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A Modular, Fully Integrated Ultra-High-Throughput Screening System Based on Confocal Fluorescence Analysis Techniques

stefan.jaeger{at}evotecoai.com

Norbert Garbow

Achim Kirsch

Hartwig Preckel

Frank U. Gandenberger

Kurt Herrenknecht

Evotec OAI/Evotec Technologies, Hamburg, Germany

Martin Rüdiger

Jonathan P. Hutchinson

Ryan P. Bingham

GlaxoSmithKline, Harlow, UK

Fernando Ramon

Ana Bardera

Julio Martin

GlaxoSmithKline, Madrid, Spain

The rapid increase in size of compound libraries, as well as new targets emerging from the Human Genome Project, require progress in ultra-high-throughput screening (uHTS) systems. In a joint effort with scientists and engineers from the biotech and the pharmaceutical industry, a modular, fully integrated system for miniaturized uHTS was developed. The goal was to achieve high data quality in small assay volumes (1-4 µL) combined with reliable and unattended operation. Two new confocal fluorescence readers have been designed. One of the instruments is a 4-channel confocal fluorescence reader, measuring with 4 objectives in parallel. The fluorescence readout is based on single-molecule detection methods, allowing high sensitivity at low tracer concentrationsand delivering an information-rich output. The other instrument isa confocal fluorescence im aging reader, where the imagesare analyzed in terms of generic patternsand quantified in units of intensity per pixel. Both readers are spanning the application range from assays with isolated targets in homogenous solution or membrane vesiclebased assays (4-channel reader) to cell-based assays (imaging reader). Results from a comprehensive test on these assay types demonstrate the high quality and robustness of this screening system.

Key Words: integrated screening system • high-throughput screening • fluorescence • single molecule detection • confocal optics • homogenous assay • cellular assay • cell imaging

Journal of Biomolecular Screening, Vol. 8, No. 6, 648-659 (2003)
DOI: 10.1177/1087057103258475


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