WO2001081896B1 - An ultra-fast nucleic acid sequencing device and a method for making and using the same - Google Patents

An ultra-fast nucleic acid sequencing device and a method for making and using the same

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Publication number
WO2001081896B1
WO2001081896B1 PCT/US2001/013101 US0113101W WO0181896B1 WO 2001081896 B1 WO2001081896 B1 WO 2001081896B1 US 0113101 W US0113101 W US 0113101W WO 0181896 B1 WO0181896 B1 WO 0181896B1
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WO
WIPO (PCT)
Prior art keywords
component
detecting
opening
region
detecting region
Prior art date
Application number
PCT/US2001/013101
Other languages
French (fr)
Other versions
WO2001081896A1 (en
Inventor
Jon Sauer
Bart Zeghbroeck
Original Assignee
Eagle Res & Dev Llc
Jon Sauer
Bart Zeghbroeck
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/653,543 external-priority patent/US6413792B1/en
Priority to EP01932615A priority Critical patent/EP1285252A1/en
Priority to US10/258,439 priority patent/US7001792B2/en
Priority to AU2001259128A priority patent/AU2001259128A1/en
Priority to JP2001578932A priority patent/JP4719906B2/en
Application filed by Eagle Res & Dev Llc, Jon Sauer, Bart Zeghbroeck filed Critical Eagle Res & Dev Llc
Publication of WO2001081896A1 publication Critical patent/WO2001081896A1/en
Publication of WO2001081896B1 publication Critical patent/WO2001081896B1/en
Priority to US11/301,259 priority patent/US8232582B2/en
Priority to US11/929,794 priority patent/US9063081B2/en
Priority to US13/409,800 priority patent/US8426232B2/en
Priority to US13/617,626 priority patent/US8546168B2/en
Priority to US14/039,142 priority patent/US9228976B2/en
Priority to US14/745,753 priority patent/US9410923B2/en
Priority to US15/231,480 priority patent/US9758824B2/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6816Hybridisation assays characterised by the detection means
    • C12Q1/6825Nucleic acid detection involving sensors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869Methods for sequencing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/48707Physical analysis of biological material of liquid biological material by electrical means
    • G01N33/48721Investigating individual macromolecules, e.g. by translocation through nanopores
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403Cells and electrode assemblies
    • G01N27/414Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS

Abstract

A system and method employing at least one semiconductor device, or an arrangement of insulating and metal layers, having at least one detecting region which can include, for example, a recess or opening therein, for detecting a charge representative of a component of a polymer, such as a nucleic acid strand, proximate to the detecting region, and a method for manufacturing such a semiconductor device. The system and method can thus be used for sequencing individual nucleotides or bases of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). The semiconductor device includes at least two doped regions, such as two n-typed regions implanted in a p-typed semiconductor layer or two p-typed regions implanted in an n-typed semiconductor layer. The detecting region permits a current to pass between the two doped regions in response to the presence of the component of the polymer, such as a base of a DNA or RNA strand. The current has characteristics representative of the component of the polymer, such as characteristics representative of the detected base of the DNA or RNA strand.

