Systems and methods for genetic and biological analysis
First Claim
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1. A system for nucleic acid sequencing, comprising:
- an array comprising a plurality of features in optical communication with a plurality of optical sensors, wherein said array is integrated with said plurality of optical sensors, wherein, during use, a feature of said plurality of features retains or immobilizes a plurality of nucleic acid molecules having sequences that are substantially identical to a nucleic acid sequence of a template nucleic acid molecule, and wherein an optical sensor of said plurality of optical sensors is in optical communication with said feature; and
one or more computer processors operatively coupled to said array, wherein said one or more computer processors are programmed to (i) bring said plurality of nucleic acid molecules in contact with nucleic acid bases in the presence of polymerizing enzymes under conditions sufficient to incorporate said nucleic acid bases into growing strands complementary to said plurality of nucleic acid molecules, wherein said plurality of nucleic acid molecules is brought in contact with said nucleic acid bases without applying an electric field to confine or isolate said nucleic acid bases within said feature, (ii) use said optical sensor to detect one or more signals indicative of said nucleic acid bases incorporated into said growing strands, and (iii) use said one or more signals detected in (ii) to identify said nucleic acid bases, to thereby generate a sequence corresponding to said nucleic acid sequence of said template nucleic acid molecule.
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Abstract
The invention relate to systems and methods for sequencing polynucleotides, as well as detecting reactions and binding events involving other biological molecules. The systems and methods may employ chamber-free devices and nanosensors to detect or characterize such reactions in high-throughput. Because the system in many embodiments is reusable, the system can be subject to more sophisticated and improved engineering, as compared to single use devices.
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Citations
31 Claims
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1. A system for nucleic acid sequencing, comprising:
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an array comprising a plurality of features in optical communication with a plurality of optical sensors, wherein said array is integrated with said plurality of optical sensors, wherein, during use, a feature of said plurality of features retains or immobilizes a plurality of nucleic acid molecules having sequences that are substantially identical to a nucleic acid sequence of a template nucleic acid molecule, and wherein an optical sensor of said plurality of optical sensors is in optical communication with said feature; and one or more computer processors operatively coupled to said array, wherein said one or more computer processors are programmed to (i) bring said plurality of nucleic acid molecules in contact with nucleic acid bases in the presence of polymerizing enzymes under conditions sufficient to incorporate said nucleic acid bases into growing strands complementary to said plurality of nucleic acid molecules, wherein said plurality of nucleic acid molecules is brought in contact with said nucleic acid bases without applying an electric field to confine or isolate said nucleic acid bases within said feature, (ii) use said optical sensor to detect one or more signals indicative of said nucleic acid bases incorporated into said growing strands, and (iii) use said one or more signals detected in (ii) to identify said nucleic acid bases, to thereby generate a sequence corresponding to said nucleic acid sequence of said template nucleic acid molecule. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 21, 23, 25, 28, 29)
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11. A system for nucleic acid sequencing, comprising:
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an array comprising a plurality of features in optical communication with a plurality of optical sensors, wherein said array is integrated with said plurality of optical sensors, wherein during use said plurality of features retains or immobilizes a plurality of nucleic acid molecules, wherein a feature of said plurality of features is configured to contain a nucleic acid molecule of said plurality of nucleic acid molecules, and wherein an optical sensor of said plurality of optical sensors is in optical communication with said feature; and one or more computer processors operatively coupled to said array, wherein said one or more computer processors are programmed to (i) bring said nucleic acid molecule in contact with nucleic acid bases in the presence of a polymerizing enzyme under conditions sufficient to incorporate at least one of said nucleic acid bases into a growing strand complementary to said nucleic acid molecule, (ii) use said optical sensor to detect one or more signals indicative of said at least one of said nucleic acid bases incorporated into said growing strand, (iii) use said one or more signals detected in (ii) to identify said at least one of said nucleic acid bases, and (iv) monitor and correct for phase error introduced during incorporation of said at least one of said nucleic acid bases into said growing strand, to thereby generate a sequence of said nucleic acid molecule. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 27, 30, 31)
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Specification