tecan journal edition 02/2004

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English Edition 2/2004 - June 2004 Tecan Journal ISSN 1660-5276 Automated Generation of Cell Lines Page 9 Reporter Gene Assay in Ustilago maydis Page 4 Automated NMR Screening to Find Lead Compounds Page 6 www.tecan.com

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The success of Tecan’s products is based on almost 25 years of experience in liquid handling, automation and detection. To make these core competencies more accessible to you,we recently adapted our management structure. Through the new organisation, customer needs and regulatory compliance are now addressed on a more global level. This means you will profit from an improved range of products and services in the future. At the same time we will continue to offer the advantage of immediate access to qualified sales and support experts in your vicinity at your local Tecan office – a service which was always highly valued by our customers.

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English Edition 2/2004 - June 2004

Tecan JournalISSN 1660-5276

Automated Generation of Cell LinesPage 9

Reporter Gene Assay inUstilago maydisPage 4

AutomatedNMR Screeningto Find LeadCompoundsPage 6

www.tecan.com

Contents

Tecan Journal 2/20042

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Editorial

Tecan Supports your Daily Work

Dear Customer

The success of Tecan’s products is based on almost25 years of experience in liquid handling, automationand detection. To make these core competencies moreaccessible to you, we recently adapted our managementstructure. Through the new organisation, customerneeds and regulatory compliance are now addressed on

a more global level. This means you will profit from an improved range of productsand services in the future. At the same time we will continue to offer the advantageof immediate access to qualified sales and support experts in your vicinity at yourlocal Tecan office – a service which was always highly valued by our customers.

This edition of the Tecan Journal contains the usual articles on interestingapplications. On page 4 you will find an article on the contribution of the Safiremonochromator detection reader to research aiming at a better understanding of the interaction between plants and pathogenic fungi, which will in the long runlead to improved methods for the control of plant diseases.

On page 6, we describe an automated application for the preparation of samplesbefore analysis by NMR. Thanks to the advances in automation technology, the useof NMR based methods for compound screening in drug discovery is on the increase.Therefore, this article is also a good demonstration of how Tecan contributes to theprogress of modern medicine.

Cell based assays play an increasingly important role in the secondary screening partof the drug discovery process. The article on page 9 describes the automation of a cellline generation method. According to the growing demand, Tecan will continue toexpand its range of products and services for the automation of cell related methods.

If you are interested in learning more about Tecan and the people standing behindthe products that support your daily work, you may be interested to watch our newcorporate video. Please see page 14, for further details.

Yours faithfully,

Aitor GaldosCEO Tecan Group Ltd.

GenomicsReporter Gene Assay in Ustilago maydis Page 4

Global NewsTecan Supports Investigation of Crimes withLarge Scale Automated DNA Typing System

Page 3

Page 6

ProteomicsAutomated NMR Screening to Find Lead Compounds

Page 12

New ProductsFast and ReliableAutomated MicroplateProcessing – Freedom EVOlyzer

Page 9

Drug DiscoveryAutomated Generation of Cell Lines

Page 15

Local NewsDriving Innovation – Tecan DemonstratesNew Products at International Exhibitions

Page 13

Tecan PlusTake Advantage of Tecan’s Helpdesk Service

Page 14

EventsPreview on Conferences and Trade Shows 2004

Global News

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Tecan has signed an agreement with theSouth African Police Service to supply, installand provide customer support for its fullyautomated forensic DNA typing system.Tecan’s experience in automating genomicsapplications will play a central role in theoperation of South Africa’s national forensicDNA databank. The ¤8.35-million contractwas secured by Tecan’s German subsidiaryafter an open invitation for internationalbids. The project is financed by a EuropeanUnion initiative to assist reconstruction anddevelopment in South Africa.1

The South African national forensic databankcontains DNA samples that may be analyzedby electrophoresis to create DNA profiles.Such methods have revolutionized forensicscience by enabling drastic improvements inthe identification of individuals whosesamples are included in suspect databanks.The government of the United States aloneplans annual investments of $60 million overthe next five years to increase the capacity forDNA identification of state and local crime labs.2

Tecan Supports Investigation of Crimes withLarge Scale Automated DNA Typing SystemTecan signs agreement with South African Police Service to provide a fully automatedDNA typing system for national forensic databank

Tecan’s solution, which is based on its large-scale TRAC3 system, will permit fullyautomated DNA typing from blood andother body fluid or from tissue samplescollected at the scene of a crime. In terms of size and throughput, the proposedinstallation for the South African PoliceService is probably unrivalled by any similarsystems currently in operation.

