A Fluid Exchange of New Ideas

---

Liquid handling is the cornerstone of virtually all laboratories. Researchers in a variety of specialties invariably use liquid-handling tools in their research. With such common and frequent use, it’s not surprising that significant progress has been made in the development of these tools during the past 40 years.

From the first mechanical fixed single pipettor in the 1960s to the fully automated robotic platforms available today, the innovation is evident. Today’s liquid-handling tools are more efficient, more accurate and more high tech.

What has been the impetus for such dramatic change? “Due to the repetitive nature of liquid handling, the needs of users have focused on accuracy, reproducibility, efficiency and ergonomics,” says Tom Burnett, director of Marketing Operations at Fisher Scientific (Ottawa, Ontario). “These needs have naturally led to the development of more precise, efficient and user-friendly tools for liquid handling.

“High throughput screening, or the ability to perform thousands of tests in parallel, has led to the development of robotic systems that fully automate the liquid-handling function and provide greater reproducibility and accuracy down to extremely low volumes,” Burnett explains. Indeed, there is much demand to accomplish more in less time. But what is old is new again and hand-held pipetters are still very much in use in today’s laboratories. They are capable of doing more and preserving the human touch.

Pipetters That Fit the Task and the User

Hand-held pipetters are commonplace in most laboratories. Today, this tool offers features that make it easier to manoeuvre than ever before. Advances in capabilities, functions, electronics and ergonomics have improved the performance and comfort of using this seemingly constant work companion.

There are a variety of pipetters available to meet every laboratory’s needs and budget. Most notably, the functions of many pipetters have been combined into one unit. The new hybrid instruments offer convenience, saving researchers the hassle of changing instruments mid-task and saving the cost of having several instruments do the job of this one.

Nichiryo Co. Ltd.’s (Tokyo, Japan) Nichipet HB Hybrid Electronic Pipetter is the first of its kind, says John Harder, general manager of Nichiryo America Inc. (Flanders, NJ). “The hybrid model combines a manual and electronic pipetter in one,” Harder says. The user has the choice of either manual or motorized mode and the option of several modes of operation, including sequence pipetting, dilution, mixing and a repeating function. The pipettor is battery-operated, with a volume setting in 1-ml increments and a counter feature so the user never loses count of the last sample dispensed. A touch pad eliminates the scrolling method of most manual pipetters.

Advancements have also been made in the tedious task of repetitive dispensing. Brinkmann Instruments Inc.’s (Westbury, NY) Eppendorf Repeater Pro Pipetter offers an electronically operated repetitive dispenser. It has the capability for pipetting, dispensing and timed dispensing — up to 100 dispensings per tip. Automatic dispensing with preset time intervals between 0.1 and 1.0 seconds is possible.

“Pipetting has come a long way,” Harder says, “from the original six-volume manual pipette still being sold today to the newer models with volumes as small as 1-ml increments.” The demand will always be for smaller, more accurate measurements. “From here, we will continue to produce instruments capable of smaller, consistently accurate volumes,” Harder says.

While having the right pipetter is critical to productivity, choosing the right pipette tip is equally important. Leaks and sample retention will cause inaccurate results and frustration for the user. While technique can play a role in ensuring accuracy, the tip lining itself is worth examining for performance.

Changes in tip design have solved some of the challenges of the pipette tip. Improvements have been made by using a thin wall diameter and beveling the tip. Some manufacturers have coated the lining of their tips with Teflon, which propels liquid. It may be trial and error on the part of the user to find the tip that works best. Like snowflakes, no two tip brands are alike.

Relieving Job Stress

Repetitive strain injury has plagued pipetter users since the technology became available. The constant repetitive motion of depressing the plunger on a manual pipetter causes physical fatigue and muscle aches. Such distractions can affect concentration and therefore affect accuracy and productivity. It is a serious concern when the health of laboratory workers is at risk.

