Tecan Journal Edition 03/2012

Tecan Journal Life Sciences and Partnering Business

Edition 3/2012

Protecting the nation pages 16-17

40 years of Cavro速 pages 6-7

Rapid, automated isolation of buffy coat benefits DNA extraction pages 20-21

Making advances in the battle against autoimmune disease pages 26-27

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CEO WELCOME TECAN JOURNAL 3/2012

Welcome to the latest issue of the Tecan Journal

Welcome

Tecan has a long history and tradition in the OEM market and, as we move into the fall, we celebrate the milestone 40th anniversary of Cavro®. For four decades, instrument designers have relied on Tecan Cavro branded components to provide innovative and reliable liquid handling products that can be applied to a wide range of applications.

As part of Tecan’s broad OEM product portfolio – from components such as pumps, valves and robotic modules, to full system solutions and instruments that partners incorporate with their specific applications and tests – the Cavro brand is a key element in the Company’s success as the ‘OEM partner of choice’ for leading diagnostic and life science companies.

We continue to enhance and broaden the functionalities of the market-leading Freedom EVO® liquid handling platform with new modules and applications. The launch of the new Air LiHa air displacement pipetting arm – which provides greater versatility than ever before – is generating a lot of interest and, to help meet ever-increasing quality and regulatory demands, we have recently released the QC Kit, offering a total solution for liquid handling performance verification testing.

This issue also includes news of Tecan’s success at the 2012 SLAS Asia Conference and Exhibition, as well as details of the forthcoming Tecan Symposium which will focus on the expanding role of mass spectrometry in life sciences and diagnostics.

Plus, we have the usual diverse array of customer applications that depend on our expertise in providing automated solutions.

We hope you enjoy the issue.

Gérard Vaillant, Acting CEO

CONTENTS TECAN JOURNAL 3/2012

page 9

Tecan Symposium comes to Boston 2

CEO Welcome

4 Tecan US relocates to bigger and better premises page 11

4 Cornelias celebrates 25 years at Tecan 5 Tecan enjoys success at 2012 SLAS Asia Conference and Exhibition 5 Increased flexibility and choice for Cavro Centris Pump 6 - 7 40 years of Cavro 8

ornell Cup success for C Tecan-sponsored team

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Tecan Symposium comes to Boston

10 Tecan showcases the Freedom EVO workstation configured for ELISAs to delegates visiting from Chinese blood centers 11 Joining the digital age pages 14 - 15

12 - 13 A winning combination for nephrology research

pages 24 - 25

Cavro Air Displacement Pipettor provides the key to automated sonochemical synthesis of nanoparticles

Contents

14 - 15 Biopharma by design 16 - 17

Protecting the nation

18 - 19 Investing in the future of drug discovery 20 - 21 Rapid, automated isolation of buffy coat benefits DNA extraction 22 - 23 Reprogramming nature 24 - 25 Cavro Air Displacement Pipettor provides the key to automated sonochemical synthesis of nanoparticles 26 - 27 Making advances in the battle against autoimmune disease 27 Leading the debate 28 Events

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CORPORATE NEWS TECAN JOURNAL 3/2012

Tecan US relocates to bigger and better premises July this year saw Tecan US relocate from the Durham premises it had occupied for the past 21 years to a new, larger facility in the nearby Morrisville area of Raleigh. This new base offers scalable space and additional training rooms to meet the needs of continued growth over the coming years. With its high ceilings and clean lines, the new building has a very modern and sleek appearance, providing a pleasant environment for visitors and employees alike. Situated close to Raleigh-Durham International Airport, hotels, restaurants and shopping at Brier Creek, the new premises are convenient for both customers attending the Company’s training facility and commuting employees.

Tecan US staff assembled outside the new premises

Cutting the ribbon at the opening ceremony

Careful planning enabled the relocation to be completed over the course of one weekend, as Peter Hornbach, Vice President of Operations, explained: “We closed slightly early on the Friday, and moved the IT portion of the business that evening. That was followed by 64 truckloads of equipment and, by mid afternoon on Saturday, we had actually moved everything in. We cleaned up on Sunday, and

Cornelias celebrates 25 years at Tecan Celebrations were in order in June, as customer service representative Cornelias Rushing reached the landmark 25 years of service at Tecan US. Cornelias joined Tecan in 1987, and has seen many changes, as she explained: “When I joined Tecan, it had been working out of a garage at the home of a former President in Chapel Hill. I came on board shortly after the Company relocated and, since then, I have been involved in two more Company moves; it’s been interesting, because each time Tecan goes up another

level. Before I joined the Company I was working in local government, so this was a really new area for me, seeing products such as the RSP 5000 and the MegaFlex.

The product range has grown and improved over the 25 years I have been working here.

When I started, the Company was just celebrating the acquisition of Cavro Scientific Instruments, and detection products were not even a part of Tecan. That’s how far my days go back!”

“My actual anniversary date was Friday June 29th, and I had been told to make sure I was in the office on that day at a certain time, but nobody would tell me why. As it was my anniversary date, I just figured they would give me my long service award, I didn’t expect anything extra. Instead, they surprised me with a beautiful cake and a

were open for business as usual on Monday morning. Everyone was very motivated and worked together, and the move went really smoothly. Everyone is thrilled with the new base, and we are very proud of the premises.”

To contact Tecan US, call +1 800 352 5128 or email sales-americas@tecan.com

“…never in my wildest dreams did I imagine being here 25 years. It’s been great, truly, a blessing.” reflections video, with pictures of me in different aspects over the years. Some of the photos were of events I had forgotten even happened, so it was really nice and I got a bit teary-eyed. The whole Company came together for the celebration and it was wonderful. I really, really appreciated it. I came here looking for a job that I could connect with, but never in my wildest dreams did I imagine being here 25 years. It’s been great, truly, a blessing.”

Corporate News TECAN JOURNAL 3/2012

Tecan enjoys success at 2012 SLAS Asia Conference and Exhibition Tecan attended the 2012 SLAS Asia Conference and Exhibition at the Grand Hyatt Shanghai, China, from 19th to 21st of June 2012. This international event hosted approximately 350 delegates over three days, bringing together research scientists and business leaders from academia and industry to discuss this year’s topic: Advances in Drug and Life Sciences R&D Through Laboratory Technology. The Conference’s educational program featured renowned local and international speakers, with presentations covering a wide range of topics related to drug discovery, from high throughput screening to the use of stem cell technologies.

Tecan China demonstrated the many advantages of automated liquid handling processes in drug discovery and life science applications in the exhibition hall, enjoying a steady flow of delegates to its booth.

A number of state-of-the-art automated solutions were in action on the booth, including a powerful Freedom EVO® drug discovery workstation equipped with a MultiChannel Arm™ 384 (MCA 384), the top class Quad4 Monochromators™-based Infinite® M1000 PRO microplate reader and the innovative HP D300 Digital Dispenser.

Tecan China’s strong multi­disciplinary team

of sales, service and applications specialists was joined by both Andrea Beccari – Global Head of Sales, Service and Commercial Operations – and Head of China and South East Asia Raymond Chan, and the event provided many opportunities to speak to key opinion leaders in the field in a relaxed environment.

Alongside the main conference and exhibition, Tecan hosted a tutorial on the launch of two new products. The new Infinite M1000 PRO multimode microplate reader with AlphaScreen® and AlphaLISA® technology was introduced by Marketing Application Specialist at Tecan Austria Dr Christian Oberdanner. Christian, who arrived at SLAS fresh from a highly successful series of roadshows to promote this powerful new system, explained the benefits of the system’s highly acclaimed absorbance, fluorescence and luminescence scanning capabilities for academic, biotechnology and pharmaceutical research. The HP D300 Digital Dispenser was also launched at the event by Dr Yingguang Wu, Head of Marketing for the Asia Pacific region. This revolutionary sample preparation tool has the potential to streamline the drug discovery process, and received widespread interest from delegates.

Tecan staff and customers were able to discuss the many drug discovery applications of the Freedom EVO workstation

Dr Christian Oberdanner introduced the new Infinite M1000 PRO reader

The 2012 SLAS Asia was hailed a great success for Tecan, once again highlighting the Company’s innovation-driven solutions and customer-focused approach to laboratory automation for drug discovery and life science laboratories.

