Tecan Journal Edition 01/2008

Tecan Journal Tecan’s Freedom EVO® makes its television debut on CSI page 10

Edition 1 / 2008

Tecan collaborates with GE Healthcare to bring increased quality and consistency to protein purification processes page 11

Automated production of microfluidic test devices with Tecan launches the Infinite® M1000 flagship multimode the Freedom EVO®/REMP microplate reader Small-Size Store™ Factory pages 12 – 13

Walter Guidon, Technical Support & Training, Tecan Schweiz AG

pages 16 – 17

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C E O WE LCOM E

We wish our customers a

very happy new year for 2008!

As we look ahead to a prosperous new year, we can reflect on 2007 as a busy and productive time for all of Tecan. Our development teams have once again delivered several novel innovative tools to add to our product portfolio, from flexible liquid handling arms to software upgrades, QC tools, a new high-end multimode microplate reader and newest additions to our OEM components portfolio. You can find out about all of these new products and more in this, the first edition of the Tecan Journal for 2008 or our website, and visitors to the Tecan stand at the LabAutomation exhibition in Palm Springs, California, in January will be able to see them first hand.

This bumper edition of the Tecan Journal celebrates several firsts: our first systems biology seminar conducted by acclaimed international scientists; the first installation of the Freedom EVO®/REMP Small-Size Store™ Factory in the US; and the Freedom EVO’s first TV debut on the forensic hit series CSI: Crime Scene Investigation! We are delighted that this starring role came on the recommendation of several prominent forensic scientists, who all agreed that Tecan’s Freedom EVO platform is one of the best systems available for processing DNA. Read on to find examples of Tecan’s outstanding solutions for customers in such diverse areas of science as diagnostics, protein sciences, forensics and agricultural research.

Enjoy this issue, Thomas Bachmann, CEO

Tecan Journal 1/2008

CO NTENTS CEO welcome A New Year message from Thomas Bachmann, CEO. page 2

Tecan’s Freedom EVO® makes its television debut in CSI: Crime Scene Investigation Customized systems designed by Tecan. page 10

Automated cherry picking with the Freedom EVOware® Hit Picking Wizard A new add-on to your Freedom EVOware. page 4

Collaboration to bring increased quality and consistency to high throughput protein application processes GE Healthcare’s protein purification products are perfect for Tecan’s workstations. page 11

Unique flexibility from the Freedom EVO® 75 The versatile 8 Plus 1 Access™ pipetting tool. page 5

The new Infinite® 200 NanoQuant The NanoQuant has been specifically developed for absorbance applications. page 5

Automated production of microfluidic test devices with the Freedom EVO®/ REMP SSS Factory Manufacturing revolutionary microfluidic card-based diagnostic arrays. pages 12-13 Automation gives scientists time for science The Freedom EVO® workstation does the liquid handling, and the scientists do the analyzing. pages 14-15

And we have a winner!

The first winner of the colorful microplate reader competition receives an Apple iPod nano. page 8

Perfecting our disposable tips for optimal performance Tecan’s disposable tips are carefully engineered to high standards for our liquid handling workstations. pages 24-25 A perfect fit for the Freedom EVO® 75 in forensic toxicology Automated screening for drugs of abuse using Tecan’s liquid handling workstation. pages 26-27

The Infinite® M1000, Tecan’s multimode flagship microplate reader, is launched at LabAutomation 2008 More flexibility, sensitivity and speed in one high-end multimode reader. pages 16-17 Evaluating automated nucleic acid extraction using Abbott RealTime™ assays Optimized nucleic acid extraction with the Freedom EVO® Clinical 75 workstation. page 18 High throughput diagnosis of infectious animal diseases with the Freedom EVOlyzer® Freedom EVOlyzer is being used to protect Sweden’s livestock from infectious diseases. page 19

Systems biology symposium, a great success A forum for leading scientists on the shores of Lake Zürich. page 9

Quality control and validation tools for your IQOQ needs Fulfilling all regulatory requirements, cost-effectively. page 23

Automating hybridization of protein biochips improves biomarker discovery The HS 4800™ Pro automates processing of biochips containing hundreds of markers. pages 28-29

New components: syringe pump and robotic processor New OEM products on show at LabAutomation. page 6 A new 384-channel head for Freedom EVO® Offering higher productivity to pharmaceutical and biotechnology research applications. page 7

Tecan is the OEM partner of choice Life science and clinical diagnostics companies are choosing Tecan to help them move into new markets. pages 22-23

Semi-automated DNA isolation from cereal crops using the Te-MagS™ module Overcome labor bottlenecks in DNA isolation by using automated DNA purification with magnetic beads. pages 30-31 Events 2008 Come and meet Tecan this year at any of these events. page 32

Improving quality and throughput of assays for genomic and proteomic research in South Africa The HS 4800™ Pro Hybridization Station is used for investigating infectious diseases. pages 20-21 Tecan Journal 1/2008

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P ROD U CT N EWS

Automated cherry picking with the Freedom EVOware® Hit Picking Wizard Tecan’s Freedom EVOware® Hit Picking Wizard is available as an add-on to your Freedom EVOware software for automated plate and compound management during hit picking. The software is suitable for a variety of hit picking applications with the Freedom EVO® platform, such as production of IC50 plates for hit confirmation, cherry picking after high throughput screening, or providing secondary screening plates for use in ADME assays.

The Hit Picking Wizard also takes care of plate logistics, such as instructing a robotic manipulator (RoMa) arm to replace source plates and swap destination plates as necessary during the process. The add-on integrates with the Freedom EVOware Sample Tracking software, so that sample tracked labware continue to be identified and tracked during the hit picking processes.

Source plates and empty plates for hit compounds are loaded into storage devices or placed on the Freedom EVO deck and compounds of interest, identified in a hit list provided by the LIMS, are pipetted into the assay plates by the Freedom EVO liquid handling arm. The workstation can also prepare controls and dilutions for further assays if required, and the software provides a full report at the end of the process.

The Hit Picking Wizard integrates fully with the main graphical user interface of both the Freedom EVOware Standard and Freedom EVOware Plus programs.

The software handles a variety of storage devices (eg. carousels, stackers and hotels) and labware (eg. REMP tubes and delivery plates, 96- and 384-well plates), and provides a simple graphical layout of the plate for straightforward hit picking.

It controls a single 1-, 2-, 4- or 8-tip liquid handling arm, and is compatible with 200 and 1,000 μl disposable tips.

Screenshots from the Freedom EVOware Hit Picking Wizard

Tecan Journal 1/2008

PRO DUCT N EWS

Unique flexibility from the Freedom EVO® 75 Tecan has launched its latest development for the constantly evolving, compact Freedom EVO® 75 robotic workstation. The 8 Plus 1 Access™ tool is a clever and cost-effective eight-channel arm for fast and flexible pipetting. This unique new arm can pipette across a microplate with eight tips simultaneously, and access an individual sample with a single versatile tip, all on the same tool.

The new option combines the best of Tecan’s liquid handling experience, giving customers: l the security of liquid level detection, down to 50 μl of conductive liquid (only for the first tip); l the flexibility of a large volume range: 2-1000 μl; l the efficiency of multi-pipetting with 1000 μl tips; l the reliability and precision of the Freedom EVO series.

The 8 Plus 1 Access arm makes routine pipetting tasks, including reagent distribution, serial dilutions and plate reformatting, fast and easy to set up, and

is ideal for applications such as ELISA, PCR set-up and nucleic acid extraction.

For example, fitting a Freedom EVO 75 with this new option and a robotic manipulator (RoMa) arm, offers a very economical solution for semi or full automation of ELISAs, reducing the time-consuming reagent addition steps by more than 80 % compared to using a single tip instrument. The simple and efficient Freedom EVO 75 can be equipped with on-board incubation, plate storage, plate washing and plate reading all controlled seamlessly through our easyto-use Freedom EVOware® software.

The 8 Plus 1 Access further enhances the outstanding liquid handling performance, reliability and flexibility of the Freedom EVO 75, which is the perfect solution for laboratories with limited space and is ideal for those labs taking the first steps towards automation.

The 8 Plus 1 Access arm is scientific instrumentation.

Not for use in human clinical or diagnostic procedures.

Capabilities of the 8 Plus 1 Access arm; eight-tip pipetting and one tip independent action

The new Infinite® 200 NanoQuant is launched, tailored for absorbance applications The Infinite® 200 NanoQuant, Tecan’s highly sensitive absorbance instrument, is being launched at LabAutomation 2008, booth 305, 27-30 January in Palm Springs, USA. The Infinite 200 NanoQuant is the first microplate reader to be developed specifically for absorbance applications with low volumes.

The new instrument represents a simplified version of the standard Infinite 200 and is available with Tecan’s new NanoQuant PlateTM, a sensitive, quartz-based tool that can measure up to 16 samples simultaneously from

just 2 μl sample volumes, and detect DNA concentrations as low as 1 ng/ μl. The NanoQuant Plate is compatible with multichannel pipettes and gives high measurement reproducibility; it is also available for standard Infinite 200 instruments.

The Infinite 200 NanoQuant reader is available with quad4 monochromators™ (Infinite M200 NanoQuant) that provide high wavelength accuracy for endpoint measurements over the entire spectral range, or with new 260 and 280 nm filters (Infinite F200 NanoQuant) with a UV-

stable coating that provide exact central wavelengths and narrower bandwidths.