Claims

- 36 -
AMENDED CLAIMS
[received by the International Bureau on 6 November 2001 (06.11.01); original claims 1-55 replaced by new claims 1-76 (12 pages)]
1. A system for detecting at least one polymer, comprising: at least one semiconductor device having at least one detecting region, adapted to passively detect a charge of a component of said polymer proximate to said detecting region.
2. A system as claimed in claim 1, wherein: said component includes a base in a nucleic acid strand: and said detecting region is adapted to detect said charge representative of said base in said nucleic acid strand.
3. A system as claimed in claim 1 , wherein: said detecting region is further adapted to generate a signal representative of said detected charge.
4. A system as claimed in claim 1 , wherein: said detecting region includes a region of said semiconductor device defining an opening in said semiconductor device having a cross-section sufficient to enable said polymer to enter said opening, such that said detecting region is adapted to detect said charge of said component in said opening.
5. A system as claimed in claim 4, further comprising: an excitation device, adapted to generate movement in said semiconductor device to facilitate movement of said polymer through said opening.
6. A system as claimed m claim 4, wherein: said opening has a diameter within the range of about 1 am to about 10 run.
7. A system as claimed in claim 4, wherein: said opening has a diameter of about 1 run.
8. A system as claimed in claim 4, wherein: said region of said detecting region includes an insulating layer defining said opening.
9. A system as claimed in claim 8, whereb: said insulating layer includes an oxide layer.
10. A system as claimed m claim 4, wherein: said region of said detecting region includes an undoped semiconductor layer.
11. A system as claimed in claim 4, wherein: said region of said detecting region includes an oxide layer defining sa d opening, said oxide layer including at least one silicon nanocrystal.
12. A system as claimed in claim 4, wherein: said opening is non-circular.
13. A system as claimed in claim , wherein: said detectmg region includes a region of said semiconductor device defining a recess in said semiconductor device, such that said detecting region is adapted to detect said charge of said component m said recess.
14. A system as claimed in claim 1, wherein: said semiconductor device includes a plurality of said detectmg regions; and each said detecting region is adapted to detect a charge representative of a component of said at least one polymer proximate thereto .
15. A system as claimed in claim 1, wherein: said semiconductor device further includes at least two doped regions; and said detecting region is adapted to pass a current between said two doped regions in response to a presence of said component proximate to said detecting region. - 38 -
16. A system as claimed m claim 1 , wherein: said semiconductor device includes a plurality of doped regions, and a respective detectmg region associated with each respective pair of said doped regions, such that each said respective detecting region is adapted, in response to a presence of a component proximate thereto, to pass a respective current between its said respective pair of doped regions.
17. A system as claimed in claim 1, further comprising: a plurality of said semiconductor devices.
18. A system as claimed in claim 1 , further comprising: a detector, adapted to detect a signal generated by said detecting region in response to said component proximate thereto.
19. A system as claimed in claim 1 , wherein: said at least one semiconductor device is adapted to passively detect said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.
20. A system as claimed in claim 1 , wherein: said at least one semiconductor device is adapted to passively detect a single said charge of said component.
21. A system as claimed in claim 1, wherein: said at least one semiconductor device is adapted to passively detect said charge of said component while said component is moving.
22. A method for detecting at least one polymer, comprising the steps of: positioning a portion of said polymer proximate to a detecting region of at least one semiconductor device; and at said detecting region, passively detecting a charge of a component of said polymer proximate to said detecting region. - 39 -
23. A method as claimed in claim 22, wherein: said component includes a base in a nucleic acid strand; and said detecting step detects said charge representative of said base in said nucleic acid strand.
24. A method as claimed in claim 22, further comprising the step of: generating at said detectmg region a signal representative of said detected charge.
25. A method as claimed in claim 22, wherein: said detecting region includes a region of said semiconductor device defining an opening in said semiconductor device having a cross-section sufficient to enable said polymer to enter said opening; and said detecting step detects said charge of said component in said opening.
26. A method as claimed in claim 25, further comprising the step of: generating movement in said semiconductor device to facilitate movement of said polymer through said opening.
27. A method as claimed in claim 25, wherem: said opening has a diameter within the range of about 1 nm to about 10 nm.
28. A method as claimed in claim 25, wherein: said opening has a diameter of about 1 nm.
29. A method as claimed in claim 22, wherein: said detecting region includes a region of said semiconductor device defining a recess in said semiconductor device; and said detecting step detects said charge of said component in said recess.
30. A method as claimed in claim 22, wherein: said semiconductor device includes a plurality of said detecting regions; and - 40 -
said detecting step includes the step of detecting, at each said detecting region, a charge representative of a component of said at least one polymer proximate thereto.
3 . A method as claimed in claim 22, wherein: said semiconductor device further includes at least two doped regions; and said method further includes the step of passing a current between said two doped regions in response to a presence of said component proximate to said detecting region.
32. A method as claimed in claim 22, wherein: said semiconductor device includes a plurality of doped regions, and a respective detecting region associated with each respective pair of said doped regions; and said method further includes the step of passing, at each said respective detecting region in response to a presence of a component proximate thereto, a respective current between its said respective pair of doped regions.