PRODUCT NEWS

Increased flexibility and choice for Cavro® Centris Pump The state-of-the-art Cavro Centris Pump is now available with a range of glass syringes and plastic valves to complement the existing portfolio of long-life ceramic components.

These new options provide customers with a greater choice of materials to suit their instrument design, bringing the advanced features of the Cavro Centris Pump to a wider range of applications.

The Cavro Centris Pump is a compact, UL-recognized syringe pump module for use in OEM laboratory instruments. Offering exceptional liquid handling characteristics – with flow rates from 5 nl/s up to 5 ml/s – it sets new industry standards for accuracy,

reliability and precision. A hallmark of the Cavro Centris Pump is its elegant and robust drive mechanism, offering a broad dynamic range from a single syringe size, and the advantages of this innovative design are now available to customers wishing to use cost-effective glass syringe and plastic valve options. Already widely used throughout the Tecan Cavro range, these high quality glass and plastic components retain the premium performance benefits of the Cavro Centris Pump, while reducing the installed cost for applications which do not require the exceptional durability offered by a ceramic fluid path. Now, more than ever, you can truly tailor your Cavro Centris Pump to your instrument and application requirements.

To find out more on Tecan’s Cavro Centris Pump, visit www.tecan.com/components

The Cavro Centris Pump offers a choice of glass or ceramic syringes

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Corporate NEWS TECAN JOURNAL 3/2012

40 years of Cavro® As we reach the milestone anniversary of 40 years of Cavro, Tecan Systems’ Site Manager Nora Tryhorn takes stock and looks forward to a prosperous and successful future for Tecan’s components business.

Our business Tecan’s name is synonymous with excellence in the world of OEM components. For 40 years now Tecan Cavro brand components have provided innovative and reliable liquid handling for instrument designers for almost any application. Our outstanding Tecan Systems team of 104 employees is based in San Jose, in sunny California. Together, our vision is to be the best-in-class – a world class manufacturer and a design center of excellence for Tecan.

87. n 19 ro i Heinz v a f C t), and on o isiti ro (lef ecan u q T ac av s of of C an’s Tec under ounder g tin e, fo the f t bra Cele y Roch one of , r p r l e a J lan p b A

A n ea rl y Ca vr o em w or ki ng on a pu m pl oy ee p

“I’ve worked in other companies and the people in Tecan are just different. Tecan Systems has really good employees who work hard, but also take the time to get to know each other.”

s at p r e m is e o r v a C vale, Early e, Sunny iv r D o k l 1234 E

Diana Morikawa, Director of Logistics and Production

Our products

Our customers

Tecan Cavro components work robustly and efficiently in applications that are critical to society as a whole. We are very aware of the huge impact our products have on public health and safety.

Talking to our customers during the entire development cycle of our products makes so much sense as we create exactly what is needed. We pride ourselves on our excellent communication channels and long-term relationships with our customers.

“The products we make at Tecan touch so many lives. We are all very proud to work for a company that makes such great products.”

Tawni Kestel, Purchasing Supervisor

“I'm proud to be part of our service department, taking on all the responsibilities that are involved.”

Bob Jackson, Service Technician

Cavro milestone timeline 1972 Cavro Scientific Instruments founded ey ob C a v en t) a n d B ef (l o te r v h a oc r s of C J er r y R ea r ly y ea e th in a t w or k

1997 MiniWash Pump, Smart Valve, Smart Peristaltic Pump

1980 Model 1500/2000 Pipettor/Dilutor

1997 MSP 9500

1985 IQ 190 Sample Processor

1994 MSP 9000

1986 SB 1200 Pump 1987 Tecan acquires Cavro 1989 RSP 9000

1994 XP 3000 1992 XL 300X 1990 XL 3000

Corporate News TECAN JOURNAL 3/2012

ro’s v a C e as tativ 2 n 9 e s 19 in epre n R r o ryh ervice T S a Nor tomer Th e Cus

Te can Sys tem s’ Sa les Te am . Le ft to rig ht ; Br uce Ste ffe r (US ), Je rr y Ma ur ice (US ), Wil li Kr att enm ach er (Eu rop e), Ch uck Fon tan a (US )

Jerry Rochte (right) and a Cavro colleag ue workin g on a pump

always room for improvement and we will continue to work hard as a team to make things better.

CA

Torleif Björnson, Director R&D

Our lean working principles We started implementing lean manufacturing in 2009 and continue to strive for the utmost efficiency. But lean principles are based on a philosophy of constant improvement and we’ll keep working to consistently find a better and faster way to do things.

R ey P an gi lin an at w or k in 19 84 – an ea rl y em p lo ye e w h o is st ill w or ki ng at th e Co m p an y to da y!

Our quality We’ve done a great job of improving our quality over the years and have seen significant improvements in our customer satisfaction levels since 2006. But there’s

“My proudest moment at Tecan was being the first person to build the new Cavro Omni Robot.”

or g flo c t u r in r e v io u s a f u ’ p man es stems The a n S y r t p r e m is c e T u o at C boldt Hum

Our people

“My proudest achievement at Tecan Systems is the high level of productivity and quality accomplished by our relatively small R&D department.”

For Tecan Systems, the secret of our success is undoubtedly our employees, several of whom have worked here for many years.

We have a great team of extremely capable people who work hard and, most importantly, have a real passion for their jobs; everyone at Tecan Systems cares about the customer.

We asked our employees what’s the best thing about working for Tecan Systems, and the answer was resounding…..THE PEOPLE!!

“We are one big happy family, helping each other!”

Jose Rodriguez, Material Handler To find out more about Tecan Cavro components, visit tecan.com/components

Kenny Tran, Track Assembler

2008 Cavro Integration Kit 1999 XE 1000 2001 Cavro relocates

to 2450 Zanker Road 2002 MSP 9250 2002 Cavro name change to Tecan Systems

2007 Cavro ceramic valves 2006 Cavro XMP 6000 2005 Cavro XLP 6000 2004 Cavro XCalibur Pump 2003 Freedom EVO® 75

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2008 Cavro Centris Pump 2008 Cavro Omni Robot 2010 Cavro ADP 2011 Cavro Omni 8-channel option, Cavro Omni gripper

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Corporate NEWS TECAN JOURNAL 3/2012

Cornell Cup success for Tecan-sponsored team A Tecan-sponsored team of students from the Weiss Laboratory for Synthetic Biology at the Massachusetts Institute of Technology (MIT), USA, recently enjoyed success at the Cornell Cup USA competition in Florida. The team came third in this inaugural running of the competition, taking advantage of the performance of a Cavro® XCalibur Pump on loan from Tecan to develop a novel and innovative liquid handling system.

The Cornell Cup USA is an embedded design competition created to empower student teams to become inventors. Sponsored by Intel, the competition was run for the first time this year, and is based on the success of the Intel China Cup, which attracts entries from over 26,000 students. Held in May at Walt Disney World’s Contemporary Resort on Lake Buena Vista, Florida, the MIT’s entry in the competition was supported by Tecan.

Dr Jonathan Babb, advisor of the MIT team, explained: “Five of our students entered the Cornell Cup USA as ‘Team Squirtle’, with $500 sponsorship from Tecan for their expenses. The team’s project brief was to design and build a smaller, lower priced and more intelligent liquid handler that would provide individual researchers with a tool for fast, accurate and tailored pipetting to meet their liquid handling needs. The students had considered making their own pump, but identified that this key component of their custom liquid handler would be very challenging to build in the time available. As Tecan was already sponsoring the team, we asked if we could use one of the Company’s pumps. We were kindly lent a Cavro XCalibur Pump (XC Pump), and the students were shown how to set up and use it.”

Jonathan continued: “Tecan’s help was invaluable, making it easy for the students to integrate the pump and connect it to their software. This allowed the team to focus on the innovative aspects and architecture of the robot, creating a system that is quite different from conventional liquid handling instruments. Their solution was a delta parallel robot with three jointed arms coming together into a point. The arms are each controlled by a servo and motor, allowing the user to determine the exact location

The winners were announced at the America Pavilion in Disney’s Epcot Center. Left to right: Jonathan Babb, Kevin Linke, Huayu Ding, Agustin Venezuela, Cory Li

Team member Agustin Venezuela demonstrates the prototype to the competition judges

‘Team Squirtle’ was awarded third place and received a $2,500 check for the development of a new liquid handling robot using the Cavro XCalibur Pump

of the pipetting tip. This design, which was inspired by the high-speed, pick and place assembly line robots used in the electronics industry to position chips on circuit boards, came third overall, winning a prize of $2,500.

