Whether it’s dispensing reagents, washing plates, or plating out bacteria, moving things around is at the core of biomedical R&D and production.
The task is increasingly done in high-throughput using robotics and automation, which take care of everything from the individual steps to coordination of the processes.
How all of this can be done better, smarter, and more accurately—starting with a common vocabulary with which to begin the discussion—and put together into productive workflows was discussed at Select Biosciences’ “European Lab Automation” held earlier this month in Hamburg.
A common language helps to facilitate discussion and move a field forward. Stefan Bammesberger, R&D engineer at the laboratory for MEMS applications at IMTEK, University of Freiburg in Germany, felt that in order to compare liquid handlers, he first needed to establish a way of categorizing them, and to find a vocabulary to discuss their performance.
He first separated dispensing technologies into those that use contact as a way of dislodging the dispensed liquid and those that do not. Because contact is a potential source of cross-contamination, a dispensing method that rather ejects the liquid may be preferable, especially for biomedical applications. Among the noncontact dispensers, two types of technologies predominate for the nanoliter to microliter range: valve-based and positive displacement, each with its own advantages and disadvantages.
Having delineated dispensing mode, Bammesberger set out to establish a terminology that could describe performance characteristics. Discussions always come down to precision (how close dispensed volumes are relative to each other) and accuracy (how close the dispensed volumes are relative to the target volume).
Yet, “when you look at how the different manufacturers characterize volumetric precision and accuracy, everybody does it somehow differently from the others, so it’s not really comparable. No standard has prevailed in the industry, and it’s really hard to compare the performance of different dispensing systems,” he said. What are necessary are parameters at once generic enough to be utilized for many different applications, yet meaningful and objective enough to allow comparison of very different liquid handlers.
Take filling a 384-well plate with an eight-channel dispenser. Usually manufacturers fill a plate and measure the volumes dispensed, but this doesn’t give insights into where the deviation from the ideal might come from.
“So I try to break it down into the very basic elements you do with a liquid handler, the most basic of which is the intra-run approach, where you have just one channel doing one thing—dispensing aliquot after aliquot,” Bammesberger explained. “Let it do the same thing several times and measure how it deviates.” He terms these “intra-run” measurements.
Building up from there, measurements looking at the reproducibility between runs are “inter-run.” On the other hand, “tip-to-tip” measurements look at deviations made when dispensing from multiple channels.
Bammesberger went on to demonstrate the applicability of his categorizations and terminology, using them as the basis with which to evaluate five commercial noncontact liquid dispensers. His sampling found that intra-run and inter-run CVs tend to be significantly smaller than the corresponding tip-to-tip CVs for a given target volume and liquid handler, prompting him to suggest that for high-precision applications, it may be beneficial to use only a single tip of a liquid handler.