Tecan Journal
Fishing for genetic information pages 12-13
The world’s largest custom monoclonal antibody production facility opens at Monash University pages 14-15
Cracking forensic workloads pages 16-17
Alf Price, Product Support: Expertline/Helpdesk, Tecan Switzerland
Edition 3 / 2008
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C E O WE LCOM E
There’s more to Tecan than meets the eye… …as the audience of last year’s AACC annual meeting soon discovered. This year, visitors to the largest clinical lab exposition taking place in Washington D.C. were already familiar with Tecan’s capabilities as an OEM provider of instruments with a dedicated design. Using our experience as creators of innovative solutions for the research sector, Tecan grows with its OEM customers by building on existing platforms and migrating into a dedicated system once an application matures. With our expertise we can also assist life science customers to transition from pure research into more regulated markets. Welcome to this edition of the Tecan Journal, where this time around we feature some of the usual and the not so usual applications which take advantage of Tecan’s products and services. Many of you will remember the exciting news of our partnership with the Monash Antibody Technologies Facility (MATF) in Australia and, in this issue, you can find out how the facility has developed, just weeks after its launch event. There’s news too from pharmaceutical laboratories making the most of Tecan’s exceptional throughput capabilities and flexibility to help speed up drug discovery and from cancer researchers who are replacing tedious, inefficient methods with automation. You can find out more about the latest Tecan Cavro® products to come from our innovative development teams, hear from yet another happy forensic customer, and read about the fascinating way that Tecan’s instruments help in the global management of salmon stocks. We hope you enjoy this issue, Thomas Bachmann, CEO
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Tecan Journal 3/2008
CO NTENTS CEO welcome
Radioimmunoassay workflows are given a boost
Thomas Bachmann, CEO, welcomes you to another issue of the Tecan Journal.
Tecan’s Freedom EVO workstation forms the basis of an automated RIA system developed in Korea.
page 2
pages 22-23
Automated parallel chromatography
Tecan and Atoll provide a solution in 96 array format.
page 4
New MCA 384 disposable tips for liquid handling New tips launched to complement the MultiChannel Arm™ head.
page 5
Fishing for genetic information
Tecan’s HS 4800™ Pro Hybridization Station gives salmon researchers the high throughput efficiency they need.
pages 12-13
MATF opens at Monash University
Dignitaries get a first glimpse of the new stateof-the-art monoclonal antibody production system.
pages 14-15
HS 4800 Hybridization Stations boost microarray consistency
Researchers in the Netherlands choose Tecan for their microarray processing service.
page 24
The LS Reloaded™ laser scanner brings flexibility to microarray development
New Freedom EVOlution™ 2.1 software for Freedom EVO® Clinical platforms
Edinburgh group develops multiplex assays for blood grouping and infectious diseases.
Sample preparation functions are boosted with splitting and archiving.
page 25
page 5
Robotics and proteomics
A partnership with a promising future in biomarker discovery.
New Tecan Cavro® products Teamwork at its best.
pages 6-7
Fully automated cell culturing from Cellerity™
An update of Cellerity’s impressive automation capabilities.
page 8
Tecan symposium 2008
‘Biologics: from benchtop to production’.
page 9
Cracking forensic workloads
A Freedom EVO workstation is helping forensic scientists to cope with a backlog of samples.
pages 16-17
pages 26-27
Events 2008
Meet Tecan at these events in 2008.
page 28
Automating the investigation of proteinprotein interactions (PPI) Tecan’s microplate washers and readers accelerate PPI screening.
pages 18-19
Responding to the Chinese earthquake efforts
Tecan donates a Freedom EVO workstation for identification of victims.
page 10
More of Tecan’s sales organizations gain quality certification Working towards consistently high quality around the world.
page 11
Speeding up drug development at Merck Freedom EVO platforms for handling sample preparation and ELISAs for pharmacokinetic/ pharmacodynamic modeling studies
pages 20-21
Tecan Journal 3/2008
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P ROD U CT N EWS
Automated parallel chromatography in 96 array format Purification of therapeutic products is a major cost factor in pharmaceutical manufacturing. Development of the purification process imposes a major bottleneck in drug production, because the various purification parameters need to be experimentally optimized for each protein-based pharmaceutical product before entering full-scale production. Application of high throughput technologies to chromatographic purification can greatly benefit process development by enabling parallel screening of the various parameters and giving rapid and reliable results. A miniaturized format would reduce the consumption of valuable samples as well as reagents and chromatographic resins. Automated parallel chromatography enables various protein purification applications, including: • expression screening to select clones with best recombinant protein expression, or cell culture screening, for mAb selection;
• condition screening to determine optimum purification conditions; • resin screening to test different resins in parallel; • method development to optimize gradient elution, for transfer to large scale purification; • sample conditioning/purification/ concentration for downstream applications like protein crystallography or MS analysis; • process analytics for bioreactor monitoring, to determine the optimal harvesting point. The Freedom EVO® liquid handling workstation, together with Atoll’s 96-array MediaScout® RoboColumn system, enables fully automated parallel column chromatography of up to eight columns, removing all manual steps from column equilibration to column regeneration, and even detection. MediaScout RoboColumns feature individual mini columns arranged on a 96-well format base plate, with each column sealing to a fixed tip of the liquid handling (LiHa) arm through a pressure tight inlet (patents pending). MediaScout RoboColumns are compression prepacked with any commercially available process separation resin in the volume range from 50 to 600 μl, and bed heights from 2.5 to 30 mm.
The Freedom EVO platform in protein chromatography configuration features a robotic manipulator (RoMa) arm that handles the MediaScout RoboColumns by its base plate, and a Te-Chrom™ holder to position the base plate securely during chromatography. Through the eight fixed metal tips on the LiHa arm, the workstation provides accurate and precise flow rates down to 16.2 cm/h, and is able to achieve fractions as small as 25 μl and simulate concentration gradients by using incremental buffer conditions. Eluted liquid can be collected in standard 96-array plates, and an optional Te-Stack™ allows fraction collection by sliding the collection plate by one row between each fraction. Analysis of the fractions can be automated with an optional reader, such as the Tecan Infinite® M200, to yield chromatographic results from the data points obtained. The system offers a powerful new tool for fully automated high throughput process development, by allowing valid chromatographic conditions to be used without the need for sophisticated LC systems. MediaScout is a registered trademark of Atoll, GmbH. ProSep is a registered trademark of Millipore Corporation. Toyopearl is a registered trademark of Tosoh Corporation.
For more information about Tecan’s automated parallel chromatography, visit www.tecan.com/proteinchromatography
High reproducibility low volume column chromatography
Rapid sample preparation for in-process monitoring
Simultaneous automated step-gradient elution for the separation of two proteins (1 mg/ml each of lysozyme and cytochrome c) on cation exchange resin (Toyopearl® SP-650S) was performed in eight 200 μl MediaScout RoboColumns on a Freedom EVO workstation. The resulting eight elution profiles were superimposed to show the excellent reproducibility.
A sample from each of eight parallel fermentation reactors was applied to eight MediaScout RoboColumns with cation exchange resin (ProSep® vA Ultra). The columns were rinsed and the antibodies were rapidly eluted, neutralized and analyzed by high performance cation exchange chromatography. The normally time-consuming sample preparation step was shortened by nearly one order of magnitude.
Tecan Journal 3/2008
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Quality disposable tips for reliable 384and 96-channel pipetting Tecan has introduced the new MCA384 disposable tips, complementing the recently launched versatile MultiChannel Arm™ 384 head. The system brings higher productivity to automated liquid handling applications, with reliable 8-, 12-, 16-, 24-, 96- and 384-channel pipetting in a broad volume range of 0.5 to 125 μl.
