Method of characterizing potential therapeutics by determining cell-cell interactions

Abstract

A method quantitatively analyzes images of two different cell types that interact in producing and maintaining a disease state or other biological condition. The two separate cell types are exposed to an agent or stimulus suspected of influencing the biological condition (e.g., the agent might be a potential therapeutic for treating a cancer). The two different cell types are co-cultured or otherwise allowed to interact with one another before and during exposure to the agent. The images of the cells show how the agent affects the cells' phenotypes, including their viability, migration patterns, etc. The method generates a quantitative phenotype for each cell type by quantitatively analyzing the cell images via an automatic procedure. The quantitative phenotypes typically take the form of a group of scalar or vector descriptors that together provide a “fingerprint.” The descriptors may be size values, positions, morphological values, intensity distributions, etc.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS [0001] This application is related to PCT patent application number PCT / US00 / 13154, filed May 12, 2000 in the name of Sabry et al. It is also related to U.S. patent application Ser. No. 09 / ______, (Attorney Docket No. CYTOP005) filed on Dec. 4, 2000 in the name of Vaisberg and Coleman. Both applications are incorporated herein by reference for all purposes.FIELD OF THE INVENTION [0002] The systems and methods described herein provide for image capturing of living, dead, or fixed cells or cell fractions used to identify information about substances used on the cells or information about the cells themselves. Accordingly, the present invention can enable researchers and scientists to identify promising candidates in the search for new and better treatments and medicines, for example, in drug discovery and development. The principles enumerated herein may, with equal facility, be applied to other applications, including but not limited to ...

AI Technical Summary

Benefits of technology

[0008] One aspect of the invention provides a method of evaluating the effect of interactions between distinct cell types. The method may be characterized by the following sequence: (a) providing a first cell culture of a first cell type and a second cell culture of a second cell type in a microenvironment; (b) imaging the first and second cell types after exposure to the agent; and (c) quantitatively evaluating one or more images obtained in (b) to identify any effects of the agent. To this end, the method employs quantitative representations of the phenotypes of the cells in the first and second cell cultures. This may show how the effects of the agent are mediated by interactions between the first and second cell cultures. The microenvironment mentioned above is typically a contained environment in which the cells of the first and second cell c

Problems solved by technology

Purified substances having a desirable combination bio-active properties are rare and often difficult to identify.

Unfortunately, the vast majority of “hits” generated by such techniques do not possess the right combination of properties to qualify as therapeutic compounds.

When these substances are subjected to low throughput cellular and animal tests to establish their therapeutic usefulness, they are typically found to fail in some regard.

Unfortunately, such tests are time consuming and costly, thus limiting the number of substances that can be tested.

Unfortunately, this system is has only a limited ability to predict a therapeutic usefulness of particular compounds or other agents.

One difficulty in predicting the clinical effectiveness of any agent is determining what concurrent effects it produces in normal cells, diseased versions of the normal cells, and other related cells.

To the extent that both cell types interact in producing or maintaining a disease state, there is no systematically rigorous technique for evaluating how a potential therapeutic affects their interaction.

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