Claims
- 1. A method of modifying electrodes of an array of electrodes, the electrodes to be modified by binding at least one respective probe molecule thereto, wherein, prior to being modified, at least one respective, protective molecule overlays each of at least two electrodes to be modified such that the at least one respective, protective molecule inhibits probe molecules from binding to the at least two electrodes, the method comprising:
(a) dissociating the at least one respective protective molecule from at least one electrode overlaid by the at least one protective molecule; and (b) contacting electrodes of each of a plurality of subsets of electrodes of the array of electrodes with a respective liquid, wherein each liquid comprises a respective, different probe molecule; and wherein, at least one electrode is subjected to both the steps of (a) dissociating and (b) contacting and, for at least one electrode subjected to both the steps of (a) dissociating and (b) contacting, the respective, different probe molecule of the respective liquid binds to the electrode.
- 2. The method of claim 1, wherein at least 2 electrodes are subjected to both the steps of (a) dissociating and (b) contacting, and wherein at least two electrodes that are subjected to both the steps of (a) dissociating and (b) contacting, are members of respective, different subsets of electrodes.
- 3. The method of claim 2, wherein at least 25 electrodes that are subjected to both the steps of (a) dissociating and (b) contacting, are members of respective, different subsets of electrodes.
- 4. The method of claim 3, wherein at least 100 electrodes that are subjected to both the steps of (a) dissociating and (b) contacting, are members of respective, different subsets of electrodes.
- 5. The method of claim 1, wherein at least some subsets of the plurality of said subsets of electrodes comprise at least 2 member electrodes but fewer than 50 member electrodes.
- 6. The method of claim 1, wherein at least some subsets of the plurality of said subsets of electrodes comprise at least 5 member electrodes but fewer than 25 member electrodes.
- 7. The method of claim 1, wherein, for at least some subsets of the plurality of said subsets of electrodes, the step of (b) contacting is performed after the step of (a) dissociating.
- 8. The method of claim 1, wherein, for at least some subsets of the plurality of said subsets of electrodes, the step of (b) contacting is performed after initiating the step of (a) dissociating.
- 9. The method of claim 1, wherein, for at least some subsets of the plurality of said subsets of electrodes, the step of (a) dissociating is performed while the subsets of electrodes are in contact with the respective liquids of the step of (b) contacting.
- 10. The method of claim 1, wherein the step of (b) contacting comprises:
contacting each subset of a first portion of the plurality of said subsets with the respective liquid; and while the subsets of the first portion of subsets remain in contact with the respective liquids, contacting each subset of a second, different portion of the plurality of said subsets with the respective liquid.
- 11. The method of claim 10, wherein, while performing the step of (b) contacting, at least 25 of said subsets of electrodes are in simultaneous contact with the respective liquid comprising a respective, different molecule.
- 12. The method of claim 11, wherein, while performing the step of (b) contacting, at least 100 of said subsets of electrodes in simultaneous contact with the respective liquid comprising a respective, different molecule.
- 13. The method of claim 1, wherein the step of (b) contacting comprises simultaneously contacting at least some subsets of the plurality of said subsets of electrodes with the respective liquid.
- 14. The method of claim 1, wherein the respective liquids comprise at least two different liquids.
- 15. The method of claim 1, wherein, for each electrode of a plurality of the electrodes, the step of (a) dissociating comprises modifying an electrical potential of the electrode, whereby the at least one respective, protective molecule dissociates from the electrode.
- 16. The method of claim 1, wherein, for each electrode of a plurality of the electrodes, the step of (a) dissociating comprises modifying an electrical potential difference between the electrode and a reference electrode, whereby the at least one respective, protective molecule dissociates from the electrode.
- 17. The method of claim 16, wherein, for each of at least two subsets of the plurality of said subsets of electrodes, the step of (b) contacting further comprises contacting a reference electrode with the respective liquid, thereby electrically contacting the electrodes of the subset of electrodes and the reference electrode.
- 18. The method of claim 16, wherein, for each of at least two subsets of the plurality of said subsets of electrodes, the step of (b) contacting further comprises contacting a respective, different reference electrode with the respective liquid, thereby electrically contacting the electrodes of the subset of electrodes and the respective, different reference electrode.
- 19. The method of claim 18, wherein, for each of at least two subsets of the plurality of said subsets of electrodes, the liquid used in the step of (b) contacting does not electrically connect the electrodes of the subset with the respective reference electrodes of other subsets of electrodes.
- 20. The method of claim 18, wherein, for each of at least two subsets of the plurality of said subsets of electrodes and the respective, different reference electrode thereof, the step of (b) contacting comprises applying at least one droplet of liquid to the subset of electrodes and reference electrode, each droplet of liquid comprising at least one of the respective, different probe molecules.
- 21. The method of claim 1, wherein, for each of at least two subsets of the plurality of said subsets of electrodes, the step of (b) contacting comprises applying at least one droplet of liquid to the subset of electrodes, each droplet of liquid comprising at least one of the respective, different probe molecules.
- 22. The method of claim 1, further comprising:
repeating the steps of (a) dissociating and (b) contacting until a respective probe molecule is bound to each of at least 50 electrodes of the array.
