Nanosensors and related technologies

• US 20100087013A1
• Filed: 06/11/2007
• Published: 04/08/2010
• Est. Priority Date: 06/12/2006
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Fang, Ying, Lieber, Charles M., Patolsky, Fernando
• Granted Patent: US 9,102,521 B2
• Time in Patent Office: Days
• US Class Current: 436/525
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4146 involving nanosized elements, e.g. nanotubes, nanowires
• CPC Class Codes: G01N 33/551 the carrier being inorganic
• CPC Class Codes: G01N 33/553 Metal or metal coated
• CPC Class Codes: H10K 85/225 comprising substituents
• CPC Class Codes: H10K 85/761 Biomolecules or bio-macromolecules, e.g. proteins, chlorophyl, lipids or enzymes

Abstract

The present invention generally relates to nanotechnology and sub-microelectronic circuitry, as well as associated methods and devices, for example, nanoscale wire devices and methods for use in determining nucleic acids or other analytes suspected to be present in a sample (for example, their presence and/or dynamical information), e.g., at the single molecule level. For example, a nanoscale wire device can be used in some cases to detect single base mismatches within a nucleic acid (e.g., by determining association and/or dissociation rates). In one aspect, dynamical information such as a binding constant, an association rate, and/or a dissociation rate, can be determined between a nucleic acid or other analyte, and a binding partner immobilized relative to a nanoscale wire. In some cases, the nanoscale wire includes a first portion comprising a metal-semiconductor compound, and a second portion that does not include a metal-semiconductor compound. The binding partner, in some embodiments, is immobilized relative to at least the second portion of the nanoscale wire, and the size of the second portion of the nanoscale wire may be minimized and/or controlled in some instances. Articles and devices of size greater than the nanoscale are also included in certain embodiments. Still other aspects of the invention include assays, sensors, kits, and/or other devices that include such nanoscale wires, methods of making and/or using such nanoscale wires, or the like.

Claims

1. A method, comprising an act of:

determining a binding constant and/or a dissociation rate constant between an analyte and a nanoscale wire having immobilized relative thereto a binding partner of the analyte by determining a change in an electrical property of the nanoscale wire, the nanoscale wire comprising a first portion and a second portion laterally defined along the length of the nanoscale wire,

wherein the second portion has a length of less than about 100 nm, has the binding partner to the analyte immobilized relative thereto, and comprises a semiconductor, and

wherein the first portion comprises a conductive transition metal-semiconductor compound, and is free of the binding partner.

2. The method of claim 90, wherein the binding partner is a nucleic acid, the method comprising determining a mismatch between the nucleic acid and the binding partner.

3. The method of claim 2, comprising determining a mismatch between the nucleic acid and the binding partner of 5 bases or less.

15. The method of claim 1, wherein the transition metal-semiconductor compound comprises a metal silicide.

89. The method of claim 1, wherein the nanoscale wire comprises the first portion, the second portion, and a third portion each laterally defined along the nanoscale wire, the second portion separating the first portion and the third portion,

wherein the third portion comprises a conductive metal-semiconductor compound and is free of the binding partner.

90. The method of claim 1, wherein the analyte is a nucleic acid.

91. The method of claim 1, wherein the transition metal comprises nickel.

92. The method of claim 1, wherein the transition metal-semiconductor compound consists essentially of a single crystal.

4-14. -14. (canceled)

16-29. -29. (canceled)

31. (canceled)

33-34. -34. (canceled)

36-38. -38. (canceled)

42. (canceled)

44-50. -50. (canceled)

52-77. -77. (canceled)

78. An article, comprising:

a nanoscale wire comprising a first portion and a second portion, each laterally defined along the nanoscale wire, the second portion comprising a semiconductor and having immobilized relative thereto a binding partner to an analyte, and the first portion being free of the binding partner and comprising a conductive transition metal-semiconductor compound,

wherein the binding partner is able to bind one or more molecules of the analyte, wherein the analyte, when bound to the binding partner, has a Debye screening length greater than the greatest dimension of the second portion of the nanoscale wire.