Martin von Lueder, President of TecanEurope, remarked “Tecan’s extensiveexperience in automating a wide range of genomic applications, including thosesupporting the forensic sciences, was a keyfactor in our successful bid for this project.Our proven ability to develop and implementpowerful customer solutions combined withour strengths in customer support and large-scale automation projects clearlydifferentiated our solution from the proposalsof our competitors.” He added: “The SouthAfrican project is one of the first nationwideDNA forensic programs to be introduced in anon-academic setting.”

Keith Morris (SAPS, left) and Martin von Lueder during the signing ceremony of the contract for the automated DNA typing system in South Africa.This project is an excellent demonstration of Tecan’s unique experience in automation of genomic applications and in integrating large scalelaboratory systems.

Christo Weitz, Senior Superintendent of theSouth African Police Service Forensic ScienceLaboratory commented: “We are extremelypleased to have the support of the EuropeanUnion and Tecan in this far-reaching projectto improve the level of service that our facilityis able to offer the people of South Africa.Undertakings of this sort protect civil libertiesand help to ensure the operation and furtherdevelopment of a judicious legal system.”

1 European program for reconstruction anddevelopment in the Republic of South Africa,Robotic automation of the crime index of theDNA criminal intelligence database, Financialagreement no. SA/99/73200/024.2 Statement from US Attorney General JohnAshcroft given to the American Academy ofForensic Sciences, February 2004.3 Tecan Robotic Assay Composer.

Genomics

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Reporter Gene Assay in Ustilago maydisEstablished by Dr. Florian Kaffarnik and Dr. Michael Feldbrügge, Max-Planck-Institute for Terrestrial Microbiology, Marburg, Germany

Ustilago maydis, a pathogencausing plant tumors Ustilago maydis, the causative agent ofmaize smut disease, is a widely distributedplant pathogen. Although economicaldamages caused by this fungus are relativelysmall, it serves as a model organism forfungal plant pathogens. For sexualdevelopment infection of a host plant isessential. This infection requires fusion ofhaploid sporidia of different mating types on the plant surface. The resulting dikaryongrow filamentously and infects the plant.The mating types of Ustilago maydis aredetermined by two gene loci, a and b. Thebiallelic a-locus is responsible for recognitionand fusion of the cells, whereas the b-locuscontrols filamentous growth. In the plantmassive proliferation of fungal materialoccurs and consequently tumors are formed.At the Max-Planck-Institute for TerrestrialMicrobiology a group of seven researchscientists works on fundamental mechanismsinvolved in signal transduction processesduring mating in Ustilago maydis.

Development of an assay forexamination of signallingmechanismsHaploid sporidia are cultivated in growingmedium and can easily be transformed byhomologous recombination. Mating typegenes of the a-locus code for apheromone/pheromone receptor system.Pheromone of one mating type binds to thecognate receptor of the other mating type.Binding leads to a morphological changefrom yeast-like to filamentous growth andformation of conjugation hyphe.Additionally, expression of the a-genes isinduced. Central regulator of these earlyevents during mating is the transcriptionfactor Prf1. Activity of Prf1 is controlled by a MAP kinase cascade. The research group at the Max-Planck-Institute investigated the possibility of other signal transductionpathways being involved in signalling afterpheromone recognition, because there werehints that cyclic AMP (cAMP) might play a role. To answer that question, promoter

analysis was performed using greenfluorescent protein (GFP) as a reporter gene.As promoters, 4 different constructs havebeen used to show whether pheromoneresponsive elements (PREs) are necessaryand sufficient for the cAMP-mediated geneexpression.