The project was all about making one tip go faster, rather than adding more tips as in conventional liquid handling systems, and we are grateful to Tecan for its support.”

To find out more about Tecan’s Cavro XCalibur Pump, visit www.tecan.com/components To find out more about the Cornell Cup, visit www.systemseng.cornell.edu/intel The team would also like to acknowledge the following co-sponsors: BBN Technologies, HighRes Biosolutions, Qiagen, Intel, Tektronix, Cornell, the MIT Department of Biological Engineering and the MIT EECS department.

Corporate News TECAN JOURNAL 3/2012

Tecan Symposium comes to Boston The fifth annual Tecan Symposium will be visiting the historical US coastal city of Boston, Massachusetts, from the 23rd to the 25th of October. Building on the success of previous events, this popular scientific meeting is being hosted by Tecan in the US for the first time, and will bring together key opinion

leaders from around the world to discuss the expanding role of mass spectrometry (MS) in life sciences and diagnostics.

This year’s scientific program will cover a broad range of topics related to MS, and will be divided into four sessions: the role of MS in basic research; collection, preparation, and storage of samples for MS; MS as a diagnostic tool; and the use of MS in applied markets.

Supported by a number of social events, this diverse agenda is designed to attract a truly multidisciplinary audience. As in previous years, places at the Symposium are limited

Boston 2012 fifth Tecan

Symposium

to ensure plenty of opportunities for open discussions and networking, giving speakers and delegates the chance to explore novel concepts, applications and solutions that might help to address unmet scientific needs, while enjoying Tecan’s hospitality.

To find out more about the Tecan Symposium, including details regarding free registration, visit www.tecan.com/symposium

Tecan Symposium key speakers Prof Sabine Becker BrainMet: novel avenues of bioimaging mass spectrometry of metals and biomolecules from micrometer to nanometer scale in the brain Prof Mitsutoshi Setou Meta-analysis of histopathological lipidomics Dr Feixia Chu Sample preparation of ancient protein samples from amber encapsulated organisms Dr Gary van Berkel Laser ablation and liquid extraction surface sampling for ambient surface sampling/ ionization MS Dr Jeffrey Hurst Chocolate spectrometry: applications of mass spectrometry in cocoa and chocolate research Dr Michael Vogeser Pitfalls associated with the use of liquid chromatography-tandem mass spectrometry in the clinical laboratory Prof Xuefan Gu Neonatal screening using tandem mass spectrometry

Dr John Brennan Mass spectrometric methods for biological screening of small molecule mixtures

Dr Andrew Hoofnagle Developing methods for LC-MS-based clinical diagnostics

Dr Nigel Clarke Mass spectrometry as an enabling technology in the clinical laboratory

Dr Mark Libardoni The role of mass spectrometry in solar system geochemistry and planetary atmospheres: past missions to state-of-the-art instrument development

Dr Graham Bench Emerging trends and technologies enabling ultrasensitive 14C measurements for biomedicine Dr Paul Tempst Aminopeptidase activities as biomarkers for cancer Dr Judith Stone Automating high throughput LC-MSMS analysis of 25-hydroxy vitamin D using liquid handlers and middleware Dr Robert Moritz The human SRMAtlas: a compendium of quantitative mass spectrometry assays for all human proteins

Dr Burak Eral eMaldi: suppressing the coffee stain effect via electrowetting for improved Maldi-MS detection Dr Zoltan Takats Mass spectrometric profiling of biological tissues: a comprehensive alternative to classical histopathology Dr Stuart Black The application of stable isotope radio mass spectrometry for forensic analysis of human skeletal remains Dr Mehdi Moini Biological clocks: high throughput identification of deterioration markers and dating of museums' proteinaceous specimens

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Corporate NEWS TECAN JOURNAL 3/2012

Tecan showcases the Freedom EVO® workstation configured for ELISAs to delegates visiting from Chinese blood centers Delegates from blood centers across China recently enjoyed a visit to Tecan’s European development facilities in order to share their experiences and give their input on performing high quality ELISAs within blood banking laboratories. Tecan demonstrated a Freedom EVO workstation specifically configured to meet the ELISA throughput demands observed in the Chinese clinical market, incorporating a range of features to streamline the blood testing workflow.

Efficient throughput is critical in hospital and blood center laboratories, requiring reliable automated solutions which are closely matched to laboratory workflows.

The Freedom EVO offers a flexible configuration which can be tailored to individual throughput requirements, with a choice of either one or two liquid handling arms, up to two HydroFlex™ microplate strip washers, a Robotic Manipulator (RoMa) Arm for plate transportation and an Infinite® F50 microplate reader. The specific requirements of the scientist’s assay can be fulfilled by the use of a variety of incubators, hotels and carriers, providing complete automation of the processing workflow.

The Freedom EVO is controlled by Tecan’s intuitive Freedom EVOware® software, and uses the TouchTools Suite™ graphical user interface (GUI) to simplify day-to-day operation of the instrument. Combined with Tecan’s new QC Kit for liquid handling performance verification testing, this flexible solution provides hospitals and blood centers in China with a straightforward and efficient way of automating testing.

Delegates from Chinese blood centers visit Tecan

The visit was arranged in response to increasing demand for automated laboratory systems in Chinese hospitals and blood centers, and reflects Tecan’s close collaboration with customers. This year’s event built on the success of the previous visit to Tecan’s Männedorf headquarters in Switzerland in 2010. In addition to seeing Tecan automation in action, delegates were given the opportunity to visit Tecan manufacturing sites in both Männedorf and Salzburg, Austria, as well as a visit to a Zurich blood bank to foster relations and exchange blood bank practices. The visit also included workshops on various aspects of potential

development, providing customers and Tecan specialists with an opportunity to discuss current and future applications, as well as the bottlenecks in processing, helping to drive forward identification of novel solutions for this important market.

DRUG DISCOVERY TECAN JOURNAL 3/2012

Joining the digital age TES Pharma is a specialist biotechnology company which performs molecular, cellular and ADME screening for drug discovery. The Company has recently purchased an HP D300 Digital Dispenser, and is now reaping the benefits of direct titration with improved assay reproducibility and more time to perform exploratory research.

TES Pharma is a small biotechnology company based in Corciano near Perugia, Italy, specializing in compound screening for pharmaceutical drug discovery. Combining an in-depth knowledge of drug design and chemistry with systems and molecular biology approaches, the Company works collaboratively with partners around the world to combine the best aspects of academia and commercial pharmaceutical development.

TES Pharma’s small yet highly skilled and experienced team works closely with the University of Perugia to rapidly develop and explore novel compounds which may be of interest in various disease states.

To standardize the Company’s workflow, as well as to free up more staff time for research activities, TES Pharma has recently invested in an HP D300 Digital Dispenser from Tecan. Graeme Robertson, a co-founder of TES Pharma, explained: “The drug discovery process is becoming increasingly highly specialized, often involving multiple partners with distinct skill sets working together to deliver novel therapeutic agents. Our core competence at TES Pharma lies in the development of advanced screening assays, and we believe that, by working closely with academic partners with expertise in individual conditions or disease areas, we can eliminate some of the drawbacks inherent in traditional drug discovery pipelines.”

“To do this we need to concentrate on our own expertise in core areas, and our HP D300 Digital Dispenser allows us to use our time more effectively, without compromising on results. As a small collaborative research facility we do not have a high enough throughput to effectively use complete laboratory automation systems,

Senior scientist Francesca De Franco displays TES Pharma’s HP D300 Digital Dispenser

but the HP D300 is easy to use and its precision dispensing eliminates the need for tedious manual dilutions. Digital titration also offers several key advantages over traditional manual protocols in terms of reducing waste of valuable compounds, limiting the DMSO content for sensitive assays and increasing reproducibility, but it is the staff time it creates that is most important, liberating skilled individuals to perform more exploratory research. It also allows us to limit the number of variables in a way that would not be possible manually, helping us to rapidly characterize novel biological activities which might otherwise be missed.”

