A Standard Operating Procedure for Assessing Liquid Handler Performance in High-Throughput Screening

Abstract

The thrust of early drug discovery in recent years has been toward the configuration of homogeneous miniaturized assays. This has allowed organizations to contain costs in the face of exponential increases in the number of screening assays that need to be run to remain competitive. Miniaturization brings with it an increasing dependence on instrumentation, which over the past several years has seen the development of nanodispensing capability and sophisticated detection strategies. To maintain confidence in the data generated from miniaturized assays, it is critical to ensure that both compounds and reagents have been delivered as expected to the target wells. The authors have developed a standard operating procedure for liquid-handling quality control that has enabled them to evaluate performance on 2 levels. The first level provides for routine daily testing on existing instrumentation, and the second allows for more rigorous testing of new dispensing technologies. The procedure has shown itself to be useful in identifying both method programming and instrumentation performance shortcomings and has provided a means to harmonizing instrumentation usage by assay development and screening groups. The goal is that this type of procedure be used for facilitating the exchange of liquid handler performance data across the industry.

Inkjet printing for pharmaceutics – A review of research and manufacturing

“…It is the second challenge for which inkjet printing was identified as a potentially important tool (Blanchard et al 1996, Lemmo et al 1997, Sittampalam et al 1997, Burbaum et al 1997, Lemmo et al 1998, Oldenburg et al 1998, Schena et al 1998, Rose 1999, Dunn and Feygin 2000, Bellavance et al 2000, Taylor et al 2002. The key features of inkjet that lend themselves to the liquid handling challenges of micro-array technologies are (i) noncontact deposition with a significant stand-off distance, ensuring that the size of the well is no longer limited by the size of the dosing nozzle, (ii) repeatability and accuracy of inkjet-deposited drops once their formation is optimised, (iii) accurate control of both individual drop volumes and total volumes by waveform and print signal controls, (iv) low reservoir volume requirements and (v) minimal space requirements for the system.…”

“…Potyrailo et al 2007 discussed the existence of applications outside pharmaceuticals for this technology, in a similar way to combinatorial chemistry. Earlier work by GlaxoSmithKline Pharmaceuticals (Taylor et al 2002) showed that piezo-actuated inkjet and capillary deposition were the only non-contact techniques that could be tailored to the correct throughput and reliability for this approach. (Boehm et al 2011).…”

“…A recognised element of ensuring successful development of 'system discovery' techniques using inkjet printing (Figure 2(1)) is that of highly precise fluid handling (Dunn and Feygin 2000, Lemmo et al 1998, Rose 1999, Taylor et al 2002, Chai et al 2013. In inkjet printing the effect on a pharmaceutical agent must be considered during:…”

Practical Considerations of Liquid Handling Devices in Drug Discovery

“…Assessment of instrument performance has become important in order to minimize falsepositive and false-negative rates in high-throughput screening (Taylor et al 2002). One of the most important figures of merit in evaluating the performance of liquid handlers is accuracy, which is commonly reported as %bias (Rose 1999):…”

“…Gravimetric measurements utilize the mass and the density (ρ) of the dispensed solution to determine the volume. It has been used extensively to calibrate and verify the accuracy of liquid dispensers (Bergsdorf et al 2006;Rhode et al 2004;Taylor et al 2002). Typically, the solution is dispensed across a pre-weighed microtiter plate, which is weighed immediately after dispensing to prevent evaporation.…”