Processes for detecting or quantifying analytes of interest
This invention provides novel compositions and processes for analyte detection, quantification and amplification. Nucleic acid arrays and libraries of analytes are usefully incorporated into such compositions and processes. Universal detection elements, signaling entities and the like are employed to detect and if necessary or desirable, to quantify analytes. Amplification of target analytes are also provided by the compositions and processes of this invention.
1. A process for detecting or quantifying non-nucleic acid analytes of interest, said process comprising the steps of:
1) providing
a) an array on a solid surface comprising a plurality of discrete areas; wherein
at least two of said discrete areas each comprise a nucleotide sequence fixed or immobilized to said discrete areas,
said at least two discrete areas comprise a first discrete area and a second discrete area, and
said nucleotide sequence on said first discrete area is different from said nucleotide sequence on said second discrete area;
b) chimeric compositions consisting of:
i) a nucleic acid portion; and
ii) a non-nucleic acid portion;
wherein
said nucleic acid portion of each chimeric composition is complementary to a nucleotide sequence of said array,
said nucleic acid portion of the chimeric composition that is complementary to the nucleotide sequence located at said first discrete area has a different sequence from that of said nucleic acid portion of the chimeric composition complementary to the nucleotide sequence located at said second discrete area,
said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said first discrete area has a binding affinity for a first non-nucleic acid analyte of interest and said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said second discrete area has a binding affinity for a second non-nucleic acid analyte of interest,
said first non-nucleic acid analyte is different from said second non nucleic acid analyte,
when said non-nucleic acid portion of a chimeric composition is a peptide or protein, said nucleic acid portion of said chimeric composition does not comprise a sequence which is either identical or complementary to a sequence that codes for said peptide or protein, and
said nucleic acid portion i) and said non-nucleic acid portion ii) are covalently attached to each other;
c) a sample containing or suspected of containing said non-nucleic acid analytes of interest, wherein
said non-nucleic acid analytes of interest comprise oligopeptides, polypeptides, oligosaccharides, polysaccharides, lipids, ligands, or combinations thereof; and
d) signal generating means;
2) contacting said array with said chimeric compositions to hybridize the nucleic acid portions of said chimeric compositions to complementary nucleotide sequences fixed or immobilized to said array;
3) contacting said array with the sample under conditions permissive of binding said non-nucleic acid analytes to said non-nucleic acid portion;
4) contacting said bound non-nucleic acid analytes with said signal generating means; and
5) detecting or quantifying the presence of said non-nucleic acid analytes by measuring said signal generating means bound to said array.
2. The process of claim 1 , wherein said solid surface is porous.
3. The process of claim 2 , wherein said porous solid surface comprises polyacrylamide or agarose.
4. The process of claim 1 , wherein said solid surface is non-porous.
5. The process of claim 4 , wherein said nonporous solid surface comprises glass or plastic.
6. The process of claim 1 , wherein said solid surface is transparent, translucent, opaque or reflective.
7. The process of claim 1 , wherein said fixed or immobilized nucleotide sequences comprise DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
8. The process of claim 7 , wherein said nucleotide sequences comprise PNA.
9. The process of claim 7 or 8 , wherein said nucleotide sequences are modified on any of the sugar, phosphate or base moieties.
10. The process of claim 1 , wherein said nucleic acid portion comprises DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
11. The process of claim 10 , wherein said nucleic acid portion comprises PNA.
12. The process of claim 10 or 11 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
13. The process of claim 1 , wherein said non-nucleic acid portions comprise peptides, proteins, ligands, enzyme substrates, hormones, receptors, drugs, or a combination of any of the foregoing.
14. The process of claim 1 , wherein said signal generating means comprises a direct signal generating means.
15. The process of claim 14 , wherein said direct signal generating means comprises a fluorescent compound, a phosphorescent compound, a chemiluminescent compound, a chelating compound, an electron dense compound, a magnetic compound, an intercalating compound, an energy transfer compound, or a combination of any of the foregoing.
16. The process of claim 1 , wherein said signal generating means comprises an indirect signal generating means.
17. The process of claim 16 , wherein said indirect signal generating means comprises an antibody, an antigen, a hapten, a receptor, a hormone, a ligand, an enzyme, or a combination of any of the foregoing.
18. The process of claim 17 , wherein said indirect signal generating means comprises an enzyme that catalyzes a reaction comprising a fluorogenic reaction, a chromogenic reaction or a chemiluminescent reaction.