Experimental designRecombinant U. maydis cells, harboringappropriate promoter GFP constructs, weretreated for 6 hours with artificial pheromoneor 18 hours with cAMP-containing media.After treatment cells were transferred to amicroplate and GFP fluorescence and opticaldensity were directly measured using aSafire microplate reader. Fluorescence servedas a measure for the amount of GFP in thecells and therefore for the activity of thecorresponding promoter. In addition, it wasnecessary to determine absorbance at600 nm (OD600), because fluorescenceintensity depends on the density of the cellculture. Hence, fluorescence was normalized

Dr. Florian Kaffarnik with the Safire microplate reader.The power of the monochromator based detection is now available in the recently introduced Safire2.

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Life cycle of Ustilago maydis. Picture of tumor on maize plant.

Flexible system with high sensitivity

to the optical density. For exact measurementof GFP fluorescence it was furthermoreimportant to adapt the excitation andemission wavelength, because the cellsexhibited autofluorescence in the range of theexcitation and emission wavelength of GFP.

Thus, for this experiment the use of amonochromator-based detection system was crucial, allowing the measurement ofthe OD600 as well as the quantification of GFP-fluorescence. The system also required a very high sensitivity to also detect smalldifferences in the expression of GFP. Tecan’sSafire also allowed the fast measurementof many samples in 96-well microplates,resulting in a high throughput to obtainstatistically significant data in a timeefficient way.

Tecan’s Safire monochromator-basedmicroplate reader – an ideal solutionThe use of Tecan’s Safire, a monochromator-based microplate reader, allows the necessarywavelength alterations and is sensitive enough

to measure the fluorescence of the cells.For the frequently changing wavelengthsSafire utilizes specially designed fast-scanning double-monochromators forhighest sensitivity making the use of optical filters for changing wavelengths in fluorescence and absorbance obsolete.While filter-based systems require filters for each new wavelength, Safire has allwavelengths on board making it effortless to tune the system according to the assay.

Genomics

For more information on the experimentsplease refer to The EMBO Journal, Vol 22,No. 21, pp 5817-5826, 2003.

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Proteomics

Figure 1: The system is based on two Tecan sample preparation platforms, a Genesis 100 (not shown) and a Genesis 150, both connected with 600MHz NMR instruments throughSampleRail systems.

Figure 2: Automation of NMR-based screeningtechnologies has enormously increased theimportance of this technique in industrialdrug research.

IntroductionAutomated NMR-based screeningtechnologies are now available and provingto be an increasingly important tool for drugdiscovery. The use of NMR for screeningchemical libraries to find lead compoundshas a number of advantages. Specificknowledge of the target function is notrequired, and neither is the developmentof a target-specific assay. Therefore, thisuniversal technique for the detection of inter-molecular interactions can be applied todrug discovery programs with very littlemethod development. NMR is extremelysensitive for weak interactions (down tomillimolar range) and can provide detailedstructural information on the ligand-bindingmode. NMR screening directly measures theinteraction between the ligand and thetarget, thereby minimizing false positives.

The Structural Chemistry Laboratory inMölndal, Sweden, is one of AstraZeneca’scompetence centers and serves the entireAstraZeneca R&D community for informationon structural chemistry. The laboratory isinvolved in pre-clinical drug discovery

projects world-wide and interacts mainlywith medicinal chemistry groups in order tohelp focus chemistry development towardsmolecules that show higher affinity to drugtarget proteins. Besides helping chemists tounderstand and optimize the interactionsbetween their lead compounds and targetmolecules, the NMR group is also involved inlead generation programs. This includes thescreening of relatively large libraries of drugfragments to find molecules with affinity toany protein of interest.

NMR screening process The system (Figures 1, 2 and 3) is based ontwo Tecan sample preparation platforms,a Genesis 100 and a Genesis 150, bothconnected with 600MHz NMR instrumentsthrough SampleRail systems (Bruker BioSpinAG). In a typical experiment to studymolecular interactions, data are acquiredthree times: at first only the test compoundis measured, then the compound togetherwith the target to analyze molecularinteractions. In the last step an establishedinhibitor is added to measure competition

between the test compound and theinhibitor (Figure 5).

