential of the Uttwiler Spätlauber by extracting plant stem cells and incorporating them into cosmetic products to keep skin cells longer fresh and young. They therefore developed PhytoCellTec™. This patented technology is based on the unique totipotency of plant cells and makes use of their wound healing mechanisms. Totipotent means, that in contrast to human cells, every plant cell has the ability to regenerate new organs or even the whole plant. The Mibelle researchers hurt a part of the plant in order to induce the formation of callus cells. This wound healing tissue consists of dedifferentiated cells which are stem cells. Callus cells are harvested and cultivated in a suspension. A helping hand came from the University of Applied Sciences in Wädenswil. The team of Professor Regine Eibl, leader cell cultivation technique, established apple suspension cells and optimized their cultivation in the wave bioreactor. This novel bioreactor is a simple perfusion system which guarantees highest productivity for all processes where product formation is proportional to cell density. To obtain the PhytoCellTec™ Malus Domestica cosmetic ingredients, the stem cells are harvested and homogenized at 1200 bar. This high pressure homogenisation technique decomposes the plant cells, releases the beneficial constituents and stabilizes oil- and water soluble components. The constituents are then – together with liposomes – encapsulated in liquid nanoparticles.

“With this method plant cells grow under laboratory conditions in isolation, outside of the intact plant”, explains Dr. Cornelia Schürch, Head of Product Development at Mibelle. “This offers the advantage of obtaining products of a high quality and a guaranteed standard.” As Mibelle is thus not restricted by seasonal harvesting, the company can look for naturally sourced active substances. “We need only a very small amount of the plant cell material to cultivate the cells”, the biochemist adds. “So there is no risk of over harvesting threatened species.” This may be a key factor in the future as more and more companies choose exotic sources from Asia, Africa or the Amazon region for their active ingredients, which raises questions about environmental sustainability. The cell cultivation in laboratory gives the possibility of manipulating the cells, exposing them to stress, ultraviolet light or special agents to obtain a higher quantity of a specific substance and improving the manufacturing output by selecting the most productive cell lines.

“The production of plant cell suspension cultures in bioreactors guarantees defined controlled process conditions and minimizes or prevents variations in product yield and quality, which simplifies process validation and product registration”, underlines cell specialist Regine Eibl. “Bioreactors significantly affect cultivation results by accomplishing and controlling the optimum environment for effective cell growth and production of bioactive substances.”

In April 2008, the Mibelle scientists presented their innovation PhytoCellTec™ Malus Domestica at the in-cosmetic™ in Amsterdam, the leading global business platform for personal care ingredients and won the European Innovation prize for cosmetics and chemistry. It is the first plant stem cell active ingredient launched on the market. I bet you ten to one that today’s Eve will not resist the temptation to test the anti-ageing effect of the Uttwiler Spätlauber…and neither will today’s Adam.

More Information: Dr. Daniel Gygax

posted: 03.06.2008

Detecting bad bugs in wine

It’s happy hour! Relax and enjoy a glass of red wine with a good conscience then some scientists tell you it protects you against heart disease, raises the good HDL cholesterol and prevents LDL, the bad one, from forming. But the wine can cause some severe problems for the winemaker before it becomes a pleasure for you. His declared enemy is Brettanomyces bruxellensis, useful for the fermentation of Belgian beers, but an insidious intruder in wine. This yeast is not a bacterium, but a unicellular type of fungus, leading frequently to wine spoilage. It’s true that yeasts are the tiny micro-organisms doing the hard job in winemaking. In freshly crushed grapes you will find many different species which disappear as soon as fermentation begins and alcohol rises. Only Saccharomyces cerevisiae remains, but decreases in number when the alcoholic fermentation is completed. When all the sugar and nutrient supplies are used up, the process is finished and we should have a stable wine. Nevertheless, when things do not develop well, it’s the time for spoilage bugs to develop, above all the feared Brettanomyces. Its metabolic activity produces chemical substances that our nose perceives as cow dung, sweaty saddle leather, bandaid, medical, spicy, barbeque sauce or monkey faeces. As up to now there did not exist any reliable and economically acceptable method to prevent these micro-organisms, the best thing to do was to try to detect and eliminate the culprit at a very early stage. With the existing microscopic analyses it was necessary to get together 1’000 to 10’000 cells in a millilitre to prove the presence of these micro-organisms. This number of cells is however more than enough to produce undesired substances. These substances have no health impact, but prevent us from enjoying the wines.

