Tecan Journal Edition 01/2007

Tecan Journal Edition 1 / 2007

Accelerating drug discovery at the Nicholas Piramal Research Centre in India page 14 – 16

Perfecting technology for the NIH Roadmap page 20 – 21

Cover shows Bats Mutamba, Product Specialist Cell-Based Systems

The first REMP Bio Sample Store™ keeps samples at – 80°C and – 20°C concurrently page 26 – 27

C E O WE LCOME

Welcome to

2007!

We set out this year with a good foundation of growth behind us as 2006 comes to a close. In the last year, we have strengthened our detection sales force and have embarked on a major improvement project that is set to overhaul our service to you, our customers. The results of our customer satisfaction survey are on their way and I would like to take this opportunity to thank all customers who were approached for their input. We very much appreciate the time you have taken to work together with us.

This edition of the Tecan Journal spotlights a number of diverse applications, including the exceptional assay development platforms now operational at Columbia University for work in the NIH Molecular Libraries initiative, and several outstanding projects from our customers around the world. New products and developments are hot off the press, including the first seamless integration of Tecan and REMP products, the Freedom EVO-SSS, which combines the Freedom EVO® liquid handling workstation with the REMP Small-Size Store™ to create a fully automated liquid handling and sample management platform. Visitors to exhibitions early in the year will have the opportunity to see this new system, alongside the new HydroFlex™ microplate washer.

“ Tecan Journal 1/2007

We have strengthened our detection sales force and have embarked on a major improvement project to overhaul our customer service

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We hope you enjoy this issue of the Tecan Journal and look forward to continuing our good relationships with you as customers and partners. I wish you all a successful and prosperous new year for 2007.

Thomas Bachmann, CEO

CONTE N TS Welcome to 2007 Thomas Bachmann, CEO, thanks you, our customers page 2

Complete compliance with Tecan components The Reduction of Hazardous Substances (RoHS) Directive 2002/95/EC has had a major effect on the entire electronics industry page 10 Developing tailored systems for our customers Tecan’s unique approach to customizing products page 11

Perfecting technology for the NIH Roadmap The new Molecular Libraries Screening Centers Network facility handles hundreds of thousands of compounds pages 20 – 21

Latest products: HydroFlex™ platform The platform’s outstanding on-line control features set new standards page 4

Freedom EVO® and REMP Small-Size Store™ (SSS) Seamless integration creates a fully automated liquid handling and sample management platform page 5

quad4 monochromatorTM technology Blocks stray light and background noise by a factor of one million times more than typical readers page 6

Tecan’s Freedom EVOlyzer® becomes SFDA-compliant in China Tecan leads the field in compliance of new regulations Compact automation with the MultiChannel Arm 96 Gripper Even more efficiency and flexibility without an additional arm page 7

A meeting of quality minds!

Our goal is to improve quality of every level of operation and to harmonize the processes shared between Tecan and our customers pages 8 – 9

High throughput screening of infectious virus entry in mammalian cells Can you imagine not having to worry about viral infections? pages 12 – 13

Searching for new chemical entities with automated bioactivity-guided cell-based assays A compound screening facility has been established in India to accelerate drug discovery pages 14 – 16

Infinite™ 200 – in search of biological insecticides Great progress has been made in research on virulence factors of insect pathogens, using Tecan’s monochromator-based Infinite M200 microplate reader page 17

Integration of Freedom EVOware® Sample Tracking with Applied Biosystems SQL*LIMS® Towards fully automated management of high throughput genotyping data pages 18 – 19

Sample management for research in Japan Pharmaceutical research scientists at Japan Tobacco Inc. rely on Tecan’s Genesis RWSTM workstations and REMP Tube Punching Module™ for their sample management pages 22 – 23

PureLink™ 96 HQ Mini Plasmid Purification Kit Automated, high throughput purification of plasmid DNA pages 24 – 25

First – 80 °C biobank – Pfizer success story The first REMP Bio Sample Store™ is able to store millions of samples at – 80 °C and – 20 °C concurrently pages 26 – 27

Events for 2007 Meet Tecan at these events during the next six months page 28

Tecan Journal 1/2007

L AT E ST P RO DUCTS

Automated plate washing and vacuum filtration with the new

HydroFlex™ platform Tecan’s new HydroFlex™ platform provides excellent performance, reliability and flexibility for a range of 96-well format applications, including washing of ELISAs, cellular assays and protein arrays, and vacuum filtration-to-waste, such as for PCR clean-up. The platform’s outstanding on-line control features set new standards for plate washers, with options including a process control (PC) manifold that monitors all wash steps, and a liquid level detection system (LLD) to monitor filling levels in wash buffers and waste bottles.

The compact and modular platform has very low residual volumes (under 2 μl) and multiple aspiration points for flatbottom wells, ensuring consistent, high quality washing. The platform’s gentle drop-wise dispense mode and movable wash head minimize cell detachment, even with weakly adherent cell lines, and the advanced pumping system includes a dispense pump with RPM (rotations per minute) control and a double-head aspiration pump for reliable performance at low service costs.

The advanced vacuum filtration option benefits many applications, such as purification of DNA after PCR steps, where unwanted reaction by-products are easily removed by using filtration membrane plates that collect the purified DNA.

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The advanced vacuum filtration option benefits many applications

Tecan Journal 1/2007

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The HydroFlex platform is easily operated as a stand-alone instrument with its built-in keypad, or by using the intuitive HydroControl™ software for simple preprogramming of wash cycles and plate parameters. The software fulfils user administration requirements, including electronic records and signatures, and allows the HydroFlex to be integrated with Tecan’s Freedom EVO® liquid handling workstations or Freedom EVOlyzer® ELISA analyzer.

L ATEST PRODU CTS

Freedom EVO® and REMP Small-Size Store™ (SSS) integration Tecan has seamlessly integrated the REMP Small-Size StoreTM (SSS) with the Freedom EVO® liquid handling workstation, creating a fully automated liquid handling and sample management platform. The REMP SSS is a fully automated storage and retrieval system that fits perfectly into a research laboratory.

It can handle samples in a variety of formats, including microplates and the REMP Tube Technology™ Consumables.

Integration of the SSS with the Freedom EVO and Freedom EVOware® enables walkaway operation for sample retrieval and processing steps. REMP Tube Technology enables desired samples to be cherry picked within the store’s controlled environment. The samples are easily transferred to Tecan’s Freedom EVO workstation using an integrated plate shuttle. Samples are decapped using the REMP ACD96™ and processed as required on the Freedom EVO workstation.

Upon completion, the samples are subsequently capped and returned to storage when they are no longer needed.

The combination of the sample storage and processing platform minimizes the time that samples are exposed to the environment and ensures they are returned to the SSS as soon as processing is completed.

Integration, furthermore, enables increased process security. The REMP Reatrix 2D Scanner can be used onboard the Freedom EVO for tube and

Fully integrated Freedom EVO and REMP Small-Size Store (SSS)

plate identification. Additionally, sample volumes, concentrations and identification numbers can be fully tracked within the software. Data

The plate carrier transports samples between the Small-Size Store (SSS) and Freedom EVO

handling is perfectly integrated, making this platform ideal for compound dissolution and reformatting factories, or genomic sample factories.

