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<strong>Tecan</strong> Journal<br />

Life Sciences and Partnering Business<br />

40 years of Cavro®<br />

pages 6-7<br />

Rapid, automated isolation<br />

of buffy coat benefits DNA<br />

extraction<br />

pages 20-21<br />

Making advances<br />

in the battle against<br />

autoimmune disease<br />

pages 26-27<br />

Edition 3/2012<br />

Protecting the nation<br />

pages 16-17


2 CEO WELCOME TECAN JOURNAL 3/2012<br />

Welcome<br />

Welcome to the latest issue of the<br />

<strong>Tecan</strong> Journal<br />

<strong>Tecan</strong> has a long history and tradition in the<br />

OEM market and, as we move into the fall,<br />

we celebrate the milestone 40th anniversary<br />

of Cavro®. For four decades, instrument<br />

designers have relied on <strong>Tecan</strong> Cavro branded<br />

components to provide innovative and<br />

reliable liquid handling products that can<br />

be applied to a wide range of applications.<br />

As part of <strong>Tecan</strong>’s broad OEM product<br />

portfolio – from components such as pumps,<br />

valves and robotic modules, to full system<br />

solutions and instruments that partners<br />

incorporate with their specific applications<br />

and tests – the Cavro brand is a key element<br />

in the Company’s success as the ‘OEM partner<br />

of choice’ for leading diagnostic and life<br />

science companies.<br />

We continue to enhance and broaden<br />

the functionalities of the market-leading<br />

Freedom EVO® liquid handling platform with<br />

new modules and applications. The launch of<br />

the new Air LiHa air displacement pipetting<br />

arm – which provides greater versatility<br />

than ever before – is generating a lot of<br />

interest and, to help meet ever-increasing<br />

quality and regulatory demands, we have<br />

recently released the QC Kit, offering a total<br />

solution for liquid handling performance<br />

verification testing.<br />

This issue also includes news of <strong>Tecan</strong>’s<br />

success at the 2012 SLAS Asia Conference<br />

and Exhibition, as well as details of the<br />

forthcoming <strong>Tecan</strong> Symposium which<br />

will focus on the expanding role of mass<br />

spectrometry in life sciences and diagnostics.<br />

Plus, we have the usual diverse array of<br />

customer applications that depend on our<br />

expertise in providing automated solutions.<br />

We hope you enjoy the issue.<br />

Gérard Vaillant, Acting CEO


page 9<br />

Cavro Air Displacement<br />

Pipettor provides the key<br />

to automated sonochemical<br />

synthesis of nanoparticles<br />

<strong>Tecan</strong> Symposium comes<br />

to Boston<br />

pages 24 - 25<br />

pages 14 - 15<br />

page 11<br />

Contents<br />

CONTENTS TECAN JOURNAL 3/2012<br />

2 CEO Welcome<br />

4 <strong>Tecan</strong> US relocates to bigger<br />

and better premises<br />

4 Cornelias celebrates 25 years<br />

at <strong>Tecan</strong><br />

5 <strong>Tecan</strong> enjoys success at 2012 SLAS<br />

Asia Conference and Exhibition<br />

5 Increased flexibility and choice<br />

for Cavro Centris Pump<br />

6 - 7 40 years of Cavro<br />

8 Cornell Cup success for<br />

<strong>Tecan</strong>-sponsored team<br />

9 <strong>Tecan</strong> Symposium comes to Boston<br />

10 <strong>Tecan</strong> showcases the Freedom EVO<br />

workstation configured for ELISAs<br />

to delegates visiting from Chinese<br />

blood centers<br />

11 Joining the digital age<br />

12 - 13 A winning combination for<br />

nephrology research<br />

14 - 15 Biopharma by design<br />

16 - 17 Protecting the nation<br />

18 - 19 Investing in the future of drug<br />

discovery<br />

20 - 21 Rapid, automated isolation of buffy<br />

coat benefits DNA extraction<br />

22 - 23 Reprogramming nature<br />

24 - 25 Cavro Air Displacement Pipettor<br />

provides the key to automated<br />

sonochemical synthesis of<br />

nanoparticles<br />

26 - 27 Making advances in the battle<br />

against autoimmune disease<br />

27 Leading the debate<br />

28 Events<br />

3


4 CORPORATE NEWS TECAN JOURNAL 3/2012<br />

<strong>Tecan</strong> US relocates to bigger<br />

and better premises<br />

July this year saw <strong>Tecan</strong> US relocate from the<br />

Durham premises it had occupied for the past<br />

21 years to a new, larger facility in the nearby<br />

Morrisville area of Raleigh. This new base<br />

offers scalable space and additional training<br />

rooms to meet the needs of continued<br />

growth over the coming years. With its high<br />

ceilings and clean lines, the new building<br />

has a very modern and sleek appearance,<br />

providing a pleasant environment for visitors<br />

and employees alike. Situated close to<br />

Raleigh-Durham International Airport, hotels,<br />

restaurants and shopping at Brier Creek,<br />

the new premises are convenient for both<br />

customers attending the Company’s training<br />

facility and commuting employees.<br />

Cutting the ribbon at the opening ceremony<br />

Celebrations were in order in June, as<br />

customer service representative Cornelias<br />

Rushing reached the landmark 25 years of<br />

service at <strong>Tecan</strong> US. Cornelias joined <strong>Tecan</strong><br />

in 1987, and has seen many changes, as she<br />

explained: “When I joined <strong>Tecan</strong>, it had been<br />

working out of a garage at the home of a<br />

former President in Chapel Hill. I came on<br />

board shortly after the Company relocated<br />

and, since then, I have been involved in two<br />

more Company moves; it’s been interesting,<br />

because each time <strong>Tecan</strong> goes up another<br />

<strong>Tecan</strong> US staff assembled outside the new premises<br />

Careful planning enabled the relocation to be<br />

completed over the course of one weekend, as<br />

Peter Hornbach, Vice President of Operations,<br />

explained: “We closed slightly early on the<br />

Friday, and moved the IT portion of the<br />

business that evening. That was followed<br />

by 64 truckloads of equipment and, by mid<br />

afternoon on Saturday, we had actually moved<br />

everything in. We cleaned up on Sunday, and<br />

Cornelias celebrates 25 years at <strong>Tecan</strong> “…never in my<br />

level. Before I joined the Company I was<br />

working in local government, so this was<br />

a really new area for me, seeing products<br />

such as the RSP 5000 and the MegaFlex.<br />

The product range has grown and improved<br />

over the 25 years I have been working here.<br />

When I started, the Company was just<br />

celebrating the acquisition of Cavro Scientific<br />

Instruments, and detection products were<br />

not even a part of <strong>Tecan</strong>. That’s how far<br />

my days go back!”<br />

“My actual anniversary date was Friday<br />

June 29th , and I had been told to make sure<br />

I was in the office on that day at a certain<br />

time, but nobody would tell me why. As it<br />

was my anniversary date, I just figured they<br />

would give me my long service award, I<br />

didn’t expect anything extra. Instead, they<br />

surprised me with a beautiful cake and a<br />

were open for business as usual on Monday<br />

morning. Everyone was very motivated and<br />

worked together, and the move went really<br />

smoothly. Everyone is thrilled with the new<br />

base, and we are very proud of the premises.”<br />

To contact <strong>Tecan</strong> US, call +1 800 352 5128<br />

or email sales-americas@tecan.com<br />

wildest dreams<br />

did I imagine<br />

being here 25<br />

years. It’s been<br />

great, truly, a<br />

blessing.”<br />

reflections video, with pictures of me in<br />

different aspects over the years. Some of<br />

the photos were of events I had forgotten<br />

even happened, so it was really nice and I<br />

got a bit teary-eyed. The whole Company<br />

came together for the celebration and it<br />

was wonderful. I really, really appreciated<br />

it. I came here looking for a job that I could<br />

connect with, but never in my wildest<br />

dreams did I imagine being here 25 years. It’s<br />

been great, truly, a blessing.”