- 23. The method of claim 22, further comprising:
repeating the steps of (a) dissociating and (b) contacting until a respective probe molecule is bound to each of at least 500 electrodes of the array.
- 24. The method of claim 1, further comprising:
repeating the steps of (a) dissociating and (b) contacting until a respective probe molecule is bound to every electrode of the array.
- 25. The method of claim 1, further comprising:
prior to performing the steps of (a) dissociating and (b) contacting, overlaying a plurality of the electrodes with at least one protective molecule by contacting the electrodes with a liquid comprising the at least one protective molecule, wherein at least one respective protective molecule binds to electrodes of the array.
- 26. The method of claim 25, wherein the at least one protective molecule comprises at least one of an alkylsiloxane, an alkylthiolate, and a fatty acid.
- 27. The method of claim 26, wherein the alkylthiolate comprises an alkanethiol having from 1 to 22 carbon atoms.
- 28. The method of claim 23, wherein, for each electrode of a plurality of electrodes, the at least one respective, protective molecule binds to the electrode by a sulfur group.
- 29. The method of claim 1, wherein the at least one of the respective, protective molecules comprises at least one of an alkylsiloxane, an alkylthiolate, and a fatty acid.
- 30. The method of claim 29, wherein the alkylthiolate comprises an alkanethiol having from 1 to 22 carbon atoms.
- 31. The method of claim 29, wherein, for each electrode of a plurality of electrodes, the at least one respective, protective molecule is bound to the electrode by a sulfur group.
- 32. The method of claim 1, wherein the probe molecules each comprise a polynucleotide.
- 33. The method of claim 32, wherein the polynucleotides of probe molecules bound to different electrodes have different sequences from one another.
- 34. The method of claim 32, wherein the probe molecules comprise a binding portion that binds the electrodes, the binding portion comprising sulfur.
- 35. The method of claim 1, wherein the array of electrodes comprises a plurality of electrode pairs, each electrode pair comprising first and second electrodes that are spaced apart by less than 1000 Angstroms, and wherein:
for at least one electrode pair of the plurality of said electrode pairs, the step of (a) dissociating comprises dissociating the at least one respective, protective molecule from only the first electrode of the electrode pair; and for at least one electrode pair of the plurality of said electrode pairs, the step of (b) contacting comprises contacting both electrodes of the electrode pair with the same respective liquid comprising the same respective, different problem molecule; and wherein, for at least one electrode pair of the plurality of said electrode pairs, the electrode pair is subjected to the step of (b) contacting and the first electrode only of the electrode pair is also subjected to the step of (a) dissociating, and wherein the respective, different probe molecule of the respective liquid binds only to the first electrode.
- 36. The method of claim 35, wherein the first and second electrodes of the electrode pairs of the array are spaced apart by less than 500 Angstroms.
- 37. The method of claim 35, wherein:
for each electrode pair of at least two electrode pairs of the plurality of said electrode pairs, the step of (a) dissociating comprises dissociating the at least one respective, protective molecule from only the first electrode of the electrode pair; for each electrode pair of at least two electrode pairs of the plurality of electrode pairs, the electrode pairs belong to different subsets of the plurality of subsets of electrodes and the step of (b) contacting comprises contacting the at least two electrode pairs with respective liquids comprising respective, different probe molecules; and wherein for each electrode pair of at least two electrode pairs contacted with respective liquids comprising respective, different probe molecules, only the first electrode of the electrode pair is also subjected to the step of (a) dissociating, and wherein the respective, different probe molecule of the respective liquid binds only to the first electrode.
- 38. The method of claim 35, wherein for at least one electrode pair having had the first electrode subjected to both the steps of (a) dissociating and (b) contacting, the method further comprises:
dissociating the at least one protective molecule from the second electrode of the electrode pair; and contacting both electrodes of the electrode pair with a liquid comprising a probe molecule to be bound to the second electrode of the electrode pair, wherein the probe molecule to be bound to the second electrode is different from the probe molecule bound to the first electrode; and wherein the probe molecule to be bound to the second electrode of electrode pair binds to the second electrode.
- 39. The method of claim 38, wherein, the probe molecule bound to one of the first and second electrodes comprises a polynucleotide.
- 40. The method of claim 35, wherein, for each electrode pair of at least two of the electrode pairs, the probe molecule bound to the other electrode comprises an intercalating group and wherein, upon contacting the electrode pair with a liquid comprising a target polynucleotide at least partially complementary to the first polynucleotide of the probe molecule bound the first electrode, the first and target polynucleotides will form a duplex region and the intercalating group will intercalate with the duplex region.
- 41. The method of claim 35, wherein, for each electrode pair of at least two of the electrode pairs, the probe molecule bound to the other electrode comprises an intercalating group and wherein, upon contacting the electrode pair with a liquid comprising a target polynucleotide at least partially complementary to the first polynucleotide of the probe molecule bound to the first electrode an electrical resistance between the first and second electrodes will be reduced.
