WO2006036388B1 - Systems and methods for detecting and analyzing polymers - Google Patents

Systems and methods for detecting and analyzing polymers

Info

Publication number
WO2006036388B1
WO2006036388B1 PCT/US2005/029878 US2005029878W WO2006036388B1 WO 2006036388 B1 WO2006036388 B1 WO 2006036388B1 US 2005029878 W US2005029878 W US 2005029878W WO 2006036388 B1 WO2006036388 B1 WO 2006036388B1
Authority
WO
WIPO (PCT)
Prior art keywords
fluorophores
emission
detection system
detection
signal
Prior art date
Application number
PCT/US2005/029878
Other languages
French (fr)
Other versions
WO2006036388A2 (en
WO2006036388A3 (en
Inventor
Martin Fuchs
John Harris
Ray Meyer
Original Assignee
Us Genomics Inc
Martin Fuchs
John Harris
Ray Meyer
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
Application filed by Us Genomics Inc, Martin Fuchs, John Harris, Ray Meyer filed Critical Us Genomics Inc
Priority to EP05810258A priority Critical patent/EP1786932A4/en
Publication of WO2006036388A2 publication Critical patent/WO2006036388A2/en
Publication of WO2006036388A3 publication Critical patent/WO2006036388A3/en
Publication of WO2006036388B1 publication Critical patent/WO2006036388B1/en

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N2021/6417—Spectrofluorimetric devices
    • G01N2021/6419—Excitation at two or more wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N2021/6417—Spectrofluorimetric devices
    • G01N2021/6421—Measuring at two or more wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
    • G01N2021/6441—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Abstract

A detection system and methods for improving the ability of the detection system to recognize labels that are disposed on a polymer. Embodiments of the invention include schemes for selecting emitters and labels used within the system in a manner that allows an increase in the number of distinct labels that can be used together in a system. In other embodiments, the detection system and methods are directed to identifying portions of a detection signal that may be associated with extra labels residing within a detection zone. In other embodiments, the detection system and methods relate to using wide field imaging detectors while reducing out of focus noise contributions to detection signals of the system. Still, other embodiments relate to the use of linear array detectors to detect labels.

