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Look Closer.
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Science is proud to be co-recipient, with Nature, of Spain’s 2007
Prince of Asturias Foundation Award – Communication and Humanities.
Since 1981, the foundation has recognized world leaders in scientific,
technical, cultural, social, and humanitarian work. We are honored
to be in their company.
Congratulations to all the 2007 winners.
Arts – Bob Dylan
Communication and Humanities – Journals Science and Nature
Concord – Yad Vashem, the Holocaust Museum in Jerusalem
International Cooperation – Al Gore
Letters – Amos Oz
Scientific and Technical Research – Ginés Morata and Peter Lawrence
Social Sciences – Ralf Dahrendorf
Sports – Michael Schumacher
Official photograph of T.R.H. the Prince and Princess of Asturias with the Laureates. Bottom row starting from the left, MichaelSchumacher, Prince of Asturias Award Laureate for Sports; Felix Zandman, Avner Shalev, chairman of the directorate of YadVashem, Prince of Asturias Award Laureate for Concord; Al Gore, Prince of Asturias Award Laureate for International Cooperation;AmosOz,PrinceofAsturiasAwardLaureate forLetters;LadyChristianeDahrendorf,wifeofRalfDahrendorf,PrinceofAsturiasAwardLaureate for Social Sciences; Ginés Morata and Peter Lawrence, Prince of Asturias Award Laureate for Scientific and TechnicalResearch; second row, David Azrieli, Moshe Haelion, Mazaltov Behar Mordoh, Isaac Querub Caro, president of Yad Vashem Spain;PerlaBittanHazan,directorofYadVashem’sIbero-America,SpainandPortugalDesk;ColinNorman,NewsEditorandAndrewSugden,InternationalManagingEditor ofScience, PrinceofAsturiasAward Laureate for CommunicationandHumanities; third rowAndrèeGeulen-Herscovici, Baruch Shub, Jaime Vándor Koppel, Zygmunt Rotter Fleischer, Anna Rzechte de Rotter, Max Mazin, honorarypresident of Yad Vashem Spain, Prince of Asturias Award Laureate for Concord; Philip Campbell, editor-in-chief of Nature andAnnette Thomas, CEO of Macmillan Ltd, Prince of Asturias Award Laureate for Communication and Humanities.
In good company…Photoscourtesy
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Hidden Words: assessment; education; graduate; mentoring; science; classroom; math; laboratory; outcomes; student; diversity; faculty; patnerships; tests; engineering
The Science Education Forum is a dynamic sourceof information and new ideas on every aspect ofscience education, as well as the science and policy of education. The forum is published in the last issue of every month and online, in collaborationwith the Howard Hughes Medical Institute.
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2008 AAAS Annual Meeting14–18 February 2008 • Hynes Convention Center, Boston
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AAAS/Science Business Office FeatureRobotics/Automation
“When you get to nanoliter volumes,
you need very fine control, and that turns
out to be very challenging.”
Lab automation – it isn’t just for Big Pharma anymore. Providers have developed arange of personal instruments to bring the benefits of automation to the masses.At the same time, new equipment and protocols are enabling the standardizationand optimization of such traditionally overlooked areas as cell culture. This articlesurveys major manufacturers to find out what’s new in life science robotics andautomation. By Jeffrey M. Perkel
One emerging industry trend, according to Douglas Gurevitch, seniordevelopment engineer at the University of California, San Diego,
and executive editor of the Journal of the Association for Laboratory
Automation, is the move toward reliable nanoliter dispensing.“Ultrasmall-volume liquid transfer has had a resurgence,” Gurevitch says.
Microfluidic lab-on-a-chip systems work at the nanoscale, but their interfaces—not to mention traditional high throughput screening robotics—have tended tooperate at the microliter level, meaning researchers still must make more materialthan they need, and generate more waste.
“Now there’s new technology out there that allows you to work at a smallerscale,” he says.
One such system is TTP LabTech’s mosquito. Commercial director JasSanghera says the company had two primary considerations in developing themosquito: maintaining the accuracy and reliability of microliter-dispensingsystems, and avoiding cross-contamination.
The second aim may be accomplished either by washing reusable componentsor using disposable pipettes. However, since washing becomes less efficient asvolumes get smaller and concentrations rise, the company embraced the latterapproach, says Sanghera. But TTP LabTech also wanted to avoid traditionaldisposable tips, as tip boxes eat up instrument deck space, and require robots tohandle them.
