Service and maintenance for liquid handling equipment are approximately the same as for a liquid chromatography system, but the type of service differs. All vendors offer typical levels of on-site service, with premium plans including preventive maintenance visits.
Post-sale support should be a top consideration for prospective buyers, says Sikander Gill. “Purchasing or selling an ALH system is easy, but maintenance requirements may overwhelm the average user. Post-sale service agreements are critical for achieving the long-term benefits of automation.”
Most manufacturers offer training at either the customer’s or the manufacturer’s location, but the trend is toward a quick start and a shallow learning curve. According to Merja Mehto of Thermo Fisher Scientific, users need to get right to work “without having to spend hours and hours in training sessions.” The length and depth of training may vary considerably depending on the instrument and workflows. “It can be just hours for the simple instruments with straightforward software or up to several days for more complicated systems.”
In the past, many companies maintained an official or unofficial automation department that supported automated liquid handling. The need for specialists has diminished as instrumentation became more reliable and robust, and software/interface took over many of the more difficult method and protocol tasks. Vendors have further responded to the “disappearing expert” through software and hardware that are more application-purposed.
Span-8 Pipette Tips Biomek P1000 | Beckman Coulter www.beckmancoulter.com
The industrialization of ALH systems has not completely eliminated the industrial specialistengineer, as similar advances have in spectroscopy or chromatography labs. Although specialists are dwindling in number, many companies still rely on them due to the nature of automation (lots of moving parts, instrument interconnectivity). Complex systems involving a liquid handling component are only as trustworthy as their weakest link. But paradoxically, more of the maintenance and troubleshooting burden has shifted onto end users.
Pipette tip calibration is even more critical for multichannel pipettors in high-throughput labs. Even relatively minor errors propagate quickly at 100 plates per day. Calibration is normally part of routine on-site service. Pipetting heads found to be out of specification are swapped for refurbished heads on the spot.
In addition to equipment vendors, numerous third-party service firms provide routine maintenance for ALH systems. Some, like Artel (Westbrook, ME), sell do-it-yourself service kits for validating the precision and accuracy of multipipette ALH systems. Given the criticality of consistency and accuracy, such kits are the way to go between service calls.
The calibration process for pipetting heads involves some high-throughput ideas. Artel’s package includes software that runs on a desktop or laptop computer, sample solutions, optical-quality verification plates (96- and 384-well formats), calibration plate, plate shaker, either of two plate readers that quantify delivered volumes at two wavelengths, and a bar code reader.
ALH systems are not black boxes like mass detectors or nuclear magnetic resonance spectrometers. Laboratories committed to automation are generally not fearful of digging into the works, says Tom Osborne, especially for mechanical parts that wear out. Another common maintenance task involves “framing” the deck every few months to ensure that pipette tips dispense where they’re supposed to. “Users can order the parts and repair the instruments themselves in some cases. More complex repair and maintenance are covered under the service contract that usually includes operational qualification— documenting that the instrument is performing within specifications.”
Labs comfortable with automation become resigned to cost of ownership, training, and frequent ordering of consumables. These factors, according to Osborne, need to be managed and factored into the ongoing costs of doing business.
ALH systems are constantly moving, sometimes 24 hours a day, seven days a week. Motion involves friction and strains that are not evident in spectrophotometers, for example. ALH operators should be prepared to change belts and check pipette stage alignments to ensure that the robotics are not drifting. Smaller-format testing sets (e.g., 1,584-well plates) demand a higher level of mechanical precision than 1mL glass tubes do. And despite constantly upgraded hardware and vendors’ dedication to interoperability, the interplay between ALH and third-party instruments is a source of error and inconsistency. “The best time to consider upkeep and preventive maintenance as part of cost of ownership is while you’re considering the acquisition of automation.” This is when potential customers should have a frank discussion with vendors about downtime, Osborne says.