MCA384 disposable tips are available in two volume sizes – 50 μl and 125 μl. The 15 μl tip will be available in the near future. The tips have been engineered with a unique sealing system, where each tip has its own internal, built-in seal. Tecan’s MCA384 disposable tips are carefully designed and produced for optimal performance with the MultiChannel Arm 384 head. The tips are supplied in newly designed racks that are color-coded and clearly labeled to indicate the tip volumes for straightforward identification on the worktable. The rack labels also document lot numbers, for easy traceability.
The new rack design for easy traceability on the worktable
The flexible MultiChannel Arm 384 head is able to switch quickly between 384and 96-channel pipetting, as well as pipetting using one row or one column of tips, even during a run, depending on the requirements of the application. The precision-built 15 μl tips allow pipetting into 1,536-well microtiter plates, while the 125 μl tips can access the bottom of a deep-well plate. For more information about Tecan’s disposable tips, visit www.tecan.com/disposabletips
Tips in action – 384 15 μl disposable tips dispensing liquid into a 1,536 microtiter plate
Freedom EVOlution™ 2.1 –
sample preparation and splitting on one platform Freedom EVOlution 2.1 is the latest version of Tecan’s software for Freedom EVO® Clinical platforms, offering additional application areas – sample splitting and archiving – in addition to all the existing sample preparation functions. The software allows laboratories to integrate several applications on one instrument.
User actions are guided by wizard-driven GUI
The new software makes it possible to automate the splitting of source tubes into multiple destination tubes, and the archiving of source tubes into archive plates, without the need for a LIS/ LIMS connection. Sample traceability is maintained by barcodes on all source and destination tubes, and the workflows are standardized, making the Freedom EVO Clinical platform ideal for all laboratories handling clinical samples for analysis or archiving.
Freedom EVOlution 2.1 is available as standard on new instruments, and as an upgrade option for existing instruments. For more information about Tecan’s Freedom EVOlution, visit www.tecan.com/evolution
3D worktable simulator for simulating runs Tecan Journal 3/2008
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Teamwork at Tecan results in
two new and innovative offerings
Tecan has recently launched the Cavro® Centris Pump and Cavro® Omni Robot – new products which both incorporate innovative and novel technologies taking OEM components to the next level. The new product lines are the result of Tecan engineers tackling a variety of challenges to create products that meet our customers’ needs.
Some of the Cavro Centris Pump project team members
Cavro Centris Pump Some years ago at Tecan Systems, an internal presentation led to an ambitious project, starting in August 2006 as a collection of ideas and sketches on a piece of paper, and culminating in Tecan’s latest syringe pump offering. The Cavro Centris Pump combines over 30 years of Tecan’s experience in making syringe pumps with new technical innovations, utilizing a novel, highly reliable drive mechanism that was developed in cooperation with Tecan’s Liquid Handling and Robotics group. “Involvement in the Cavro Centris Pump project ran interdepartmentally throughout Tecan Systems, from marketing, manufacturing to obviously R&D, and our development team consisted of about nine people,” explained David Wold, senior product manager. “But the cooperative effort also extended to the liquid handling experts at Tecan Switzerland, who have truly been a partner from the very beginning, offering us valuable input. For example, it was their feedback that prompted us to redesign the electronics drive using a more sophisticated and powerful chipset and, as a result, the Tecan Journal 3/2008
Cavro Centris Pump is by far the quietest Tecan Cavro syringe pump. This updated drive electronics also allows us finer control of each increment of the stepper motor, even at very slow strokes, so this pump is also our smoothest dispensing product.” Rich Filice, project manager, added: “We weren’t willing to settle with something that was merely good, so we took the additional time and expense to develop something really great. Each of us tackled challenges, and the result is something that we can all be very proud of.”
Precision-paired ceramic parts give high accuracy and unprecedented longevity
“The easiest way to improve upon a product is to add new features and components, but instead we stripped everything away to leave just the essence of what is needed, creating a new premium product line and reducing the part count by around 30 % in the process,” continued David. “When we showed the pump at trade shows and around 15 customer sites in Australia, Europe, Asia and the US, we offered plenty of hands-on time to play with the pump; it didn’t take long for engineers to appreciate the elegance, high performance and reliability of the new design.” Rich added: “We are now developing a wash option that can be integrated with the pump to protect the precision-engineered gap between the ceramic surfaces, making it suitable for use with a broader range of chemicals. We’ll be busy for a while yet!”
Cavro Centris Pump - offers a broader working volume range compared to other syringe pumps
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Some of the Cavro Omni Robot project team members
Cavro Omni Robot The Cavro Omni Robot project started in late 2006 with an open brainstorming session, driven by a desire to develop a superior flexible robotic OEM component. Even at this early stage, customers were already the driving force, as Rich Loo, project leader, explained: “We were very conscious that many of our customers wanted a two-axis robot, but our product line-up at the time could only offer a three-axis version.” Claudio Bui, director of marketing, added: “We wanted to provide our customers with a degree of flexibility that just wasn’t available in any other product on the market.” A key feature of the Cavro Omni Robot is its closed-loop positioning system, which uses magnetic encoder feedback technology for accurate positioning of the robot for each axis. The technology is used in other industries, but Tecan is the first to use it in the OEM instrumentation industry, and the engineers enjoyed the challenge of integrating the technology.
Cavro Omni Robot – modular design for a complete OEM liquid handling solution
Gary Barron, program manager for engineering, elaborated: “We worked with new technologies that we had never used before, so we were learning as we were going. It was an exciting time, even a little scary! It was critical that we were able to find the right people with the necessary experience and skills, because some of the design aspects of this product were new, even to us.”
“It was very well received. They could all see the simple and elegant design, and they also liked its modularity, because they can benefit from it by really getting a good head start in their development projects.”
Gary continued: “As the program manager, I worked closely with both Rich and Sean Leu, software manager, and Peter Muerset, system integration engineer, really helped to bring the hardware and software sides together. We wouldn’t have a product now, if Peter hadn’t been on the team.” Rich agreed: “We identified quite early on that the mechanical, electrical and software teams were all doing a good job but they somehow didn’t quite match up at their interfaces, and Peter’s experience with the integration of Tecan instruments from his time at Tecan Switzerland really helped pull it all together to work as a system.” In total, around 17 people were intimately involved throughout the project, including project leaders, mechanical engineering, electrical engineering, software, firmware and manufacturing.
For more information about Tecan Cavro products, visit www.tecan.com/oemcomponents
“Now that we have celebrated the release of the Cavro Omni Robot, we are planning our next adventures already. Watch this space!” concluded Rich.
Cavro Omni Robot – with closed loop positioning, designed to meet the most demanding accuracy standards
“We have taken the Cavro Omni Robot all over Europe, the US and Australia, to trade shows as well as directly meeting numerous customers,” said Rich. “Several prospective customers are already very interested and are just waiting to get their hands on our new toy.” Claudio added:
Tecan Journal 3/2008
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Cellerity™
– fully automated cell culturing cells for delivery on specific dates by automatically scheduling and performing the required tasks to grow sufficient cells, providing real-time feedback and alerts by email. The labor-intensive, error-prone yet critical task of cell harvesting is made easy by the Cellerity, which can optimize each cell line’s harvesting protocols for the unique Te-Flipper™ module to reliably execute the dissociation of adherent cells. The tedious chore of cell counting is also automated, eliminating operator variability to yield reproducible results. Cellerity allows dilution of harvested cell suspensions to required densities, and calculates cell growth rate, determines viability and document cell size, morphology and aggregation rate. Cellerity in standard configuration has the capacity for eight different bulk media, so the platform can simultaneously grow and maintain many cell lines. Up to 80 l of media can be stored in the refrigerator, and required amounts are warmed to approximately 30 °C immediately before use. Cellerity’s incubator monitors and controls the temperature and, optionally, the atmospheric CO2, N2 and/or O2.