The instrument can perform absorbance measurements with standard microplates (6- to 384-wells) as well as half-well 96-well plates, and is easy to run with the latest i-Control™ software that features tools for rapid DNA/RNA quantification.

The Infinite 200 NanoQuant can be upgraded with the additional detection modes that are available with the standard Infinite 200 as required.

Tecan Journal 1/2008

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P ROD U CT N EWS

A new generation of Tecan OEM components Visitors to LabAutomation will be able to see Tecan’s new generation of liquid handling technology components, the new pump and the new robot.

New pump The new pump was developed to complement and extend our current range of syringe pumps, including the Tecan CavroÂŽ XCalibur and Tecan Cavro XLP. The new pump increases standards for accuracy and precision through a new, simple but rigid direct drive pumping mechanism. The use of long-life ceramics for the fluidic path ensures unbeatable longevity, even for solvents. It also offers a broader working volume range from a single syringe size compared to other similar pumps, enabling users to do more with one pump than ever before. The new pump features increased on-board diagnostics, so the user can interrogate the pump for its critical performance criteria.

New robot The innovative new robot provides users with the security of knowing exactly what the product is doing and where the pipetting probe is located at all times, minimizing probe positioning error. Its simple design promises the same robustness and reliability that is characteristic of Tecan’s products, while its modularity offers superior flexibility, making the new robot easily configurable for many different applications. The new robot is designed for easy integration, being both easy to install and to operate, making it the ideal OEM robotics component choice. It is encased so that all working parts are hidden to sport a finished professional appearance.

New pump shown with 1.25ml syringe

New robot shown in single arm configuration

Tecan Journal 1/2008

PRO DUCT N EWS

A new 384-channel head for the Freedom EVO®

Simultaneous pipetting of 384 wells

Tecan is launching a new 384-channel head for the Freedom EVO® liquid handling workstations, offering higher productivity to automated liquid handling processes in pharmaceutical and biotechnology research applications. The MultiChannel Arm™ 384 can be mounted onto Tecan’s Freedom EVO 100, 150 or 200 platforms, increasing the efficiency and speed of pipetting processes for better throughput, and delivering a greater level of flexibility.

both disposable tips and washable stainless steel tips, which can be automatically interchanged during a run. Alternatively, the head can rapidly mount 96 tips, or just a row of 24 or a column of 16 tips, for pipetting controls or conducting in-plate serial dilutions.

An optional gripper can be mounted on the pipetting head to move plates or tip racks, for added functionality. This flexible tool is a great asset for all your pipetting applications.

The head features a very broad volume range of 0.5 μl to 125 μl. It works with

In addition to the MultiChannel Arm, up to two other independent arms can be

fitted onto the Freedom EVO at the same time, offering multi-functionality and true parallel processing. The new 384channel head is fully compatible with all Freedom EVO options, and many third party devices.

Not for clinical diagnostics use.

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P ROD U CT N EWS

And we have a winner!

HydroFlex and Sunrise in the different colors available

Discussion continues to rage over whether orange, blue, red or bright green is the best color for our new HydroFlex™ 3-in-1 platform and the popular Sunrise™ microplate reader. Many of you have joined in with your thoughts and for a chance to win one of these instruments in one of the available colors, or an Apple iPod nano 8GB. Mrs Annamari Heiskanen of Glykos Finland Ltd in Helsinki, Finland, is the first winner of the iPod nano from the October draw. Annamari voted for red as her favorite colored Sunrise reader and won herself a shiny iPod in magenta.

Cell biologist Annamari Heiskanen works as a project manager at the biotech company Glykos Finland Oy in Helsinki. Glykos Finland Oy specializes in glycobiology and carbohydrate chemistry, offering product development and services to multinational customers in the field of functional foods and pharmaceuticals. The company’s innovative development of bioactive carbohydrate molecules has led to a

Tecan Journal 1/2008

variety of applications, such as biomarker screening from cell and cancer glycomes, as well as a product for treating gastric ulcers and development of functional food components. “The company is growing rapidly so we need new, reliable workhorse instruments for our laboratories,” said Annamari. “It is a bonus if they also look inspiring!”

There is still time to join the debate. Visit us at www.tecan.com/colors for your chance to win one of these prizes. A draw will be held at the end of every month until March 2008 for the iPod nano, and a separate draw in January 2008 for the HydroFlex or Sunrise.

Mrs Annamari Heiskanen of Glykos Finland, receives her new iPod nano from Hanna Laiho at PLD Finland Oy

COR POR ATE N EWS

CO R PO R ATE N EWS

Systems biology symposium, a great success Our systems biology symposium, held in mid-September on the shores of Lake Zürich, presented a rare opportunity for leading scientists working at the forefront of research to meet together in an informal atmosphere. The event was attended by researchers representing many of the world’s major research institutes, and several prominent scientists gave presentations on their current and future initiatives in this fastmoving field.

The event was arranged in association with Alan Sawyer, Head of the EMBL Monoclonal Antibodies Core Facility, who chaired the first day. He began proceedings with a presentation about

the new monoclonal antibody production facility currently under construction at Tecan’s headquarters in Männedorf and on site at Monash Antibody Technologies Facility (MATF) at Monash University, Australia, where he is soon to take up a position as Director.

Alan said: “The timing of this event was perfect. Some colleagues and I had discussed how we could bring together top class scientists working in systems biology and, almost simultaneously, Tecan approached me expressing an interest in just such a forum. The result has been an intensely stimulating environment, with plenty of opportunity for in-depth, constructive discussions on a more

intimate level than is normally possible at larger scientific meetings.”

Our Senior Vice President, Carl Severinghaus, said: “The entire event has been a very rewarding experience and it was a privilege to bring so many luminaries together and hear first hand about their latest projects. We have also been able to learn more about the role of automation in systems biology and have a better understanding of how Tecan can provide the ideal automation solutions for these applications.”

A similar event is already being planned for 2008.

Participants at the Tecan Symposium 2007

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CO R POR ATE N EWS

Tecan’s Freedom EVO®

makes its television debut in CSI: Crime Scene Investigation

Freedom EVO for DNA extraction

Sheila Thomas (left) and Barbara Wesley with the Freedom EVO

A Tecan Freedom EVO® 150 liquid handling workstation recently starred in a one-hour special episode of the longrunning, forensic science-based television show CSI: Crime Scene Investigation.

Sheila Thomas, Product Integrator on the hit show that shoots at Universal Studios in California, USA, approached Tecan on behalf of the television program and explained: “It is part of my job to help make the show realistic by finding the correct items for the set. We have a great team of technical advisors who have extensive law enforcement backgrounds but, since technology is constantly changing, we like to stay on the cutting edge by asking for the recommendations of current crime scene investigators who are out in the field every day. We contacted several law enforcement agencies and I also met with various forensic experts at the 2007 International Association of Identifications Conference, who all agreed that Tecan’s Freedom EVO platform is one of the best systems available for processing DNA.” Tecan Journal 1/2008

Tecan’s engineers configured the Freedom EVO workstation for automated DNA extraction from forensic samples and sent the system to Hollywood, where it was installed into CSI’s on-set laboratory.

During the episode, the CSI lab technician, Wendy Simms, processes some DNA samples using the Freedom EVO. She has just finished running the samples when special agents Malone, Grissom and Willows enter the lab to discuss the identity of several different cases. The platform is clearly in view throughout the scene and was essential to the storyline because it provided proof that the DNA was not a match for the missing boy.

“I wanted to thank everyone at Tecan for all the hard work they put into getting the Freedom EVO up and running for our show,” Sheila said. “Our director is a perfectionist and he was very pleased with how the Freedom EVO performed.

We got it in one take!”

The special episode aired in the USA on November 8th 2007.

imagination at work

Application B IO PHA R M A

Collaboration to bring increased quality and consistency to

high throughput protein application processes Tecan and GE Healthcare have announced a collaboration in the area of protein handling and screening. The two leading companies are working together to optimize the combination of Tecan’s automated instrumentation with GE Healthcare’s pre-packed chromatography media, specifically in the area of high throughput protein applications.

Pipetting into the MultiTrapTM plate

The combination of the throughput, precision and robustness of a Tecan automation platform with the reproducibility, efficiency and minimal cross-contamination of GE Healthcare’s pre-packed MultiTrap™ 96-well plate protein purification technology, will enable scientists to move forward more quickly in their research and focus on their areas of expertise.

“We know from our customers that the development of efficient multi parallel approaches to the cloning, expression, screening, purification and crystallization of proteins is extremely important in protein research,” said Roland Durner,

Market Manager at Tecan. “With this collaboration we are providing protein scientists with standardization, quality, consistency and reliability in protein expression screening.”

“As the biotech industry’s focus on proteins intensifies, the value for researchers of bringing together the complementary strengths of GE Healthcare and Tecan in protein separation, detection and laboratory automation is clear,” said Konstantin Fiedler, General Manager, GE Healthcare Protein Sciences. “This collaboration is designed to provide customers with a seamless experience between GE’s

chemistry and Tecan’s hardware, bringing maximum efficiency and reliability to their workflow.”

The first application resulting from this collaboration focuses on protein expression screening. It provides a complete solution, optimizing multi parallel screening of tagged proteins, screening and optimization of expression buffer conditions and identification of protein constructs.

