Systems and methods for genetic and biological analysis
First Claim
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1. A method for sequencing a nucleic acid sample, comprising:
- a. providing a plurality of particles adjacent to a sensor array, wherein an individual particle of said plurality is positioned adjacent to an individual sensor of said sensor array and is coupled to a nucleic acid molecule generated from said nucleic acid sample, and wherein said individual sensor provides a virtual wall during sequencing that isolates said individual sensor from other sensors of said sensor array;
b. hybridizing a primer to said nucleic acid molecule;
c. performing a primer extension reaction by contacting said nucleic acid molecule with nucleotide bases in the presence of a polymerase adjacent to said nucleic acid molecule;
d. detecting signals indicative of incorporation events associated with one or more of said nucleotide bases during said primer extension reaction;
e. monitoring and correcting for phase error introduced during said primer extension reaction; and
f. generating a sequence of said nucleic acid sample at reduced phase error.
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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
23 Claims
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1. A method for sequencing a nucleic acid sample, comprising:
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a. providing a plurality of particles adjacent to a sensor array, wherein an individual particle of said plurality is positioned adjacent to an individual sensor of said sensor array and is coupled to a nucleic acid molecule generated from said nucleic acid sample, and wherein said individual sensor provides a virtual wall during sequencing that isolates said individual sensor from other sensors of said sensor array; b. hybridizing a primer to said nucleic acid molecule; c. performing a primer extension reaction by contacting said nucleic acid molecule with nucleotide bases in the presence of a polymerase adjacent to said nucleic acid molecule; d. detecting signals indicative of incorporation events associated with one or more of said nucleotide bases during said primer extension reaction; e. monitoring and correcting for phase error introduced during said primer extension reaction; and f. generating a sequence of said nucleic acid sample at reduced phase error. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A method for sequencing a nucleic acid sample at reduced phase error, comprising:
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a. providing a plurality of particles adjacent to a sensor array, wherein an individual particle of said plurality is positioned adjacent to an individual sensor of said sensor array and is coupled to a nucleic acid molecule generated from said nucleic acid sample; b. hybridizing a primer to said nucleic acid molecule; c. performing a primer extension reaction by contacting said nucleic acid molecule with nucleotide bases in the presence of a polymerase adjacent to said nucleic acid molecule; d. using said individual sensor, measuring local impedance changes within a Debye layer associated with said individual particle during said primer extension reaction; e. monitoring and correcting for phase error introduced during said primer extension reaction; and f. generating a sequence of said nucleic acid sample at reduced phase error. - View Dependent Claims (18, 19, 20, 21, 22, 23)
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Specification