Product
Review
Running on automatic Laboratory robotics and workstations One of the differences between robotic arm systems and workstations can be seen in the cost. A system built around a robotic arm costs more than $100,000, whereas workstations can run from $10,000 to $100,000 depending on the sophistication level. However, it is the application, as much as cost, that often determines the choice of design. Just as the vision of robotics has changed, the business of manufacturing these items also has evolved. "A lot of companies have come and gone," says Kramer. "In the early days, there was a lot of 'hobby' in it." Today's manufacturers are meeting higher standards. In some cases, manufacturers arefillingcontracts that guarantee reliability and even contain penalty clauses for late deliveries or poor equipment. Says Kramer, "This type of hardball playing is common in factory robotics but only showed up in laboratory automation in roughly the last year." Another sign of the changing business climate is a shorter time for delivery. Jim Harness, chief scientist with Bohdan Automation, recalls that at one time it was a custom-built business. It could take up to one year for an order to befilled,the system installed, and the lab personnel trained. Today, Bohdan aims for 60- to 90-day delivery. "We have built over 200 styles of workstations in the last four years and could not keep up with demand if each unit were builtfromscratch. So don't need to customize each der we have constructed a library of software and hardware modules to build thing requested " he Other manufacturers report faster deliveries as well The current market for robotics is dominated by applications for pharmaceutical and biotechnology companies, particularly in the fast-growingfieldsof drug discovery, using combinatorial chemistry techniques, and high-throughput screening of candidate drugs, such as those derived from natural compounds. Other customers cited by manufacturers include the food and beverage, chemical, and petrochemical industries.
Pharmaceutical and biotechnology applications dominate this fast-growing market In the celebrated sciencefictionliterature of the 1950s, robots were described as giant metal machines constructed to be stronger and smarter than their human masters. The robots and robot-like workstations now finding a niche in analytical laboratories bear little resemblance to that original vision. Small, agile, quick, and boringly reliable are some of the key features that define today's machines. The science fiction writers of the 1950s can't be faulted for getting the details wrong; manufacturers of laboratory automation also have seen their designs evolve over the last decade. "The whole vision of how we use the robot in the laboratory has changed," says Gary Kramer, group leader of NIST's chemical sensing and automation technology group. "You want to use the robot for things that you can't figure out how to do easily any other
way." These unique needs range from massive robotic systems to handle the thousands of samples generated in highthroughput drug-discovery programs to stand-alone devices that drone away at repetitive tasks. The original vision of laboratory robotics centered around a human-like arm that would handle many analytical tasks. Now manufacturers design arms to be a "mover of stuff," says Kramer. Operations such as transferring or filtering solutions are handled in modules around the arm. Workstations represent a newer vision of robotics. These automated stand-alone units devoted to certain procedures, such as liquid handling or sample preparation are growing in popularity. Some workstations can be interconnected or work with robotic arms, and some use their own dedicated robotic arm.
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Product
Review
Table 1 . Typical w o r k s t a t i o n s
Company
Cyberlab 36 Del Mar Drive Brookfield, CT 06804 800-292-3752
URL Liquid handling
www.cyber-lab.com C-200/C-300: uses up to 4 independent z-axis tools, including single and multichannel pipetting (4, 8,12, or 96 channels), fixed and disposable pipetting tips; variable spacing; plate and tube grippers; bar code reader; label print and apply; liquid level sensor. C-300 has 54" x 24" working area with 54 plate positions, each of which holds 12 standard height microwell plates or 3 deepwell plates. C-200: up to 4 independent zaxis tools, including gripping and pipetting; can grip any size containers; various tip sizes; fixed and disposable tips; single and 4-channel syringe pumps; uncapping and recapping; weighing; mixing; bar code reader; HPLC injection; standard software for constructing routines; remote diagnostics capability.
Sample preparation
Gilson 3000 W. Beltline Hwy. P.O. Box 620027 Middleton, Wl 53562-0027 800-445-7661 www.gilson.com 215: xyz robot with stationary rack design; single-piston pumping system; handles 200 to 25000-uL syringes; liquid level sensing probe; option of direct HPLC injection. 221 XL and 222 XL: xyz robot with 123-mm vertical arm and generally configured with peristaltic pump.
www.sourceforautomation.com
www.zymark.com RapidPlate-96:96-well simultaneous pipetting; workstation functions as stand-alone or in a fully automated system; 6position turntable that accommodates plates, deepwell plates, and pipette tips; dispenses 5 to 200 u.l; is usable for plate replication, reagent addition, and serial dilutions.