MultiTrap is a trademark of GE Healthcare.

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automated liquid handlin g

Automated production of microfluidic test devices with the Freedom EVO®/REMP SSS Factory Akonni Biosystems is the latest company in the USA to acquire a Freedom EVO®/REMP SmallSize Store™ Factory, relying on the platform for fully automated liquid handling and sample management during manufacturing of its revolutionary TruArray™ microfluidic card-based diagnostic arrays.

Akonni Biosystems Inc, based in Maryland, USA, specializes in providing geneticbased diagnostic and disease surveillance tools for human diseases. The company has developed the TruArray™ product line, a microfluidic-based diagnostic microarray for fast genetic testing in a single portable device that is suitable for use by health practitioners.

Prof Andrei Mirzabekov at the Engelhardt Institute in Moscow, Russia, originally invented the underlying gel-drop microarray technology in 1988 and it was further developed and optimized at the Argonne National Laboratory in Chicago, Illinois. The technology was licensed to Akonni Biosystems, founded in 2003, for use in medical applications and the company has since developed its microfluidic devices, which automate the processing of every gel-drop (from 10 to 4,200) on the array. Each gel-drop behaves as a microscopic test tube that can be tailored to carry out a specific diagnostic biochemical test and, by packing hundreds or thousands of geldrops onto the array, a small volume from a single clinical sample can be analyzed for hundreds or thousands of disease markers simultaneously, yet independently. The microfluidic device performs on-chip PCR within each gel-drop and is inserted into a portable instrument for processing, allowing accurate, on-the-spot testing to be performed for a variety of diseases.

Akonni’s portable array reader

Tecan Journal 1/2008

Manufacturing these tiny devices requires precision robotics, as Dr Charles (Chuck) Daitch, founder of Akonni Biosystems,

explained: “The TruArray™ products are disposable in vitro diagnostic tests that contain a lot of different parts and require careful assembly. The injection-molded plastic that contains the microfluidics components has to be sterilized initially, and then the various reagents are assembled for printing the biomolecular centers of the array using automated liquid handling.”

“The Freedom EVO/REMP SSS platform is ideal for the set-up and support tasks required to produce our array products at a suitably high volume with appropriate quality control,” Chuck continued. “All our samples and reagents can be kept at low temperatures in the REMP SSS using the REMP Tube Technology™ consumables, and the components that couple the REMP SSS to the Freedom EVO will automatically retrieve the required reagents for our printing robots to assemble and print the TruArray™ tests.

For example, if we have an order for one million tests for a particular marker, the platform will simply pull out the

The Freedom EVO/REMP SSS platform

SA MPLE M AN AGEM ENT

Opening of the laboratory at Akonni Biosystems

The team at Akonni Biosystems

necessary reagents from the REMP SSS using barcode recognition and prepare them for printing the tests as and when required. The Freedom EVO/REMP SSS is a great help to the printing robots because it can automatically organize and prepare source plates for printing, as well as automatically handle our sample inventory and organizational needs. We are also working with engineers at Tecan to incorporate a number of additional features into the platform, including an analytical system to quantify and normalize the biomolecular centers we produce, prior to storage in the REMP SSS and preparation of the printing source plates on the Freedom EVO platform.”

“We chose Tecan because we were confident of the quality of the products,” Chuck said. “Our colleagues at the Argonne National Laboratory use many instruments from Tecan, including automated hybridization systems and liquid handling platforms.”

The REMP SSS is a fully automated storage and retrieval system that can handle samples in a variety of formats, including microplates and REMP Tube

Technology consumables. Integration of the REMP SSS with the Freedom EVO and Freedom EVOware® software allows walkaway operation for sample retrieval and processing steps. Chosen samples are identified by barcode and cherry-picked from within the store’s controlled environment and transferred to the Freedom EVO workstation using an integrated plate shuttle. Tubes can be decapped using an automated capper/decapper (REMP ACD96™) device and processed as required and, after processing, the samples are recapped and returned to storage. This combination of automated sample

storage and processing minimizes the time that samples are exposed to the environment and increases process security. Sample volumes, concentrations and identification numbers can be fully tracked within the software, and data handling is perfectly integrated, making this platform ideal for compound dissolution and reformatting factories, or genomic sample factories.

Akonni has recently moved to new facilities designed to accommodate its scaled-up production facilities, which include a clean room with four robots for printing and producing the arrays, as well as the integrated Freedom EVO/REMP SSS platform. The grand opening of the laboratory was held in November 2007 and sponsored in part by Tecan.

Scientific instrumentation. Not for use in human clinical or diagnostic procedures.

TruArray is a trademark of Akonni Biosystems Inc.

Akonni’s TruArray™ microfluidic device

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liquid handlin g and robotics

Automation gives scientists time for science In Yokohama, Japan, RIKEN (The Institute of Physical and Chemical Research) has just completed a structural genomics and proteomics project to determine numerous protein structures, for which the researchers chose Tecan’s liquid handling workstations to prepare the protein samples for NMR spectroscopy and X-ray crystallography.

RIKEN Yokohama Institute in Yokohama (photo courtesy of RIKEN)

RIKEN was organized 90 years ago as Japan’s first comprehensive research institute for natural sciences, carrying out high level basic and applied research in a wide range of fields including physics, engineering, chemistry and biology. RIKEN scientists enjoy a unique environment, as researchers in diverse fields work alongside each other and are exposed to stimulation that they would not normally experience at other research institutes.

Since 1998, RIKEN’s Genomic Sciences Center (GSC) has carried out comprehensive genomic studies, creating the term ‘omic space’ to describe the levels of biological phenomena from genome, through transcriptome, proteome, metabolome to phenome.

Currently, six groups within the GSC carry out research at each of these levels.

In response to the rapidly increasing availability of genome sequences and cDNA resources, the RIKEN Structural Genomics/Proteomics Initiative (RSGI) was formed in 2001 to promote structural genomics research by coordinating the Tecan Journal 1/2008

efforts of these and other research groups in RIKEN. Since FY 2002 the RSGI has been involved in the Protein 3000 Project (the National Project on Protein Structural and Functional Analyses) organized by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, to propel research in protein structure and function and obtain deeper insight into biological networks.

“Although structural genomics research is now being carried out throughout the world, we, in Japan, commenced the Protein 3000 Project in the early days of structural genomics,” explained Dr Masaaki Aoki, senior scientist in the NMR Pipeline Methodology Research Team of the Protein Research Group at the GSC. “For five years, our group has been responsible for a program for comprehensive studies within the Protein 3000 Project, and has carried out NMR analysis of approximately 300 protein structures a year. Our set-up is probably quite unusual – we have integrated various systems at the world’s leading

edge into our pipeline at the NMR Facility Yokohama Institute, including Tecan’s workstations.”

“In the Protein Research Group we prepare protein samples for threedimensional structural analysis by NMR spectroscopy or X-ray crystallography.

At the beginning of the project, this was performed manually but, to handle the increasing sample numbers and to obtain experimental results that endure scrutiny, robotic systems were introduced to automate each process in the pipeline.

Data reproducibility and consistency are the main advantages of process automation and, to achieve this, it is essential that the instruments perform stably and reliably.”

Dr Aoki continued: “Tecan’s Genesis RWSTM 150 and Genesis RWS 200 systems perform the rearraying of cDNA clones and PCR primers into 96- and 384-well plates. The Genesis 150 uses plate hotels and handles 45 plates, while the Genesis 200 uses a carousel and can handle 189

liquid handling and robotics (Left) The Genomic Sciences Center NMR complex (photo courtesy of RIKEN)

(Below) The Protein Research Group’s Freedom EVO workstation set-up, including the custommade tilting carrier which is tilted to the right (as shown) when reaction solutions are collected from flat-bottom wells

prepare linear templates that can be introduced directly into the cell-free system for protein synthesis. Because cloning is not required, this system is extremely quick. The protein synthesis, from cDNA to protein product, can be finished in a day or two and there is no need to worry about biological obstacles like toxic protein products that may kill living cells. It is also much easier to automate the cell-free reaction compared to protein expression and purification from living cells. All steps from synthesis to purification are automated on the Freedom EVO platform yielding, on average, 2 mg of protein.”

The Protein Research Group members (from l to r): Hitomi Saito, Dr Masaaki Aoki, Takeshi Nagira, Kazuharu Hanada, Masaomi Ikari and Yasuko Tomo

plates in one run. The Freedom EVO® 200 platform carries out the automated synthesis and affinity purification of proteins, and can process 96 samples per run, operating up to four times a week. A tilting carrier has been installed to allow efficient collection of reaction solutions from flat-bottom wells with dialysis membranes, and Tecan’s MIO™ shaking incubators have been integrated, as well as an automated centrifuge underneath the platform.”

“We first screen for proteins that yield suitable quality and quantity of product, because we need proteins that can be prepared in milligram amounts in soluble form for analysis using current technologies like NMR or X-ray crystallography. We then study and optimize the synthesis and purification parameters of each protein. Manually finding these conditions for hundreds of proteins is hard work, but the process itself is essentially a monotonous task so we automate this procedure, screening for the best conditions using the Freedom EVO workstation.”

“We have developed several unique technologies for protein preparation during this project, including two-step PCR and cell-free protein synthesis, because cloning all the genes of interest, expressing them in living cells and harvesting the cells to extract the proteins are extremely labor-intensive and time-consuming processes.