79. The article of claim 78, wherein the analyte comprises a nucleic acid.

86. The article of claim 78, wherein a single molecule of the analyte, when bound to the binding partner, has a Debye screening length than the greatest dimension of the second portion of the nanoscale wire.

87. The article of claim 78, wherein the transition metal-semiconductor compound consists essentially of a single crystal.

88. The article of claim 78, wherein the nanoscale wire comprises the first portion, the second portion, and a third portion each laterally defined along the nanoscale wire, wherein the third portion is free of the binding partner and comprises a conductive transition metal-semiconductor compound.

80-85. -85. (canceled)

93. A method, comprising an act of:

diffusing at least a portion of a transition metal laterally into a first portion of a semiconductor nanoscale wire, but not into a second portion of the nanoscale wire, to create a nanoscale wire wherein the first portion consists essentially of a single crystal of a conductive transition metal-semiconductor compound, and wherein the second portion is essentially free of the transition metal.

30. The method of claim 93, further comprising:

immobilizing a reaction entity to the second portion of the nanoscale wire.

32. The method of claim 93, wherein the transition metal comprises nickel.

35. The method of claim 30, wherein the reaction entity is a nucleic acid.

39. The method of claim 93, comprising controlling the size of the second portion of the nanoscale wire by controlling the temperature of the nanoscale wire during the diffusing step.

40. The method of claim 39, comprising heating the nanoscale wire to diffuse the transition metal into the nanoscale wire, and cooling the nanoscale wire when the second portion is less than a predetermined size.

41. The method of claim 30, wherein the act of immobilizing the reaction entity to the second portion of the nanoscale wire comprises attaching a silane comprising an aldehyde moiety to the nanoscale wire, and attaching a reaction entity to the silane.

94. The method of claim 93, comprising:

diffusing at least a portion of a first transition metal into a first portion of a semiconductor nanoscale wire but not into a second portion of the nanoscale wire, and diffusing a second transition metal into a third portion of a semiconductor nanoscale wire but not into a second portion of the nanoscale wire, the second portion separating the first portion and the third portion, to create a semiconductor wire wherein the first portion consists essentially of a single crystal of a first transition metal-semiconductor compound, the third portion consists essentially of a single crystal of a second transition metal-semiconductor compound, and the second portion comprises a semiconductor.

95. The method of claim 94, wherein the first transition metal and the second transition metal are essentially identical.

96. The method of claim 93, wherein the transition metal-semiconductor compound comprises a metal silicide.

97. An article, comprising:

a nanoscale wire comprising a first portion and a second portion laterally defined along the length of the nanoscale wire, the first portion consisting essentially of a single crystal of a transition metal-semiconductor compound, and the second portion comprising a semiconductor and having a length of less than about 100 nm.

43. The article of claim 97, wherein the transition metal comprises nickel.

51. The article of claim 97, wherein the nanoscale wire is part of a FET.

98. The article of claim 97, wherein the nanoscale wire further comprises a third portion being defined laterally along the nanowire, the second portion separating the first portion and the third portion, the third portion consisting essentially of a single crystal of the transition metal-semiconductor compound.

99. The article of claim 97, wherein the second portion has a length of less than about 50 nm.

100. The article of claim 97, wherein the second portion has a length of less than about 30 nm.

101. The article of claim 97, wherein the transition metal-semiconductor compound comprises a metal silicide.

102. The article of claim 97, wherein the second portion further comprises a binding partner to an analyte immobilized relative thereto.

103. The article of claim 102, wherein the analyte is a nucleic acid.

104. The article of claim 102, wherein the binding partner is a nucleic acid.

105. The article of claim 102, wherein the article comprises a plurality of nanoscale wires, each comprising distinguishable nucleic acids immobilized relative thereto.