Verifying Liquid-Handler Performance for Complex or Nonaqueous Reagents: A New Approach

Abstract

Multichannel volume dispensing devices, such as automated liquid handlers, are widely used in drug discovery assays and other high-throughput screening processes. The performance of these systems is heavily based on the ability to deliver proper volumes of specific reagents. For instance, because concentrations of species within an assay are volume dependent, assay integrity and the subsequent interpretation of assay results are directly tied to liquid-handler performance. When liquid handlers are used to aspirate/dispense aqueous-based reagents, there are many accepted methodologies used to calibrate/verify the system's ability to properly perform within a user's tolerance window. In other situations, however, liquid handlers are used to dispense complex or nonaqueous reagents, such as dimethyl sulfoxide (DMSO), serum, and aqueous-based mixtures with detergents, for which there may not be standard, or simple, methodologies to verify liquid-handler performance. Discussed herein is the recent research on broadening existing methods for accurately assessing liquid-handler performance when dispensing complex or nonaqueous reagents. Accurate and reliable adjustment of liquidhandler protocols for varied reagent types could have farreaching adoption in all scientific communities. Using this methodology, target aliquots of multiple solutions were dispensed with a calibrated syringe and subsequently validated via dual-dye ratiometric photometry. Various custom sample solutions were prepared to incorporate (a) 75–90% DMSO (v/v), (b) 20% glycerol (v/v), and (c) 50% ethanol (v/v). (JALA 2006;11:172-80)