Claims

57AMENDED CLAIMS[received by the International Bureau on 30 October 2006 (30.10.2006)]
1. A detection system for analyzing a polymer having three or more distinct fluorophores, each fluorophore having an excitation wavelength and a corresponding emission bandwidth, the detection system comprising: a polymer interrogation zone constructed and arranged to accept the polymer; at least three different emitters, each of the emitters constructed and arranged to emit an excitation signal at a substantially continuous level and substantially at an excitation wavelength of a corresponding one of the at least three fluorophores such that each fluorophore emits a distinct emission signal within its respective emission bandwidth and each distinct emission signal has an emission maximum separated by at least 60 nm from any other of the emission maximums; and a detector constructed and arranged to distinctly detect the emission signal from each of the at least three fluorophores.
2. A detection system for analyzing a polymer having three or more distinct fluorophores, each fluorophore having an excitation wavelength and a corresponding emission bandwidth, the detection system comprising: a polymer interrogation zone constructed and arranged to accept the polymer; at least three different emitters, each of the emitters constructed and arranged to emit an excitation signal at a substantially continuous level and substantially at an excitation wavelength of a corresponding one of the at least three fluorophores such that each fluorophore emits a distinct emission signal within its respective emission bandwidth that does not overlap any other of the distinct emission signals at normalized intensities above 70%; and a detector constructed and arranged to detect the distinct emission signal from each of the at least three fluorophores.
3. The detection system of claim 2, wherein each of the emitters is constructed and arranged to emit its excitation signal within the excitation wavelength of one of the at least three distinct fluorophores such that each fluorophore emits a distinct emission signal within its respective emission bandwidth that does not overlap any other of the distinct emission signal at normalized intensities above 50%. 58
4. The detection system of claim 3, wherein each of the emitters is constructed and arranged to emit its excitation signal within the excitation wavelength of one of the at least three distinct fluorophores such that each fluorophore emits a distinct emission signal within its respective emission bandwidth that does not overlap any other of the distinct emission signal at normalized intensities above 30%.
5. A detection system for analyzing a polymer having three or more distinct fluorophores, each fluorophore having an excitation wavelength and a corresponding emission bandwidth, the detection system comprising: a polymer interrogation zone constructed and arranged to accept the polymer; at least three different emitters, each of the emitters constructed and arranged to emit an excitation signal at a substantially continuous level and substantially at an excitation wavelength of a corresponding one of the at least three fluorophores such that each fluorophore emits a distinct emission signal within its respective emission bandwidth, each of the at least three emitters and corresponding at least three fluorophores selected from a group consisting of: an emitter emitting an excitation signal substantially at a wavelength of 488 nm and a corresponding fluorophore having an emission maximum substantially located at 512 nm, an emitter emitting an excitation signal substantially at a wavelength of 532 nm and a corresponding fluorophore having an emission maximum substantially located at 575 nm, an emitter emitting an excitation signal substantially at a wavelength of 633 nm and a corresponding fluorophore having an emission maximum substantially located at 665 nm, and an emitter emitting an excitation signal substantially at a wavelength of 750 nm and a corresponding fluorophore having an emission maximum substantially located at 775nm or 806 nm; and a detector constructed and arranged to detect the distinct emission signal from each of the at least three fluorophores.
6. The detection system of claim 1, wherein the at least three fluorophores are selected from the group consisting of: Bodipy FL fluorophore, Tamra fluorophore, Alexa 647 fluorophore, Alexa 750 fluorophore, and IR 38 fluorophore. 59
7. The detection system of any of claims 1-5, wherein the detector comprises a plurality of detectors.
8. The detection system of claim 7, wherein the plurality of detectors comprises a plurality of avalanche photon detectors.
9. The detection system of any of claims 7-8, further comprising: a plurality of dichroic mirrors constructed and arranged to direct each of the distinct emission signals into one of the plurality of detectors.
10. The detection system of any of claims 1-9, further comprising: a polychroic mirror adapted to prevent excitation signals emitted from the at least three different emitters from reaching the detector.
11. The detection system of any of claims 1-10, further comprising: a bandpass filter for removing noise from each of the emission signals.
12. The detection system of any of claims 1-11, wherein the polymer is a nucleic acid.
