Tecan Journal Edition 01/2011

Tecan Journal Life Sciences ❙ Clinical Diagnostics ❙ Forensics ❙ OEM ❙ Business and Technical News

Edition 1/2011

Australian wine – in search of perfection page 14-15

Infinite® 200 PRO provides a comprehensive solution for cell-based measurements page 5

Seeing is believing pages 18-19

High throughput HIV screening with Freedom EVOlyzer® pages 26-27

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CEO WELCOME TECAN JOURNAL 1/2011

As Tecan’s 30th anniversary celebrations come to a close, we’ll be looking ahead to another exciting and promising year, with the unveiling of novel technologies at this year’s Lab Automation Conference in Palm Springs, California. This annual event traditionally gives the international scientific community the first chance to see technological breakthroughs that will help to push the boundaries of laboratory research and development, and this year will be no exception, with the introduction ‘of the Cavro® Air Displacement Pipettor (ADP) technology for the Cavro Omni Robot liquid handling platform. This new innovative technology will complement our premium liquid displacement technology, allowing Tecan to offer the best of both worlds for automated liquid handling.

Next generation sequencing will still be a hot topic for visitors and our automated library preparation will be prominent on the Tecan booth, along with several applicationbased solutions, some in association with our industrial partners. In addition, you will have an opportunity to see the new HydroSpeed™ microplate washer that is setting the standard for ease-of-use and application flexibility.

Details of many of these new products and technologies can be found in this issue of the Tecan Journal, as well as the usual mix of news, events and outstanding customer testimonials describing what Tecan solutions do best, plus a report about wine production in Australia that will make us all think differently the next time we raise our glasses!

Enjoy,

Welcome

Thomas Bachmann, CEO

CONTENTS TECAN JOURNAL 1/2011

page 4

Advanced Cell Protection™ settings for washing of adherent and loosely adherent cells

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page 6

CEO welcome

4 Cavro® ADP – a new innovation for liquid handling 4

Innovative HydroSpeed plate washer launched

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Infinite® 200 PRO provides a comprehensive solution for cell-based measurements

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Integrated Adaptive Focused AcousticsTM for the Freedom EVO®

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Tecan enjoys success at China Forum on Transfusion Medicine 2010

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Read. Wash. Win(ner)!

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Automated solutions for cell biology

10-12 A meeting of minds for worldrenowned scientists 13 page 10

Automated multiplex assays offer novel newborn screening solution

page 26-27

High throughput HIV screening with Freedom EVOlyzer®

Contents

14-15 In search of perfection 16-17 Creative customer competition – We love our Tecan 18-19 Seeing is believing 20

Multichannel head 384 vital to investigation of gene regulatory networks

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Moving on to new challenges – Martin von Lueder

22-23 Improved plate washing for ELISpot assays 24-25 Innovation in action 26-27 High throughput HIV screening with Freedom EVOlyzer® 28-29 Crystal clear results 30-31 Ensuring quality and reliability 31

Leading the debate

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Events

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PRODUCT NEWS TECAN JOURNAL 1/2011

Cavro® ADP – a new innovation for liquid handling Tecan has launched the new Cavro Air Displacement Pipettor (ADP), a compact, pneumatic pipetting solution for easy integration and exceptional liquid handling performance. The Cavro ADP is a fully programmable, pneumatic pipetting module designed for integration into instruments requiring minimal maintenance or where space is at a premium. Using pneumatic technology in a Tecan Cavro product for the first time, this innovative module gives you an automated pipetting solution that is smaller than ever before, using air displacement to aspirate and dispense fluids. Correct operation is monitored by onboard pressure-based liquid level detection and self-diagnostics.

Excellent pipetting performance is demonstrated from 1-1000 μl, using a range of Tecan’s high quality disposable tips, and an integrated tip ejector allows tips to be ejected by a simple command. The Cavro ADP’s tip sensor can determine if a disposable tip has not been correctly picked up, or has fallen off the probe, flagging and logging errors to increase process security and aid validation of customer instrumentation, particularly for diagnostic applications.

To find out more about the Cavro Air Displacement Pipettor, visit www.tecan.com/components

Innovative HydroSpeed™ plate washer launched The HydroSpeed plate washer is an advanced system for optimized washing of cells, beads and ELISAs in 96- and 384-well formats. It offers full control over critical wash parameters, via an intuitive touchscreen interface, with extra gentle drop-wise dispensing and tunable aspiration settings to help avoid loss of material and maximize assay efficiency.

The HydroSpeed features advanced Cell Protection™ settings for washing of adherent and loosely adherent cells, allowing the user to dial-in extra gentle wash parameters to suit their cells, microplates and application. The system’s innovative Anti-Clogging™ function takes the hassle out of ELISA washing by automatically rinsing and soaking the wash head when the instrument is idle between runs, and the Easy X-change system allows rapid removal and replacement of wash

heads for intense ultrasonic cleaning.

The HydroSpeed uses a patent pending design with two magnets per well for high performance magnetic bead washing, offering fast bead settling and excellent recovery rates, and can also be equipped with a vacuum filtration module for processing of non-magnetic beads.

The HydroSpeed can be used in conjunction with Tecan’s Connect™ plate stacker for greater throughput efficiency, allowing semi-automated processing of up to 50 plates, or integrated into a Freedom EVO® liquid handling platform to offer fully automated processing for cell-, beadand ELISA-based assay workflows.

To find out more on Tecan’s HydroSpeed plate washer, visit www.tecan.com/cell-protection

HydroSpeed offers reproducible washing for magnetic bead-based assays

HydroSpeed plate washer

PRODUCT NEWS TECAN JOURNAL 1/2011

Infinite® 200 PRO provides a comprehensive solution for cell-based measurements The new Gas Control Module (GCM™) for the Infinite 200 PRO is a breakthrough for cell-based assays, offering precise regulation of oxygen or carbon dioxide levels within the reader chamber for the first time. Variations in environmental conditions can lead to inconsistent and unreliable data for cell-based optical studies, due to changes in the pH and color of the media during incubation. The GCM provides a more stable culture environment over time, making it ideally suited to in vitro investigation of eukaryotic cell lines and allowing the duration of cell-based experiments to be extended without adversely affecting results.

The GCM also ensures greater biological relevance for a wide range of studies, by allowing assays to be performed under hypoxic or physiological conditions. This will extend the experimental window of microplate-based investigations using anaerobic or facultative anaerobic bacteria, allowing incubation within the reader chamber. It also allows the Infinite 200 PRO to be used for a range of biomedical studies, providing researchers with a simple mechanism for studying cell behavior under changing environmental conditions, mimicking events such as ischemia or oxidative shock for in vitro investigation.

To find out more on Tecan’s Infinite 200 PRO and Gas Control Module, visit www.tecan.com/gcm

Infinite 200 PRO with Gas Control Module

Integrated Adaptive Focused Acoustics™ for the Freedom EVO Tecan is collaborating with Covaris, Inc. to integrate Adaptive Focused Acoustics (AFA) non-contact acoustic sample preparation technology into Freedom EVO workstations.

High quality, reproducible sample preparation is the critical first step in improving analytical results, and Covaris’ highly controlled AFA system sets the standard for today’s rapidly advancing analytical technologies and sophisticated assays. This joint offering will be available to customers worldwide, providing a scalable, turnkey solution for automated sample preparation, compound management and next generation sequencing applications.

Kevin Moore, Tecan’s Director of Market and Application Management for BioPharma, commented: “AFA is gaining widespread acceptance in the compound management

community for rapid thawing, mixing and dissolution of samples, as well as for DNA shearing for next generation sequencing.

We are extremely pleased to be working together with Covaris to provide valuable automated solutions to our customers working in these areas.”

To find out more about this application, visit www.tecan.com/covaris Adaptive Focused Acoustics is a trademark of Covaris, Inc.

