Comparison of Automation Equipment in High Throughput Screening

Abstract

This report compares several types of liquid handling equipment presently used in HTS. The devices include 96-well automated pipettors such as the Carl Creative PlateTrac™ (Harbor City, CA), Matrix PlateMate™ (Hudson, NH), Tomtec Quadra-96T? (Hamden, CT) and a Zymark RapidPlate-96™ (Hopkinton, MA) integrated into a full robotic system. A general set of considerations including ease of programming, assay-completion time, accuracy and precision of liquid dispensing, and low-volume pipetting were evaluated. Both a protease screen and a cell-based reporter gene assay were used as model systems for comparison. The data indicate that the Carl Creative PlateTrac has an advantage in several areas. These include the ease in programming, reduction in assay run time, and increased accuracy and precision in liquid dispensing, especially for volumes of 1 μl or less. However, both the Matrix Platemate and Zymark robotic systems may be used to perform complicated multi-step tasks involving multidirectional plate transfer, which is not possible on the current PlateTrac. Advantages and limitations of each piece of equipment are discussed further in this report.

Use of Operating Windows in the Assessment of Integrated Robotic Systems for the Measurement of Bioprocess Kinetics

“…However, inherent to their use is the need to understand the general limitations of liquid handling equipment and those of integrated detection devices. The most common liquid handling difficulties are tip carryover contamination (18), speed of liquid handling, liquid handling accuracy and precision (19, 20), and the speed of the detection device. Speed of liquid handling, liquid handling accuracy and precision, and the speed of the detection device have all been addressed in this work.…”

“…For additions made from each type of tip, it has been assumed throughout this study that when the initiating reagent is added to the bulk fluid within the well, it will be rapidly mixed. This is a reasonable assumption when a small volume of reagent is dispensed within the bulk of a low‐viscosity fluid and then shaken (19, 22, 23). At present there are no published data as to whether mixing in high‐viscosity phases in microwells will influence the measurement of bioprocess kinetics.…”

“…Materials. Generally accepted models of a low‐viscosity aqueous phase, RO water, and a low‐viscosity organic phase, dimethyl sulfoxide (DMSO) (Sigma, Poole, Dorset, U.K.), were used to determine liquid handling accuracy and precision (18, 19). To model a Newtonian, high‐viscosity liquid, 80% (w/w) glycerol (Sigma, Poole, Dorset, U.K.) was used (20).…”

Quantification and prediction of jet macro-mixing times in static microwell plates

“…To date, microwell experimentation has mainly been applied to high throughput drug discovery (Delvin, 1997;Lamsa et al, 2004;Wegener et al, 2003) and the routine performance of laboratory assays (Kolb, 1994;Wang et al, 2003). Here the focus has been on understanding the reliability and operation of the liquid handling robots used to perform experiments (Astle and Akowitz, 1996;Berg et al, 2001;Stevens et al, 1998). For bioprocess studies it is equally important to understand how the physical environment within a microwell impacts on the reproducibility and scalability of the data obtained (Berg et al, 2001;Lye et al, 2003).…”

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

“…Some air displacement devices can be converted to positive displacement using a "backfill" mode in which the air is replaced with a noncompressible fluid. Air and positive displacement mechanisms have been described [25][26][27][28] as they apply to compound and reagent transfers, whereas pin tools have more commonly been applied to compound or oligonucleotide transfers. 29,30 Noncontact dispensing has improved significantly in recent years and has begun to offer expanded utility in HTS.…”