Edition 2/2011

Tecan JournalLife Sciences and Partnering Business

Ensuring quality foodproduction in Italy

page 30-31

Culturing adult hippocampal precursor cellspages 22-23

A plate of live fi sh!pages 24-25

Living in harmony is probably the best medicine you will needpage 26-27

Wel

com

e

Welcome to the latest edition of the Tecan Journal.

The Tecan philosophy has always been to deliver market-led innovations that fulfi ll the laboratory automation needs of our customers. The fast-paced development of the life sciences sector means we are also continually seeking new, ground-breaking, third party products and technologies that enhance the broad product range of our Life Sciences Business. In this issue you will fi nd details of several exciting new collaborations, including an automated colony picking solution designed specifi cally for Freedom EVO® platforms, and agreements with Attana AB and Sword Diagnostics for the distribution of biosensor and immunoassay detection technologies which will further strengthen our portfolio.

Also in this issue we have details of how researchers have been benefi ting from our latest detection off erings – the HydroSpeed™ plate washer and the Gas Control Module (GCM™) for the Infi nite® 200 PRO reader – demonstrating the importance of the close ties Tecan has with its life science customers. This experience and profound knowledge is also vital to our OEM business, and we were recently able to announce a new agreement with DiaSorin for the supply of a fully automated clinical ELISA workstation for use with DiaSorin’s MUREX product line, based on our existing clinical ELISA platform, the Freedom EVOlyzer®, with an integrated Sunrise™ absorbance reader and a HydroFlex™ microplate washer.

We hope you enjoy the issue,

Thomas Bachmann, CEO

2 CEO WELCOME TECAN JOURNAL 2/2011

2 CEO welcome

4 EVO Logic simplifi es Genesis™ trade-in

5 Tecan and Attana sign North America distribution agreement

5 Tecan and HP to develop new drug-dispensing solutions for research

6-7 LabAutomation 2011

8 New sample preparation solutions for Roche 454™ next generation sequencing

8 Tecan and SciRobotics off er integrated colony picking for molecular biology

9 Application-focused consumables for life sciences

10-11 A real winner for multiple sclerosis research

12-13 The cutting edge of assay development

14-15 On track to personalized medicine: the right drug for the right patient

16-17 A leading light for drug discovery

18-19 Bridging the gap with Automatic Genomics

20-21 Breathing new life into cell-based studies

22-23 Culturing adult hippocampal precursor cells

24-25 A plate of live fi sh!

26-27 Living in harmony is probably the best medicine you will need

28-29 Miniaturized FISH

30-31 Ensuring quality food production

31 Leading the debate

32 Events

page 4

page 6-7

page 28-29

Cont

ents

page 18-19

EVO Logic™ simplifi es switch to the Freedom EVO platform, without disrupting existing laboratory processes

Freedom EVO-based system provides an aff ordable way of performing large scale FISH screening of cytological specimens

3CONTENTS TECAN JOURNAL 2/2011

EVO Logic™ simplifi es Genesis™ trade-inThe Genesis workstation has been superseded by our more powerful Freedom EVO® platform and, from January 2012, we will no longer be providing support for the Genesis. Last year, many customers took advantage of our special off er to make the transition to Freedom EVO workstations, and our network of service and application specialists has been working closely with these customers to ensure this change has been as smooth as possible.

To further simplify switching to the Freedom EVO platform without disrupting existing laboratory processes, Tecan has developed EVO Logic. Designed to run alongside the new platform’s Freedom EVOware® software, this open and fl exible

solution is intended for laboratories currently using the Logic software for the Genesis platform, and helps to ensure full compatibility with existing working practices, protocols and LIMS interfaces. EVO Logic’s sample-driven architecture makes it easy to transfer existing protocols and begin using your Freedom EVO workstation, without the need for extensive process validation or staff training.

To fi nd out more on Tecan’s EVO Logic software, visit www.tecan.com/evologic

4 PRODUCT NEWS TECAN JOURNAL 2/2011

The Attana Cell 200 system

Tecan and HP have entered into an agreement to commercialize a new automation solution for pharmaceutical drug discovery, based on HP’s high performance inkjet dispensing technology. This innovative system will accelerate and improve the evaluation of novel drug

candidates in pharmaceutical development, by allowing researchers to assess potential drug compounds at very low concentrations.

Intended for research use only, the product is expected to be commercially available later this year, and is designed to improve

accuracy when testing drug interactions and evaluating drug eff ectiveness. The HP branded instruments and supplies, which will initially be marketed in the United States and Europe, will be exclusively distributed, serviced and supported through Tecan’s Life Sciences Business.

The announcement was celebrated with a champagne toast in the Tecan booth at SBS

The commercialization agreement was announced at SBS in Orlando, Fl. Joe Dody, Business Manager from HP, and Mark Hozza, Vice President and General Manager from Tecan, unveiled the instrument

Tecan and HP to develop new drug-dispensing solutions for research

Tecan and Attana sign North America distribution agreement

To fi nd out more about the Attana range, visit www.attana.com

Tecan has signed an exclusive distribution agreement with Attana AB – a leading manufacturer of quartz crystal microbalance

biosensor instruments – for the distribution, service and support of Attana’s instruments and assay technology in North America.

Attana’s label-free biosensors employ quartz crystal microbalance (QCM) technology to follow the interaction between drug candidates and receptors in their natural environment, providing valuable information about not only the specifi c interaction with the receptor, but also off -target interactions. This technology can be used to determine a candidate compound’s specifi city, target affi nity and binding kinetics for a wide range of biomolecules and macromolecular structures, helping to improve the success of pre-clinical trials by providing researchers with biologically relevant information.

“Through this agreement we are able to off er customers a complete solution for biomolecular investigation,” commented Gabriela Suhoschi, Marketing Manager at Attana. “Tecan’s sample management and detection solutions are complementary to our own molecular characterization technologies and, as an innovative company with a strong presence in North America, Tecan was a logical choice of partner.”

Attana’s biosensor technology is already well established in both the biopharma and academic sectors in North America, and this agreement will ensure a rapid, fl exible service for the Company’s customers. Tecan will supply Attana’s complete portfolio of innovative cellular and molecular characterization systems, biosensor chips and consumables – as well as providing technical and service support in the region – working closely with Attana engineers and application specialists to provide the best solution for customers.

5CORPORATE NEWS TECAN JOURNAL 2/2011

LabAutomation 2011Continuing the partnership theme, Tecan was joined on the booth by Sword Diagnostics, who introduced delegates to the innovative Sword™ Detection System, a high performance immunoassay reporter technology which takes advantage of the flexibility of Tecan’s Infinite M1000 and Infinite M200 PRO series readers. Tecan instruments could also be seen on a number of other booths throughout the exhibition hall, including Artel’s, where the Company’s Multichannel Verification System (MVS) technology for liquid handling performance validation was being demonstrated on a Freedom EVO platform.

Alongside the main exhibition, a series of industry sponsored technical workshops provided delegates with greater insight into the day-to-day application of these latest advances in laboratory automation. Tecan continued its support for this initiative by hosting a session on interfacing with Freedom EVOware®, as well as providing support for an MVS workshop by Artel, and we are already planning for next year’s show!

This year’s ALA LabAutomation Conference celebrated 15 years of bringing together science, technology and industry to showcase the latest developments in laboratory automation. Held in Palm Springs Convention Center, California, this annual event provides a unique opportunity to meet like-minded colleagues from around the world, while exploring exciting new developments in laboratory automation. With attendance up on last year, Tecan enjoyed another successful exhibition, and customers old and new visited the Tecan booth to discover the Company’s latest offerings for the life science sector.