The REMP Reatrix 2D Scanner can be used onboard the Freedom EVO

Tecan Journal 1/2007

L AT E ST P RO DUCTS

One million times more with Our exclusive quad4 monochromatorTM technology, as featured in our InfiniteTM M200 and Safire2TM monochromator microplate readers, guarantees improved sensitivity, accuracy, flexibility and speed. Unwanted stray light is the most critical factor affecting the performance and sensitivity of microplate readers, but the quad4 technology blocks stray light and the resulting background noise by a factor of 106 times more than typical dual mono­ chromator-based plate readers.

The unique quad4 configuration consists of two monochromators for excitation and two monochromators for emission, connected in series. The technology eliminates the need for cut-off filters to reduce stray light, providing more accurate spectral scans and avoiding the artificial peak shifts seen when monochromators are used in combination with filters. Fluorescence scans can be performed up to six times faster with quad4, compared with instruments containing two monochromators combined with cut-off filters. The advanced technology ensures consistent performance across the entire wavelength spectrum and allows you to tune in any wavelength without having to optimize filters.

The Safire2 microplate reader comes with quad4 monochromators

“ Tecan Journal 1/2007

Fluorescence scans can be performed up to six times faster with quad4

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L ATEST PRODU CTS

Tecan’s Freedom EVOlyzer® becomes SFDA-compliant in China Automating ELISAs with the Freedom EVOlyzer

Tecan has successfully registered its automated ELISA analyzer, the Freedom EVOlyzer®, with the State Food and Drug Administration (SFDA) in China. New Chinese National Standards for medical electrical equipment were introduced in May 2006 and the Freedom EVOlyzer is one of the first clinical devices to become SFDA-compliant, meaning that Tecan is leading the field in its rapid implementation of the new regulations.

Seven Freedom EVOlyzer workstations were immediately ordered for customers in China following the registration.

The instrument’s high speed, flexibility

and walkaway features are proving to be particularly important for hospitals and blood bank laboratories, and the automated ELISA platform is currently unrivaled in China.

Mark Wang, Chief Representative of Tecan China, explained: “Tecan is well equipped to serve customers in China, with a permanent office in Beijing established in 2005, as well as a strong distribution network and nine highly trained application specialists to support the customer base.”

The Freedom EVOlyzer has been designed to comply with the 98/79/EC directive on

in vitro diagnostic medical devices. The workstation already has plenty of satisfied customers in Europe, offering a wide range of automation options for all typical ELISA steps, including sample distribution, reagent pipetting, incubation, washing, reading and data generation. The new Freedom EVOlyzer software version 1.5, released in July 2006, includes improved error handling, more flexible scheduling and 20% faster pipetting capabilities.

Not all of the above mentioned applications have been cleared for use in all countries, please contact your local sales office for specific information

Compact automation with the MultiChannel Arm 96 Gripper Tecan’s MultiChannel Arm module is now available with a Gripper as an optional add-on. The Gripper is a small module which fastens to either side of the head of the MultiChannel Arm, with fingers to grip objects such as plates and tube racks to move them around in the workstation. The Gripper can also carry out simple manipulations, eg. assembling and disassembling the Te-VacS™ vacuum separation module, giving even more efficiency and flexibility to the platform without the addition of another arm to the system.

The Gripper is an economic solution for a platform with a small to moderate throughput of 10 to 20 plates per day, and is ideal for users on a limited budget, as well as users who need a fully automated system but are reluctant to commit to a large set-up with three independent arms.

Tecan Journal 1/2007

Q ualit y A ssurance

A meeting of

quality minds!

As part of our continued commitment to excellent quality and regulatory compliance, Tecan has started a new initiative of holding regular quality review meetings with many of its partner companies and customers. The overall goal of the new initiative is to improve quality at every level of operation, to harmonize the processes shared between Tecan and our customers and, above all, to improve the relationship we have with them.

The meetings follow a clear and structured agenda and give all parties the opportunity to openly discuss Tecan’s quality performance, both for existing products and for the development of new products, to review the quality issues that might have occurred in the previous year and to define clear targets for the next year in a detailed manner.

Many of the customers approached so far are the larger, highly regulated companies in the life science sector, who already have strong relationships with regulatory authorities and are very open to mutual cooperation. They often have a clear definition of their quality goals and have processes in place to achieve these targets.

Tecan Journal 1/2007

An important factor of these meetings is that the right people are involved – they have the right amount of detailed information to hand and can make the critical decisions when required to do so.

One of the first companies to benefit from this initiative is TriPath Imaging, Inc. Laura Nea, Vice President of Quality Assurance at TriPath Imaging, Inc., is very enthusiastic about Tecan’s unique approach to quality issues: “Two years ago, Günter Weisshaar, Senior Vice President of Quality Assurance and Regulatory Affairs at Tecan, gave us a presentation on his global strategy for quality and proposed a formal agreement whereby the two companies could define their expectations, both for quality and

for specific product lines. One facet of this agreement included regular discussions and updates. For each of our meetings, an agenda is planned to cover any recent concerns, and we are able to discuss any issues where we feel Tecan could lend expertise to help us resolve matters together. At the same time, we can develop joint goals for the following year, whether that’s concerning reliability, delivery, or particular projects.”

“This is the first time a supplier has approached us in this way and we have been very happy to participate in strengthening the relationship between the two companies. I believe that ultimately we are able to provide a better service to our customers, and that they experience increased reliability as a result.”

Q ualit y A ssurance

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Tecan strives to exceed our customers’ expectations. Our goal is to continuously improve the quality of our products and processes in an environment that promotes compliance, integrity and teamwork Günter Weisshaar, Executive Vice-President Global Quality & Regulatory Compliance

“Tecan is a critical supplier for us and Günter’s approach to communication and proactive visits have really opened the door. It is clear that the more we communicate, the quicker the issues are resolved and the less frustration there is on both sides. This approach to quality management is extremely proactive and very refreshing.”

The response from customers already enjoying Tecan’s new, more open philosophy for quality has been welcomed with open arms by Günter: “The reaction so far has been overwhelmingly positive which is very encouraging. Early on in our negotiations, it became clear that an important starting point is to define and share everyone’s expectations, from Tecan’s point of view as well as that of the customers. The meetings smooth the paths of communication between the respective quality and regulatory departments, not just on a personal level but also in the ways we work together, ensuring that everyone receives the

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correct information in acceptable time frames, and in such a way that they can act and react accordingly. We very much look forward to adopting the same approach with many more of our customers.”

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This is the first time a supplier has approached us in this way and we have been very happy to participate in strengthening the relationship between the two companies

Laura Nea, Vice President of Quality Assurance, TriPath Imaging, Inc.

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Tecan Journal 1/2007

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COM PO N E N TS

Complete compliance with Tecan components The Reduction of Hazardous Substances (RoHS) Directive 2002/95/EC came into effect on July 1st 2006, banning new electrical and electronic equipment containing more than acceptable levels of hazardous materials from being placed on the EU market. This directive has had a major impact on the entire electronics industry and, here at Tecan, we tackled the issue head on! of man hours over the course of 12 months. As an example of this effort for one product, an individual Cavro® XLP™ pump contains hundreds of individual components and the electronic circuit board within the pump contains as many as 150 different parts, each of which had to be properly analyzed, coded and documented as proof of compliance.