The mosquito uses a bandolier of 36,000 disposable tips (equivalent to 95
boxes of 384 tips) on a tape reel about the size and thickness of 35-mm film. Thetape feeds into the mosquito horizontally and then rotates 90 degrees to bringthe tips into contact with the apparatus and samples. Each tip, like the barrel of asyringe, can aspirate, dispense, and mix reagents as needed, in volumes between25 nl and 1.2 µl. Once used, the tape rotates back to its original horizontal positionand exits the instrument.
Though the mosquito has remained largely unchanged since its release severalyears ago, new applications have emerged, says Sanghera, such as real-time PCR,crystallography, and MALDI mass spectrometry sample deposition. And the userbase is growing, he says; academic institutions now comprise the majority ofusers.
Labcyte designed its nanoliter dispensing system around a different principle.“When you get to nanoliter volumes, you need very fine control, and that turns
out to be very challenging,” says Richard Ellson, the company’s chief technologyofficer. “It’s difficult to make holes used in conventional dispensers all the samesize and to make sure they do not change in size, as compounds in the screeninglibraries will often stick to materials.”
The Labcyte Echo 555 system overcomes these issues via a completelynoncontact approach. Echo systems use sound energy to determine both the levelof hydration and volume of DMSO-based samples in each well of amicrotiter plate.They then focus a burst of energy customized for the fluid composition directlyat the meniscus to eject precise 2.5-nl droplets into an overhanging,
Look for these Upcoming ArticlesMass Spectrometry — February 22
Proteomics 1—March 7
Biomarker Discovery— March 28
continued >
NANO TO NEXT GEN:AUTOMATION GETS PERSONAL
Inclusion of companies in this article does not indicateendorsement by either AAAS or Science, nor is it meant toimply that their products or services are superior to those ofother companies.C
REDIT:TTPLABTECH
LIFE SCIENCE TECHNOLOGIESAAAS/Science Business Office Feature
346www.sciencemag.org/products
Robotics/Automation
inverted destination plate, which comprises anywhere from 96 to3,456 wells.
“As you get smaller and smaller, surface tension forces get verylarge in relation to gravity,” Ellson explains. “The drops stick becausethere’s enough surface tension to hold the drop on the ceiling of theinverted plate.” That is true even of larger volumes, he adds, whichmeans the Echo can transfer into prefilled wells.
Multiple droplets can be ejected into a single well to achievelarger volumes, and the system is flexible enough to eject differentvolumes from different wells, or from a single source well intomultiple destination wells.
Though the initial systems were designed specifically to handlesamples in DMSO (as is common with pharmaceutical compoundlibraries), the systems can also be calibrated to work with aqueoussamples, says Ellson. The Echo 520, to be released at this month’sLabAutomation 2008 meeting in Palm Springs, California, will havethis capability out of the box, he adds.
Next Generation PipettesNot all liquid handling advances are robotic. Two companies havereinvented the handheld pipette itself, bringing consumer-productaesthetics to the lab bench.
Launched this past October, Viaflo’s Vision electronic pipettesfeature a full-color LCD display and iPod-like touchwheel userinterface that was consciously designed to appeal to young,technically savvy lab workers.
According to Viaflo Marketing Director Marc Hamel, theinstruments score high on the “wow” scale at product shows. “It’sthe first product I’ve been involved with that has real stoppingpower,” he says.
Users easily navigate simple menu options and set aspirate anddispense volumes using the pipette’s touch-sensitive touchwheel,just as they select songs on their MP3 player. Favorite volumescan be preset and selected for easy task-switching, and can evenbe beamed to the pipette from a PC via Bluetooth connectivity. Andthe system is programmable, with 10 commonly used pipettingmodes (such as aspirate, dispense, mix, and purge) that can be usedindividually or linked together to build custom protocols.
ThermoFisherScientifichasadoptedanotherapproach tosimplifymanual pipettes: voice-activation. Speak the words “two-three-zero”to the company’s new Matrix Hybrid Pipette, for instance, and theinstrument display will read “23.0 µl,” says Craig Weiss, director ofmarketing for Thermo’s Matrix Liquid Handling Products. Users canalso control the volume by scrolling up and down on a digital display,or by selecting from one of a series of user-defined preset volumes.
All of which serves to increase productivity, Weiss says. “You paysome very highly educated people high dollars to do very manuallabor. People are starting to see that the more you can automatethat, the more it frees these highly skilled individuals to do the
core research, versus hours turning pipette knobs while pipettingby hand.”