At the beginning of the screen, the emptyNMR tubes sit in spinners (holders) mountedon the Genesis workbench. After pipetting500 µl of buffer into the tubes, one or severalcompounds of interest are added (up to 12can be pooled in one tube). Then the spinneris picked up by the Robotic Manipulator Arm(RoMa) (Figure 4) and moved to a trolley,which is mounted on the SampleRail. Thistrolley moves the sample to the NMRspectrometer and places it into the magnetfor data acquisition. When data has beenacquired the sample is moved back to theGenesis and put into its original position.For the screening of molecular interactions a small amount of protein is added to thetest compounds and the sample is measuredagain in the spectrometer. In a third step, asmall amount of an established inhibitor isadded to the protein-compound mixture andthe sample is measured once more. Whenworking with oxidation-sensitive proteinsArgon gas is dispensed onto the top of thesample after each pipetting step.

Automated NMR Screening to Find Lead CompoundsRutger Folmer, Structural Chemistry Laboratory, AstraZeneca R&D, Mölndal, Sweden

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Proteomics

Figure 3: The automated NMR system at the Structural Chemistry Laboratory of AstraZeneca in Mölndal, Sweden.

A total of three pipetting needles are usedfor the entire process, all mounted on theLiquid Handling Arm (LiHa) of the TecanGenesis platform: One needle connected to a 1 ml syringe for pipetting the protein andbuffer, a needle with low-volume option and250 µl syringe for the compounds, and athird needle for dispensing the Argon gas.A special carrier is provided to keep theprotein cooled at 4°C to increase its stability.

Advantages of automationWhen comparing the automated systemwith the conventional manual screen theadvantages of automation are obvious.Instead of preparing each sample manuallythe automated system can prepare NMRsamples “on the fly”. The Genesis system islinked to a software program (NMR-MCP),which in turn communicates with Bruker’ssoftware packages, controlling theSampleRail and the data acquisition in the NMR spectrometer. Connecting all thecomponents of the system allows samples tobe prepared just in time for data acquisition.

This is a very important feature as manyproteins become quite unstable under theconditions in which they are measured.Prior to using the automated system,a larger number of samples had to beprepared in one step in order to get thedesired throughput, which had a significantinfluence on the quality of the measurement.With the Genesis-SampleRail system,samples can be measured 24 hours a day immediately after they are prepared,which significantly increases both throughputand quality. Certainly, the system alsoprevents pipetting errors, one of the mostlikely errors when manually pipettingcompounds from 384-well plates.

Previously, the Structural ChemistryLaboratory at AstraZeneca used a lesscomprehensive system without the liquidhandling options. Although the NMR wasable to process samples 24 hours a day, allpipetting steps were performed manuallyand this limited the measurements largelyto normal working hours. Besides the timelimit for preparing samples it was also an

error prone task. With the fully automatedsystem in place, researchers can accomplishother more challenging and rewarding tasksthan pipetting.

ConclusionAutomation of the well-established NMR-based screening has enormously increasedthe importance of this technique inindustrial drug research. Today NMRscreening is applied in many areas such as macromolecular interactions, fragment-based drug design and the analysis of drugmetabolism. The technique constantlybenefits from novel applications of well-established methods as well as from newemerging innovations in NMR research.By eliminating error prone manual tasks and increasing speed and throughput of the method, automated solutions, as inmany other research fields, have broughta big boost to the role of NMR screeningtechniques in the research process of thepharmaceutical industry.

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Proteomics

Figure 4: The spinner is picked up by the Robotic Manipulator Arm and moved to a trolley, which ismounted on the SampleRail. This trolley moves the sample to the NMR spectrometer and places itinto the magnet for data acquisition.

Figure 5: NMR is extremely sensitive for weak interactions (down to millimolar range) andprovides detailed structural information on the ligand-binding mode.