To find out more about Direct Digital Titration, visit www.tecan.com/digitaltitration To find out more about TES Pharma, visit www.tespharma.com

“ The HP D300 is easy to use and its precision dispensing eliminates the need for tedious manual dilutions.”

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READERS TECAN JOURNAL 3/2012

A winning combination for nephrology research In the last edition of the Tecan Journal we announced the winner of the Tecan Award 2011, Svenja Kristina Holle from the University Hospital of Münster, whose team has developed an ex vivo method for investigating the dynamics of organic cation transport in proximal tubules of the kidney, using an Infinite® 200 PRO microplate reader.

Svenja Holle

“ We can now study 100 assays at one time, which has increased the number of experiments that can be carried out with one animal enormously.”

F irst place

Siegfried Sasshofer presents Svenja with the Tecan Award 2011

The Experimental Nephrology laboratory of the Department of Internal Medicine D at the University Hospital of Münster (Universitäts Krankenhaus Münster – UKM), Germany, has used Tecan’s Infinite 200 PRO microplate readers to further develop its cell-based techniques for the investigation of cell membrane transport in the proximal tubules of the kidney. The team has established a novel ex vivo fluorescence technique which enables parallel analysis of numerous samples in a 384-well microplate format, making this type of study far easier to perform, while significantly increasing the number of experiments which can be carried out with a limited amount of biological material. Svenja, a medical student at UKM, explained: “Organic cation transporters (OCTs) are crucial for the renal excretion of endogenous organic cations such as the monoamine neurotransmitters dopamine and noradrenaline, as well as the 40-50 % of pharmaceutical drugs that are positively charged. Until now, organic cation transporters could only be examined using time-consuming fluorescence or radiotracer methods; the technique and set-up procedures were very tedious. We have successfully used our Infinite 200 PRO readers – we have both an Infinite M200 PRO and an Infinite F200 PRO – to develop a microplate reader-based method that can be adapted to almost any kind of freshly isolated biological material and transport system by using a suitable fluorescent substrate. The method enables us to study OCTs in freshly isolated proximal tubules of mouse kidneys, an ex vivo environment, and has significantly increased

our throughput, as we can now place three proximal tubules in each well of a 384-well plate, depending only on the isolation capacity.”

The properties and regulatory mechanisms of organic cation transport in proximal tubules of mouse kidneys are of particular interest with regard to the emerging role of transgenic mouse models in pharmacological, physiological or pathophysiological studies.

Svenja continued: “We investigated the dynamics of organic cation transport by flux experiments with a fluorescent transporter substrate, ASP+, which undergoes a shift in the emission spectrum from 550 nm to 590 nm when it is transported into cells.

Each individual well of a 384-well microplate accommodates three segments of freshly isolated mouse proximal tubules, each approximately 200 µm long. ASP+ is added to each well, and the increase in cellular fluorescence is recorded. By making fluorescence measurements, we can quantify cellular accumulation of ASP+, which is proportional to the extent of organic cation transport. We can also take advantage of the Infinite 200 PRO’s dual injection module to study the properties of OCTs to determine the affinities of known or unknown substrates; substrates with high affinities to organic cation transporters will inhibit the uptake of ASP+. The method also allows us to screen for substrates and drugs which interfere with OCTs, which may open new therapeutic approaches to reducing drug-induced damage of the kidney by nephrotoxic drugs.”

READERS TECAN JOURNAL 3/2012

Previously, UKM’s Experimental Nephrology laboratory analyzed the dynamics of OCT processes using an inverted fluorescent microscope imaging system, but this restricted measurement to a very small number of isolated tubule segments per kidney and animal, due to tedious and time-consuming set-up procedures for each segment. “The new method is far easier to use, and does not require a lengthy training period. Before, we could only examine one tubule at a time using the inverted microscope, but the new microplate reader-based technique allows us to perform several assays in parallel. We can now study up to 300 assays at one time, which has increased the number of experiments that can be carried out with one animal enormously; this is a huge advantage and has significantly reduced both the time and cost of experiments,” concluded Svenja.

To find out more on Tecan’s Infinite 200 PRO series, visit www.tecan.com/infinite200pro

As the 2011 winner of the Tecan Award, Svenja’s prize was a weekend in the romantic city of Salzburg, which included a tour of Tecan’s Detection Headquarters in Grödig, Austria. Svenja described her visit to Austria: “Our trip to Salzburg began with a short visit to Tecan’s production site on Friday morning. It was really interesting for me to see the inside of the microplate reader that I’ve worked with for such a long time, and to hear about other promising developments at Tecan. I gave a presentation about my research, and I really appreciated everybody’s interest in my work; we had a valuable discussion and I received some really good suggestions for improving our technique even further.”

“Afterwards, it was a great honor for me to receive the Tecan Award. The rest of the weekend was spent enjoying the sights of Salzburg. Of course, we took the hard climb up to Hohensalzburg Castle, where we were rewarded with an amazing view over the city and the panorama of the Alps. We also loved having the delicious breakfast in our fantastic hotel right beside the Salzach, the river which parts Salzburg into its historic city centre and the new town. All in all, we will always remember our great weekend trip to Salzburg with a smile!”

Svenja prepares to analyze samples in the Infinite 200 PRO

To find out more about UKM’s Experimental Nephrology laboratory, visit www.campus. uni-muenster.de/892.html?&L=1

Hohensalzburg Castle, one of the largest medieval castles in Europe

Svenja enjoying an informative tour of Tecan’s production site

Svenja and Richard enjoying the magnificent view across Salzburg

The Salzach river in Salzburg

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DRUG DISCOVERY TECAN JOURNAL 3/2012

Biopharma by design Isogenica provides peptide, protein and antibody discovery and design services to pharmaceutical and biotechnology companies, and has invested in two Freedom EVO® liquid handling platforms to increase its capacity for the selection of next generation molecules.

Isogenica Ltd, based at Chesterford Research Park near Cambridge, UK, specializes in the discovery, identification and design of new therapeutic peptides, proteins and antibodies for pharmaceutical and biotechnology companies. The Company’s proprietary technology – CIS display – enables rapid library construction and selection, generating faster hits and better leads to reduce discovery time and improve the quality of candidate options. To meet the demand for higher throughput, Isogenica has purchased two Freedom EVO 200 platforms for the selection of next generation molecules and for running ELISAs. Neil Cooley, Operations Manager at Isogenica, explained: “Our clients provide us with a target molecule and we use our CIS display technology to discover binders to that target. We have automated this technology on the Freedom EVO platform to make it less labor-intensive and to increase our throughput, allowing us to do more of these selections in parallel.”

Tecan held comprehensive discussions with Isogenica to establish the Company’s exact needs and design the most appropriate platforms for their selection and ELISA protocols. Two Freedom EVO 200 workstations were chosen, each equipped with a Robotic Manipulator (RoMa) Arm, an eight-channel Liquid Handling (LiHa) Arm with low-volume disposable tips and a MultiChannel Arm™ (MCA) 96. The selection platform also has an integrated Infinite® F200 PRO multimode reader for PicoGreen® analysis of DNA levels,

an LPT 220 EVO™ Carousel, an extended Z-axis RoMa, low disposable tip ejector option and a dust cover, and is used to run a protocol based on the Company’s CIS display technology. This platform also takes advantage of Tecan’s SBS format disposable tip boxes, allowing large quantities of tips to be stored on the Carousel for increased walkaway times.

Neil continued: “Tecan offered a cost-effective solution and the Company has a good reputation; we also liked the training that was provided with the system. They took the time to get to know exactly what we needed and to ensure that we understood what options were available to us – and the advantages of each option – including presentations that explained the benefits of different semi-automated versus fully integrated systems. It was particularly tricky deciding whether to have everything integrated on the candidate selection platform or not, where to put all the options we needed and how to get the highest throughput.”

Although the Company has had the workstations for less than a year, the advantages of automating the selection protocol can already be observed. Automating the process enables multiple target molecules to be tested against a number of libraries under different selection conditions, offering the capability to multiplex across a 96-well plate. This provides more versatility

“... the big advantage of automating the selection process is that it allows a larger number of selection conditions and different types of library – peptides, scaffolds or even antibodies – to be tested with their target molecule, providing them with greater choice.”

and improves consistency, which is an important consideration, as well as allowing many more selections to be performed than would be possible manually. The maximum number of selections that can be comfortably performed at one time manually is 12 to 16.