<strong>Tecan</strong> enjoys success at 2012 SLAS<br />

Asia Conference and Exhibition<br />

<strong>Tecan</strong> attended the 2012 SLAS Asia Conference<br />

and Exhibition at the Grand Hyatt Shanghai,<br />

China, from 19th to 21st of June 2012. This<br />

international event hosted approximately 350<br />

delegates over three days, bringing together<br />

research scientists and business leaders from<br />

academia and industry to discuss this year’s<br />

topic: Advances in Drug and Life Sciences<br />

R&D Through Laboratory Technology. The<br />

Conference’s educational program featured<br />

renowned local and international speakers,<br />

with presentations covering a wide range of<br />

topics related to drug discovery, from high<br />

throughput screening to the use of stem cell<br />

technologies.<br />

<strong>Tecan</strong> China demonstrated the many<br />

advantages of automated liquid handling<br />

processes in drug discovery and life science<br />

applications in the exhibition hall, enjoying<br />

a steady flow of delegates to its booth.<br />

A number of state-of-the-art automated<br />

solutions were in action on the booth,<br />

including a powerful Freedom EVO® drug<br />

discovery workstation equipped with a<br />

MultiChannel Arm 384 (MCA 384), the<br />

top class Quad4 Monochromators-based<br />

Infinite® M1000 PRO microplate reader and<br />

the innovative HP D300 Digital Dispenser.<br />

<strong>Tecan</strong> China’s strong multi disciplinary team<br />

PRODUCT NEWS<br />

The state-of-the-art Cavro Centris Pump is<br />

now available with a range of glass syringes<br />

and plastic valves to complement the existing<br />

portfolio of long-life ceramic components.<br />

These new options provide customers with<br />

a greater choice of materials to suit their<br />

instrument design, bringing the advanced<br />

features of the Cavro Centris Pump to a wider<br />

range of applications.<br />

The Cavro Centris Pump is a compact,<br />

UL-recognized syringe pump module for<br />

use in OEM laboratory instruments. Offering<br />

exceptional liquid handling characteristics –<br />

with flow rates from 5 nl/s up to 5 ml/s –<br />

it sets new industry standards for accuracy,<br />

of sales, service and applications specialists<br />

was joined by both Andrea Beccari – Global<br />

Head of Sales, Service and Commercial<br />

Operations – and Head of China and South<br />

East Asia Raymond Chan, and the event<br />

provided many opportunities to speak<br />

to key opinion leaders in the field in<br />

a relaxed environment.<br />

Alongside the main conference and exhibition,<br />

<strong>Tecan</strong> hosted a tutorial on the launch of two<br />

new products. The new Infinite M1000 PRO<br />

multimode microplate reader with<br />

AlphaScreen® and AlphaLISA® technology<br />

was introduced by Marketing Application<br />

Specialist at <strong>Tecan</strong> Austria Dr Christian<br />

Oberdanner. Christian, who arrived at<br />

SLAS fresh from a highly successful series<br />

of roadshows to promote this powerful<br />

new system, explained the benefits of the<br />

system’s highly acclaimed absorbance,<br />

fluorescence and luminescence scanning<br />

capabilities for academic, biotechnology<br />

and pharmaceutical research. The HP D300<br />

Digital Dispenser was also launched at the<br />

event by Dr Yingguang Wu, Head of Marketing<br />

for the Asia Pacific region. This revolutionary<br />

sample preparation tool has the potential<br />

to streamline the drug discovery process, and<br />

received widespread interest from delegates.<br />

CORPORATE NEWS TECAN JOURNAL 3/2012<br />

<strong>Tecan</strong> staff and customers were able to discuss<br />

the many drug discovery applications of the<br />

Freedom EVO workstation<br />

Dr Christian Oberdanner introduced the new<br />

Infinite M1000 PRO reader<br />

The 2012 SLAS Asia was hailed a great<br />

success for <strong>Tecan</strong>, once again highlighting<br />

the Company’s innovation-driven solutions<br />

and customer-focused approach to laboratory<br />

automation for drug discovery and life<br />

science laboratories.<br />

Increased flexibility and choice for Cavro® Centris Pump<br />

reliability and precision. A hallmark of the<br />

Cavro Centris Pump is its elegant and robust<br />

drive mechanism, offering a broad dynamic<br />

range from a single syringe size, and the<br />

advantages of this innovative design are now<br />

available to customers wishing to use cost-effective<br />

glass syringe and plastic valve options. Already<br />

widely used throughout the <strong>Tecan</strong> Cavro range,<br />

these high quality glass and plastic<br />

components retain the premium performance<br />

benefits of the Cavro Centris Pump, while<br />

reducing the installed cost for applications which<br />

do not require the exceptional durability offered<br />

by a ceramic fluid path. Now, more than ever, you<br />

can truly tailor your Cavro Centris Pump to your<br />

instrument and application requirements.<br />

To find out more on <strong>Tecan</strong>’s Cavro Centris<br />

Pump, visit www.tecan.com/components<br />

The Cavro Centris Pump offers a choice<br />

of glass or ceramic syringes<br />

5


6 CORPORATE NEWS TECAN JOURNAL 3/2012<br />

40 years of Cavro®<br />

As we reach the milestone anniversary of 40 years of Cavro, <strong>Tecan</strong> Systems’ Site Manager<br />

Nora Tryhorn takes stock and looks forward to a prosperous and successful future for <strong>Tecan</strong>’s<br />

components business.<br />

Celebrating <strong>Tecan</strong>’s acquisition of Cavro in 1987.<br />

Jerry Rochte, founder of Cavro (left), and Heinz<br />

Abplanalp, one of the founders of <strong>Tecan</strong><br />

An early Cavro employee<br />

working on a pump<br />

Jerry Rochte (left) and Bob Caveney<br />

at work in the early years of Cavro<br />

Our business<br />

<strong>Tecan</strong>’s name is synonymous with excellence<br />

in the world of OEM components. For 40<br />

years now <strong>Tecan</strong> Cavro brand components<br />

have provided innovative and reliable liquid<br />

handling for instrument designers for almost<br />

any application. Our outstanding <strong>Tecan</strong><br />

Systems team of 104 employees is based<br />

in San Jose, in sunny California. Together,<br />

our vision is to be the best-in-class – a world<br />

class manufacturer and a design center of<br />

excellence for <strong>Tecan</strong>.<br />

“I’ve worked in other companies and the people<br />

in <strong>Tecan</strong> are just different. <strong>Tecan</strong> Systems has<br />

really good employees who work hard, but<br />

also take the time to get to know each other.”<br />

Diana Morikawa, Director of Logistics<br />

and Production<br />

Our products<br />

<strong>Tecan</strong> Cavro components work robustly and<br />

efficiently in applications that are critical to<br />

society as a whole. We are very aware of the<br />

huge impact our products have on public<br />

health and safety.<br />

“The products we make at <strong>Tecan</strong> touch so<br />

many lives. We are all very proud to work for<br />

a company that makes such great products.”<br />

Tawni Kestel, Purchasing Supervisor<br />

Cavro milestone timeline<br />

1972 Cavro Scientific Instruments founded<br />

1980 Model 1500/2000 Pipettor/Dilutor<br />

1985 IQ 190 Sample Processor<br />

1986 SB 1200 Pump<br />

1987 <strong>Tecan</strong> acquires Cavro<br />

1989 RSP 9000<br />

Our customers<br />

Early Cavro premises at<br />

1234 Elko Drive, Sunnyvale,<br />

Talking to our customers during the entire<br />

development cycle of our products makes<br />

so much sense as we create exactly what is<br />

needed. We pride ourselves on our excellent<br />

communication channels and long-term<br />

relationships with our customers.<br />

“I'm proud to be part of our service department,<br />

taking on all the responsibilities that are<br />

involved.”<br />

Bob Jackson, Service Technician<br />

1997 MiniWash Pump, Smart<br />

Valve, Smart Peristaltic Pump<br />

1997 MSP 9500<br />

1994 MSP 9000<br />

1994 XP 3000<br />

1992 XL 300X<br />

1990 XL 3000


CA<br />

Jerry Rochte (right) and a Cavro<br />

colleague working on a pump<br />

Rey Pangilinan at work in 1984 –<br />

an early employee who is still working<br />

at the Company today!<br />

Our quality<br />

We’ve done a great job of improving<br />

our quality over the years and have seen<br />

significant improvements in our customer<br />

satisfaction levels since 2006. But there’s<br />

1999 XE 1000<br />

2001 Cavro relocates<br />

to 2450 Zanker Road<br />

2002 MSP 9250<br />

2002 Cavro name<br />

change to <strong>Tecan</strong><br />

Systems<br />

Nora Tryhorn in 1992 as Cavro’s<br />

Customer Service Representative<br />

always room for improvement and we will<br />

continue to work hard as a team to make<br />

things better.<br />

“My proudest achievement at <strong>Tecan</strong> Systems<br />

is the high level of productivity and quality<br />

accomplished by our relatively small R&D<br />

department.”<br />

Torleif Björnson, Director R&D<br />

Our lean working principles<br />

The <strong>Tecan</strong> Systems’ Sales Team. Left to right;<br />

Bruce Steffer (US), Jerry Maurice (US), Willi<br />

Krattenmacher (Europe), Chuck Fontana (US)<br />

We started implementing lean<br />

manufacturing in 2009 and continue to strive<br />

for the utmost efficiency. But lean principles<br />

are based on a philosophy of constant<br />

improvement and we’ll keep working to<br />

consistently find a better and faster way<br />

to do things.<br />

“My proudest moment at <strong>Tecan</strong> was being<br />

the first person to build the new<br />

Cavro Omni Robot.”<br />

Kenny Tran, Track Assembler<br />

2007 Cavro ceramic valves<br />

2006 Cavro XMP 6000<br />

2005 Cavro XLP 6000<br />

2004 Cavro XCalibur Pump<br />

2003 Freedom EVO® 75<br />

CORPORATE NEWS TECAN JOURNAL 3/2012<br />

Our people<br />

2008 Cavro Integration Kit<br />

The manufacturing floor<br />

at <strong>Tecan</strong> Systems’ previous<br />

Humboldt Court premises<br />

For <strong>Tecan</strong> Systems, the secret of our success<br />

is undoubtedly our employees, several of<br />

whom have worked here for many years.<br />

We have a great team of extremely capable<br />

people who work hard and, most importantly,<br />

have a real passion for their jobs; everyone<br />

at <strong>Tecan</strong> Systems cares about the customer.<br />

We asked our employees what’s the best<br />

thing about working for <strong>Tecan</strong> Systems, and<br />

the answer was resounding…..THE PEOPLE!!<br />

“We are one big happy family, helping<br />

each other!”<br />

Jose Rodriguez, Material Handler<br />

To find out more about <strong>Tecan</strong> Cavro<br />

components, visit<br />

tecan.com/components<br />

2008 Cavro Centris Pump<br />

2008 Cavro Omni Robot<br />

2010 Cavro ADP<br />

2011 Cavro Omni 8-channel<br />

option, Cavro Omni gripper<br />

7


8 CORPORATE NEWS TECAN JOURNAL 3/2012<br />

Cornell Cup success for<br />

<strong>Tecan</strong>-sponsored team<br />

A <strong>Tecan</strong>-sponsored team of students from the Weiss Laboratory for Synthetic Biology at the<br />

Massachusetts Institute of Technology (MIT), USA, recently enjoyed success at the Cornell Cup<br />

USA competition in Florida. The team came third in this inaugural running of the competition,<br />

taking advantage of the performance of a Cavro® XCalibur Pump on loan from <strong>Tecan</strong> to develop<br />

a novel and innovative liquid handling system.<br />

The Cornell Cup USA is an embedded design<br />

competition created to empower student<br />

teams to become inventors. Sponsored by<br />

Intel, the competition was run for the first<br />

time this year, and is based on the success<br />

of the Intel China Cup, which attracts entries<br />

from over 26,000 students. Held in May at<br />

Walt Disney World’s Contemporary Resort<br />

on Lake Buena Vista, Florida, the MIT’s entry<br />

in the competition was supported by <strong>Tecan</strong>.<br />

Dr Jonathan Babb, advisor of the MIT team,<br />

explained: “Five of our students entered the<br />

Cornell Cup USA as ‘Team Squirtle’, with $500<br />

sponsorship from <strong>Tecan</strong> for their expenses. The<br />

team’s project brief was to design and build<br />

a smaller, lower priced and more intelligent<br />

liquid handler that would provide individual<br />

researchers with a tool for fast, accurate<br />

and tailored pipetting to meet their liquid<br />

handling needs. The students had considered<br />

making their own pump, but identified that<br />

this key component of their custom liquid<br />

handler would be very challenging to build<br />

in the time available. As <strong>Tecan</strong> was already<br />

sponsoring the team, we asked if we could use<br />

one of the Company’s pumps. We were kindly<br />

lent a Cavro XCalibur Pump (XC Pump), and the<br />

students were shown how to set up<br />

and use it.”<br />

Jonathan continued: “<strong>Tecan</strong>’s help was<br />

invaluable, making it easy for the students to<br />

integrate the pump and connect it to their<br />

software. This allowed the team to focus<br />

on the innovative aspects and architecture<br />

of the robot, creating a system that is quite<br />

different from conventional liquid handling<br />

instruments. Their solution was a delta<br />

parallel robot with three jointed arms coming<br />

together into a point. The arms are each<br />

controlled by a servo and motor, allowing<br />

the user to determine the exact location<br />

The winners were announced at the America Pavilion in Disney’s Epcot Center. Left to right:<br />

Jonathan Babb, Kevin Linke, Huayu Ding, Agustin Venezuela, Cory Li<br />

Team member Agustin Venezuela demonstrates<br />

the prototype to the competition judges<br />

of the pipetting tip. This design, which was<br />

inspired by the high-speed, pick and place<br />

assembly line robots used in the electronics<br />

industry to position chips on circuit boards,<br />

came third overall, winning a prize of $2,500.<br />

The project was all about making one tip<br />

go faster, rather than adding more tips as<br />

in conventional liquid handling systems,<br />

and we are grateful to <strong>Tecan</strong> for its support.”<br />

‘Team Squirtle’ was awarded third place and<br />

received a $2,500 check for the development of a new<br />

liquid handling robot using the Cavro XCalibur Pump<br />

To find out more about <strong>Tecan</strong>’s<br />

Cavro XCalibur Pump, visit<br />

www.tecan.com/components<br />

To find out more about the Cornell Cup,<br />

visit www.systemseng.cornell.edu/intel<br />

The team would also like to acknowledge the<br />

following co-sponsors: BBN Technologies, HighRes<br />

Biosolutions, Qiagen, Intel, Tektronix, Cornell, the<br />

MIT Department of Biological Engineering and the<br />

MIT EECS department.