Automated NMR-screening

for effective drug development

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IntroductionCell lines play a key role in the process ofdrug discovery wherein stably transfectedcells work as a system to (over-) expressfunctional proteins under native conditions(e.g. GPCRs, ion channels, nuclear receptors)or can fulfill the function of an in vitro modelfor tissues or organs. By investigating thebehavior of living cells following treatmentwith drugs, highly valuable insight can begenerated to predict the interaction andspecific effect of drugs on the expressedprotein. Advanced analysis technologies suchas kinetic methods or reporter assays areused to measure the reaction of a cell underthese different experimental conditions.

This article presents a procedure that releasesthe user from almost all repetitive tasks bygenerating cell lines automatically using aTecan Genesis Workstation system.

Material and methodsInstrumentsTecan Genesis Workstation 200/8 with Te-MO 96: 500 µl syringes, standard volumetips, standard wash station, fast wash pump,Te-MO 96 (Fig 6). Te-Stack for Te-MOdisposable tips.

Automated Generation of Cell LinesDr. Eward Pap and Dr. Silke Grueneberg, Aventis Pharma Deutschland GmbH,LG High Throughput Screening, Frankfurt am Main

Laminar flow cabinet

Liconic StoreX 200™ robotic incubator

Microscope: High precision motorized-focuswith a motorized X-Y stage for moving 384plates from well to well

Chemicals and accessoriesTransfecting reagent, FuGENE 6®Transfecting system (Roche)

Cells: Hamster or human cells

TransfectionFresh cells are positioned onto the Genesisworktable where the transfection is performedaccording to the supplier’s recommendationsusing the Liquid Handling Arm (LiHa).After transfection and antibiotic selectionthe transfected cells are diluted to singlecells into 384 plates (Fig 2).

After growing the single cells to colonies theTe-MO prepares several plate copies withdifferent cell numbers from these 384 platesby detaching the cells with trypsin.The medium is completely removed and thecells are washed once with the appropriateamount of PBS. After that trypsin is addedimmediately and the cells are incubated for

Drug Discovery

Figure 1: With the open concept of the Tecan robotic platforms, several modules and third party devices can be combined to a fully automated cell linegeneration system.

2-5 min before fresh medium is added.Cells are gently mixed by pipetting and theresulting cell suspension is transferred to the daughter plates. Several copies of thatplate are made, each with a different volumeof cell suspension resulting in plates withvarious cell densities. In a final step the wellsare filled with fresh medium and the cells canbe cultivated under appropriate conditions.

Identification of transfected cellsCell inspection and single cell colonyidentification is made by an automatedmicroscope that incorporates a high precisionmotorized-focus and a motorized X-Y stagefor automated image capture of all wells ofa 384-well plate.

The image processing software calculatesthe number and growth rate of cell coloniesper well represented in a list (Fig 3), which isconverted into a worklist for Gemini.

Cells of a certain well are picked and collectedin a new mother plate at a defined positionusing the LiHa. Detaching and suspensionprocedures are as described above.

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Drug Discovery

Cell maintenanceIncubation of cells takes place in either 96 or 384 well plates in a Liconics StoreX 200system at 37°C and approx. 95% humidity.After three days the medium is exchangedusing the following procedure: The roboticmanipulator of the Genesis Workstation placesthe plate from the StoreX onto the Te-MO.The old medium is completely removed and fresh medium is added immediately.This process must be performed quicklywithout letting the cells become dry.

The media can be purchased ready to usewith all ingredients included or can beprepared freshly by adding further componentson the Workstation. Media and plates withoutlids must be handled under sterile conditions.Therefore the complete workstation ishoused within a laminar flow cabinet.

ResultsTransfection: By choosing the appropriatesystem and protocols transfection can beperformed using the LiHa. The transfectionefficiency is similar to manually performedprotocols (Fig 4).