In a project supported by the CTI, the Swiss innovation promotion agency, experts in analytics, microbiology and molecular biology invented a new and more sensitive method of detection. Under the leadership of Jürg Gafner, Professor at the Agroscope Changins-Wädenswil Research Station ACW in Wädenswil, specialists of the Zürich University of Applied Sciences (ZHAW) in Wädenswil and the University of Applied Sciences Western Switzerland HES-SO in Sion formed a R&D network in order to develop an innovative detection system for Brettanomyces bruxellensis. A helping hand came from industrial partners like the Biolytix AG for molecular biological analyses, the supermarket chain COOP, the ETS Laboratory specialized in equipment for science and technology, and Lallemand Inc., a Canadian based producer of yeast and bacteria. The result of this intense cooperation is a very rapid detection system that delivers data within 25 minutes without any prior enrichment step. “The necessary cell density is 1’000 to 10’000 times lower than with conventional microscopic methods and only 2 millilitres of test materials are needed”, comments biologist Jürg Gafner. “We can detect the yeast species even in mixtures and in the future we will be able to distinguish between living and dead micro-organisms. The good price-performance ratio gives the system a real chance on the market.”

So please lean back and enjoy your glass of wine – thanks to this excellent network collaboration Brettanomyces bruxellensis will not impair your happy hour pleasure anymore.

Website: www.acw.admin.ch


The yeast Brettanomyces bruxellensis, a major cause of wine spoilage worldwide (picture ACW)


Lab place at the Agroscope Changins-Wädenswil Research Station ACW in Wädenswil

More Information: Juerg Gafner

posted: 28.03.2008

Networking – the way to success

Start-ups are the most dynamic forces in the life sciences and biotech scene. But often they lack the necessary resources for basic research and rapid application development to secure the desired market shares. To solve this problem, the HeiQ Materials AG has created a clever model. This spin-off company of ETH Zürich was founded in 2005. Its aim is to develop inorganic nanocomposite particles. Fields of application for HeiQ’s particles are the textile, plastics, coating, cosmetic and medical sectors. For CEO Carlo Centonze an R&D network is the ideal instrument to implement HeiQ’s ideas. HeiQ decentralizes specific steps of its research and development, tries to win the support of the most expert research partners in the field, but takes charge of the project coordination.

An example of this procedure is the realization of a healthcare focused product application development of HeiQ’s silver-silica powder, a nanocomposite structure composed of silver nanoparticles supported throughout a matrix of amorphous silicon dioxide. The agglomerated SiO2 matrix forms a particle with a size of about 1 µm containing many silver particles of 5 – 20 nanometer. The silver particles act as a reservoir, releasing silver ions, strongly active agents against bacteria. Very problematic and widespread micro-organisms in the healthcare sector are for instance Metycilin Resistant Staphylococcus aureus (MRSA). It is a spherical bacterium, living frequently on the skin or in the nose, and becoming more and more resistant against existing antibiotics. To develop a new barrier additive for medical devices, HeiQ asked for help the best brains in the network: Empa St. Gallen, the University of Basel, the ETH Zurich, the INKA (Institut für nanotechnische Kunststoff-Anwendungen), and the FHNW (Hochschule für Life Sciences) became partners in a project supported by the CTI, the Swiss Innovation Promotion Agency.

The outcome is a strongly antimicrobial nanocomposite made of 20% silver metal and 80% amorphous silicon oxide which has an excellent dispersion in polymers and liquids, shows light stability and thermal stability even for processing above 400°C. These outstanding results convinced the German B. Braun, who supplies products and process-orientated services to the healthcare industry worldwide, to get exclusive rights for special applications in their medical implants. With 33’000 collaborators, realizing a turnover of 3.3 billion Euro in 50 countries, B. Braun is one of the ‘big players’ around the globe. “Without our R&D network this partnership would not have been possible”, says Carlo Centonze. “The R&D network gives us the chance to work with top scientists for basic research and allows HeiQ a rapid application development backed-up by reliable and reproducible results. This capability makes us unique as a start-up and trustworthy in the eyes of a demanding multinational group.”

