Life science labs increase the adoption of automated liquid handling in the name of reducing cost, improving accuracy, and increasing productivity.

Life scientists have relied on liquid handling—the method by which a specific volume of a liquid can be transferred from one container to another—for ages. From mouth-pipettors to manual pipettors to today’s automated liquid handling workstations, liquid handlers have vastly improved over the years. And that improvement has very little sign of waning, as many life science labs, especially those in the pharmaceutical and biotechnology industries, are gradually moving away from the use of labor-intensive manual liquid handling methods toward automated methods.

Automation is now more critical than ever and integral to increasing a laboratory’s overall efficiency, as well as improving the precision and reproducibility of key research assays. As in many areas of life science research, automation and liquid handling is also extremely important to the pharmaceutical industry. With stringent demands for accuracy and quantitative sample data, these instruments are necessary for everything from high throughput screening and 50% inhibitory concentrations (IC50) determinations to secondary screening, ADME (absorption, distribution, metabolism, and elimination) testing, and pharmacokinetic testing.

Bioscience Technology Liquid Handling Cover“Automated liquid handling platforms are proven to address simple to complex needs in throughput, precision and sample volumes for applications ranging from molecular biology to cellular screening,” says Nance Hall, vice president and general manager, Automation & Detections Solutions at PerkinElmer, Waltham, Mass.

Automated liquid handling is commonplace in the drug discovery process because compound screening methods require the processing of several plates or tubes, simultaneously.

“In order to process all of these samples, barcoding capabilities on the automated platform are a necessity,” says Jamie Grossi, product manager, Automation, Eppendorf North America, Hauppauge, N.Y. Software packages are designed for the purpose of tracking samples in a given screening run. “Researchers will also have the need to cherry pick samples from the plates they run that they would like to do further analysis on,” says Grossi.

Other software programs have built-in features that enable researchers to identify samples for further on analysis, import data necessary for associated liquid handling responsibilities for those samples directly into a method file, from which the commands are then executed. With these software packages, researchers can execute the file themselves or use a LIMS system to perform this task. “The automation of this task prevents possible manual mistakes of pipetting the wrong sample from the wrong well of a plate or from the wrong tube,” says Grossi.

Caliper Life Sciences, Hopkinton, Mass., is another major provider of liquid handling solutions to the pharmaceutical and biotechnology industries, with “a broad suite of automated solutions to meet the needs of high and low throughput users alike,” says Kevin Keras, business unit manager, Automation, Consulting, Engineering and Services (ACES) at Caliper Life Sciences. “When identifying targets or screening compounds, the liquid handler serves only a part of the process,” says Keras. Integration of liquid handlers into turnkey systems with other parts of the process, such as incubators, washers, and readers, is paramount to Caliper’s approach to providing liquid handling solutions. In addition, automated pipetting systems must be pre-configured with multiple hardware accessories to meet the needs of today’s pharmaceutical and biotechnology labs. By incorporating thermomixers, vacuum stations, and heating and cooling elements among other accessories, such systems can be used in both upstream and downstream processing of samples, as well as for pre- and post-PCR (polymerase chain reaction) applications within genomic workflows.

Agilent Bravo Liquid Platform
The Agilent Bravo Liquid Platform (Source: Agilent Technologies)

In fact, there are many genomics applications for liquid handlers. These include nucleic acid sample preparation, PCR, genotyping, and more. PCR and genotyping workflows are also possible using liquid handling systems in which PCR clean-up can be easily automated and scaled up to complete systems for automated genotyping.

“Many steps in Next Generation Sequencing sample preparation benefit from automation, including library preparation and target enrichment steps providing increases in throughput and reduced sample-to-sample variation,” says Brad Nelson, marketing manager of Automated Solutions at Agilent Technologies, Santa Clara, Calif. Small inhibitory RNA (siRNA) library creation and other critical steps can also be automated via liquid handling platforms.

Some of the most important features in any automation platform are capacity, dispensing volume, throughput, and walk-away capabilities. Capacity is the maximum number of samples that can be processed in a specific protocol or run. Dispensing volume is the maximum volume of liquid dispensed in a given run. Throughput is the number of samples that can be processed in a given amount of time. And, walk-away capabilities enable the user to initiate a protocol or run and determine the level of user-intervention required, enabling them to “walk-away” from the instrument and return later to evaluate the completed results.