A selection of automated workflow solutions based on the Freedom EVO® platform were in action, including automated library preparation for next generation sequencing, as well as the latest detection products, such

as the HydroSpeed™ plate washer and the patent pending Gas Control Module (GCM™) for the Infinite® 200 PRO reader. Visitors were also able to see the Attana range of quartz crystal microbalance systems on the Tecan booth for the first time. Catering to the biopharmaceutical sector, Attana’s molecular characterization instruments perfectly complement Tecan’s liquid handling portfolio, and users of these systems in North America will now be able to benefit from Tecan’s extensive service and support network (see Corporate News on page 5).

6 CORPORATE NEWS TECAN JOURNAL 2/2011

Caroline HuberSenior Market Manager Genomics & Forensics

Read more about Tecan’s partnership with Attana on page 5

Jessica MerlinoSales Engineer Liquid Handling

CORPORATE NEWS TECAN JOURNAL 2/2011 7

Pickolo colony-picker on the Freedom EVO workstation

New sample preparation solutions for Roche 454™ next generation sequencing

Tecan and SciRobotics offer integrated colony picking for molecular biology

This latest innovation is part of Tecan’s ongoing commitment to the genomics market, working with leading technology providers to offer integrated automation solutions that help laboratories deal with large sample populations and increasingly complex workflows.

To find out more on Tecan’s genomics solutions, visit www.tecan.com/genomics

454, 454 Life Sciences, 454 Sequencing, GS FLX, GS Junior, emPCR, PicoTiterPlate and REM are trademarks of Roche.

To find out more about automated molecular biology workflows on Tecan’s Freedom EVO platforms, visit www.tecan.com/cellbiology

To learn more about SciRobotics’ Pickolo colony-picker, go to www.scirobotics.com

Pickolo is a trademark of SciRobotics Ltd.

Tecan has been working in collaboration with 454 Life Sciences™, part of Roche Applied Science, to automate emulsion PCR (emPCR™) sample preparation using Freedom EVO® workstations. Integration of the REM™ e System onto the Freedom EVO platform allows complete automation of emPCR enrichment and sequence primer annealing steps for Roche’s 454 Sequencing™ Systems, dramatically simplifying the sequencing workflow.

The Freedom EVO/REM e combination offers a fully automated, walkaway procedure that replaces hours of dedicated manual processing, increasing sequencing productivity and consistency for Roche 454 GS formats. This cost-effective solution has been developed by Roche, to suit various throughput needs on the Freedom EVO 75

SciRobotics’ Pickolo™ colony-picker can be integrated onto the Freedom EVO liquid handling workstation to provide customers with a complete solution for automation of molecular biology workflows: from cloning to PCR sequencing or cell-based screening.

Developed and supplied by SciRobotics specifically as an add-on for the Freedom EVO platform, the Pickolo enables fully automated colony picking from agar plates in both Petri dish and multi-well plate formats. The combination of high resolution digital imaging technology and flexible, easy-to-use analysis software enables selection of individual colonies based on user-defined criteria – including size, shape and color – and can be extended to fluorescence-based applications with the addition of a Tecan detection instrument.

for use with GS FLX™ sequencers. Protocols for the GS Junior™ System will be made available by Roche soon.

“Automation offers us an attractive alternative to manual protocols for the purification and isolation of amplified beads,” said Associate Professor Tomas Johansson, from the Department of Biology at Lund University. “The entire process can be reduced from around eight hours manually to just less than four hours of automated procedure, with no loss of performance. In addition, automated protocols are available for various choices in emPCR, giving the opportunity to divide a PicoTiterPlate™ into anything between 2 and 16 library regions to match our processing requirements.”

“Incorporation of colony picking onto Freedom EVO platforms has generated a huge amount of interest from our customers, offering them the end-to-end automation for molecular biology that they have long desired,” said Dr Tamara Brown, Market Manager for Cells and Proteins at Tecan. “The Pickolo system can be quickly and easily installed on existing Freedom EVO workstations, providing a cost-effective, off-the-shelf solution.”

Pickolo enables automated picking of up to 800 colonies per hour, and is fully interfaced with Tecan’s reliable Freedom EVOware® software, ensuring seamless integration with upstream and downstream processes for improved molecular laboratory productivity.

Roche REM e device integrated onto the Freedom EVO platform

8 PRODUCT NEWS TECAN JOURNAL 2/2011

Tecan continuously strives to provide quality consumables which meet the changing needs of life sciences research. The recent trend towards high content, cell-based screening has seen an increase in demand for automation of this type of assay, and Tecan now off ers disposable tips for Freedom EVO liquid handling (LiHa) arms in Tecan Sterile purity.

Previously only available in Tecan Standard or Tecan Pure formats, LiHa disposable tips are now available in Tecan’s highest purity level, and are ideally suited to cell-based assays and screens, as well as microbiology applications. Available in 50, 200 and 1,000 µl volume sizes, either as fi ltered or non-fi ltered options, tip racks are individually packaged in new SBS-format boxes with an automation-friendly lid to minimize the risk of contamination. The SBS-format increases fl exibility on the worktable, as well as off ering higher throughput and longer walkaway times, by ensuring full compatibility with the Freedom EVO’s storage and automation devices. In accordance with Tecan’s high quality standards, all Tecan Sterile LiHa disposable tips are lot tested by an external, accredited laboratory to ensure tips are sterile and free from human DNA, RNase, DNase, PCR inhibitors and pyrogens/endotoxins. In

addition, each box of tips is supplied with a lot specifi c Certifi cate of Conformity (CoC) which guarantees purity level specifi cations and off ers full product traceability.

Tecan has also recently launched a new 25 ml trough designed to minimize waste of reagents when using the LiHa arm. The conical base design of this trough reduces the dead volume for conductive liquid level detection (cLLD) by a third compared to the standard shaped Tecan trough, making it ideally suited for use with the valuable reagents now commonplace in many assays. Currently available in Tecan Pure format, this innovative yet simple product helps to reduce reagent costs while being fully compatible with existing hardware.

To fi nd out more on Tecan’s high quality consumables, visit www.tecan.com/consumables

New Tecan trough design minimizes dead volume

Application-focused consumables for life sciences

Tecan Sterile LiHa disposable tips

9PRODUCT NEWS TECAN JOURNAL 2/2011

The Center for Neurologic Diseases at the Brigham and Women’s Hospital, Harvard Medical School, Massachusetts, is a group of multidisciplinary biomedical research laboratories investigating the causes of, and new treatment strategies for, chronic neurological diseases, with an emphasis on multiple sclerosis (MS), Alzheimer’s disease and Parkinson’s disease.

Focusing on the deregulation of the immune response in MS, Dr Francisco Quintana’s laboratory uses a systems biology strategy to explore the signaling pathways affected, combining experimental models and clinical samples to develop a better understanding of the disease. Dr Quintana explained: “MS is a neurological disorder caused by an autoimmune response to the central nervous system (CNS), however, little is currently known about the roles of the innate and the adaptive immune response in different stages of the disease. We are

In the last Tecan Journal we announced that Dr Francisco Quintana from the Harvard Medical School had become the first ever winner of the Tecan Detection Award. Dr Quintana’s laboratory is using a range of Tecan instruments – including a HS 4800™ Pro hybridization station, a PowerScanner™ and an Infinite® F200 microplate reader – as part of a systems biology approach to studying the role of the immune response in multiple sclerosis.

A real winner for multiple sclerosis research

investigating the signaling mechanisms which control the immune response to discover unique biomarkers which might characterize particular stages of MS, the activity of specific pathogenic mechanisms or indicate who is likely to respond to a given treatment. We are also trying to identify novel therapeutic targets, to develop new drugs to help alleviate patients’ symptoms.”