Adaptive Focused Acoustics (AFA) sample preparation technology on the Freedom EVO workstation

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CORPORATE NEWS TECAN JOURNAL 1/2011

Tecan enjoys success at China Forum on Transfusion Medicine 2010 Tecan recently attended the 5th National Congress of the Chinese Society of Blood Transfusion (CSBT) and China Forum on Transfusion Medicine 2010 at the Pride International Conference Centre of Chengdu in Sichuan Province, China. This international event attracted more than 1,000 experts from around the world to discuss the current challenges, trends and innovations in blood transfusion medicine. The symposium provided an excellent opportunity for both Chinese and international delegates to exchange ideas and share their experiences, and was accompanied by an exhibition showcasing the latest medical devices and technologies designed to support this sector.

Tecan China worked closely with its local distributors to demonstrate the many advantages of automated liquid handling processes in this area, enjoying a steady flow of visitors to watch its state-of-the-art solutions, such as the powerful Freedom EVOlyzer® ELISA processing workstation, in action.

Alongside the main symposium and exhibition, Tecan hosted a satellite symposium on quality assurance and automated process security in the clinical environment. Günter Weisshaar, Head of Quality Assurance and Regulatory Affairs at Tecan, gave a presentation on the Company’s medical device product life cycle, detailing

Mr Jinming Li speaking at CSBT

Tecan representatives and guests at CSBT (left to right): Yingguang Wu, Yuan Zhang, Jinming Li, Günter Weisshaar, Kirsti Tavast, Cary Shang

how this improves patient safety while better meeting the processing and regulatory needs of its customers. Tecan also invited Mr Jinming Li, Director of the Immunization Division and the National Center for Clinical Laboratory, Chinese Ministry of Health, to speak on the importance of automation during ELISA processing and genetic testing in blood banks, providing the audience with a user’s perspective on the many advantages of laboratory automation.

The satellite symposium builds on Tecan’s success in China as a leading supplier of sampling and ELISA processing instruments to the CSBT, and follows the recent visit to Tecan’s headquarters in Männedorf by the directors and presidents of blood centers and blood banks across China to share experiences and exchange ideas.

Libby Zhu on the Tecan booth at CSBT

CORPORATE NEWS TECAN JOURNAL 1/2011

Read. Wash. Win(ner)!

© Tourismus Salzburg

Tecan is pleased to announce the winner of the first ever Tecan Detection Award.

The award is designed to celebrate the innovation and ingenuity of our loyal customers, and we have been overwhelmed by your response to this inaugural competition. We received a lot of strong entries (look out for some of these in future issues of the Tecan Journal), and we would like to thank all those who submitted abstracts of their work.

Choosing just a single winner was very difficult, but we would like to congratulate Dr Francisco Quintana from the Center for Neurologic Diseases at the Brigham and Women’s Hospital, Harvard Medical School, Massachusetts, for his pioneering work on the progression of Multiple Sclerosis (MS) using human and zebrafish antigen microarrays.

MS is a neurological disease caused by an autoimmune response to the central nervous system, however there is currently no reliable method to monitor the participation of innate and adaptive immune response in different stages of the disease.

Dr Quintana’s team has used a systems biology approach to study the role of immune response in MS, developing human and zebrafish antigen microarrays to identify signaling pathways that participate in MS pathogenesis and progression. Development of these arrays was performed using Tecan’s HS 4800™ Pro hybridization station and PowerScanner™, together with an Infinite® F200 microplate reader for screening anti-zebrafish monoclonal antibodies, quantifying cytokines and measuring dual luciferase reporter assays.

To reward this creative approach to using our instruments, Tecan will be inviting Dr Quintana to visit Tecan Austria, where he will have a chance to see the fascinating world of Tecan detection instruments first-hand, while enjoying a stay in the beautiful and romantic city of Salzburg.

A close second place went to Dr Jeff Mumm from the Department of Cellular Biology and Anatomy, Medical College of Georgia, for his work on reporter-based drug screening using Tecan’s Infinite M1000 and live zebrafish!

And Ms Elisa Masi from the Department of Plant, Soil and Environmental Science at the University of Florence, Italy, was awarded third place for her plan to use an Infinite 200 multimode reader to measure the effect of gravity changes during parabolic flight on the levels of reactive oxygen species in plant cells.

Thank you again to everyone who took part in this year’s Tecan award and, for those of you who missed out, look out for details of how to enter the 2011 Tecan Award later in the year.

To learn more about the Tecan award, visit www.tecan.com/award

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cell biology TECAN JOURNAL 1/2011

Automated solutions for cell biology Tecan and Miltenyi Biotec are working together to develop a range of automated solutions for cell biology, based on the powerful MACS® magnetic bead technology.

Miltenyi Biotec, based in Bergisch Gladbach, Germany, is a leading provider of cell biology solutions, and is committed to advancing scientific understanding and medicine by providing products and services for biomedical research and cellular therapy.

The Company’s MACS technology, the gold standard method for magnetic cell separation, combines the use of MACS MicroBeads (nano-sized superparamagnetic particles coupled to specific antibodies), patented MACS Columns and MACS Separators (strong permanent magnets) to perform a wide range of separation, cultivation and analytical processes for cells and biomolecules.

Collaborating with Tecan has allowed Miltenyi Biotec to fully integrate its MultiMACS™ Separator family of biomolecular and cellular separation devices onto the Freedom EVO® liquid handling platform. The MultiMACS Cell24 Separator, for example, employs unique magnetic bead technology to isolate viable and unaltered cells from almost any cell type. Plus, for the extraction of RNA, the MultiMACS M96thermo Separator not only allows working in 96-well formats, but also enables one step RNA isolation and cDNA synthesis.

Miltenyi Biotec’s instrument software has been updated with automation protocols, and Tecan has provided software drivers to allow straightforward incorporation of additional Miltenyi instruments – such as the MACSQuant™ Analyzer, a bench-top cell analyzer for highly sensitive multicolor flow analysis – onto the Freedom EVO. Dr Simon Mauch, Global Marketing Manager for automated cell separation at Miltenyi Biotec, explained: “Laboratory automation is something we have been considering

From left to right front row: Dr Simon Mauch, Marketing Manager Automation; Dr Oliver Schilling, Project Manager Automation; Dr Tim-Oliver Stolle, Marketing Manager MACS Molecular From left to right back row: Dr Uwe Janssen, Business Development; Dr Markus Zumbansen, Project Manager Automation

for some time, as some of our customers wanted integrated, automated systems, and so this plan has evolved strategically over a number of years. Initially we discussed doing this automation in house, however it became clear that we needed a strong, reliable partner to help us achieve our goal. Our specialty is in magnetic cell separation and cell analysis using a vast portfolio of reagent solutions as well as small bench-top devices. Being the market leader in automated cell separation and having many thousands of our bench-top instrument solutions successfully placed in the market, we understand that good service is essential to our customers. It was therefore important that we collaborated with a leading company in the field of automation, that could provide our customers with an equally strong technical support network, and Tecan was the obvious choice. We already had a very good

relationship with Tecan, it was a name our customers knew and was simply the best fit for our purposes.”

“Many companies entering the automation market for the first time find that they have to redesign their product portfolio to be automation friendly. In our case, the products that we are integrating onto Tecan platforms were originally developed with the aim of producing fully automated systems, so we already had a number of instruments that, although not complete workstations, were suitable for integration into a liquid handling platform. We had worked with Tecan to automate our MultiMACS test system in house, and so had begun to develop protocols and scripts to enable Tecan’s software to control the instrument, and these could be easily transferred onto the new systems.”

CELL BIOLOGY TECAN JOURNAL 1/2011

Simon continued: “From a technical point of view, it was mainly simple things that made the Tecan system so suitable for our needs.