- 42. The method of claim 1, further comprising:
for at least one electrode to which a respective, different probe molecule is bound, contacting the electrode with a liquid comprising a second protective molecule, wherein the second protective molecule also binds to the electrode.
- 43. A method of modifying electrodes of an array of electrode pairs, each electrode pair comprising a first and second electrode, the first and second electrodes of the electrode pairs to be modified by binding at least one respective probe molecule thereto, wherein, prior to being modified, at least one respective, protective molecule overlays each of the first and second electrodes of at least one electrode pair such that the at least one respective, protective molecule inhibits probe molecules from binding to the first and second electrodes, the method comprising:
(a) dissociating the at least one protective molecule from the first electrode of at least one electrode pair without dissociating the at least one protective molecule from the second electrode of the at least one electrode pair, the first and second electrodes of the at least one electrode pair being spaced apart by less than 1000 Angstroms; and (b) contacting the first and second electrode of at least one electrode pair of the array of electrode pairs with a liquid comprising a first probe molecule; and wherein, for at least one first electrode of at least one electrode pair subjected to the step of (b) contacting, the first electrode is also subjected to the step of (a) dissociating, wherein the first probe molecule of the liquid binds to the first electrode.
- 44. The method of claim 43, further comprising:
for at least one electrode pair comprising a first electrode to which the first probe molecule was bound, (c) dissociating the at least one protective molecule from the second electrode of the at least one electrode pair; (d) contacting electrodes of each of a second plurality of electrode pairs of the array of electrode pairs with a liquid comprising a second probe molecule to be bound to a second electrode of at least one electrode pair; and wherein, at least one second electrode is subjected to both the steps of (c) dissociating and (d) contacting and for, each second electrode subjected to both the steps of (c) dissociating and (d) contacting, the second probe molecule of the liquid binds to the second electrode.
- 45. The method of claim 43, wherein the first probe molecule comprises a polynucleotide.
- 46. The method of claim 45, wherein the polynucleotide of the first probe molecule comprises a phosphorothiolated polynulceotide.
- 47. The method of claim 44, wherein the second probe molecule comprises an intercalating group configured to intercalate with double stranded polynucleotides.
- 48. A method of modifying electrodes of an array of electrodes, electrodes of the array to be modified by binding at least one respective probe molecule thereto, wherein, prior to being modified, at least one respective protective molecule overlays each of at least two electrodes to be modified such that the at least one respective, protective molecule inhibits probe molecules from binding to electrodes of the at least two electrodes, the method comprising:
(a) contacting a plurality of electrodes of the array of electrodes with a liquid comprising a probe molecule; (b) dissociating the at least one protective molecule from at least one of the electrodes in contact with the liquid comprising the probe molecule, wherein, for each electrode in contact with the liquid and subjected to the step of (b) dissociating, the probe molecule of the liquid binds to the electrode.
- 49. The method of claim 48, wherein the step of dissociating is performed without first removing the liquid used in the step of (a) contacting.
- 50. The method of claim 48, wherein, for at least one electrode, the step of (b) dissociating comprises modifying an electrical potential of the at least one electrode.
- 51. The method of claim 48, wherein, for at least one electrode, the step of (b) dissociating comprises modifying an electrical potential difference between the at least one electrode and a reference electrode.
- 52. The method of claim 48, further comprising:
(c) contacting a plurality of electrodes of the array of electrodes with a liquid comprising a different, probe molecule; and (d) dissociating the at least one protective molecule from at least one electrode in contact with the liquid used in the step of (c) contacting, wherein, the different, probe molecule of the liquid binds to the at least one electrode.
- 53. The method of claim 52, wherein, for at least one electrode, the step of (d) dissociating comprises modifying an electrical potential of the at least one electrode, whereby the at least one molecule dissociates from the at least one electrode.
- 54. The method of claim 52, wherein, for at least one electrode, the step of (d) dissociating comprises modifying an electrical potential difference between the at least one electrode and a reference electrode, whereby the at least one molecule dissociates from the at least one electrode.
- 55. The method of claim 52, further comprising:
repeating the steps of (c) dissociating and (d) contacting until a respective probe molecule is bound to each of at least 50 electrodes of the array.
- 56. The method of claim 52, further comprising:
repeating the steps of (c) dissociating and (d) contacting until a respective probe molecule is bound to at least 500 electrodes of the array.
- 57. The method of claim 52, further comprising:
repeating the steps of (c) dissociating and (d) contacting until a respective probe molecule is bound to every electrode of the array.
- 58. The method of claim 48, further comprising:
prior to performing the steps of (a) contacting and (b) dissociating, overlaying each of a plurality of the electrodes with at least one protective molecule by contacting the electrodes with a liquid comprising the at least one protective molecule, wherein at least respective one protective molecule binds to electrodes of the array.
- 59. The method of claim 58, wherein the at least one of the respective, protective molecules comprises at least one of an alkylsiloxane, an alkylthiolate, and a fatty acid.
- 60. The method of claim 59, wherein the alkylthiolate comprises an alkane thiol having from 1 to 22 carbon atoms.
- 61. The method of claim 58, wherein, for each electrode of a plurality of electrodes, the at least one respective, protective molecule binds to the electrode by a sulfur group.