The Air Out ThereSeahorseBioscienceofNorthBillerica,Massachusetts, is automatingan up-and-coming area of bioscience research: mitochondrialactivity.
“The mitochondrion has become the focus for a whole bunchof different diseases,” says Steve Chomicz, vice president of salesand marketing. “Whether neurodegeneration, cancer, diabetes, orobesity—all the research leads them to focus on targets that involvethe mitochondria.”
The best way to study that, he says, is through measurements inliving cells of glycolysis and oxygen consumption, two indicators ofcellular bioenergetics andmitochondrial function. And that is exactlywhat Seahorse Bioscience’s XF24 Analyzer does.
The XF24 uses a disposable cartridge that can be lowered justabove a microlayer of cells in a microplate well to create a transientmicroenvironment in which changes in pH and oxygen levels canbe optically detected in up to 24 wells at once. Up to four drugscan be added during this process, Chomicz says, thereby enablingexperiments that are not possible using traditional oxygen-sensingequipment such as Clark electrodes and radiolabels.
“Scientists have said repeatedly that the drug delivery option isone of the most powerful features of the instrument, because youcan do live agonist/antagonist measurements and dose-responsecurves,” says Chomicz. “That cannot be done with Clark electrodes,so they like that very much.”
Chomicz says the system software is constantly being upgradedbased on user feedback, and new sensors (for instance, for glucoseand CO
2) are in development.
Personal AutomationA number of companies have shifted focus from large-scale roboticsdown to smaller, so-called personal automation. According toWendyLauber, director of product management for biopharma at Tecan, “Itis a market need to have all of the power of the high-endmarket withthe pricing requirements of the low-end market.”
Tecan, for instance, recently released a low-end addition toits Freedom EVO line of liquid handlers, the Freedom EVO 75,which features a dual-pipetting mode “8 Plus 1 Access 8 arm,”says Lauber.
Operating in either an eight- or single-channel mode, “It givesyou two functions in one, because at this low entry range, cost is aconcern,” she says.
Promega is also embracing this automation trend.“Larger liquid handlers tend to have a high learning curve,
where a customer must maintain a certain level of automationexpertise,” says Cristopher Cowan, Promega’s integrated solutionsand engineering group manager. As a result, labs are forced to keeptrained specialists on staff, which is precisely the opposite of whatautomation is supposed to achieve, he says.
“It’s crazy: the lab is buying an open platform to increasethroughput and lower the head count, and yet you need that extrahead count to maintain it.”
Personal automationdevices like Promega’sMaxwell16 (releasedfall 2006), Cowan says, are smaller and simpler than traditionalrobotics systems. Just plug in the appropriate reagent cartridge—theMaxwell 16 can extract DNA, RNA, or protein from up to 16 samplessimultaneously—and come back in about 30 minutes to continued >
LIFE SCIENCE TECHNOLOGIESAAAS/Science Business Office Feature
The Labcyte Echo 555 system focuses a burst of
energy directly at the meniscus to eject precise 2.5-nl
droplets into an overhanging destination plate.
LIFE SCIENCE TECHNOLOGIESAAAS/Science Business Office Feature
CREDITS:R.STEARNS/C.BROWN/LABCYTE
Robotics/Automation
LIFE SCIENCE TECHNOLOGIESAAAS/Science Business Office Feature
www.sciencemag.org/products 347
Robotics/Automation
collect your materials.The company’s second-generation instrument, released fall 2007,
features a “very different and more robust design,” says Cowan.More important, it can elute samples in a smaller volume (and thus,at a higher concentration); while the original Maxwell 16 extractssamples in 300 µl, the so-called low-elution volume (LEV) protocolelutes in as little as 20 µl.
Alsoentering thepersonalautomationarena isQiagen,acompanythat has for years sold larger-scale automation equipment.
In January 2007 the company automated its spin column–basednucleic acid sample preparation kits with the QIAcube, which canprocess up to 12 samples at about the same speed as a techniciandoing the job manually, says Wolfgang Leibinger, business directorfor automation.
This month, says Leibinger, the company plans to roll out themedium throughput QIAsymphony, bringing the simplicity ofQiagen’s earlier low throughput BioRobot EZ1 to a higher through-put audience.