Cherry picking with LiHa: Using the fullyautomated microscope, cell colonies can beidentified and a list of their well positions in the 384-well can be prepared. This list isconverted into a worklist for Gemini/FACTS,which is the control software of the TecanGenesis Workstation 200/8. The LiHaperforms cherry picking of the coloniesaccording to the worklist and collects thecells into new mother plates. By these steps,new mother plates of cell lines are prepared.

Figure 2: Schematic workflow of the cellgeneration process.

Figure 3: Detection of successfully transfected cells in a 384 well plate. The microscope creates alist, which is converted into a Gemini worklist to pick cells from the mother plate into a newdaughter plate.

Cell maintenance with StoreX and Te-MO on a Genesis Workstation (Fig 5): The cellmaintenance procedure allows mediumexchange every 3 days. The use of the Te-MOwith a sterile filter disposable tip (diti) and a slow aspirate and dispense speed enablesthe medium in 384-well to be exchanged inless than 60 seconds. The Te-Stack fed withup to 12 racks provides the system with newditis. New daughter plates can be created ifrequired for further purposes.

Discussion Recently, the generation of cell lines has becomea standardized process due to the use ofcommercially available, validated transfectionmethods. Furthermore, the handling of a largenumber of cell clones treated with the sameprotocol and under identical conditions makescell line generation highly suitable forautomation.

Figure 6: Fully automated generation of stable cell lines and cell maintenance with Te-MO.

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Comparison of automated and traditional cell line generation processesExisting process New automated process

Transfection Manual Automated by LiHa or,optionally, manual

Antibiotic selection Manual Automated by LiHa

Limited dilution into 384-well Semiautomated with dispenser Semiautomated withdispenser

Detection of single cells Via microscope, Via microscope,manually transfer from manually transfer from incubation unit to incubation unit to microscope microscope

Picking of positive cells Manual Automated via LiHa

Cell maintenance procedure Manual Automated via Te-MOon Genesis

Drug Discovery

The application described here represents anautomated approach for cell line generation.It includes the automated transfection,antibiotic selection and cell maintenance of the successfully transfected cells on a compact Tecan Workstation system.Due to the open concept of the Tecan roboticplatform, the Tecan workstation combinesTecan’s Te-Stack and Te-MO system withintegrated 3rd party storage and reagentsupplying devices to a complete, fullyautomated cell line generation system (Fig 6).

The automated approach relieves the userfrom repetitive tasks. By retaining the overalltime for the complete process, the effectiveworking time is reduced by about 50–60%compared to the manual procedure.

Figure 4: Successfully transfected human embryonic kidney cells 293 express a green fluorescence.

Figure 5: The direct integration of the LiconicStoreX 200 robotic incubator to the Genesisenables automated cell maintenance processes.

The automated approachrelieves the user from

repetitive tasks

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Fast and Reliable Automated MicroplateProcessing – Freedom EVOlyzer®Tecan’s new Enzyme Immuno Assay (EIA) analyzer is a flexible workcenter that fits inevery laboratory

Freedom EVOlyzer includes state of the art reader, washer and incubation units and will beavailable in four sizes - 75, 100, 150, 200 - ideal for low to high throughput and various batch size requirements.

Parallel sample pipetting and continuousloading enables optimized scheduling ofFreedom EVOlyzer.

A graphical editor tool allows easy definitionof processes.

New Products

The Freedom EVOlyzer is Tecan’s newEnzyme Immuno Assay (EIA) analyzerenabling fully automated microplateprocessing. Freedom EVOlyzer is available in different sizes for all throughput andbatch size requirements and includes highquality components dedicated to fast andreliable EIA automation.

The Freedom EVOlyzer comes with 1-, 2-, 4- or 8- tip liquid handling arm and anindependently operating roboticmanipulator arm. It offers a maximum of 12 RT and 12 independently heated incubationchambers, up to 32 plate storage positionsand full automation of all washing andreading steps by Tecan’s reliable ColumbusWasher and the well proven Sunrise reader.The new loading interface enables continuousand flexible operation of the system.

All Freedom EVO standard safety features are included.