“In addition to clinical samples, we use several animal models of MS to study inflammation of the CNS. We have both mouse and zebrafish disease models, and use a variety of in vitro techniques to characterize these models and understand the underlying molecular mechanisms for what we observe in the animals. A majority of these studies involve fluorescence- or luminescence-based methods, including enzyme activity assays, gene reporter/gene function assays and ELISAs. To follow these assays we use an Infinite F200 microplate

The HS 4800 Pro allows the Center for Neurologic Diseases to process up to 48 slides per run

Dr Francisco Quintana

10 MICROARRAYS TECAN JOURNAL 2/2011

reader, which is ideally suited to this kind of work. The instrument’s multimode capabilities allow us to perform various assay types on a single platform, and we are very happy with its performance.”

To support the group’s research, Dr Quintana has also established a microarray core facility which develops and runs antigen and reverse phase protein microarrays for a wide range of studies. “We are able to fabricate our own antigen microarrays, using an automated system to spot up to 600 different proteins, peptides or lipids of interest onto slides,” Dr Quintana continued. “We then hybridize these with samples from either MS patients or animal models using an HS 4800 Pro hybridization station. The arrays are read with the PowerScanner, and are analyzed by the group’s bioinformatician, with the help of Tecan’s software. We use these arrays to identify potential biomarkers for MS, elucidate mechanisms of patho- genesis and ascertain which signaling pathways are activated in response to therapeutic interventions. For example,

we use antigen arrays to identify lipids that might be important in the progression of MS.”

“When we initially set up this facility, we explored systems from a number of different manufacturers, and the service we received from Tecan was outstanding. We were able to test the instruments in our own laboratory, which is a real bonus as it allows you to use the instrument with your own samples, and the Tecan representative was extremely knowledgeable. The HS 4800 Pro was also the only competitively priced hybridization station that allowed us to run multiple samples in parallel. While most systems could only run 4 or 8 slides, the HS Pro enables us to process up to 48 multi-segment slides per run.”

“Automation was a major consideration when assessing microarray instruments. Although we were already performing a majority of these studies manually, automation reduces the ‘noise’ inherent in manually processed experiments,

helping to improve the quality of results and simplify data interpretation. Coupling the HS Pro with the walkaway operation provided by the PowerScanner also gives us the capacity we need as a core facility, without causing an excessive drain on resources,” Dr Quintana concluded.

To find out more on Tecan’s microarray solutions, visit www.tecan.com/microarray

To find out more on The Center for Neurologic Diseases, visit brain.bwh.harvard.edu

The PowerScanner offers walkaway scanning for higher throughput

The orange ribbon is a symbol of Multiple Sclerosis awareness

11MICROARRAYS TECAN JOURNAL 2/2011

Sword Diagnostics, based in Chicago, Illinois, was founded in 2005 to commercially develop United States Navy technology originally intended for biological weapon detection. Sword has become a leading authority in making diagnostic tests more sensitive, and its Sword Detection System provides outstanding sensitivity for scientists studying and quantifying low-abundance biomarkers in ever-decreasing sample volumes.

Mitch Gaver, Director of Business Development and Marketing at Sword, explained: “The Sword technology is based on Raman spectroscopy; the patented Sword Peroxidase Reagent has a very low Raman signal until it is oxidized by horseradish peroxidase, when it gives a high signal. The stronger signal of this technology off ers greater sensitivity compared with traditional colorimetric or chemiluminescent assays, so our customers get better performance from their assays in terms of sensitivity, precision and accuracy, particularly at very low target concentrations. Alternatively, it allows

Tecan has partnered with Sword Diagnostics, a leader in detection chemistries, to optimize the sensitivity of immunoassays using the patented Sword™ Detection System on the fl exible Infi nite® M200 and Infi nite M1000 microplate readers.

The cutting edge of assay development

the customer to reduce their sample sizes, permitting more tests for the same amount of sample. However good their existing assay is, a vast majority of researchers want more sensitivity, and our customers have been very excited about the enhanced sensitivity this technology brings.”

Dr Neal Siegel, Chief Scientist at Sword, added: “Our chemistry focuses on improving signal detection; by directly substituting a given assay’s existing detection chemistry, we get improved performance without the need to make any substantial changes to other aspects of the assay. Substrates such as tetramethylbenzidine (TMB) have fundamental limitations to their detection, and we are able to overcome these. In addition, by working with our customers and with Tecan’s experts in detection hardware to optimize the assay, we have been able to further improve the detection limits for our reagents, something that cannot be readily achieved with TMB*. This will not be surprising to assay development scientists; when any new

12 READERS TECAN JOURNAL 2/2011

detection system is introduced into an existing assay, further adaptation or optimization of the assay to the new detection system is often benefi cial.”

“Tecan is an excellent choice as instrument provider for this technology,” explained Dr Charlie Ginsburgh, Senior Scientist at Sword. “In the early stages of our product development, we thought we would need an instrument that would specifi cally detect Raman scattering. This would not be ideal in many respects, not least because potential customers would need to buy a new instrument just to take advantage of the chemistry. As we reviewed diff erent instrument options, we discovered that Tecan’s Infi nite series readers have outstanding optics for fl uorescence detection, and are easily able to detect the Raman signal. By partnering with Tecan, we are able to off er a new substrate technology that will improve assay performance, using kits and instruments our customers already have in the laboratory. Our chemistry is manufactured in an ISO certifi ed facility, and works very well on Tecan’s Quad4 Monochromators™-based Infi nite M200 and M1000 plate readers, with no special modifi cations required.”

Mitch concluded: “The new technology was received with great interest by visitors to LabAutomation in January. Many assays are based on horseradish peroxidase detection, and so we have initially concentrated on this substrate, however we are already looking

at other types of molecules and substrates, and eventually hope to apply this technology to direct labels. In addition, although the Sword Detection System is currently authorized for research use only, our goal is to also incorporate the technology into diagnostic tests.”

Sword Detection System enhances immunoassay sensitivity

To fi nd out more on Tecan’s Infi nite series, visit www.tecan.com/detection

To learn more about Sword Diagnostics, go to www.sworddiagnostics.com

*Technical notes describing Sword Diagnostics technology in use with Tecan’s Infi nite M200 and Infi nite M1000 multimode readers are available at www.tecan.com/infi nitem1000literature and www.tecan.com/infi nite200proliterature

13READERS TECAN JOURNAL 2/2011

Left to right: Matthew Rosenow, Kostantinos Petritis and Linda Nagore with the SISCAPA system

Protein biomarkers have the potential to completely change the way in which diseases are diagnosed and treated. The Center for Proteomics at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona, is actively involved in biomarker discovery, verification, and validation, as Dr Konstantinos Petritis, Associate Professor and Laboratory Head, explained: “Many protein biomarkers provide an indication of a person’s state of health, and can be used to identify individuals at risk of developing particular diseases. Our goal is to identify protein biomarkers to improve early disease detection or to predict a patient’s response to a specific treatment, through non-invasive sampling of readily accessible body fluids, such as blood plasma. These markers will help to inform clinical decisions, bringing us much closer to the realization of personalized medicine; the delivery of the right drug to the right patient at the right time.”

Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA) is a key proteomic technology used in biomarker assay development. During biomarker discovery, TGen works with between 20

Scientists at the Translational Genomics Research Institute in the US have recently taken delivery of a Stable Isotope Standards with Capture by Anti-Peptide Antibody (SISCAPA) sample preparation system.

On track to personalized medicine: the right drug for the right patient

and 100 samples, which are easily prepared manually. However, once the biomarkers have been identified, verification and clinical validation must be performed, and the challenge is to process hundreds, or even thousands, of samples. TGen has several mass spectrometers that can accommodate large numbers of samples, but the process of verification and validation is extremely long and labor intensive, involving many critical stages that must be performed reproducibly. It may take several days to prepare just a few samples, and this has been the rate-limiting step for TGen’s proteomic work.