One way to overcome downtime resulting from instrument glitches is to build redundancy into analytical operations. This is most often seen in chromatography labs, where methods reside on all instruments or on a central server, and components may be swapped among instruments. Obviously not every laboratory can do this, even for relatively low-priced instruments, and only well-heeled industrial labs would even consider it for ALH systems. “Most labs can’t afford redundancy,” Osborne observes, “but if the value of the automated application is high enough, then this strategy is something to consider.”
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Alternatives to full-scale automation
Throughput does in fact play a determining role in whether to acquire or upgrade automation equipment. At several hundred plates per day the numbers essentially decide; at the low end, particularly for tasks such as dissolution, serial dilution, plate replication or reformatting, or incremental dispensing to multiple plates, semi automated, parallel dispensing systems might provide greater value than a full-blown ALH can.
Known for its multichannel manual pipettes, Integra Biosciences (Hudson, NH) has recently introduced a product, ViaFlow 96, that is mostly manual in critical operations of pipetting and plate handling. The 96-channel dispensing head is controlled by push-button actuation, and pipette tip positions are stored on the instrument for both dispensing and withdrawal, as with fully automated systems. Because dispensing is controlled electronically, pipetting times are brisk—about eight seconds for 96 wells.
“An instrument like this allows technicians to handle up to 50 plates as easily as with a robot,” says Alexander Studer, Ph.D., of Integra Biosciences. The ViaFlow 96 addresses simplicity, ease of use, and learning curve but not, unfortunately, versatility. “If you’re thinking of picking eight samples from a 96-well plate, this instrument is not for you,” Dr. Studer admits.
One would expect the “sweet spot” market for such an instrument to be cash-strapped, low-throughput labs that cannot afford full automation. While that demographic is certainly part of the market, in fact high- and low-automation end-user groups overlap significantly. Almost every lab at times operates in low-throughput mode, requires one-off plate prep for a few dozen plates, or has all available automated systems occupied. “A lot of people who have all the bells and whistles sometimes want a backup or the ability to run several plates, but setting up the full-featured instrument is too much trouble,” Studer says.
A step up from Integra’s approach are “personal” ALH systems that satisfy what Gilson’s Greg Robinson calls a “personal solution-based model.” Desktop ALH systems fill a niche market segment between manual pipetting and full-throttle automation for low- to medium-throughput applications. Tecan and Agilent, both of high-throughput robotics fame, and Qiagen also sell “personal” liquid handlers, as do Eppendorf (Hauppauge, NY), Biohit, and Dornier-LTF.
Biohit (Helsinki, Finland; now part of Sartorius) touts the world’s most compact ALH, the desktop-sized Roboline™, which uses a single pipettor to deliver reagents to microtiter plates (up to 96-well) or tubes under computer control.
Roboline represents a natural progression from the hand-operated pipettes and electronic models that put Biohit on the map. According to the company, electronic pipettes comprise just six percent of the manual pipette market, but demand for them is growing twice as fast as for hand-operated models (ten percent per year vs. five percent). Roboline is fully automated, but unlike full-featured ALH systems, Biohit claims full walk-up usability by novice technicians.
Automated Liquid Handling Personal Workstation Roboline | Biohit | www.biohit.com
Similarly Dornier-LTF (Lindau, Germany) has introduced a “personal pipetting robot,” the PIROs, which like Roboline boasts a desktop-size footprint and capability for biosafety cabinet operation.
Jesse Cassidy, automation product manager at Eppendorf, says personal ALH customers would not typically buy a fully automated system, and vice versa, but some crossover exists. “It depends on what they’re using it for.” Some large labs will use Eppendorf ’s epMotion® system for low-criticality operations like sample aliquoting or to get their feet wet with automation. The drawback of these instruments, however, is that anything they can do, large systems can do better.
Eppendorf ’s entry-level benchtop ALH has basic features similar to those of its competitors’ instruments. But the company also sells higher-end models with more deck positions, plate grippers, mixing, heating, vacuum, and variable volume capabilities.