Chemically Encoded Spatially Addressed Library Screening Platforms

Abstract

Provided herein are encoded split pool libraries useful, inter alia, for forming highly diverse and dense arrays for screening and detection of a variety of molecules.

1 .- 75 . (canceled) 
     
     
         76 . An ordered array for use in a high throughput biological screening assay, said ordered array comprising a solid support comprising a plurality of wells, wherein each of said plurality of wells further comprises an immobilized microparticle, and wherein each of said immobilized microparticles is covalently attached to:
 (i) a ligand domain conjugated to a first functionalized group on the surface of said immobilized microparticle; and   (ii) a nucleic acid domain conjugated to a second functionalized group on the surface of said immobilized microparticle,   
       wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein, 
       wherein said nucleic acid domain identifies said ligand domain, and 
       wherein said first and second functionalized groups on the surface of said immobilized microparticle are different. 
     
     
         77 . The ordered array of  claim 76 , wherein said ligand domain is a plurality of ligand domains conjugated to a plurality of said first functionalized groups on the surface of said immobilized microparticle. 
     
     
         78 . The ordered array of  claim 76 , wherein said nucleic acid domain is a plurality of nucleic acid domains conjugated to a plurality of said second functionalized groups on the surface of said immobilized microparticle. 
     
     
         79 . The ordered array of  claim 76 , wherein said ligand domain comprises a plurality of chemical building blocks, and wherein said nucleic acid domain comprises a plurality of nucleic acids identifying said plurality of chemical building blocks. 
     
     
         80 . The ordered array of  claim 76 , wherein each of said first and second functionalized groups is independently selected from the group consisting of an amino group, a carboxyl group, a thiol group, and a hydroxyl group. 
     
     
         81 . The ordered array of  claim 76 , wherein said ordered array is screened for activity against a biomolecule selected from the group consisting of a hormone, a cytokine, a protein, an antibody, a nucleic acid, a lipid, a carbohydrate, a cellular membrane antigen, a receptor, a whole cell, a whole cell lysate, a eukaryotic cell, and a virus. 
     
     
         82 . The ordered array of  claim 81 , wherein said biomolecule is selected from the group consisting of a whole cell, a whole cell lysate, a eukaryotic cell, and any component thereof. 
     
     
         83 . The ordered array of  claim 81 , wherein said nucleic acid is mRNA. 
     
     
         84 . The ordered array of  claim 76 , wherein said peptide comprises at least one moiety selected from the group consisting of a naturally occurring amino acid, a non-naturally occurring amino acid, and a mimetic of a naturally occurring amino acid. 
     
     
         85 . The ordered array of  claim 76 , wherein said peptide further comprises a portion having non-peptide functionality. 
     
     
         86 . The ordered array of  claim 76 , wherein said wherein said peptide is selected from the group consisting of a macrocyclic peptide, an acyclic precursor to a macrocyclic peptide, a peptidomimetic, a polyamide, and a macrolactam. 
     
     
         87 . The ordered array of  claim 76 , wherein said nucleic acid domain is cleavable from said immobilized microparticle with a cleaving agent. 
     
     
         88 . The ordered array of  claim 87 , wherein said cleaving agent is selected from the group consisting of an acid, an alkali agent, UV irradiation, and light irradiation. 
     
     
         89 . The ordered array of  claim 88 , wherein said cleaving agent does not cleave said ligand domain from the surface of said immobilized microparticle. 
     
     
         90 . The ordered array of  claim 76 , wherein either said ligand domain or said nucleic acid domain is cleaved from the surface of said immobilized microparticle. 
     
     
         91 . The ordered array of  claim 76 , wherein each of said ligand domain and said nucleic acid domain are cleaved from the surface of said immobilized microparticle. 
     
     
         92 . The ordered array of  claim 88 , wherein said acid is trifluoroacetic acid. 
     
     
         93 . The ordered array of  claim 88 , wherein said alkali agent is ammonium hydroxide, ammonia, methylamine, or a mixture of ammonium hydroxide and methylamine. 
     
     
         94 . The ordered array of  claim 76 , wherein said ordered array is located within a detection device. 
     
     
         95 . The ordered array of  claim 76 , wherein said ordered array comprises a density selected from the group consisting of at least 10,000 microparticles per square millimeter, at least 50,000 microparticles per square millimeter, at least 150,000 microparticles per square millimeter, and at least 250,000 microparticles per square millimeter. 
     
     
         96 . The ordered array of  claim 76 , wherein said high throughput biological screening assay is selected from the group consisting of a microarray screen, a fluorescence binding assay, a colorimetric binding assay, and an electrochemical binding assay.