We developed the two-step PCR to complement the cell-free reaction, to

“The three-dimensional coordinate data were one of the final output of the Protein 3000 Project, and have been deposited in the Protein Data Bank (PDB), a database containing structural data of proteins that is freely accessible on the internet by everyone. In addition, from August 2007, supported by MEXT, our structural analysis pipeline is on general release as ‘The program for creating innovation by sharing advanced research facilities: The strategic industrial use’ (http://ynmr.riken.jp/, only in Japanese).

We at RIKEN set up this facility for the Protein 3000 Project and, with this project now successfully completed, we would like others, for example people from pharmaceutical enterprises or university researchers, to be able to use it for their own protein analyses.”

“Although automation has increased our throughput, for us it is not simply chasing the numbers, it is the benefit we derive.

Rather than go home at night exhausted from the monotony, we let the Freedom EVO carry out the monotonous work overnight to yield data in a report for us to analyze in the morning. We study the results, decide what to do next, and we go home at night exhausted by the brain work instead – this is how we work,” concluded Dr Aoki.

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R EA D E R S

The Infinite® M1000 Tecan’s multimode flagship microplate reader, is launched at LabAutomation 2008

The Infinite® M1000 brings flexibility, sensitivity and speed in one high-end, multimode reader, bridging the gap between research, assay development and screening.

Tecan is launching the Infinite M1000, its new flagship microplate reader, at LabAutomation 2008, booth 305, 27-30 January in Palm Springs, USA. The highend detection system offers top-of-therange quality and performance with robust and innovative new technology.

The Infinite M1000 joins the Infinite 200 and Infinite 500 series of detection systems, and is the successor to Tecan’s high performance Safire2™ microplate reader. The new platform gives excellent flexibility through its next-generation premium quad4 monochromators™, but it also provides the uncompromising sensitivity and speed typically associated with filter-based systems.

The instrument’s special combination of flexibility, sensitivity and speed is ideal for bridging the drug discovery gap between research, assay development and screening in the biopharmaceutical industry, as well as for advanced research laboratories with multiple users and everchanging applications. The platform’s modular concept allows upgrades to new detection modes at any time if further applications are required.

Tecan Journal 1/2008

The Infinite M1000 shown with optional injector box

The Infinite M1000 has an optional state-of-the art injector module that allows the use of up to two injectors for dispensing reagents, to replace a manual pipetting step or trigger fast kinetic reactions in fluorescence, luminescence and absorbance modes. The injectors have variable volume and speed settings and can be used in combination with the ratio mode to allow fast switching of wavelengths for a wide range of applications. The instrument can be easily combined with a stacker module for batch processing of up to 50 microplates.

Tecan has introduced special on-board control functions for the Infinite M1000 that allow, for example, pre-programmed measurement workflows to be initiated at the touch of a button on the instrument itself, avoiding the need to go back to your PC in between workflows.

Apart from multi-channel absorbance measurements, the fully loaded platform offers you a wide range of detection modes such as fluorescence intensity top and bottom measurements, time resolved fluorescence (TRF), fluorescence

R EADER S

Image of the quad4 monochromators

Infinite M1000 –

features at a glance l

l

l

l

l l

l

l

A stacker module can be used for batch processing

resonance energy transfer (FRET) and fluorescence polarization (FP).

Furthermore, the Infinite M1000 has been especially optimized for TR-FRET based assays as well as glow luminescence, fast luminescence and dual color luminescence assays.

The Infinite M1000 supports a broad spectrum of applications including the latest biomolecular assays for primary and secondary screening; receptor-ligand binding studies and other molecular interaction assays; kinase assays; protease

l

High-end multimode microplate reader Equipped with premium quad4 monochromators Provides a wide range of detection modes and plate formats Optimized for luminescence and TR-FRET-based assays Modular and upgradeable Offers injector, stacker and barcode options Includes special on-board control functions for plate in/out and starting measurements Controlled by easy to use, workflow-oriented i-Control™ software Compatible with Magellan™ software for comprehensive data evaluation and processing

assays; G protein-coupled receptor assays; cell-based assays; DNA/RNA quantification; and applications based on UV fluorometry.

If you would like to learn more about our new flagship microplate reader, see www.tecan.com/highend or please visit us at the Tecan booth during LabAutomation 2008 – we look forward to seeing you!

For availability of products in your country for the identified application areas, please contact your local Tecan sales organization. For further reference, please refer to www.tecan.com Product names and configurations as well as technical details are subject to change and the current product offerings may differ from those outlined in the text.

Tecan Journal 1/2008

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C L I N I CA L D I AGNOSTICS

Evaluating automated nucleic acid extraction using Abbott RealTime™ assays with the Freedom EVO® Clinical 75 workstation Tecan’s Freedom EVO® Clinical 75 performs fully automated RNA and DNA extraction from up to 24 samples in 3 hours, using magnetic microparticle processing. The Laboratory LABCONOWL in Bad Salzuflen, Germany evaluated the instrument’s performance in combination with the Abbott RealTime™ HIV-1 and HCV assays, and compared it to the previously validated Abbott m2000™ processing system. and incubation, magnetic capture and washing, and elution, all of which are optimized in ready-to-use protocols provided by Tecan. The subsequent PCR amplification and real-time detection are performed on Abbott’s m2000rt™.

The Freedom EVO Clinical 75 workstation for nucleic acid extraction

Nucleic acid extraction is the most critical and labor-intensive step in nucleic acid-based diagnostic assays. The overall sensitivity of the assay is determined by the nucleic acid yield, its purity and the amount of sample equivalent that can be transferred to the amplification reaction.

Manual sample preparation methods are labor-intensive and are also susceptible to contamination, handling variation and error. Tecan’s Freedom EVO Clinical 75 provides fully automated extraction of nucleic acids from a broad range of clinical samples. The workstation includes a fully integrated Te-MagS™ magnetic bead separation module for efficient separation of target molecules.

Dr Carsten Tiemann, director of molecular diagnostics at Laboratory LABCON-OWL, has evaluated the performance of the Freedom EVO Clinical 75 as a front-end extraction system in combination with the Abbott RealTime™ HIV-1 and HCV virological PCR assays. The automated steps of the extraction system include sample and reagent pipetting, heating Tecan Journal 1/2008

Automating the extraction method using the Freedom EVO Clinical 75 showed high reliability of extraction, with HCV and HIV viral load measurements that correlated well with those obtained using the Abbott m2000™ system (Figure 1).

Reliable detection of low levels of HCV and HIV viral load after sample extraction on the Freedom EVO Clinical 75 could also be proven (Figure 2). Sensitivity, precision and linearity were comparable between both extraction systems, and no cross-contamination was observed when tested with strongly positive HIV and HCV reference material. The Freedom EVO Clinical 75 allows purification of viral nucleic acids from human plasma in reproducible yield, purity and amount for reliable, sensitive and specific detection and quantitation of RNA viruses using the Abbott RealTime™ HIV-1 and HCV assays.

“Molecular diagnostics can be optimized thanks to the reproducibility and precision of the Freedom EVO Clinical 75, and its capacity to handle small sample numbers of a broad range of different specimen types, such as bacterial cell culture, swabs, feces and urine,” said Dr Carsten Tiemann. “Beside other available instruments the Freedom EVO Clinical 75 is a good additional option to maximize cost-effectiveness.”

Figure 1: Precision and linearity when using the Freedom EVO Clinical 75 were similar to those obtained using the m2000sp™ for sample preparation in combination with the Abbott RealTime™ HIV-1 assay.

DNA extractions were compared using the m2000sp™ and Freedom EVO Clinical 75, using dilution series of the Calibrator B from the Abbott RealTime™ HIV-1 assay.

Figure 2: Sensitivity of the Abbott RealTime™ HCV assay, tested on patient samples diluted in NHP with two different sample input volumes (0.2 and 0.5 ml) using the Freedom EVO Clinical 75 or the m2000sp™.

Reference 1. Tiemann C, Knoop D, Dunn C, Huber C, Schaffer S. Performance evaluation of a new instrument for genomic or viral DNA or RNA extraction with HIV-1 and HCV viral load assays. Poster presented at the Third European Congress of Virology in Nürnberg, Germany, 1-5 September, 2007.

The Freedom EVO Clinical 75 is not available for sale in the USA and Canada. m2000, m2000rt and RealTime are trademarks of Abbott Molecular, Inc.

C LI N ICAL DIAGN O STI CS

High throughput diagnosis of infectious animal diseases with the Freedom EVOlyzer® Dr Lena Renström, Swedish National Veterinary Institute, Uppsala, Sweden

The Swedish National Veterinary Institute (SVA) in Uppsala, Sweden, depends on a Tecan Freedom EVOlyzer® for automating ELISAs during routine diagnostic screening of animal diseases such as Porcine Reproductive and Respiratory Syndrome (PRRS).

PRRS, a viral disease in pigs that causes a range of reproductive and respiratory disorders, has spread throughout Europe, resulting in major production losses. The disease first occurred in Sweden in the summer 2007, at which time Sweden was free of PRRS and was not vaccinating pigs for the disease. The SVA in Uppsala screens animal samples in a control program for PRRS and other serious infectious diseases, and requires quick, reliable and automation-friendly assays in order to respond immediately to sudden disease outbreaks.