13. The detection system of claim 12, wherein the polymer is DNA or RNA.
14. The detection system of claim 13, wherein the nucleic acid is genomic DNA.
15. A detection system of claim 12, wherein the RNA is miRNA, siRNA, or RNAi.
16. The detection system of any of claims 1-14, wherein the at least three different emitters comprise four different emitters and the at least three different fluorophores comprise four different fluorophores.
17. A detection system of any of claims 1-16, wherein the emitters comprise lasers.
18. A detection system of any of claims 1-17, wherein the excitation signals comprise coherent light. 60
19. A method of detecting emissions of three or more distinct fluorophores bound to a polymer, the method comprising: selecting three or more fluorophores, each of the fluorophores characterized by an excitation wavelength and a corresponding emission bandwidth, the emission bandwidth of each of the fluorophores not overlapping the emission bandwidth of any other of the fluorophores at normalized intensities above 70%; attaching the three or more fluorophores to the polymer in a sequence specific manner; illuminating each of the fluorophores with an excitation signal at a substantially continuous level and within the excitation wavelength of the corresponding fluorophores, thereby causing each of the fluorophores to emit an emission signal within the emission bandwidth of the fluorophore; detecting and analyzing the emission signal of each of the fluorophores.
20. The method of claim 19 wherein, selecting three or more fluorophores comprises selecting three or more fluorophores, each of the fluorophores characterized by an excitation bandwidth and a corresponding emission bandwidth, the emission bandwidth of each of the fluorophores not overlapping the emission bandwidth of any other of the fluorophores at normalized intensities above 50%.
21. The method of claim 20, wherein selecting three or more fluorophores comprises selecting three or more fluorophores, each of the fluorophores characterized by an excitation bandwidth and a corresponding emission bandwidth, the emission bandwidth of each of the fluorophores not overlapping the emission bandwidth of any other of the fluorophores at normalized intensities above 30%.
22. A method for analyzing a polymer, the method comprising: selecting at least three distinct fluorophores and at least three different excitation signals each emitted from a corresponding emitter, each of the at least three fluorophores having an excitation wavelength and a corresponding emission bandwidth, each of the excitation signals having an excitation wavelength of a corresponding one of the at least three fluorophores such that each fluorophore emits a distinct emission - 61 -
signal having an emission maximum within its respective emission bandwidth, each of the at least three excitation signals and corresponding at least three fluorophores selected from a group consisting of: an excitation signal having a wavelength of 488 nm and a corresponding fluorophore having an emission maximum substantially located at 512 nm, an excitation signal having a wavelength of 532 nm and a corresponding fluorophore having an emission maximum substantially located at 575 nm, an excitation signal having a wavelength of 633 nm and a corresponding fluorophore having an emission maximum substantially located at 665 nm, and an excitation signal having a wavelength of 750 nm and a corresponding fluorophore having an emission maximum substantially located at 775nm or 806 nm; binding the at least three fluorophores to a polymer in a sequence specific manner; illuminating each of the fluorophores with the corresponding emitter that emits an excitation signal at a substantially continuous level; and detecting and analyzing the emission signal of each of the fluorophores for analysis.
23. The method of any of claims 19-22, wherein selecting three or more fluorophores comprises selecting three or more different fluorophores from a group consisting of: Bodipy FL fluorophore, Tamra fluorophore, Alexa 647 fluorophore, Alexa 750 fluorophore, and IR 38 fluorophore.
24. The method of any of claims 19-23, wherein selecting at least three distinct fluorophores and at least three emitters comprises selecting four fluorophores and four emitters.
25. The method of any of claims 19-24, wherein the polymer is a nucleic acid.
26. The method of claim 25, wherein the polymer is DNA or RNA.
27. The method of claim 26, wherein the nucleic acid is genomic DNA.
28. The method of claim 26, wherein the RNA is miRNA, siRNA, or RNAi.
29. The method of any of claims 25-28, wherein the polymer is a single polymer.
30. The method of any of claims 19-29, further comprising: removing the excitation signal from each of the emission signals with a polychroic filter.
31. The method of any of claims 19-30, wherein detecting the emission signal from each of the fluorophores comprises: separating each of the emission signals from one another with dichroic filters.
32. The method of any of claims 19-31, wherein detecting the emission signal from each of the fluorophores comprises: passing the emission signal of some of the fluorophores through a bandpass filter.
33. The method of any of the claims 19-32, wherein illuminating each of the fluorophores with the excitation signal comprises eliminating each of the fluorophores with a laser beam.