To maximize the convenience for the routineoperator and to allow for safe process control,Freedom EVOlyzer offers a guided graphicaluser interface in several languages, designedto support touch screen operation.Complementary user management, fullprocess traceability and documentationfulfill the requirements of a routinediagnostic laboratory.

New software for increasedthroughput and safetyAll EVOlyzer products are driven by the newEVOlyzer software to reduce effort and costfor application setup and operator training.Freedom EVOlyzer uses parallel pipetting fortransfer of samples to multiple plates, which

speeds up operation by optimal utilization of system resources. The high speedperformance of Freedom EVOlyzer isguaranteed through the combined use of independent plate transport, a 16 channelwashing unit and continuous loading ofsamples, reagents and plates by a newloading interface.

To secure safe operation, the EVOlyzersoftware controls all liquid levels, schedulesall necessary interactions and guides theoperator by LED signals on the loadinginterface to execute required reloading steps.Monitoring of user interactions combineshigh speed performance with the highestpossible process and operator safety.

Tecan Plus

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Broad reach of customer supportWhether you need assistance in reliableautomation, precise and safe liquid handling,maintenance and operation of automationor detection systems, our services are inplace to assist you. We’re able and ready to offer the expertise you might require to ensure the effective use and high-performance operation of our sophisticated,leading-edge instruments and systems.

Support wherever you areThe high level of our Customer SupportServices offers immediate advantages toyou. Helpdesks are maintained at Tecansubsidiaries worldwide and trained qualifiedspecialists are available to help you in yourlocal language. Most calls to our local helplines are handled by the local expert orpassed on to a qualified field specialist.For more intricate problems, members ofTecan’s highly skilled R&D and productionteams are readily at hand.

Take Advantage of Tecan’s Helpdesk Service A call to your local helpdesk gives you access to a network of highly qualified experts

A service offering high valueWe aim to provide you with courteous,timely and efficient service that will exceed your expectations. Customer focus is paramount and therefore we continuallytailor our services and solutions to yourrequirements. But we don’t stop there.We’re confident that whatever yourrequirements, whatever your challenges,our experts find the ideal solution. It’s allpart of Tecan’s comprehensive service thathas been designed to give you peace of mind.Therefore, just call your local helpdesk!

Comprehensive customer support is provided from a competent, enthusiastic team of friendly support staff in your local Tecan office.

For immediate support pleasecall your nearest helpdesk:Austria +43 62 46 89 33 256

Belgium +32 15 42 13 19

France +33 820 88 77 36

Germany +49 1805 83 22 633 or +49 1805 TECAN-DE

Italy +39 02 215 21 28

Japan/Tokyo +81 42 334 88 10 Osaka +81 6 63 05 85 11

Netherlands +31 18 34 48 174

Portugal +351 21 000 82 16

Spain +34 93 490 01 74

Scandinavia +46 317 54 40 00

Switzerland +41 1 922 82 82

UK +44 118 930 0300

USA +1 800 832 26 87 or 1 800 TECAN-US

Events

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Tecan on the RoadPreview on Conferences and Trade Shows 2004

Date Event Location

Sweden:13-18 June IFBLS 2004 Stockholm http://www.vardforbundet.se/

ifbls2004/index.asp

France:22-25 June GTBIO Lyon http://www.ibcp.fr/rhaser/gtbio/

UK:11-15 July ISBT 2004 Edinburgh http://www.isbt-web.org/

16-17 November Labautomation Europe London http://labautomationeurope.com

Netherlands:1-5 November Het Instrument 2004 Utrecht www.hetinstrument.nl

Germany:24-27 November Medica Düsseldorf www.medica

North America:12-16 June ALA LabFusion Boston, MA http://labautomation.org/LF/LF04/

17-27 July ACA Chicago, IL http://www.uic.edu/orgs/aca2004/

25-29 July AACC Los Angeles, CA http://www.aacc.org/2004AM/default.stm

8-13 August Drug Discovery Boston, MA www.drugdisc.com

11-15 September SBS Orlando, FL www.sbsonline.com

Japan:29 September – 1 October The Japan Society for Clinical Yokohama http://www1.sphere.ne.jp/jidouka/

Laboratory Automation

Always up to date: http://www.tecan.com/index/com-ev-entry.htm

Have you ever wished to know more about Tecan and the people standing behind the productsthat support your daily work? If yes, you are likely to want to see our new corporate video“Tecan – Powering Advanced Medicine”. It gives a brief overview of the company. In addition,for each of Tecan’s business areas, product managers highlight the prominent features of theirproducts.