In contrast, the microplate format used by the automated process enables 96 selections to be performed simultaneously.

Automation of the DNA/protein binding ELISA protocol on the Freedom EVO has also proved popular with staff, and has significantly increased Isogenica’s screening capacity. When the ELISA is semi-automated using 96-well plates, one person can process

DRUG DISCOVERY TECAN JOURNAL 3/2012

Isogenica’s selection platform offers multiplexing capabilities in a 96-well format

up to 48 plates a day. Automation has also enabled the Company to miniaturize its assays into 384-well plates, which allows many more clones to be screened with the same targets in the same time period. “We need to keep the amount of target used to a minimum, and moving to 384-well plates reduces the amount of material we need,” said Neil. “The platforms’ ease of use has also encouraged widespread use of the systems; staff became comfortable with operating the instruments very quickly. As a result, we have extended the functions that we currently carry out on the Freedom EVO beyond those initially envisaged.”

Isogenica’s clients also reap the benefits of automation. When a larger number of selections need to be performed, it is now possible to run one large batch of samples on the Freedom EVO, rather than several small batches manually, enabling more rapid and consistent delivery of peptide or protein candidates. “For our clients, the big advantage of automating the selection process is that it allows a larger number of selection conditions and different types of library – peptides, scaffolds or even antibodies – to be tested with their target molecule, providing them with greater choice,” concluded Neil.

To find out more on Tecan’s drug discovery solutions, visit www.tecan.com/drugdiscovery To find out more about Isogenica, visit www.isogenica.com

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GENOMICS TECAN JOURNAL 3/2012

Protecting the nation Russia’s Central Tuberculosis Research Institute is using a Freedom EVO® workstation to help in the fight against tuberculosis. The platform provides fast and secure sample preparation, allowing molecular diagnosis of M. tuberculosis infection in just a few hours.

Founded in 1921, the Central Tuberculosis Research Institute of the Russian Academy of Medical Science (CTRI RAMS), Moscow, is a global leader in the development and application of advanced techniques for the effective control of tuberculosis (TB).

The Institute consists of nine research divisions, including four 400-bed clinical departments, and the Institute’s multidisciplinary research team studies every aspect of the diagnosis, pathology and transmission of TB. Diagnosis of TB, and determination of antimicrobial sensitivity, generally takes 6 to 14 weeks using classical microbiological methods, delaying provision of appropriate treatment and contributing to the high TB-associated mortality rate in Russia.

To reduce this lengthy detection time, the CTRI RAMS’ Department of Microbiology – led by Professor Larisa Chernousova – is investigating new approaches to improve the diagnosis of tuberculosis, including a novel genetic technique based on PCR (polymerase chain reaction). Larisa explained: “A vital step in this highly sensitive method is the extraction of DNA from patients’ sputum samples. This is a monotonous and labor-intensive process when performed manually, requiring high levels of concentration to avoid cross-contamination between samples and subsequent false positive results, and so is ideally suited to automation.”

Working in collaboration with Syntol – a specialized clinical diagnostic company in Russia – the Institute has developed an automated protocol that allows safe and effective handling of potentially highly contagious M. tuberculosis samples without the need for costly biosafety measures.

This technique uses an inactivation buffer to kill any mycobacterium present, offering safe handling of patient material without compromising the quality of the extracted DNA. The workflow was initially developed on a Freedom EVO 75 before being transferred to the Department’s Freedom EVO 150 workstation. It includes dilution of the sputum samples and addition of the inactivation buffer using the instrument’s Liquid Handling (LiHa) Arm, magnetic extraction of the M. tuberculosis DNA from clinical samples and microbial cultures, transfer of the extracted genetic material to PCR tubes, and online PCR amplification.

Professor Chernousova continued: “Extraction of 48 samples takes just 95 minutes, allowing us to process up to 144 samples a day if required. Once the extraction process is complete, the recovered DNA is transferred directly to PCR tubes and automatically loaded onto a thermocycler for amplification. This provides true walkaway processing and significantly increases the laboratory’s throughput, while also lowering the cost per test.”

“Even a microdrop of aerosol containing genetic material could cause contamination in this process, but none of our negative controls showed amplification by PCR.”

GENOMICS TECAN JOURNAL 3/2012

From left to right: Professor Larisa Chernousova, Tatiana Smirnova and Dmitry Varlamov from the CTRI RAMS’ Department of Microbiology

Due to the high sensitivity of the PCR-based technique, minimizing the risk of errors and cross-contamination was crucial, and so the laboratory carried out rigorous testing and validation prior to bringing the Freedom EVO 150 platform into routine operation. “We were very happy with the performance of the system during our carry-over studies,” Larisa added. “Even a microdrop of aerosol containing genetic material could cause contamination in this process, but none of our negative controls showed amplification by PCR. We have also been impressed by the flexibility and open architecture of the platform, and now plan to use additional Tecan workstations for complete automation of our bacteriology workflows in the future – from preparation of reagents and media to culture seeding and incubation.”

In the first four months of operation, the laboratory has prepared over 500 clinical samples for analysis. The Freedom EVO workstation offers considerable time savings while reducing the labor required. “This helps the laboratory to identify the causative agent of a patient’s symptoms much faster, providing clinical staff with the right information to effectively treat patients far earlier,” Professor Chernousova concluded.

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

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DRUG DISCOVERY TECAN JOURNAL 3/2012

Investing in the future of drug discovery Osaka University’s International Drug Discovery Incubation Group opened its doors to drug discovery researchers in western Japan in April 2011, providing access to high throughput technologies including Tecan’s Freedom EVO® liquid handling workstations and Infinite® M1000 microplate reader.

In Japan, Osaka has been known as the city of medicine since the 17th century.

The chemical industry, helped particularly by pharmaceutical companies, is today the most lucrative of Osaka’s industries and shows great promise for future growth.

This setting is ideal for the International Drug Discovery Incubation Group at Osaka University’s Office for University-Industry Collaboration to serve as a shared-use facility funded by the Japan Science and Technology Agency (JST). The Group’s primary purpose is to accelerate collaborative research between academia and industry by directly supporting the drug discovery research activities of universities and businesses throughout the Kansai region of Japan.

Dr Yoon-Jeong Kim, Leader of the International Drug Discovery Incubation Group, explained how the thinking behind much of the Group’s strategy stems from the pharmaceutical industry’s ‘gap issue’.

Dr Yoon-Jeong Kim

Osaka University’s International Drug Discovery Incubation Group

“The whole process from hit discovery to final drug-to-market was traditionally handled within a pharmaceutical company. It would routinely take 15 to 20 years for a new target to be developed into a drug which would have a 25 year patent, resulting in the actual trading life of 10 years for that drug. In the early 2000s, an average candidate success rate was only one in ten thousand. As a result, pharmaceutical companies began to focus their activities on the later phases of drug development, to help them recover their investment more quickly. At the same time, they tried to extend the period of the patent of drugs that were already on the market by changing the drug formulation.”

“Universities continued to work on early stages of drug discovery and the discovery of new targets, but a gap between this work and the later development phases performed by pharmaceutical companies began to widen. As a result, there are very few new

candidates coming through the drug discovery portfolio. With a rush of patents having expired around 2010, many companies are now struggling to maintain a steady stream of business revenue.”

“This gap is a big problem throughout the pharmaceutical industry which must be addressed. We are tackling this issue head on by furnishing our laboratories with a variety of modern, high throughput instruments and employing methods that traditionally only pharmaceutical companies would have used.”

The Group has two Freedom EVO workstations: a Freedom EVO 100 used mainly for plate replication, and a custom-configured Freedom EVO 200 equipped with a Liquid Handling Arm, an integrated incubator, a Tecan Carousel HS™ for microplate logistics, a plate washer, and an Infinite M1000 microplate reader. This system is fitted with a

DRUG DISCOVERY TECAN JOURNAL 3/2012

“I remembered many strong advantages for using Tecan and I knew these would also be relevant for our Group here.”