“When we started our initial evaluation, most of our electronic part suppliers were already making manufacturing changes and converting their components to meet the directive so we did not have to find new suppliers,” said Gary. “However, it was much less straightforward for mechanical parts, which was complicated by the lack of choice in finishes and pretreatments that met the RoHS requirements.”

Gary Barron, the RoHS compliance project leader for Tecan Systems in San Jose, USA, explained how he managed the investigation and compliance assurance of the many thousands of parts used in Tecan’s OEM components.

The directive restricts the use of lead, mercury, hexavalent chromium, polybrominated biphenyl (PBB) and polybrominated diphenyl ether (PBDE) flame retardants to 1,000 ppm, and cadmium to 100 ppm.

These six materials are commonly found in electrical and electronic products but the increasing use of electronic equipment and shorter lifecycles has led to greater quantities being discarded in landfill sites, resulting in potentially harmful accumulations.

Tecan Journal 1/2007

“The first thing we did was to map out and evaluate our current status; listing all of our products for which the directive was applicable, breaking each one into its own component parts, and embarking on an enormous program to check out the compliance status of each of these.

The result was that approximately half required further investigation by our dedicated engineers, who had to carry out the research and determine what further action was needed.”

The sheer volume of work meant the involvement of every department within Tecan Systems – from sales and marketing who were the customers’ primary point of contact, to those that worked behind the scenes in purchasing, materials, engineering and quality inspection. This effort took thousands

“We made a huge effort to complete the project by July 2006, allowing plenty of time to order all the new product parts, rebuild the products and still give our customers the time they needed to incorporate the upgraded component into their systems. Many Tecan OEM components are used for platforms that require FDA evaluation and certification, so some customers required more time for evaluation to ensure that the RoHS components would not have an impact on their systems.”

Steve Levers, president of Tecan Systems, commented: “Thanks to our thorough approach, we are confident that our components meet the RoHS Directive, providing our customers with peace of mind for the foreseeable future.”

APPLICATION B IOPHA RNMTS A COMPONA

Developing tailored systems for our customers Kathryn Coleman is manager of the Tecan Integration Group (TIG) in North Carolina, US, responsible for the development and construction of the systems featured on pages 20 – 21 for Columbia University. We talked to her about Tecan’s unique approach to customizing products for customers who need just that little bit extra than off-the-shelf solutions.

Tell us about the TIG facility in North Carolina.

I am the manager of the facility at Tecan’s US base in Research Triangle Park, leading a team of hardware and software specialists who are dedicated to customizing Tecan products for our customers, from biopharma, biotech and forensic laboratories. Our facility here consists of a large laboratory integration area that can handle multiple system set-ups.

Apart from the TIG team, who else gets involved with customization projects?

A team leader is assigned to each individual project and it is their job to coordinate the team effort at Tecan. This leader manages the project, working closely with the sales, engineering, software and development teams, and also with the field applications staff within Tecan. The whole process begins with comprehensive discussions with the customer and the sales person to fully understand what is required and how we can achieve the best outcome, in time and in budget. Then, together, the whole

team develops a solution that exactly meets each customer’s requirements.

So, why customize?

The Tecan product portfolio includes really good, flexible, off-the-shelf systems that are just what many of our customers need from their instruments. For the remaining few, the base platforms often meet 90% of a customer’s requirements but what makes us unique in the life science liquid handling arena is our inhouse capability to customize them and provide that extra 10% of functionality. It may not sound a lot but, for some of our customers, it’s the difference that makes a good instrument even better; the icing on the cake!

What does customization usually entail?

That varies tremendously depending on the complexity of what is required.

For some customers, it’s just a simple matter of making a custom-carrier for more unusual sample tubes or vessels.

Others may want to integrate third party equipment and we can make adapter plates and drivers to integrate them into our standard Freedom EVOware® software. The really complex cases like that of Columbia University are major projects. For those systems, we developed the specifications, designed

Project managers at work

several custom hardware parts, wrote and integrated dedicated drivers, and programmed several protocol templates.

It wasn’t just a hardware set-up, but also the programming, testing and verification. These final stages are, of course, critical parts of every customization project, whatever its size.

At the end of the day, we aim to deliver a system that meets all the customers’ specifications and does exactly what the customer needs it to do – that’s what customization is all about!

“ Kathryn Coleman, Manager Tecan Integration Group (TIG) US

The whole team develops a solution that exactly meets each customer’s requirements

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High throughput screening of infectious

virus entry in mammalian cells Researchers at the Institute of Molecular Systems Biology (IMSB)*, ETH Zurich, have two Freedom EVO® 200 liquid handling workstations that have been custom developed for high throughput screening of infectious virus entry in mammalian cells. The large-scale study aims to create a profile of all the mammalian genes involved in infection by 11 major viruses, and is estimated to be complete within a year. use of many endocytic pathways for host entry. Major mechanisms include the clathrin-mediated uptake route, caveloae-mediated endocytosis, lipidraft mediated endocytic pathways and macropinocytosis.

Custom developed Freedom EVO 200 liquid handling workstation

Can you imagine not having to worry about viral infections – no more flu, no risk of chicken pox, maybe even the end of HIV? This could only be possible in a world where viruses are less able to develop resistance to anti-viral therapies. It might sound too good to be true – but it’s a very real dream for Dr Lucas Pelkmans, assistant professor at the IMSB, and his colleagues. Their theory is simple: rather than try to attack the virus, you change the entry mechanisms that viruses use to infect mammalian cells – almost like Tecan Journal 1/2007

changing the door locks. Since the entry mechanism proteins are expressed by the host cells and not by viruses, it would be difficult for a virus to adapt to the change.

Such anti-viral therapies are a long way off, but the team at the Swiss Federal Institute of Technology (ETH), Zurich, is already identifying the specific sets of host genes that different viruses depend on to infect cells. Endocytosis – the process by which cells absorb material – can occur in a variety of ways, and it is well established that viruses make

Dr Pelkmans is looking at how viruses hijack these pathways and has recently embarked on a genome-wide study to individually silence 7,000 mammalian genes using RNA interference (RNAi), and measure how each silencing affects the abilities of 11 different viruses, including influenza, herpes and SV40, to infect mammalian hosts. The 7,000 genes have been chosen for their potential involvement in the process, based on protein structure and DNA sequence.

By systematically silencing each gene, a corresponding decrease or increase in viral transfection of cells can be measured, giving a functional host genetic profile of virus entry for each virus type studied, which directly reflects how the virus enters and infects the cell.

This huge project depends on a fully automated system that transfects thousands of cells with short interfering RNA (siRNA) molecules. Genetically silenced and control cells are then infected with the viruses and the corresponding viral transfection rates are analyzed. The laboratory has two Tecan Freedom EVO 200 workstations that have been custom developed to fully automate the procedure.

APPLICATION B IOPHA R M A

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The first workstation carries out all the transfection and infection assays in 384well plates using a Te-MO™ 384-channel pipetting head. A reverse transfection procedure is used, where the siRNAs and reagents are plated out in advance; these plates can be stored at – 80 °C for several months. The workstation then plates out cells (from HeLa cell lines) into the wells and transfects them with siRNAs (Qiagen). The cells are then automatically infected with viruses, and fixed and stained for analysis.