Dr Petritis continued: “We needed a high throughput, automated workflow to standardize biological sample preparation, limit sample-to-sample variability and enhance downstream mass spectrometry-based analysis for large scale verification studies, but there was no suitable system on the market. Every stage of our workflow was analyzed to try to find a solution. There are, for example, light-sensitive reactions, stages that need to be completed rapidly, and other stages that require plate shaking or temperature control. To meet all these requirements we needed to integrate many different modules, from multiple vendors, onto a single, automated liquid handling platform. Tecan provided a nicely integrated system and then worked with us to customize it to our needs. With such a complex platform, and so many different components to integrate, Tecan’s experience of incorporating many of these instruments into other customers’ systems was a real strength. Everything is controlled by Freedom EVOware® Plus, and, as Tecan already had the drivers, the whole package came together very neatly without incurring any additional costs.”

The system has been designed to, for example, take human plasma samples presented in cryovials, aliquot them into 96-well plates, and then process them to generate a 96-well plate that is ready for mass spectrometry (MS) analysis. This LiCONiC™ incubator integrated onto the SISCAPA sample preparation system

14 LIQUID HANDLING & ROBOTICS TECAN JOURNAL 2/2011

LiCONiC incubator integrated onto the SISCAPA sample preparation system

processing is fully automated, and includes denaturation, reduction, alkylation and digestion of the proteins, as well as antibody capture and elution of the resulting peptides of interest. In addition, the platform is fl exible enough to perform advanced functions, allowing processing of other biofl uids and the analysis of cell or tissue lysates. TGen also performs quantitative protein assays – using a Tecan Infi nite® M200 PRO multimode plate reader – and trypsin optimization, as well as QA/QC functions. Dr Petritis concluded: “The main reason for purchasing the SISCAPA workstation was to prepare samples

for analysis by MS. The new, automated system will allow us to prepare up to a thousand samples a day if necessary, rather than the 10 or 20 we can do manually, eliminating this bottleneck. This is a great strength of the automated SISCAPA sample preparation system.”

To fi nd out more about Tecan’s Freedom EVO liquid handling platform, visit www.tecan.com/freedomevo

To fi nd out more about the Translational Genomics Research Institute, visit www.tgen.org/research

TGen’s SISCAPA system consists of:

• Freedom EVO® 200 liquid handling platform

• 8-channel liquid handling (LiHa) arm

• Robotic manipulator (RoMa) arm

• Temperature controlled carriers

• Symbol MS954 barcode scanner

• Thermoshake and Teleshake microplate shakers

• XPeel™ seal peeler

• VSpin™ centrifuge

• LiCONiC incubators and plate hotels

• KingFisher® Flex magnetic processor

• Infi nite M200 PRO multimode microplate reader

• PlateLoc sealer

VSpin is a trademark of Agilent Technologies, XPeel is a trademark of Nexus Biosystems, KingFisher is a registered trademark of Thermo Fisher Scientifi c Inc. and its subsidiaries and LiCONiC is a trademark of LiCONiC Instruments.

Left to right: Matthew Rosenow, Konstantinos Petritis and Linda Nagore with the SISCAPA system

15LIQUID HANDLING & ROBOTICS TECAN JOURNAL 2/2011

Euroscreen is a pre-clinical drug discovery company based in Gosselies, Belgium, focusing on development of small molecule drugs for unmet clinical needs. Specializing in G-protein coupled receptors (GPCRs), Euroscreen works with a number of major pharmaceutical manufacturers to develop and optimize fi rst-in-class candidate compounds targeting GPCRs. In addition to its research activities, Euroscreen also operates a high throughput screening (HTS) service (Euroscreen FAST) providing customized GPCR screening and services for biotechnology companies and pharmaceutical manufacturers worldwide.

Euroscreen FAST carries out a variety of drug development studies on behalf of its customers – including lead optimization, candidate profi ling, target characterization and ligand identifi cation – using its extensive in-house library of GPCR assays, as well as the Tango™ GPCR assay system from Life Technologies. To ensure high quality results across its broad range of assays, Euroscreen needed a multimode microplate reader off ering optimal performance in both fl uorescence and luminescence modes, as research scientist Laurent Meeus explained: “We develop and run numerous assays in support of our clients’ drug development activities, requiring a reader with a great deal of fl exibility to accommodate the varying needs of each project. In addition, we recently signed a licensing agreement with Life Technologies to use its Tango GPCR assay system, and so wanted a reader off ering optimal performance for these

Euroscreen S.A. has chosen Tecan’s fl exible Infi nite® F200 PRO multimode plate reader for a variety of screening applications in drug discovery and characterization.

A leading light for drug discovery

assays. We assessed multimode readers from various manufacturers, and Tecan’s Infi nite F200 PRO represented the best combination of performance and value, as well as benefi ting from Tecan’s high quality technical support.”

Jerôme Bernard, managing director for services activities at Euroscreen, added: “By using the Infi nite F200 PRO in conjunction with our existing Tecan liquid handling workstation, we are now able to off er high throughput screening for small molecule GPCR ligands, using fl uorescent or luminescent reporter systems. The platform is able to automatically cherry-pick positive results for verifi cation and, once hits have been confi rmed, it then prepares serial dilutions of these compounds to establish dose response curves.”

“As well as small molecule screening, we perform a large number of deorphanization studies, identifying biological ligands for so-called ‘orphan’ GPCRs. This is currently an important area of drug discovery, identifying novel druggable targets for numerous diseases. We have a large collection of human and animal tissue extracts, and both the Tecan workstation and reader are vital to this work, allowing us to screen large libraries of natural ligands for possible agonists or antagonists to a target GPCR.”

“The main advantage of this automated set-up is the amount of time it saves per assay,” Laurent continued. “Our liquid handling workstation is equipped with

16 READERS TECAN JOURNAL 2/2011

a Carousel™, allowing a large number of plates to be loaded onto the system for high throughput processing without the need for constant manual intervention. The system is very easy to use, and automation of both liquid handling and screening ensures excellent reproducibility.”

“Although this platform is predominantly used for GPCR work, the fl exible nature of the Infi nite reader allows us to take advantage of its high throughput capabilities for other assays should the need arise,

Dr Laurent Meeus with the Infi nite F200 multimode reader

and our instrument is also confi gured for both Fluo-4 and HTRF® assays. This provides a back-up for other readers in the laboratory, off ering additional capacity and ensuring we are able to meet our commitment to clients. The support we receive from Tecan is also very important in this respect. We have a good relationship with Tecan’s application specialists and engineers, and they have always been quick to respond to our needs. Although the Infi nite F200 PRO is a relatively new instrument, we have been very happy with its performance. It combines ease

of use with fast measurements and good reproducibility, perfectly fulfi lling our needs.”

To fi nd out more on Tecan’s Infi nite 200 PRO, visit www.tecan.com/infi nite200

To learn more about Euroscreen, go to www.euroscreen.com

Tango is a trademark of Life Technologies, Inc.HTRF is a registered trademark of Cisbio International.

17READERS TECAN JOURNAL 2/2011

The Centro Nacional de Investigaciones Cardiovasculares (CNIC), in Madrid, Spain, is an institute for cardiovascular research, jointly funded by the Spanish Government and some of the biggest private companies in the country. The CNIC aims to bring together the best of Spanish cardiovascular research and provide it with a modern infrastructure and ample funding to carry out world-leading biomedical research. Dr Sergio Callejas, a support scientist in the genomics unit, explained: “The genomics unit is involved in gene and miRNA expression, and DNA content studies, using three main technologies – microarray platforms, high throughput sequencing and qPCR. The Automatic Genomics project began about two years ago when we purchased a Freedom EVO liquid handling platform for high throughput screening. We looked at the various instruments available and selected the Freedom EVO system because it was so flexible, provided good value for money and was recommended by other users. We have a Freedom EVO 200 workstation equipped with liquid handling (LiHa), MCA 96 and robotic manipulator (RoMa) arms and controlled by Freedom EVOware® software. One of the most useful functions of the Freedom EVO is that it has the flexibility to configure the aspiration and dispensing of different classes of liquid, allowing very accurate determination of fluid volumes. Currently we are focusing on completely automating our qPCR experiments, but we have also used the Freedom EVO to automate most of our protocols for microarrays, labeling and hybridization.”