34. A detection system for analyzing a polymer, the detection system comprising: a first detection zone disposed in a first area of a microchannel and adapted to detect a polymer having first and second polymer portions to create a first detection signal when the polymer is in the first zone; a second detection zone disposed in a second area of the microchannel that is different from the first area, the second detection zone adapted to detect the second polymer portion to create a second detection signal when the second portion is in the second area; a data processor adapted to comparing the first and second detection signals and identify components that are not common to both the first and second detection signals.
35. The detection system of claim 34, wherein the second detection zone is substantially overlapped with the first detection zone. - 63 -
36. The detection system of claim 35, wherein the first detection zone and the second detection zone are substantially circular, the second detection zone being concentric with the first detection zone and the second detection zone being disposed entirely within the first detection zone.
37. The detection system of any of claims 34-36, wherein the first detection zone has a diameter of approximately 1.00 microns and the second detection zone has a diameter of approximately 0.50 microns.
38. The detection system of any of claims 34-37, further comprising: an emitter for illuminating the first detection zone, the emitter adopted to emit on excitation signal having low intensity components and high intensity components.
39. The detection system of claim 38, wherein the first detection zone covers areas having both low and high intensity components of the excitation signal while the second detection zone covers areas having substantially only high intensity components of the excitation signal.
40. The detection system of claim 39, wherein the data processor is adapted to remove at least some portions of emission signals associated with the first detection zone of the low intensity components of the excitation signal from the first detection signal to improve the identification of the second polymer portion by the first detection signal.
41. The detection system of any of claims 34-40, wherein the polymer is a nucleic acid.
42. The detection system of claim 41, wherein the polymer is DNA or RNA.
43. The detection system of claim 42, wherein the polymer is genomic DNA.
44. The detection system of claim 42, wherein the RNA comprises miRNA, siRNA, or RNAi. - 64 -
45. The detection system of any of claims 34-44, wherein the first and second detection zones are adapted to detect a polymer or polymer portion having a label that fluoresces.
46. The detection system of any of claims 34-45, wherein the polymer comprises a plurality of polymers, each of the first and second polymer portions comprising separate polymers.
47. A method of analyzing a polymer in a detection system, the method comprising: passing a plurality of polymers comprising a first polymer portion and a second polymer portion through a first detection zone to create a first detection signal, the first detection zone disposed in a first area of the microchannel; passing the second portion of polymers through a second detection zone to create a second detection signal, the second detection zone disposed in a second area of the microchannel; identifying components of the first detection signal that are associated with the second polymer portion by comparing the first detection signal with the second detection signal; and detecting components of the first detection signal associated with the second polymer portion to analyze the polymers.
48. The method of claim 47, further comprising: modifying the first detection signal by removing components of the first detection signal that are not also associated only with the second detection signal to improve the identification of the second polymer portion by the first detection signal.
49. The method of claim 47, wherein passing the plurality of polymers comprises moving both the first detection zone and the second detection zone relative to the first and second portion of polymers .
50. The method of claim 47, wherein passing the plurality of polymers comprises flowing the plurality of polymers within a fluid through the microchannel. - 65 -
51. The method of any of claims 47-50, wherein the polymer is a nucleic acid.
52. The method of claim 51 , wherein the polymer is DNA or RNA.
53. The method of claim 52, wherein the polymer is genomic DNA.
54. The method of claim 52, wherein the RNA is miRNA, siRNA, or RNAi.
55. The method of any of claims 47-54, wherein passing the second portion of polymers through the second detection zone comprises passing the second portion of polymers through the second detection zone that is completely overlapped with the first detection zone.
56. The method of any of claims 47-55, wherein passing a plurality of polymers through the first detection zone comprises passing a plurality of polymers through the first detection zone defined by a high intensity region and a low intensity region; and further wherein passing the second portion of polymers through the second detection zone comprises passing the second portion of the polymer through the second detection zone that does not include the low intensity region.