The second Freedom EVO platform has two fully integrated Cell Works microscopes and a Te-Stack™ stacker module. The entirely automated workstation loads the 384-well plates onto the microscopes to image the cells and, when the imaging is complete, each plate is removed and replaced with a new one. The captured images are then analyzed to provide a quantitative measurement of the proportion of cells that are infected with the virus. The total number of cells is automatically counted, based on nuclear staining (DAPI), and the total number of infected cells is also determined, based on expression of a reporter gene carried by the virus, such as green fluorescent protein, or antibody detection of a viral-specific protein.

Dividing the total number of infected cells by the total number of cells provides an infection index; the control indices are compared with those obtained for cells that have been subjected to RNAi for a single gene, to indicate that gene’s importance in viral infection. The viral infection rates of the laboratory’s control cells are normally around 10%, allowing an infection increase or decrease of up to one order of magnitude to be measured as a result of the RNAi.

From left to right: Berend Snijder, Manuel Bauer and Raphael Sacher, with their Freedom EVO 200

All measurements are performed in triplicate, 10,000 cells are measured per well, and at least three different siRNAs are used per gene, to exclude false negatives or false positives. Analyzing the effects of silencing 7,000 genes on one virus, in triplicate and with three independent siRNAs, requires 207 384-well plates; it takes about two weeks using the automated set-up and including all data analysis. A reliable barcoding system and sophisticated LIMS are essential for managing the process!

For Dr Pelkmans and his colleagues, the fully automated and integrated set-up is critical to the project. In particular, the fact that even the imaging and analysis are fully automated saves a vast amount of time and labor, as well as maintaining consistency.

“When the system is fully operational, we hope to be able to just press ‘start’ and the system will screen 207 plates, requiring only little manual intervention.

Most of the time, we really don’t have to worry about whether it’s working or not, because it is,” said Dr Pelkmans. “We have already seen some very exciting results; the approach clearly allows us to group viruses together in a way that you would not be able to predict from classical virus groupings.”

It seems that the real complexity of a viral infection does not come from the virus, but from the host. A typical entry pathway involves at least 300 – 500 human genes, with complicated mechanisms that include membrane trafficking, microtubule-mediated transport, cytoskeletal and cell signaling – all of which are important for successful viral infection. New ways of grouping viruses together will help us to better understand the real complexities of viral entry and, in the future, it may be possible to develop anti-viral approaches that target host cellular genes instead of viral components.

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We have already seen some very exciting results

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*The IMSB is part of a Swiss-wide initiative, Systems X, which aims to develop and enhance systems biology research in Switzerland.

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Searching for new chemical entities with automated bioactivity-guided cellbased assays Asha Almeida, Giridharan Periyasamy, Balakrishna Shankar, Amit Khanna, Hitesh Goswami, Prabhu Padmanabhan, Prabakar Sampath, Arun Srinivasan, Arun Balakrishnan and Somesh Sharma Screening & Biotechnology, Department of Pharmacology, Nicholas Piramal Research Centre, NPIL, Mumbai, India

The Nicholas Piramal Research Centre (NPRC) is the research wing of the pharmaceutical company, Nicholas Piramal India Limited. In 2005, a compound screening facility was established for the NPRC in Mumbai, India, to accelerate identification of lead compounds for drug discovery from natural products and small molecule libraries. The facility depends on a Freedom EVO® 200 liquid handling workstation to automate a wide range of biochemical and cell-based assays that identify candidate compounds for the treatment of cancers, metabolic diseases and inflammatory disorders. This is one of the first fully functional, integrated screening facilities in India.

The center’s Freedom EVO 200 is equipped with a Te-MO™ 96-channel pipetting head, an 8-channel liquid handling (LiHa) arm and a robotic manipulator (RoMa) arm. A Safire2™ microplate reader and 96 PW™ microplate power washer are also integrated with the platform, along with third party instruments that include a Cytomat®

Tecan Journal 1/2007

(from Heraeus) and centrifuge (from Hettich). This automated set-up was chosen to increase the throughput rate of cell-based end point assays, receptor ligand binding studies, kinase assays, protease assays, molecular interaction assays and sample library generation. The platform is programmed to perform the assays using Tecan’s Freedom EVOware® Plus software, which combines pipetting and scheduling in a single, scalable package. Being able to automate all the assays using a variety of different cell lines with a single platform was a critical factor when deciding which robot to choose.

The Tecan platform allows simultaneous testing of hundreds of compounds in triplicate against many assays relevant to diseases such as cancers, inflammatory and metabolic disorders. The Safire2’s multimodality makes it suitable for automatically measuring many different assay endpoints, including absorbance, fluorescence, chemiluminescence, fluorescence polarization, FRET (fluore­ scence resonance energy transfer) and other modes.

Automated screening of natural product libraries Chemical substances derived from animals, plants and microbes have been used to treat human disease since the dawn of medicine. This tradition is the basis of alternative medicine as practised in Indian culture, eg. ayurveda, siddha, unani, homeopathy, etc. Investigating natural products as a source of novel human therapeutics is one of the major objectives of high throughput screening at NPRC, and an assortment of sample libraries consisting of unique, unrelated natural and synthetic compounds are screened for leads. Specific libraries are assayed across different disease targets and, when a positive lead is obtained, this is subjected to bioactivity-based fractionation until the novel molecule is identified and structurally elucidated.

Sources of interest at the NPRC include herbal, marine, actinomycetes and fungal products, which are screened with disease relevant phenotypic assays to prioritize and isolate compounds or extracts with anti-cancer, anti-inflammatory and antidiabetic potential.

APPLICATION B IOPHA R M A

From left to right: Amit Khanna, Prabakar Sampath, Prabhu Padmanabhan, Arun Srinivasan, Hitesh Goswami, Giridharan Periyasamy, Balakrishna Shankar, Arun Balakrishnan, Asha Almeida

Figure 1: Screening output of an anticancer screen using natural products from multiple sources on the high throughput screening system

Bioactivity-based fractionation The bioactivity of the natural product extract is validated using cell-based assays that have been set up in-house as a primary screen for each therapeutic area. The primary screen is repeated many times to further localize and isolate the active ingredient. These prioritized compounds are then put through secondary screens that are specifically designed and established for individual disease targets, allowing us to postulate the novel molecule’s possible mechanism of action. At present, our throughput using the Freedom EVO allows us to generate around 10,000 data points per week. The workstation is used continuously to run multiple experiments in a single day and our screening strategy is novel in profiling the leads across all disease targets to define the effect of the molecule, prior to its inclusion for animal studies.

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The Tecan platform allows simultaneous testing of hundreds of compounds against many assays relevant to cancers, inflammatory diseases and metabolic disorders

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Figure 2: Effect of different solvent extracts of the plant SN-001 on the proliferative index of multiple cancer cells Tecan Journal 1/2007

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Figure 3: Bioacitivity-guided fractionation using multiple solvent extracts of the plant SN-001 on the proliferative index of multiple cancer cells

Figure 4: Isolation of a pure molecule from the active fraction 3 with antiproliferative activity on cancer cells using bioacitivityguided fractionation

We have identified extracts with unique (single target) as well as dual activities (two or more targets). The activity of some of these potential hits is graphically represented in Figures 1 – 5; these data are indicative of natural product scaffolds within the extracts that may be responsible for dual or unique target effects. Automating our assays using the Freedom EVO 200 system has made life much easier and has significantly contributed to reducing the hit-to-lead transformation time.

