Since the inception of the variable volume pipette in the 1960s, researchers have been sacrificing the precision of their liquid transfers for ease of use, efficiency, and speed. However, a new trend towards decreasing reaction volumes in genomics laboratories has called into question the capabilities of various liquid handling solutions, especially since lower volumes tend to increase the impact of liquid handling imprecision on experimental results. With precision medicine and drug discovery relying so heavily on the findings published by translational genomics laboratories in academia and biotechnology, the reproducibility of data has never been so salient and highly scrutinized.
Today, researchers generally regard automated workstations as the most reproducible liquid handling solutions, as automated liquid handling (ALH) systems remove many of the obstacles associated with user-variability. Researchers assess the volumetric performance of these devices mainly by measuring the imprecision of liquid transfers, expressed quantitatively through coefficients of variation (CVs). ALH platforms often dispense extremely precisely, and published CVs for target liquid deliveries in the range of tens to hundreds of microliters (µL) tend to be less than 1%. However, for most ALH systems these specifications deteriorate as target volumes approach 1 µL. In fact, the most widely utilized liquid handling platforms publish specifications including CVs as high as 6% at 0.5 µL.
In this experiment, the MANTIS Liquid Handler delivered target volumes of Artel Sample Solutions into each well of meticulously characterized Artel 96- or 384-well Verification Plates. Following centrifugation and mixing, the Artel MVS read the concentration of the sample solution and provided, through the graphical user interface of the Artel MVS Software, a CV value for each plate. One discrete target volume was selected for each 96- or 384-well microplate in order to provide a compelling set of liquid deliveries.
Eleven target volumes were chosen over the three microfluidic MANTIS chip types in order to provide a comprehensive review of the liquid handling imprecision associated with the MANTIS. In accordance with best practices, each run for each target volume was tested in triplicate to ensure statistical significance.
All volumetric tests performed with the HV and LV chip types utilized Artel 384-well Verification Plates. All tests perfomed with the CF chip type utilized Artel 96-well Verification Plates. Lower density plates were utilized for all CF testing to accommodate the 200 µL dispense volume and ensure consistency across all testing for this chip type.
Over the entire volume range, all CVs, and Root Mean Squared (RMS) of CVs, were less than or equal to 1.5%.
Figure 1. Measured Performance of the FORMULATRIX® MANTIS® Liquid Handler
The reproducibility of experiments between genomics labs can be largely impacted by the imprecision of liquid transfers, especially at low nanoliter-scale volumes.
Evidenced by the data published in this application note, the MANTIS boasts CVs well under 2%, even at volumes as low as 0.1 µL, providing researchers with a solution that facilitates the generation of trustworthy results in highly sensitive methods such Next Generation Sequencing (NGS) and qPCR.
As more and more researchers move to sub-10 µL reaction volumes in their genomics workflows, it will become more critical than ever before to ensure highly precise liquid handling within these volume ranges.