<strong>Tecan</strong> Symposium<br />

comes to Boston<br />

The fifth annual <strong>Tecan</strong> Symposium will be<br />

visiting the historical US coastal city of Boston,<br />

Massachusetts, from the 23rd to the 25th of<br />

October. Building on the success of previous<br />

events, this popular scientific meeting is<br />

being hosted by <strong>Tecan</strong> in the US for the first<br />

time, and will bring together key opinion<br />

<strong>Tecan</strong> Symposium key speakers<br />

Prof Sabine Becker<br />

BrainMet: novel avenues of bioimaging mass<br />

spectrometry of metals and biomolecules from<br />

micrometer to nanometer scale in the brain<br />

Prof Mitsutoshi Setou<br />

Meta-analysis of histopathological lipidomics<br />

Dr Feixia Chu<br />

Sample preparation of ancient protein<br />

samples from amber encapsulated organisms<br />

Dr Gary van Berkel<br />

Laser ablation and liquid extraction surface<br />

sampling for ambient surface sampling/<br />

ionization MS<br />

Dr Jeffrey Hurst<br />

Chocolate spectrometry: applications of mass<br />

spectrometry in cocoa and chocolate research<br />

Dr Michael Vogeser<br />

Pitfalls associated with the use of liquid<br />

chromatography-tandem mass spectrometry<br />

in the clinical laboratory<br />

Prof Xuefan Gu<br />

Neonatal screening using tandem<br />

mass spectrometry<br />

leaders from around the world to discuss<br />

the expanding role of mass spectrometry<br />

(MS) in life sciences and diagnostics.<br />

This year’s scientific program will cover a<br />

broad range of topics related to MS, and will<br />

be divided into four sessions: the role of MS<br />

in basic research; collection, preparation, and<br />

storage of samples for MS; MS as a diagnostic<br />

tool; and the use of MS in applied markets.<br />

Supported by a number of social events, this<br />

diverse agenda is designed to attract a truly<br />

multidisciplinary audience. As in previous<br />

years, places at the Symposium are limited<br />

Dr John Brennan<br />

Mass spectrometric methods for biological<br />

screening of small molecule mixtures<br />

Dr Nigel Clarke<br />

Mass spectrometry as an enabling<br />

technology in the clinical laboratory<br />

Dr Graham Bench<br />

Emerging trends and technologies<br />

enabling ultrasensitive 14C measurements<br />

for biomedicine<br />

Dr Paul Tempst<br />

Aminopeptidase activities as biomarkers<br />

for cancer<br />

Dr Judith Stone<br />

Automating high throughput LC-MSMS<br />

analysis of 25-hydroxy vitamin D using<br />

liquid handlers and middleware<br />

Dr Robert Moritz<br />

The human SRMAtlas: a compendium<br />

of quantitative mass spectrometry assays<br />

for all human proteins<br />

CORPORATE NEWS TECAN JOURNAL 3/2012<br />

Boston 2012<br />

fifth <strong>Tecan</strong><br />

Symposium<br />

to ensure plenty of opportunities for open<br />

discussions and networking, giving speakers<br />

and delegates the chance to explore novel<br />

concepts, applications and solutions that<br />

might help to address unmet scientific<br />

needs, while enjoying <strong>Tecan</strong>’s hospitality.<br />

To find out more about the <strong>Tecan</strong> Symposium,<br />

including details regarding free registration,<br />

visit www.tecan.com/symposium<br />

Dr Andrew Hoofnagle<br />

Developing methods for LC-MS-based<br />

clinical diagnostics<br />

Dr Mark Libardoni<br />

The role of mass spectrometry in solar system<br />

geochemistry and planetary atmospheres:<br />

past missions to state-of-the-art instrument<br />

development<br />

Dr Burak Eral<br />

eMALDi: suppressing the coffee stain effect<br />

via electrowetting for improved MALDi-MS<br />

detection<br />

Dr Zoltan Takats<br />

Mass spectrometric profiling of biological<br />

tissues: a comprehensive alternative to<br />

classical histopathology<br />

Dr Stuart Black<br />

The application of stable isotope radio mass<br />

spectrometry for forensic analysis of human<br />

skeletal remains<br />

Dr Mehdi Moini<br />

Biological clocks: high throughput identification<br />

of deterioration markers and dating of<br />

museums' proteinaceous specimens<br />

9


10 CORPORATE NEWS TECAN JOURNAL 3/2012<br />

<strong>Tecan</strong> showcases the Freedom EVO®<br />

workstation configured for ELISAs<br />

to delegates visiting from Chinese<br />

blood centers<br />

Delegates from blood centers across China<br />

recently enjoyed a visit to <strong>Tecan</strong>’s European<br />

development facilities in order to share<br />

their experiences and give their input on<br />

performing high quality ELISAs within blood<br />

banking laboratories. <strong>Tecan</strong> demonstrated<br />

a Freedom EVO workstation specifically<br />

configured to meet the ELISA throughput<br />

demands observed in the Chinese clinical<br />

market, incorporating a range of features<br />

to streamline the blood testing workflow.<br />

Efficient throughput is critical in hospital<br />

and blood center laboratories, requiring<br />

reliable automated solutions which are<br />

closely matched to laboratory workflows.<br />

The Freedom EVO offers a flexible configuration<br />

which can be tailored to individual<br />

throughput requirements, with a choice of<br />

either one or two liquid handling arms, up<br />

to two HydroFlex microplate strip washers,<br />

a Robotic Manipulator (RoMa) Arm for<br />

plate transportation and an Infinite® F50<br />

microplate reader. The specific requirements<br />

of the scientist’s assay can be fulfilled by<br />

the use of a variety of incubators, hotels and<br />

carriers, providing complete automation of<br />

the processing workflow.<br />

The Freedom EVO is controlled by <strong>Tecan</strong>’s<br />

intuitive Freedom EVOware® software,<br />

and uses the TouchTools Suite graphical<br />

user interface (GUI) to simplify day-to-day<br />

operation of the instrument. Combined<br />

with <strong>Tecan</strong>’s new QC Kit for liquid handling<br />

performance verification testing, this flexible<br />

solution provides hospitals and blood centers<br />

in China with a straightforward and efficient<br />

way of automating testing.<br />

Delegates from Chinese blood centers visit <strong>Tecan</strong><br />

The visit was arranged in response<br />

to increasing demand for automated<br />

laboratory systems in Chinese hospitals<br />

and blood centers, and reflects <strong>Tecan</strong>’s close<br />

collaboration with customers. This year’s<br />

event built on the success of the previous<br />

visit to <strong>Tecan</strong>’s Männedorf headquarters in<br />

Switzerland in 2010. In addition to seeing<br />

<strong>Tecan</strong> automation in action, delegates<br />

were given the opportunity to visit <strong>Tecan</strong><br />

manufacturing sites in both Männedorf and<br />

Salzburg, Austria, as well as a visit to a Zurich<br />

blood bank to foster relations and exchange<br />

blood bank practices. The visit also included<br />

workshops on various aspects of potential<br />

development, providing customers and <strong>Tecan</strong><br />

specialists with an opportunity to discuss<br />

current and future applications, as well as<br />

the bottlenecks in processing, helping to<br />

drive forward identification of novel<br />

solutions for this important market.


Joining the digital age<br />

TES Pharma is a small biotechnology<br />

company based in Corciano near Perugia,<br />

Italy, specializing in compound screening for<br />

pharmaceutical drug discovery. Combining<br />

an in-depth knowledge of drug design and<br />

chemistry with systems and molecular<br />

biology approaches, the Company works<br />

collaboratively with partners around the<br />

world to combine the best aspects of<br />

academia and commercial pharmaceutical<br />

development.<br />

TES Pharma’s small yet highly skilled and<br />

experienced team works closely with the<br />

University of Perugia to rapidly develop<br />

and explore novel compounds which may<br />

be of interest in various disease states.<br />

To standardize the Company’s workflow,<br />

as well as to free up more staff time for<br />

research activities, TES Pharma has recently<br />

invested in an HP D300 Digital Dispenser<br />

from <strong>Tecan</strong>. Graeme Robertson, a co-founder<br />

of TES Pharma, explained: “The drug discovery<br />

process is becoming increasingly highly<br />

specialized, often involving multiple partners<br />

with distinct skill sets working together<br />

to deliver novel therapeutic agents. Our<br />

core competence at TES Pharma lies in the<br />

development of advanced screening assays,<br />

and we believe that, by working closely<br />

with academic partners with expertise in<br />

individual conditions or disease areas,<br />

we can eliminate some of the drawbacks<br />

inherent in traditional drug discovery<br />

pipelines.”<br />

“To do this we need to concentrate on our<br />

own expertise in core areas, and our<br />

HP D300 Digital Dispenser allows us to<br />

use our time more effectively, without<br />

compromising on results. As a small<br />

collaborative research facility we do not have<br />

a high enough throughput to effectively use<br />

complete laboratory automation systems,<br />

but the HP D300 is easy to use and its<br />

precision dispensing eliminates the need for<br />

tedious manual dilutions. Digital titration<br />

also offers several key advantages over<br />

traditional manual protocols in terms of<br />

reducing waste of valuable compounds,<br />

limiting the DMSO content for sensitive<br />

assays and increasing reproducibility, but<br />

it is the staff time it creates that is most<br />

important, liberating skilled individuals to<br />

perform more exploratory research. It also<br />

allows us to limit the number of variables in<br />

a way that would not be possible manually,<br />

helping us to rapidly characterize novel<br />

biological activities which might otherwise<br />

be missed.”<br />

To find out more about<br />

Direct Digital Titration, visit<br />

www.tecan.com/digitaltitration<br />

To find out more about TES Pharma,<br />

visit www.tespharma.com<br />

DRUG DISCOVERY TECAN JOURNAL 3/2012<br />

TES Pharma is a specialist biotechnology company which performs molecular, cellular<br />

and ADME screening for drug discovery. The Company has recently purchased an<br />