Figure 5: Effect of a synthetic compound on the production of proinflammatory cytokines in LPS-stimulated monocytes

The set-up was fully installed at the NPRC and running three different experimental protocols within a month of its arrival in Mumbai, thanks to the excellent training that Tecan provided to its Indian distributor, Bioscreen. We are planning to increase the output to 20,000 or more data points per week by switching to 384well format assays, which should have happened by the end of 2006. Nicholas Piramal India Ltd is already beginning to see the benefits of the high throughput screening platform: in just two months, the automated screening facility has managed to complete a workload that would have taken an entire year to complete when performed manually.

Summary High throughput screening on an automated platform is an efficient way for establishing robust assays that can yield reliable, reproducible data in phenotypic cell-based screens. Complex cellular assays can be standardized for screening natural product-based libraries, bioactivity-guided fractionation, isolation of active molecules and reducing hit-tolead identification time. Our investment in the technologically advanced Freedom EVO 200 system has helped us increase sample source and assay throughput, speed up chemical isolation and rapidly identify common compounds by biological and chemical means.

Cytomat® is a registered trademark of Thermo Fisher Scientific

Tecan Journal 1/2007

READER

Infinite™ 200

in search of biological insecticides The Microbial Ecology and Host-Pathogen Interaction Laboratory (EMIP), of the INRA Institute in Montpellier, France, has already made great progress in research on virulence factors of insect pathogens, using Tecan’s monochromator-based Infinite™ M200 microplate reader. The researchers, led by Dr Alain Givaudan, are studying the biochemistry, physiology and genetics of the bacterial virulence factors, with a view to developing a new means of biological control for the integrated pest management of crops.

Dr Givaudan, head of the Virulence Factors and Bacterial Genomics group, explained: “We are studying insectpathogenic bacteria, Xenorhabdus and Photorhabdus, which are symbionts of entomopathogenic nematodes. When the nematodes attack an insect, the bacteria are able to invade the insect and release virulence factors which lead to the death of the host insect. But, before we can monitor bacterial gene expression in vivo, we are first studying the virulence factor expression during

the course of bacterial growth in vitro.

We have chosen the Infinite M200 for our work because it is able to maintain shaking cultures over long periods and because various parameters, such as the temperature, agitation and the frequency of measurements, can all be programmed very easily using Tecan’s Magellan™ software. The instrument is very easy to use, and really allows us to obtain plenty of results in a short space of time.”

“To study real-time gene expression we are using novel green fluorescent protein (GFP) variants, with half-lives as short as 40 minutes, as reporter molecules.

The optical density (bacterial growth) and fluorescence (gene expression) of shaking bacterial cultures, in black 96-well microplates, are simultaneously monitored every 30 minutes over 48 hours. Our studies have so far revealed that the expression of virulence factor is transient during bacterial growth.”

The laboratory already has plans to use the very flexible Infinite M200 in other related projects. For example, another group in EMIP is studying the taxonomy of bacterial entomopathogens and determining the genetic relatedness among the bacteria by performing fluorometric hybridizations in microplates, and measuring the fluorescence using the Infinite M200.

Bacterial cells containing a transcriptional fusion with the destabilized GFP(AAV) were cultured in LB broth. Bacterial growth (in blue) and fluorescence (green line) were monitored using the Infinite M200. As shown on the figure, the burst of expression of this specific gene occurred at the end of the exponential growth phase. The instability of dGFP revealed that the gene expression is transient during the stationary phase Tecan Journal 1/2007

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S O F T WA R E

Integration of Freedom EVOware® Sample Tracking with Applied Biosystems SQL*LIMS® Towards fully automated management of high throughput genotyping data The Genomics Platform team at the Parco Tecnologico Padano (PTP) provides a high throughput genotyping service in the AgBiotech area using its automated platform that includes three Freedom EVO® workstations and two automated analyzers. Tecan’s Freedom EVOware® Sample Tracking software is being set up as a bridge to send the data generated from the Tecan instruments to the fully integrated laboratory information management system (LIMS) for further processing.

Pietro Piffanelli (far left), Gert Sclep (far right) and the PGP team

The PTP is located in the Lombardy region of Italy and is recognized as a center of excellence in the agro-biotechnology sector. The research and development unit focuses on both animal and plant genomics. In 2005, the PTP Genomics Platform (PGP) team was created to provide a central high throughput genotyping service for all internal projects and to coordinate the DNA national project on genomics platforms. The PGP performs molecular genomics analyses for approximately 70 agro-biotech Tecan Journal 1/2007

researchers within the PTP, as well as other research centers and universities in Italy. It has developed a fully automated platform to process the large sample numbers it receives to a high standard.

The platform consists of two distinct pre-processing and processing areas.

The incoming samples are logged into the LIMS and aliquoted into microplates using a Freedom EVO 75 liquid handling workstation. A Freedom EVO 150 workstation with an integrated

GENios™ microplate reader next carries out isolation, quantification and normalization of genomic DNA or RNA. The samples enter into the processing area where a second Freedom EVO 150 workstation is set up for high throughput purification of genotyping reactions using a Te-MO™ 96 head and low volume head, enabling reduction of reaction volumes.

Finally, the samples are analyzed using a 7900HT Fast Real-Time PCR System or a 48-capillary 3730 DNA Analyzer from Applied Biosystems. All Freedom EVO workstations are equipped with a barcode reader (Tecan PosIDTM) which facilitates LIMS mediated tracking of the microplates throughout the entire process.

“We chose Tecan instruments because of the robustness of their components,” explained Dr Pietro Piffanelli, the team’s Scientific Coordinator, “and because we found the Tecan liquid handlers represent the best combination of hardware technology and state-of-the-art software solutions.”

In order to fully integrate the platform’s multiple instruments with the laboratory’s existing LIMS, scientists at the PGP are using Tecan’s Freedom EVO Sample Tracking software to create a

SOFTWA R E

“

There were no major hurdles in combining the Sample Tracking software with our existing LIMS

PGP set-up

”

bridge for transferring all data between the Freedom EVO workstations and the LIMS. The PGP’s SQL*LIMS® from Applied Biosystems records and tracks all the samples, the processing steps performed and the data generated. This means the platform has two software systems running concurrently: the Sample Tracking manages all the data from the Tecan instruments and transfers them to the SQL*LIMS®, which incorporates them with the rest of the tracked data for further processing.

Gert Sclep, the PGP team’s bioinformatician and LIMS specialist, was directly involved in the implementation of the current system, as he explained: “There were no major hurdles in combining the Sample Tracking software with our existing LIMS; different database management systems underlie the two programs, which introduced a slight incompatibility that we have successfully overcome to form one coherent database system.

It took about a month to link the two systems, and another month for the synchronization of the GENios reader data. We are now in the third phase of implementation, in which actual plate manipulation steps performed on a Freedom EVO workstation are stored in the Sample Tracking database and transferred to the SQL*LIMS® database.”

The completed integration will represent an enormous upgrade of the automation capacity of the entire platform. All the data from the Tecan instruments and workstations will be automatically

Schematic of workflow and LIMS/Sample Tracking

entered into the LIMS, relieving the analysts from laborious, manual data input. This has major advantages for the quality of service the PGP team can provide. “We estimate that manual input has an error rate of about three per cent, so minimizing our manual input operations will significantly decrease this error percentage,” explained Gert.