For instance, we required a gripper that is able to handle labware/microplate from the short and the long side. Tecan offers this as a standard feature, whereas other systems either don’t have this facility, or include it as an option. The robotic manipulator (RoMa) arm works better with our system than other robotic arms, making integration straightforward. Reliability was also very important and, having used Tecan platforms for many years, we knew that we could count on both the workstations and Tecan’s support.”

“We have a Cellerity™ and two Freedom EVO workstations which we use for in-house research projects, protocol development, and beta testing. Protocols are transferable between cell types, so we have some general methods available and work with customers

to optimize the application for their specific purposes. Automation is very individualized, but there are some applications, for example diagnostic applications, that are requested by more than one customer. Once these have been developed, they can be promoted as ‘off-the-shelf’ solutions.”

Application development involves very close cooperation between Tecan and Miltenyi Biotec, as well as joint visits to customers to get an understanding of the customer’s needs and to develop the concept. Simon concluded: “This collaboration is an example of how two very different types of specialty can come together to produce a complete solution for the customer. Tecan’s expertise is as an instrument company, with a strong engineering base, while Miltenyi Biotec specializes in reagents, specialized consumables, and small bench-top devices.

Similarly, Tecan provides the primary support on technical issues, while Miltenyi

The MultiMACS™ Separator family offers fully automated separation of biomolecules and cells

Biotec handles queries relating to reagents and protocol optimization. Our extensive, combined knowledge in these two very different areas makes this an extremely interesting collaboration, which will be of great benefit to our clients.”

To find out more on Tecan’s applications, visit www.tecan.com/miltenyi To find out more on Miltenyi Biotec, visit www.miltenyibiotec.com MultiMACS and MACSQuant are trademarks and MACS is a registered trademark of Miltenyi Biotec.

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CORPORATE NEWS TECAN JOURNAL 1/2011

A meeting of minds for worldrenowned scientists

A world-class line-up of speakers

Salzburg in Austria was the beautiful autumn setting for Tecan’s third symposium, where key thought leaders from Europe, the US, Asia and Australia came together to discuss this year’s topic – Applying Genomic Technologies – in an informal and stimulating atmosphere.

The packed two day program focused on a number of different aspects of applied genomics, with the broad spectrum of speakers providing unique insight into the advantages and limitations of current technology.

The first session began with an overview of some of the exciting new technologies currently in development. Introduced by Marc Feiglin, Tecan’s Chief Technology Officer of Life Sciences, and led by Dr David Galas from the Strategic Partnerships Institute for Systems Biology, USA, this session offered delegates a preview of what these latest innovations will bring to the laboratory environment and how they might impact the whole spectrum of

genomics applications. The emphasis then turned to the application of genomics, discussing the impact of this relatively new field of science on human health, in human identification for forensic applications, and on food and the environment. Topics ranged from the genomics behind consumer and over-the-counter healthcare products to the latest techniques and trends for criminal investigation and missing persons casework, as well as details of how genomics methodologies have led to more effective procedures for monitoring water and food supplies for contamination.

A key element of the program was the significant amount of time set aside for question and answer forums at the end of

CORPORATE NEWS TECAN JOURNAL 1/2011

Dinner at the Gwandhaus in Salzburg

each session, allowing delegates to openly discuss issues surrounding this technology with some of the leading experts in the field. And discussions did not stop at the symposium door, with speakers and attendees alike taking advantage of the rare opportunity presented by having so many prominent figures together in one place. “The symposium provides Tecan with a valuable opportunity to interact with key players and thought leaders from both academia and industry, helping us to understand the current trends in this cutting-edge area of science and technology, as well as the bottlenecks and problems that are encountered in applying these technologies,” said host Marc Feiglin. “In addition, it offers an unrivalled opportunity for our guests to engage with their peers, not only from within their industry or area of specialty, but also from other areas. This helps to identify the commonalities between diverse areas of research, stimulating cross-fertilization of ideas and accelerating our understanding of the natural world.’’

Abstracts from the symposium can be found on the Tecan website, at www.tecan.com/symposium2010

Dr David Galas offered the audience a fascinating insight into the complexity of interpreting the human genetics revolution

Round table discussion featuring Dr Rinaldis, Dr Galas, Dr Shapiro and Dr Hattori (left to right)

Dr Barbara Zehentner, Renate Wohlgemuth and Cornelia Kegele (left to right) toasting the success of the symposium

Happy 30th Birthday Tecan!

Delegates enjoyed a range of captivating presentations

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CORPORATE NEWS TECAN JOURNAL 1/2011

Tecan Symposium speakers Thursday 7th October Dr David galas Senior Vice President of Strategic Partnerships Institute for Systems Biology, USA

Dr Frederic Zenhausern Director, Center for Applied NanoBioscience University of Arizona, USA

The revolution in human genetics – deciphering complexity

The 6th vital sign: a rationale for genomic profiling

Dr Emanuele de Rinaldis Senior Research Fellow King’s College London, UK

Dr Jim Fleming Vice President and Director Labcorp, USA

Molecular dissection of triple-negative breast cancers: integrated-omics approaches

Molecular testing and the changing face of medicine

Dr Ehud Shapiro Professor of Computer Science and Biology Weizmann Institute of Science, Israel

Dr Josef Thalhamer Head of Gene Vaccines Salzburg University, Austria

Uncovering the human cell lineage tree in health and disease

gene vaccination against allergic diseases

Dr Masahira Hattori Professor University of Tokyo, Japan Metagenomics of human gut microbiomes

Dr Jay Tiesman Principal Scientist, Global Biotechnology Division Proctor and Gamble, USA Putting the ‘consumer’ in consumer genomics

Dr Kári Stefansson Executive Chairman and President of Research deCODE, Iceland Population genetics and its impact on human health

Friday 8th October Dr Ron Fourney Director, National Services and Research Branch RCMP, Canada Outlook for next generation methods for forensic analysis and human identification Dr Tom Callaghan Special Assistant to EAD FBI Laboratory, USA Rapid point of collection DNA analysis for human identification

Dr Pingfan Rao Professor Fuzhou University, China Applications of biotechnology in food processing

Dr bernard berger Senior Scientist Nestlé Research Centre, Switzerland bacterial genomics for probiotics

Dr Angela van Daal Associate Professor Bond University, Australia

Dr Alain Houde Research Scientist Agriculture and Agri-Food Canada, Canada

Forensically relevant SNP markers

Development and application of tools for the detection of food-borne viruses

Dr Christian Lauber Senior Scientist University of Colorado, USA

Dr Syed A. Hashsham Professor Michigan State University, USA

Forensic identification using skin bacterial communities

DNA microchips for detection of microorganisms in water and food samples

PARTNERSHIPS TECAN JOURNAL 1/2011

Automated multiplex assays offer novel newborn screening solution Tecan is collaborating with Luminex® Corporation to develop an innovative, automated newborn screening solution designed to rapidly identify potential health issues in infants. Luminex’s Luminex 200™ instrument with xMAP® technology is being integrated with Tecan’s Freedom EVO® liquid handling platform and HydroFlex™ washer to create the 996x™. xMAP technology allows large numbers of biological tests to be performed and analyzed simultaneously, and xMAP newborn assays offer high throughput testing for multiple biomarkers linked to critical diseases. Screening enables early detection of potential health problems, allowing effective treatment to be initiated, and the 996x will provide a walkaway automated solution for cost-effective, multiplexed newborn screening. This new platform, which is expected to be launched in 2011, will help laboratories enhance efficiency, save vital resources and analyze more samples, more quickly.