Steering committee members of the International Drug Discovery Incubation Group. Front row, left to right: Dr Toshimasa Yasuhara, Dr Hachiro Senoo, Dr Zenichi Terashita. Back row, left to right: Dr Kazuto Nunomura, Dr Yoon-Jeong Kim and Dr Bangzhong Lin

New approach – dealing with drug discovery A strategy to fill the gap between new targets and preclinical drug discovery

New targets

Hit discovery

Hit validation

Lead optimization

Preclinical

Ph-l

Ph-ll

Ph-lll

GAP

HEPA filter because many users are performing cell-based assays which require aseptic conditions. Plates are transferred automatically to the Infinite M1000 to collect the data for some assays, but both the reader and the plate washer can be used independently, even while the Freedom EVO 200 is performing unrelated tasks.

Dr Kim added: “These instruments are very popular, and are being used almost every day.

Many scientists who use our facilities are performing high throughput (HT) methods for the first time and, as an organization dedicated to supporting research, we provide a substantial amount of specialized training as required. We teach various techniques from how to process compounds and set up cell-based assays to data collection, and we train researchers so that they can independently perform HT methods themselves. In reality, this probably forms the bulk of our work.”

Dr Kim had already had positive experience of working with Tecan’s liquid handling workstations from his earlier career in a major pharmaceutical company: “I remembered many strong advantages for using Tecan and I knew these would also be relevant for our Group here. Tecan has a lot of experience in the types of applications we were looking for. We wanted a HT robot that allows many tasks to be performed by a small number of people, and Tecan’s Freedom EVO workstation was chosen as a platform to fulfill this concept. We were confident that the Company and its instruments would be a good fit for our laboratory. Tecan’s technical staff members are constantly in touch to support us and ensure that the instruments are working as efficiently and reliably as possible.”

He concluded: “In the future, we plan to develop our group with the addition of more instruments that would benefit researchers

who use the Incubation Group’s facilities.

Clearly, if we stick to the old ways of doing things, we will inevitably meet difficulties.

There are always processes that need new techniques to push them forward and, with a broad range of innovative instruments, we are working to build a set-up that will do just that.”

To find out more on Tecan’s Freedom EVO liquid handling workstation, visit www.tecan.com/freedomevo To find out more on Tecan’s Infinite M1000 microplate reader, visit www.tecan.com/infinitem1000 To find out more about the International Drug Discovery Incubation Group at Osaka University, visit www.uic.osaka-u.ac.jp/JST/index.htm (Japanese)

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Biobanking TECAN JOURNAL 3/2012

Rapid, automated isolation of buffy coat benefits DNA extraction

Tecan and the Integrated BioBank of Luxembourg (IBBL) have successfully co-developed an automated platform for buffy coat extraction based on a Freedom EVO® 200 workstation, relieving scientific staff from this time-consuming task and significantly increasing the yield of DNA. Biobanks such as the IBBL have a vital role to play in modern medical research, providing high quality biospecimens, as well as the technology and scientific expertise to enable researchers to evaluate data against medical records and environmental factors. The IBBL was established following a 2008 Government agreement to form a strategic partnership with three US research centers – the Translational Genomics Research Institute (TGen), the Institute for Systems Biology and the Partnership for Personalized Medicine.

Working closely with the Luxembourg Personalized Medicine Consortium (PMC), the IBBL collects, stores, and analyzes biological samples and associated clinical

Fay Betsou, Chief of Biospecimen Science at the IBBL

“The results are amazing; the yield is 10­-15 % higher using the automated process.”

data, from neighboring countries as well as Luxembourg itself, which are then made available to research organizations.

In addition to somatic disease collections for cancer, type 2 diabetes and Parkinson’s disease research, there is also a normal population cohort collection from healthy people – a collaboration with CRP Santé – that acts as a control.

Today, through its own investigations and partnerships with internationally recognized research centers, the IBBL’s world-class scientists are at the forefront of innovative biospecimen research. Fay Betsou, Chief of Biospecimen Science at the IBBL, commented: “Research often tends to focus on biomarker identification and validation rather than specimen validation, but this is a basic critical issue that could completely invalidate experimental results. Innovative biospecimen research is a very important – yet extremely rare – initiative that is quite specific to the IBBL.” The IBBL’s biospecimen collection and biorepository contain high quality tissues and body fluids, maintained according to strict quality requirements. The associated biorefinery analysis and research service produces high quality analytes, such as DNA, RNA and protein, maintains technology for high throughput gene sequencing and gene expression, and conducts biospecimen research.

In addition, an informatics platform securely maintains clinical and biospecimen data.

Conny Mathay explains the biobanking process to students studying for the University Certificate on Principles of Biobanking

A key target biospecimen for IBBL and many biobanks and diagnostic laboratories is the buffy coat, the layer of leukocytes and platelets that forms when unclotted blood is centrifuged or allowed to stand, and is often used for DNA extraction. Traditionally, the process of manually isolating the buffy coat from whole blood is slow, tedious and very dependant on the skill and dexterity of the technician separating the layers. To eliminate this time-consuming and variable element of sampling, the IBBL and Tecan joined forces to co-develop an automated procedure on a Freedom EVO 200 platform.

Fay explained: “Our sample throughput, although relatively low at present, is expected to increase five-fold in the near future, and we were initially looking for a flexible liquid handling system that could meet this demand.

We also have particularly strict requirements

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Thomas La Mela/Shutterstock.com

Biobanking TECAN JOURNAL 3/2012

The IBBL team with the Freedom EVO

in terms of time; it is crucial to minimize the delay between sample collection and freezing, and speed is essential. We looked at the existing options and spoke to several different suppliers before choosing Tecan.

From the beginning, we could see that as well as performing classical liquid handling, there was a real possibility of automating buffy coat extraction using the Freedom EVO. This was never going to be an easy process, largely because of the variation in individual sample volumes and the quantity, viscosity and texture of the buffy coat layer itself, but we had several meetings with Tecan’s technical teams and, over the next couple of months, worked together to co-develop an automated method.”

All of the IBBL’s blood samples initially have a hemocytometer count and CRP measurement performed to generate basic background data such as blood cell count and inflammatory status. Centrifuged blood

collection tubes are placed on the Freedom EVO platform, which is equipped with Robotic Manipulator (RoMa), eightchannel Liquid Handling (LiHa) and Pick and Place (PnP) Arms, a Tube Inspection Unit (TIU), an Xtr-96 flatbed scanner (FluidX), Xsd-96Pro and Xsd-48Pro modules (FluidX), and a BDK module to provide HEPA-filtered air on the worktable. The workstation, which is also used for aliquoting serum, plasma and urine, has been optimized to maximize the yield and quality of the buffy coat, and to minimize the risk of cross-contamination. Tubes are transferred to the TIU, which identifies the position of the buffy coat layer using a laser beam. The buffy coat is then aspirated by the LiHa using a spiral movement, and transferred to its destination tube. “The LiHa pipettes the buffy coat layer with very precise orientation and speed, standardizing the process and eliminating technician-to-technician variation,” Fay added.

During the validation process, IBBL found the automated system gave a purer buffy coat product with less contamination from red blood cells and hemoglobin and a similar distribution of white blood cells, as well as an average DNA yield significantly higher than that obtained by manual extraction.

“The results are amazing; the yield is 10-15 % higher using the automated process.

Altogether, isolating the buffy coat manually is a tortuous task but the Freedom EVO system now processes 24 samples in just 16 minutes. We are very satisfied with the system and are looking forward to working with Tecan on another biospecimen research project in the near future,” concluded Fay. To find out more about Tecan’s biobanking solutions, visit www.tecan.com/biobanking To find out more about IBBL, please visit www.ibbl.lu

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GENOMICS TECAN JOURNAL 3/2012

Reprogramming nature Researchers in the Synthetic Biology Center at the Massachusetts Institute of Technology are using a Freedom EVO® workstation to aid the development of genetic circuits. By automating the laborious liquid handling protocols, the platform has increased throughput from just a few samples to hundreds of experiments a day.

Genetic circuits are an exciting area of synthetic biology, with potential applications in areas as diverse as biofuel production and medicine. These plasmid constructs have the ability to regulate the function of host bacterial, yeast or mammalian cells, reprogramming them to produce novel substances, change appearance or exhibit different behavior. Researchers in the Synthetic Biology Center at the Massachusetts Institute of Technology (MIT), USA, are working on several collaborative projects to develop genetic circuits for a variety of applications. Dr Jonathan Babb, a researcher at MIT, explained: “If you think about it in engineering terms, we are building a machine by taking specific DNA sequences and putting them together in different combinations to form genetic circuits.

