Electrochemical arrays
First Claim
Patent Images
1. A method for synthesizing a nucleic acid comprising:
- (a) providing a first nucleic acid having a 3′
-terminal and a 5′
-protecting group;
(b) covalently coupling said 3′
-terminal of the first nucleic acid to an electrode; and
(c) cleaving said 5′
-protecting group from said first nucleic acid by passing a current therethrough under reaction conditions in which said first nucleic acid remains covalently coupled to said electrode to provide a nucleic acid having a deprotected 5′
terminal.
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Abstract
The present invention relates to methods for synthesizing nucleic acids. The invention also relates to the production of an array of nucleic acids as well as methods for making such an array. Electrochemical methods may be used to both fabricate and interrogate the nucleic acid arrays.
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Citations
26 Claims
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1. A method for synthesizing a nucleic acid comprising:
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(a) providing a first nucleic acid having a 3′
-terminal and a 5′
-protecting group;
(b) covalently coupling said 3′
-terminal of the first nucleic acid to an electrode; and
(c) cleaving said 5′
-protecting group from said first nucleic acid by passing a current therethrough under reaction conditions in which said first nucleic acid remains covalently coupled to said electrode to provide a nucleic acid having a deprotected 5′
terminal. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. An array of nucleic acids comprising:
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a microelectronic substrate having at least a first surface;
a plurality of different nucleic acids attached to the first surface of the substrate at a density exceeding at least 1000 different nucleic acids/cm2, wherein each of the different nucleic acids is attached to the surface of the microelectronic substrate in a different known location, and has a different determinable sequence;
a plurality of different binding detection electrodes on said first surface; and
wherein each different nucleic acid has a different binding detection electrode operatively associated therewith. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
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18. A method of making an array of nucleic acids comprising:
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(a) providing a plurality of nucleotides with a 3′
-terminal and a 5′
-protecting group;
(b) covalently coupling the 3′
-terminal of one of the nucleotides to a first surface of a microelectronic substrate, the nucleotides having different predetermined sequences and being attached at different localized areas having a width of less than 100 microns on the first surface of a microelectronic substrate;
(c) cleaving said 5′
-protecting group from the first nucleotide attached to the microelectronic substrate by passing a current therethrough under reaction conditions in which said first nucleotide remains covalently coupled to said electrode to provide elongated oligonucleotides; and
(d) covalently coupling a 3′
-terminal of a subsequent nucleotide having a 3′
-terminal and a 5′
-protecting group to the first nucleotide to produce further elongated oligonucleotides; and
wherein each of said first nucleotide coupled to the microelectronic substrate has a different binding detection electrode operatively associated therewith. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26)
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Specification