The Centro Nacional de Investigaciones Cardiovasculares has developed Automatic Genomics, a software application that enables automation of medium throughput qPCR assays on the Freedom EVO® liquid handling platform.

Bridging the gap with Automatic Genomics

“We found Freedom EVOware very user-friendly and easy to use, but we needed to include many variables – in terms of the number of genes, samples and different constructs – in our experiments, and editing the scripts could be quite time consuming for an inexperienced operator. It was easier for us to make any changes in a Microsoft Excel® file, creating a worklist that could be read by Freedom EVOware. Tecan had given us some basic Freedom EVOware training, and, combining Freedom EVOware’s open and extensible architecture with our knowledge of Microsoft Excel and Visual Basic®, we developed Automatic Genomics, an Excel-based application with a Visual Basic interface1. Automatic Genomics enables users with limited programming experience to design 384- well plates for qPCR, and create all the necessary commands to enable the Freedom EVO to generate them.”

Sergio continued: “Initially we had planned to develop an application just for our own use, but, after speaking to staff at other institutes, we discovered that there were many small and medium sized laboratories that were interested in this software, and decided to make Automatic Genomics widely available. You can configure any Freedom EVO platform for this application, which was challenging as each laboratory’s worktable is different, with plate positions varying according to the individual user’s requirements. In addition to introducing all the parameters needed to design 384 -well plates for qPCR through the Visual Basic interface, Automatic Genomics can prepare templates for the ABI Prism® 7900HT qPCR system, with considerable time savings for the user. No previous knowledge

18 GENOMICS TECAN JOURNAL 2/2011

The CNIC team (left to right):  Ana Dopazo, Sergio Callejas, Rebeca Alvarez and Alberto Benguria

of Microsoft Excel, and only minimal knowledge of Freedom EVOware, is required for the user to optimize plate design in terms of the number of genes, samples and controls.”

“Our sample throughput varies and, at the moment, Automatic Genomics covers sample transfer from 1.5 ml tubes to 96-well plates, qPCR master mix dispensing and qPCR plate loading. We can run small experiments, with just 10 samples and three or four genes, or larger experiments involving several 384-well plates, and automation has really improved this process.”

Sergio concluded: “We used to do everything manually, loading 384-well plates by hand, which is very labor intensive and prone to human error, and it was not possible to do more than two or three plates in a day. Now that we have Automatic Genomics and the Freedom EVO, manual handling errors have been eliminated and, depending on the number of samples and genes involved, we can usually prepare one 384-well plate in about 20 minutes, significantly increasing our sample throughput.”

To find out more on Tecan’s Freedom EVO, visit www.tecan.com/freedomevo

Automatic Genomics is a product of CNIC. For more information about CNIC and Automatic Genomics, including license agreements, visit www.cnic.es/en/unidades/genomica

1. Callejas, S., Alvarez, R. and Dopazo A. (2011). Automatic Genomics: a user-friendly program for the automatic designing and plate loading of medium-throughput qPCR experiments. Biotechniques 50 (1): 46-50.

Microsoft, Excel, and Visual Basic are registered trademarks of Microsoft Corporation in the United States and/or other countries. ABI Prism is a registered trademark of Life Technologies.

19GENOMICS TECAN JOURNAL 2/2011

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. Tecan developed the Gas Control Module (GCM™) for the Infi nite 200 PRO multimode microplate reader to allow precise regulation of oxygen or carbon dioxide levels within the reader chamber, providing a more stable culture environment over time and allowing the duration of cell-based experiments to be extended without adversely aff ecting results.

Thanks to the close relationship between Tecan Austria and the University of Salzburg, Priv-Doz Dr Kristjan Plaetzer from the Division of Physics and Biophysics has been assessing the advanced capabilities of the patent pending GCM for cell-based optical studies. Kristjan explained: “One of the major issues in cell biology has always been the relatively long time course of experiments, particularly for eukaryotic cells. Even rapidly dividing cells, such as cancer cells, still have a doubling time of 16 to 24 hours. For this reason, cell biology research over the last 30-40 years has mainly concentrated on cellular structures, using microscopes and colorimetric dyes to study phenotypic changes in these systems. However, structural biology is just one aspect of a living system, governed by a series of dynamic processes, and research has more recently turned towards investigation of cellular processes.”

The recently launched Gas Control Module for the Infi nite® 200 PRO is off ering researchers at the University of Salzburg a new approach to the investigation of cellular processes, allowing incubation of cells within the reader for the fi rst time.

Breathing new life into cell-based studies

“Fluorescence- and luminescence-based techniques are widely used to follow the kinetics of cellular processes over time, but these investigations are generally limited by the stability of the culture environment. Cultures need to be transferred between a CO2 incubator and the reader at regular intervals to produce quantitative kinetic data, however the time course of many biological processes is between 24 and 48 hours, leading to gaps in the data when researchers need to rest. The development of the GCM for the Infi nite 200 PRO eliminates this obstacle to research, by allowing cultures to be incubated within the reader without aff ecting the resulting data.”

“We fi rst began working with Tecan many years ago, and have always been very impressed by its instruments and services,” Kristjan added. “We even still have our original SPECTRAFluor™ reader, which works reliably, so we are certainly convinced of the quality of Tecan equipment. The fl exibility of the Infi nite M200 PRO is also a real advantage in a research environment, as the Quad4 Monochromators™ system allows us to run a wide spectrum of assays. If you want to perform a new assay, you simply scan for the most appropriate excitation wavelength and can start using it straight away, without the need to buy new fi lter sets. The dual injector module further increases the fl exibility of the instrument, particularly for luminescence measurements, and the latest version of the

20 READERS TECAN JOURNAL 2/2011

system’s i-control™ software is well suited to cell-based studies. You can easily set the incubation temperature and defi ne the plate type, and it off ers a large number of pre-defi ned parameters for specifi c assay kits. Overall, this makes the Infi nite 200 PRO Kristjan Plaetzer (left) and Victoria Engelhardt

(Photo: Kolarik)

an ideal tool for process biology, in the same way the microscope is a tool for structural biology.”

To fi nd out more on Tecan’s Infi nite 200 PRO multimode readers, visit www.tecan.com/infi nite200

21READERS TECAN JOURNAL 2/2011

Researchers at the DFG Center for Regenerative Therapies, based in Dresden, Germany, are investigating adult neurogenesis – the production of new neurons in the adult brain. Dr Gerd Kempermann, Professor for Genomics of Regeneration at the CRTD, explained: “Small scale generation of new neurons from a population of resident stem cells in the adult brain occurs exclusively in two areas, the hippocampus and the olfactory bulb. We are investigating why these new neurons are in the hippocampus and how they contribute to hippocampal function. An intriguing aspect of this study is that adult neurogenesis is regulated by both physical and cognitive activity, but how does something as broad as physical exercise or cognitive stimuli affect hippocampal stem cells and stimulate the production of a new neuron? Activity-dependent control requires the convergence of very many regulatory factors, and is extremely complicated. To understand this complex regulation, the impact of the genetic background, and how different aspects of regulation target different aspects of development from the precursor cells, a variety of in vitro studies are necessary. Neurogenesis is a highly polygenic trait, and so we screen for specific genetic parameters in isolated precursor cells. This requires performing repeated experiments on precursor cells from the hippocampus with a standardized, reliable system for cell culturing, and this is where we take advantage of the Freedom EVO’s liquid handling capabilities.”