A collection of these circuits can then be loaded into a host cell, reprogramming it.

The Weiss Laboratory at MIT recently published an example of this approach, where a genetic circuit triggers apoptosis in cancer cells, but not in healthy cells, offering diagnosis and treatment in one step.

Another potential application is in biofuel development, re-engineering bacteria to efficiently produce fuels such as biodiesel.”

“Although we use a modular approach, development of these genetic circuits is still very time-consuming and labor-intensive, and so we purchased a Freedom EVO 150 platform to meet our liquid handling needs.

This platform effectively transforms what is already done in electronics – pushing buttons to activate software and hardware to produce the desired circuit – to our synthetic biology experiments. Scaling up this process on a robotic system also gives us higher throughput and repeatability without the variability inherent in manual procedures.”

“We specifically chose a Tecan system for this application because the software and hardware are easy to extend, and we wanted the flexibility to experiment with different combinations of modules. The Freedom EVOware® software has an open architecture, making it easy to write and develop scripts and connect the instrument to our own systems and software, and the design of the hardware undoubtedly helps with the integration of our own modules and apparatus onto the worktable. For example, we wanted to be able to store enzymes at -20 oC on the deck, and were able to get an

GENOMICS TECAN JOURNAL 3/2012

automation-friendly chiller that could do this at fairly low cost, without having to make any major modifications to the platform.”

“We have also been able to devise our own colony picking procedures for cell-based screening, and to set up and run an ordinary, low-cost gel station on the platform. The Freedom EVO is able to automatically load and run gels on the gel station, despite the lack of a communication port on this device, eliminating the need for a lot of expensive additional hardware. The flexibility and programmability of the Freedom EVO are invaluable for this, allowing us to rapidly develop in-house solutions and create the elaborate algorithms that are required to perform the many different steps necessary for the assembly of genetic circuits. We have successfully demonstrated that every step in the process can be automated and run completely unattended, and are now scaling up to high throughput mode, which will see multiple 96-well plates processed per day.”

RoMa Arm LiHa Arm

Tecan Freedom EVO 150 at MIT Weiss Lab Hotel Hotel

37-60 °C incubator

Tips

-20 °C

Cover storage Stackable tips

Plate reader

Deep-well plate Magnet 4 °C

Tubes

Camera position

Ge

lc on tro

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Gel box

Scanner

User output Waste

User input

The MIT Weiss Laboratory’s Freedom EVO platform

“Tecan’s technical expertise has also been important to the success of our work, and we receive excellent application support from the Company. My colleagues and I attended a Tecan users’ meeting in Boston last October, specifically to find a solution to the complex issue of pipetting minute volumes of our suspensions on the Freedom EVO platform with the existing liquid classes. Tecan’s application specialists were able to give us a new liquid class that would not only be able

to handle the volume and viscosity we wanted, but also direct the pipette tip to twist around and tap the side of the vessel, so that any drop of liquid would come off.

We also have very good ongoing support from Tecan locally – for general advice and troubleshooting – and are kept up-to-date with new technologies and solutions which could further our research.”

To learn more about Tecan’s genomics solutions, visit www.tecan.com/genomics To find out more about the Synthetic Biology Center at the Massachusetts Institute of Technology, visit synbio.mit.edu

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COMPONENTS TECAN JOURNAL 3/2012

Cavro® Air Displacement Pipettor provides the key to automated sonochemical synthesis of nanoparticles Go2 Technologies, a specialized engineering solutions provider, has used Tecan’s Cavro Air Displacement Pipettor to develop a novel automated method for labor-intensive sonochemical synthesis procedures.

Go2 Technologies in Dayton, Ohio, USA, has taken advantage of state-of-the-art manufacturing and engineering technology, combined with leading-edge robotics and the Cavro Air Displacement Pipettor (ADP), to establish an innovative automated process for sonochemical synthesis of nanoparticles for the generation of hydrogen gas.

Sonochemical synthesis – chemistry driven by ultrasound waves – relies on high intensity sound waves, which are only present near a powerful sonic probe. This makes it difficult to perform large-scale reactions and, as a result, chemists are usually forced to perform labor-intensive batch procedures consisting of numerous small syntheses.

To automate these procedures – and decrease labor costs significantly – Go2 Technologies has developed the RADS robotic synthesis machine. Kent Walker, Partner/Owner at Go2 Technologies, explained: “The University of Dayton Research Institute and the Air Force Research Laboratory at Wright-Patterson Air Force Base, Ohio, were creating air-stable organically-capped aluminum nanoparticles for the production of hydrogen gas from water, which involved manually pipetting three different materials – alane, titanium isopropoxide, and oleic acid – inside a glovebox. This is a very labor-intensive procedure for a single operator, and we were approached to develop an automated method that could robotically dispense, mix, sonicate and verify, essentially to produce a robotic synthesis machine to automate the manual pipetting and dispensing stages within the enclosure.”

The robotic arm holds the Cavro ADP

“The really big challenge of the whole process was liquid dispensing; we needed something compact and lightweight that could cover a large range of volumes, from 15 µl to 10 ml.

Some of the chemicals used are pretty harsh on plastics, and pumping these materials through a mechanical piece of equipment was causing them to degrade and break down quickly. This was where the Cavro ADP really came into play. We looked at standard dispensing-type pumping systems but, typically, these wanted to bring the liquids into the device. The nature of the liquids used meant that we needed to find a non-contact mechanism for dispensing and pumping, with tips that were either disposable, or could be removed and replaced during the process.

Accurate, reliable dispensing of liquid volumes was also vital. I had previous experience with Tecan and was familiar with its products, so we approached Tecan Systems. The Cavro ADP was the key to making the whole dispensing process happen because it doesn’t touch the liquid, it just brings it into the end of a disposable pipette tip.”

Kent continued: “The system design is unique.

Unlike the more standardized XYZ robotic components, the Cavro ADP is free standing and is manipulated by a Mitsubishi vertical articulating robotic arm. The Cavro ADP needed to be used as a pick and place-type unit rather than being permanently mounted, so we created custom fixtures and tools from

COMPONENTS TECAN JOURNAL 3/2012

“The Cavro ADP has been vital to the success of the project.”

From left to right: Kent Walker, Scott Schoessow and Allen Poe from Go2 Technologies

which the robotic arm could pick it up when required. We use the Cavro ADP with Tecan’s disposable tips, and have modified the tip racks to fit our application. Each of the liquids that we pipette has its own rack of tips and, once they have been used, we just dispense them into a waste container within the purge box. All these adaptations had to be extremely precise, to ensure that everything worked reliably and reproducibly.”

“As well as implementing the robotic solution, we had to develop a custom airtight chamber that could be purged with nitrogen. After talking to several vendors about the inner chamber we realized that these products were so standardized that they really didn’t fit our solution, and so we designed and built the purge box ourselves.

This stainless steel enclosure was specifically sized to house all the equipment required, including the vertical articulating arm, the Cavro ADP, and the reagents, vials and trays.

We had to allow sufficient space for the robotic arm to operate – pipetting with the Cavro ADP, capping and uncapping vials and moving them to a sonic probe – and to accommodate any cables.”

“We can now perform batch processing of samples by placing them in individual vials inside the glovebox, and process an entire grid of these vials in one run. A batch of up to 56 vials can be processed, with each one taking around 20 minutes to complete.

You just load the cell, close the box and purge it with nitrogen, then start the run

The robotic arm manipulates the Cavro ADP within the purge box

and walk away. Consistency is essential for the synthesis to work, and the Cavro ADP has been vital to the success of the project,” concluded Kent.

To find out more on Tecan’s Cavro ADP, visit www.tecan.com/components To find out more about Go2 Technologies, visit www.go2technologies.com

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MICROARRAY TECAN JOURNAL 3/2012

Making advances in the battle against autoimmune disease Scientists at the National Institute of Molecular Genetics in Italy rely on the Freedom EVO® platform for automated diagnostic screening of sera from patients suffering from autoimmune diseases.