57. The method of any of claims 47 '-56, wherein identifying the components of the first detection signal that are associated with the second polymer portion comprises comparing a histogram of signal intensities for the first detection signal with a histogram of signal intensities for the second detection signal.
58. The method of any of claims 47-57, wherein modifying the first detection signal comprises removing low intensity components from the first detection signal that are not also present in second detection signal.
59. The method of any of claims 47-58, wherein passing aplurality of polymers through a first detection zone comprises passing a plurality of polymers through a circular detection zone having a diameter of approximately 1.00 microns; and - 66 -
further wherein, passing the second portion of polymers through a second detection zone comprises passing a plurality of polymers through a second circular detection zone having a diameter of approximately 0.50 microns and being substantially centered within the first detection zone.
60. A detection system to detect a label disposed on a polymer, the detection system comprising: a channel constructed and arranged to receive the polymer carried in a carrier fluid, the channel having a sample area defined by upper and lower channel surfaces separated from one another by a channel height less than about 0.500 microns; an emitter constructed and arranged to illuminate the sample area with an excitation signal to excite the label in the sample area, thereby causing the label to emit an emission signal; and a detector constructed and arranged to detect a detection signal from a detection zone disposed within the sample area, the detection signal including the emission signal, the detection zone being disposed at least partially within the sample area.
61. The detection system of claim 60, wherein channel height is less than about 0.100 microns.
62. The detection system of claim 60, wherein channel height is less than about 0.050 microns.
63. The detection system of any of claim 60, wherein the sample area of the channel has a channel width less than about 250 microns.
64. The detection system of any of claim 60, wherein the sample area is constructed and arranged to receive not more than 50 nanoliters/second of carrier fluid.
65. The detection system of any of claims 60-64, wherein the emitter is a laser.
66. The detection system of claim 65, wherein the laser is one or more lasers selected from the group consisting of: a laser emitting light substantially at a wavelength of 488 - 67 -
nm, a laser emitting light substantially at a wavelength of 532 nm, a laser emitting light substantially at a wavelength of 633 nm, and a laser emitting light substantially at a wavelength of 750 nm.
67. The detection system of any of claims 60-66, wherein the polymer is a nucleic acid.
68. The detection system of claim 67, wherein the nucleic acid is DNA or RNA.
69. The detection system of claim 68, wherein the RNA is miRNA, siRNA, or RNAi.
70. The detection system of any of claims 60-68, wherein the label is a fluorophore.
71. The detection system of claim 70, wherein the fluorophore is one or more fluorophores selected from the group consisting of: a fluorophore having an emission maximum substantially located at 512 nm, a fluorophore having an emission maximum substantially located at 575 nm, a fluorophore having an emission maximum substantially located at 665 nm, a fluorophore having an emission maximum substantially located at 775nm, and a fluorophore having an emission maximum substantially located at 806 nm.
72. The detection system of any of claims 60-70, wherein the upper or lower surface of the channel are adapted to transmit the excitation signal or detection signal without contributing noise.
73. The detection system of claim 72, wherein the material is fused silica.
74. The detection system of any of claims 60-72, wherein the detector comprises a CCD array.
75. The detection system of claim 74, wherein the CCD array comprises a linear CCD array. - 68 -
76. A method to detect a label disposed on a polymer, the method comprising: providing a carrier fluid containing the polymer; providing a channel constructed and arranged to receive the earner fluid, the channel having a sample area defined by upper and lower channel surfaces separated from one another by a channel height less than about 0.500 microns; exciting the label with an excitation signal, causing the label to emit an emission signal; and detecting the emission signal.
77. The method of claim 76, wherein channel height is less than about 0.100 microns.
78. The method of claim 76, wherein channel height is less than about 0.050 microns.
79. The method of any of claims 76-78, wherein the sample area of the channel has a channel width less than about 250 microns.
80. The method of any of claims 76-79, wherein the sample area is constructed and arranged to receive not more than 50 nanoliters/second of carrier fluid.
81. The method of any of claims 76-80, wherein the emitter is a laser.
82. The method of claim 81, wherein the laser is one or more lasers selected from the group consisting of: a laser emitting light substantially at a wavelength of 488 nm, a laser emitting light substantially at a wavelength of 532 nm, a laser emitting light substantially at a wavelength of 633 nm, and a laser emitting light substantially at a wavelength of 750 nm.