The CRTD is working with a Freedom EVO 150 workstation optimized for cell culturing, which is equipped with liquid handling (LiHa), robotic manipulator (RoMa) and Pick and Place (PnP) arms, two thermo carriers and a tilting carrier. The tilting carrier is an ideal add-on when working with different multiwell plates for cultivating cells, enabling a complete medium exchange. A StoreX™ STX 110-IC incubator, a Rotanta 46 RSC centrifuge and a Cellavista™ Analyzer are also integrated onto the system. Dr Kempermann’s group is looking at adherent primary cell cultures,

Scientists studying adult neurogenesis at the CRTD, the DFG Center for Regenerative Therapies Dresden, are using a Freedom EVO® liquid handling platform for cell culture maintenance.

Culturing adult hippocampal precursor cells

Fixed tip pipetting from a six-well cell culture plate on the tilting rack

22 CELL BIOLOGY TECAN JOURNAL 2/2011

where cells grow on the surface of a culture plate. The advantage of adherent precursor cells is the homogeneity of the culture, allowing access to individual cells, rather than small clusters of cells. These clusters, known as neurospheres, tend to be very heterogeneous, so the cells have a variable access to growth factors depending on the size of the agglomerate and the cell’s position within that structure. However, adherent cultures are more difficult to handle and require a lot of attention, since passaging takes quite some time. In order to grow enough cells for the assays, the cultivation of primary cells from the adult hippocampus requires an extremely consistent, standardized method that allows production of a large number of cells, in numerous wells, and achieves reliable, reproducible results. Dr Kempermann commented: “This is hard to do manually, and may be error-prone, and this is where the Freedom EVO is really beneficial to our work”.

He continued: “We have had a very good relationship with Tecan from the beginning, and the interaction with their development specialists has been extremely helpful.

Our workstation is based on an off-the-shelf platform, but has been customized to meet our needs. One of the reasons for choosing the Freedom EVO was the integration of a Cellavista Analyzer. The Cellavista can assess the confluency in individual wells – cells are passaged at a confluency of about 80 % – and then decide whether or not that particular cell culture needs passaging, which is a major advantage.”

Harvesting is especially crucial when cultivating neuronal cells. It is important to obtain literally all cells when trypsinization takes place, and this tedious procedure can only really be managed successfully by a well trained and experienced person. By automating the process, the Freedom EVO takes on the role of the skilled operator, eliminating the human errors that can arise with manual protocols. This frees the researcher to perform other tasks, and results to date are comparable with those achieved manually.

Dr Kempermann concluded: “The system is still evolving, and the protocols will be further fine-tuned. At the moment, this

is small scale and not high throughput; it is really a preparatory stage to allow us to establish how this could work and how large we could actually grow using this kind of system. This automated method will make it easy to expand our work in the future, allowing us to scale up to whatever conditions and number of cells we require.”

To find out more on Tecan’s cell culture solutions, visit www.tecan.com/cellbiology

To find out more about the DFG Center for Regenerative Therapies Dresden, visit www.crt-dresden.de/research/crtd-core-groups/kempermann

Cellavista is a trademark of Roche, and StoreX

is a trademark of LiCONiC Instruments.

The Freedom EVO workstation at the DFG Center for Regenerative Therapies Dresden

23CELL BIOLOGY TECAN JOURNAL 2/2011

A plate of live fi sh!

Scientists in the Department of Cellular Biology and Anatomy at GHSU have developed a high throughput system for reporter-based drug screening assays in living zebrafi sh disease models. Dr Jeff Mumm, Assistant Professor at GHSU, explained: “Quantitative microplate reader systems have revolutionized the pace of drug discovery, enabling the development of reporter-based in vitro and in silico assays that allow high throughput screening (HTS). This strategy has resulted in dramatic increases in compound hit rates in recent years. However, biological validation – confi rmation of the benefi t of drug candidates in living disease models – has become a bottleneck in the drug discovery process due to a lack of HTS-compatible in vivo assay platforms. The zebrafi sh is a vertebrate model system that is amenable to both disease modeling and HTS

The inaugural Tecan Detection Award, designed to celebrate our customers’ innovation and ingenuity, received many strong entries. A very close contest eventually saw Dr Jeff Mumm from Georgia Health Sciences University (GHSU), US, awarded second place for his work on reporter-based drug screening using Tecan’s Infi nite® M1000 and live zebrafi sh!

methodologies, off ering unique advantages to the drug screening process. Quantifying reporter levels in living zebrafi sh provides a versatile means of alleviating the biological validation bottleneck. Accordingly, we have developed a simple, rapid and cost-eff ective method for detecting fl uorescent reporter changes in individual zebrafi sh disease models over time.”

“My research focuses on regeneration, and our laboratory develops models for degenerative disease states. We are predominantly studying retinal neuron regeneration, investigating how various sub types of retinal neurons can be regenerated, and trying to identify the factors that allow regeneration to occur. However, the techniques used for our research are also being applied to other high profi le diseases, such as diabetes and Parkinson’s

disease, looking at how to regenerate insulin-producing beta cells in the pancreas and dopaminergic neurons respectively. By building a system that enables us to study localized loss of specifi c cell types, we can develop more targeted therapeutic approaches that allow us to intervene in a more specifi c manner than globally-induced proliferation of stem cells.”

“Using a nitroreductase-based system of targeted cellular ablation – a methodology borrowed from cancer therapeutics – an enzymatic activity of a type not normally present is introduced into the cell types that we want to kill. Initially the enzyme is completely innocuous, but, once a prodrug is introduced, the enzyme converts this into a toxin, enabling us to very specifi cally kill certain cells without aff ecting the surrounding environment. We have adapted this method to the zebrafi sh, with the intention of extending regenerative studies from the tissue level, where we’re regenerating nerve, bone and muscle, to the level of individual cell types within tissues.”

Dr Mumm continued: “To study regeneration you need a time-resolved assay that allows you to trace when the cells are present, when they have disappeared and when they have returned. We needed a microplate reader that was capable of accurately detecting fl uorescent signals in zebrafi sh and chose Tecan’s Infi nite M1000. The Infi nite M1000 provides us with z-focusing capabilities and a superb signal-to-noise ratio (>500:1), increasing our assay sensitivity by nearly an order of magnitude and allowing us to look at signals that have a much lower intensity. This is very important with, for example, beta cell regeneration, where cell numbers are quite low in larval stage fi sh. Although we could study older fi sh, the number of adult fi sh that can be screened is signifi cantly lower than the number of juvenile or larval stage fi sh; we use 96-well plates for larval stage fi sh but would need to use six-well plates for adults. We have been able to increase the assay robustness by performing ratiometric

Performing in vivo HTS assays using the Infi nite M1000: Dr Jeff Mumm (background), Steven Walker (at microscope) and Junko Ariga

24 READERS TECAN JOURNAL 2/2011

measurements of two diff erent fl uorophores, one linked to the targeted cell type and another to a neighboring control cell population – we’re getting very, very good z-factor scores – and the Quad4 Monochromators™ technology is key to this.”

“Using the Infi nite M1000, we have been able to quantify the loss and regeneration of targeted cells in zebrafi sh disease models, as well as small molecule-induced changes in disease-linked molecular signaling pathways. Importantly, high signal-to-noise ratios allow us to monitor changes in individual fi sh, which accounts for wide reporter level variance across populations by normalizing signals to each individual’s ground state, and enabling us to detect long-term changes over several days. We have optimized the system by characterizing autofl uorescence issues and identifying the reporter variants that provide optimal signal-to-noise ratios, and are developing customized multi-well formats suited to HTS applications.” Dr Mumm concluded: “The Infi nite M1000 has allowed us to develop a simple, cost-eff ective, automated quantitative method which will benefi t a wide variety of high throughput chemical and/or genetic screens, using fl uorescent and/or luminescent reporter detection in live zebrafi sh.”

