ARRAYS OF OPTICAL CONFINEMENTS AND USES THEREOF
First Claim
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1. An apparatus comprising:
- an array of waveguides on a solid support, said array having a fill fraction greater than about 0.0001, wherein said waveguides are suitable for holding a biological reagent, and wherein said waveguides provide an effective observation volume that permits observation of individual molecules present in said biological reagent; and
an optical system operatively coupled to the waveguides that detects signals from the effective observation volume of said waveguides.
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Abstract
The present invention relates to optical confinements, methods of preparing and methods of using them for analyzing molecules and/or monitoring chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost single-molecular analysis.
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Citations
47 Claims
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1. An apparatus comprising:
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an array of waveguides on a solid support, said array having a fill fraction greater than about 0.0001, wherein said waveguides are suitable for holding a biological reagent, and wherein said waveguides provide an effective observation volume that permits observation of individual molecules present in said biological reagent; and an optical system operatively coupled to the waveguides that detects signals from the effective observation volume of said waveguides. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 39, 40, 41, 42, 43)
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34. A method of detecting a biological analyte, comprising:
optically capturing the analyte within an optical confinement that is created by (a) providing an array of waveguides having a fill fraction greater than about 0.0001; and (b) illuminating at least one waveguide within the array that is suspected to contain the analyte with an incident light beam thereby detecting the analyte. - View Dependent Claims (35, 36, 37, 38)
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44. A method of sequencing a plurality of target nucleic acid molecules, comprising:
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(a) providing an array of waveguides having a fill fraction greater than about 0.0001; (b) mixing in the waveguides the plurality of target nucleic acid molecules, primers complementary to the target nucleic acid molecules, polymerization enzymes, and more than one type of nucleotides or nucleotide analogs to be incorporated into a plurality of nascent nucleotide strands, each strand being complementary to a respective target nucleic acid molecule; (c) subjecting the mixture of step (b) to a polymerization reaction under conditions suitable for formation of the nascent nucleotide strands by template-directed polymerization of the nucleotides or nucleotide analogs; (d) illuminating the waveguides with an incident light beam; and (e) identifying the nucleotides or the nucleotide analogs incorporated into the each nascent nucleotide strand. - View Dependent Claims (45, 46, 47)
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Specification