83. The method of any of claims 76-82, wherein the polymer is a nucleic acid.
84. The method of claim 83, wherein the nucleic acid is DNA or RNA.
85. The method of claim 84, wherein the RNA is miRNA, siRNA, or RNAi. - 69 -
86. The method of any of claims 76-85, wherein the label is a fluorophore
87. The method of claim 86, wherein the fluorophore is one or more fluorophores selected from the group consisting of: a fluorophore having an emission maximum substantially located at 512 nm, a fluorophore having an emission maximum substantially located at 575 nm, a fluorophore having an emission maximum substantially located at 665 nm, a fluorophore having an emission maximum substantially located at 775nm, and a fluorophore having an emission maximum substantially located at 806 nm.
88. The method of any of claims 76-87, wherein the upper or lower surface of the channel are adapted to transmit the excitation signal or detection signal without contributing noise.
89. The method of claim 88, wherein the material is fused silica.
90. The method of any of claims 76-89, wherein the detector comprises a CCD array.
91. The method of claims 90, wherein CCD array is a linear CCD array.
92. A detection system to detect a label disposed on a polymer, the detection system comprising: a channel adapted to allow a carrier fluid containing a polymer to pass in a flow direction through the channel and through a detection zone within the channel; an emitter constructed and arranged to emit an excitation signal as a sheet of light into the detection zone; and a detector constructed and arranged to detect a detection signal emanating from the detection zone from a direction substantially orthogonal to the sheet of light, the detection signal including an emission signal from the label when the label is present in the zone and excited by the excitation signal.
93. The detection system of claim 92, wherein the detector has a focal plane lying substantially within the sheet of light. - 70 -
94. The detection system of any of claims 92-93, further comprising: a cylindrical lens adapted to form the sheet of light.
95. The detection system of any of claims 92-94, wherein the sheet of light is disposed in the channel such that substantially all of the carrier fluid passes through the sheet of light when passing through the channel.
96. The detection system of any of claims 92-95, wherein the emitter comprises a plurality of emitters, each constructed and arranged to emit its own excitation signal.
97. The detection system of any of claims 92-96, wherein the detection zone has a thickness of 0.5 microns.
98. The detection system of any of claims 92-97, wherein the emitter is a laser.
99. The detection system of claim 98, wherein the laser is one or more lasers selected from the group consisting of: a laser emitting light substantially at a wavelength of 488 nm, a laser emitting light substantially at a wavelength of 532 nm, a laser emitting light substantially at a wavelength of 633 nm, and a laser emitting light substantially at a wavelength of 750 nm.
100. The detection system of any of claims 92-99, wherein the polymer is a nucleic acid.
101. The detection system of claim 100, wherein the nucleic acid is DNA or KNA.
102. The detection system of any of claims 92-100, wherein the label is a fluorophore
103. The detection system of claim 102, wherein the fluorophore is one or more fluorophores selected from the group consisting of: a fluorophore having an emission maximum substantially located at 512 nm, a fluorophore having an emission maximum substantially located at 575 nm, a fluorophore having an emission maximum - 71 -
substantially located at 665 nm, a fluorophore having an emission maximum substantially located at 775nm, and a fluorophore having an emission maximum substantially located at 806 nm.
104. The detection system of any of claims 92- 103 , wherein the detector comprises a CCD array.
105. The detection system of claim 104, wherein the CCD array is a linear CCD array.
106. A method for detecting a label on a polymer having the label, the method comprising: providing a carrier fluid containing the polymer; providing a channel having a detection zone located within the channels; flowing the carrier fluid through the channel in a flow direction and through a detection zone in the channel; emitting an excitation signal as a sheet of light into the detection zone; and detecting, with a detector, an emission signal from the label when the label is present in the zone and excited by the excitation signal, the detector located in a direction substantially orthogonal to the sheet of light.
107. The method of claim 106, wherein the detector has a focal plane lying substantially within the sheet of light.
108. The method of any of claims 106-107, further comprising: forming the sheet of light from a laser beam by passing the light through a cylindrical lens.
109. The method of any of claims 106-108, further comprising: passing substantially all of the carrier fluid through the sheet of light as the fluid traverses the channel.
110. The method of any of claims 106-109, wherein emitting an excitation signal comprises emitting a plurality of excitation signals. - 72 -
