Liquid handling: Challenges and Solutions
Is the handling of liquids part of your laboratory procedures? Is laboratory liquid dispensing something that you will automate or have automated? The vast majority of you will say yes. Liquid handling is indeed the most common laboratory unit operation, automated or not. Improving liquid handling capability is the focus on much on-going technology development. Yet it remains at the core of what makes manual to automated assay translation difficult (See ALA 2008 Laboratory Automation Survey). To learn more about this paradox, we talked to Doug Gurevitch, Senior Development Engineer at the University of California San Diego, and co-instructor of the ALA Liquid Handling Boot Camp short course.
Doug defines liquid handling automation as computer or microprocessor controlled movement or dispensing of liquid. This includes auto-samplers, auto-fractionators and collectors, pumps, valves, electrophoretic, electro-osmotic and magneto-restricted flow systems as well as automated robotic pipetting systems. Doug feels the biggest technology shift has been the continued trend toward handling of smaller and smaller volumes, making it possible to reduce sample and reagent consumption and so reducing assay costs. The inkjet and ultrasonic technologies have made routine and repeatable nano-liter dispensing possible.
Doug also points out that this small-volume evolution has increased the complexity and cost of liquid handling automation. Accurate and precise automated small volume dispensing is the result of high quality engineering. Routine nanoliter dispensing with an 8% C.V. is in many ways an engineering marvel. If one really needs to work with such small volumes, one should expect to pay a premium price for such technology. The good news is that this technology now actually works.
In his Liquid Handling Boot camp short course, Doug says that the most common problem people report is the difficulty in translating manual assays into automated assays. Many people think that automating a process is going to solve all their problems. But the fact is that before automating one needs to have an assay that works manually, with defined quality control metrics so that one can really know when an assay is working or not. Doug indicates that this issue is not new. People have always been getting themselves in trouble by automating assays before they are really ready to be automated.
How does he advise people to develop their manual assays to minimize the translation-to-automation issues? Thinking about how pipetting steps will need to be "ganged" in an automated system is important. One may be accustomed to interleaving the pipetting of various volumes in a manual mode, whereas an automated system may be most efficient when liquid transfers of a given volume are done to all samples at once. It's also necessary to consider how automation may or may not deal with problematic solutions or buffers. Any solution that is viscous, or that tends to be frothy or foamy, must be diluted to minimize the potential for problems with automated pipetting. A 100% glycerol solution can be managed manually, but is really not amenable to automated handling.
Doug's crystal ball predicts that the drive toward smaller volumes will continue. More effort will go into linking the macro liquid handling world with the micro world, to minimize the waste of solutions now involved in making that transition. He also feels that more emphasis should be placed on lower cost technology to address the needs of small or academic labs.
Until next time,
Domo Arigato, Mr. Roboto!