The Institute chose the Freedom EVOlyzer workstation for its fully integrated and automated ELISA processor. This open platform is able to combine kits from different manufacturers and adjust to the sample load and kits to be run each day. The Freedom EVOlyzer can automate a wide range of ELISAs with small sample numbers, as well as providing automated processing of large sample numbers using several standard assays.

The Freedom EVOlyzer 150 at the SVA in Uppsala is configured with four fixed pipetting tips, one ambient temperature incubator and one heated incubator, storage for 24 microplates, an eightchannel washer and an absorbance reader. It is able to process hundreds of samples every day.

Jane Borg explains to her colleague, Gunnel Svedlund, the schedule for running ELISAs on the Freedom EVOlyzer platform

with alternating rows of antigen-coated and normal wells, and results are obtained by measuring optical density at 650 nm.

ELISA automation has greatly speeded up large-scale screening for animal disease, and hundreds of samples can be tested on the instrument every day.

In the framework of control programs, 3,000-5,000 samples are currently being analyzed yearly using three different

ELISA tests for, respectively, PRRS, classical swine fever and Aujeszky’s disease. Tests for poultry diseases, including Newcastle disease and avian influenza, are currently being validated for automation on the Freedom EVOlyzer platform. *HerdChek is a trademark or a registered trademark of IDEXX Laboratories Inc. The Freedom EVOlyzer is certified according to the IVD directive 98/79/EC and is an Annex III-compliant open system for ELISA processing.

The Freedom EVOlyzer

PPRS is detected using the IDEXX HerdChek* PPRS 2XR Antibody Test Kit (IDEXX B.V., Netherlands), which detects antibodies to both European and North American strains of PPRS virus in swine serum by ELISA. The kit can be used to monitor a suspicious herd or to check whether animals are vaccinated. Samples and controls are tested in 96-well plates Tecan Journal 1/2008

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M products and washers SOicroarray F TWA R E

Improving quality and throughput of assays for genomic and proteomic research in South Africa The Centre for Proteomic and Genomic Research (CPGR) has several Tecan instruments for automated processing of multiple batches of microarrays simultaneously, including an HS 4800™ Pro Hybridization Station with the new QuadChamber™ and a HydroFlex™ system.

The CPGR in Cape Town, South Africa, is a world-class technology center funded by the Cape Biotech Trust and PlantBio. The center was founded in 2006 as a not-forprofit organization that, among other projects, focuses on diagnostics research for diseases that are prevalent in South Africa, such as tuberculosis (TB), HIV/ AIDS, malaria and cancers. Increasingly, the CPGR is also involved in plant biotechnology research and in food safety.

“Our main goals at the CPGR are to increase the South African research output and knowledge base, while becoming sustainable through providing services and collaborative projects to scientists in academia and industry,” explained Dr Reinhard Hiller, Managing Director of the CPGR. “To achieve these goals we need to use automated systems to minimize our manual procedures and assay costs as far as possible, while increasing the quality of our results at the

The LS Reloaded laser scanner

Tecan Journal 1/2008

same time. So far, we have established a high throughput biological research platform with a number of systems from Tecan and other companies, such as Applied Biosystems and Affymetrix. We are now fully equipped for processing almost all existing slide-based microarray formats, including genomic DNA, microRNA (miRNA) and protein microarrays. We also have facilities for RT-PCR based gene expression profiling, genotyping, as well as state-of-the-art mass spectrometry-based proteomics.”

“I chose the Tecan HS 4800™ Pro Hybridization Station for automated microarray processing because I have previously had fantastic experience with this system, it is really versatile,” Reinhard continued. The HS 4800 Pro performs all steps of the hybridization process, from pre-hybridization through to drying, of single, dual and even quadruplex microarrays. These capabilities are vital to the scientists at the CPGR: “We have also adapted a number of different microarray-based assays for automation with the HS 4800 Pro,” said Reinhard.

“For example, we are using lots of miRNA microarrays from Exiqon (Denmark), who has pre-developed protocols for Tecan’s hybridization stations so we can deliver excellent results with the system, straight away.”

“We also use the HS 4800 Pro for processing a number of custom protein and peptide microarray assays, for example, for allergy diagnosis or infectious disease research,” Reinhard continued. “One example is a collaborative project using high density TB peptide

assays to screen for potential diagnostic antibodies for TB. New, reliable, simple and quick tests are urgently needed for TB diagnosis, which is particularly difficult to diagnose in children with HIV. Automation has hugely improved the quality of our results and we are now testing hundreds of samples with these microarrays in a follow-up study.”

“We are also using protein microarrays developed by VBC-GENOMICS (Vienna, Austria) for the diagnosis of allergic diseases. These diagnostic arrays contain hundreds of allergen molecules immobilized in four identical microarrays on a single microscopy slide.

While originally designed for manual processing, we are now adapting these miniaturized antibody-capturing assays to a four-plex and 16-plex format on the HS 4800 Pro and the Tecan HydroFlex™, respectively. Thereby, we are going to increase assay throughput and quality while dramatically reducing the costs per data-point.”

The CPGR has recently purchased a HydroFlex platform from Tecan for automated incubation and washing of microplate-based immunoassay formats. “Tecan has customized the HydroFlex for us so that we can process 16-plex protein microarray slides, such as the cytokine arrays from GenTel BioSciences. These arrays are used for cytokine profiling, which is important for research in many disease areas,” added Reinhard. “To name just one example, highly automated cytokine profiling assays are very important in the context of monitoring clinical trials, where the

Microarray products and washers Dr Reinhard Hiller

Rachel van Dyk inserting slides into the HS 4800 Pro

consistency of results is a key prerequisite.

However, using these cytokine arrays is only the first step towards implementing more multiplex antibody capturing and sandwich antibody assays that come in eight- or 16-plex formats.”

The CPGR also plans to use Tecan’s recently developed QuadChamber™ for automating 4-pack Microarrays from Agilent. The QuadChamber is designed for simultaneous processing of four individual, whole-genome microarrays printed on a single glass slide, using the HS 4800 Pro. This is the first fully automated system that can independently handle four arrays on one slide with no cross-contamination between the arrays. Reinhard said. “I am confident that the QuadChamber will work, the results I have seen previously on pilot projects from Tecan look very promising. Currently, we are using malaria expression arrays printed by Operon in a dual format with excellent results and we are going to run the first protein arrays in a four-plex format shortly. We have recently decided to implement an LS Reloaded™ laser scanner from Tecan in order to increase the throughput and

The HS 4800 Pro Hybridization Station

versatility of the microarray scanning process at the CPGR. In addition to offering high resolution scanning of existing slide-based microarray formats at outstanding consistency, the LS Reloaded is also capable of analyzing microarrays printed in 96-well formats. This opportunity allows the rapid validation of results generated on our discovery platforms (eg. mass spectrometry), the screening of biomedical extracts for specific antibody binding or the development of low density diagnostic microarray formats. Also, the LS Scanner works neatly in line with the HS 4800 Pro when transferring slides processed on the latter directly into the scanner with minimal manual manipulations.”

“We are now talking to Tecan about adding a Freedom EVO® liquid handling workstation to our collection. Among other applications, the Freedom EVO would be ideal for automated DNA and RNA extraction, for the preparation of serum samples for multiplex immunoassays on our Luminex platform, for the parallel depletion of samples subjected to mass spectrometry analysis, and for all the liquid handling needed to prepare 384-well plates for our Applied Biosystems 7900 RT-PCR platform,” Reinhard added. “This would be another step towards turning our laboratory into a high throughput microarray and biomarker analysis platform.”

The applications described here are not available in the US outside of the research market.

The HydroFlex system

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Q UA L IT Y

Tecan is the OEM partner of choice for life science and clinical diagnostics companies moving into new markets For companies planning to produce new products designed specifically for the clinical diagnostics market, successful product development is only part of the challenge. Our expertise in quality and regulatory issues, as well as years of experience in providing instruments to diagnostics laboratories, puts Tecan in a unique position to help you take your application from the life science market to the clinical/IVD market, or to take your existing clinical diagnostics products into new geographical areas.

Any instrument for clinical use has to meet a variety of regulations and comply with national and international standards, such as those set by the US FDA, the in vitro diagnostic directives (IVD-D) and CE marking. An instrument’s performance must be robust and reliable and, for an application-dedicated diagnostics platform in particular, it must deliver reproducible and valid results.

To achieve these standards, an ideal OEM partner needs to provide a great deal more than just the required systems design, engineering and technology expertise. We believe that our understanding of this, combined with our regulatory knowledge and team approach that unites our marketing and dedicated regulatory departments, make our OEM service unique.

What capabilities does Tecan bring to meet your business and compliance requirements?

Tecan’s OEM solutions are widely known throughout the life sciences for their high quality and robustness, but you might be surprised if you knew the extent of our partnerships. We design, manufacture and supply complete systems, as well as components, to many well-known companies specifically for use in clinical and/or in vitro diagnosticsbased processes. We are commonly asked to take existing, manual methods and develop an automated system for them that will meet all necessary US FDA, IVD-D/CE or other marking requirements.

With our expertise and support, acquiring the necessary documentation to meet regulatory requirements can be achieved

Tecan develops a close partnership with OEM companies Tecan Journal 1/2008

in a smooth and timely fashion, whether you are launching your product in Europe, the USA, Asia or beyond. Our plants are also ISO 13485-certified and are registered with the appropriate governmental agencies as medical device establishments, so you can be sure that your Tecan components are produced to the highest possible standards. Several top-tier IVD and life science companies have already taken advantage of our comprehensive OEM offering.

