Methods of generating nanoarrays and microarrays

Abstract

The methods described herein provide a means of producing an array of spatially separated proteins. The method relies on covalently attaching each protein of the plurality of proteins to a structured nucleic acid particle (SNAP), and attaching the SNAPs to a solid support.

1 .- 17 . (canceled) 
     
     
         18 . A method of forming an array, comprising:
 a) coupling a nucleic acid origami to an attachment site of a solid support;   b) coupling to the nucleic acid origami a seed oligonucleotide, wherein the seed oligonucleotide is attached to a single biological entity; and   c) after coupling the seed oligonucleotide to the nucleic acid origami, growing the seed oligonucleotide by a polymerization reaction.   
     
     
         19 . The method of  claim 18 , wherein the nucleic acid origami comprises a long nucleic acid strand hybridized to more than one short nucleic acid strand. 
     
     
         20 . The method of  claim 19 , wherein a short nucleic acid strand of the more than one short nucleic acid strands hybridizes to two segments of the long nucleic acid strand. 
     
     
         21 . The method of  claim 19 , wherein a short nucleic acid strand of the one or more short nucleic acid strands is complementary to one or more short nucleic acid strands. 
     
     
         22 . The method of  claim 21 , wherein a short nucleic acid strand of the one or more short nucleic acid strands is complementary to the seed oligonucleotide. 
     
     
         23 . The method of  claim 22 , further comprising hybridizing the seed oligonucleotide to the short nucleic acid strand of the one or more short nucleic acid strands. 
     
     
         24 . The method of  claim 19 , wherein a short nucleic acid strand of the one or more short nucleic acid strands has one or more segments that are not complementary to the long nucleic acid strand. 
     
     
         25 . The method of  claim 24 , wherein a segment of the short nucleic acid strand that is not complementary is at least 10 nucleotides long. 
     
     
         26 . The method of  claim 19 , wherein the seed oligonucleotide comprises a nucleotide sequence that is complementary to the long nucleic acid strand. 
     
     
         27 . The method of  claim 25 , further comprising hybridizing the seed oligonucleotide to the long nucleic acid strand. 
     
     
         28 . The method of  claim 18 , wherein the nucleic acid origami comprises at least 100 short nucleic acid strands. 
     
     
         29 . The method of  claim 18 , wherein the nucleic acid origami comprises at least 10 folds. 
     
     
         30 . The method of  claim 18 , wherein step (b) comprises coupling the seed oligonucleotide to the nucleic acid origami distal to a region of the nucleic acid origami that contacts the attachment site. 
     
     
         31 . The method of  claim 18 , wherein step (b) comprises coupling the seed oligonucleotide to the nucleic acid origami to form a linker that attaches to the biological entity. 
     
     
         32 . The method of  claim 31 , wherein the linker comprises a rigid outpost of the nucleic acid origami. 
     
     
         33 . The method of  claim 32 , wherein the rigid outpost is distal to a region of the nucleic acid origami that contacts the attachment site. 
     
     
         34 . The method of  claim 18 , wherein the attachment site comprises a filamentous molecule. 
     
     
         35 . The method of  claim 34 , wherein the filamentous molecule comprises an oligonucleotide. 
     
     
         36 . The method of  claim 34 , wherein step (a) comprises coupling the nucleic acid origami to the filamentous molecule. 
     
     
         37 . The method of  claim 36 , wherein coupling the nucleic acid origami to the filamentous molecule comprises coupling a single-stranded oligonucleotide of the nucleic acid origami to the filamentous molecule. 
     
     
         38 . The method of  claim 18 , wherein the polymerization reaction comprises a chain-growth polymerization reaction. 
     
     
         39 . The method of  claim 18 , wherein the polymerization reaction comprises a step-growth polymerization reaction. 
     
     
         40 . The method of  claim 18 , further comprising (d) detecting the single biological entity that is attached to the solid support via the nucleic acid origami. 
     
     
         41 . The method of  claim 18 , wherein the single biological entity comprises a single protein. 
     
     
         42 . The method of  claim 18 , wherein the single biological entity is covalently attached to the seed oligonucleotide. 
     
     
         43 . The method of  claim 18 , wherein the nucleic acid origami is non-covalently coupled to the attachment site. 
     
     
         44 . The method of  claim 18 , wherein the nucleic acid origami is covalently coupled to the attachment site.