An overview of the Cellerity system
Maintenance, expansion, harvesting and plating of cell lines is essential for many laboratories, but the process is hugely laborious and time-consuming, sometimes even requiring attention during the weekends. With the increasing amount of cell culture work performed in today’s life science laboratories, automation is becoming a necessity rather than a luxury. The Cellerity system fully automates various cell culture and downstream processes, providing consistent, high quality cells in a walkaway instrument. The modular system is based on the industryproven Freedom EVO® platform, with a modified liquid handling configuration Tecan Journal 3/2008
that is capable of both rapid bulk media dispensing and precise small volume pipetting, including the MultiChannel Arm™ pipetting option for dispensing cells into plates of up to 1,536 wells. The key to unattended operation is having the right resources available in the right quantity and at the right time. Cellerity, aided by its intuitive CellGEM™ (Cell Growth, Expansion and Maintenance) scheduling software, supports this need by anticipating usage and consumption of labware and other resources, based on a production schedule. The software guides users through all cell culturing processes and maintenance actions, and even allows users to request assay-ready
Several manufacturers supply automation-friendly flasks that are fully compatible with the Cellerity, such as the Corning® RoboFlask®, which has standard microplate dimensions and a pierceable septum cap to maintain sterility during media exchange. Cellerity’s robotic manipulator (RoMa) arm handles culture vessels through automated processes, and all liquid handling operations are performed in a sterile enclosure. Scientific instrumentation. Not for use in human clinical or in-vitro diagnostic procedures. Corning® and Roboflask® are registered trademarks of Corning Incorporated and its subsidiaries. For more information about Tecan’s Cellerity system, visit www.tecan.com/cellerity
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corporate news
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Tecan symposium 2008
‘Biologics: from benchtop to production’ Tecan is keenly looking forward to hosting the second Tecan symposium on September 16-19, 2008 in Oerlikon, Zürich, Switzerland, following last year’s hugely successful inaugural event. The annual scientific forum offers an intimate opportunity for leading scientists and a varied range of Tecan users to meet and discuss emerging scientific issues in connection with Tecan’s fields of expertise. The 2008 symposium, entitled: ‘Biologics: from benchtop to production’, will cover the rapidly growing areas of biotherapeutics, stem cell research and regenerative medicine. The formal program will be held over four sessions: • advances and opportunities in stem cells • from cells to therapy • high throughput applications • optimization and production of therapeutic proteins and antibodies.
Scientists at the forefront of their respective fields will present on various cutting-edge initiatives in research and application of biologics, followed by open, in-depth discussions with the invited audience. The first Tecan symposium was held in September 2007 in Erlenbach, Zürich, Switzerland, focusing on the subject of systems biology, and was chaired and jointly organized by Alan Sawyer, director of the Monash Antibody Technologies Facility in Australia. Alan will return in 2008 to present his valued input on high throughput monoclonal antibody production. With many luminaries in research and industry already confirmed to attend, this year’s meeting promises to be another successful event, and is eagerly anticipated by all at Tecan. www.tecan.com/symposium2008
Zürich The different cell populations in the hippocampus of the adult mouse during neurogenesis. Image taken with a confocal microscope at 40x magnification. Image supplied courtesy of Professor Kempermann, CRTD.
2008
second Tecan
Symposium Tecan Journal 3/2008
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CO R POR ATE N EWS
Tecan rallies its expertise and equipment for the Chinese earthquake efforts Tecan has donated a Freedom EVO® 150 liquid handling workstation to help process forensic samples for human identification in the aftermath of the May 12 earthquake in the Sichuan Province of China.
The earthquake, which measured 7.9 on the Richter scale, caused major devastation in the Province, with more than 87,000 people reported killed or missing in latest figures (from the World Health Organization). Many of the victims have still to be identified and, though a daunting task, the work required to identify the remains is an important priority for the Chinese Government, to help families and the entire community as a whole to come to terms with their loss. Large quantities of samples have been collected and the donation, including a Freedom EVO 150, specially configured for human identification, plus consumables such as pipette tips and magnetic beads,
Tecan Journal 3/2008
will be an enormous boost to processing them. The system was installed in the Center of Forensic Science Service, Public Security Department of Sichuan Province in July, and will be supported by Eastwin, Tecan’s distributor in China. Tony Mamone, Senior Market Manager for Forensics at Tecan, said: “We welcome the opportunity to use our expertise to help in this humanitarian crisis. It is critical for families to identify their loved ones to bring them some degree of closure, and we are thankful that our instruments can be of use to China’s relief efforts.” The Freedom EVO workstation is particularly well-suited to forensic applications such as human identification because of its reliability, accuracy and capacity for very high throughputs.
It is also very easy to use, with several processes already covered by validated, ‘ready-to-run’ protocols. Tecan instruments support all major chemistries and are scalable to grow with any laboratory’s changing throughput requirements. Specially configured Freedom EVO workstations, similar to that supplied to China, are installed in many forensic laboratories around the world, including those of the South African Police Service, the Royal Canadian Mounted Police, and several local and national forensic departments. The instruments were also used in human identification of victims from the World Trade Center. For more information about Tecan’s forensic solutions, visit www.tecan.com/forensics
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q UA LIT Y
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Achieving consistently high quality around the world As part of its core commitment to quality, Tecan is driving ahead with the implementation of a uniform quality management system in all of its global organizations. Following the ISO certification of the first sales organization in France in 2006, Tecan Benelux, Tecan China and Tecan UK are now also certified according to ISO 13485/2003, and it is anticipated that Tecan Germany will be certified before the end of the year.
Tecan Benelux team
Günter Weisshaar, Tecan’s Executive Vice President Global Quality and Regulatory Compliance, leads the implementation at a global level, while Erika Hildebrandt, Quality Manager for Tecan Europe, and Jeanne Wu, Quality Manager for Tecan China, manage the projects locally. Erika explained; “The main focus of all the changes is to ensure that our customers everywhere will receive the same consistently high standard of service and support from Tecan. We can already see the benefits at Tecan France. Installations, maintenance and overall customer service have all improved as we are able to record
Erika Hildebrandt and Gary Steeden, happy that the audit of Tecan UK has been finished successfully
and track customers’ requests more easily and respond more quickly. With the certification of these additional countries, our customers around the world will now be able to enjoy the same advantages as our customers in France.” Erika led other European projects in close association with Patrick Daeninck, Business Manager for Tecan Benelux, and Cindy Dhoop, local quality specialist in Benelux and with Jill Warren, Office Manager for Tecan UK, and Gary Steeden, Service & Consumables Manager and local quality specialist in the UK. Erika continued; “We have now established a local quality specialist in each territory, and I have worked closely with them to implement the project. It really is a team effort.” “The experience gained in the earlier operations has really helped to optimise the process, and the certification of additional countries is progressing at great speed. The accreditation of France took one year, Benelux nine months and the UK six months, so we’re streamlining all the time. We’re now ready to take on Germany, the biggest of our European sales organisations, and should complete certification there before the end of the year.” At Tecan China, Jeanne was heavily supported by Cathy Zhang, Back Office Manager and Mark Wang, Chief Representative of Tecan China and, backed by the whole of the Tecan China team, they prepared the certification audit. Jeanne said: “Tecan China relies much on the distributors for direct customer
Gary Steeden and Roger Morgan (Field service engineer) looking at the Service procedure
Looking at a Tecan UK procedure
contact, so it was hugely beneficial to improve the distributor training system. Various elements were considered into the process, like global requirements, business needs, distributor capability and further development of the Chinese market.” Günter concluded: “As with certification of our earlier facilities, we have chosen to work with TÜV Product Service, a well-known global notified body with a particular expertise in the medical device business and a strong reputation for high standards. This long-term project is really gathering momentum and we are well on our way to structuring all sales and service activities throughout our sales organizations in a similar way. Our teams have achieved a tremendous amount already, and I am positive that our customers will quickly feel the benefits.”