What does Tecan’s OEM process involve?

Each of our customers is different, so at the beginning of every partnership we work together to exactly define the aims.

By ensuring that we understand precisely what the product’s functions and uses are, we can concentrate our resources

QUA ITY COMPO N ALNTS

and capabilities in helping that product to meet its market needs. We draw up a detailed development plan together that includes the supply agreement and quality agreement, and clarifies each side’s responsibilities.

How is Tecan’s team approach of combining marketing and regulatory staff unique?

Our marketing and sales staff work closely with the customers to better understand the application that the customer wants to bring to market.

Based on this understanding and on consultation with our regulatory staff, we will assist you in determining whether an off-the-shelf, standard product or an OEM-specific, customerbranded product would be the best option for you, given the various markets intended for product launch. Our meetings with you will clearly define a road map of not only the financial and technical issues that must be addressed, but also how change management will work during your OEM product life cycle, where the areas of responsibility lie for submission of documentation and for validation, and how we can assist you with these various aspects.

The ongoing partnership between our marketing and our regulatory staff helps to guide you through the regulatory jungle and to ensure that there are no surprises for you when the time comes for you to submit your documents or registration in a given country.

Has Tecan made any US FDA submission of its products or registered them as IVD/ CE compliant?

Yes. We have not only successfully obtained IVD/CE marking for some of our Tecan products in the EU, but we and/ or our OEM customers have successfully registered co-branded and customerlabeled devices in South America, Asia, the Asia-Pacific and the US. Some of these registered systems are used in highly regulated environments in the US, the EU and other countries.

Together, Tecan’s outstanding qualities in this sector make us your ideal OEM partner. Contact us to see how we can help you expand your markets.

Quality control and validation tools for your IQOQ needs

Most laboratories are subject to increasingly strict regulations, such as GLP (Good Laboratory Practice), GMP (Good Manufacturing Practice), CLIA 88, ISO 9001 or ISO 13485, defined by regulatory authorities like the FDA, EMEA, etc. Our advanced QC tools help you to fulfill all regulatory requirements for your Tecan microplate readers and scanning devices in an efficient, cost-effective way, with accurate instrument checking and complete documentation.

We offer three different QC plates: l QC Pac™ 1 and QC Pac 2 for all absorbance readers (eg. Sunrise™) l MultiCheck™ for all multimode readers 2 (eg. Infinite® series, Safire ™) l LaserCheck™ for all microarray scanners (eg. LS Reloaded™)

Each QC tool verifies the functionality of all major instrument components and checks all measurement modes, allowing a complete one-step installation and operational qualification (IQOQ) of your instrument with a single reusable QC plate, and without the need for any liquid handling steps. The Tecan QC software handles all measurements and calculations automatically, requiring a minimum of effort from the operator, and provides secure computer-generated report files and user administration. For the highest level of quality control, National Institute of Standards and Technology (NIST) traceability is provided for each absorbance and wavelength reference on the QC plates. An annual service procedure within each of these tools ensures that reference values are accurate and still valid and that Tecan’s QC tools can be used with the utmost confidence.

For further information on our QC tools, visit http://www.tecan.com/qctools

Tecan Journal 1/2008

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SERV I C E S A N D CONSUM AB L E S

Perfecting our disposable tips for optimal performance Tecan’s conductive disposable tips are no ordinary consumable, but highly specialized, custom-developed tips from Eppendorf, perfectly designed for Tecan’s automated Genesis and Freedom EVO® series liquid handling instruments. Each tip is individually inspected using Eppendorf’s state-of-the-art technology to ensure it meets Tecan’s exact requirements, giving customers complete confidence in every pipetting step.

Tecan’s conductive disposable tips are manufactured by Eppendorf, exclusively for Tecan, to meet a number of critical technical specifications for high quality, automated pipetting. “Our partnership began fifteen years ago, when we first approached Eppendorf with a list of special requirements for a conductive disposable tip,” said Dr Bernd Maisenhoelder, Consumables Product Manager at Tecan. “We also needed the tip to be produced in very large quantities while maintaining extremely high standards of quality and reproducibility.”

Within a year, the two companies had developed a suitable conductive disposable tip portfolio that is welcomed

by Tecan’s customers worldwide.

Perfectly formed for Tecan’s customers

Quality checking at Eppendorf

Tecan Journal 1/2008

Tecan’s automated liquid handling workstations are carefully designed, developed and produced for use in a wide range of laboratory workflows; every component of each module has been selected to play its part – including the conductive disposable tips. Using disposable tips is essential to many life science applications, particularly for minimizing cross-contamination in clinical diagnostic labs, and drug discovery procedures. However, it is equally important that the tip has been manufactured to the appropriate quality standards to ensure correct pipetting.

What is special about Tecan’s disposable tips? The main features are their conductivity, their very high purity, their excellent reliability, their coaxiality and other geometrical aspects that have been optimized to fit Tecan’s workstations, and their extremely high quality, which is guaranteed through a number of processes.

“One of the fundamental requirements for the tips was to develop a universal nose cone,” said Dr Barbara Koeppen, Executive Director for Customized Solutions at Eppendorf. “Tecan’s tips are available in four different volume sizes – 10, 50 (available in 2008), 200 and 1,000 µl – but it is vital that each one has the same nose cone geometry so they all fit Tecan’s instrument perfectly.”

SERVIC ES AN D CO N SUM A B LES

Tip production at Eppendorf

Disposable tips in situ on Tecan liquid handling workstation

Another essential specification is the coaxiality, which means that when viewed from above, the tip’s two orifices are perfectly concentric. This is particularly important for automated liquid handling because even the slightest deviation could result in the tip missing the well, as Barbara explained.

“It’s not just about the tip being straight, but about the bottom of the tip being perfectly aligned with the liquid handling channel. If the coaxiality is not correct then the tip can be slightly bananashaped. For example, when pipetting in 384-well formats, a small deviation from the center can mean the tip completely misses the well.”

“The conductivity of Tecan’s disposable tips was a major part of the development,” said Michael Blumentritt, Product Line Manager, Consumables at Eppendorf. “The conductivity of the tips plays a key role in the liquid level sensing technology of Tecan’s workstations.

The disposable tips are manufactured from conductive polypropylene, which translates a signal to the workstation when the tip makes contact with liquid.”

State-of-the-art quality control A variety of different quality checks take place during the tip manufacturing processes. “Our production process conforms to several ISO certification requirements, such as DIN ISO 9001 and DIN EN 13485, and these are audited regularly,” said Barbara. “We then have several technologies in place to measure a variety of parameters during the

manufacturing process. For example, we have an on-line optical inspection system that ensures each tip is present in the box and fully molded, and photographs every tip to check the perfect shape of the functional parts of the tip, which are essential for their accuracy and precision.

For tips with filters, the filter pore size is measured and the seal of the filter is inspected to ensure it is perfect. We also perform a variety of application checks on the tips, such as leakage tests, analysis of their wetting behavior, residual moisture and so on.”

The disposable tips are suitable for all laboratory liquid handling applications and are particularly recommended for any kind of application that requires a high degree of purity, such as for diagnostic and pharmaceutical applications, or applications involving DNA. Advantages of using Tecan’s disposable tips l

l

“Any tip that does not meet Tecan’s specifications is rejected and, if the fault is detected during a manufacturing process, we turn off the relevant machine and fix the problem to make sure we do not produce any more imperfect tips. The majority of tips rejected by our rigorous on-line inspection process have been shown to be fine to use, but we prefer to err on the side of caution.

While Eppendorf in general exercises unique quality standards, for Tecan tips, we go a step further to meet the specific requirements for Tecan’s workstations.”

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Minimizes risk of carryover, which helps to avoid false-positive results (eg. in diagnostics).

Reduces the chance of biological samples being contaminated (eg. RNase).

Increases throughput by minimizing tip washing steps.

Enhances pipetting performance and results through optimized design.

“Tecan is our most important customer for conductive tips and our partnership works very well. There are many contributing factors that go beyond the quality of the product, such as Tecan’s efficient logistics and shipment processes, and responsive customer service,” added Barbara.

Tip production at Eppendorf Tecan Journal 1/2008

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A P P L I CATI ON B IOP HARM A

A perfect fit for the

Freedom EVO 75 ®

in forensic toxicology

Immunalysis Corporation, in California, USA, provides customized semi and fully automated drugs of abuse screening solutions to forensic toxicology laboratories and works closely with Tecan, tailoring the Freedom EVO® 75 liquid handing workstation as the platform of choice for its customers.

Immunalysis Corporation develops and produces a variety of assays, including ELISA, HEIA, enzyme and RIA formats for measuring illicit and legal prescription drugs in the wide range of biological matrices encountered by toxicologists, from urine and blood to hair and tissue extracts, as well as others. As Michael Vincent, Vice President of Operations at Immunalysis, explained: “Our screening solutions are entire panels of ELISA test kits, typically processing from 24 to 96 samples and controls in each run, using panels of six to fifteen assays.

Immunalysis tests work with a common sample dilution to enhance throughput; our customers no longer need to perform multiple dilutions for different tests but can run an entire panel of tests using the same sample dilution.”