The EZ1 is a relatively small, easy-to-use robot for processingnucleic acids fromup to six samples at once. Simply insert amagneticcard with the protocol, add prefilled reagents, and go. Now, thatsimplicity is coming to the microplate level, says Leibinger, whichmakes such robotics more accessible.
“I see this as a major mind-shift,” he says. “What we have seenin the past is if you have these complex instruments, and the guywho used it leaves the lab, the instrument is often not used anymorebecause no one has the confidence to work with it.”
To achieve this simplicity, Qiagen departed from the typicallab robot aesthetic. The QIAsymphony has a deck, for instance,but rather than dealing with it directly, users load sample kits anddisposables through drawers. A robotic arm then takes the materialand places it in its appropriate position. Similarly, the system has noexternal computer, instead relying on a touch-screen interface.
Automating Cell Culture WorkAnother relatively new trend in lab robotics is cell cultureautomation, says Brad Nelson, director of marketing for instrumentsand workstations at Velocity11, which was recently acquiredby Agilent Technologies.
Cell culture places special demands on lab automation, Nelsonsays. For instance, the devices must be able to fit inside a standardhood footprint and yet not disrupt the flow of air that keeps thehoods sterile.
Velocity11’s Bravo liquid handler was “designed specifically to beable to operate inside a standard [laminar] fume hood,” says Nelson,who notes, “if you create a device that looks like a giant block, youwill disrupt the flow.”
The Automation Partnership (TAP) also automates cell cultureinstrumentation. TAP’s new Sonata, for instance, is designed to helpbiopharma companies evaluate and optimize cell lines and cultureconditions before scaling up to larger batch sizes.
Intended as an intermediary between the research andmanufacturing stages of biopharmaceutical development, thesystem uses parallel processing to mimic the conditions insidebioreactors, which are too large and cumbersome to optimizedirectly. “Sonata enables, say, 200 flasks to be incubated and forall the processing of feeding, maintenance, sampling, measuringmetabolites, viability, and so on to be carried out automatically,”says Rosemary Drake, director of business development.
“You get much more data, you can be more thorough, and youcan reduce the time it takes to identify the best clones and cultureconditions to take forward into the next phase of development,”she says.
Major VendorsMajor automation vendors have not been idle, either.
PerkinElmer, for instance, continues to develop application-specific workstations based on its JANUS platform, says Nance Hall,vice president and general manager of the automation and detectionsolutions business. Among its new offerings are workstationsspecifically designed for forensics and cellular screening, as well as anew AlphaLISA Automated solution, which uses PerkinElmer’s novelassay design as an alternative to enzyme-linked immunosorbantassays (ELISAs).
Unlike traditional ELISAassays,whichare cumbersomeandutilizeseveral separation steps, says Hall, AlphaLISA “is a novel, no-washtechnology easily automated and providing less assay variation thanELISA.” By eliminating washing, AlphaLISA also removes ELISA’smost time-consuming steps, she adds.
For those who need to keep all their disparate automation piecesunder control, Thermo Fisher Scientific will shortly be launching anew “mover-independent” software platform, says Hansjoerg Haas,director of marketing for lab automation and cellular imaging. Suchsoftware will allow users who have robots from multiple vendors tocontrol all of them using a single software tool, rather than with acollection of incompatible programs.
Beckman Coulter,meanwhile, has begun automating the processof flow cytometry, says Keith Roby, applications product managerfor automation. “It’s easy to do four or eight tubes by hand,” hesays. “When you start getting up to 24 tubes, it’s very easy to makepipetting mistakes.”
Now scale that up to 96 samples, he continues, and mistakes areinevitable. “That’s where automation comes in: it will do the samething every time; human error is taken out.”
And that’s a lesson that applies nomatter what process youmightbe automating.
The Automation Partnershipwww.automationpartnership.com
Beckman Coulterwww.beckmancoulter.com
Labcytewww.labcyte.com
PerkinElmerwww.perkinelmer.com
Promegawww.promega.com
Qiagenwww.qiagen.com
Seahorse Biosciencewww.seahorsebio.com
Tecanwww.tecan.com
Thermo Fisher Scientificwww.thermofisher.com
TTP LabTechwww.ttplabtech.com
University of California,San Diegowww.ucsd.edu
Velocity11 (an AgilentTechnologies company)www.velocity11.com
Viaflowww.viaflo.com
Featured Participants
Jeffrey M. Perkel is a freelance science writer based in Pocatello, Idaho.
DOI: 10.1126/science.opms.p0800021
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