Günter Weisshaar (back row, third from right) and the team at Tecan China Tecan Journal 3/2008
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M I C ROA R R AY P ROD UCTS
Fishing for genetic information The high throughput efficiency provided by Tecan’s HS 4800™ Pro Hybridization Station makes all the difference to researchers in Canada looking at the spawning patterns of salmon stocks, and at the effect that changes in the environment have on fish survival and migration.
Sockeye on the Adams River spawning ground
In today’s fast-changing environment, the global management of fish stocks in our oceans is a problem that is now being addressed from a genomics perspective. Dr Kristina Miller, head of Molecular Genetics at the Pacific Biological Station in British Columbia, Canada, has been overseeing a genomics-based research program looking at fish populations since 2004: “The aim of the program is to use genomics technologies to better understand the physiology of migrating fish and to develop tools to assess salmon condition for use in the management of wild salmon stocks. We are particularly focused on predicting how salmon will respond physiologically and behaviorally to the changing conditions in the aquatic environment,” she explained. Salmon are born in a stream and spend one to two years there before migrating out into the ocean. Depending on the species, they can spend one to four years in the ocean, before returning to the same stream in which they were born, where they will reproduce and die. Kristina continued: “Salmon migrate a very long distance and it is a daunting Tecan Journal 3/2008
Capturing sockeye in the Fraser River
task to predict in any given year how many fish will come back from each stock. In the past, managers relied on overall abundance estimates to decide when and where to open and close fisheries, but now, using genetically-based stock identification done in my lab, we can tell managers within 18-24 hours what stocks are present in a mixed stock test fishery. This technology has allowed the inseason management of salmon in British Columbia to move towards stock-based management, specifically targeting fisheries on healthy, abundant stocks and implementing conservation strategies for stocks that need protection.” With the success of the stock ID program, the team has moved on to more challenging tasks, using genomics to develop tools that can stage the condition and predict the behavior and fate of migrating salmon. The team uses a combination of molecular biology, population genetics and telemetry technologies to compile all the information it can on the salmon populations under investigation. Of these, cDNA microarray technology is a
particularly important technique, based on microarray slides developed for salmon and containing over 16,000 spotted gene elements in Ben Koop’s laboratory at the University of Victoria, British Columbia, for the Genomic Research on Atlantic Salmon Project (GRASP). This linkage of genomics with telemetry has allowed them to use wild-caught salmon to identify behavior- and fateassociated biomarkers. As Kristina explained: “By combining genomics with radio tagging we can go out into the ocean, capture a number of fish and insert radio tags into their oral cavities, allowing us to track their movements all the way back to the spawning ground. Simultaneously we take non-lethal biopsy samples of gill or muscle tissue, and by then extracting and amplifying RNA in the laboratory we can gain an insight into the physiological state of the salmon at the time of tagging. The ability of salmon to adjust to stressful factors such as increases in water temperature and changes in salinity are all critical for survival. We are continually searching for physiological and genetic reasons why
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Tecan’s LS Reloaded, Tecan’s HS 4800 Pro Hybridization Station
some fish stocks are able to withstand high water temperatures, and others are not; why some can easily reconfigure their gills to make the shift from a high saline marine environment to a low saline freshwater environment, but others can’t; and even why some fish enter the river at the wrong time and face conditions that they are not adapted to withstand.” The team has successfully used this approach on wild-caught salmon to provide a mechanistic understanding of salmon condition and fate. Importantly, they have discovered biomarkers in salmon that can predict how quickly salmon will enter the river and their probability of making it to the spawning grounds. Since the early days of the program, the workload of processing microarrays has steadily increased, as each new set of results leads to further lines of investigation. The group soon turned to automation and now relies heavily on the HS 4800 Pro Hybridization Station from Tecan, which replaced manual techniques and routinely runs 24 microarray slides every day.
Shaorong Li in the lab
Kristina commented: “One of the most important things for me is minimizing technical variance and this is a huge advantage of the HS 4800 Pro. Apart from the time it saves us on throughput, this instrument gives us an exceptionally high consistency rate. From having a drop-out rate of around 20 %, we now rarely have to repeat any slides and then not for hybridization problems.” Laboratory technician, Shaorong Li, agreed: “Before we had this instrument we used a manual approach which was time-consuming and much less efficient. However, with the Tecan platform, you can load the samples and leave it overnight and when you return in the morning, everything is done and the slides are dry and ready for scanning. It has high throughput capability and the slide quality is much better than the traditional manual approach. Crucially, results are consistent and technical variance is reduced, and this, combined with the time and money-saving aspects, make this system a clear winner in efficiency.” Kristina and her team developed the entire hybridization protocol and shared this with the group at the University of
Victoria, who initially provided the microarray slides. She added: “We made it clear to them that the HS 4800 Pro system was essential to the success of our experiments and they, in turn, purchased one on this recommendation.” The bottleneck in the process is now reading the slides once they have been hybridized, and the team in British Columbia is already tackling this with the purchase of Tecan’s LS Reloaded™ scanner with auto-loading facility. Kristina concluded: “We would like to soon progress to running 48 slides a day, which the HS 4800 Pro system can handle easily, but we couldn’t even consider this without increasing our capacity to load and read the slides after processing. The LS Reloaded will make a huge difference to this, allowing us to just walk away while it loads and processes the slides far quicker than we could before.” For more information about Tecan’s HS 4800 hybridization stations, visit www.tecan.com/hs4800 For more information about Tecan’s LS Reloaded laser scanner, visit www.tecan.com/ls Tecan Journal 3/2008
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P ROTE I N S C I ENC E
The world’s largest custom monoclonal antibody production facility opens at Monash University The partnership between Tecan and the Monash Antibody Technologies Facility has come to fruition with the opening of the new state-of-the-art custom monoclonal antibody production system at Monash University in Victoria, Australia. This unique facility has the capacity to produce thousands of different monoclonal antibodies per year for use in research, diagnostics and therapeutic applications.
The new Monash Antibody Technologies Facility had its grand opening on August 6th 2008, attended by a number of important dignitaries from the Australian government, academia and the life science industry. The two hundred square meter facility houses cutting edge equipment, including 10 Freedom EVO® liquid handling workstations, and,
Mark Dreyfus, Alan Sawyer and Kim Carr tour the facility
Dignitaries from the Australian Government and Monash University join members of the MATF team at the event Tecan Journal 3/2008
although still in its relative infancy, it already boasts impressive capabilities for high throughput production of custom-made, high-affinity monoclonal antibodies. Michael Spiegel, deputy director of the Monash Antibody Technologies Facility, said: “We are the largest capacity and probably the most sophisticated and technologically advanced custom antibody facility in the world. There are already 50 academic projects in the pipeline and we are members of the structural genomic consortium, an international pilot project for creating binding agents to all human proteins and protein binders. We are also finalizing deals with several major corporations concerning the development of anywhere between 200 and 500 antibodies per year. We are truly an international facility and there are a number of companies in the United States, Europe and Australia who are very interested in our work.”
This exciting new venture, partially funded by the Victorian State Government, is a component of an extensive 2008 development program set to strengthen Monash University’s rising profile as a center of excellence in the international medical research community. At its core, the 10 integrated Freedom EVO liquid handling workstations that fully automate all stages of the monoclonal antibody production process are going through final stages of optimization. Michael added: “In just one year, and with Tecan’s back-up, we have renovated a whole new space, brought in the automated systems and have them already producing antibodies, with optimization progressing at a steady pace. The fusion station and ELISA stations are fully operational, as are the REMP sample storage and retrieval system, tube labelling and reception injection capabilities.”
Monash
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The new state-of-the-art facility at Monash
“Right now we have the ability to make one thousand new targets a year per full time employee,” Michael continued. “We can do 24 fusions a day, all of which would yield something between 1,000-1,500 clones, and this is really interesting for pharmaceutical and biotech companies trying to come up with therapeutic antibodies. We can theoretically make about 5,000 new targets a year and there is no other facility that can achieve those numbers and really apply it to both research and to commercial production. The level of antibody production the market requires, however, is still well beyond what we can do with the new facility. We are starting to resolve the bottleneck but are really just at the tip of the iceberg and the next step will be to progress and develop the facility to expand even further.”