111. A detection system for detecting a first and second distinct labels on a polymer, the detection system comprising: a detection zone adapted to receive the polymer for detection; an emitter for exciting each of the first and second distinct labels on the polymer when in the detection zone, causing each of the first and second distinct labels to emit a first and second emission signal, respectively; an mirror adapted to substantially separate the first and second emission signals from one another; and a wide field detector adapted to receive the first and second emission signals on spatially separate portions of a detection surface.
112. A method of detecting a first and a second distinct label on a polymer, the method comprising: providing a detection zone; placing the polymer and the label into the detection zone; emitting an excitation signal for exciting the first and second distinct labels, causing the first and second labels to emit a first and second emission signal, respectively; substantially separating the first and second emission signals from one another; and detecting the first and second emission signals on a spatially separated portions of a detector.
113. A detection system for analyzing a polymer having a label, the detection system comprising: a channel adapted to provide a carrier fluid containing a polymer through the channel in a flow direction; a detection zone lying within the channel, the detection zone comprising a substantially linear array, the array arranged in a direction substantially orthogonal to the flow direction; - 73 -
an emitter constructed and arranged to emit an excitation signal into the detection zone, the excitation signal comprising a sheet of light extending into the detection zone; and a detector constructed and arranged to detect an emission signal from the label when the label is present in the detection zone and excited by the excitation signal.
114. The method of claim 113, wherein the detector is a linear CCD array.
115. The detection system of claim 1, wherein the detector comprises a plurality of detectors.
116. The detection system of claim 115, wherein the plurality of detectors comprises a plurality of avalanche photon detectors.
117. The detection system of claim 115, further comprising: a plurality of dichroic mirrors constructed and arranged to direct each of the distinct emission signals into one of the plurality of detectors.
118. The detection system of claim 1, further comprising: a polychroic mirror adapted to prevent excitation signals emitted from the at least three different emitters from reaching the detector.
119. The detection system of claim 1, further comprising: a bandpass filter for removing noise from each of the emission signals.
120. The detection system of claim 1, wherein the at least three different emitters comprise four different emitters and the at least three different fluorophores comprise four different fluorophores.
121. A detection system of claim 1 , wherein the emitters comprise lasers .
122. A detection system of claim 1, wherein the excitation signals comprise coherent light. - 74 -
123. The method of claim 19 wherein, selecting three or more fluorophores comprises selecting three or more fluorophores, each of the fluorophores characterized by an excitation bandwidth and a corresponding emission bandwidth, the emission bandwidth of each of the fluorophores not overlapping the emission bandwidth of any other of the fluorophores at normalized intensities above 50%.
124. The method of claim 123, wherein selecting three or more fluorophores comprises selecting three or more fluorophores, each of the fluorophores characterized by an excitation bandwidth and a corresponding emission bandwidth, the emission bandwidth of each of the fluorophores not overlapping the emission bandwidth of any other of the fluorophores at normalized intensities above 30%.
125. The method of claim 19, wherein selecting three or more fluorophores comprises selecting -three or more different fluorophores from a group consisting of: Bodipy FL fluorophore, Tamra fluorophore, Alexa 647 fluorophore, Alexa 750 fluorophore, and IR 38 fluorophore.
126. The method of claim 19, wherein selecting at least three distinct fluorophores and at least three emitters comprises selecting four fluorophores and four emitters.
127. The method of claim 19, wherein the polymer is a nucleic acid.
128. The method of claim 19, further comprising: removing the excitation signal from each of the emission signals with a polychroic filter.
129. The method of claim 19, wherein detecting the emission signal from each of the fluorophores comprises: separating each of the emission signals from one another with dichroic filters.
130. The method of claim 19, wherein detecting the emission signal from each of the fluorophores comprises: - 75 -
passing the emission signal of some of the fluorophores through a bandpass filter.
131. The method of claim 19, wherein illuminating each of the fluorophores with the excitation signal comprises eliminating each of the fluorophores with a laser beam.
PCT/US2005/029878 2004-08-23 2005-08-23 Systems and methods for detecting and analyzing polymers WO2006036388A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP05810258A EP1786932A4 (en) 2004-08-23 2005-08-23 Systems and methods for detecting and analyzing polymers