Pietro added: “With the automated setup of our genotyping platform, we can generate up to 5,000 genotyping data points in a day, depending on the assay protocols. This means that at full capacity we expect to generate around one million data points annually.”

our ISO 9001 certification. The feedback that we have received from our customers so far is very encouraging, both for the quality of our service and the quality of the data that we have generated for them.”

SQL*LIMS is a registered trademark of Applied Biosystems

“The technical assistance we received from the Tecan Italy team has been instrumental and of high quality, enabling us to be fully operational with all three liquid handling workstations in just a few months and we are now halfway through Tecan Journal 1/2007

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BIOPHARMA

Perfecting technology for Scientists at Columbia University have created three flexible, fully automated workstations based on Freedom EVO® 200 platforms for the assay development work they are performing as part of the NIH Molecular Libraries Roadmap initiative.

A year into the NIH Roadmap initiative, a team of researchers at Columbia University has established a truly remarkable, purpose-built assay facility in the middle of Manhattan. The new 6,000 square foot facility, which has been set up from scratch, is one of ten screening centers in the US that together form the MLSCN, the Molecular Libraries Screening Centers Network. The centers aim to bring in a range of different types of assays from the scientific community, both enzymatic and high content cellbased assays, and use them to screen a large set of compounds, looking for those Tecan Journal 1/2007

that perturb specific functions in the cell or bind specific proteins and could consequently be further developed for use as biological probes.

Many of the Columbia team members were previously involved in other screening efforts at the Sloan-Kettering Cancer Center in New York, including Geoffrey Barger, the Automation Integration Manager. Geoff was an integral part of the planning and construction of the screening workstations in association with the Tecan Integration Group based in North Carolina in the US, and is now running all three systems single-handed!

Planning started in 200 , as Geoff explained: “We started with a concept that set out what we wanted to do, and we quickly learned that we wanted to do just about everything! We needed a very flexible system that could handle a wide range of labware, volumes, reading techniques, and assay types; anything from cell culture, adenovirus production, enzymatic assays or cell-based assays.

We needed a completely automated system. From there, we constructed a wish-list and gave a full brief to over 10 companies, looking for a single source vendor to take care of all peripherals, software and full project management.

For me this was a critical phase because I

asked the companies for their best efforts and, most importantly, gave them the opportunity to think outside of the box, to create something completely new and innovative.”

“Tecan came back to us with what I considered to be the right mindset to achieve just what we needed. Although the instruments themselves are offthe-shelf models, the way they are put together to make a comprehensive system is very different, very creative, and just what we needed. The flexibility and modularity of the hardware were also important, as was the intuitive scheduling software. The people too were an important factor for choosing Tecan.

They were willing at all stages to look at different designs, different platforms and different configurations in great detail, and they took their time to develop these concepts together with us. We could then decide what we liked and didn’t like and, through that process we learned everything that Tecan is capable of. Not only have we ended up with a very stable and productive platform, but we also have an intimate knowledge of the systems, how they’re put together and what their capabilities are. This is what allowed us to get things up and running faster than was thought possible.”

BIOPHARMA

the NIH Roadmap All three units are now integrated in biosafety level 2 enclosures provided by BigNeat. These units are housed within a biosafety level 2+ room, with restricted access, special paint, special ceiling tiles, flooring, etc. The enclosures have Hepa filtered air in to protect the products and Hepa filtered air out to protect the personnel and environment. A typical assay starts with the compound and empty assay plates in a LPX 0 room temperature carousel from Liconic. The assay plates progress through a series of reagent additions and incubations which vary depending on the complexity of the assay. The platforms are equipped with various modules and options, including liquid handling arms, a Te-MO™ 96 multipipettor, PowerWasher™ 8 plate washers, a plate sealer, Columbus™ plate washer etc.

For cell-based assays the team has a high capacity, high resolution, laser line scanning confocal microscope called the INcell Analyzer 000 (Amersham/GE).

This serves as the basic workhorse for the high content analysis and is located in a dedicated room. However, for enzymatic assays, there is an Infinite™ 200 microplate reader integrated onto each of the three decks so the analysis of these assays can be performed entirely on these platforms.

The customized platforms are equipped with various modules and options

Dr Lars Branden, Associate Director of the Genome Center, Project Director and Director of Automation, continued: “For the NIH project our goal for year 2 is to screen and possibly supersede 10 assays with up to 100,000 compounds per screen, and for year to screen 20 assays with 00,000 compounds. Amazing as it might seem, neither of these targets gets close to our capacity. It might be a challenge for the imaging systems but not the automation system. Another major project we have is creating arrayed adenovirus-based genomic libraries of human genes using the Te-FlipperTM and RoboFlasks® implemented on one of the platforms, which successfully produces around 150 adenovirus clones per week or more, depending on the logistical planning.”

Geoff agreed: “We have the capacity, the systems are ready and waiting, and so we are now a full screening center and would like to develop collaborations with academia and industry. We are reaching out to the scientific community in the US and abroad and have already had good initial feedback from other research groups.”

He concluded: “I personally have never seen an automated system quite like this one; it is truly fully automated; an engineer’s dream! At every stage, the interaction with the team at Tecan US has been imperative for us to succeed and the way they have backed us up is tremendous. I can’t stress enough that it’s the people at Tecan that really have made the difference.”

RoboFlask® is a registered trademark of Corning Inc.

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Sample management for pharmaceutical research in Japan Pharmaceutical research scientists at Japan Tobacco Inc. (JT) rely on Tecan’s Genesis RWS™ workstations and REMP Tube Punching Module™ (TPM) for their sample management, to handle the enormous number of compounds with pharmaceutical potential that are being studied in their laboratory.

No longer just a tobacco company, JT in Tokyo, Japan, has three pillar business operations of tobacco, foods and pharmaceuticals. Since 1987, JT has been striving to build a distinctive research and development-driven pharmaceutical business of international recognition, aiming to create original drugs for a variety of fields like diabetes, lipid metabolism, immunology, inflammation, viral diseases and bone disorders.

JT researchers (from left to right): Hiroshi Sahara, Nobuko Fujimoto, Miwa Kamabe and Akira Ohta

“

We evaluate hundreds of thousands of compounds for their effect upon a target molecule

”

Tecan Journal 1/2007

Senior researcher Dr Akira Ohta manages compound samples for seed discovery, where he and his colleagues are working on the early stages of drug discovery and are responsible for the management and supply of compounds. “We are searching for seed compounds; substances with specific or unique effects upon potential target molecules, like enzymes, receptors and functional proteins or protein-protein interactions,” explained Dr Ohta. “To

find these compounds, we first evaluate hundreds of thousands of compounds for their effect upon a target molecule and, from these, a few thousand are selected for further tests. This second round of evaluations involves different tests, using different concentrations to study dose response, and tests to determine whether there is specificity to the target.

These tests require a larger amount of the compound solutions of a greater volume, or of a higher concentration, are prepared and stored to be called up when required. The process of repeated evaluations continues on each compound over several rounds to narrow our focus, selecting substances with special effects from a large starting number, and eventually reducing this to 20 or 30 seed compounds. Once a few seed compounds have been identified, many related compounds are synthesized, and those which are considered suitable for pharmaceutical applications are selected for further development.”