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Michael concluded: There is a real need for this facility and when people hear what we can do here they are very excited. We recently made our one year presentation to the Victorian government to give them an update of what we have achieved so far and what we are planning in the future. The government representatives were impressed and, more importantly, were extremely satisfied with their investment in the facility. Gavin Jennings, the Victorian government minister for Innovation and Environment cut the ceremonial ribbon at the opening ceremony, and guests included Kim Carr, the federal minister for innovation, the Chancellor, Vice Chancellor and Deputy Vice Chancellor of Research at Monash University and Carl Severinghaus, Tecan’s Senior Vice President.
For more information about Tecan’s Freedom EVO platform and our Protein Science solutions, visit www.tecan.com/tig www.tecan.com/proteinscience For more information about Monash University, visit www.monash.edu.au
Gavin Jennings and Kim Carr
There is a real need for this facility and when people hear what we can do here they are very excited.
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University
Carl Severinghaus and Michael Spiegel
Tecan Journal 3/2008
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and don’t forget
FO R E N S I C S
Catching up on crime
A Freedom EVO® 100 liquid handling workstation is cracking the workload of the Missouri State Highway Patrol Laboratory, Jefferson City, Missouri, USA, automating all the steps of DNA purification and tackling a backlog of thousands of forensic samples.
crime
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Tecan Journal 3/2008
The Missouri State Highway Patrol Laboratory in Jefferson City covers all forensic disciplines, including trace evidence, toxicology, drugs, firearms and fingerprinting, with 10 criminologists entirely dedicated to all types of DNA cases, ranging from theft and burglary through to sexual assault and homicide. During the past five years, with the emergence of more reliable and accessible DNA technologies, the laboratory has seen higher numbers of low level DNA samples, no longer coming just from bloodstains on the floor or evidence of sexual assault, but now taken from anything a suspect may have touched, like door handles and drinking glasses. Then, two years ago, the state of Missouri ruled that DNA should be collected from all crimes, not just violent ones, increasing sample numbers even further. Together these factors have resulted in a 50 % rise in DNA samples the laboratory receives over the last three years. Brian Hoey, supervisor of the DNA unit at the Highway Patrol Laboratory, explained: “We are currently facing a backlog of 1,300 cases, or approximately 6,000 samples, representing nearly one year’s workload for us. Before the policy changes, we relied on manual techniques for DNA preparation but the issue of throughput became overwhelming. At the same time, laboratory space was an important consideration. All the forensic disciplines are housed together here,
in an area of 11,000 square feet. We already stagger shifts to manage the number of people working at any one time and it was obvious that we needed to bring in an instrument to cope with the workflow. I visited other laboratories with similar requirements to ours, saw Tecan workstations in operation and soon recognised that the Freedom EVO workstation could do everything I wanted it to. To take the jump to automation, I wanted to be sure that we would be able to perform all the steps of DNA purification – extraction, quantification and amplification – on a single platform, removing the need for any manual intervention.” Validation too, of course, was an important consideration that Brian had to take into account: “We follow guidelines set down by the American Society of Crime Laboratory Directors Laboratory Accreditation Board that specify the validation of every instrument used in criminology investigations. Our internal validation procedures test for three things: sensitivity, precision and reproducibility. We look at samples that are environmentally insulted, such as contamination with oil, grease or dirt, and including sexual assault samples, like semen and vaginal swabs. We also test samples from different animals to see if the instrument operates differently with, for example, deer blood rather than human blood. Finally, we check traceability, another element of the validation process, ensuring that the
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Shawn Bailes and Shena Latcham, principal Tecan Freedom EVO investigators
sample bar coding system will help us to track samples through a chain of custody. We fully expect to see more consistency in our results with automation compared to manual procedures, and the instrument will be able to extract DNA from low level samples virtually every time, without the hit and miss problems associated with human error in manual procedures.” The laboratory is now at the point of running blood and buccal swab samples to accustom the operators to the instrument, reagents and workflow. Brian continued: “Once we start to get good data and know how to operate the instrument, we will simply set up a 96-well plate, place it in the instrument and this will validate at the same time as the samples are run, allowing all the validation to be completed within one or two runs. This is quite a contrast to what we had to do in the past, where validation could go on for years. We’re also sharing this data with other laboratories in similar stages of validation through our Tecan representative.”
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According to current timescales, the Freedom EVO workstation will go online in the Autumn of 2008, with the Tecan system performing the steps of DNA extraction and quantification using realtime PCR. Brian added: “The workstation is working very well, freeing the analysts to open up more evidence and gather samples, and the bottleneck is moving from the wet chemistry to the data analysis so we are currently investigating how to address this.” He concluded: “I know the anxieties that we had when first considering automation and I would like to be the first to reassure other people who are currently going through those same concerns. I am very excited about our set-up now and am more than willing for people to come and see our workstation in action. From my initial impressions, and from what I’ve now learnt from experience, I truly believe this is the best instrument currently available for forensic applications such as ours. With the help of the Tecan application support team, we have developed a system that does exactly what we need.”
For more information about Tecan’s forensic solutions, visit www.tecan.com/forensics
From my initial impressions, and from what I’ve now learnt from experience, I truly believe this is the best instrument currently available for forensic applications such as ours.
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Tecan Journal 3/2008
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WAS H E RS
Automation of time-consuming washing and detection steps accelerates screening of proteinprotein interactions The Protein Interaction Screening Unit at the German Cancer Research Center, Heidelberg, has automated the co-immune precipitation method for investigating protein-protein interactions (PPIs) using Tecan’s HydroFlex™ washer and Infinite® F200 microplate reader, increasing throughput up to 100-fold compared to manual methods, and greatly accelerating PPI screening. for investigating mammalian systems so we have concentrated on developing more physiological methods that are equally fast and cheap. I believe that the most promising of these methods that could take over from the Y2H method within five years is co-immune precipitation of two proteins from transiently transfected cells (BarriosRodiles et al., 2005). A particularly important advantage of this method is that it can be easily automated.” The team at DKFZ has dedicated two Tecan instruments to automating its coprecipitation assay: a HydroFlex washer with smart-MBS option for processing magnetic Dynal® beads; and an Infinite 200 microplate reader with Connect™ stacker, allowing processing of batches of up to 50 microplates of any appropriate format without any manual intervention.
Tecan’s HydroFlex washer for processing of magnetic beads
The German Cancer Research Center (DKFZ) in Heidelberg carries out basic scientific research into mechanisms of cancer development and identification of cancer risk factors, feeding these results into new approaches in the prevention, diagnosis and treatment of cancer. DKFZ has several core facilities offering specialized services internally and externally, including the Protein Tecan Journal 3/2008
Interaction Screening unit, led by Dr Manfred Koegl. Automation is playing an important role in improving the services these facilities offer, as Manfred explained: “Researchers for many decades have increased their understanding of proteins by looking for PPIs, largely relying on the successful and cost-effective Yeast Two-Hybrid (Y2H) method. However, the Y2H method has several disadvantages
Dr Koegl described the basis of the method developed by his team: “The 96well microplate containing a suspension of magnetic beads and proteins of interest in each well is washed in the HydroFlex and transferred, using the Connect stacker, to the Infinite 200 reader for the luminescence measurements.” Optimizing the washing stage was critical but made straightforward by the flexibility of the HydroFlex. “We discovered that the protein complexes could fall apart if washing goes on for too long,
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with above-background luciferase activity, detected as bioluminescence, point to an interaction between the two tagged proteins present.” “The effectiveness of this method is due to luciferase being so exquisitely sensitive in its detection. Each well of a 96-well microplate contains a different potential binding partner for the affinity-tagged protein we are analyzing, so we can test for 96 different PPIs in one microplate and we usually test one protein against many. For example, if I have a protein that I suspect has a role in transcriptional regulation, then I screen it against many different known transcriptional coregulators.”