19. A process for detecting or quantifying non-nucleic acid analytes of interest, said process comprising the steps of:
1) providing
a) an array on a solid surface comprising a plurality of discrete areas; wherein
at least two of said discrete areas each comprise a nucleotide sequence fixed or immobilized to said discrete areas,
said at least two discrete areas comprise a first discrete area and a second discrete area, and
said nucleotide sequence on said first discrete area is different from said nucleotide sequence on said second discrete area;
b) chimeric compositions consisting of:
a nucleic acid portion; and
a non-nucleic acid portion;
wherein
said nucleic acid portion of each chimeric composition is complementary to a nucleotide sequence of said array,
said nucleic acid portion of the chimeric composition that is complementary to the nucleotide sequence located at said first discrete area has a different sequence from that of said nucleic acid portion of the chimeric composition complementary to the nucleotide sequence located at said second discrete area,
said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said first discrete area has a binding affinity for a first non-nucleic acid analyte of interest and said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said second discrete area has a binding affinity for a second non-nucleic acid analyte of interest,
said first non-nucleic acid analyte is different from said second non-nucleic acid analyte,
when said non-nucleic acid portion of a chimeric composition is a peptide or protein, said nucleic acid portion of said chimeric composition does not comprise a sequence which is either identical or complementary to a sequence that codes for said peptide or protein, and
said nucleic acid portion i) and said non-nucleic acid portion ii) are covalently attached to each other;
c) a sample containing or suspected of containing said non-nucleic acid analytes of interest, wherein
said non-nucleic acid analytes of interest comprise oligopeptides, polypeptides, oligosaccharides, polysaccharides, lipids, ligands, or combinations thereof; and
d) signal generating means;
2) contacting said chimeric compositions with the sample under conditions permissive of binding said non-nucleic acid analytes to said non-nucleic acid portion;
3) contacting said array with said chimeric compositions to hybridize the nucleic acid portions of said chimeric compositions to complementary nucleotide sequences fixed or immobilized to said array;
4) contacting said bound non-nucleic acid analytes with said signal generating means; and
5) detecting or quantifying the presence of said non-nucleic acid analytes by measuring said signal generating means bound to said array.
20. The process of claim 19 , wherein said solid surface is porous.
21. The process of claim 20 wherein said porous solid surface comprises polyacrylamide or agarose.
22. The process of claim 19 , wherein said solid surface is non-porous.
23. The process of claim 22 , wherein said non-porous solid surface comprises glass or plastic.
24. The process of claim 19 , wherein said solid surface is transparent, translucent, opaque or reflective.
25. The process of claim 19 , wherein said fixed or immobilized nucleotide sequences comprise DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
26. The process of claim 25 , wherein said nucleotide sequences comprise PNA.
27. The process of claim 25 or 26 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
28. The process of claim 19 , wherein said nucleic acid portion comprises DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
29. The process of claim 28 , wherein said nucleic acid portion comprises PNA.
30. The process of claim 28 or 29 , wherein said nucleic, acid portion is modified on any of the sugar, phosphate or base moieties.
31. The process of claim 19 , wherein said non-nucleic acid portions comprise peptides, proteins, ligands, enzyme substrates, hormones, receptors, drugs, or a combination of any of the foregoing.
32. The process of claim 19 , wherein said signal generating means comprises a direct signal generating means.
33. The process of claim 32 , wherein said direct signal generating means comprises a fluorescent compound, a phosphorescent compound, a chemiluminescent compound, a chelating compound, an electron dense compound, a magnetic compound, an intercalating compound, an energy transfer compound, or a combination of any of the foregoing.
34. The process of claim 19 , wherein said signal generating means comprises an indirect signal generating means.
35. The process of claim 34 , wherein said indirect signal generating means comprises an antibody, an antigen, a hapten, a receptor, a hormone, a ligand, an enzyme, or a combination of any of the foregoing.
36. The process of claim 35 , wherein said indirect signal generating means comprises an enzyme that catalyzes a reaction comprising a fluorogenic reaction, a chromogenic reaction or a chemiluminescent reaction.