BenchMate II: sample prepartion, including SPE, solution filtration, liquid handling, mixing, dilutions of up to 1:10,000; HPLC sample and standard injection; autosampling for UV/vis; holds up to 200 samples; automatic sample tracking.
Automated dissolution module: handles up to 12 samples with networked system capacity of 72 unattended samples; changing of depth filters; sample transfer to on-line HPLC/UV/vis; optional image capture of dissolution process.
Solid-phase extraction
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Zymark Zymark Center Hopkinton, MA 01748-1668 508-435-9500
ASTED XL: sample cleanup using a unique on-line membrane dialysis and trace enrichment system; sample concentration cartridge; automated on-line deproteinization of samples; HPLC injection; column-switching techniques.
Automatic dissolution
RSN
Source for Automation 327 Fiske St. Holliston, MA 01746 508-429-3377
ASPEC XL: handles up to 108 samples and 15 solvents; automatic column conditioning; multiple fraction collection; multiple extractions by loading fractions from previous columns; can combine 1-, 3-, and 6-mL syringe barrel columns in one protocol; HPLC injection. ASPEC XL4: multiprobe SPE for high-throughput LC/MS and GC/MS applications; up to 108sample capacity; processes 4 samples in parallel. 401
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MultiDose: handles up to 8 batches with up to 24 time points/batch; on-line filtration and transfer to an HPLC, collection device, or spectrophotometer; sample collection times as fast as 5 min; up to 5 media choices for each 8batch run; full instrument validation includes method validation. RapidTrace: modular extraction workstation with 100-sample capacity; 10 independent units process samples simultaneously; performs all SPE steps using positive pressure; accepts 1or 3-mL syringe barrel columns; 8 solvent/reagent lines per module; on-line mixing and multiple method capacity on each module.
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SciLog 14 Ellis Potter Ct. Madison, Wl 53711 -2478 800-955-1993
Sagian P.O. Box 68356 Indianapolis, IN 46268 800-352-4975
Bohdan Automation 1500 McCormick Blvd. Mundelein, IL 60060 847-680-3939
Hamilton 4970 Energy Way Reno, NV 89502 800-648-5950
Robotic Dispensing Station: 10 different racks; handles vials of 0.2 to 25 mL; self-calibrating gravimetric dispensing; modest price; stores up to 10 dispensing programs; can dispense sterile solutions, acids, bases, and organics; choice of peristaltic, piston, magnetic-gear pump heads.
(under construction) MultiPette 96-Channel Automated Pipettor: 6-position deck enables automated pipetting; handles standard, deepwell, or 384-well plates; fixed and disposable pipette tips; volumes of 1 to 200 nL; Windows-configured software; "robot-friendly" design; RS-232 communication.
www.bohdaninc.com Compound distribution and labeling for chemical and biological analysis: previously purified synthetic compounds are transferred to GC vials and microtiter plates; septum piercing/Ar atmosphere cannula; bar code labeling; capacity of 200 vials, 4 microplates, and 176 compounds.
www.hamiltoncomp.com ML2200: automated system using single- or multiple-channel pipetting with an intrapositional resolution of 0.1 mm; sample sizes from 10 nL to 10 mL; large deck handles various vessels, tools, and standard or deepwell microplates; used for highthroughput screening, molecular biology protocols, genetic screening, anc clinical assays.
ORCA MP96 Workstation: sampie preparation, including a 1-m rail with ORCA robot; 96channel liquid handling system; bar code reader; and carousel.
HPLC Analysis: extracts solid samples, then filters, dilutes, and injects the solution into the HPLC; capacity is 40 samples, fliters, filtrate tubes, and dilution tubes; sample injections can be bracketed with 3 different standards; option of UV-flow cell delivery instead of HPLC. MS or LC/MS Analysis: dilutes, mixes, filters, and injects samples into a MS; 3 different solvents for dilution, vortex mixer, filtering with a disposable pipette, capping/uncapping station, bar code labels, capacity of 280 samples/ run. MALDI-TOF Analysis: synthesized compounds are diluted with 5 to 100 jiL of matrix reagent and transferred to MALDI-TOF analysis plate; 6-channel pipettor; volumes transferred to analysis plate are from 1 to 3 |xL.
ML2200 Sample Preparation: instrument accesses various vessels; sample can be transferred, diluted, mixed, or, in the case of SPE, extraction, injected into an HPLC.