(L to R) Kerstin Hettler, Frank Schwarz, Christiane Rutenberg and Manfred Koegl
resulting in the loss of some PPIs, but the HydroFlex washes the magnetic bead suspension very quickly and thoroughly. Two wash cycles effectively reduce the background from the initial one million counts to that of the instrument, but we found that routinely washing four times eliminates false positives due to spurious PPIs and still doesn’t result in any loss of beads. It is easy to test these wash variables on the HydroFlex so we can be sure that we are working under optimal conditions, and this ease-of-handling and speed of wash are, for us, the most important features of the washer.” A major advantage of automation is the throughput his team can now achieve, as Dr Koegl explained: “Washing one 96-well microplate takes less than five minutes so we can easily wash 10 microplates in less than an hour. We are currently testing only 200-400 PPIs in one experiment, but I expect that further automation will increase the throughput to 1,000 PPIs per day. Manually, using the standard co-immune precipitation protocol, 12 PPIs are typically done per day, followed by gel electrophoresis and Western blotting.” “A further advantage of the precipitation method over the Y2H method is that it uses mammalian cells, HEK293 (Human Embryonic Kidney cells) that can be stimulated with certain triggers so that PPIs form under physiological conditions. PPIs are regulated in time and space, for
example, proteins that interact in signal transduction only do so when that signal transduction pathway is stimulated.” “The precipitation method uses two tagged proteins: one is affinity-tagged with Protein A which binds to an invariant part (FC) of any immunoglobulin (IgG) molecule for fast and efficient purification; and the second protein is tagged with a luciferase for detection of the protein-protein complex. HEK293 cells are transfected to express the protein of interest and proteins being investigated for binding to the protein of interest, so protein-protein complexes form inside the cell. Cells are lyzed by a mild detergent, and magnetic beads coated with IgG are added. The Protein A-tagged protein binds to the magnetic beads and if it forms a complex with the luciferase-tagged protein, the latter will be indirectly bound to the beads. Before washing, the raw extract contains over one million counts per well. The washing steps follow incubation, removing all proteins not bound to the protein of interest, reducing the luciferase count down to below 50 per well if no proteins bind to the proteins of interest, and representing a 20,000-fold purification in the shortest possible time. Those proteins still bound to the protein of interest after washing are detected by abovebackground levels of bioluminescence measured by the Infinite reader. Wells
Dr Koegl concluded: “Before we release our new automated co-immune precipitation method, we are aiming to assemble large arrays of around 1,000 proteins that we can offer to customers for testing in their PPI screening assays. Our objective is to form arrays from public clone collections arranged in groups according to cellular pathways and processes, such as proteins involved in certain signal transduction pathways, or in DNA repair. This information, together with the increased throughput the co-precipitation assay offers, will give our fellow scientists an alternative to methods like Y2H screening.” Dynal is a registered trademark of Dynal Biotech ASA, Oslo, Norway References: Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL. High-throughput mapping of a dynamic signaling network in mammalian cells. Science. 2005 307:1621-5 For more information on Tecan’s HydroFlex as well as the corresponding application note, visit www.tecan.com/hydroflex For more information about Tecan’s Infinite 200 multi-mode reader, visit www.tecan.com/Infinite200
Tecan Journal 3/2008
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A P P L I CATI ON B IOP HARM A
Speeding up drug development at Merck Scientists in the Drug Metabolism and Pharmacokinetics Department at Merck Research Laboratories, Pennsylvania, USA, value the flexibility of their two Freedom EVO® platforms for handling sample preparation and ELISAs in pharmacokinetic/ pharmacodynamic modeling studies.
(L to R) Dave Chen, Thorsten Verch, John Mehl, Kou-Chang Yin and Laura Hong
Drug metabolism and pharmacokinetics (DMPK) is indispensable in drug discovery and development, spanning all stages through pre-clinical and clinical trials, and into the post-marketing phase. An important area within DMPK, pharmacokinetic/pharmacodynamic modelling (PK/PD), helps to improve the prediction of drug action, and can potentially bring costs down for complex drug development programs.
Tecan Journal 3/2008
Pharmacokineticists working on large molecule clinical PK/PD projects rely mainly on data from the ELISA method for their PK/PD modelling. Head of the Clinical PK/PD ELISA Lab, Dave Chen, explained the importance of automation in his laboratory: “Our ELISA results have to be of the very highest quality so automated systems are essential to give us very high throughput, accuracy and, in the long term, consistent results from our samples. We provide a bioanalytical
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“
Apart from our three main challenges of high throughput, accuracy and consistency, we have found that the Tecan systems also meet other very important requirements for PK/PD analysis.
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solution for large-scale analysis of proteins, such as antibodies in serum, and we routinely support two types of project, each with quite separate needs. Firstly, there are pre-clinical studies, where the most important concern is throughput – dealing with a very high sample load in a very short space of time. Secondly, for clinical trials, consistency of results over a long period of time is the crucial factor. I came to Merck with several years’ experience in establishing just the kind of system that I could see was required here in the Clinical PK/PD ELISA Lab. In that time, I had evaluated many different systems on the market and had decided that Tecan instruments were my choice for very high throughput protein analysis, largely because they could meet the requirements of both pre-clinical and clinical studies.” There were already two Tecan Freedom EVO platforms available in the Clinical PK/ PD ELISA Lab and Dave quickly set to work to optimize these instruments for the department’s routine workload. “I had already had good experiences of working with the Tecan support team in the US so knew I would be able to rely on them again to help me establish an efficient workflow with the Freedom EVO systems. Within a few months, both platforms were fully functioning. The Freedom EVO 150 is equipped with a Liquid Handling (LiHa)
arm and handles standard calibrations, quality controls, sample preparation and plate loading steps, while the Freedom EVO 200 platform is potentially adapted for fully automated, very high throughput, ELISA processing, complete with a Multichannel Arm™ (MCA), a microplate reader and a washer. Each instrument is controlled through Freedom EVOware® Plus software, which fully coordinates preparation of standards and quality controls, sample dilution, ELISA processing and data interface with LIMS. “Apart from our three main challenges of high throughput, accuracy and consistency, we have found that the Tecan systems also meet other very important requirements for PK/PD analysis,” Dave added. “Flexibility is essential because we are continually changing the ELISA methods that we’re working on. Freedom EVOware software is a critical aspect here because it allows us to change the programmed ELISA protocol according to each specific project. Freedom EVOware is an open system that is very easy to use – we have established a number of protocols and don’t need to reprogram each time, the software does that for us, automatically matching the program with our requirements. At the end of all this, the platform itself is so easy to operate, just a matter of clicking a button and walking away.”
