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.

1 . A method for preparing a spatially-addressable chemical library array, comprising the steps of: 
 a) providing a disc shaped planar substrate as a solid phase, wherein the substrate comprises reactive groups on its surface, the reactive groups being masked by laser-removable protecting groups, the surface further bearing formatting features that enable reproducible and accurate irradiation of surface sites by the laser of a recordable CD-ROM mechanism;    b) preparing the library by light-directed synthesis on the planar substrate, wherein the light comprises laser radiation, and wherein the laser radiation is directed to pre-selected synthesis sites on the surface of the substrate by the CD-ROM mechanism under the control of a computer; and    c) removing some or all residual protecting groups.    
     
     
         2 . A method for identifying the members of a spatially-addressable chemical library array that bind a given analyte, comprising the steps of: 
 a) providing a spatially-addressable chemical library array bound to the surface of a disc-shaped substrate, wherein the surface bears formatting features that enable reproducible and accurate irradiation of synthesis sites by the laser of a CD-ROM mechanism, wherein the library members are attached to the synthesis sites, and wherein the synthesis sites are arranged on the surface so as to be individually irradiatable by the laser of the CD-ROM mechanism;    b) exposing said substrate, bearing said library, to a solution of said analyte, under conditions that permit specific binding of said analyte to as subset of members of the library;    c) removing the analyte that has not bound specifically to a subset of members of the library;    d) labeling the analyte that has bound to a subset of members of the library with a label, said label having the capacity to either emit light upon laser irradiation or to modify some measurable property of light from an interrogating laser;    e) by means of a CD-ROM mechanism under computer control, irradiating a selected synthesis site on the surface of the substrate bearing the library and bearing the optionally labeled analyte bound to a subset of members of the library, with an interrogating laser;    f) by means of CD-ROM mechanism under computer control either detecting emitted light or measuring said measurable property in the reflected or transmitted beam of the interrogating laser, determining if the property has been changed due to the presence of analyte or label at the irradiated synthesis site, and recording the results of said determination;    g) repeating steps (e) and (f) at other synthesis sites, irradiating synthesis sites systematically until all synthesis sites have been irradiated; and    h) correlating the location of synthesis sites bearing analyte with the structure of the chemical library member synthesized at each such site, the structure being deduced by reference to a stored chronology.    
     
     
         3 . A method for preparing a spatially-addressable chemical library array, comprising the steps of: 
 a) providing a disc shaped planar substrate as a solid phase, wherein the substrate comprises reactive groups on its surface, the reactive groups being masked by laser-removable protecting groups, the planar substrate further bearing formatting features that enable reproducible and accurate irradiation of selected surface sites when the substrate is rotated;    b) preparing the library by light-directed synthesis on the planar substrate, wherein the light comprises laser radiation, and wherein the laser radiation is directed to pre-selected synthesis sites on the surface of the substrate under the control of a computer; and    c) removing some or all residual protecting groups.    
     
     
         4 . A method for identifying the members of a spatially-addressable chemical library array that bind a given analyte, comprising the steps of: 
 a) providing a spatially-addressable chemical library array bound to the surface of a disc-shaped substrate, wherein the surface bears formatting features that enable reproducible and selective laser irradiation of selected library members when the substrate is rotated, and wherein the library members are arranged on the surface so as to be individually irradiatable by the laser;    b) exposing said substrate, bearing said library, to a solution of said analyte, under conditions that permit specific binding of said analyte to a subset of library members;    c) removing the analyte that has not bound specifically to a subset of library members;    d) labeling the analyte that has bound to a subset of library members with a label, said label having the capacity to either emit light upon laser irradiatiation or to modify some measurable property of light from a laser;    e) under computer control, and by reference to the formatting features, rotating the substrate and/or translating the laser radially, so as to bring a selected library member having a given spatial location and/or logical address on the substrate into a position where it may be irradiated by the laser;    f) under computer control, irradiating said selected synthesis site on the surface of the substrate with the laser;    g) under computer control, detecting emitted, reflected, or transmitted light from the site of the selected library member.    h) either measuring said measurable property in the reflected or transmitted light and determining if the property has been changed due to the presence of analyte or label at the site of the irradiated library member, or measuring the amount of emitted light.    i) recording the spatial location and/or logical address of the library member, together with the result of the measurement of step (h) at the site of the selected library member, said result being indicative of the amount of analyte bound to the selected library member;    j) repeating steps (e) through (i), irradiating library members systematically until all selected library members have been irradiated; and    k) correlating the spatial location and/or logical address of library members to which the analyte has bound, with the structure of the library member at each such spatial location or logical address.    
     
     
         5 . A method of employing laser light of a laser and laser detector mechanism in a manner analogous to the reading of a CD-ROM under computer control for both the synthesis and optical assay inspection of chemically reactive compounds on a substrate surface of an optical disc having digitally encoded, optically readable, information for conducting said synthesis and optical assay inspection comprising: 
 providing an optical disc having digitally encoded optically readable information to be read by a laser and laser detector mechanism;    providing a spatially addressable array of sites of chemically reactive compounds on a substrate surface of said disc, one or more of the reactive compounds being masked by laser-removable chemical protecting compounds said one or more of the reactive compounds being capable of binding selectively to an analyte when activated by the removal of an associated protecting compound.    removing said one or more laser-removable protecting compounds by synthesis thereof using said laser under the control of a computer associated with said mechanism and using said encoded information to perform said synthesis to activate said one or more reactive compounds;    exposing said one or more of said reactive compounds on said substrate surface to analyte under conditions permitting specific binding of a selected analyte to at least one of said reactive compounds;    using said laser and laser detector mechanism to conduct an optical inspection of said array sites of chemical compounds under the control of said computer and using said encoded information to perform an optical assay inspection thereof to identify the presence of one or more of a selected analyte bound to one or more of said reactive compounds.    
     
     
         6 . The method of  claim 5  including the step of labeling an analyte that is bound with a label which is capable of emitting light upon laser irradiation.  
     
     
         7 . The method of  claim 5  including the step of labeling an analyte that is bound with a label which is capable of modifying a measurable property of light from said laser.  
     
     
         8 . The method of  claim 5  including using said associated computer for direct control of a laser beam of said mechanism during synthesis and direct access to a primary signal generated by the reading optics of said mechanism during the assay.  
     
     
         9 . The method of  claim 5  wherein said disc includes a cover layer which is optically transparent to the wave length of said laser, sealed at the circumference and at an inner annular edge, and incorporates ports for the introduction and withdrawal of reagent solutions.