SA MPLE M ANAGEM E N T

Genesis / TPM / Carousel set-up

JT’s Central Pharmaceutical Research Institute in Osaka

Close-up of TPM in the Genesis

Dr Ohta’s group has two Genesis RWS workstations in the laboratory – one equipped with liquid handling modules to dissolve and aliquot the compounds into individual tubes, while the other uses an integrated robotic manipulator (RoMa) arm to transport racks of tubes to and from the Tube Punching Module, and Tecan’s Carousel HS™. The TPM cherry picks the compounds by punching out the required tubes from Source Tube Racks (STBR) and into Destination Tube Racks (DTBR), and the DTBRs are stacked in the Carousel to be taken away and used for the evaluation of the compounds.

The group uses REMP’s 384 Tube Technology™, which comprises 384 individually sealed tubes, secured within one tube rack. The compound solution is dispensed into each of the small, 40 μl tubes, which are then heat-sealed and stored. Dr Ohta explained why he is particularly pleased with this set-up: “Integrating the 384 Tube Technology into our workflow was straightforward,

“The Genesis/TPM system is extremely easy to use, and one person can control the process just by pressing a few buttons or clicking on the PC monitor with the mouse. Although the installation area is relatively small and it occupies minimal bench space, the system is now able to pick hundreds of tubes in an hour. Using an automated and barcoded system such as this for so many plates is essential to eliminate the human error that would be inevitable if we attempted to handle this kind of throughput manually.”

Dr Ohta concluded: “For the future, we are looking for a system capable of storing the compounds frozen in the STBR with direct, automated access, and of a size around REMP’s Small-Size Store™ (SSS) or Mid-Size Store™ (MSS), for even greater efficiency in our sample management. The recent merger of Tecan and REMP gives us even greater confidence that we will receive an integrated maintenance and technical service for our instruments.”

and was an economical use of our funds. This system helps to minimize the absorption of moisture during the cherry picking step, improving the quality of the compound solution.

Our standardized procedure involves dissolving the compounds in dimethyl sulfoxide (DMSO) which is highly hygroscopic and can be affected by water vapor in the air; water absorbed by the DMSO causes the dissolved compound to precipitate. Before we started using the 384 Tube Technology, precipitation of the compound for this reason was common in the DMSO solutions, and resulted in a lower level of activity in the cherry picked compounds compared to original activity levels. Now, with the 384 Tube Technology, the DMSO solution of the compound is sealed within small tubes and directly transferred to the DTBR using the TPM; compound precipitation is kept to a minimum and the related loss of activity of the compounds has been virtually eliminated.”

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A P P L I CAT I O N B IOPHARM A

PureLink 96 ™

PureLink 96 HQ Mini Plasmid Purification Kit ™

Automated, high throughput purification of plasmid DNA

The ever-increasing demand for high throughput (HTP) applications for molecular techniques, particularly plasmid DNA purification methods, has led to a number of new automated purification procedures in life sciences laboratories. To meet the needs of these automated methods, Invitrogen offers you the PureLink™96 HQ (High Quality) Mini Plasmid Purification Kit. This kit provides a universal 96-well plate design that not only is compatible with most automated liquid handling platforms but also has the ability to deliver the high quality plasmid DNA necessary for today’s stringent applications. Use the PureLink™96 HQ Mini Plasmid Purification Kit with your robotic system to quickly

generate high mini-prep yields with low genomic DNA contamination and nondetectable RNA contamination, without compromising quality.

Workhorse for plasmid prep purification The PureLink™96 HQ Mini Plasmid Purification Kit is based on an alkaline / SDS cell lysis procedure, followed by neutralization of the lysate and selective plasmid DNA binding to glass microfiber filters. The bound DNA is then washed to remove impurities from the original sample (such as genomic DNA and RNA), and the clean DNA is eluted in a lowsalt buffer. This DNA isolation method is typically faster and easier to perform than anion exchange methods. There’s no need

Figure 1: 1. Wash station 2. Disposable tip (DiTi) waste 3. Disposable tip carrier 4. Wash Buffer 5. Elution Buffer 6. Resuspension Buffer 7. Lysis Buffer 8. Neutralization/Binding Buffer 9. Te-Shake shaker with deep-well plate Tecan Journal 1/2007

for alcohol precipitation or desalting, making it ideal for HTP studies.

Validated HTP procedure using Tecan automated robot To get you started on your HTP applications, we have validated a robust procedure to isolate plasmid DNA from bacteria in a 96-well format using the PureLink™96 HQ Mini Plasmid Purification Kit and a Tecan Freedom EVO® automated liquid handling platform with Freedom EVOware® software.

The Freedom EVO separation system with the Te-VacS™ vacuum separation module allows for walkaway automated processing. Pipetting is performed by the liquid handling (LiHa) arm, while the robotic manipulator (RoMa) arm performs all transports of the plates and assembling steps of the Te-VacS vacuum manifold.

Briefly, the PureLink™96 HQ Mini Plasmid Purification Kit script opens with the deck layout as shown in Figures 1 and 2.

The pelleted cell culture plate is placed on the Te-Shake™ orbital mixer. Cell resuspension, lysis, and neutralization buffers are added sequentially, with shaking between each buffer addition.

The binding and clarification plates are

APPLICATIONS B IOPHA R M A

Figure 2: The Freedom EVO workstation layout

The filter is then washed with buffer W1 before addition of elution buffer. This script allows for anywhere from 1 to 96 samples to be processed at a time, with up to 1.5 × 109 cells per well in <1 hour per 96-well plate.

Figure 3: High quality plasmid DNA is obtained using the Purelink™96 HQ Mini Plasmid Purification Kit

Figure 4: The Freedom EVO provides uniformity and consistency in DNA yield and quality

deployed to the Te-VacS using the RoMa. The neutralized lysate is transferred to the clarification plate, whereupon the vacuum is applied. The cleared lysate is collected in the binding plate and transferred to the second Te-VacS manifold and the vacuum applied to bind the plasmid DNA to the glass fiber matrix.

High quality, uniform and consistent results Plasmid DNA extracted from the PureLink™96 HQ Mini Plasmid Purification Kit via the Tecan robot is of extremely high quality as evidenced by the absence of RNA, extremely low genomic DNA contamination, and high supercoiled to nicked form ratios (Figure 3). In addition, uniformity and consistency in DNA yield and quality among the different wells indicate that the Freedom EVO separation system provides a very reproducible method of automated plasmid DNA isolation (Figure 4). Well-to-well variation was on average <10% for the automated protocol. The resulting plasmid DNA is transfection quality, with low endotoxin levels, and suitable for use in fluorescent sequencing with >98% accuracy of base identity for a 600-base read.

“

The Freedom EVO platform with the Te-VacS vacuum separation module allows walkaway automated processing

”

Efficient, quick, reliable and easily automated HTP method The PureLink™96 HQ Mini Plasmid Purification Kit provides an efficient, quick, reliable, and easily automated HTP method for plasmid DNA sample preparation. Similar scripts have also been written for the PureLink™96 PCR Purification Kit and PureLink™96 RNA Purification Kit on Freedom EVOware software.

This article is reprinted with permission from Invitrogen. For more infromation, visit www.invitrogen.com/purelink PureLink is a trademark of Invitrogen

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First – 80 °C biobank

Pfizer success story This new automated storage and retrieval system from REMP is a key component of Pfizer’s biobank and is a result of customer-focused collaboration leading to state-of-the-art storage solutions.