He continued “In addition, there are a few complications specific to our work in protein analysis, all of which the Freedom EVO systems handle without problems. These include biological matrices rather than buffers, various dilution factors and the necessity to dilute samples within that calibration range. These are all crucial to our work in PK/PD studies and the results we have in comparing manual methods with the Freedom EVO in validation were very impressive.” In conclusion, Dave predicted that automation will continue to grow in his laboratory: “We need to continue to develop our automated systems in order to support the increasing demand for the results of our studies. I am preparing to have Freedom EVO platforms working 24 hours a day when studies need.” For more information about Tecan’s ELISA solutions, visit www.tecan.com/elisa
Tecan Journal 3/2008
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Li quid H andlin g
Freedom EVO® gives RIA workflows a boost Shin Jin Medics, Inc., a manufacturer of in vitro immunodiagnostic products, has developed a workflow solution for radioimmunoassays (RIAs), the RIA Automated Laboratory System (RALSystem), using Tecan’s Freedom EVO platform as a critical component.
probe, a very small sample capacity and a long processing time; it was relatively inefficient and, as a result, most assays were still performed manually. Mr Seung-Jae Lee, manager of diagnostic instrument engineering at Shin Jin Medics, explained the basis of the new automated solution: “The whole system has been designed to be very simple and easy to use, and it is capable of rapidly processing a large number of samples. We started developing the RALSystem last year, consisting of Tecan’s Freedom EVO 150 liquid handling workstation combined with our instruments, the gamma counter (Dream Gamma-10), washer (Dream TW20) and shaker (Dream Shaker). We chose the Freedom EVO for the sample handling of the workflow because of its flexibility and compatibility with our own systems, particularly with the gamma counter.” (L to R) Mr Seong-Yun Lee, Seung-Jae Lee and Hyun-Il Kim
Shin Jin Medics, based in Koyang-Si, South Korea, and founded in 1992, develops and provides a range of RIA- and ELISA-based diagnostic kits and instruments. RIA is similar to ELISA as an in vitro diagnostic method, but where ELISA uses a reporter enzyme, RIA uses a radioisotope for sensitive and quantitative assay signals, measured using a gamma counter. As an RIA devices manufacturer, Shin Jin Medics is one of only two companies in the world that manufactures gamma counters and has now turned its attention to automating workflows. Until recently, there was only one commercially available automatic instrument for RIA workflows. However, this system had only a single
Tecan Journal 3/2008
“The RIA workflow on the RALSystem starts with dispensing samples and reagents on the Freedom EVO platform, which has a large capacity and a fast dispensing speed for efficient processing of samples,” continued Mr Lee. “The samples are human serum, and the Freedom EVO takes 10 minutes to distribute 100 samples into 500 reaction tubes. The tubes are incubated on our shaker to react, usually for about 30 minutes to one hour, and washed by our washer, which can wash up to 20 tubes at once. The tubes are then analyzed in our gamma counter, which has 10 detectors to cover a wide energy range of various radioisotopes. The counter has a large capacity, and up to 500 tubes can be put on its deck for analysis.”
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kit’s protocol. For example, using our RIAKEY® kits, the RALSystem takes less than 80 minutes for five RIA tests (CA19-9, CA125, AFP, CEA, and TSH) with 100 patient samples, compared to several more hours it would take to do these assays manually.”
Mr Seong-Yun Lee
“We have also developed a proprietary tube rack that is compatible with all four devices and carries the total workflow through the system. This is the unique feature of the RALSystem, that it is fully integrated and automated, and this was made possible by the flexibility of the Freedom EVO. It is not necessary for the user to transfer the racks from one instrument to the next, minimizing human error and saving labor and time. The user also benefits from added protection from exposure to radioactivity in this way. The whole process, from sample distribution to results takes about one or two hours, depending on the assay
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“We have been using the Freedom EVO routinely in the RALSystem since the beginning of 2008, and everything has worked smoothly, without a problem. We received comprehensive training from Tecan Switzerland for running and maintaining the instruments, as well as application and software support from Dr Yingguang Wu from Tecan Japan, so, even before we started, we understood a lot about the Freedom EVO.” Mr Lee is also impressed with the Freedom EVO’s software. “It was largely thanks to the versatile software that we were able to design and integrate our own racks for the RALSystem. We found the software easy to use, and it was simple to modify it for different types of assays. We also developed our own sample handling program, which the Tecan software fully supports. The
RALSystem workflow handles both sample flow and information flow, so it is possible to apply a worklist fetched from a file saved on the centralized server, and we can also control all of the system data through a central PC. Altogether, I believe that, with the RALSystem, an effective automated RIA system has finally been realized,” he concluded. The RALSystem was displayed at the 6th International Conference on Isotopes (ICI 2008) at Seoul in May 2008, and was enthusiastically received by visitors and potential customers. RIAKEY® is a registered trademark of Shin Jin Medics, Inc. For more information about Tecan’s ELISA solutions, visit www.tecan.com/elisa
Mr Seung-Jae Lee
This is the unique feature of the RALSystem, that it is fully integrated and automated, and this was made possible by the flexibility of the Freedom EVO.
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M I C ROA R R AY P ROD UCTS
Microarray hybridization service with HS 4800™ Microarray scientists at the Netherlands Cancer Institute (NKI) in Amsterdam, have chosen four HS 4800 hybridization stations to automate their microarray processing service, which they use to support scientific research at the institute. The NKI is a large research facility adjacent to the Antoni van Leeuwenhoek Hospital (AVL), that includes a Central Microarray Facility (CMF) to support microarray-based research for the scientists in the institute. “There are eight of us in the CMF, four working mainly in the laboratory, and four bioinformaticians who work on analysis of results,” explained Dr Ron Kerkhoven, head of the CMF. “Our work is very variable – we handle a lot of human samples that come from the hospital tissue bank, where thousands of tumor samples are stored. Many scientists working here conduct large scale research using that resource, looking for fingerprints for certain types of cancers. Other research in NKI focuses on mouse models for cancer, so we also receive mouse tissues to analyze, as well as samples for various cell and tissue culture-based experiments.”
Dr Ron Kerkhoven and Wim Brugman, technician, with one of NKI’s HS 4800 hybridization stations
NKI uses four HS 4800 hybridization stations for its microarray processing service Tecan Journal 3/2008
Wim Brugman operating the HS 4800
“We used to perform all our microarray hybridizations manually, using little incubators that were submerged in a water bath. We have been handling expression arrays for some years and became quite proficient with the manual technique, and we taught the technique to many researchers to hybridize microarrays in their own labs. However, their results were variable compared to those from our facility, so we decided to switch strategy, where people send their samples to us, and we perform the microarray analysis. We now have a more production-style setting in our laboratory, covering RNA extraction, DNA amplification and hybridization. In order to manage the throughput, we automated the hybridization process with two Tecan HS 4800 hybridization stations in April 2005, which brought us greater reproducibility of results and allowed standardization of the process. It was a big step forward, and we now have four HS 4800 hybridization stations in our laboratory.”
happy with their performance. With our present set-up, we can process up to 48 slides in a day,” elaborated Dr Kerkhoven. “Our current levels run at between 5,000 and 6,000 arrays every year.”
“Once we fine-tuned the hybridization conditions to deal with the viscous fluids used in our procedure, we had a protocol that is very compatible with the Tecan hybridization stations, and we are very
“When we first decided to automate the process we looked at many hybridization stations, but all failed our requirements except the HS 4800, which really fulfilled all of our needs,” concluded Dr Kerkhoven.
Most of the microarray work at CMF is carried out on arrays that are designed and fabricated in-house. “The Tecan system is completely compatible with most of the arrays we use. Besides our own, we have used Agilent and Nimblegen arrays, which also work well – the only practical difference, of course, is that the commercial arrays have higher densities.” “One of the best features of the HS 4800 is that the whole hybridization process is fully automated, from sample injection to nitrogen drying and, because of that, all the conditions are very standardized. We usually hybridize overnight, and the results are waiting for us the next day. The slides are completely safe and sealed until we take them out for scanning.”
For more information about Tecan’s HS 4800 hybridization stations, visit www.tecan.com/hs4800
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Developing microarray-based assays for blood typing and diagnosis of infectious diseases Scientists at the University of Edinburgh are developing multiplex assays in microarray formats to accelerate routine blood typing and diagnosis of infectious diseases. Their assay development depends on a Tecan LS Reloaded™ laser scanner for automated scanning of both microplates and slides. Dr Colin Campbell, Research Fellow at the university’s Division of Pathway Medicine, leads a research group that focuses on the development of biochips to study interactions between specific biological pathways, within and between cells, and to look at how these pathways change in diseased states. Pathway medicine is a relatively new discipline within systems biology and understanding the interactions between biomolecules and functional systems, such as those controlling cell function and hostpathogen interactions, may provide important clues to the mechanisms underlying disease processes. Dr Campbell’s group is currently applying the research findings to microarray-based diagnostic assays, as he explained: “We are developing microarray technology and assays designed to improve both
the understanding and diagnosis of infectious diseases, especially those caused by herpes viruses or HIV. The assays will allow routine detection of such diseases using tiny volumes of blood and providing results within just 10 minutes or so, with minimal user intervention.” The group has been using a Tecan microarray laser scanner, the LS Reloaded, for about two years for developing the new microarrays. “Our Tecan scanner gives us the level of versatility that we need and that other scanners could not provide,” he said. “For example, we can make very sensitive measurements and the scanner allows a high degree of flexibility in choice of materials and chip geometries. This means that we can scan from underneath or above and can use silicon wafers and non-standard chip sizes.