33. A method as claimed in claim 22, wherein: said positioning step positions a respective portion of each of a plurality of said polymers proximate to a respective detecting region of a respective semiconductor device; and said detecting step detects, at each said respective detecting region, a charge representative of a component of said respective polymer proximate to said respective detecting region.
34. A method as claimed in claim 22, further comprising the step of: detecting a signal generated by said detecting region in response to said component proximate thereto.
35. A method as claimed in claim 22, wherein: said detecting passively detects said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component. - 41 -
36. A method as claimed in claim 22, wherein: said detecting passively detects a single said charge of said component.
37. A method for manufacturing a device for detecting a polymer, comprising the steps of: providing a semiconductor structure comprising at least one semiconductor layer; and creating a detecting region in said semiconductor structure, said detecting region being adapted to passively detect a charge of a component of said polymer proximate to said detecting region.
38. A method as claimed in claim 37, wherem: said component includes a base in a nucleic acid strand; and said creating step creates said detecting region which is adapted to detect said charge representative of said base in said nucleic acid strand.
39. A method as claimed in claim 37, further comprising the step of: creating an opening in said semiconductor structure, said opening having a cross- section sufficient to enable a portion of said polymer to pass theretlirough, and being positioned in relation to said detecting region such that said detecting region is adapted to detect said charge representative of said component in said opening.
40. A method as claimed in claim 39, wherein said opening creating step includes the step of: forming an undoped semiconductor layer on a wall of said semiconductor layer forming said opening to decrease said cross-section of said opening.
41. A method as claimed in claim 39, wherein said opening creating step includes the step of: forming an oxide layer on a wall of said semiconductor layer forming said opening to decrease said cross-section of said opening, said oxide layer including at least one silicon nanocrystal. - 42 -
42. A method as claimed in claim 39, wherein said opening creating step includes the step of: forming an insulating layer on a wall of said semiconductor layer forming said opening to decrease said cross-section of said opening.
43. A method as claimed in claim 42, wherem said opening creating step further includes: forming said insulating layer including an oxide.
44. A method as claimed in claim 39, wherein: said opening has a diameter within the range of about 1 nm to about 10 nm.
45. A method as claimed in claim 39, wherem: said opening has a diameter of about 1 nm.
46. A method as claimed m claim 37, further comprising the step of: creating a recess m said semiconductor structure, positioned in relation to said detecting region such that said detecting region is adapted to detect said charge representative of said component in said recess.
47. A method as claimed in claim 37, further comprising the steps of: creating at least two doped regions in said semiconductor layer, said doped regions being positioned with respect to said detecting region such that said detecting region is adapted to pass a current between said doped regions in response to said component of said polymer proximate thereto.
48. A method as claimed in claim 47, wherein: said doped region creating step creates said doped regions having a first doping such that said doped regions are separated by a portion of said semiconductor layer having a second doping. - 43 -
49. A method as claimed in claim 47, wherein: said doped region creating step creates said doped regions as a stack of doped regions, each having a first doping and being separated by a layer having a second doping.
50. A method as claimed in claim 47, wherein: each of said doped regions includes a -type doping.
51. A method as claimed in claim 47, wherein: each of said doped regions includes anjn-type doping.
52. A method as claimed in claim 37, wherein: said detecting region is adapted to passively detect said charge of said component without a portion of said semiconductor clevice binding with said component or chemically reacting with said component.
53. A method as claimed in claim 37, wherein: said detecting region is adapted to passively detect a single said charge of said component.
54. A system for detecting at least one polymer, comprising: at least one structure comprising an insulating layer and at least one metal layer, arranged to form at least one detecting region adapted to passively detect a charge of a component of said polymer proximate to said detecting region.
55. A system as claimed in claim 54, wherein: said insulating layer contacts said metal layer.
56. A system as claimed in claim 54, wherein: said structure comprises two metal layers, said insulating layer being disposed between said two metal layers. - 44 -
Figure imgf000010_0001
said detecting region is adapted to detect said harge of said component in said
58. A system as claimed in claim 5:7, further comprising: an excitation device, adapted to generjate movement in said structure to facilitate movement of said polymer through said opening.
59. A system as claimed in claim 57, wherein: said opening is non-circular.
60. A system as claimed in claim 5-4, wherein: said detecting region includes a region of said structure defining a recess in said structure, such that said detecting region is adapted to detect said charge of said component in said recess.
61. A system as claimed in claim 54, wherein: said at least one structure is adapted to passively detect said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.
62. A system as claimed in claim 54, wherein: said at least one structure is adapted to passively detect a single said charge of said component.
63. A method for manufacturing a device for detecting a polymer, comprising the steps of: providing a structure comprising an insulating layer and at least one metal layer; and - 45 -
creating a detecting region in said structure, said detecting region being adapted to passively detect a charge of a component of said polymer proximate to said detecting region.
Figure imgf000011_0001
id i i charge representative of said base in said nucleic acid strand.
65. A method as claimed in claim 63, further comprising the step of: creating an opening in said structure, said opening having a cross-section sufficient to enable a portion of said polymer to pass therethrough, and being positioned in relation to said detecting region such that] said detecting region is adapted to detect said charge representative of said component in said opening.