Autoimmune diseases are caused by an inappropriate immune response that results in the body attacking its own tissues and generating autoantibodies. The prevalence of these diseases is increasing worldwide, with only limited diagnostic tools available. The National Institute of Molecular Genetics (INGM), based on the IRCCS Ospedale Maggiore campus in Milan, Italy, is a non-profit research foundation that was set up to perform research into the discovery and initial development of innovative therapies and diagnostics for tumors and autoimmune diseases. As an advanced research center, INGM is creating a well-defined niche of activities in the field of human proteomics research, taking advantage of its location to establish strong connections with hospital clinics. Its diverse network of public and private collaborations with leading Italian and international institutes and biotechnology companies is playing a key role in the identification of new therapeutic targets, and the development of new diagnostic methods for neoplastic and autoimmune diseases.

INGM’s proteomic group focuses its research on the development of reliable and automation­-friendly assays for screening large sets of sera for new biomarkers in autoimmune diseases. Mauro Bombaci, group leader of the protein microarray laboratory – which specializes in method development and the validation of novel candidates – described the Group’s work: “We are a multidisciplinary research center involved in the discovery of new signature profiles in autoimmune diseases. Our work involves the use of protein microarrays to perform a variety of assays – including biomarker identification, antibody specificity profiling, protein-protein interaction studies and drug target discovery – and we are currently turning our attention to the development

INGM

The INGM team with the Freedom EVO. Left to right: Antonella Sinisi, Mauro Bombaci, Angela Cardaci

of a protein microarray containing poorlycharacterized recombinant human proteins that are predicted to be surface-exposed or secreted.”

“We need to be able to perform a wide variety of tasks and implement new processes, from general liquid handling for a range of different purposes, to running ELISA, DELFIA® and Bio-Plex® assays. High throughput screening is also important, helping us to be competitive in the marketplace. To achieve these goals, we have invested in a Freedom EVO 150 workstation equipped with Liquid Handling (LiHa) and Robotic Manipulator (RoMa) Arms, an integrated Infinite® F200 multimode microplate reader, an ambient temperature incubator, a HydroSpeed™ washer, a Variomag® Teleshake, a heating plate and various hotels that allow us to store up to 15 microplates. We also have a HS 4800™ Pro hybridization station and an Infinite M200 microplate reader.”

Mauro continued: “We use our Freedom EVO workstation to run fully automated DELFIA TRF assays. The DELFIA is a robust, high performance immunodetection assay that uses Eu-labelled anti-human IgG to detect antibodies in sera, offering several advantages over conventional ELISAs, such as enhanced sensitivity and a wider dynamic range. As we often use sera from patients suffering from infectious diseases, we prepare our sera dilutions prior to analysis in a sterile clean room, then use the Freedom EVO workstation to perform the assay, analyzing the samples and controls in 96-well microplates.

Automating DELFIA protocols on the Freedom EVO enables us to screen large sample numbers to validate new biomarkers in autoimmune diseases.”

“Before we purchased the Freedom EVO, we used manual and semi-automatic processes to perform our assays. The system is reliable and easy to use, and allows us to process

TALK TO TECAN TECAN JOURNAL 3/2012

hundreds of samples in a day, taking just two to three hours for each assay. By fully automating the DELFIA method on the Freedom EVO workstation, we are now able to perform in one day what it used to take us three days to do,” concluded Mauro.

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

“ By fully automating the DELFIA method on the Freedom EVO workstation, we are now able to perform in one day what it used to take us three days to do.”

Simon Fogarty, Director of Application Sciences, Tecan US, Inc.

Leading the debate Mass spectrometry (MS) has long been associated with the analysis of small molecules and their metabolites as part of the drug discovery and development process. However, over the last 10 years there has been a significant increase in the use of MS in a clinical setting, driven by a number of technical innovations – expanding the range of molecules that can be detected – and the development of more user-friendly software and bioinformatics tools.

MS applications now include biomarker analysis, identifying genes, lipids, proteins and metabolites that have diagnostic potential in disease management; forensic toxicology applications, particularly in the analysis of pain management drugs and their metabolites; and lipid profile analysis to reveal alterations that occur in metabolic diseases.

The National Institute of Molecular Genetics, Milan

To support MS customers, Tecan has developed a range of sample preparation applications and protocols on the Freedom EVO liquid handling platform. From simple sample handling, aliquoting and dilution protocols to MALDI target plate set-up and advanced sample processing such as protein crash, liquid-liquid and solid-phase extraction protocols.

Recognizing the growing importance of this technique to both Tecan and its customers, this year’s Tecan Symposium in Boston, USA, will focus on MS. Titled Mass spectrometry – the expanding role in life sciences and diagnostics, the Symposium will feature speakers from a number of organizations using MS techniques in the clinical environment. Presentations will cover the use of MS technology in a range of areas including protease analyses as cancer biomarkers, automation of sample handling for analysis of 25-hydroxy vitamin D by LC-MSMS, and its use in assays where samples are precious or minimal, such as pediatrics and neonates.

Antonella Sinisi using the HS 4800 Pro hybridization station

Email talk@tecan.com to tell us about how Tecan can help to further expand the role of MS in life sciences and diagnostics.

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EVENTS 2012 TECAN JOURNAL 3/2012

Meet Tecan at these events Americas Microarray World Congress

San Diego, CA, USA

25 – 26 Sept 2012

BioProcess International

Providence, RI, USA

09 – 11 Oct 2012

AAPS Annual Meeting & Exposition 2012

Chicago, IL, USA

14 – 18 Oct 2012

ISHI 23rd International Symposium on Human Identification

National Harbor, MD, USA

15 – 18 Oct 2012

Tecan Symposium 2012

Boston, MA, USA

23 – 25 Oct 2012

ASHG American Society of Human Genetics 2012

San Francisco, CA, USA

06 – 10 Nov 2012

Sydney, Australia

27 – 28 Sept 2012

Asia and Pacific A&PD 6th Alzheimer's and Parkinson's Disease Symposium BPN BioProcessing Network Conference

Melbourne, Australia

16 – 18 Oct 2012

Analytica China Shanghai Conference

Shanghai, China

16 – 18 Oct 2012

CSBT The 6th National Congress of the Chinese Society of Blood Transfusion

Guangzhou, China

07 – 09 Nov 2012

AACB Australasian Association of Clinical Biochemists Conference

Melbourne, Australia

15 – 19 Nov 2012

The Japanese Society for the Study of Xenobiotics Annual Meeting

Chiba, Japan

20 – 22 Nov 2012

The Annual Meeting of the Molecular Biology Society of Japan

Fukuoka, Japan

11 – 14 Dec 2012

Basel, Switzerland

24 – 27 Sept 2012

Europe, Middle East and Africa MipTec Conference & Exhibition Scanlab 2012

Copenhagen, Denmark

25 – 27 Sept 2012

HET Instrument 2012

Amsterdam, Netherlands

25 – 28 Sept 2012

ELRIG Pharmaceutical Flow Cytometry & Imaging

Alderley Park, UK

10 – 11 Oct 2012

SIDILV Conference

Sorrento, Italy

24 – 26 Oct 2012

ESBB European, Middle Eastern & African Society for Biopreservation & Biobanking Conference

Granada, Spain

07 – 10 Nov 2012

Medica Exhibition

Düsseldorf, Germany

14 – 17 Nov 2012

Tecan are pioneers in automated liquid handling and innovative life science solutions. For over 30 years we continue to enable and support our customers to make the world a healthier and safer place.

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

Tecan Australia +61 3 9647 4111 Austria +43 62 46 89 33 Belgium +32 15 42 13 19 China +86 21 220 63 206 Denmark +45 70 23 44 50 France +33 4 72 76 04 80 Germany +49 79 51 94 170 Italy +39 02 92 44 790 Japan +81 44 556 73 11 Netherlands +31 18 34 48 17 4 Singapore +65 644 41 886 Spain +34 93 490 01 74 Sweden +46 31 75 44 000 Switzerland +41 44 922 89 22 UK +44 118 9300 300 USA +1 919 361 5200 Other countries +43 62 46 89 33 www.tecan.com Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Günter Bolzern/Zürich www.bolzern.net Editor in Chief: Tecan Trading AG, Cornelia Kegele Project Lead: Tecan Trading AG, Cornelia Kegele/Antonietta Allocca Editor: kdm/UK www.kdm-communications.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, journal@tecan.com, www.tecan.com To register for the Tecan Journal please go to www.tecan.com/journal © 2012 Tecan Trading AG, Switzerland, all rights reserved.

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

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

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