Ergonomics has taken centre stage with manufacturers in recent years. By first incorporating ergonomics into the design, today’s pipetters have seen marked improvement in user-friendly design. Enormous gains were met with the development of the electronic pipetter, introduced less than a decade ago. Not only does the electronic pipetter make the job less tedious and more comfortable, it also drastically reduces the potential for human error.

Other advances in ergonomics include more lightweight construction. Generally, the electronic pipetter may be heavier but the decreased workload offsets the added weight. Even so, designers have taken steps to ensure a user-friendly design. Nichiryo’s Nichipet HB Hybrid Electronic Pipetter, mentioned earlier, has its battery pack strategically placed to nicely balance the pipetter, making it comfortable to hold.

Advancements in the grip design have made pipetters more ergonomically correct. A slimmer grip is generally easier for any size hand to hold and results in fatigue-free operation. Manufacturers have added ribbed housing for a comfortable, secure grip and a finger rest to minimize hand fatigue.

Moving Forward with Automation

Robotics in liquid handling were introduced in the early 1980s. The demand for automation began with the pharmaceutical industry. Pressure on the industry to reduce time-to-market pushed manufacturers to create instrumentation that was faster while still being accurate and cost efficient.

The market leaders met this new requirement by developing automated instruments that speedily, tirelessly and accurately performed the once tedious and time-consuming task of the lab tech. Liquid handling tasks such as pipetting, diluting, dispensing and washing are being carried out by these technological wonders.

Rather than resulting in eliminated jobs, automation has changed the dynamics of the laboratory worker. “The job has evolved,” explains Jason Green, product manager for Bio-Tek Instruments Inc. (Winooski, VT). “They have more time to absorb the data and the results are more accurate with automation.

“Our goal is to be in line with their needs and where they’re going,” Green says. One example of this thinking is Bio-Tek’s Precision 2000, a solution for automated 96-/384-well microplate liquid handling. “A laboratory may have a current need for a 96-well and eventually need a 384-well microplate,” Green says. “We always like to add value to our components.” Added value comes in the form of bulk reagent dispensing in Bio-Tek’s Precision 2000. This workstation completely replaces manual pipetting and is fully equipped with a user-configurable six-station platform and robot compatibility. An external keypad and open design allow flexibility with setup options and give the user the ability to create, edit, copy and delete files. Virtually any liquid transfer parameters can be customized.

With automation comes the technological ability to manage minute volumes of liquid. Screening multiple compounds in parallel has always been an option in research but recent advances in the tools have led to rapid acceleration in the volume of compounds that can be screened in the same time frame.

Advances in liquid-handling automation have allowed researchers to move from tubes to multi-well plates ranging from a few wells to 1,536 in the same footprint. Beyond microplates, microarrays now allow the screening of thousands of substrates on a single slide. The pharmaceutical industry has been a leader in the screening of compound libraries and has worked closely with manufacturers to accelerate the development of the latest liquid-handling tools.

Taking yet another step in the process and automating it is a centrifugally driven microfluidic lab on a disc. The lab disc looks like a CD with multiple layers, and accomplishes much more than a single task. Its layers include the software that controls the assay; heating elements for thermal control and activation of active valves; and microscale fluid paths, reaction chambers and valves. Fluid moves along these pathways by capillary action or centrifugal forces produced by the spinning disc. A multitasker, the sealed disc is capable of mixing, diluting, washing, pumping, metering, filtrating, heating, detecting and many more assay steps without human intervention.

Today, full automation is commonplace in high throughput life science laboratories. Yet, virtually every laboratory can benefit from automation. There are numerous automated liquid handling instruments that are small, application-specific designs with lower price tags. “When choosing a new instrument for liquid handling, make sure it’s robot compatible,” Green suggests. By choosing a component that can be integrated into a robotic system, a lab can keep its options open for a future with automation.

Future demands will likely require more laboratories to choose automation. “Life science is growing. We’ve just hit the tip of the iceberg. There is so much more to do,” Green says. Indeed, genomics, proteomics, gene expression and drug-discovery research are just gearing up for amazing discoveries.