Colin Campbell and Stuart Ember, protein microarray technician, studies results on the LS Reloaded
“We recently developed a microarraybased assay for ABO and Rhesus blood group typing, and are now developing this further to bring all the pretransfusion testing for other blood groups and infectious diseases together on one microarray,” Dr Campbell continued. “Our ultimate aim is to develop a single microarray-based test that will include all the critical antigens that must be matched for successful blood transfusion to take place.” Tecan’s LS Reloaded microarray laser scanner is recommended for research use only. For more information about Tecan’s LS Reloaded laser scanner, visit www.tecan.com/ls
Alan Ross, senior technical officer, operating the LS Reloaded Tecan Journal 3/2008
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P ROTE I N S C I ENC E
Robotics and proteomics: A partnership with a promising future in biomarker discovery
Robotics and High throughput proteomics was the goal of researchers in France who turned to Tecan to automate their sample preparation protocols for biomarker discovery in patient samples.
Freedom EVO 100 with integrated Te-Stack
The search is on for novel disease biomarkers that will ultimately lead to a more tailored and personalized approach to treatment for a number of diseases, including many cancers, diabetes and all kinds of metabolic diseases. For researchers like Dr Patrick Ducoroy, manager in the Clinical Innovation Proteomic Platform (CLIPP, based at Dijon and Besancon in France), of which the health department is based at the Hospital and Cancer Center in Dijon, high sample numbers and throughput are critical factors for getting good results. As Patrick explained: “These things are of paramount importance to us in order to identify good, robust biomarkers for investigation. It is also vitally important to standardize the procedures and the treatment of samples and, in this early discovery phase, stringent quality control is a must. Quite simply, automation is essential to achieve all these objectives.” To this end, Patrick’s laboratory uses two versatile Freedom EVO® liquid handling platforms to extract purified protein samples from patients’ blood, for longterm storage or further downstream analysis using mass spectrometry. “Our two Tecan robots are integrated and totally compatible with one another; they use exactly the same software for their operation, and therefore automation and standardization of the pipetting procedures during sample preparation are maximized,” he said.
Pipetting with the MultiChannel Arm Tecan Journal 3/2008
Patrick is a firm believer in the use of quality control and considers the Freedom EVO platforms crucial to achieve a standardized procedure that can be reproduced in good faith, time and time again. The Freedom EVO 200 has an 8-tip liquid handling arm for sample aspiration from tubes. For the clinical studies, the Freedom EVO 200 is used to aliquot the samples, which arrive in different types of tubes, to 96-well microplates, which are compatible with the MultiChannel Arm™ 96 in the Freedom EVO 100. Protein and peptide purification is carried out in the Tecan Freedom EVO 100, which also allows for additional downstream analysis of protein and peptide samples. “Both the Freedom EVO 200 and the Freedom EVO 100 include a 37 °C incubator for performing protein digests directly after purification in order to retrieve the peptides”, Patrick added. “The main advantage of our Tecan systems is the ability to process 96 patients in parallel in one hour, from the initial step of putting the sample tubes onto the first worktable, to isolate the plasma, purify the peptide and put the peptide on the target matrix, ready for mass spectrometry. The rapid processing helps us to achieve excellent reproducibility – we have analyzed the reproducibility of our instruments over time and we have had very good results. It is very important that we can process a very high number of patients in one week; ultimately we are aiming for a thousand and Tecan’s technology will be central to us achieving this goal”.
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PROTEI N SC I E N C E
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proteomics Another important consideration is that it is imperative to minimize crosscontamination between patient samples at all costs, and this concern is addressed with the Freedom EVO’s ability to switch to using disposable tips. The tips are changed between samples, and this is key for the avoidance of contamination. In addition, all source tubes and destination plates are identified through their barcodes with Tecan’s PosID™ positive identification system. For analysis and identification of the separated proteins, and for the detection of new biomarkers in clinical studies by profiling comparison, the team uses Matrix Assisted Laser Desorption Ionization (MALDI) mass spectrometry. In this technology, the ionized protein samples are accelerated through an analysis chamber (vacuum or flight tube) to separate the molecules according to their mass to charge ratio. The timeof-flight (TOF) analyzer determines the mass of a peptide by the amount of time it takes to reach the detector within the flight tube. Afterwards they employ a variety of different statistical tools for the treatment and analysis of the data obtained. Interestingly, the team is currently working with Tecan to obtain an informatics software solution, which will hopefully lead to good traceability of process between the Freedom EVO software and the mass spectrometer software.
Scientific instrumentation. Not for use in human clinical or in vitro diagnostic procedures.
The team at Clinical Innovation Proteomic Platform (CLIPP), Dijon, France
Support from the Tecan engineers has been critical to the success of the project. Patrick added: “We have had very good support from Tecan, particularly with regard to modifying the different parameters of the robotic workstations. I am sure this has helped us to achieve such excellent reproducibility of results, with the throughput that we need.”
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For more information about Tecan’s Protein Science solutions, visit www.tecan.com/proteinscience
Tecan’s technology will be central to us achieving our goal.
Worktable with carriers and labware
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Integrated Te-VacSTM vacuum separation module Tecan Journal 3/2008
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EV E NTS 20 0 8
Meet Tecan at these events in 2008 Americas International Symposium of Human Identification (ISHI)
Hollywood, CA
13-16 Oct 2008
National CODIS Conference
San Francisco, CA
October 2008
American Association of Pharmaceutical Scientists Annual Meeting 2008 (AAPS)
Atlanta, GA
16-20 Nov 2008
The American Society for Cell Biology (ASCB)
San Francisco, CA
13-17 Dec 2008
The Japanese Society for the Study of Xenobiotics
Kumamoto, Japan
30-31 Oct 2008
Biochemistry and Molecular Biology 2008
Kobe, Japan
09-12 Dec 2008
DGTI Annual Congress of the German Society for Transfusion Medicine and Immunohematology
Düsseldorf, Germany
16-19 Sep 2008
5th Annual Conference German United Society of Clinical Chemistry and Laboratory Medicine (DGKL)
Mannheim, Germany
21-24 Sep 2008
ELRIG - Drug Discovery
Bournemouth, UK
23-24 Sep 2008
Biotech Forum and Scanlab
Copenhagen, Denmark
23-25 Sep 2008
16. Jahrestagung der Deutschen Gesellschaft für Immungenetik -DGI
Essen, Germany
25-27 Sep 2008
3rd ESF Functional Genomics Conference
Innsbruck, Austria
01-04 Oct 2008
MipTec
Basel, Switzerland
14-16 Oct 2008
Expoquimia
Barcelona, Spain
20-24 Oct 2008
Laboratory Middle East LabME
Abu Dhabi, UAE
11-13 Nov 2008
Medica
Düsseldorf, Germany
19-22 Nov 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 in Chief: Tecan Trading AG, Cornelia Kegele Project Lead: Tecan Trading AG, Cornelia Kegele 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. Cellerity, CellGEM, Connect, Freedom EVOlution, HS 4800, HydroFlex, LS Reloaded, MCA, PosID, Te-Chrom, Te-Flipper, Te-VacS and Te-Stack are trademarks and Cavro, Freedom EVO, 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. © 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 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 +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 3/2008