This work was supported in part by a March of Dimes Basil O’Connor Starter Scholar Award, grant #FY 5-2010-7.

To fi nd out more on Tecan’s Infi nite M1000, visit www.tecan.com/Infi niteM1000

To fi nd out more about the Department of Cellular Biology, Georgia Health Sciences University, visit www.georgiahealth.edu/som/cba

Individually arrayed, 1 day old transgenic fi sh embryos (left & center), and 5 day old transgenic fi sh larvae (right)

25READERS TECAN JOURNAL 2/2011

Researchers at The Institute of Traditional Chinese Medicine and Natural Products, Jinan University, China, are using a Tecan multimode microplate reader to investigate the mechanism of immunosuppression caused by stress, aiming to discover eff ective natural solutions.

Living in harmony is probably the best medicine you will need

The Institute of Traditional Chinese Medicine and Nature Products at Jinan University is one of the leading institutes for Chinese medicine and natural products, with more than 100 full-time researchers and a considerable number of postgraduate students. For many years Dr Kurihara, a Professor and Deputy Director of the Institute, has focused his research on investigation into stress, discovering numerous interesting relationships between stress and a person’s health. A respected expert in the fi eld, Dr Kurihara believes that stress not only makes a person more susceptible to health problems, but is the cause, either directly or indirectly, of some diseases.

A team of researchers at the Institute, led by Dr Kurihara, is currently investigating the mechanism of immunosuppression caused by stress, attempting to discover eff ective natural remedies which can restore the immune system to a normal level. Dr Kurihara explained: “Our studies found a correlation between immune response and antioxidant capacity in immunocytes. We have developed a cheap, effi cient assay to monitor the concentration of free radicals in a cell, and use it as an important indicator of a cell’s health status; stress-induced immunosuppression will lower metabolic activity and raise the concentration of free radicals and, as a consequence, the cell – and subsequently the patient – becomes more susceptible to disease.”

“Our assay relies on two fl uorescent dyes which can be bleached by free radicals. When developing the assay, the dyes were carefully selected such that one was distributed within the cell and the other outside the cell, monitoring intra- and extra-cellular activity respectively. The assay requires kinetic measurement of fl uorescence intensity for at least two hours, and we rely on Tecan’s GENios™ multimode microplate reader for this.”

Dr Kurihara continued: “Natural products and extracts with the ability to restore the altered immune system are also screened using the GENios reader; application of the compound or extracts reduces the rate at which the dye is bleached, partially restoring fl uorescence in proportion to the product’s

Miss Yifang Li (left) and Dr Hiroshi Kurihara (right) with the Tecan reader

26 READERS TECAN JOURNAL 2/2011

ability to scavenge free radicals. The combination of a simple, cost-effective assay and the flexible and reliable GENios reader provides researchers with a powerful and economical screening platform.”

One of Tecan’s selling points has always been the robustness and longevity of its instruments. Although the GENios reader is an older generation instrument that can no longer be purchased, it clearly demonstrates the durability of Tecan equipment, continuing to perform well and proving a real asset to the Institute. “We have had the GENios reader in our laboratory for over five years, and it is usually in operation seven or eight hours a day, five days a week. It has proved very reliable, which is crucial to our work, as we operate to very tight schedules and cannot imagine what would happen if the instrument failed. In addition, being able to perform the assay in a microplate format keeps costs very low, almost negligible. Tecan’s local partner, Eastwin, provides impressive customer service, responding very quickly to any queries and helping us to plan our instrument maintenance, ensuring that its performance always meets specification.”

Dr Kurihara concluded: “We have a good relationship with Tecan and are pleased to have had the GENios reader in our department for so long. With multimode microplate readers becoming ever more essential for life science applications, it really is hard to imagine our laboratory without one.”

Tecan GENios multimode reader

To find out more on Tecan’s detection solutions, visit www.tecan.com/detection

27READERS TECAN JOURNAL 2/2011

Tethis SpA, part of Genextra Group, is based in Milan, Italy, and specializes in developing new applications for the biotechnology and drug discovery fields using nanomaterials. The Company has recently automated its microfluidic fluorescence in situ hybridization (FISH) assay, by customizing a Freedom EVO 75 liquid handling platform to meet the specifications of the microFIND chip. microFIND is a novel miniaturized device for handling cytological specimens, based on state-of-the-art, patented nanocoating technology, which performs miniaturized FISH protocols for the identification of chromosomal aberrations.

Tethis has automated its microFIND™ technology by adapting a Freedom EVO® liquid handling platform with accessories to accommodate the characteristics of this microfluidic device. The resulting system, known as autoFIND-F75, provides an affordable way of performing large scale FISH screening of cytological specimens.

Miniaturized FISH

Massimo Gatelli, General Manager at Tethis, explained: “The microFIND project evolved from the idea of developing a new technique for FISH, by performing the assay inside a disposable microfluidic device. An important issue to consider when designing a microfluidic assay for cells is the flow of liquid inside the microfluidic channels. The cells need to remain inside the device, but a strong liquid flow tends to detach non-adherent cells unless they have been very well fixed. To overcome this problem, a nanomaterial coating with the capability to firmly attach cells was developed for the inside of the microfluidic

device. We use a patented method known as PMCS (pulse microplasma cluster source), which can directly apply nanomaterials to any kind of surface. With microFIND, the film is deposited over a glass microscope slide, allowing us to attach the cells to the slide very tightly, minimizing losses during the assay. The film is completely transparent, so the optical properties of the slide are unchanged and the analytical protocols do not need to be altered.”

“While developing the microfluidic chip, Tethis searched for a partner to provide the best available liquid handling platform for automation of the assay. We wanted a liquid handling system that could manage everything – the samples, reagents and probes – and chose a Freedom EVO 75, equipped with a two-channel liquid handling (LiHa) arm, as the starting point for automating our FISH assay. Once the Freedom EVO had been adapted with accessories to accommodate the microFIND chip, we had autoFIND-F75, a fully automated system for miniaturized FISH. At the moment, there are a limited number of ways in which laboratories can automate this type of procedure, and these usually result in increased consumption of reagents. autoFIND-F75 fully automates the FISH assay without increasing the cost of the test, reducing the volumes of sample, reagents and probes that are required and producing the processed sample on a glass slide, ready to be placed on a microscope for analysis.”

Massimo continued: “The assay also has the ability to process scarce cell samples, which is important in situations where

Rita Fallico checking a slide processed on the automated FISH system

28 LIQUID HANDLING & ROBOTICS TECAN JOURNAL 2/2011

the sample contains only a few cells, for example multiple myeloma. With standard FISH protocols, analyzing this type of sample can be quite difficult, but with our assay it becomes easier and more affordable. Our microFIND technology offers users the unique opportunity to perform FISH assays starting with specimens of living cells, and avoids cytogenetic pellet preparation and manipulation. The nanotech coating sticks even non-adherent cells to the slide surface, which are then processed for FISH analysis. This approach is particularly suitable for situations where the initial specimen contains just a few cells, as it is vital to avoid the loss of cells which occurs during cytogenetic pellet preparation. Using our automated procedure, if you begin with 2,000 cells, you will finish with 2,000 cells, so there will be plenty of cells to analyze.”

“Using the autoFIND-F75 system, based on the compact Freedom EVO 75 platform, we can process up to 64 tests per batch, and with the larger Freedom EVO platforms we

could obviously increase this further. The initial development period, during which Tethis adapted the hardware, was followed by an in-depth collaboration with Tecan on a number of topics, for example the graphical user interface (GUI) and the optimization of tip positioning parameters to ensure the highest possible reproducible results. Tip positioning is quite critical for microfluidics, where just a tenth of a millimeter is crucial. We are now in the final phase of development, defining assay protocols and working with our customers to validate them.”