Compound Dissolution: weighs compounds; dilutes to desired concentration and vortex mixes; transfers compounds to microplates for high-throughput screening; up to 5 place-balance capability; capacity for 288 samples and 3 microplates/run.
GPC/SPE sample preparation for GC analysis: analyzes pesticides based on EPA method and involves 2 workstations in tandem; one station weighs, dilutes, mixes, and filters samples prior to GPC column; other station collects, desorbs, dries, redissolves, and processes sample for GC analysis; capacity of 24 samples/run.
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ML2200 SPE Workstation: automates sample processing with 1-, 3-, and 6-mL columns; handles all critical steps, including dilutions, conditioning, internal standard and sample addition, washing, and elution; 5 solvents are simultaneously available; SPE Flow Controller regulates positive pressure and flow rate to ensure consistent sample processing; up to 40 samples/h; multiple fractions can be collected and automatically injected for HPLC analysis. 408
Analytical Chemistry News & Features, Aprll 1, 1997 257 A
Product
Review
Table 2 . Typical specialized w o r k s t a t i o n s
Company Workstation descriptions
Cyberlab Protein Crystallization: performs both hanging drop and bridge method; covered reagent rack; nest for 6 plates; cover slip manipulator; automatic grease applicator; pipette tips; optional cooling nest.
Bohdan Automation Loss on Drying: samples are placed in drying pans, analyzed, and discarded; capacity of 30 vials/run. Oil Sample Preparation for ICP and FT-IR: for engine oil and transmission fluid samples.
Source for Automation Solid-dosage Assay System: performs content uniformity, composite assay, and stability testing; handles 6 different batches and volumes up to 500 ml_; transfers to HPLC/UV/vis or fills autosampler vials. Stand-alone Extractor: for dissolving solid dosage products. Water Tablet Processing System: performs content, uniformity, and composite assays on pharmaceuticals with interface to Millenium 2010 and 2020 HPLC systems.
Zymark Hamilton Tablet Processing Oil Sample Preparation Workstation: for QC batch Workstation: unique liqrelease, stability testing, uid level detection technology allows sample or formulation development; 500-mL capacity for preparation of oil and other solutions assays with serial dilutions; HPLC injection; undetectable by capaciUV/vis; internal analytical tance or conductive balance for monitoring sensors. operations; 100-sample capacity. TurboVap Concentration: a family of workstations for automated evaporation.
RSN
401
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Tables 1,2, and 3 list eight manufacturers consulted for this review of laboratory robotics and workstations. Tables 1 and 2 describe features of workstations for liquid handling, sample preparation, solid-phase extraction, and specialized tasks; Table 3 highlights features of selected robotic arms. Readers are cautioned that several manufacturers of automated systems are missing from the lists (they were unable to make publication deadlines); and other sources of companies, such as the annual LabGuide, should be consulted for a more comprehensive list of manufacturers.
cally and usually more reliable than robotic arm systems. Moreover, these units can provide a data trail for regulatory compliance and are typically designed to be operated by nonexperts. The commercial workstations vary in their level of sophistication, making it possible to automate even some simple procedures. "Automation benefits anyone running more than 150 samples in a day," says Juliette Schick, president of SciLog, which manufactures a moderately priced workstation. Larger workloads may be needed to justify more sophisticated workstations. According to Bob Trinka, director of sales for Cyberlab, some purchasers
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calculate that a workstation will replace a $40,000-a-year technician and are looking for a one- to two-year payback period. However, does it take an expert to introduce a workstation into a laboratory? Kramer says,"No. If you are just buying one workstation and you have someone with good mechanical skills, who gets on well with computers and who wants to learn automation—my advice is 'Go for it'." Most workstations are installed as stand-alone units, say manufacturers. Workstations operate best when there are one to three functions being automated; more operations or less defined analytical steps need the sophistication of
To arm or not
From the beginning, automation held the promise of freeing analysts from what James Martin, director of marketing at Source for Automation, calls cumbersome, time-consuming, and repetitive tasks. That is especially true for the quality control (QC) lab, which must routinely test products such as pharmaceuticals or foods prior to release, often with a welldefined analytical procedure dictated by regulatory requirements, he says. In these laboratories, workstations are typically the best solution. "Workstations are often more 'hardwired' and are better in QC labs, where the analytical steps are well understood," says James Little, Zymark senior vice-president. The experts agree that, properly set up and running, workstations do save laboratories ttme and money. Because workstations can be designed and dedicated to a single, specific task, they are—in general—simpler mechani258 A
Table 3. Representative robotic a r m s
Product Company Description Arm motion Grip width Payload (kg) Software Modules
RSN
Analytical Chemistry News & Features, April 1, 1997
ORCA Sagian Rail-mounted with rail lengths of 1, 2, and 3 m. 6 axes (± 0.25-mm precision); reach, 58.4 cm; height, 78 cm 0 to 40 mm; option of up to 80 mm 0.5 continuous, 2.5 transient Windows-based methods development software Storage carousels and racks, plate and tip lift, CO2 incubator, 96-well filtration manifold, microplate sealer, microplate lid removal, bar code label print and apply, vial crimping, 96-channel automated pipeftor.