HP D300 Digital Dispenser, and is now reaping the benefits of direct titration with<br />

improved assay reproducibility and more time to perform exploratory research.<br />

Senior scientist Francesca De Franco displays TES Pharma’s HP D300 Digital Dispenser<br />

“ The HP D300 is easy to<br />

use and its precision<br />

dispensing eliminates<br />

the need for tedious<br />

manual dilutions.”<br />

11


12 READERS TECAN JOURNAL 3/2012<br />

A winning combination for<br />

nephrology research<br />

In the last edition of the <strong>Tecan</strong><br />

Journal we announced the<br />

winner of the <strong>Tecan</strong> Award<br />

2011, Svenja Kristina Holle<br />

from the University Hospital<br />

of Münster, whose team has<br />

developed an ex vivo method<br />

for investigating the dynamics<br />

of organic cation transport in<br />

proximal tubules of the kidney,<br />

using an Infinite® 200 PRO<br />

microplate reader.<br />

Svenja Holle<br />

“ We can now study 100<br />

assays at one time, which<br />

has increased the number<br />

of experiments that can be<br />

carried out with one animal<br />

enormously.”<br />

Siegfried Sasshofer presents Svenja with the <strong>Tecan</strong> Award 2011<br />

The Experimental Nephrology laboratory of<br />

the Department of Internal Medicine D at the<br />

University Hospital of Münster (Universitäts<br />

Krankenhaus Münster – UKM), Germany, has<br />

used <strong>Tecan</strong>’s Infinite 200 PRO microplate<br />

readers to further develop its cell-based<br />

techniques for the investigation of cell<br />

membrane transport in the proximal tubules<br />

of the kidney. The team has established a<br />

novel ex vivo fluorescence technique which<br />

enables parallel analysis of numerous samples<br />

in a 384-well microplate format, making this<br />

type of study far easier to perform, while<br />

significantly increasing the number of<br />

experiments which can be carried out with a<br />

limited amount of biological material. Svenja,<br />

a medical student at UKM, explained: “Organic<br />

cation transporters (OCTs) are crucial for the<br />

renal excretion of endogenous organic cations<br />

such as the monoamine neurotransmitters<br />

dopamine and noradrenaline, as well as the<br />

40-50 % of pharmaceutical drugs that are<br />

positively charged. Until now, organic cation<br />

transporters could only be examined using<br />

time-consuming fluorescence or radiotracer<br />

methods; the technique and set-up procedures<br />

were very tedious. We have successfully used<br />

our Infinite 200 PRO readers – we have both<br />

an Infinite M200 PRO and an Infinite F200 PRO<br />

– to develop a microplate reader-based<br />

method that can be adapted to almost any<br />

kind of freshly isolated biological material<br />

and transport system by using a suitable<br />

fluorescent substrate. The method enables us<br />

to study OCTs in freshly isolated proximal<br />

tubules of mouse kidneys, an ex vivo<br />

environment, and has significantly increased<br />

F irst place<br />

our throughput, as we can now place three<br />

proximal tubules in each well of a 384-well<br />

plate, depending only on the isolation<br />

capacity.”<br />

The properties and regulatory mechanisms<br />

of organic cation transport in proximal<br />

tubules of mouse kidneys are of particular<br />

interest with regard to the emerging role of<br />

transgenic mouse models in pharmacological,<br />

physiological or pathophysiological studies.<br />

Svenja continued: “We investigated the<br />

dynamics of organic cation transport by flux<br />

experiments with a fluorescent transporter<br />

substrate, ASP+, which undergoes a shift<br />

in the emission spectrum from 550 nm<br />

to 590 nm when it is transported into cells.<br />

Each individual well of a 384-well microplate<br />

accommodates three segments of freshly<br />

isolated mouse proximal tubules, each<br />

approximately 200 µm long. ASP+ is added<br />

to each well, and the increase in cellular<br />

fluorescence is recorded. By making<br />

fluorescence measurements, we can quantify<br />

cellular accumulation of ASP+, which is<br />

proportional to the extent of organic cation<br />

transport. We can also take advantage of the<br />

Infinite 200 PRO’s dual injection module to<br />

study the properties of OCTs to determine<br />

the affinities of known or unknown substrates;<br />

substrates with high affinities to organic<br />

cation transporters will inhibit the uptake<br />

of ASP+. The method also allows us to screen<br />

for substrates and drugs which interfere<br />

with OCTs, which may open new therapeutic<br />

approaches to reducing drug-induced<br />

damage of the kidney by nephrotoxic drugs.”


Previously, UKM’s Experimental Nephrology<br />

laboratory analyzed the dynamics of OCT<br />

processes using an inverted fluorescent<br />

microscope imaging system, but this<br />

restricted measurement to a very small<br />

number of isolated tubule segments per<br />

kidney and animal, due to tedious and<br />

time-consuming set-up procedures for each<br />

segment. “The new method is far easier to<br />

use, and does not require a lengthy training<br />

period. Before, we could only examine<br />

one tubule at a time using the inverted<br />

microscope, but the new microplate<br />

reader-based technique allows us to perform<br />

several assays in parallel. We can now<br />

study up to 300 assays at one time, which<br />

has increased the number of experiments<br />

that can be carried out with one animal<br />

enormously; this is a huge advantage and<br />

has significantly reduced both the time<br />

and cost of experiments,” concluded Svenja.<br />

To find out more on <strong>Tecan</strong>’s Infinite 200 PRO<br />

series, visit www.tecan.com/infinite200pro<br />

As the 2011 winner of the <strong>Tecan</strong> Award,<br />

Svenja’s prize was a weekend in the romantic<br />

city of Salzburg, which included a tour of<br />

<strong>Tecan</strong>’s Detection Headquarters in Grödig,<br />

Austria. Svenja described her visit to Austria:<br />

“Our trip to Salzburg began with a short<br />

visit to <strong>Tecan</strong>’s production site on Friday<br />

morning. It was really interesting for me to<br />

see the inside of the microplate reader that<br />

I’ve worked with for such a long time, and<br />

to hear about other promising developments<br />

at <strong>Tecan</strong>. I gave a presentation about my<br />

research, and I really appreciated everybody’s<br />

interest in my work; we had a valuable<br />

discussion and I received some really good<br />

suggestions for improving our technique<br />

even further.”<br />

“Afterwards, it was a great honor for me<br />

to receive the <strong>Tecan</strong> Award. The rest of the<br />

weekend was spent enjoying the sights of<br />

Salzburg. Of course, we took the hard climb<br />

up to Hohensalzburg Castle, where we were<br />

rewarded with an amazing view over the city<br />

and the panorama of the Alps. We also loved<br />

having the delicious breakfast in our fantastic<br />

hotel right beside the Salzach, the river which<br />

parts Salzburg into its historic city centre and<br />

the new town. All in all, we will always<br />

remember our great weekend trip to Salzburg<br />

with a smile!”<br />

Svenja prepares to analyze samples in the Infinite 200 PRO<br />

To find out more about UKM’s Experimental<br />

Nephrology laboratory, visit www.campus.<br />

uni-muenster.de/892.html?&L=1<br />

Hohensalzburg Castle, one of the largest medieval<br />

castles in Europe<br />

Svenja and Richard enjoying the magnificent<br />

view across Salzburg<br />

READERS TECAN JOURNAL 3/2012<br />

Svenja enjoying an informative tour of <strong>Tecan</strong>’s<br />

production site<br />

The Salzach river in Salzburg<br />

13


14 DRUG DISCOVERY TECAN JOURNAL 3/2012<br />

Biopharma by design<br />

Isogenica provides peptide, protein and antibody discovery and design<br />

services to pharmaceutical and biotechnology companies, and has invested<br />

in two Freedom EVO® liquid handling platforms to increase its capacity<br />

for the selection of next generation molecules.<br />

Isogenica Ltd, based at Chesterford Research<br />

Park near Cambridge, UK, specializes in the<br />

discovery, identification and design of new<br />

therapeutic peptides, proteins and antibodies<br />

for pharmaceutical and biotechnology<br />

companies. The Company’s proprietary<br />

technology – CIS display – enables rapid<br />

library construction and selection, generating<br />

faster hits and better leads to reduce<br />

discovery time and improve the quality of<br />

candidate options. To meet the demand for<br />

higher throughput, Isogenica has purchased<br />

two Freedom EVO 200 platforms for the<br />

selection of next generation molecules and<br />

for running ELISAs. Neil Cooley, Operations<br />

Manager at Isogenica, explained: “Our clients<br />

provide us with a target molecule and we<br />

use our CIS display technology to discover<br />

binders to that target. We have automated<br />

this technology on the Freedom EVO platform<br />

to make it less labor-intensive and to increase<br />

our throughput, allowing us to do more of<br />

these selections in parallel.”<br />

<strong>Tecan</strong> held comprehensive discussions with<br />

Isogenica to establish the Company’s exact<br />

needs and design the most appropriate<br />

platforms for their selection and ELISA<br />

protocols. Two Freedom EVO 200 workstations<br />

were chosen, each equipped with a Robotic<br />

Manipulator (RoMa) Arm, an eight-channel<br />

Liquid Handling (LiHa) Arm with low-volume<br />

disposable tips and a MultiChannel Arm<br />

(MCA) 96. The selection platform also has an<br />

integrated Infinite® F200 PRO multimode<br />

reader for PicoGreen® analysis of DNA levels,<br />

an LPT 220 EVO Carousel, an extended<br />

Z-axis RoMa, low disposable tip ejector<br />

option and a dust cover, and is used to run a<br />

protocol based on the Company’s CIS display<br />

technology. This platform also takes<br />

advantage of <strong>Tecan</strong>’s SBS format disposable<br />

tip boxes, allowing large quantities of tips to<br />

be stored on the Carousel for increased<br />

walkaway times.<br />

Neil continued: “<strong>Tecan</strong> offered a cost-effective<br />

solution and the Company has a good<br />

reputation; we also liked the training that<br />

was provided with the system. They took<br />

the time to get to know exactly what we<br />

needed and to ensure that we understood<br />

what options were available to us – and<br />

the advantages of each option – including<br />

presentations that explained the benefits<br />

of different semi-automated versus fully<br />

integrated systems. It was particularly<br />

tricky deciding whether to have everything<br />

integrated on the candidate selection<br />

platform or not, where to put all the<br />

options we needed and how to get<br />

the highest throughput.”<br />

Although the Company has had the<br />

workstations for less than a year, the<br />

advantages of automating the selection<br />

protocol can already be observed. Automating<br />

the process enables multiple target<br />

molecules to be tested against a number of<br />

libraries under different selection conditions,<br />

offering the capability to multiplex across a<br />

96-well plate. This provides more versatility<br />

“... the big advantage of<br />

automating the selection<br />

process is that it allows a<br />

larger number of selection<br />

conditions and different<br />

types of library – peptides,<br />

scaffolds or even antibodies<br />

– to be tested with their<br />

target molecule, providing<br />

them with greater choice.”<br />

and improves consistency, which is an<br />

important consideration, as well as allowing<br />

many more selections to be performed than<br />

would be possible manually. The maximum<br />

number of selections that can be comfortably<br />

performed at one time manually is 12 to 16.<br />

In contrast, the microplate format used by<br />

the automated process enables 96 selections<br />

to be performed simultaneously.<br />

Automation of the DNA/protein binding<br />

ELISA protocol on the Freedom EVO has<br />

also proved popular with staff, and has<br />

significantly increased Isogenica’s screening<br />

capacity. When the ELISA is semi-automated<br />

using 96-well plates, one person can process


Isogenica’s selection platform offers multiplexing capabilities in a 96-well format<br />