Project team members from Luminex and Tecan (left to right): Kyle Knight (Luminex), Renate Kehrli and Christoph Beck (Tecan)

To find out more about Tecan’s Freedom EVO workstations, visit www.tecan.com/freedomevo To find out more on Luminex Corporation or xMAP technology, visit www.luminexcorp.com Luminex 200 and 996x are trademarks, and Luminex and xMAP are registered trademarks of Luminex Corporation.

xMAP technology integrated onto Freedom EVO platform to create 996x

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LIQUID HANDLING TECAN JOURNAL 1/2011

In search of perfection Researchers at The Australian Wine Research Institute are taking advantage of the flexible Freedom EVO® platform to help investigate a wide range of factors affecting the quality of wine.

characteristics. Automation is vital to this, allowing a large number of small-scale fermentations to be carried out in parallel, and so we looked at various robotic solutions when designing the new laboratory.”

Members of the AWRI team (left to right): Angus Forgan, Tina Tran and Simon Schmidt

The Australian Wine Research Institute (AWRI) is an industry-owned research and development center based in Adelaide, and has been helping to improve the consistency and quality of Australia’s wine production for over 55 years. The multidisciplinary team at the AWRI studies all aspects of viticulture, from the properties of the yeast strains and grape varieties used to the aroma, flavor and packaging of the finished product, as well as studies of consumer preferences. With such a broad field of investigation, the AWRI team employs a wide range of chemical, microbiological and molecular biology techniques to help winemakers improve and refine their wines and production processes.

Angus Forgan, Research Laboratory Manager at the AWRI, explained the Institute’s work: “We look at all stages of wine production, identifying and characterizing compounds which affect aroma and flavor, where these compounds arise and how to enhance or eliminate them during

the production process. Identifying the individual compounds responsible for a given characteristic, as well as whether it is a function of the grape, the yeast strain, the fermentation technique or the packaging, helps us to guide grape growers and winemakers, giving them better tools to produce the flavors they want in the future.”

The AWRI has recently moved from its original building to a new, purpose-built facility, allowing the research and development team to implement high throughput screening for the first time.

“An important aspect of our work is wine yeast strain development, looking for specific yeast strains that will lead to predictable, favorable characteristics in a wine,” Angus continued. “Over the years we have established an extensive wine yeast culture collection, gathered from throughout the wine industry, as well as developing many strains in house, and wanted the ability to screen this collection for various

The AWRI chose a Freedom EVO 150 workstation to meet its automation needs, equipped with liquid handling (LiHa) and MultiChannel (MCA) pipetting arms, a robotic manipulator (RoMa) arm with an extended Z-axis to access below the worktable, an integrated Infinite® M200 multimode microplate reader and various ancillaries including an incubator, a wash station and a vacuum manifold assembly.

Comprehensive support is provided by the highly trained team at Tecan Australia, assisting users in developing applications and maintaining the system.

“Because we are a research group, flexibility is vital, and the Freedom EVO workstation allows us to perform a wide variety of different tasks, as well as continuously developing and implementing new processes. The platform’s high throughput capabilities have changed the way we design our experiments, significantly expanding the scope of any given study. For yeast screening trials, the increased throughput allows us to test many different strains in parallel. By miniaturizing each fermentation – from over 100 ml down to just 100 or 200 μl – we can process hundreds of samples in a day, rather than the very limited number that could be achieved manually.”

“It is a very versatile platform, and has certainly changed our approach to large scale studies. We also use the Freedom EVO for a number of other applications, such as enzymatic assays to determine the amount

LIQUID HANDLING TECAN JOURNAL 1/2011

Hunter Valley, Australia

of sugar left in a ferment, and encourage all our staff to think about how they can use the platform to advance their research.

Although the instrument’s Freedom EVOware® software is very easy to use, we have a core team of users responsible for programming the system and setting up new processes, and everyone else in the laboratory is trained to operate their specific programs. This strategy has worked very well for us, and the biggest problem we now face is scheduling time for all the different projects to use the system. Its ability to run completely unattended – overnight and at weekends – is a big help in this respect, and has really improved our productivity.”

“As an industry-driven organization, we are also keen on promoting collaborative research projects to help accelerate research in the field. There are a number of other research organizations located on the same science precinct with an interest in viticulture, including the University of Adelaide, the Commonwealth Scientific and Industrial Research Organisation and the South Australian Research and Development Institute, and we encourage researchers from these institutes to work with our staff to take advantage of the high throughput capabilities of the Freedom EVO system.”

To find out more about Tecan’s Freedom EVO workstation, visit www.tecan.com/freedomevo To find out more on The Australian Wine Research Institute, visit www.awri.com.au

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CORPORATE NEWS TECAN JOURNAL 1/2011

Creative customer competition Earlier this year we launched a competition inviting you to show us how much you love your Tecan and win a party for your team. We have received some great, creative photos showing just how important Tecan systems are to your teams, a selection of which are illustrated. We hope you enjoy working with your instruments as much as we love making them for you.

Kristen Tamburro, UNC, USA

winner & have one FaronWe only a t a g ut A prize‌ b d the Institute n a Polish Gorecka acology, of Pharm nces, ie c y of S Academ very as rated Poland w hly hig

W I NNER mara, Gema Santa , Spain ar M a rm ha P

Burak Tiryakioglu, EUROIMMUN, Turkey

CORPORATE NEWS TECAN JOURNAL 1/2011

And rew F latley , Helm Zen trum holtz M端n chen Germ , any

Nataly, FGI Giarriah, Russia

lle, Institute Bree Rumba Bioscience, r la cu ole for M alia tr us A

Rosemary Nelson, St ryker Biotech, USA

Stefan Alata lo, Octapharma, Sweden

ended hly comm Also hig k, IVD u er Selc was Yen Germany GmbH,

Novartis Jeanette Wu, opical Tr Institute for pore ga in S s, se Disea

Thomas Edmond s, In De Rec herche S stitut ervier, France

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READERS TECAN JOURNAL 1/2011

Seeing is believing Scientists at the Center for Integrated Protein Science Munich have taken advantage of the 3D scanning capabilities of Tecan’s Infinite® M1000 microplate reader.

Heinrich Leonhardt, Professor of Molecular Human Biology at LMU

Dr Carina Frauer, a postdoctoral researcher in Professor Leonhardt’s group

The Center for Integrated Protein Science Munich (CIPSM), based at Ludwig-Maximilians University Munich (LMU), Germany, focuses on the study of epigenetics using a number of different technologies. In addition to using live cell imaging, live microscopy, dynamic imaging techniques and super-resolution microscopy, CIPSM scientists have been capitalizing on the 3D scanning capabilities1 of the premium Quad4 Monochromators™ -based Infinite M1000 microplate reader to investigate nanobodies, as well as its flexibility and sensitivity for multicolor interaction studies.

Professor Heinrich Leonhardt, Professor of Molecular Human Biology at LMU, explained: “Conventional antibodies are large molecules consisting of two heavy chain and two light chain proteins and are not ideally suited for studies in living cells. Nanobodies are relatively simple proteins about a tenth the size of human antibodies, and consist of a single heavy chain. They are effective alternatives to conventional antibodies, possessing similar antigen-binding characteristics but with enhanced stability and reduced size, and have the advantage that they are functional inside living cells. This allows them to be fused with fluorescent marker proteins and used to trace antigens within the cell. Using reverse-transcription PCR (RT-PCR), we can amplify the antigen binding domain, make recombinant libraries and isolate specific binders. These binders are then expressed in E. coli, purified and used for live-cell studies, or coupled to matrices for affinity purification applications.”

Dr Carina Frauer, a scientist at LMU, described the process: “We use nanobodies for a number of different applications,

including various binding assays, and we try to combine the in vivo studies with the biochemical assays. GFP-binding nanobodies coupled to sepharose beads (GFP-Trap®, ChromoTek) are used to capture GFP fusion proteins for purification and biochemical characterization. The immobilized GFP fusions are then incubated with fluorescently labeled DNA substrates or peptides and any unbound substrate is washed away.”