- 62. The method of claim 48, wherein the at least one protective molecule comprises at least one of an alkylsiloxane, an alkylthiolate, and a fatty acid.
- 63. The method of claim 62, wherein the alkylthiolate comprises an alkane thiol having from 1 to 22 carbon atoms.
- 64. The method of claim 48, wherein, for each electrode of a plurality of electrodes, the at least one protective molecule is bound to the electrode by a sulfur group.
- 65. The method of claim 48, wherein the probe molecules each comprise a polynucleotide.
- 66. The method of claim 65, wherein the polynucleotides of each of a plurality of the probe molecules have different sequences.
- 67. The method of claim 65, wherein the probe molecules comprise a binding portion that binds the electrodes, the binding portion comprising at least one sulfur atom.
- 68. The method of claim 48, wherein the array of electrodes comprises a plurality of electrode pairs, each electrode pair comprising first and second electrodes that are spaced apart by less than 1000 Angstroms, and wherein:
for at least one electrode pair of the plurality of said electrode pairs, the step of (a) dissociating comprises dissociating the at least one respective, protective molecule from only the first electrode of the electrode pair; and for at least one electrode pair of the plurality of said electrode pairs, the step of (b) contacting comprises contacting both electrodes of the electrode pair with the same respective liquid comprising the same respective, different problem molecule; and wherein, for at least one electrode pair of the plurality of said electrode pairs, the electrode pair is subjected to the step of (b) contacting and the first electrode only of the electrode pair is also subjected to the step of (a) dissociating, and wherein the respective, different probe molecule of the respective liquid binds only to the first electrode.
- 69. The method of claim 68, wherein,
for each electrode pair of at least two electrode pairs of the plurality of said electrode pairs, the step of (a) dissociating comprises dissociating the at least one respective, protective molecule from only the first electrode of the electrode pair; for each electrode pair of at least two electrode pairs of the plurality of electrode pairs, the electrode pairs belong to different subsets of the plurality of subsets of electrodes and the step of (b) contacting comprises contacting the at least two electrode pairs with respective liquids comprising a respective, different probe molecules; and wherein for each electrode pair of at least two electrode pairs contacted with respective liquids comprising respective, different probe molecules, only the first electrode of the electrode pair is also subjected to the step of (a) dissociating, and wherein the respective, different probe molecule of the respective liquid binds only to the first electrode.
- 70. The method of claim 68, wherein for at least one each electrode pair having had the first electrode subjected to both the steps of (b) dissociating and (c) contacting, the method further comprises:
dissociating the at least one protective molecule from the second electrode of the electrode pair; contacting both electrodes of the electrode pair with a liquid comprising a probe molecule to be bound to the second electrode of the electrode pair, wherein the probe molecule to be bound to the second electrode is different from the probe molecule bound to the first electrode; and wherein the probe molecule to be bound to the second electrode of electrode pair binds to the second electrode.
- 71. The method of claim 70, wherein, for each electrode pair of a plurality of electrode pairs, the probe molecule bound to one of the first and second electrodes comprises a first polynucleotide.
- 72. The method of claim 71, wherein, for each electrode pair of a plurality of electrode pairs, the probe molecule bound to the other electrode comprises an intercalating group and wherein, upon contacting the electrode pair with a liquid comprising a target polynucleotide at least partially complementary to the first polynucleotide of the probe molecule bound to the first electrode, the first and target polynucleotides form a duplex region and the intercalating group intercalates with the duplex region polynucleotides.
- 73. A method of modifying electrodes of an array of electrodes, the electrodes to be modified by binding at least one respective probe molecule thereto, the method comprising:
(a) addressing at least one electrode of the array of electrodes with a dissociation potential; (b) contacting electrodes of the array of electrodes with a liquid comprising a probe molecule; (c) contacting electrodes of the array of electrodes with a liquid comprising a protective molecule; and wherein at least a first electrode subjected to the step of (a) addressing is (i) subjected to the step of (b) contacting while not concurrently being subjected to the step of (a) addressing and (ii) subjected to the step of (c) contacting while not concurrently being subjected to the step of (a) addressing, and wherein at least one probe molecule and at least one protective molecule bind to the first electrode.
- 74. The method of claim 60, further comprising:
repeatedly:
(d) addressing at least one different electrode with a dissociation potential; (e) contacting electrodes of the array with a liquid comprising a different probe molecule; (f) contacting electrodes of the array with a liquid comprising a protective molecule; and wherein at least a second electrode subjected the step of (d) addressing is (1) subjected to a step of (e) contacting while not concurrently being subjected to a step of (d) addressing and (2) subjected to a step of (f) contacting while not concurrently being subjected to a step of (d) addressing, and wherein at least one different probe molecule and at least one protective molecule bind to the second electrode.
