Methods to increase the capacity of high content cell-based screening assays

Abstract

The present invention involves the pooling of multiple high content cell-based screening assays, and carrying out a primary screen in a one or more channels of a fluorescence detection device, which drastically increases the number of simultaneous high content cell-based screening events that can be carried out. Subsequent deconvolution of primary screen “hits” (ie: those wells or locations on an array of locations in which the one or more test compounds caused a change in the fluorescence signal(s) from the fluorescent reporter molecules in the cells) enables much more rapid generation of high content cell screening data than was previously possible, and at significantly reduced costs.

Description

CROSS REFERENCE [0001] This application claims priority to U.S. Provisional Patent Application 60 / 274,969 filed Mar. 12, 2001.FIELD OF THE INVENTION [0002] The present invention related to the fields of drug discovery, cell biology, and molecular biology. BACKGROUND OF THE INVENTION [0003] Drug discovery is a long, multiple step process involving identification of specific disease targets, development of an assay based on a specific target, validation of the assay, optimization and automation of the assay to produce a screen, high throughput screening of compound libraries using the assay to identify “hits”, hit validation, and hit compound optimization. The output of this process is a lead compound that goes into pre-clinical studies and, if validated, eventually into clinical trials. In this process, the screening phase is distinct from the assay development phases, and involves testing compound efficacy in living biological systems. [0004] Historically, drug discovery is a slow a...

AI Technical Summary

Benefits of technology

[0010] The present invention fulfills the need in the art for methods to increase the capacity to provide high content information on the effect of a test compound on cellular events of interest, while maintaining the “hit” rate, and dramatically reduce the cost and time required to carry out high content cell-based screening, and is further applicable to methods for high throughput screening of a variety of biological targets.

Problems solved by technology

Historically, drug discovery is a slow and costly process, spanning numerous years and consuming hundreds of millions of dollars per drug created.

Therefore, the vast majority of wells screened in a microplate format yield a negative response, necessitating the screening of a large number of wells to detect a response of interest, which significantly impacts the capacity requirements of such high content cell-based screening assays.

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