“We then measure the fluorescence using the Infinite M1000 reader, which gives us the sensitivity we need and allows us to distinguish between the various fluorescent labels by using very specific settings. The labels have been carefully chosen to enable us to simultaneously compare different DNA substrates that are in direct competition with each other, as this allows us to directly determine sequence specificity. The fluorescence of the DNA or peptide labels and the immobilized GFP fusion are measured, and their ratio calculated, to quantify specific DNA or peptide binding. We also use DNA substrates containing a mechanism-based inhibitor for methyltransferases, and determine the formation of irreversible covalent complexes with active methyltransferases. This provides a measure of catalytic activity, so we have essentially established a non-radioactive methyltransferase activity assay.”

Professor Leonhardt added: “An important aspect of this assay is that we can actually quantify the protein. There are many binding assays available, but they don’t usually quantify the protein itself. Our assay enables quantification of the protein; the input, bound and unbound fractions. We have also been able to use the 3D scanning capability

READERS TECAN JOURNAL 1/2011

GFP + control nanobody

GFP + enhancer nanobody

3D scanning makes it easy to study nanobody-induced changes to the spectral properties of GFP

of the M1000 to study nanobody-induced changes of the spectral properties of GFP in living cells. The results are really beautiful.”

Professor Leonhardt concluded: “The instrument is flexible, easy to use and very fast, which has increased the speed of the assay. The software is simple to understand and, if we need any additional advice, Tecan is happy to help. We focus on developments in technology and the application of new methods, and the instrument’s versatility really helps in this.”

Carina continued: “We co-expressed GFP in cells with specific nanobodies which modulate the spectral properties of GFP. 3D scanning shows excitation and emission on the same plot, very nicely illustrating the shift in GFP fluorescence excitation and emission wavelengths induced by nanobody binding.”

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For more information on Tecan’s Infinite M1000, visit www.tecan.com/infinitem1000 For more information on CIPSM, visit www.cipsm.de GFP-Trap is a registered trademark of ChromoTek GmbH.

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1. Kirchhofer, A., Helma, J., Schmidthals, K., Frauer, C., Cui, S., Karcher, A., Pellis, M., Muyldermans, S., Casas-Delucchi, C.S., Cardoso, M.C., Leonhardt, H., Hopfner, K.P., Rothbauer, U. (2010). Modulation of protein properties in living cells using nanobodies. Nat Struct Mol Biol. Jan;17(1):133-8. Epub 2009 Dec 13.

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CH2 Fc

CH3 Schematic comparison of conventional and camelid antibodies to nanobodies (left to right)

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LiQUiD HANDLiNg TECAN JOURNAL 1/2011

Multichannel head 384 vital to investigation of gene regulatory networks The École Polytechnique Fédérale de Lausanne (EPFL) is using Tecan’s Freedom EVO® workstation equipped with a MultiChannel ArmTM (MCA) 384 to study the interaction between genes and their respective regulatory transcription factors. The MCA 384 offers great flexibility, due to its adapter plate concept, which makes it possible to change from disposable tips to fixed tips during a run without user intervention.

Scientists at EPFL in Lausanne, part of the Swiss Federal Institute of Technology and one of Europe’s leading science and technology institutions, are investigating the interaction of genes with regulatory transcription factors.

Gene regulatory networks play a vital role in metazoan development and function and can be implicated in disease. However, the interactions between genes and their respective regulatory transcription factors, which form the basis of gene regulatory networks, have been poorly characterized.

The laboratory’s aim is to identify the regulatory elements that control metazoan gene expression and the transcription factors that bind to them using high throughput technologies. EPFL’s overall goal is to reverse engineer the gene regulatory networks that control development and function.

EPFL has a library of transcription factors that scientists are using for the study of gene regulatory networks in Drosophila, performing screening assays on a Freedom EVO liquid handling platform. Jean-Daniel Feuz, laboratory technician at EPFL, explained: “Our laboratory uses a Freedom EVO workstation equipped with a MultiChannel Arm 384, which is particularly beneficial to our work, a robotic manipulator (RoMa) arm, a Carousel™, two incubators and a centrifuge. We have a library of about 750 transcription factors to screen and the MCA 384 is ideal for this purpose.”

“Our plates are housed in the Carousel and we use the MCA 384, equipped with disposable tips, to transfer the yeast cells containing the regulatory elements of interest to a 384-well plate, and then add our library of transcription

factors. We also add polyethylene glycol (PEG) to the plate, as we are performing lithium acetate (LiAc) transformation, using the MCA 384 with fixed tips. The Freedom EVO has two integrated incubators – one at 30 °C and the other at 42 °C – and the RoMa arm transfers the plate to each of these at the appropriate times in the assay. Once the incubation stages have been completed, the plate is placed in the centrifuge and the transformed yeast cells are spun down. The final stages of the assay involve the MCA 384 removing the PEG from the plate to leave just the yeast, which is resuspended in water and spotted on a single agar plate. The plate is then placed in a 30 °C incubator where it can be monitored, allowing us to see whether the transformation has been successful.”

Jean-Daniel concluded: “We have had the Freedom EVO for over a year now, and it enables us to complete a run – 750 transformations – in only two hours.

Previously we had to do everything manually, which was much more time consuming.

Automation, and particularly the flexibility offered by the MCA 384, has transformed our workflow.”

For more information on Tecan’s MultiChannel Arm 384, visit www.tecan.com/mca384 For more information on EPFL, visit www.epfl.ch Left to right: Jean-Daniel Feuz, Korneel Hens and Bart Deplancke

CORPORATE NEWS TECAN JOURNAL 1/2011

Moving on to new challenges – Martin von Lueder President of Tecan Europe, Martin von Lueder, talks about his years with Tecan.

My 26 years with Tecan have been fantastic; I have enjoyed this time very much and have built a tremendous feeling of mutual trust with my colleagues. My working life did not start in the laboratory world, but in the totally different environment of event management for the music industry.

However, I quickly joined a US microplate company in 1980, progressed to sales manager, and was approached by the owner of Salzburger Labor Technik (SLT) to open direct sales operations in Germany for the company’s microplate readers and washers.

This was 2nd of January 1985; it was an exciting time and, although I started alone, the business soon grew. The eighties were years of outstanding growth for this kind of technology; there were lots of new and potential applications for microplates, including the intensive search for diagnostic tools and methods for AIDS, and we were developing excellent products. Really it was no great surprise when, in December 1987, Tecan bought SLT. I continued in my role as Country Manager, SLT became Tecan Austria, and the German sales team consistently achieved the highest European reader and washer sales, thanks to their dedication. In the 1990s, I took over responsibility for direct sales of the full Tecan product portfolio in Switzerland and then Austria and, in 2003, was made President of Tecan Europe, overseeing nine sales organisations. Europe is small in distance compared to the US – we can effectively fly everywhere in just an hour or two – but there are so many diverse cultures and people are very different. I have always respected that in my role; it’s what makes Europe so interesting and I like it.

When I look at our organization, the sales and the service back-up, it is clear that the team spirit has been key to the success of the company. Good teams and good relationships between colleagues are essential, to give each other that extra drive that’s needed and be truly responsible for our business. I want to thank all my colleagues throughout the Tecan organization for supporting me for all

these years. Together we have reached many goals, and their support has been a great advantage for our company. I’m looking forward to a number of new, perhaps more relaxed challenges, not as an employee but still with plenty to keep me busy. I send good wishes to all my colleagues and customers and look forward to watching Tecan continue to grow in the next 26 years and beyond.

Martin von Lueder, President of Tecan Europe

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WASHERS TECAN JOURNAL 1/2011

Improved plate washing for ELISpot assays Researchers at the University of Modena and Reggio Emilia, Italy, have introduced automated washing for Enzyme-Linked ImmunoSpot (ELISpot) assays, using the HydroFlex™ microplate washer.