- 75. The method of claim 73, further comprising:
(g) addressing at least one electrode of the array of electrodes with a dissociation potential, wherein at least one electrode that was subjected to the step of (a) addressing and was (1) subjected to the step of (b) contacting while not concurrently being subjected to the step of (a) addressing and (2) subjected to the step of (c) contacting while not concurrently being subjected to the step of (a) addressing is not subjected to the step of (g) addressing; (h) contacting electrodes of the array of electrodes with a liquid comprising a different probe molecule; (i) contacting electrodes of the array of electrodes with a liquid comprising a protective molecule; and wherein at least a second electrode subjected to the step of (g) addressing is (1) subjected to the step of (h) contacting while not concurrently being subjected to the step of (g) addressing and (2) subjected to the step of (i) contacting while not concurrently being subjected to the step of (g) addressing, and wherein at least one probe molecule and at least one protective molecule bind to the second electrode.
- 76. The method of claim 73, wherein the step of (a) addressing comprises modifying an electrical potential of the at least one electrode.
- 77. The method of claim 73, wherein the step of (a) addressing comprises modifying an electrical potential difference between the at least one electrode and a reference electrode.
- 78. The method of claim 73, wherein the step of (c) contacting is performed after the step of (b) contacting.
- 79. The method of claim 73, wherein at least one of the steps of (b) contacting and (c) contacting are performed after the step of (a) addressing.
- 80. The method of claim 73, further comprising:
prior to the steps of (a) addressing, (b) contacting, and (c) contacting, overlaying a plurality of the electrodes with at least one respective, protective molecule by contacting the electrodes with a liquid comprising the at least one respective, protective molecule, wherein at least one respective, protective molecule binds to electrodes of the array.
- 81. The method of claim 80, wherein the step of (a) addressing dissociates the at least one protective molecule from the at least one electrode.
- 82. The method of claim 80, wherein the at least one protective molecule comprises at least one of an alkylsiloxane, an alkylthiolate, and a fatty acid.
- 83. The method of claim 82, wherein the alkylthiolate comprises an alkane thiol having from 1 to 22 carbon atoms.
- 84. The method of claim 80, wherein, for each electrode of a plurality of electrodes, the at least one protective molecule binds to the electrode by a sulfur group.
- 85. The method of claim 73, wherein the at least one protective molecule comprises at least one of an alkylsiloxane, an alkanethiolate, and a fatty acid.
- 86. The method of claim 85, wherein the alkylethiolate comprises an alkane thiol having from 1 to 22 carbon atoms.
- 87. The method of claim 85, wherein, for each electrode of a plurality of electrodes, the at least one protective molecule is bound to the electrode by a sulfur group.
- 88. The method of claim 74, wherein the probe molecules each comprise a polynucleotide
- 89. The method of claim 88, wherein the polyntucleotides of different probe molecules have different sequences.
- 90. The method of claim 88, wherein the probe molecules comprise a binding portion that binds the electrodes, the binding portion comprising sulfur.
- 91. A method of forming an electrical connection between a first electrode and a second electrode of an electrode pair:
binding a first molecule to the first electrode, the first molecule comprising a first single stranded polynucleotide; binding a second molecule to the second electrode, the second molecule comprising an intercalating group configured to intercalate with double stranded polynucleotides; and contacting the electrode pair with a second single stranded polynucleotide at least partially complementary to the first polynucleotide, wherein the first and second polynucleotides form a duplex region and the intercalating group intercalates with the duplex region thereby forming the electrical connection between the first and second electrodes.
- 92. The method of claim 91, wherein binding the first molecule to the first electrode comprises binding a sulfur group of the first molecule to the first electrode.
- 93. The method of claim 92, wherein sulfur group comprises a phosphorothioate group.
- 94. The method of claim 91, wherein the second molecule comprises a conductive oligomer disposed intermediate the intercalating group and a second portion of the second molecule that is associated with the second electrode.
- 95. The method of claim 91, wherein the second molecule is free of polynucleotides.
- 96. The method of claim 91, wherein binding the second molecule to the second electrode comprises binding a sulfur group of the second molecule to the second electrode.
- 97. The method of claim 91, wherein the intercalating group comprises at least one of (i) ethidium bromide or acridine and (ii) a derivative of ethidium bromide or a derivative or acridine.
- 98. The method of claim 91, comprising:
prior to the step of binding the first molecule to the first electrode, overlaying at least one protective molecule upon the first electrode, whereby the at least one protective molecule inhibits association of the first and second molecules with the first electrode; wherein the step of binding the first molecule to the first electrode comprises:
contacting the first and second electrodes with a liquid comprising the first molecule; and modifying an electrical potential difference between the first electrode and a reference electrode to thereby deprotect the first electrode, whereupon the first molecule binds to the first electrode.
- 99. The method of claim 98, comprising:
prior to the step of binding the second molecule to the second electrode, overlaying at least one protective molecule upon the second electrode, whereby the at least one protective molecule inhibits association of the first and second molecules with the second electrode; wherein the step of binding the second molecule to the second electrode comprises:
contacting the first and second electrodes with a liquid comprising the first molecule; and modifying an electrical potential difference between the second electrode and a reference electrode to thereby deprotect the second electrode, whereupon the second molecule binds to the second electrode.