Immunalysis’ customers often share the common goal of testing for a wide range of drugs, but the ELISA panels and the processes required to run them vary considerably, depending on various factors, including geographical location, legal considerations, and laboratory throughput. These varied requirements call for a flexible approach to automation and for several years, the team at Immunalysis has worked closely with colleagues at Tecan, perfecting unique solutions for each individual customer.

Tecan Journal 1/2008

Robert Gabardy, from Forensic Sales at Immunalysis, said: “We are essentially a one-stop shop for our customers, so the instruments are delivered directly to us from Tecan, allowing our Application Group to program each customer’s specific requirements and application into their workstation. We then go to the customer’s laboratory to install the equipment and bring consumables so they can run assays within two or three days. We also train the users on how to define the tests, configure the workstations, and how to perform proper maintenance and trouble-shooting.”

In recent years, the Freedom EVO 75 has been the platform of choice for Immunalysis, as Michael explained: “The Freedom EVO 75 workstation is a robust instrument that gives our customers the accuracy and safety assurances that are vital for their work. It can process up to six plates in one run, ideal for medium throughputs, and the Freedom EVOware® software that runs it is very flexible with many options. An excellent feature for forensic toxicology is that the Freedom EVO 75, using Freedom EVOware, takes enough sample for all the required tests in just one aspiration, so that each sample tube is only entered once, and then dispenses different volumes to each independent test. This is very important

for our customers because, with proper techniques, there is virtually no risk that samples from one person could ever be contaminated with those from another individual. Perhaps the most important factors for continuing to choose this instrument for our customers, though, are its excellent sample tracking properties.

When so many samples are going through multiple assays, the integrity of the testing is critical and the Freedom EVO 75 maintains this admirably.”

The Freedom EVOware tracks the entire process, from the initial sample tube to the final assay microplate, and keeps track of the position of each sample in all six plates. When a sample is ultimately read on the microplate reader, the application program Magellan™ accesses the pipetting file and shares the data. The software tracks where all the samples are as well as where there have been errors, such as short samples or clots, and reports all this in addition to the final results for each microplate. Immunalysis’ single case reporting software will accumulate all this data so that the user has all of those test results at his or her disposal on a single piece of paper. To do this manually could result in errors, so sample and error tracking cannot be overstated in their importance.

APPLICATIO N B IO PHA R M A

“The assurance of automated sample and error tracking is vital for our customers because their results will often be presented in a court of law and can have a direct bearing on a verdict of driving under the influence, or for confirming a cause of death, or other equally critical issue,” Michael added.

Rochelle Timbang, from the Application Group at Immunalysis, continued: “The liquid handling flexibility of Tecan’s Freedom EVOware software allows us to modify the system and customize parameters, such as speed of aspiration and dispensing to handle different types of matrices. Our customers work most frequently with blood as the biological matrix and, because blood needs to be aspirated more slowly than urine, this needs to be taken into consideration. If insufficient blood is picked up, this could give a false negative result. The software is very easy to customize and to use, both

for the Application Group to initially configure the instrument and train customers, and for the users themselves to manipulate a few specified parameters, such as sample volumes and sample numbers.”

Michael concluded: “A significant advantage of Tecan’s Freedom EVO family of instruments is that, once we have configured the Freedom EVO 75 platform, the same software and characteristics can be extrapolated to larger platforms in the same series. This means that our customers can easily upgrade their systems if their throughput requirements grow, with minimal retraining of operators. We enjoy a very good relationship with our colleagues at Tecan and, although Immunalysis is the customers’ first port of call, Immunalysis and our customers know that Tecan’s application specialists and service group are there for advice and support should it be required.”

The Freedom EVO 75 at Immunalysis

The team at Immunalysis (from l to r, Kelvin Barnes, Robert Gabardy, Jeremy George, Rochelle Timbang)

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M I C ROA R R AY PROD U CTS

Automating hybridization

of protein biochips improves biomarker discovery Protagen AG, based in Dortmund, Germany, provides protein analysis, proteomics and bioinformatics tools and services to pharmaceutical and biotech companies.

The company develops and produces special protein arrays for both antibody characterization (the UNIchip®) and biomarker discovery, and depends on two Tecan HS 4800™ Pro Hybridization Stations for automated processing of these biochips.

Protagen AG was originally founded by a clinical proteomics group at the Ruhr University of Dortmund in 1997, where it began performing high quality proteomic analysis for biomarker identification.

It now provides a variety of tools and services for 2D gel- or mass spectrometrybased research and drug development, including GMP-compliant protein analysis services for pharmaceutical and biotech companies; software tools for mass spectrometry, such as for detecting post-translastional protein modifications; and protein array-based products for biomarker discovery and antibody development. The company focuses on identifying biomarkers for its own business development, such as specific diagnostic markers for multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and cancer indications. The biomarker discovery program has recently been made available to interested pharma and biotech companies.

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The HS 4800 Pro Hybridization Station

Protagen uses its propietary UNIclone® technology platform for biomarker discovery; this high throughput protein array technology was originally developed

by Prof Dolores Cahill and her colleagues when working at the Max Planck Institute of Molecular Genetics in Berlin. Scientists at Protagen have built this platform into a program called UNIarray®, which handles everything from study design to systematic discovery and evaluation, to delivery of a prototype biochip suitable for clinical use. Sets of putative markers on quantitative protein biochips are now being developed for use by researchers in the pharmaceutical and biotech industry.

Protagen depends on two HS 4800™ Pro Hybridization Stations for automated processing of its protein biochips during the manufacturing and testing processes.

“After we have found a set of putative biomarkers, the crucial step forward is to test them in quantitative terms in larger

patient cohorts, and this requires a highly reproducible chip processing procedure,” explained Dr Jens Beator, Director of the Protein Biochips business unit at Protagen. “Each chip usually includes a few hundred biomarkers that need to be quantified in a single assay, so careful standardization is extremely important for reproducible analysis. Processing the chips manually is subject to human variability so we always process all of our chips under identical conditions using the HS 4800 Pro Hybridization Stations.”

“It was relatively straightforward to optimize the assay for automation on the HS 4800 Pro and develop standard operating procedures,” Jens continued.

“Fortunately, we were able to use an application note from another Tecan customer that provided good starting conditions that we could optimize from, and we also had support from an application specialist at Tecan. Pre-

MIC ROAR R Ay PRO DUCTS

The Protagen UNIchip®, showing the nitrocellulose coating

customized HS 4800 Pro platforms that are suitable for our biochips were already available. Each of the HS Pro stations has 24 chip slots so we can process 48 samples with each run, which takes around three hours. In the past we had to perform the assays manually, which required many man hours from our technicians but now those staff are free to do other work.”

On 5 November 2007, Protagen celebrated its tenth anniversary with a day of special events that began with the company receiving Germany’s Land of Ideas 2007 prize for its innovation. The Land of Ideas initiative awards a prize to 365 landmarks of all kinds; cultural, social and industrial.

Only nine places related to biotech have been selected in 2007. One landmark is active on each day of the year, as part of a joint program between the Federal Government and German industry, supported by Germany’s president.

Scientists at the Protein Biochips unit (from l to r): Dr Jens Beator, Angelika Lueking, Claudia Gutjahr, Kirsten Schulte and Verena Trappe

“The anniversary day began with a press conference, including representatives from the state government, our founders, investors and press officials,” Jens explained. “After the prize was awarded, we gave guided tours of our facilities to members of the public and demonstrated some of the key technologies within our laboratories. In parallel, we held a very well-received scientific symposium during the afternoon, with talks from Prof Hans Lehrach and Dolores Cahill, as well as Prof Helmut Meyer, the main founder of Protagen and one of our key medical proteomics collaborators.”

The system and application described here are for research use only in the USA UNIchip® is a registered trademark of Protagen AG

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LIQU I D H A N D L I NG AN D ROB OTICS

Semi-automated DNA isolation from cereal crops using the

Te-MagS™ module

Sanja Baric, Stefanie Unterholzner and Josef Dalla Via Research Centre for Agriculture and Forestry Laimburg, I-39040 Auer/Ora, Italy

Members of the Research Centre for Agriculture and Forestry Laimburg, led by Sanja Baric (front row, second from right), together with the Director of the Research Centre, Josef Dalla Via (front row, far right)

The Molecular Biology Laboratory at the Research Centre for Agriculture and Forestry Laimburg in South Tyrol, northern Italy, is currently involved in a research project that focuses on the genetic characterization of local cereal landraces.

In addition to botanical and agronomic information, the project is using genetic data to establish and maintain a germplasm collection. The study aims to analyze microsatellite markers from large numbers of samples and, in order to achieve this, it was necessary to develop a semi-automated DNA extraction method that would yield high quality DNA from various grain species.

Automating plant DNA isolation using magnetic bead technology Isolation of DNA from plant tissue represents a crucial step for the quality and outcome of subsequent downstream applications, such as PCR, sequencing or genotyping. However, this step can also be a considerable bottleneck in many extensive plant genotyping studies.