Standing, from left: Giovanni Riva, Patrizia Barozzi, Leonardo Potenza, Eleonora Zanetti Sitting: Daniela Vallerini

Incubation of T-cells in the presence of specific stimulus (Ag), in wells coated with cytokine-specific Ab

During incubation cells become activated by the stimulus and start to produce and secrete cytokine that binds to the capture Ab Automated washing of the plate on the HydroFlex using the program “E1” Incubation with alkaline phosphatase-conjugated detection mAb Automated washing of the plate on the HydroFlex using the program “E1” Addition of substrate solution which turns into coloured spots Automated washing of the plate on the HydroFlex using the program “E1”

Schematic assay procedure of ELISpot including the wash steps performed with Tecan’s HydroFlex microplate washer

Hematologists at the University of Modena and Reggio Emilia’s Department of Oncology and Hematology use ELISpot assays to perform detailed studies on the immune response of patients to viral, fungal and tumor antigens. Historically the group, led by Professors Mario Luppi and Giuseppe Torelli, has focused its studies on human herpes virus-8 (HHV8) and over the last 10 years has turned its attention to monitoring the T-cell immune response in post-transplant and leukemic patients.

The aim of this immunological monitoring is to try to correlate the presence of an immune response with the development of a particular disease. Generally, when a person shows an immune response they will not have the disease, as this is the body’s defense mechanism against a virus or tumor.

Conversely, the lack of an immune response can result in recurring and life-threatening infections.

Dr Giovanni Riva, a postdoctoral scientist at the laboratory, said: “We are essentially performing clinical research studies, and what makes our approach a little bit different is that we start with the patient and then move the research into the laboratory. We have very close links to a local medical center and, by working with their clinicians, we are able to obtain samples directly from patients, either by venipuncture or bone marrow aspiration.

This allows us to study the immune response in both peripheral blood and bone marrow samples, which is quite a new field of study.

We have also expanded our field of research to include the study of polymorphisms in an attempt to correlate genetic differences

WASHERS TECAN JOURNAL 1/2011

HydroFlex microplate washer

and disease, and are investigating some new applications involving siRNA (small interfering RNA), performing in vitro studies with siRNA-carrying immunoliposomes to try and identify possible treatments for some lymphomas.”

The department uses the Enzyme-Linked ImmunoSpot (ELISpot) assay, a very sensitive immunoassay, for the detection of secreted cytokines at the single cell level. The ELISpot technique can be applied to any system requiring single cell level investigation of protein secretion, although it is primarily used in T-cell analysis. Because of its high sensitivity, it has proved a valuable tool for the study of small populations of active cells, and is commonly used for investigation of specific immune responses in disease. ELISpot is a standard tool for the development and monitoring of new vaccines and vaccine candidates, and is also well suited to field studies.

The washing stages of the ELISpot assay are critical and can be performed either

manually with a multichannel pipette, or using an automated plate washer.

Giovanni explained: “We used to carry out the washing stages of the assay manually, but this was very time consuming and labor intensive. Incubation times tended to be inconsistent, and the assay was not reproducible if performed in this way. As we are looking for different cytokines we can have quite a number of plates to wash – perhaps 10 plates a day, two or three days a week – often at different times. We wanted to improve the methodology, and decided to change to automated washing using the HydroFlex plate washer. We now have a standardized, reproducible, automatic plate washing method, which frees staff time, allowing them to perform other tasks.”

Giovanni concluded: “We have been able to use the standard HydroFlex protocols, just making small changes to adapt them for our specific needs, and the instrument has proved very reliable and simple to use.

We just define the protocol for washing, insert a plate and then everything is done

automatically. The HydroFlex is a great improvement to the ELISpot assay and our laboratory.”

To find out more on Tecan’s HydroFlex, visit www.tecan.com/hydroflex To find out more about the University of Modena, Department of Oncology and Hematology, visit www.unimore.it/en/

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LIQUID HANDLING TECAN JOURNAL 1/2011

Innovation in action A successful partnership between Tecan and the Hochschule für Technik in Rapperswil, Switzerland, has resulted in the development of a new technology called Array Liquid Arrival Check (ArrayLAC) that shows great potential for built-in process control in Tecan pipetting platforms. ArrayLAC will be ideal for real time and parallel volume measurement in microplates before and after pipetting steps.

Hochschule für Technik in Rapperswil, Switzerland

Tecan’s Innovation and Incubation (I&I) department was established in 2007 with the specific goal of developing technologies to be used in future product development, thereby significantly strengthening Tecan’s position as a leader in technology. Since then, several successful technology projects have been completed, one of the most recent being the development of ArrayLAC. Dr Alois Krutzenbichler, Head of I&I, explained: “In the initial phases of establishing I&I, it was very clear that it would be important to match the right ideas to the right people. ArrayLAC technology has been one of the most outstanding examples of how this is the best approach for optimum success.”

ArrayLAC was developed in association with the Hochschule für Technik (University of Applied Sciences) in Rapperswil (HSR), near Zurich, which is renowned for maintaining close contacts and cooperation between academia and industry, and is proactively involved in applied research and development through its network of 17 institutes. Professor Werner Hinn, from the Department of Electrical Engineering at HSR, heads the Institute for Micro-electronics and Embedded Systems (IMES), and explained: “It is very important for our students and academic staff alike to know what is happening in the industry, and this is what initially attracted me to the HSR. We first had contact with Tecan as an industrial partner twenty years ago, when we were asked to look into liquid level detection circuits. Since then, we have collaborated

on a number of projects, including, since late 2007, a system for checking liquid arrival based on our long tradition in capacity sensing applications.”

Dr Krutzenbichler added: “In the past, several teams working on similar projects have tried to perform volume measurements based on changes in electrical capacity between the wells of a microplate. Through the ArrayLAC project, we were the first to overcome the core problem of crosstalk between the wells, reducing it to a level that has never been reached before and that we honestly had not even dared hope for.

The result is a demonstrator, showing the patented ArrayLAC technology that achieves this outstanding performance, which is now ready to go into product development.”

Prototype tests show that ArrayLAC technology is extremely fast, robust and sensitive, detecting addition of as little as 1 µl of liquid to a filled microplate well.

The technology is compact, light, fully autonomous, and takes less than a second to measure all 96 wells in a standard microplate, alerting the user if an incorrect volume of liquid has been pipetted into the wells.

“The collaboration with Tecan has been extremely fruitful and interesting,” said Professor Hinn. “Members of the team at Tecan were keen to get the project off the ground and develop a thorough understand of what we were trying to achieve. We had many meetings and

LIQUID HANDLING TECAN JOURNAL 1/2011

constant communication along the way to aid this process, and have already started discussions about new ideas and future collaborations; Tecan has worked very hard as an industrial partner and this has made the whole project so interesting and, hopefully, very successful. I really appreciate the fantastic cooperation we have had.”

Dr Krutzenbichler concluded: “With ArrayLAC, we are able to show that, given time to focus on a project and the right people in your team, there is still the potential to overcome the limitations inherent even in well-known and established technologies such as capacitive sensor systems. We are very proud that this project, in particular, has by far exceeded all our initial expectations.”

The ArrayLAC collaboration team (left to right): Werner Hinn, Manuel Meier, Markus Wolf, Johann L. Camenisch, David Kress, Simon Künzi

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CLiNiCAL DiAgNOSTiCS TECAN JOURNAL 1/2011

High throughput HIV screening with Freedom EVOlyzer® ViroMed, a provider of laboratory testing services based in Minneapolis, USA, chose six Freedom EVOlyzers to support high throughput ELISA testing for a substantial HIV screening project.

Gina Trebilcock, Laboratory Operations Manager and Associate Vice President of ViroMed, explained: “High throughput, efficiency and reliability were critical to meeting the short eight hour turnaround time we had to achieve for this project. We were able to evaluate the instrument in our laboratory prior to purchase, and could see that it would meet our throughput requirement of between 30 and 100 ELISA plates per day. We encountered no cross contamination or carryover, both critical issues for us to consider.”