Based on HeiQ’s new silver technology two new products will be put on the market in 2008: one is an extremely durable antimicrobial textile finish, the other is a highly resistant antimicrobial coating for plastic and metal surfaces. In February 2008, the HeiQ crew will extend its R&D network beyond Switzerland and start a project with the University of Cambridge. HeiQ today works on a daily basis with nine cutting edge research institutes

The HeiQ model ‘networking for innovation’ – a way to success.

More Information: Dr. Daniel Gygax

posted: 05.03.2008

Brains networking for innovative technologies

The BÜHLMANN Laboratories AG in Schönenbuch has a good nose for focussing on niche markets, not being addressed by the big diagnostics companies because of the limited market volume. The SME develops and produces for the Life Sciences industry, holds market shares with products to make easer diagnosis, to prove the therapeutic efficiency of drugs and to predict changes in patient conditions. In order to always be one step ahead of its competitors, BÜHLMANN was looking for a technology platform for a quantitative, easy and rapid determination of biomarkers for diagnosis and prognosis in toxicology, cardiovascular and other risk verifications as well as wellness and successful ageing purposes. On one hand BÜHLMANN is interested in gamma hydroxybutyrate (GHB), an easily producible chemical substance. GHB is used by physicians to treat disorders in the sleep-awake rhythm, by bodybuilders to get muscle power, and in the techno scene as a pep pill. Nevertheless, its consumption is risky as it causes a state of confusion and drowsiness, may lead to traffic accidents. The new enzyme test allows for the first time to detect smallest traces of the drug in the urine by an easy and fast procedure. On the other hand, BÜHLMANN is developing a new, non-radioactive enzyme test to determine the presence of vitamin B6. Especially elderly people and pregnant women may be lacking this vitamin important for protein metabolism, red blood cell metabolism and proper functioning of the nervous and immune systems. Recent studies show that a deficiency can provoke cardiovascular diseases. The company also wants to realize a test for monitoring oxidative stress, resulting in cardiovascular problems, dementia and diabetes. For this demanding technology step, the BÜHLMANN crew asked Daniel Gygax, Life Sciences technology expert and professor at the Fachhochschule Nordwestschweiz (FHNW), for advice. He started off a CTI project, supported by the Innovation Promotion Agency, and called in the Basle University Hospital. The FHNW researchers had the tricky task to realize the biological components. Therefore they produced suitable recombinant and highly active enzymes, developed modified – that means catalytically inactive enzymes - for the specific binding of the target molecules. The laboratory physicians at the Basle University Hospital will have the job to test these diagnostic assays und validate them in clinical studies. Although the work is not finished yet (in autumn 07), Michel Angelo Sciotti has already taken stock of his experience. „For the time being we are in the optimization phase for two of the tests, vitamin B6 and GHB, and will soon validate them”, says the FHNW project leader. This project symbolizes the biotechnet objectives: Let’s link the best brains available in order to realize innovations and put them on the market ‘just in time’!

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posted: 21.11.2007

Pictures Summer School 2007

The pictures from Summer School 2007 can be seen at the biotechnet gallery.

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posted: 05.11.2007

Annual report 2006

The annual report 2006 is now available in the download-section.

More Information: webmaster

posted: 11.06.2007

New Corporate Design for Swissbiotechnet

The Swissbiotechnet has a new corporate identity and name. It is now officially called biotechnet Switzerland. This name was already commonly used. The new CI and branding was jointly developed and designed by aeschbacher consulting and Büro für Kommunikationsdesign, Basel. The IT tasks were done by the IT services from FHNW. Ursula Graf from biotechnet comments: "The executive board is thrilled by the new CI and highly confident that the improved branding will be very successful. The new CI and design will officially be launched at the Olten Meeting on November 15th."

More Information: Ursula Graf, Zürcher Hochschule Winterthur

posted: 13.11.2006