up to 48 plates a day. Automation has also<br />

enabled the Company to miniaturize its<br />

assays into 384-well plates, which allows<br />

many more clones to be screened with the<br />

same targets in the same time period. “We<br />

need to keep the amount of target used to<br />

a minimum, and moving to 384-well plates<br />

reduces the amount of material we need,”<br />

said Neil. “The platforms’ ease of use has also<br />

encouraged widespread use of the systems;<br />

staff became comfortable with operating the<br />

instruments very quickly. As a result, we have<br />

extended the functions that we currently<br />

carry out on the Freedom EVO beyond those<br />

initially envisaged.”<br />

Isogenica’s clients also reap the benefits<br />

of automation. When a larger number of<br />

selections need to be performed, it is now<br />

possible to run one large batch of samples<br />

on the Freedom EVO, rather than several<br />

small batches manually, enabling more rapid<br />

and consistent delivery of peptide or protein<br />

candidates. “For our clients, the big advantage<br />

of automating the selection process is<br />

that it allows a larger number of selection<br />

conditions and different types of library –<br />

peptides, scaffolds or even antibodies – to be<br />

tested with their target molecule, providing<br />

them with greater choice,” concluded Neil.<br />

DRUG DISCOVERY TECAN JOURNAL 3/2012<br />

To find out more on <strong>Tecan</strong>’s drug discovery<br />

solutions, visit<br />

www.tecan.com/drugdiscovery<br />

To find out more about Isogenica,<br />

visit www.isogenica.com<br />

15


16 GENOMICS TECAN JOURNAL 3/2012<br />

Protecting the nation<br />

Russia’s Central Tuberculosis Research Institute is using a Freedom EVO® workstation to help in<br />

the fight against tuberculosis. The platform provides fast and secure sample preparation, allowing<br />

molecular diagnosis of M. tuberculosis infection in just a few hours.<br />

Founded in 1921, the Central Tuberculosis<br />

Research Institute of the Russian Academy<br />

of Medical Science (CTRI RAMS), Moscow,<br />

is a global leader in the development and<br />

application of advanced techniques for<br />

the effective control of tuberculosis (TB).<br />

The Institute consists of nine research<br />

divisions, including four 400-bed<br />

clinical departments, and the Institute’s<br />

multidisciplinary research team studies<br />

every aspect of the diagnosis, pathology<br />

and transmission of TB.<br />

Diagnosis of TB, and determination of<br />

antimicrobial sensitivity, generally takes<br />

6 to 14 weeks using classical microbiological<br />

methods, delaying provision of appropriate<br />

treatment and contributing to the high<br />

TB-associated mortality rate in Russia.<br />

To reduce this lengthy detection time,<br />

the CTRI RAMS’ Department of Microbiology<br />

– led by Professor Larisa Chernousova –<br />

is investigating new approaches to improve<br />

the diagnosis of tuberculosis, including<br />

a novel genetic technique based on PCR<br />

(polymerase chain reaction). Larisa explained:<br />

“A vital step in this highly sensitive method<br />

is the extraction of DNA from patients’<br />

sputum samples. This is a monotonous and<br />

labor-intensive process when performed<br />

manually, requiring high levels of<br />

concentration to avoid cross-contamination<br />

between samples and subsequent false<br />

positive results, and so is ideally suited<br />

to automation.”<br />

Working in collaboration with Syntol –<br />

a specialized clinical diagnostic company<br />

in Russia – the Institute has developed<br />

an automated protocol that allows safe<br />

and effective handling of potentially highly<br />

contagious M. tuberculosis samples without<br />

the need for costly biosafety measures.<br />

This technique uses an inactivation buffer<br />

to kill any mycobacterium present, offering<br />

safe handling of patient material without<br />

compromising the quality of the extracted<br />

DNA. The workflow was initially developed<br />

on a Freedom EVO 75 before being transferred<br />

to the Department’s Freedom EVO 150<br />

workstation. It includes dilution of the<br />

sputum samples and addition of the<br />

inactivation buffer using the instrument’s<br />

Liquid Handling (LiHa) Arm, magnetic<br />

extraction of the M. tuberculosis DNA from<br />

clinical samples and microbial cultures,<br />

transfer of the extracted genetic material<br />

to PCR tubes, and online PCR amplification.<br />

Professor Chernousova continued:<br />

“Extraction of 48 samples takes just 95<br />

minutes, allowing us to process up to 144<br />

samples a day if required. Once the extraction<br />

process is complete, the recovered DNA is<br />

transferred directly to PCR tubes and<br />

automatically loaded onto a thermocycler<br />

for amplification. This provides true walkaway<br />

processing and significantly increases the<br />

laboratory’s throughput, while also lowering<br />

the cost per test.”<br />

“Even a microdrop of aerosol<br />

containing genetic material<br />

could cause contamination<br />

in this process, but none of<br />

our negative controls showed<br />

amplification by PCR.”


From left to right: Professor Larisa Chernousova, Tatiana Smirnova and Dmitry Varlamov from the CTRI<br />

RAMS’ Department of Microbiology<br />

Due to the high sensitivity of the PCR-based<br />

technique, minimizing the risk of errors<br />

and cross-contamination was crucial,<br />

and so the laboratory carried out rigorous<br />

testing and validation prior to bringing<br />

the Freedom EVO 150 platform into routine<br />

operation. “We were very happy with the<br />

performance of the system during our<br />

carry-over studies,” Larisa added. “Even a<br />

microdrop of aerosol containing genetic<br />

material could cause contamination in this<br />

process, but none of our negative controls<br />

showed amplification by PCR. We have also<br />

been impressed by the flexibility and open<br />

architecture of the platform, and now plan<br />

to use additional <strong>Tecan</strong> workstations for<br />

complete automation of our bacteriology<br />

workflows in the future – from preparation<br />

of reagents and media to culture seeding<br />

and incubation.”<br />

In the first four months of operation, the<br />

laboratory has prepared over 500 clinical<br />

samples for analysis. The Freedom EVO<br />

workstation offers considerable time savings<br />

while reducing the labor required. “This<br />

helps the laboratory to identify the causative<br />

agent of a patient’s symptoms much<br />

faster, providing clinical staff with the right<br />

information to effectively treat patients far<br />

earlier,” Professor Chernousova concluded.<br />

To find out more on <strong>Tecan</strong>’s genomics<br />

solutions, visit www.tecan.com/genomics<br />

GENOMICS TECAN JOURNAL 3/2012<br />

17


18 DRUG DISCOVERY TECAN JOURNAL 3/2012<br />

Investing in the future<br />

of drug discovery<br />

Osaka University’s International Drug Discovery Incubation Group opened its doors<br />

to drug discovery researchers in western Japan in April 2011, providing access to high<br />

throughput technologies including <strong>Tecan</strong>’s Freedom EVO® liquid handling workstations<br />

and Infinite® M1000 microplate reader.<br />

In Japan, Osaka has been known as the<br />

city of medicine since the 17 th century.<br />

The chemical industry, helped particularly<br />

by pharmaceutical companies, is today<br />

the most lucrative of Osaka’s industries<br />

and shows great promise for future growth.<br />

This setting is ideal for the International<br />

Drug Discovery Incubation Group at Osaka<br />

University’s Office for University-Industry<br />

Collaboration to serve as a shared-use<br />

facility funded by the Japan Science and<br />

Technology Agency (JST). The Group’s<br />

primary purpose is to accelerate<br />

collaborative research between academia<br />

and industry by directly supporting the drug<br />

discovery research activities of universities<br />

and businesses throughout the Kansai<br />

region of Japan.<br />

Dr Yoon-Jeong Kim, Leader of the<br />

International Drug Discovery Incubation<br />

Group, explained how the thinking behind<br />

much of the Group’s strategy stems from<br />

the pharmaceutical industry’s ‘gap issue’.<br />

Dr Yoon-Jeong Kim<br />

Osaka University’s International Drug Discovery Incubation Group<br />

“The whole process from hit discovery to final<br />

drug-to-market was traditionally handled<br />

within a pharmaceutical company. It would<br />

routinely take 15 to 20 years for a new target<br />

to be developed into a drug which would<br />

have a 25 year patent, resulting in the actual<br />

trading life of 10 years for that drug. In the<br />

early 2000s, an average candidate success<br />

rate was only one in ten thousand. As a result,<br />

pharmaceutical companies began to focus<br />

their activities on the later phases of drug<br />

development, to help them recover their<br />

investment more quickly. At the same time,<br />

they tried to extend the period of the patent<br />

of drugs that were already on the market<br />

by changing the drug formulation.”<br />

“Universities continued to work on early<br />

stages of drug discovery and the discovery<br />

of new targets, but a gap between this work<br />

and the later development phases performed<br />

by pharmaceutical companies began to<br />

widen. As a result, there are very few new<br />

candidates coming through the drug<br />

discovery portfolio. With a rush of patents<br />

having expired around 2010, many companies<br />

are now struggling to maintain a steady<br />

stream of business revenue.”<br />

“This gap is a big problem throughout the<br />

pharmaceutical industry which must be<br />

addressed. We are tackling this issue head<br />

on by furnishing our laboratories with<br />

a variety of modern, high throughput<br />

instruments and employing methods<br />

that traditionally only pharmaceutical<br />

companies would have used.”<br />

The Group has two Freedom EVO workstations:<br />

a Freedom EVO 100 used mainly for plate<br />

replication, and a custom-configured<br />

Freedom EVO 200 equipped with a Liquid<br />

Handling Arm, an integrated incubator,<br />

a <strong>Tecan</strong> Carousel HS for microplate logistics,<br />

a plate washer, and an Infinite M1000<br />

microplate reader. This system is fitted with a


Steering committee members of the International Drug Discovery Incubation Group. Front row, left to<br />

right: Dr Toshimasa Yasuhara, Dr Hachiro Senoo, Dr Zenichi Terashita. Back row, left to right: Dr Kazuto<br />

Nunomura, Dr Yoon-Jeong Kim and Dr Bangzhong Lin<br />

New approach – dealing with drug discovery<br />

A strategy to fill the gap between new targets and preclinical drug discovery<br />