- 100. The method of claim 91, wherein the method further comprises forming a respective electrical connection between a first and a second electrode of each of a plurality of electrode pairs, for each electrode, the method comprising:
binding a first molecule to the first electrode, the first molecule comprising a first polynucleotide; binding a second molecule to the second electrode, the second molecule comprising an intercalating group configured to intercalate with double stranded polynucleotide compounds; and contacting the first and second molecules with a second polynucleotide at least partially complementary to the first polynucleotide, wherein the first and second polynucleotides form a duplex region and the intercalating group intercalates with the duplex region thereby forming the electrical connection between the first and second electrodes.
- 101. The method of claim 100, comprising binding first molecules comprising respective, different first polynucleotides to the first electrodes of respective, different electrode pairs, whereby the first polynucleotides bound to different first electrodes will selectively form duplex regions with different, second polynucleotides.
- 102. The method of claim 100, wherein, for each electrode pair, the method comprises:
prior to the step of binding the first molecule to the first electrode, overlaying at least one protective molecule upon the first electrode, whereby the at least one protective molecule inhibits binding of the first and second molecules with the first electrode; wherein the step of binding the first molecule to the first electrode comprises:
contacting the first and second electrodes with a liquid comprising the first molecule; and modifying an electrical potential difference between the first electrode and a reference electrode to thereby deprotect the first electrode whereupon the first molecule binds to the first electrode.
- 103. The method of claim 102, wherein, for each electrode pair, the method comprises:
prior to the step of binding the second molecule to the second electrode, overlaying at least one protective molecule upon the second electrode, whereby the at least one protective molecule inhibits binding of the first and second molecules with the second electrode; wherein the step of binding the second molecule with the second electrode comprises:
contacting the first and second electrodes with a liquid comprising the second molecule; and modifying an electrical potential difference between the second electrode and a reference electrode to thereby deprotect the second electrode whereupon the second molecule binds to the second electrode.
- 104. The method of claim 100, wherein, for each electrode pair, the step of binding a first molecule to the first electrode comprises:
contacting at least two subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different first molecule; and for each of at least two subsets of electrode pairs, modifying an electrical potential difference between the first electrode of at least one of the electrode pairs and a reference electrode, whereby the respective first molecule binds with the first electrode.
- 105. The method of claim 104, comprising:
contacting at least two subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different compound; and for each of at least two subsets of electrode pairs, modifying an electrical potential difference between the first electrode of at least one of the electrode pairs and a reference electrode, whereby the respective first molecule binds to the first electrode.
- 106. The method of claim 105, comprising:
repeating the steps of contacting at least two subsets of electrode pairs and modifying an electrical potential difference between the first electrode of at least one electrode pair of each subset until each of the first electrodes has been bound with a respective first molecule.
- 107. The method of claim 87, wherein, for each electrode pair, the step of binding a second molecule to the second electrode comprises:
contacting a number N subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different second molecule and N is an integer greater than 1 and less than Na; and for each subset of the N subsets of electrode pairs, modifying an electrical potential difference between the second electrode of at least one of the electrode pairs and a reference electrode, whereby the respective second molecule binds to the second electrode.
- 108. The method of claim 107, comprising:
contacting a number N′ subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different compound and N′ is an integer greater than 1 and less than Na; and for each subset of the N′ subsets of electrode pairs, modifying an electrical potential difference between the second electrode of at least one of the electrode pairs and a reference electrode, whereby the respective second molecule binds to the second electrode.
- 109. The method of claim 108, comprising:
repeating the steps of contacting subsets of electrode pairs and modifying an electrical potential difference between the second electrode of at least one electrode pair of each subset until each of the second electrodes has been bound with a respective second molecule.
- 110. A method of preparing a sensor, the method comprising:
binding a first molecule to a first electrode, the first molecule comprising a first single stranded polynucleotide; binding a second molecule to a second electrode, the second molecule comprising an intercalating group configured to intercalate with double stranded polynucleotides; wherein, if the first electrode pair is contacted with a liquid comprising a second single stranded polynucleotide sequence at least partially complementary to the first polynucleotide sequence, the first and second polynucleotide sequences will form a duplex region and the intercalating group will intercalate with the duplex region thereby modifying an electrical characteristic of the first and second electrodes, whereby the presence of the at least partially complementary polynucleotide may be determined.
- 111. The method of claim 110, wherein binding the first molecule with the first electrode comprises binding a sulfur group of the first molecule with the first electrode.
- 112. The method of claim 110, wherein the sulfur group comprises a phosphorothioate group.
- 113. The method of claim 110, wherein the second molecule comprises a conductive oligomer disposed intermediate the intercalating group and a portion of the second molecule that is bound to the second electrode.
- 114. The method of claim 113, wherein the conductive oligomer comprises at least one of a saccharide and an aromatic group.
- 115. The method of claim 113, wherein the conductive oligomer is free of polynucleotides.
- 116. The method of claim 114, wherein the portion of the second molecule that is bound to the second electrode comprises sulfur.
- 117. The method of claim 114, wherein the intercalating group comprises at least one of (i) ethidium bromide or acridine and (ii) a derivative of ethidium bromide or a derivative of acridine.