Pfizer also makes an important contribution to the provision of Switzerland’s healthcare with over 150 medicines.

Utilizing the enormous potential of biological samples Thanks to the sequencing of the human genome and the continually improving analytical methods in the field of molecular biology, biological samples have acquired a new significance and value. Where samples were once gathered for specifically stated purposes, had limited use, and were stored for archival purposes, they can now be stored under the best possible conditions for multiple uses in further studies.

Pfizer’s big chill Pfizer is the world’s largest pharmaceutical company with the largest privately financed research organization.

Over 115,000 employees in more than 150 countries work towards improving health. Its business activities encompass the fields of prescription medicines, overthe-counter medicines and veterinary medicines. Thanks to continuous research and development as well as long-term planning, Pfizer is repeatedly successful in being able to offer effective medicines in the fight against and alleviation of diseases.

Tecan Journal 1/2007

Modern investigative methods in the fields of ‘personalized medicine’, pharma­ cogenomics, pharmacometabonomics and proteomics now provide far better insight into the modes of action of different therapeutics, enabling them to be optimized and administered more easily and accurately. Properly stored clinical trial samples have the potential to expedite development of investigational new medicines, thereby accelerating their delivery to patients. The biological samples can help researchers uncover pathways and metabolic processes which may have been previously inaccessible or undiscovered.

SA MPLE M ANAGEM E N T

The pharmaceutical industry has recognized this enormous research potential and the value to both scientists and patients of making these study samples available worldwide. This requires samples to be stored under precisely defined conditions at extremely low temperatures. They must not be subjected to any freeze-thaw cycles and any temperature fluctuations within the system must be minimized. The multitude of samples and defined storage conditions practically rule out any kind of manual handling of samples. This critical storage process needs to be automated in order to obtain samples of the best possible quality.

Fully automated storage at – 80 °C and – 20 °C REMP has had long-standing experience in the design and construction of storage systems for chemical compounds. The objective of the Pfizer biobank project was to ensure the precisely defined, fully automated storage of biological samples at temperatures of – 80 °C and – 20 °C, and to safeguard the best possible quality of such samples over extended periods of time.

Based on proven storage technology The first REMP Bio Sample Store™ was developed jointly with Pfizer Global Research and Development, and is able to store millions of samples at – 80 °C and – 20 °C concurrently, and under controlled dry-air conditions to prevent frost buildup. For the design, the proven concept of REMP’s – 20 °C storage solution for chemical compounds was modified by fitting additional large, automated freezer compartments that operate at – 80 °C. New door mechanisms to ensure the time-critical opening of the compartments were also developed. In order to avoid mechanical problems, due to the low temperature environment, only passive mechanical components were used. Newly developed software algorithms further guarantee optimally selected storage locations and best possible access to samples. The integrated Tube Punching Module™ ensures that cherrypicking or reformatting of samples always occurs at – 20 °C, within the Bio Sample Store. The storage unit has fully redundant cooling and robotic systems, which allow service and maintenance to occur without any loss of system use or effect on the controlled storage environment.

The world’s first large scale, automated – 80 °C storage facility Pfizer’s biobank is the world’s first large scale automated store for biological samples in which samples can be stored at both – 80 °C and – 20 °C. Equipped with REMP’s patented Tube Technology™, Pfizer operates a complete system that minimizes the number of freeze-thaw cycles subjected to a sample, thereby maximizing optimal sample quality. All of the basic conditions were developed in cooperation with Pfizer according to their requirements. Thanks to its long-standing experience in building automated storage facilities and managing large scale projects, REMP was the first company to set up an automated – 80 °C store, and in record time. The store was installed and commissioned on schedule. Key dates: contract signed – June 2004; FAT (factory acceptance test) – April 2005; SAT (site acceptance test) – March 2006.

This article was kindly provided by Pfizer Photos: Tim Cook/The Day Publishing Company (New London, CT)

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EV E N TS 2 0 07

Meet Tecan at these events in the first half of the year Americas Lab Automation 2007 (ALA)

Palm Springs, CA

28 Jan 2007

MD & M West

Anaheim, CA

13 Feb 2007

American Academy of Forensic Sciences (AAFS)

San Antonio, TX

19 Feb 2007

Pittcon 2007

Chicago, IL

25 Feb 2007

Genomic & Proteomic Sample Preparation

Boston, MA

10 Apr 2007

American Association for Cancer Research (AACR)

Los Angeles, CA

14 Apr 2007

Society for Biomolecular Sciences 2007 (SBS)

Montreal

15 Apr 2007

American Society for Microbiology (ASM)

Toronto

21 May 2007

Tokyo

25 Mar 2007

The Pharmaceutical Society of Japan

Toyama

28 Mar 2007

The 6th International BioExpo

Tokyo

20 Jun 2007

Forum Life Science

Munich

14 Feb 2007

Screening Europe

Barcelona

20 Feb 2007

Cell Line Development and Engineering 2007

Vienna

06 Mar 2007

18. Jahrestagung – Deutsche Ges. für Humangenetik

Bonn

07 Mar 2007

Genomic Disorders 2007

Cambridge

21 Mar 2007

Sanguin Spring Seminars

Amsterdam

19 Apr 2007

MC-GARD Molecular Profiling of the genome

Amsterdam

02 May 2007

MipTec 2007

Basel

07 May 2007

AMT – Advances in Microarray Technology

Edinburgh

15 May 2007

– 106th General Meeting

Asia and Pacific RIM Japanese Society for Bioscience, Biotechnology and Agrochemistry

Europe, Middle East and Africa

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, Beat Glauser/www.beatglauser.com, Tim Cook/The Day Publishing Company (New London, CT) Editor: kdm/UK www.kdm-communications.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Switzerland AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com,www.tecan.com 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.

For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative.

This brochure may contain reference to applications and products which are not available in all markets. Please check with your local sales representative.

Carousel HS, Columbus, Genesis RWS, GENios, HydroFlex, HydroControl, Infinite, Magellan, PosID, Power Washer, quad4 monochromators, Safire2, Te-Flipper, Te-MO, Te-Shake, Te-Stack and Te-VacS are trademarks and Cavro, Freedom EVO, Freedom EVOlyzer and Freedom EVOware are registered trademarks of Tecan Group Ltd., Männedorf, Switzerland.

Tecan is in major countries a registered trademark of Tecan Group Ltd., Männedorf, Switzerland.

ACD96, MCD8, REMP Bio Sample Store, REMP Mid-Size Store, REMP, Small-Size Store, REMP Tube Punching Module and REMP Tube Technology, are trademarks of REMP AG, Oberdiessbach, Switzerland. © 2007 Tecan Trading AG, Switzerland, all rights reserved.

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 www.tecan.com Tecan Austria +43 62 46 89 33 Belgium +32 15 42 13 19 China +86 10 586 95 936 Denmark +45 70 23 44 50 France +33 4 72 76 04 80 Germany +49 79 51 94 170 Italy +39 02 215 21 28 Japan +81 44 556 73 11 Netherlands +31 18 34 48 17 4 Portugal +351 21 000 82 16 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 ROW +43 62 46 89 33 REMP Switzerland +41 31 770 70 70 Japan +81 44 542 70 21 USA +1 508 429 2200

Tecan Journal 1/2007