37. A process for detecting or quantifying non-nucleic acid analytes of interest, said process comprising the steps of:
1) providing
a) an array on a solid surface comprising a plurality of discrete areas; wherein
at least two of said discrete areas each comprise a nucleotide sequence fixed or immobilized to said discrete areas,
said at least two discrete areas comprise a first discrete area and a second discrete area, and
said nucleotide sequence on said first discrete area is different from said nucleotide sequence on said second discrete area;
b) chimeric compositions consisting of:
i) a nucleic acid portion; and
ii) a non-nucleic acid portion;
wherein
said nucleic acid portion of each chimeric composition is complementary to a nucleotide sequence of said array,
said nucleic acid portion of the chimeric composition that is complementary to the nucleotide sequence located at said first discrete area has a different sequence from that of said nucleic acid portion of the chimeric composition complementary to the nucleotide sequence located at said second discrete area,
said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said first discrete area has a binding affinity for a first non-nucleic acid analyte of interest and said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said second discrete area has a binding affinity for a second non-nucleic acid analyte of interest,
said first non-nucleic acid analyte is different from said second non-nucleic acid analyte,
when said non-nucleic acid portion of a chimeric composition is a peptide or protein, said nucleic acid portion of said chimeric composition does not comprise a sequence which is either identical or complementary to a sequence that codes for said peptide or protein, and
said nucleic acid portion i) and said non-nucleic acid portion ii) are covalently attached to each other;
c) a sample containing or suspected of containing said non-nucleic acid analytes of interest, wherein
said non-nucleic acid analytes of interest comprise oligopeptides, polypeptides, oligosaccharides, polysaccharides, lipids, ligands, or combinations thereof; and
d) signal generating means;
2) contacting said array with said chimeric compositions to hybridize the nucleic acid portions of said chimeric compositions to complementary nucleotide sequences fixed or immobilized to said array;
3) labeling said non-nucleic acid analytes of interest with said signal generating means;
4) contacting said array with the labeled non-nucleic acid analytes to bind said non-nucleic acid analytes to said non-nucleic acid portion; and
5) detecting or quantifying the presence of said non-nucleic acid analytes by measuring said signal generating means bound to said array.
38. The process of claim 37 , wherein said solid surface is porous.
39. The process of claim 38 , wherein said porous solid surface comprises polyacrylamide or agarose.
40. The process of claim 37 , wherein said solid surface is non-porous.
41. The process of claim 40 , wherein said non-porous solid surface comprises glass or plastic.
42. The process of claim 37 , wherein said solid surface is transparent, translucent, opaque or reflective.
43. The process of claim 37 wherein said fixed or immobilized nucleotide sequences comprise DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
44. The process of claim 43 , wherein said nucleotide sequences comprise PNA.
45. The process of claim 43 or 44 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
46. The process of claim 37 , wherein said nucleic acid portion comprises DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
47. The process of claim 46 , Wherein said nucleic acid portion comprises PNA.
48. The process of claim 46 or 47 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
49. The process of claim 37 , wherein said non-nucleic acid portions comprise peptides, proteins, ligands, enzyme substrates, hormones, receptors, drugs, or a combination of any of the foregoing.
50. The process of claim 37 , wherein said signal generating means comprises a direct signal generating means.
51. The process of claim 50 , wherein said direct signal generating means comprises a fluorescent compound, a phosphorescent compound, a chemiluminescent compound, a chelating compound, an electron dense compound, a magnetic compound, an intercalating compound, an energy transfer compound, or a combination of any of the foregoing.
52. The process of claim 37 , wherein said signal generating means comprises an indirect signal generating means.
53. The process of claim 52 , wherein said indirect signal generating means comprises an antibody, an antigen, a hapten, a receptor, a hormone, a ligand, an enzyme, or a combination of any of the foregoing.
54. The process of claim 53 , wherein said indirect signal generating means comprises an enzyme that catalyzes a reaction comprising a fluorogenic reaction, a chromogenic reaction or a chemiluminescent reaction.
