Spatially addressable combinatorial chemical array in cd-rom format

Abstract

A method for preparing very large spatially-addressable arrays of chemical compounds by light-directed synthesis is provided, wherein the light is provided by a laser and the compounds are arrayed on a rotating disc in a CD-ROM format. A method for assaying the resulting array with a CD-ROM mechanism is also provided.

Description

PRIORITY INFORMATION [0001] This is a divisional application of U.S. application Ser. No. 09 / 269,092, filed Mar. 18, 1999 which is a 371 of PCT / US97 / 16738 which was filed on Sep. 19, 1997, and which claims the priority of provisional application Ser. No. 60 / 026,415 filed Sep. 20, 1996 which are hereby incorporated in their entireties by reference herein.FIELD OF THE INVENTION [0002] The invention has applications in the fields of chemistry, drug discovery, and genomics. The invention relates to: (1) methods for conducting chemical reactions on a support surface with spatial selectivity; (2) the spatially addressable arrays of compounds (chemical libraries) produced thereby; and (3) methods for detecting specific members of these arrays of compounds, including methods of assaying for the specific binding of substances such as receptors, antibodies or other ligands, as well as methods of assaying for biological activity or other desirable property. The invention employs laser light un...

AI Technical Summary

Benefits of technology

The present invention provides an alternative method of preparing and assaying a spatially addressable array of compounds on a planar support using light-directed synthesis. The use of laser light and a spinning disc makes it possible to selectively and reproducibly irradiate over 109 individual locations on a single CD-array. The CD-arrays can be used for various applications such as drug discovery and DNA sequencing. The invention overcomes limitations of current methods and provides a more efficient and cost-effective way of preparing and assaying compound arrays.

Problems solved by technology

All of these methods are capable of generating large libraries (i.e., libraries containing a large number of compounds), but none of them are amenable to rapid screening of the libraries for binding activity, biological activity, or other desirable properties.

Robotic systems are available for microtiter plate assays, but screening a large library by such a method remains a massive undertaking.

In addition to the great effort involved, the testing of complex mixtures is limited by the low concentration of any individual species in the mixture, and is susceptible to false positive results from the additive effects of large numbers of weakly active species.

In practice, deconvolution has had limited success in probing large libraries of compounds.

The photolithographic method of synthesis, however, is cumbersome, and requires a substantial investment in very specialized equipment.

The scale of library synthesis is limited by the size of the masks and by the translational reach of the scanning device, which together limit the accessible surface for synthesis to a few square centimeters.

In practice this technique is presently limited to arrays of 104 to 105 compounds.