You can access the video on our website in a streaming format. Alternatively, please visit us atone of the events listed above or call your nearest Tecan office for a demonstration by one ofour sales representatives.

Tecan – Powering Advanced Medicine

Local News

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Tecan JournalCustomer Magazine of Tecan Group Ltd.ISSN 1660-5276

Circulation: 9,000 copies (German),10,500 copies (English)Publisher: Tecan Group Ltd.Editor: Dr. Josef SyfrigAddress: Tecan Group Ltd.,Seestrasse 103, CH-8708 Männedorf, SwitzerlandTel: +41 1 922 88 88 Fax: +41 1 922 88 90E-Mail: [email protected]: http://www.tecan.com

Design, Editing and Layout: Northbank CommunicationsMeadowside, Mountbatten Way, Congleton CW12 1DN, UKE-Mail: [email protected] and Printing: DAZ Druckerei Albisrieden AGGrafische Dienstleistungen, Albisriederstrasse 252a, CH-8047 ZürichCopyright: All rights are reserved by Tecan JournalPhotos and Illustrations: Tecan Germany GmbH,Tecan Group Ltd, Northbank CommunicationsTypography: Type set in Thesis from LucasFontsSubscription: For a free subscription to Tecan Journal, pleasecontact your nearest sales office (see back cover of this issue) or send an e-mail to: [email protected]

Masthead

Driving Innovation – Tecan DemonstratesNew Products at International Exhibitions

Forum LABO 2004, Paris, France.Pittcon 2004, Chicago, Illinois, USA.LabAutomation2004, San Jose, California, USA.

This spring, Tecan participated at several international exhibitions and demonstrated important new laboratory automation and detection products.

Tecan’s booth at LabAutomation2004 exhibition on February 2-4 in San Jose, California, USA, featured the following products for the first time ata major trade show:

Cellerity – A powerful cell and protein production system providing a high-throughput solution for fully automated cell culture maintenance,cell-line expansion and harvesting with minimal process development.

Freedom EVOware® – A software for controlling robotic platforms providing an unmatched combination of flexibility and ease-of-use forbeginners with no experience and automation experts setting up complex multi-device schedules.

Safire2 – A monochromator-based microplate reader combining improved flexibility in an easy-to-use modular format with a wide range of high-speed fluorescence techniques.

Cavro™ XLP 6000 – A high performance syringe pump with 6,000 (standard 6,000/48,000) increment resolution.

In addition, Tecan lead numerous workshops and poster presentations with strategic partners including Amersham, Corning, Invitrogen and Millipore.

Other international exhibitions where visitors could see demonstrations of Tecan’s new and existing solutions this Spring included Pittcon in Chicago, Illinois, USA, from March 8-11 and Forum LABO in Paris, France, from March 23-26.

You no longer have to choose one reader for assay development and another for highthroughput screening. The monochromator-based Safire2 has the speed, sensitivity,flexibility and capacity to do a great job of both, and anything in between. The fastscanning mode of Safire2 enables recording of excitation spectra, emission spectra orabsorbance spectra with high speed comparable to diode array spectrometers. Safire2 givesthe two readouts required for ratiometric assays, such as FP or FRET, almost simultaneously,making the need for two detection channels redundant. Its modular design allows easyupgrading, making Safire2 the reader of choice for most applications, includinghomogeneous, ratiometric biomolecular assays, HTS applications, multi-labeling assays,cell-based assays, DNA and RNA quantification, reporter gene assays, and many more.

One microplate reader suited for both Assay Development and HTS

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Genomics • Proteomics • Drug Discovery • Clinical Diagnostics