Emanuele Barborini, Head of Tethis Research, commented: “The microFIND approach to FISH may provide many advantages for clinical laboratories. But however good your product is, you still need to convince the potential users that it will be beneficial to them to adopt the technology, and the product must fit easily into hospital and laboratory routines. Adapting the Freedom EVO platform to accommodate

the microFIND chip has allowed us to handle a complex methodology and offer our customers an instrument that provides automated, high throughput FISH, which appears very simple and is easy to use.”

To find out more on Tecan’s Freedom EVO 75, visit www.tecan.com/freedomevo75

To find out more on Tethis and microFIND, visit www.tethis-lab.com

microFIND is a trademark of Tethis SpA.

Fully automated microfluidic FISH analysis

29LIQUID HANDLING & ROBOTICS TECAN JOURNAL 2/2011

Scientists working in the diagnostic serology department of the Laboratorio Tre Valli, Italy, rely on a Freedom EVO® liquid handling platform to monitor the health of livestock and ensure the quality of their food products.

Ensuring quality food production

farms, screening them to ensure that they are free from disease, and checking that vaccination programs have been eff ective. It is important to ensure that livestock are healthy even if they display no symptoms, and, if we should detect a problem, to act quickly and prevent the disease spreading. Our serology department receives samples from 1,400 poultry farms and over 400 pig farms for analysis by ELISA, and we have automated this process on a Freedom EVO 200 platform”.

“Our system is equipped with 8-channel liquid handling (LiHa), robotic manipulator (RoMa) and multi-channel (MCA 96) arms, a Carousel™, a Sunrise™ microplate absorbance reader and a 16 -channel HydroFlex™ microplate washer. When we were choosing the system, price, compatibility and performance of the individual modules were important to us, and we visited Tecan in Switzerland to look at the instrument in detail before making our purchase. Once the system had been installed, we received on-site training from Tecan and found the system very easy to use.”

Fabio Perini with the Freedom EVO workstation

The Laboratorio Tre Valli, based in San Martino Buon Albergo, Italy, is a part of the Veronesi Group, a family run business specializing in the production and sale of fresh and processed meat products. Veronesi’s team of veterinarians, agronomists, biologists and technicians combine experience and tradition with research and the application of new technologies, using sophisticated analytical systems to guarantee the quality of its products. The Company’s ‘from farm to fork’ philosophy means following the entire supply chain – from animal feed and farms to the fi nished product – to actively monitor each phase of the production process.

Dr Luigi Sperati, laboratory director, explained: “We monitor the health of our animals from the moment they arrive at our

30 FOOD ANALYSIS TECAN JOURNAL 2/2011

TALK TO TECAN TECAN JOURNAL 2/2011 31

Fabio Perini, who is responsible for the serology department, continued: “We use ELISA techniques to screen the animals for more than 20 diff erent diseases – including Aujeszky’s disease and PRRS in pigs, Newcastle disease and avian fl u in poultry, and IBR and BVD in cattle – and the Freedom EVO now manages all our various samples and ELISA plates, improving our laboratory workfl ow. Around half of the assays are prepared in house, and we purchase kits for the remaining assays from external suppliers. After sample preparation, which involves separating the serum from the blood sample, the technician simply needs to place the ELISA plate onto the Freedom EVO and start the run. Samples and 96-well plates are identifi ed by barcodes, increasing sample security, and the entire process is controlled by the Freedom EVOware® Plus software, which has been adapted to our needs with the help of Tecan’s software engineers.”

“Our system was designed to accommodate all the modules required for the eight diff erent analyses that we perform in a day, and can be fully loaded with everything we need for the entire day’s workload. On average, it takes 1 hour and 45 minutes to run one 96-well plate, and we can process up to 27 plates – around 2,500 samples – in a nine hour period.” Fabio concluded: “The Freedom EVO provides us with walkaway automation that allows us to perform the same range of analyses while giving the operator additional time to carry out other essential laboratory tasks, secure in the knowledge that the system will reliably generate the fi nal analytical data.”

To fi nd out more on Tecan’s Freedom EVO workstations, visit www.tecan.com/food

Leading the debateIn the current economic climate, many companies are looking more closely than ever at where to focus their resources. It makes sense for every company to concentrate eff orts on their core strengths and, in the diagnostics industry (IVD market), this often means investing in fundamental research rather than in developing instruments. For example, molecular diagnostics is one of the fastest growing areas of research, where there is still plenty to learn about the underlying chemistry and biology. In such a potentially powerful area of science, it is logical for companies with relevant portfolios to focus their investments on getting ahead in the knowledge game.

Although some diagnostics companies still have instrument development capabilities in house, a fully integrated solution is a major investment in time and money, and an emphasis on developing test menus often makes better business sense. For smaller and fast-growing companies, the skills are simply not there. In either case, there is an increasing need for reliable partners who can take the strain and develop instrumentation as original equipment manufacturers (OEM).

Tecan is uniquely placed to partner these companies, with arguably the broadest product off ering in the industry. From system components – enabling technologies like pumps and syringes – through to open platform instrumentation, we off er completely dedicated solutions according to specifi c applications and workfl ow requirements. Our real strength, however, lies in the proactive approach we take to developing these platforms. Our understanding of life science applications is invaluable in this regard, as are our thorough knowledge of global quality assurance and regulatory compliance issues, and our global service and support organization. We continue to build on this unique blend of know-how and technology, focusing our resources on what we do best, so that IVD companies can do the same.

Email talk@tecan.com to tell us what you think about focusing resources in the clinical diagnostics industry.

Bernhard Grob, Senior Vice President, Head Partnering Business

31

Meet Tecan at these events

Headquarters: Tecan Group Ltd., Seestrasse 103, CH-8708 Männedorf, SwitzerlandT +41 44 922 88 88 F +41 44 922 88 89 info@tecan.com

TecanAustria +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

Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276Design: OTM/London www.otmcreate.comPhotography: Marc Wetli/Zürich www.wetli.com, Günter Bolzern/Zürich www.bolzern.net, Susanne Völlm/Zürich www.susannevoellm.chEditor in Chief: Tecan Trading AG, Cornelia KegeleProject Lead: Tecan Trading AG, Cornelia Kegele/Tanja SagerEditor: kdm/UK www.kdm-communications.comPrint: DAZ Druckerei Albisrieden AG/Zurich www.daz.chAddress: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com, www.tecan.comTo 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

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Liquid Handling & Robotics | Detection | Components | Services & Consumables

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EVENTS 2011 TECAN JOURNAL 2/2011

Americas

American Society for Mass Spectrometry (ASMS 2011) Denver, CO 05 – 09 June 2011

World Pharma Congress Philadelphia, PA 07 – 09 June 2011

American Association for Clinical Chemistry (Clinical Lab Expo 2011) Atlanta, GA 24 – 28 July 2011

MicroArray World Congress 2011 South San Francisco, CA 29 – 30 Sept 2011

Asia and Pacific

National Clinical Medical Conference Beijing, China 24 – 28 May 2011

The 1st China Drug Safety & Quality Control Conference 2011 Beijing, China 25 – 26 May 2011

The 10th International BioForum and BioExpo Japan Tokyo, Japan 29 June – 01 July 2011

AIMS NZIMLS South Pacific Congress Gold Coast, Australia 08 – 12 Aug 2011Chinese International Equipment Exhibition & Academic Seminar of Crime Investigation, Narcotics Control, Counter-terrorism and Economic Crime Beijing, China 10 – 12 Aug 2011

Europe, Middle East and Africa

European Lab Automation Hamburg, Germany 30 June – 01 July 2011

ELRIG Manchester, UK 07 – 08 Sept 2011

MipTec Basel, Switzerland 20 – 24 Sept 2011