Biochemically activated electronic device
First Claim
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1. A method of nucleic acid sequencing, comprising:
- (a) contacting a nucleic acid molecule to be sequenced with a polymerase attached to a solid support charge sensor with an oligonucleotide tether;
(b) contacting the nucleic acid molecule and the polymerase with different nucleotide types, wherein each of the different nucleotide types is respectively attached to an oligonucleotide capable of hybridizing to a complementary region of the oligonucleotide tether and includes a unique label that can be detected by the solid support charge sensor when the label is in proximity of a screening length of the charge sensorwherein the polymerase catalyzes incorporation of one of the different nucleotide types to a nascent nucleic acid strand complementary to the nucleic acid molecule and wherein the oligonucleotide of the one of the different nucleotide types hybridizes to the complementary region of the oligonucleotide tether and brings the unique label within proximity of the screening length; and
(c) detecting a distinguishable signal using the charge sensor in response to the incorporation of the one of the different nucleotide types into the nascent nucleic acid strand complementary to the nucleic acid molecule to be sequenced.
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Abstract
A method of nucleic acid sequencing. The method can include the steps of (a) providing a polymerase tethered to a solid support charge sensor; (b) providing one or more nucleotides, whereby the presence of the nucleotide can be detected by the charge sensor; and (c) detecting incorporation of the nucleotide into a nascent strand complementary to a template nucleic acid.
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Citations
20 Claims
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1. A method of nucleic acid sequencing, comprising:
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(a) contacting a nucleic acid molecule to be sequenced with a polymerase attached to a solid support charge sensor with an oligonucleotide tether; (b) contacting the nucleic acid molecule and the polymerase with different nucleotide types, wherein each of the different nucleotide types is respectively attached to an oligonucleotide capable of hybridizing to a complementary region of the oligonucleotide tether and includes a unique label that can be detected by the solid support charge sensor when the label is in proximity of a screening length of the charge sensor wherein the polymerase catalyzes incorporation of one of the different nucleotide types to a nascent nucleic acid strand complementary to the nucleic acid molecule and wherein the oligonucleotide of the one of the different nucleotide types hybridizes to the complementary region of the oligonucleotide tether and brings the unique label within proximity of the screening length; and (c) detecting a distinguishable signal using the charge sensor in response to the incorporation of the one of the different nucleotide types into the nascent nucleic acid strand complementary to the nucleic acid molecule to be sequenced. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A method of detecting incorporation of nucleotides, comprising:
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(a) contacting a nucleic acid molecule to be sequenced with a polymerase, attached to a solid support charge sensor with an oligonucleotide tether; (b) contacting the nucleic acid molecule and the polymerase with four different nucleotide types, wherein each of the four different nucleotide types is respectively attached to an oligonucleotide capable of hybridizing to a complementary region of the oligonucleotide tether and includes a charge unique label that can be detected by the solid support charge sensor when the unique charge label is in proximity of a screening length of the charge sensor, wherein the polymerase catalyzes incorporation of one of the four different nucleotide types to a nascent nucleic acid strand complementary to the nucleic acid molecule and wherein the oligonucleotide of the one of the four different nucleotide types hybridizes to the complementary region of the oligonucleotide tether and brings the unique charge label within proximity of the screening length; (c) detecting a distinguishable signal of the unique charge label using the charge sensor; and (d) identifying the incorporated one of the four different nucleotide types by the distinguishable signal.
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Specification