“Each of these attributes would be addressed by a variety of things, such as different deck sizes, the ability to add storage devices to them, dispense volume ranging from nanoliters to milliliters, and the ability to optimize the dispense heads so that they can be configured on that instrument to optimize that volume for precision pipetting,” says Hall.

Obvious move toward automation
For the above reasons and more, “several of the larger biopharmaceutical, pharmaceutical and biotech companies have already realized the inherent benefits of using automation within their liquid handling applications as opposed to manual efforts and have begun driving the use of automation in an effort to remove the manual pipette from the researcher’s hand,” says Grossi. “Ergonomic groups will note the decrease of repetitive stress injuries that employees go through.” Other advantages of automated liquid handling over manual pipetting include greater consistency and reproducibility in data produced. “In other areas of industry such as clinical and diagnostic, management has noted that it is more cost effective in the long term purchasing an automated liquid handler than hiring a technician to perform basic liquid handling tasks,” says Grossi.

“There is a trend toward using more automated liquid handlers, although the trend is shifting from a throughput focus to a consistency of process focus,” says Keras, who adds that it is not that “throughput is unimportant, but that there is a growing interest in low throughput systems solutions, as protocol complexity increases and sample-to-sample consistency becomes paramount.”

Vendors that sell automated liquid handlers have also noted the trend in their market space. “The automated liquid handling market continues to grow while the manual liquid handling market is relatively flat. As pharmaceutical and biotech organizations invest more to find new biological drug candidates, many drug discovery applications are moving toward genomics,” says Nelson. Such vendors have responded to the demand for automated liquid handlers by improving their current systems or developing new ones.

Despite improvements to automate liquid handling systems, there still is a nagging need to calibrate them. However, “there a difference between calibration methods for automated and manual systems,” says Keras. “Anytime you have a manual process, you have the subjectivity and variability of the various people who might perform the calibration, over time... One of the main benefits of automated pipetting versus manual is repeatability. A properly calibrated liquid handler will outperform manual pipetting.”

Perkinelmer cell::explorer
The robotic automation platform, cell::explorer contains multiple instruments to perform the required detection, liquid handling, washing, and plate movement/storage to enable a fully automated solution for high content and cellular screening applications. (Source: PerkinElmer)

Nelson explains the differences in calibration method by saying, “the differences are due to the fact that automated devices often have more pipetting channels (up to 384 channels at one time as opposed to one channel to 16-channel hand pipettors), and automated devices can pipette as low as 0.3 microliter with coefficients of variation less than 5%. This can force the calibration techniques for automated liquid handing to be more precise.”

There are also safety benefits of choosing to use an automated liquid handler. “Automated instruments can also help maintain consistency in multi-user environments and minimize safety concerns from cross-contamination and improper sample handling,” says Hall.

Like many other industries struggling to keep a foothold in the current economic landscape, all of the life science industries must contain their operational costs. “One way to manage these escalating costs is by adding instrumentation that increases efficiency throughout the workflow. The industry continuously looks for innovative solutions that are able to deliver flexible products that are capable of adapting to their changing needs without compromising their high performance requirements. By delivering flexible solutions without additional complexity, automation becomes invaluable,” says Hall. “Streamlined automation workstations will enable higher productivity from sample prep to results generation, allowing highly skilled scientists the time to focus on interpretive functions and data analysis while leaving the repetitive functions to instruments.”

In summary, liquid handling is part of every life science application. The days of mouth pipetting are long gone, and even manual pipettors have seen their hay-day. Currently, most professional life science laboratories contain some form of automation, with automated liquid handling being a small part of their automated armamentarium. Advancements in life science have been seemingly synchronous with continued improvement in automated liquid handlers over the years. Such improvements have freed laboratory technicians from performing the repetitive duties of vast amounts of manual liquid handling, thus allowing more time for data analysis and interpretation. If vendors of automated liquid handlers continue to develop handlers at the current pace, the trend toward automated liquid handling is likely to continue unabated.

This article was published in Bioscience Technology magazine: Vol. 34, No. 4, April, 2010, pp. 1, 8-11.