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Assay Miniaturization for Ultra-High Throughput Screening of Combinatorial and Discrete Compound Libraries: A 9600-Well (0.2 Microliter) Assay System

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Ji-Hu Zhang

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Tongming Chen

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Anthony Maffia, III

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Karl F. Blom

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Andrew P. Combs

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Thomas D.Y. Chung

DuPont Merck Pharmaceutical Company, Department of Leads Discovery, Wilmington, DE 19880-0400

Combinatorial chemistry has opened a new realm of chemical entities in the search for novel therapeutics. Combinatorial chemistry is currently adding hundreds of thousands of compounds to similar numbers available from years of synthesis by medicinal chemistry. It is not unreasonable to expect that over the next several years, nearly a million compounds will be available for screening against each therapeutic target. The number of potential targets will also be increasing with the advances in genomics. With the increasing number of compounds to be screened against an increasing number of targets, it is becoming increasingly difficult and costly to obtain the required amounts of key biological material needed to screen these compounds. One obvious solution is to miniaturize the assays so that the biological reagent supply doesn't need to increase. To this end, we have developed an ultra-high throughput screening system comprised of a new plate design (9600-well), detection system, and liquid handling system. This new format is capable of performing assays in as little as 0.2 Al. The results obtained from this system compare favorably to those obtained in the standard 96-well format.

Journal of Biomolecular Screening, Vol. 3, No. 1, 55-62 (1998)
DOI: 10.1177/108705719800300108


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