New<br />

targets<br />

Hit<br />

discovery<br />

Hit<br />

validation<br />

GAP<br />

HEPA filter because many users are<br />

performing cell-based assays which require<br />

aseptic conditions. Plates are transferred<br />

automatically to the Infinite M1000 to collect<br />

the data for some assays, but both the reader<br />

and the plate washer can be used<br />

independently, even while the Freedom EVO 200<br />

is performing unrelated tasks.<br />

Dr Kim added: “These instruments are very<br />

popular, and are being used almost every day.<br />

Many scientists who use our facilities are<br />

performing high throughput (HT) methods<br />

for the first time and, as an organization<br />

dedicated to supporting research, we provide<br />

a substantial amount of specialized training<br />

as required. We teach various techniques<br />

from how to process compounds and set<br />

up cell-based assays to data collection,<br />

and we train researchers so that they<br />

can independently perform HT methods<br />

themselves. In reality, this probably forms<br />

the bulk of our work.”<br />

Lead<br />

optimization<br />

Dr Kim had already had positive experience<br />

of working with <strong>Tecan</strong>’s liquid handling<br />

workstations from his earlier career in a major<br />

pharmaceutical company: “I remembered<br />

many strong advantages for using <strong>Tecan</strong> and<br />

I knew these would also be relevant for our<br />

Group here. <strong>Tecan</strong> has a lot of experience<br />

in the types of applications we were looking<br />

for. We wanted a HT robot that allows many<br />

tasks to be performed by a small number<br />

of people, and <strong>Tecan</strong>’s Freedom EVO<br />

workstation was chosen as a platform to<br />

fulfill this concept. We were confident that<br />

the Company and its instruments would<br />

be a good fit for our laboratory. <strong>Tecan</strong>’s<br />

technical staff members are constantly<br />

in touch to support us and ensure that<br />

the instruments are working as efficiently<br />

and reliably as possible.”<br />

He concluded: “In the future, we plan to<br />

develop our group with the addition of more<br />

instruments that would benefit researchers<br />

DRUG DISCOVERY TECAN JOURNAL 3/2012<br />

“I remembered many strong<br />

advantages for using <strong>Tecan</strong><br />

and I knew these would<br />

also be relevant for our<br />

Group here.”<br />

Preclinical Ph-l Ph-ll Ph-lll<br />

who use the Incubation Group’s facilities.<br />

Clearly, if we stick to the old ways of doing<br />

things, we will inevitably meet difficulties.<br />

There are always processes that need new<br />

techniques to push them forward and,<br />

with a broad range of innovative instruments,<br />

we are working to build a set-up that will<br />

do just that.”<br />

To find out more on <strong>Tecan</strong>’s<br />

Freedom EVO liquid handling workstation,<br />

visit www.tecan.com/freedomevo<br />

To find out more on <strong>Tecan</strong>’s Infinite M1000<br />

microplate reader, visit<br />

www.tecan.com/infinitem1000<br />

To find out more about the International<br />

Drug Discovery Incubation Group at<br />

Osaka University, visit<br />

www.uic.osaka-u.ac.jp/JST/index.htm<br />

(Japanese)<br />

19


20 BIOBANkING TECAN JOURNAL 3/2012<br />

Rapid, automated isolation of buffy<br />

coat benefits DNA extraction<br />

<strong>Tecan</strong> and the Integrated BioBank of Luxembourg (IBBL) have<br />