Zymate XP Robot Zymark Circular systems and railmounted track 6 axes; 37-cm vertical at 32-cm reach Various interchangeable hands 1.5 continuous Windows-based methods development software Storage carousel and racks, microplate and CO2 incubators, pipetting modules, reagent addition, plate washer, bar code reader, plate reader, shaker, centrifuge, plate turntable, cover removal, weighing, filtration, SPE, tablet dissolution, and others.
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a robotic arm system. "Robotic systems have more flexibility and work best early on in research, when the methodology is not well defined," says Little. Arms are either fixed in one spot, accessing modules arranged around it in a 360° circle, or mounted on a track to service units along its path. The arm's job is to move microwell plates, autosampler vials, or reagents into appropriate modules or in some cases workstations. Little describes it as "pick and place". The combination of arms and modules, or workstations, has real advantages. Trinka recently compared the efficiency of a tracked robot handling a compound dissolution in collaboration with a liquid-handling workstation versus the robot alone. His data demonstrated that the robotworkstation team increased productivity by 130%. Where these types of systems pay off the most is in high-throughput drug discovery and screening programs. The automated systems developed to handle these chores can cost millions of dollars to set up, require full-time experts in automation to design and maintain, and demand a huge financial commitment to operate. However says Kramer for these types of applications robotics is the only way to go
device are magnified at the end. "Experts who put these sophisticated systems together must know what is reliable and do their own reliability testing before putting a unit into a committed design." How well various equipment integrates is also a consideration. "No one company builds everything you are going to need to construct a system," says Kramer. "And the commercial equipment does not all operate by the same set of instructions or play by the same set of rules." There are other considerations in setting up an automated system, points out Kramer. An automated system goes through a surprising number of disposable items, such as pipette tips, autosampler vials, filters, and containers. Even the microliter amounts of solvents being consumed can add up to large volumes in high-throughput operations. "You have to get these ancillary materials into the lab and get them out. You can create your own little Superfund site."
No one company builds everything you are going to need.
Considerations Before introducing any component into an automated laboratory, Kramer recommends testing it as a stand-alone unit for reliability and reproducibility. "Reproducibility was a serious problem in the beginning of robotics," he says. At that time, systems were designed to handle half-inch diameter tests tubes, but analysts pushed the design constraints of this equipment by requiring it to access smaller objects. Today's robots are being built to reliably handle 96-well microwell plates, extraction cartridges autosampler vials and so on However those benchmarks will probably be pushed as well as industry makes the jump to 384-well plates for example Manufacturers are now designing systems to meet those demands Reliability, another important aspect, is a function of individual components and system design, says Kramer. Because robotic systems are linked to operate serially, even small losses of reliability at each
Nor can one use any pipette tip or autosampler vial. "If a pipette tip is crooked and a human uses it, no problem. If a robotic systems uses it, then it can be a major problem." The disposables need to be of high quality to ensure reliability. Thus, procurement of supplies and waste disposal are important issues for an automated laboratory.
Future trends The current drivers for new robotic technology are the high-throughput screening and combinatorial chemistry markets, says Kramer. That trend should continue, and he even envisions that the next big step will be automation of the candidate drug screening, such as running in vitro tests on a massive scale. "It's the next logical step," he says. Experts also expect automation to become more sophisticated. At the same time, robotics will be driven to work in smaller dimensions, such as the 384-well plate. "These systems are still too large," says Little. "People would like to work with smaller samples." The robotic devices themselves will also get smaller, freeing up valuable benchtop space. "Future designs won't look like the ones today," he adds. Science fiction writers be warned. Alan Newman
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