66. A method as claimed in claim 65, wherein: said opening is non-circular.
67. A method as claimed in claim 63, further comprising the step of: creating a recess in said structure, positioned in relation to said detectmg region such that said detecting region is adapted to] detect said charge representative of said component in said recess.
68. A method as claimed in claim ώ, wherein: said detecting region passively detects! said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.
69. A method as claimed in claim 63, wherein: said detecting region passively detects a single said charge of said component.
70. A system for detecting at least one polymer, comprising: - 46 -
a plurality of detecting devices, each having at least one detecting region, adapted to passively detect a charge of a component of said polymer proximate to said detecting region; and a reader, adapted to selectably obtain a respective reading from each of said detecting devices, said respective readings representing respective charges detected by said detecting devices.
71. A system as claimed in claim 170, wherem at least one of said detectmg devices comprises: at least one semiconductor device having at least one said detecting region, adapted to detect a charge representative of a component of said polymer proximate to said detecting region.
72. A system as claimed in claim 170, wherein at least one of said detecting devices comprises: a structure comprising an insulating layer and at least one metal layer arranged to define at least one said detecting region, adapted to detect a charge representative of a component of said polymer proximate to said detecting region.
73. A system as claimed in claim 70, wherein: said detecting devices are each adapted to passively detect said charge of said component without a portion of said semiconductor device binding with said component or chemically reacting with said component.
74. A system as claimed in claim 70, wherein: said detectmg devices are each adaptedito passively detect a single said charge of said component.
75. A system for detecting at least one polymer, comprising: at least one semiconductor device having at least one detecting region, adapted to detect a charge representative of a component of said polymer proximate to said detecting region, said detecting region including a region of said semiconductor device - 47 -
defining an opening in said semiconductor device having a cross-section sufficient to enable said polymer to enter said opening, such that said detecting region is adapted to detect said charge of said component in said opening; and said region of said detecting region includes an oxide layer defining said opening, said oxide layer including at least one silicon nanocrystal.
76. A method for manufacturing a;|device for detecting a polymer, comprising the steps of: providing a semiconductor structure comprising at least one semiconductor layer; creating a detecting region in said semiconductor structure, said detecting region being adapted to detect a charge representative of a component of said polymer proximate to said detecting region; and creating an opening in said semiconductor structure, said opening having a cross- section sufficient to enable a portion of said] polymer to pass therethrough, and being positioned in relation to said detecting region] such that said detecting region is adapted to detect said charge representative of said component in said opening; wherein said opening creating step includes the step of forming an oxide layer on a wall of said semiconductor layer forming said opening to decrease said cross-section of said opening, said oxide layer including at leask one silicon nanocrystal.
PCT/US2001/013101 2000-04-24 2001-04-24 An ultra-fast nucleic acid sequencing device and a method for making and using the same WO2001081896A1 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
EP01932615A EP1285252A1 (en) 2000-04-24 2001-04-24 An ultra-fast nucleic acid sequencing device and a method for making and using the same
US10/258,439 US7001792B2 (en) 2000-04-24 2001-04-24 Ultra-fast nucleic acid sequencing device and a method for making and using the same
AU2001259128A AU2001259128A1 (en) 2000-04-24 2001-04-24 An ultra-fast nucleic acid sequencing device and a method for making and using the same
JP2001578932A JP4719906B2 (en) 2000-04-24 2001-04-24 Field effect transistor device for ultrafast nucleic acid sequencing
US11/301,259 US8232582B2 (en) 2000-04-24 2005-12-13 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US11/929,794 US9063081B2 (en) 2000-04-24 2007-10-30 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US13/409,800 US8426232B2 (en) 2000-04-24 2012-03-01 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US13/617,626 US8546168B2 (en) 2000-04-24 2012-09-14 Method and apparatus for detecting nucleotides
US14/039,142 US9228976B2 (en) 2000-04-24 2013-09-27 Method and apparatus for detecting nucleotides
US14/745,753 US9410923B2 (en) 2000-04-24 2015-06-22 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US15/231,480 US9758824B2 (en) 2000-04-24 2016-08-08 Ultra-fast nucleic acid sequencing device and a method for making and using the same

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US19913000P 2000-04-24 2000-04-24
US60/199,130 2000-04-24
US21768100P 2000-07-12 2000-07-12
US60/217,681 2000-07-12
US09/653,543 2000-08-31
US09/653,543 US6413792B1 (en) 2000-04-24 2000-08-31 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US25958401P 2001-01-04 2001-01-04
US60/259,584 2001-01-04

Related Parent Applications (2)

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US09/653,543 Continuation-In-Part US6413792B1 (en) 2000-04-24 2000-08-31 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US14/745,753 Continuation-In-Part US9410923B2 (en) 2000-04-24 2015-06-22 Ultra-fast nucleic acid sequencing device and a method for making and using the same

Related Child Applications (3)

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US10/258,439 A-371-Of-International US7001792B2 (en) 2000-04-24 2001-04-24 Ultra-fast nucleic acid sequencing device and a method for making and using the same
US10258439 A-371-Of-International 2001-04-24
US11/301,259 Division US8232582B2 (en) 2000-04-24 2005-12-13 Ultra-fast nucleic acid sequencing device and a method for making and using the same

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WO2001081896B1 true WO2001081896B1 (en) 2002-02-14

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JP (1) JP4719906B2 (en)
AU (1) AU2001259128A1 (en)
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