55. A process for detecting or quantifying non-nucleic acid analytes of interest, said process comprising the steps of:
1) providing
a) an array on a solid surface comprising a plurality of discrete areas; wherein
at least two of said discrete areas each comprise a nucleotide sequence fixed or immobilized to said discrete areas,
said at least two discrete areas comprise a first discrete area and a second discrete area, and
said nucleotide sequence on said first discrete area is different from said nucleotide sequence on said second discrete area;
b) chimeric compositions consisting of:
i) a nucleic acid portion; and
ii) a non-nucleic acid portion;
wherein
said nucleic acid portion of each chimeric composition is complementary to a nucleotide sequence of said array,
said nucleic acid portion of the chimeric composition that is complementary to the nucleotide sequence located at said first discrete area has a different sequence from that of said nucleic acid portion of the chimeric composition complementary to the nucleotide sequence located at said second discrete area,
said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said first discrete area has a binding affinity for a first non-nucleic acid analyte of interest and said non-nucleic acid portion of the chimeric composition that has a nucleic acid portion that is complementary to the nucleotide sequence of said second discrete area has a binding affinity for a second non-nucleic acid analyte of interest,
said first non-nucleic acid analyte is different from said second non-nucleic acid analyte,
when said non-nucleic acid portion of a chimeric composition is a peptide or protein, said nucleic acid portion of said chimeric composition does not comprise a sequence which is either identical or complementary to a sequence that codes for said peptide or protein, and
said nucleic acid portion i) and said non-nucleic acid portion n) are covalently attached to each other;
c) a sample containing or suspected of containing said non-nucleic acid analytes of interest, wherein
said non-nucleic acid analytes of interest comprise oligopeptides, polypeptides, oligosaccharides, polysaccharides, lipids, ligands, or combinations thereof; and
d) signal generating means;
2) labeling said non-nucleic acid analytes of interest with said signal generating means;
3) contacting said chimeric compositions with the labeled non-nucleic acid analytes to bind said non-nucleic acid analytes to said non-nucleic acid portion;
4) contacting said array with said chimeric compositions to hybridize the nucleic acid portions of said chimeric compositions to complementary nucleotide sequences fixed or immobilized to said array; and
5) detecting or quantifying the presence of said non-nucleic acid analytes by measuring said signal generating means bound to said array.
56. The process of claim 55 , wherein said solid surface is porous.
57. The process of claim 56 , wherein said porous solid surface comprises polyacrylamide or agarose.
58. The process of claim 55 , wherein said solid surface is non-porous.
59. The process of claim 58 , wherein said non-porous solid surface comprises glass or plastic.
60. The process of claim 55 , wherein said solid surface is transparent, translucent, opaque or reflective.
61. The process of claim 55 , wherein said fixed or immobilized nucleotide sequences comprise DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
62. The process of claim 61 , wherein said nucleotide sequences comprise PNA.
63. The process of claim 61 or 62 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
64. The process of claim 55 , Wherein said nucleic acid portion comprises DNA, RNA, a DNA analog, an RNA analog, or combinations thereof.
65. The process of claim 64 , wherein said nucleic acid portion comprises PNA.
66. The process of claim 64 or 65 , wherein said nucleic acid portion is modified on any of the sugar, phosphate or base moieties.
67. The process of claim 55 , wherein said non-nucleic acid portions comprise peptides, proteins, ligands, enzyme substrates, hormones, receptors, drugs, or a combination of any of the foregoing.
68. The process of claim 55 , wherein said signal generating means comprises a direct signal generating means.
69. The process of claim 68 , wherein said direct signal generating means comprises a fluorescent compound, a phosphorescent compound, a chemiluminescent compound, a chelating compound, an electron dense compound, a magnetic compound, an intercalating compound, an energy transfer compound, or a combination of any of the foregoing.
70. The process of claim 55 , wherein said signal generating means comprises an indirect signal generating means.
71. The process of claim 70 , wherein said indirect signal generating means comprises an antibody, an antigen, a hapten, a receptor, a hormone, a ligand, an enzyme, or a combination of any of the foregoing.
72. The process of claim 71 , wherein said indirect signal generating means comprises an enzyme that catalyzes a reaction comprising a fluorogenic reaction, a chromogenic reaction or a chemiluminescent reaction.
73. The process of claim 1 , wherein said non-nucleic acid analytes comprise ligands comprising nonpeptide antigens, hormones, enzymes, substrates, vitamins, drugs, nonpeptide signal molecules, or combinations thereof.
74. The process of claim 19 , wherein said non-nucleic acid analytes comprise ligands comprising non-peptide antigens, hormones, enzymes, substrates, vitamins, drugs, non-peptide signal molecules, or combinations thereof.
75. The process of claim 37 , wherein said non-nucleic acid analytes comprise ligands comprising non-peptide antigens, hormones, enzymes, substrates, vitamins, drugs, non-peptide signal molecules, or combinations thereof.
76. The process of claim 55 , wherein said non-nucleic acid analytes comprise ligands comprising non-peptide antigens, hormones, enzymes, substrates, vitamins, drugs, non-peptide signal molecules, or combinations thereof.