- 118. The method of claim 113, comprising:
prior to the step of binding the first molecule to the first electrode, overlaying at least one protective molecule upon the first electrode, whereby the at least one protective molecule inhibits binding of the first and second molecules to the first electrode; wherein the step of binding the first molecule to the first electrode comprises:
contacting the first and second electrodes to with a liquid comprising the first molecule; and modifying an electrical potential difference between the first electrode and a reference electrode to thereby deprotect the first electrode, whereupon the first molecule binds to the first electrode.
- 119. The method of claim 118, comprising:
prior to the step of binding the second molecule with the second electrode, overlaying at least one protective molecule upon the second electrode, whereby the at least one protective molecule inhibits binding of the first and second molecules to the second electrode; wherein the step of binding the second molecule to the second electrode comprises:
contacting the first and second electrodes with a liquid comprising the second molecule; and modifying an electrical potential difference between the second electrode and a reference electrode to thereby deprotect the second electrode whereupon the second molecule binds with the second electrode.
- 120. The method of claim 110, wherein the substrate comprises an electrode pair array comprising a number Na electrode pairs, each electrode pair comprising a first and second electrode pair and wherein, for each electrode pair, the method comprises:
binding a first molecule to the first electrode, the first molecule comprising a first polynucleotide; binding a second molecule to a second electrode, the second molecule comprising an intercalating group configured to intercalate with double stranded polynucleotide compounds; and wherein, if the first electrode pair is contacted with a liquid comprising a second polynucleotide sequence at least partially complementary to the first polynucleotide sequence, the first and second polynucleotide sequences will form a duplex region and the intercalating group will intercalate with the duplex region of the first and complementary polynucleotides thereby modifying an electrical characteristic of the first and second electrodes whereby the presence of the at least partially complementary polynucleotide may be determined.
- 121. The method of claim 120, comprising binding first molecules comprising respective, different first polynucleotides to the first electrodes of respective, different electrode pairs, whereby the first polynucleotides bound to different first electrodes will selectively form duplex regions with different second polynucleotides.
- 122. The method of claim 120, wherein, for each electrode pair, the method comprises:
prior to the step of binding the first molecule to the first electrode, binding at least one protective compound to the first electrode, whereby the at least one protective compound inhibits binding of the first and second molecules to the first electrode; wherein the step of binding the first molecule to the first electrode comprises:
contacting the first and second electrodes with a liquid comprising the first molecule; and modifying an electrical potential difference between the first electrode and a reference electrode to thereby deprotect the first electrode whereupon the first molecule binds to the first electrode.
- 123. The method of claim 120 wherein, for each electrode pair, the method comprises:
prior to the step of binding the second molecule to the second electrode, binding at least one protective compound with the second electrode, whereby the at least one protective compound inhibits binding of the first and second molecules to the second electrode; wherein the step of binding the second molecule to the second electrode comprises:
contacting the first and second electrodes with a liquid comprising the second molecule; and modifying an electrical potential difference between the second electrode and a reference electrode to thereby deprotect the second electrode whereupon the second molecule binds to the first electrode.
- 124. The method of claim 120, wherein, for each electrode pair, the step of binding a first molecule with the first electrode comprises:
contacting a number N subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different first molecule and N is an integer greater than 1 and less than Na; and for each subset of the N subsets of electrode pairs, modifying an electrical potential between the first electrode of at least one of the electrode pairs and a reference electrode, whereby the respective first molecule binds to the first electrode.
- 125. The method of claim 124, comprising:
contacting a number N′ subsets of the electrode pairs with a respective liquid, wherein each liquid comprises a respective, different compound and N′ is an integer greater than 1 and less than Na; and for each subset of the N′ subsets of electrode pairs, modifying an electrical potential between the first electrode of at least one of the electrode pairs and a reference electrode, whereby the respective first molecule binds to the first electrode.
- 126. The method of claim 125, comprising:
repeating the steps of contacting subsets of electrode pairs and modifying an electrical potential until each of the first electrodes has been bound to a respective first molecule.
- 127. The method of claim 120, wherein, for each of the N subsets of electrode pairs, contacting the subset with a respective liquid comprises applying at least one aliquot of the respective liquid to the subset.
- 128. The method of claim 127, wherein the electrode pairs of each subset of electrode pairs are isolated from aliquots of liquid applied to other subsets of electrode pairs.
- 129. A method of forming an electrical connection between a first electrode and a second electrode of an electrode pair, the electrode pair comprising the first and second electrodes, wherein a surface of the first electrode is bound with a first molecule, the first molecule comprising a first single stranded polynucleotide and a surface of the second electrode is bound with a second molecule, the second molecule comprising an intercalating group configured to intercalate with double stranded polynucleotides, comprising:
contacting the first and second molecules with a second single stranded polynucleotide at least partially complementary to the first polynucleotide, wherein the first and second polynucleotides form a duplex region and the intercalating group intercalates with the first and second polynucleotides thereby forming the electrical connection between the first and second electrodes.
- 130. The method of claim 129, further comprising determining an electrical characteristic of the first and second electrodes whereby the presence of the second polynucleotide may be determined.