successfully co-developed an automated platform for buffy coat<br />

extraction based on a Freedom EVO® 200 workstation, relieving<br />

scientific staff from this time-consuming task and significantly<br />

increasing the yield of DNA.<br />

Biobanks such as the IBBL have a vital role<br />

to play in modern medical research, providing<br />

high quality biospecimens, as well as the<br />

technology and scientific expertise to enable<br />

researchers to evaluate data against medical<br />

records and environmental factors. The IBBL<br />

was established following a 2008 Government<br />

agreement to form a strategic partnership<br />

with three US research centers – the<br />

Translational Genomics Research Institute<br />

(TGen), the Institute for Systems Biology and<br />

the Partnership for Personalized Medicine.<br />

Working closely with the Luxembourg<br />

Personalized Medicine Consortium (PMC),<br />

the IBBL collects, stores, and analyzes<br />

biological samples and associated clinical<br />

Fay Betsou, Chief of Biospecimen Science<br />

at the IBBL<br />

“The results are amazing; the<br />

yield is 10 -15 % higher using<br />

the automated process.”<br />

data, from neighboring countries as well<br />

as Luxembourg itself, which are then<br />

made available to research organizations.<br />

In addition to somatic disease collections<br />

for cancer, type 2 diabetes and Parkinson’s<br />

disease research, there is also a normal<br />

population cohort collection from healthy<br />

people – a collaboration with CRP Santé –<br />

that acts as a control.<br />

Today, through its own investigations and<br />

partnerships with internationally recognized<br />

research centers, the IBBL’s world-class<br />

scientists are at the forefront of innovative<br />

biospecimen research. Fay Betsou, Chief of<br />

Biospecimen Science at the IBBL, commented:<br />

“Research often tends to focus on biomarker<br />

identification and validation rather than<br />

specimen validation, but this is a basic critical<br />

issue that could completely invalidate<br />

experimental results. Innovative biospecimen<br />

research is a very important – yet extremely<br />

rare – initiative that is quite specific to the IBBL.”<br />

The IBBL’s biospecimen collection and<br />

biorepository contain high quality tissues<br />

and body fluids, maintained according to<br />

strict quality requirements. The associated<br />

biorefinery analysis and research service<br />

produces high quality analytes, such as DNA,<br />

RNA and protein, maintains technology for<br />

high throughput gene sequencing and gene<br />

expression, and conducts biospecimen research.<br />

In addition, an informatics platform securely<br />

maintains clinical and biospecimen data.<br />

Conny Mathay explains the biobanking process to<br />

students studying for the University Certificate on<br />

Principles of Biobanking<br />

A key target biospecimen for IBBL and many<br />

biobanks and diagnostic laboratories is<br />

the buffy coat, the layer of leukocytes and<br />

platelets that forms when unclotted blood is<br />

centrifuged or allowed to stand, and is often<br />

used for DNA extraction. Traditionally, the<br />

process of manually isolating the buffy coat<br />

from whole blood is slow, tedious and very<br />

dependant on the skill and dexterity of the<br />

technician separating the layers. To eliminate<br />

this time-consuming and variable element<br />

of sampling, the IBBL and <strong>Tecan</strong> joined forces<br />

to co-develop an automated procedure on<br />

a Freedom EVO 200 platform.<br />

Fay explained: “Our sample throughput,<br />

although relatively low at present, is expected<br />

to increase five-fold in the near future, and we<br />

were initially looking for a flexible liquid<br />

handling system that could meet this demand.<br />

We also have particularly strict requirements


The IBBL team with the Freedom EVO<br />

in terms of time; it is crucial to minimize<br />

the delay between sample collection and<br />

freezing, and speed is essential. We looked<br />

at the existing options and spoke to several<br />

different suppliers before choosing <strong>Tecan</strong>.<br />

From the beginning, we could see that as well<br />

as performing classical liquid handling, there<br />

was a real possibility of automating buffy<br />

coat extraction using the Freedom EVO.<br />

This was never going to be an easy process,<br />

largely because of the variation in individual<br />

sample volumes and the quantity, viscosity<br />

and texture of the buffy coat layer itself,<br />

but we had several meetings with <strong>Tecan</strong>’s<br />

technical teams and, over the next couple<br />

of months, worked together to co-develop<br />

an automated method.”<br />

All of the IBBL’s blood samples initially have a<br />

hemocytometer count and CRP measurement<br />

performed to generate basic background<br />

data such as blood cell count and<br />

inflammatory status. Centrifuged blood<br />

collection tubes are placed on the<br />

Freedom EVO platform, which is equipped<br />

with Robotic Manipulator (RoMa), eightchannel<br />

Liquid Handling (LiHa) and Pick and<br />

Place (PnP) Arms, a Tube Inspection Unit (TIU),<br />

an Xtr-96 flatbed scanner (FluidX), Xsd-96Pro<br />

and Xsd-48Pro modules (FluidX), and a BDK<br />

module to provide HEPA-filtered air on the<br />

worktable. The workstation, which is also<br />

used for aliquoting serum, plasma and urine,<br />

has been optimized to maximize the yield<br />

and quality of the buffy coat, and to minimize<br />

the risk of cross-contamination. Tubes are<br />

transferred to the TIU, which identifies the<br />

position of the buffy coat layer using a laser<br />

beam. The buffy coat is then aspirated by the<br />

LiHa using a spiral movement, and transferred<br />

to its destination tube. “The LiHa pipettes the<br />

buffy coat layer with very precise orientation<br />

and speed, standardizing the process and<br />

eliminating technician-to-technician<br />

variation,” Fay added.<br />

BIOBANkING TECAN JOURNAL 3/2012<br />

During the validation process, IBBL found the<br />

automated system gave a purer buffy coat<br />

product with less contamination from red<br />

blood cells and hemoglobin and a similar<br />

distribution of white blood cells, as well as<br />

an average DNA yield significantly higher<br />

than that obtained by manual extraction.<br />

“The results are amazing; the yield is 10-15 %<br />

higher using the automated process.<br />

Altogether, isolating the buffy coat manually<br />

is a tortuous task but the Freedom EVO<br />

system now processes 24 samples in just<br />

16 minutes. We are very satisfied with the<br />

system and are looking forward to working<br />

with <strong>Tecan</strong> on another biospecimen research<br />

project in the near future,” concluded Fay.<br />

To find out more about <strong>Tecan</strong>’s biobanking<br />

solutions, visit www.tecan.com/biobanking<br />

To find out more about IBBL,<br />

please visit www.ibbl.lu<br />

21<br />

Thomas La Mela/Shutterstock.com


22 GENOMICS TECAN JOURNAL 3/2012<br />

Reprogramming nature<br />

Researchers in the Synthetic<br />

Biology Center at the<br />

Massachusetts Institute of<br />

Technology are using a<br />

Freedom EVO® workstation to<br />

aid the development of genetic<br />

circuits. By automating the<br />

laborious liquid handling<br />

protocols, the platform has<br />

increased throughput from<br />

just a few samples to hundreds<br />

of experiments a day.<br />

Genetic circuits are an exciting area of<br />

synthetic biology, with potential applications<br />

in areas as diverse as biofuel production<br />

and medicine. These plasmid constructs<br />

have the ability to regulate the function<br />

of host bacterial, yeast or mammalian<br />

cells, reprogramming them to produce<br />

novel substances, change appearance or<br />

exhibit different behavior. Researchers<br />

in the Synthetic Biology Center at the<br />

Massachusetts Institute of Technology (MIT),<br />

USA, are working on several collaborative<br />

projects to develop genetic circuits for a<br />

variety of applications. Dr Jonathan Babb,<br />

a researcher at MIT, explained: “If you think<br />

about it in engineering terms, we are building<br />

a machine by taking specific DNA sequences<br />

and putting them together in different<br />

combinations to form genetic circuits.<br />

A collection of these circuits can then be<br />

loaded into a host cell, reprogramming it.<br />

The Weiss Laboratory at MIT recently<br />

published an example of this approach,<br />

where a genetic circuit triggers apoptosis<br />

in cancer cells, but not in healthy cells,<br />

offering diagnosis and treatment in one step.<br />

Another potential application is in biofuel<br />

development, re-engineering bacteria to<br />

efficiently produce fuels such as biodiesel.”<br />

“Although we use a modular approach,<br />

development of these genetic circuits is still<br />

very time-consuming and labor-intensive,<br />

and so we purchased a Freedom EVO 150<br />

platform to meet our liquid handling needs.<br />

This platform effectively transforms what<br />

is already done in electronics – pushing<br />

buttons to activate software and hardware to<br />

produce the desired circuit – to our synthetic<br />

biology experiments. Scaling up this process<br />

on a robotic system also gives us higher<br />

throughput and repeatability without the<br />

variability inherent in manual procedures.”<br />

“We specifically chose a <strong>Tecan</strong> system<br />

for this application because the software<br />

and hardware are easy to extend, and we<br />

wanted the flexibility to experiment with<br />

different combinations of modules. The<br />

Freedom EVOware® software has an open<br />

architecture, making it easy to write and<br />

develop scripts and connect the instrument<br />

to our own systems and software, and the<br />

design of the hardware undoubtedly helps<br />

with the integration of our own modules and<br />

apparatus onto the worktable. For example,<br />

we wanted to be able to store enzymes at<br />

-20 oC on the deck, and were able to get an


automation-friendly chiller that could do this<br />

at fairly low cost, without having to make any<br />

major modifications to the platform.”<br />

“We have also been able to devise our own<br />

colony picking procedures for cell-based<br />

screening, and to set up and run an ordinary,<br />

low-cost gel station on the platform. The<br />

Freedom EVO is able to automatically load<br />

and run gels on the gel station, despite the<br />

lack of a communication port on this device,<br />

eliminating the need for a lot of expensive<br />

additional hardware. The flexibility and<br />

programmability of the Freedom EVO are<br />

invaluable for this, allowing us to rapidly<br />

develop in-house solutions and create the<br />

elaborate algorithms that are required to<br />

perform the many different steps necessary<br />

for the assembly of genetic circuits. We have<br />

successfully demonstrated that every step<br />

in the process can be automated and run<br />

completely unattended, and are now scaling<br />

up to high throughput mode, which will see<br />

multiple 96-well plates processed per day.”<br />

LiHa Arm<br />

<strong>Tecan</strong> Freedom EVO 150 at MIT Weiss Lab<br />

Tips<br />

Waste<br />

Cover storage<br />

Stackable<br />

tips<br />

User input<br />

The MIT Weiss Laboratory’s Freedom EVO platform<br />

“<strong>Tecan</strong>’s technical expertise has also been<br />

important to the success of our work, and<br />

we receive excellent application support from<br />

the Company. My colleagues and I attended<br />

a <strong>Tecan</strong> users’ meeting in Boston last October,<br />

specifically to find a solution to the complex<br />

issue of pipetting minute volumes of our<br />

suspensions on the Freedom EVO platform<br />

with the existing liquid classes. <strong>Tecan</strong>’s<br />

application specialists were able to give us<br />

a new liquid class that would not only be able<br />

Hotel<br />

Deep-well plate<br />

Magnet<br />

GENOMICS TECAN JOURNAL 3/2012<br />

4 °C<br />

RoMa Arm<br />

37-60 °C<br />

incubator<br />

Tubes<br />

Gel controls<br />

Camera<br />

position<br />

Gel box<br />

Hotel<br />

-20 °C<br />

Plate<br />

reader<br />

Scanner<br />

User output<br />

to handle the volume and viscosity we<br />

wanted, but also direct the pipette tip to<br />

twist around and tap the side of the vessel,<br />

so that any drop of liquid would come off.<br />

We also have very good ongoing support<br />

from <strong>Tecan</strong> locally – for general advice and<br />

troubleshooting – and are kept up-to-date<br />

with new technologies and solutions which<br />

could further our research.”<br />

To learn more about <strong>Tecan</strong>’s genomics<br />

solutions, visit www.tecan.com/genomics<br />

To find out more about the Synthetic Biology<br />

Center at the Massachusetts Institute of<br />

Technology, visit synbio.mit.edu<br />

23


24 COMPONENTS TECAN JOURNAL 3/2012<br />

Cavro® Air Displacement Pipettor<br />

provides the key to automated<br />

sonochemical synthesis of nanoparticles<br />

Go2 Technologies, a specialized engineering solutions provider, has used<br />

<strong>Tecan</strong>’s Cavro Air Displacement Pipettor to develop a novel automated<br />