The Freedom EVOlyzer offers high throughput ELISA processing

ViroMed Laboratories, Inc. (ViroMed) – a wholly owned subsidiary of Laboratory Corporation of America Holdings (LabCorp) – provides a broad menu of laboratory testing services to public and private healthcare providers, government agencies and pharmaceutical companies throughout the United States. The Company has extensive experience in high volume, rapid turnaround testing, and chose six Freedom EVOlyzer systems for a recent HIV screening project.

The volume of samples for this ten month project varied greatly, ranging from 2,500 to 8,000 or more samples per day, five days a week, and ViroMed relied on the Freedom EVOlyzers to provide timely and accurate results, while completely eliminating manual operation.

With assistance from Tecan application specialists, ViroMed was able to ‘go live’ and have the instruments in routine operation within two months of delivery.

Gina continued: “The transition to the Freedom EVOlyzer was easy, and the training required was minimal. We were already familiar with Tecan instruments, and the Freedom EVOlution™ software is intuitive and user-friendly, prompting the operator with specific instructions. It took approximately two weeks to install and set up all the instruments, and the rest of the time was spent on internal validations, custom programming for data reduction, and interfacing each of the systems to our centralized LIS database.”

The Freedom EVOlyzer has the flexibility to deal with the varied requirements of ELISA kits from a range of different suppliers. Gina said: “We were running a commercially available ELISA kit, and the Freedom EVOlyzers were programmed according to the kit manufacturer’s instructions, with the testing protocol stored in the

CLINICAL DIAGNOSTICS TECAN JOURNAL 1/2011

Freedom EVOlution Run Control software.

The Freedom EVOlyzers use barcode identification for all samples, with each barcode assigned to an ELISA plate map.

We worked with the application specialist to do some custom programming to meet our client’s specific requirements, and the software was able to carry out the data reduction, automatically transferring the results to our internal LIS system without the need for manual intervention. This improved our efficiency, creating a more robust, continuous process.”

“The Freedom EVOlyzer was also able to handle variable sample volumes effectively.

Samples during this project ranged from tubes that were completely full to those with minimum serum volumes, and the platforms’ liquid sensing capabilities allowed accurate pipetting from these varying tube volumes. Another advantage was that the Freedom EVOlyzers could cope with variable throughputs, so the lab was able to operate the instruments with just a few plates or fully loaded with six plates.”

One of six Freedom EVOlyzer platforms used for the HIV screening project

Gina concluded: “Once all six Freedom EVOlyzers were installed and operational, they performed exactly as they did during the evaluation process. They proved reliable, offered consistent performance and met our expectations.”

To find out more on Tecan’s Freedom EVOlyzer workstations, visit www.tecan.com/freedomevolyzer To find out more on Tecan’s clinical diagnostics solutions, visit www.tecan.com/clinicaldiagnostics

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PROTEOMICS TECAN JOURNAL 1/2011

Crystal clear results The Protein Expression Purification Crystallization Core at Case Western Reserve University is designed to perform high throughput crystallization trials, taking advantage of the automation capabilities of Tecan’s CrysScreen™ software and Freedom EVO® liquid handling platform to optimize crystallization parameters.

Dr Harry Gill, Director of the PEPCC laboratory

PEPCC Freedom EVO workstation

The Protein Expression Purification Crystallization Core (PEPCC) at Case Western Reserve University, Ohio, is a state-of-the-art automated facility designed to help researchers optimize protein crystallization for X-ray crystallography analysis. High throughput technologies are vital for rapid determination of optimal crystal growth conditions, allowing fast formulation of precisely controlled precipitation conditions and minimizing the quantity of protein and reagents required. Dr Harry Gill, Assistant Professor and Director of the PEPCC, explained: “Protein crystallization is an empirical science, requiring thousands of solution compositions to be tested for each protein to establish the optimal conditions for generation of protein crystals with well formed lattices that diffract X-rays. The advent of rapid genetic sequencing technologies means that many structural genomics laboratories and consortia are now looking at the three dimensional structures of

proteins on a genome-wide scale. The high throughput offered by laboratory automation is essential for these large scale studies, precisely controlling not just the concentrations and ratios of the target protein, buffers and precipitants, but also the liquid handling characteristics which can significantly influence crystal formation.

Automation minimizes the variation inherent in manual techniques, and helps us to rapidly identify the conditions needed to crystallize a particular protein.”

“The PEPCC was established to provide a highly efficient system for elucidating crystallization conditions for a variety of soluble and membrane proteins, and we use a three step robotic workflow to perform large scale protein crystallization trials. The first step is drop-setting nanoliter amounts of protein onto 96-well plates using a mosquito® Crystal automated drop-setter (TTP LABTech). The plates are then incubated

PROTEOMiCS TECAN JOURNAL 1/2011

in a Rock Imager (Formulatrix), a fully automated incubation and imaging system which has been specially designed for protein crystallization. Once a hit – evidence of crystallization – has been identified by this system, data is exported to our Freedom EVO workstation, and we use its CrysScreen software to design and prepare an experiment in which crystallization parameters – such as pH, salt and precipitant concentration – are adjusted to optimize crystal formation. This new set of parameters is then tested using the drop-setter and incubation system, and the cycle is repeated until a high quality crystal structure is achieved.”

“We have also taken advantage of the Freedom EVO’s flexibility to increase our productivity in other areas. It is one of the most versatile systems on the market, and our workstation is configured to perform high throughput plasmid preparation in addition to optimization of crystallography. We also have an Infinite® M1000 multimode plate reader incorporated onto the Freedom EVO platform, enabling us to rapidly screen large libraries of DNA clones and to perform a broad range of spectrophotometric assays. The ability to fully integrate this reader into the Freedom EVO is a real bonus, as the Infinite M1000 is probably the most sensitive multimode instrument on the market for measurements in the deep UV spectrum. These measurements would normally have to be performed in a fluorometer to achieve the necessary sensitivity, requiring tedious manual reading of individual cuvettes. The Infinite reader is able to offer the same performance in an automation-friendly 96-well format, thanks to its premium Quad4 Monochromators™.

This instrument really is at the cutting edge of reader design, and is an indispensable tool in my research.”

Harry concluded: “Automation of high throughput crystallization trials is crucial, ensuring accurate pipetting while minimizing the amount of protein required for each experiment. When we originally set up the PEPCC, we evaluated a variety of liquid handling systems for this role. The availability of the specialized CrysScreen software, together with the flexibility of the Freedom EVO platform, made the Tecan system an obvious choice for this role. Thanks to CrysScreen, we are able to set up crystallization trials very quickly, achieving in minutes what would have taken almost a week to perform manually.”

Rock Imager

Dr Gill would like to thank LCDR Matthew Swiergosz for his assistance with the Defense University Research Instrumentation Program (DURIP) awards and Char Rogge for her assistance with Action and Investment Funds created by the Ohio Board of Regents.

To find out more about Tecan’s Freedom EVO workstations, go to www.tecan.com/freedomevo To learn more about the PEPCC, visit www.pepcc.case.edu mosquito is a registered trademark of TTP LABTech.

Imaging, viewing and storage

mosquito

High throughput crystallization screening cycle

Experiment optimization, formatting and dispensing

Nanoliter protein drop setting

Tecan Freedom EVO High throughput protein fluorescence assays

PEPCC protein crystallization workflow

High throughput DNA purification

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QUALITY TECAN JOURNAL 1/2011

Ensuring quality and reliability Validation is a Good Manufacturing Practice (GMP) requirement with benefits for both Tecan and its customers.

Validation is a regulatory requirement which enables manufacturers to achieve a high level of quality, even in situations where it is not possible to test each individual component or product. The processes that are most likely to be selected for validation are those whose results cannot be measured without rendering a product unusable.