- 131. The method of claim 130, wherein the electrical characteristic is a conductance, a resistance, an impedance, or a capacitance.
- 132. The method of claim 129, wherein the first molecule comprises a sulfur group bound to the first electrode.
- 133. The method of claim 132, wherein the sulfur group comprises a phosphorothioate group.
- 134. The method of claim 132, wherein the second molecule comprises a conductive oligomer disposed intermediate the intercalating group and a portion of the second molecule that is bound to second electrode.
- 135. The method of claim 134, wherein the conductive oligomer comprises at least one of a saccharide and an aromatic group.
- 136. The method of claim 134, wherein the conductive oligomer is essentially free of polynucleotides.
- 137. The method of claim 129, wherein the intercalating group comprises at least one of ethidium bromide, acridine, and derivatives thereof.
- 138. An apparatus for preparing an array of modified surfaces, comprising:
a device configured to at least:
contact electrodes of each of a number N subsets of electrodes an array of electrodes with a respective liquid, wherein each liquid comprises a respective, different compound and N is an integer greater than 1; and for each subset of the N subsets of electrodes, modify an electrical potential between at least a first electrode of the subset of electrodes and a reference electrode, whereby the respective compound of the fluid contacting the first electrode binds to the first electrode.
- 139. The apparatus of claim 138, wherein the device is configured to:
contact surfaces of each of a number N′ subsets of the electrodes of the array of electrodes with a respective liquid, wherein each liquid comprises a respective, different compound and N′ is an integer greater than 1; for each subset of the N′ subsets of electrodes, modify an electrical potential between at least a second electrode and a reference electrode, whereby the respective compound binds to the second electrode.
- 140. The apparatus of claim 138, wherein the device is configured to:
repeatedly contact subsets of surfaces of the array of surfaces with a respective liquid, each liquid comprising a respective, different compound; and modify an electrical potential between at least one electrode of the subset of electrodes and a reference electrode until a respective, different compound has been bound with each electrode of the array of electrodes.
- 141. The apparatus of claim 138, wherein the device comprises:
a plurality of droplet preparation devices, wherein each droplet preparation device is in fluid communication with a respective reservoir comprising a respective one of the different compounds; and a droplet delivery device configured to deliver droplets prepared by the droplet preparation devices to predetermined subsets of the N subsets of electrodes to thereby contact the predetermined subsets with respective liquid.
- 142. The apparatus of claim 141, wherein the droplet preparation devices each comprise a capillary configured to prepare a droplet of fluid.
- 143. The apparatus of claim 141, wherein the droplet preparation devices are configured to prepare droplets by at least one of thermally modifying a pressure of the liquid, piezo-electrically modifying a pressure of the liquid, and ultrasonically modifying a pressure of the liquid.
- 144. The apparatus of claim 138, wherein the device is configured to:
bind at least one respective, protective molecule to the electrodes of the array, whereby the at least one respective, protective compound inhibits association of the respective, different compounds with electrodes.
- 145. A sensor, comprising:
a substrate comprising a first electrode pair comprising first and second electrodes; a first molecule bound with the first electrode, the first molecule comprising a first polynucleotide; a second molecule bound with the second electrode, the second molecule comprising a group configured to intercalate with double stranded polynucleotide compounds; and wherein, upon contacting the first electrode pair with a liquid comprising a second polynucleotide sequence at least partially complementary to the first polynucleotide sequence, the first and second polynucleotide sequences form a duplex region and the intercalating portion intercalates with the duplex region, thereby modifying an electrical characteristic of the first and second electrodes whereby the presence of the at least partially second polynucleotide may be determined.
- 146. The sensor of claim 145, wherein the modified electrical characteristic comprises at least one of a conductance, a resistance, an impedance, and a capacitance.
- 147. The sensor of claim 145, wherein the substrate comprises a number Na electrode pairs, each electrode pair comprising a first and second electrode pair and each electrode pair comprises:
a first molecule bound with the first electrode, the first molecule comprising a first polynucleotide; a second molecule bound with the second electrode, the second molecule comprising a group configured to intercalate with double stranded polynucleotide compounds; and wherein, upon contacting the electrode pair with a liquid comprising a second polynucleotide sequence at least partially complementary to the first polynucleotide sequence, the first and second polynucleotide sequences form a duplex region and the intercalating portion intercalates with the duplex region thereby modifying an electrical characteristic of the first and second electrodes whereby the presence of the at least partially complementary second polynucleotide may be determined.
- 148. The sensor of claim 145, wherein respective, different first polynucleotides are found with the first electrodes of respective, different electrode pairs, whereby the first polynucleotides bound to different first electrodes will selectively form duplex regions with different second polynucleotides.
- 149. The sensor of claim 145, wherein a distance between the first and second electrodes is less than 500 Angstroms.
RELATED APPLICATIONS
[0001] This application claims priority, under 35 U.S.C. § 119(e), of U.S. Provisional Patent Application No. 60/382,074, filed on May 22, 2002, which application is incorporated herein, by reference, in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60382074 |
May 2002 |
US |