method for labor-intensive sonochemical synthesis procedures.<br />

Go2 Technologies in Dayton, Ohio, USA,<br />

has taken advantage of state-of-the-art<br />

manufacturing and engineering technology,<br />

combined with leading-edge robotics and<br />

the Cavro Air Displacement Pipettor (ADP),<br />

to establish an innovative automated process<br />

for sonochemical synthesis of nanoparticles<br />

for the generation of hydrogen gas.<br />

Sonochemical synthesis – chemistry driven<br />

by ultrasound waves – relies on high intensity<br />

sound waves, which are only present near a<br />

powerful sonic probe. This makes it difficult<br />

to perform large-scale reactions and,<br />

as a result, chemists are usually forced to<br />

perform labor-intensive batch procedures<br />

consisting of numerous small syntheses.<br />

To automate these procedures – and decrease<br />

labor costs significantly – Go2 Technologies<br />

has developed the RADS robotic synthesis<br />

machine. Kent Walker, Partner/Owner at Go2<br />

Technologies, explained: “The University of<br />

Dayton Research Institute and the Air Force<br />

Research Laboratory at Wright-Patterson Air<br />

Force Base, Ohio, were creating air-stable<br />

organically-capped aluminum nanoparticles<br />

for the production of hydrogen gas from<br />

water, which involved manually pipetting<br />

three different materials – alane, titanium<br />

isopropoxide, and oleic acid – inside a<br />

glovebox. This is a very labor-intensive<br />

procedure for a single operator, and we<br />

were approached to develop an automated<br />

method that could robotically dispense, mix,<br />

sonicate and verify, essentially to produce a<br />

robotic synthesis machine to automate the<br />

manual pipetting and dispensing stages<br />

within the enclosure.”<br />

The robotic arm holds the Cavro ADP<br />

“The really big challenge of the whole process<br />

was liquid dispensing; we needed something<br />

compact and lightweight that could cover<br />

a large range of volumes, from 15 µl to 10 ml.<br />

Some of the chemicals used are pretty harsh<br />

on plastics, and pumping these materials<br />

through a mechanical piece of equipment<br />

was causing them to degrade and break<br />

down quickly. This was where the Cavro ADP<br />

really came into play. We looked at standard<br />

dispensing-type pumping systems but,<br />

typically, these wanted to bring the liquids<br />

into the device. The nature of the liquids used<br />

meant that we needed to find a non-contact<br />

mechanism for dispensing and pumping,<br />

with tips that were either disposable, or could<br />

be removed and replaced during the process.<br />

Accurate, reliable dispensing of liquid volumes<br />

was also vital. I had previous experience with<br />

<strong>Tecan</strong> and was familiar with its products, so<br />

we approached <strong>Tecan</strong> Systems. The Cavro ADP<br />

was the key to making the whole dispensing<br />

process happen because it doesn’t touch<br />

the liquid, it just brings it into the end of<br />

a disposable pipette tip.”<br />

Kent continued: “The system design is unique.<br />

Unlike the more standardized XYZ robotic<br />

components, the Cavro ADP is free standing<br />

and is manipulated by a Mitsubishi vertical<br />

articulating robotic arm. The Cavro ADP<br />

needed to be used as a pick and place-type<br />

unit rather than being permanently mounted,<br />

so we created custom fixtures and tools from


“The Cavro ADP has been<br />

vital to the success of<br />

the project.”<br />

which the robotic arm could pick it up when<br />

required. We use the Cavro ADP with <strong>Tecan</strong>’s<br />

disposable tips, and have modified the tip<br />

racks to fit our application. Each of the liquids<br />

that we pipette has its own rack of tips and,<br />

once they have been used, we just dispense<br />

them into a waste container within the<br />

purge box. All these adaptations had to be<br />

extremely precise, to ensure that everything<br />

worked reliably and reproducibly.”<br />

“As well as implementing the robotic<br />

solution, we had to develop a custom<br />

airtight chamber that could be purged with<br />

nitrogen. After talking to several vendors<br />

about the inner chamber we realized that<br />

these products were so standardized that<br />

they really didn’t fit our solution, and so we<br />

designed and built the purge box ourselves.<br />

This stainless steel enclosure was specifically<br />

sized to house all the equipment required,<br />

including the vertical articulating arm, the<br />

Cavro ADP, and the reagents, vials and trays.<br />

We had to allow sufficient space for the<br />

robotic arm to operate – pipetting with the<br />

Cavro ADP, capping and uncapping vials<br />

and moving them to a sonic probe – and to<br />

accommodate any cables.”<br />

“We can now perform batch processing of<br />

samples by placing them in individual vials<br />

inside the glovebox, and process an entire<br />

grid of these vials in one run. A batch of up<br />

to 56 vials can be processed, with each one<br />

taking around 20 minutes to complete.<br />

You just load the cell, close the box and<br />

purge it with nitrogen, then start the run<br />

The robotic arm manipulates the Cavro ADP within the purge box<br />

COMPONENTS TECAN JOURNAL 3/2012<br />

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

and walk away. Consistency is essential for<br />

the synthesis to work, and the Cavro ADP<br />

has been vital to the success of the project,”<br />

concluded Kent.<br />

To find out more on <strong>Tecan</strong>’s Cavro ADP,<br />

visit www.tecan.com/components<br />

To find out more about Go2 Technologies,<br />

visit www.go2technologies.com<br />

25


26 MICROARRAY TECAN JOURNAL 3/2012<br />

Making advances in the battle against<br />

autoimmune disease<br />

Scientists at the National Institute of Molecular Genetics in Italy rely<br />

on the Freedom EVO® platform for automated diagnostic screening<br />

of sera from patients suffering from autoimmune diseases.<br />

Autoimmune diseases are caused by an<br />

inappropriate immune response that<br />

results in the body attacking its own<br />

tissues and generating autoantibodies. The<br />

prevalence of these diseases is increasing<br />

worldwide, with only limited diagnostic<br />

tools available. The National Institute of<br />

Molecular Genetics (INGM), based on the<br />

IRCCS Ospedale Maggiore campus in Milan,<br />

Italy, is a non-profit research foundation<br />

that was set up to perform research into<br />

the discovery and initial development of<br />

innovative therapies and diagnostics for<br />

tumors and autoimmune diseases. As an<br />

advanced research center, INGM is creating<br />

a well-defined niche of activities in the<br />

field of human proteomics research, taking<br />

advantage of its location to establish strong<br />

connections with hospital clinics. Its diverse<br />

network of public and private collaborations<br />

with leading Italian and international<br />

institutes and biotechnology companies<br />

is playing a key role in the identification<br />

of new therapeutic targets, and the<br />

development of new diagnostic methods<br />

for neoplastic and autoimmune diseases.<br />

INGM’s proteomic group focuses its<br />

research on the development of reliable and<br />

automation -friendly assays for screening<br />

large sets of sera for new biomarkers in<br />

autoimmune diseases. Mauro Bombaci, group<br />

leader of the protein microarray laboratory<br />

– which specializes in method development<br />

and the validation of novel candidates<br />

– described the Group’s work: “We are a<br />

multidisciplinary research center involved<br />

in the discovery of new signature profiles<br />

in autoimmune diseases. Our work involves<br />

the use of protein microarrays to perform<br />

a variety of assays – including biomarker<br />

identification, antibody specificity profiling,<br />

protein-protein interaction studies and<br />

drug target discovery – and we are currently<br />

turning our attention to the development<br />

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

of a protein microarray containing poorlycharacterized<br />

recombinant human proteins<br />

that are predicted to be surface-exposed or<br />

secreted.”<br />

“We need to be able to perform a wide variety<br />

of tasks and implement new processes, from<br />

general liquid handling for a range of<br />

different purposes, to running ELISA, DELFIA®<br />

and Bio-Plex® assays. High throughput<br />

screening is also important, helping us to be<br />

competitive in the marketplace. To achieve<br />

these goals, we have invested in a Freedom<br />

EVO 150 workstation equipped with Liquid<br />

Handling (LiHa) and Robotic Manipulator<br />

(RoMa) Arms, an integrated Infinite® F200<br />

multimode microplate reader, an ambient<br />

temperature incubator, a HydroSpeed<br />

washer, a Variomag® Teleshake, a heating<br />

plate and various hotels that allow us to store<br />

up to 15 microplates. We also have a HS<br />

4800 Pro hybridization station and an<br />

Infinite M200 microplate reader.”<br />

INGM<br />

Mauro continued: “We use our Freedom EVO<br />

workstation to run fully automated DELFIA<br />

TRF assays. The DELFIA is a robust, high<br />

performance immunodetection assay that<br />

uses Eu-labelled anti-human IgG to detect<br />

antibodies in sera, offering several advantages<br />

over conventional ELISAs, such as enhanced<br />

sensitivity and a wider dynamic range. As we<br />

often use sera from patients suffering from<br />

infectious diseases, we prepare our sera<br />

dilutions prior to analysis in a sterile clean<br />

room, then use the Freedom EVO workstation<br />

to perform the assay, analyzing the samples<br />

and controls in 96-well microplates.<br />

Automating DELFIA protocols on the<br />

Freedom EVO enables us to screen large<br />

sample numbers to validate new biomarkers<br />

in autoimmune diseases.”<br />

“Before we purchased the Freedom EVO, we<br />

used manual and semi-automatic processes<br />

to perform our assays. The system is reliable<br />

and easy to use, and allows us to process


hundreds of samples in a day, taking just two to three<br />

hours for each assay. By fully automating the DELFIA<br />

method on the Freedom EVO workstation, we are now<br />

able to perform in one day what it used to take us<br />

three days to do,” concluded Mauro.<br />

To find out more on <strong>Tecan</strong>’s microarray solutions,<br />

visit www.tecan.com/microarray<br />

To find out more about INGM, visit www.ingm.org<br />

“ By fully automating the DELFIA<br />

method on the Freedom EVO<br />

workstation, we are now able to<br />

perform in one day what it used<br />

to take us three days to do.”<br />

The National Institute of Molecular Genetics, Milan<br />

Antonella Sinisi using the HS 4800 Pro hybridization station<br />

TALk TO TECAN TECAN JOURNAL 3/2012<br />

Simon Fogarty, Director of Application Sciences, <strong>Tecan</strong> US, Inc.<br />

Leading the debate<br />

Mass spectrometry (MS) has long been associated with the analysis of<br />

small molecules and their metabolites as part of the drug discovery and<br />

development process. However, over the last 10 years there has been<br />

a significant increase in the use of MS in a clinical setting, driven by a<br />

number of technical innovations – expanding the range of molecules<br />

that can be detected – and the development of more user-friendly<br />

software and bioinformatics tools.<br />

MS applications now include biomarker analysis, identifying genes,<br />

lipids, proteins and metabolites that have diagnostic potential in<br />

disease management; forensic toxicology applications, particularly in<br />

the analysis of pain management drugs and their metabolites; and lipid<br />

profile analysis to reveal alterations that occur in metabolic diseases.<br />

To support MS customers, <strong>Tecan</strong> has developed a range of sample<br />

preparation applications and protocols on the Freedom EVO liquid<br />

handling platform. From simple sample handling, aliquoting and<br />

dilution protocols to MALDI target plate set-up and advanced sample<br />

processing such as protein crash, liquid-liquid and solid-phase<br />

extraction protocols.<br />

Recognizing the growing importance of this technique to both<br />

<strong>Tecan</strong> and its customers, this year’s <strong>Tecan</strong> Symposium in Boston,<br />

USA, will focus on MS. Titled Mass spectrometry – the expanding role<br />

in life sciences and diagnostics, the Symposium will feature speakers<br />

from a number of organizations using MS techniques in the clinical<br />

environment. Presentations will cover the use of MS technology in<br />

a range of areas including protease analyses as cancer biomarkers,<br />

automation of sample handling for analysis of 25-hydroxy vitamin D by<br />

LC-MSMS, and its use in assays where samples are precious or minimal,<br />

such as pediatrics and neonates.<br />

Email talk@tecan.com to tell us about how <strong>Tecan</strong> can help to further<br />

expand the role of MS in life sciences and diagnostics.<br />

27


28 EVENTS 2012 TECAN JOURNAL 3/2012<br />

Meet <strong>Tecan</strong> at these events<br />

Americas<br />

Microarray World Congress San Diego, CA, USA 25 – 26 Sept 2012<br />

BioProcess International Providence, RI, USA 09 – 11 Oct 2012<br />

AAPS Annual Meeting & Exposition 2012 Chicago, IL, USA 14 – 18 Oct 2012<br />

ISHI 23rd International Symposium on Human Identification National Harbor, MD, USA 15 – 18 Oct 2012<br />

<strong>Tecan</strong> Symposium 2012 Boston, MA, USA 23 – 25 Oct 2012<br />

ASHG American Society of Human Genetics 2012<br />

Asia and Pacific<br />

San Francisco, CA, USA 06 – 10 Nov 2012<br />

A&PD 6th Alzheimer's and Parkinson's Disease Symposium Sydney, Australia 27 – 28 Sept 2012<br />

BPN BioProcessing Network Conference Melbourne, Australia 16 – 18 Oct 2012<br />

Analytica China Shanghai Conference Shanghai, China 16 – 18 Oct 2012<br />

CSBT The 6th National Congress of the Chinese Society of Blood Transfusion Guangzhou, China 07 – 09 Nov 2012<br />

AACB Australasian Association of Clinical Biochemists Conference Melbourne, Australia 15 – 19 Nov 2012<br />

The Japanese Society for the Study of Xenobiotics Annual Meeting Chiba, Japan 20 – 22 Nov 2012<br />

The Annual Meeting of the Molecular Biology Society of Japan<br />

Europe, Middle East and Africa<br />

Fukuoka, Japan 11 – 14 Dec 2012<br />

MipTec Conference & Exhibition Basel, Switzerland 24 – 27 Sept 2012<br />

Scanlab 2012 Copenhagen, Denmark 25 – 27 Sept 2012<br />

HET Instrument 2012 Amsterdam, Netherlands 25 – 28 Sept 2012<br />

ELRIG Pharmaceutical Flow Cytometry & Imaging Alderley Park, UK 10 – 11 Oct 2012<br />

SIDILV Conference Sorrento, Italy 24 – 26 Oct 2012<br />

ESBB European, Middle Eastern & African Society for Biopreservation &<br />

Biobanking Conference<br />

Granada, Spain 07 – 10 Nov 2012<br />

Medica Exhibition Düsseldorf, Germany 14 – 17 Nov 2012<br />

<strong>Tecan</strong> are pioneers in automated liquid handling and innovative life science solutions. For over 30 years<br />

we continue to enable and support our customers to make the world a healthier and safer place.<br />

Headquarters:<br />

<strong>Tecan</strong> Group Ltd., Seestrasse 103, CH-8708 Männedorf, Switzerland<br />

T +41 44 922 88 88 F +41 44 922 88 89 info@tecan.com<br />

<strong>Tecan</strong><br />

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<br />

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<br />

Switzerland +41 44 922 89 22 Uk +44 118 9300 300 USA +1 919 361 5200 Other countries +43 62 46 89 33<br />

www.tecan.com<br />

<strong>Tecan</strong> Journal, Customer Magazine of <strong>Tecan</strong> Trading AG., ISSN 1660-5276<br />

Design: OTM/London www.otmcreate.com<br />

Photography: Günter Bolzern/Zürich www.bolzern.net<br />

Editor in Chief: <strong>Tecan</strong> Trading AG, Cornelia Kegele<br />

Project Lead: <strong>Tecan</strong> Trading AG, Cornelia Kegele/Antonietta Allocca<br />

Editor: kdm/UK www.kdm-communications.com<br />

Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch<br />

Address: <strong>Tecan</strong> Trading AG, Marketing Communications,<br />

Seestrasse 103, CH-8708 Männedorf, Switzerland,<br />

journal@tecan.com, www.tecan.com<br />

To register for the <strong>Tecan</strong> Journal please go to www.tecan.com/journal<br />

© 2012 <strong>Tecan</strong> Trading AG, Switzerland, all rights reserved.<br />

<strong>Tecan</strong> Group Ltd. makes every effort to include accurate and up-to-date information within this<br />

publication, however, it is possible that omissions or errors might have occurred. <strong>Tecan</strong> Group Ltd.<br />

cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy<br />

or completeness of the information provided in this publication. Changes in this publication can<br />

be made at any time without notice. All mentioned trademarks are protected by law. In general,<br />

the trademarks and designs referenced herein are trademarks, or registered trademarks, of <strong>Tecan</strong><br />

Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks.<br />

Product names and company names that are not contained in the list but are noted herein may<br />

be the trademarks of their respective owners. For technical details and detailed procedures of the<br />

specifications provided in this document please contact your <strong>Tecan</strong> representative.<br />

This journal may contain reference to applications and products which are not available in all<br />

markets. Please check with your local sales representative: www.tecan.com/contact

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