Giuseppe Grignano, Global Compliance Validation Manager at Tecan, explained: “Validation is beneficial to both Tecan and its customers. It is essential that any product, particularly in the medical sector, is faultless, and validation ensures a high standard of product quality, safety and reliability. At Tecan, we identify potential risks at every stage of development and production and, if the product does not perform as expected, we can address the issue in house prior to marketing the instrument. Being proactive in this way has given Tecan a reputation for quality and reliability – guaranteeing that every product we market is of a high quality, is safe and stable, and meets customer expectations – and this is one of the main reasons customers choose Tecan.”

“Design validation is just one aspect of the overall validation process. Validation also involves manufacturing processes for which the output cannot be verified. This encompasses the software system used to support quality activities, inspection activities, handling of non-conformance and complaints, and corrective and preventive action (CAPA). To support the management of the validation process, and to achieve full compliance status, Tecan has a Global Master Validation Plan, along with specific Master Validation Plans for individual sites and departments. These are key elements, not only for monitoring ongoing compliance, but also for meeting site business goals in terms of operational performance, quality and efficiency. The results of this monitoring are regularly reviewed by senior management, which gives them an overview of the situation and allows them to ensure validation projects are running according to schedule, taking corrective action if necessary.”

Product development and validation using the V-model standard

Initialization

Operation System Acceptance

V- Model

Requirements Design Phase

Verification Phase

System/ Functional Specifications

System/ Functional Test

Detailed Design

Integration

Module Specifications

Unit Test

Realization

Risk Management (Supporting Process)

TALK TO TECAN TECAN JOURNAL 1/2011

“Tecan has developed a validation process following the V-model life cycle industry standard, which outlines all the requirements for correct execution of the validation process.

We establish the objectives we want to achieve for each phase of the validation, and formal testing verifies that these defined objectives are met. Our validation protocols include details of how testing should be performed, in what environment, and what acceptance criteria must be met to establish that a product performs as specified.

All testing activities are documented and supported by statistical data to demonstrate compliance, such as analysis of variance and/or process capability studies, and records of staff training are also maintained. This ensures that the validation has been performed correctly, and that there is evidence that the required parameters and specifications of the product are met at all times.”

Giuseppe continued: “During customer audits, we are frequently asked how a product has been tested and subsequently validated during its development and production. Customers like the way we record our testing activities in detail, and we have received very good feedback about the quality of our validation procedures. If a customer needs to submit validation data to a regulatory authority, for example to prove that the platform they are using for their application has been properly developed and tested, then Tecan can provide them with a copy of this data and the supporting documentation. By relying on our documentation, the customer only has to validate their specific application, saving them time and money while still achieving full compliance for regulatory submission.”

Giuseppe concluded: “It’s a win-win situation, with proper validation building a solid foundation for quality and success.”

The Validation Program covers all aspects of the validation within Tecan

Global

Local Site

Area/ Department

Tecan Global Master Validation Plan

Site MVP

MasterValidation ValidationPlans Plans Master

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Frederic Vanderhaegen, Senior Vice President, Head BU Life Science

Leading the debate Tecan’s greatest strength has always been in staying close to researchers, anticipating their needs and understanding their workflows, and this has fuelled the growth and success of our company for over 30 years.

During this time, the life science world has expanded and subdivided into discrete segments, and these changes have triggered a recent structural reorganization of our company.

The term ‘life science’ now encompasses many demanding niches with distinct technological requirements quite different from one another. By realigning our company structure, we aim to sharpen the focus on each of these niches, making their challenges and opportunities more transparent.

Our new strategy must account for customers demanding more turnkey solutions, deeper expertise and dedicated systems that address smaller processing volumes, bottlenecks in sample preparation, higher detection sensitivity and user-friendly software. Our goal is to identify the most critical priorities for each of these applications, and to mould our strategic focus around their individual challenges. We will develop our product portfolio with this in mind, driving innovation and keeping a look out for new technologies and partnerships that will add value to our offering and benefit our customers.

Thank you for your past support, your encouragement and your future commitment to Tecan.

Email talk@tecan.com to tell us what you think about the significance of the changes to the life science arena, Tecan and how technology companies can help to address Global Master these changes.

Validation Plan Site MVP

Master Validation Plan

EVENTS 2011 TECAN JOURNAL 1/2011

Meet Tecan at these events from now until July of this year Americas

Lab Automation 2011 (ALA)

Palm Springs, CA

29 Jan – 02 Feb 2011

Biomarker Assay Development

San Diego, CA

31 Jan – 02 Feb 2011

MSACL 2011

San Diego, CA

05 – 09 Feb 2011

MS&M West 2011

Anaheim, CA

08 – 10 Feb 2011

American Academy of Forensic Sciences (AAFS 2011)

Chicago, IL

21 – 26 Feb 2011

Pittcon 2011

Atlanta, GA

13 – 18 Mar 2011

SBS 2011

Orlando, FL

27 – 31 Mar 2011

microRNA in Human Diseases & Development

Cambridge, MA

28 – 30 Mar 2011

The 59th ASMS Conference on Mass Spectrometry (ASMS 2011)

Denver, CO

05 – 09 June 2011

American Association for Clinical Chemistry (AACC) Annual Meeting (Clinical Lab Expo 2011)

Atlanta, GA

24 – 28 June 2011

Lorne, Australia

06 – 10 Feb 2011

Asia and Pacific

The 36th Lorne Conference on Protein Structure and Function The 23 Lorne Cancer Conference

Lorne, Australia

10 – 12 Feb 2011

Lorne Infection and Immunity Conference 2011

Lorne, Australia

16 – 18 Feb 2011

Japan Society for Bioscience, Biotechnology and Agrochemistry (JSBBA)

Kyoto, Japan

25 – 28 Mar 2011

The 10 International Bio Forum and Bio Expo Japan

Tokyo, Japan

29 June – 01 July 2011

rd

th

Europe, Middle East and Africa

ARABLAB

Dubai, UAE

07 – 10 Mar 2011

Laborama 2011

Brussels, Belgium

24 – 25 Mar 2011

Tecan. For all your laboratory automation needs.

Liquid Handling & Robotics | Detection | Components | Services & Consumables Headquarters: Tecan Group Ltd., Seestrasse 103, CH-8708 Männedorf, Switzerland T +41 44 922 88 88 F +41 44 922 88 89 info@tecan.com

Tecan Austria +43 62 46 89 33 Belgium +32 15 42 13 19 China +86 21 289 86 333 Denmark +45 70 23 44 50 France +33 4 72 76 04 80 Germany +49 79 51 94 170 Italy +39 02 92 44 790 Japan +81 44 556 73 11 Netherlands +31 18 34 48 17 4 Singapore +65 644 41 886 Spain +34 93 490 01 74 Sweden +46 31 75 44 000 Switzerland +41 44 922 89 22 UK +44 118 9300 300 USA +1 919 361 5200 Other countries +43 62 46 89 33

www.tecan.com

Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Marc Wetli/Zürich www.wetli.com, Günter Bolzern/Zürich www.bolzern.net, Susanne Völlm/Zürich www.susannevoellm.ch Editor in Chief: Tecan Trading AG, Cornelia Kegele Project Lead: Tecan Trading AG, Cornelia Kegele/Tanja Sager Editor: kdm/UK www.kdm-communications.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com, www.tecan.com To register for the Tecan Journal please go to www.tecan.com/journal © 2011 Tecan Trading AG, Switzerland, all rights reserved.

Tecan Group Ltd. makes every effort to include accurate and up-to-date information within this publication, however, it is possible that omissions or errors might have occurred. Tecan Group Ltd. cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided in this publication. Changes in this publication can be made at any time without notice. All mentioned trademarks are protected by law. In general, the trademarks and designs referenced herein are trademarks, or registered trademarks, of Tecan Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks.

Product names and company names that are not contained in the list but are noted herein may be the trademarks of their respective owners. For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative.

This journal may contain reference to applications and products which are not available in all markets. Please check with your local sales representative: www.tecan.com/contact