Plant cells are surrounded by a rigid cellulose-containing cell wall that must be mechanically disrupted to release Tecan Journal 1/2008

The Research Centre for Agriculture and Forestry Laimburg works closely with the farming industry in South Tyrol in a variety of agricultural research projects, from fruit and wine production to plant protection, vegetable cultivation, agricultural chemistry and fish farming. The researchers have recently applied a semi-automated procedure for extracting DNA from large numbers of cereal crop samples, using the Te-MagS™ module, to increase throughput and reduce the labor bottleneck.

nucleic acids into solution. Furthermore, plant cells are rich in polysaccharides and secondary metabolites that can be co-purified with DNA and, subsequently, might inhibit enzymatic reactions.

Traditional cetyl-trimethylammonium bromide (CTAB)-based protocols for DNA isolation from plant material involve several centrifugation steps, make use of harmful organic solvents, and generally have a low potential for automation.

To overcome these issues, we established an automated DNA extraction procedure using a Te-MagS module, configured to hold 48 microcentrifuge tubes, integrated with a Freedom EVO® 100 liquid handling workstation with four channels for disposable tips and lower disposable tip eject option. DNA binds reversibly to paramagnetic silica-coated particles in solution, and buffers used for extraction are aspirated by pipetting while the paramagnetic particles are captured by magnets. No further centrifugation steps or vacuum filtration are required and, after preparation of the plant lysate, the DNA isolation process runs without any additional manual intervention.

DNA extraction procedure for cereal crops Our protocol uses the Wizard® Magnetic 96 DNA Plant System (Promega, Madison, USA) and comprises two major steps: (i) manual preparation of the plant lysate and (ii) automated DNA isolation (Figure 1). Fresh leaf tissue obtained from young cereal seedlings is homogenized directly in Lysis Buffer A supplied with the DNA extraction kit. After centrifugation of the homogenate, the supernatant is manually transferred to 1.5 ml microcentrifuge tubes – ready to be placed in the Te-MagS unit on the Freedom EVO workstation (Figure 2). The manual transfer of the lysate is considered an important step to avoid carryover of plant debris, which could potentially clog the pipetting tips during automated liquid handling. Once the tubes containing the lysate have been placed into the Freedom EVO, the extraction procedure is fully automated and no further manual handling is required. The tubes with the final DNA eluates from all 48 samples can be removed after 90 minutes.

LIQ U I D H AN DLI N G AN D RO B OTI CS Results The semi-automated DNA purification protocol using the Te-MagS yielded high quality DNA from different wheat species and hybrids as well as from oat and rye (Figure 3). DNA quantity generally ranged from 100 to 300 ng per mg of fresh plant tissue. Accurate amplification of diverse microsatellite loci indicated that DNA isolates were free of PCRinhibiting substances. By the application of the semi-automated procedure it was possible to at least double the throughput for DNA isolation in comparison to the conventional approach.

Moreover, automation could save about 60 % of manual labor time, which might be particularly beneficial for laboratories with limited human resources.

Summary The semi-automated method for DNA extraction established in the Research Centre for Agriculture and Forestry in Laimburg, was set up to fulfill medium throughput requirements. However, if required, the processing speed and throughput of magnetic bead purification can be increased by using any Freedom EVO workstation with an eight-channel liquid handling arm integrated with a Te-MagS module configured to hold 96-well microtiter plates. Automating the Wizard® Magnetic 96 DNA Plant System on the workstation could allow sufficient amounts of high quality genomic DNA to be obtained from several cereal crops for analysis in extensive population studies, assisted breeding programs, disease diagnosis or GMO detection.

The present work is part of the GENESAVE project, which was funded by the European Union under its Interreg IIIA program between Italy and Austria, and the Governments of South Tyrol (Italy) and Tyrol (Austria). The authors thank Guido Cimoli, Application Specialist from Tecan, for his support during the establishment of the automated DNA extraction procedure.

STEP 1: Preparation of plant lysate • Preparation of plant tissue • Addition of DNA extraction buffer • Disruption of plant tissue in a bead mill • Centrifugation of the homogenate • Transfer of the lysate

STEP 2: Isolation of DNA Conventional CTAB protocol • Incubation of plant lysate at 65°C • Addition of chloroform:isoamyl alcohol 24:1 • Centrifugation • Transfer of liquid phase to fresh tubes • Addition of isopropanol • Incubation in freezer • Centrifugation • Aspiration of liquid • Addition of washing ethanol • Centrifugation • Aspiration of ethanol • Drying of DNA pellet in vacuum centrifuge • Addition of TE buffer • Tapping of tubes to dissolve DNA pellet

Automated protocol • Addition of paramagnetic particles (PP) • Mixing and incubation to bind DNA • Trapping of PP & aspiration of liquid • Resuspension of PP in washing buffer • Trapping of PP & aspiration of buffer • Resuspension of PP in washing buffer • Trapping of PP & aspiration of buffer • Drying of paramagnetic particles • Resuspension of PP in TE buffer • Elution of DNA in TE buffer • Transfer of DNA eluate to fresh tubes

Figure 1: Comparison of the automated (left) and the conventional CTAB-based protocol (right) for plant DNA extraction (Step 2). The automated protocol uses the Wizard® Magnetic 96 DNA Plant System (Promega) on a Tecan Freedom EVO 100 workstation with four pipetting channels and the Te-MagS magnetic separation unit. The manual procedure for the preparation of plant lysate from 48 samples (Step 1) remains identical for both extraction types. Fully automated steps are coded in green, while those requiring manual intervention are coded in red.

Figure 2: Collaborator of the Molecular Biology Laboratory preparing the Tecan Freedom EVO 100 for automated DNA extraction.

Figure 3: Genomic DNA obtained from different cereal species or hybrids. Nucleic acid was isolated from approximately 30 to 40 mg of fresh leaf material from young seedlings, which was ground directly in 300 µl Lysis Buffer A (Wizard® Magnetic 96 DNA Plant System, Promega) using a bead mill (Mixer Mill 300; Retsch, Haan, Germany). After centrifugation, 125 µl of the supernatant was transferred to 1.5

ml microcentrifuge tubes and placed on the Freedom EVO. DNA was captured by the addition of MagneSil™ Paramagnetic Particles (Promega).

Following two washing steps, DNA was eluted in 75 µl of TE buffer, pH 7.5, and transferred to fresh microcentrifuge tubes. Five µl of DNA eluate was run on a 1 % ethidium bromide stained agarose gel in TAE buffer M size marker; 1, 2 Triticale; 3 Aegilops squarrosa; 4 Triticum boeoticum; 5 T. monococcum; 6 T. dicoccoides; 7 T. dicoccum; 8 T. turgidum; 9 T. aestivocompactum; 10 T. sphaerococcum; 11, 13, 14 T. aestivum; 12 T. spelta; 15, 16, 17 Avena sativa; 18, 19, 20 Secale cereale.

Wizard is a registered trademark and MagneSil is a trademark of Promega Corporation USA.

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EV E NTS 2 0 0 8

Meet Tecan at these events in the first quarter of 2008 Americas LabAutomation

Palm Springs, CA

27- 29 Jan 2008

American Academy of Forensics Sciences (AAFS)

Washington, DC

18-23 Feb 2008

LRIG Midwest Automation and Stem Cell Conference

Madison, WI

2-3 April 2008

SBS

St Louis, MO

6-10 April 2008

LRIG South East Technology Exhibition

May 2008

LRIG Mid-Atlantic

East Brunswick, NJ

May 2008

ISBER

Bethesda, MD

18-21 May 2008

American Society for Microbiology (ASM)

Boston, MA

1-5 June 2008

The Pharmaceutical Society of Japan

Yokohama, Japan

26-28 March 2008

Japanese Society for Bioscience, Biotechnology and Agrochemistry

Nagoya, Japan

26-29 March 2008

The 7th National Clinical Diagnostic Laboratory Conference

Jinan, China

7-12 June 2008

2ème colloque Génomique Fonctionnelle du Foie

Paris, France

16-18 Jan 2008

4èmes Assises de Génétique Humaine et Médicale

Lille, France

17-19 Jan 2008

Statusseminar Chiptechnologien 2008

Frankfurt, Germany

31 Jan-1 Feb 2008

USGEB 2008

Lausanne, Switzerland

6-7 Feb 2008

Analytica

Munich, Germany

1-4 April 2008

IQPC Compound Management

London, UK

May 2008

HET Instrument

Utrecht, the Netherlands

20-23 May 2008

Advances in Microarray Technology

Barcelona, Spain

7-8 May 2008

ESHG -40th European Human Genetics Conference

Barcelona, Spain

31 May -3 June 2008

Forum Labo & Biotech

Paris, France

3-6 June 2008

Asia and Pacific

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 Editor: kdm/UK www.kdm-communications.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com,www.tecan.com 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.

8 Plus 1 Access, Genesis RWS, HS 4800, HydroFlex, i-Control, LaserCheck, LS Reloaded, Magellan, MIO, MultiChannel Arm, MultiCheck, NanoQuant Plate, QC Pac, quad4 monochromators, QuadChamber, Safire2, Sunrise and Te-MagS are trademarks and Cavro, Freedom EVO, Freedom EVOlyzer, Freedom EVOware and Infinite are registered trademarks of Tecan Group Ltd, Männedorf, Switzerland.

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

REMP ACD96, REMP Small-Size Store and REMP Tube Technology are trademarks of REMP AG, Oberdiessbach, Switzerland. © 2008 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 92 44 790 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 +41 44 922 81 25 REMP Switzerland +41 31 770 70 70 Japan +81 44 542 70 21 USA +1 508 429 2200

Tecan Journal 1/2008