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US60376004P 2004-08-23 2004-08-23
US60/603,760 2004-08-23

Publications (3)

Publication Number Publication Date
WO2006036388A2 WO2006036388A2 (en) 2006-04-06
WO2006036388A3 WO2006036388A3 (en) 2006-10-19
WO2006036388B1 true WO2006036388B1 (en) 2006-12-14

Family

ID=36119345

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/029878 WO2006036388A2 (en) 2004-08-23 2005-08-23 Systems and methods for detecting and analyzing polymers

Country Status (3)

Country Link
US (3) US7351538B2 (en)
EP (1) EP1786932A4 (en)
WO (1) WO2006036388A2 (en)

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69825601T2 (en) 1997-02-12 2005-04-28 Chan, Eugene Y, Brookline METHOD FOR THE ANALYSIS OF POLYMERS
US6696022B1 (en) * 1999-08-13 2004-02-24 U.S. Genomics, Inc. Methods and apparatuses for stretching polymers
EP1354064A2 (en) 2000-12-01 2003-10-22 Visigen Biotechnologies, Inc. Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity
JP2005504275A (en) * 2001-09-18 2005-02-10 ユー．エス． ジェノミクス， インコーポレイテッド Differential tagging of polymers for high-resolution linear analysis
AU2003228649A1 (en) * 2002-04-23 2003-11-10 U.S.Genomics, Inc. Compositions and methods related to two-arm nucleic acid probes
US7371520B2 (en) * 2002-05-28 2008-05-13 U.S. Genomics, Inc. Methods and apparati using single polymer analysis
US7282330B2 (en) * 2002-05-28 2007-10-16 U.S. Genomics, Inc. Methods and apparati using single polymer analysis
JP2005533256A (en) * 2002-07-17 2005-11-04 ユー．エス． ジェノミクス， インコーポレイテッド Methods and compositions for analyzing polymers using chimeric tags
EP1586068B1 (en) * 2003-01-23 2008-07-30 U.S. Genomics, Inc. Methods for analyzing polymer populations
JP2006522940A (en) * 2003-04-10 2006-10-05 ユー．エス． ジェノミクス， インコーポレイテッド Manipulating polymers in microchannels
WO2005012575A1 (en) * 2003-08-01 2005-02-10 U.S. Genomics, Inc. Methods and compositions related to the use of sequence-specific endonucleases for analyzing nucleic acids under non-cleaving conditions
US20050048498A1 (en) * 2003-08-29 2005-03-03 Applera Corporation Compositions, methods, and kits for assembling probes
US7198900B2 (en) * 2003-08-29 2007-04-03 Applera Corporation Multiplex detection compositions, methods, and kits
JP2007518107A (en) 2004-01-13 2007-07-05 ユー．エス． ジェノミクス， インコーポレイテッド Detection and quantification of analytes in solution using polymers
US7595160B2 (en) * 2004-01-13 2009-09-29 U.S. Genomics, Inc. Analyte detection using barcoded polymers
US20050221408A1 (en) * 2004-03-19 2005-10-06 U.S. Genomics, Inc. Compositions and methods for detection of single molecules
WO2006017274A2 (en) * 2004-07-13 2006-02-16 U.S. Genomics, Inc. Systems and methods for sample modification using fluidic chambers
US7351538B2 (en) * 2004-08-23 2008-04-01 U.S. Genomics Systems and methods for detecting and analyzing polymers
US8685711B2 (en) 2004-09-28 2014-04-01 Singulex, Inc. Methods and compositions for highly sensitive detection of molecules
US9040305B2 (en) * 2004-09-28 2015-05-26 Singulex, Inc. Method of analysis for determining a specific protein in blood samples using fluorescence spectrometry
EP1805500A4 (en) * 2004-09-28 2008-05-07 Singulex Inc System and method for spectroscopic analysis of single particles
US7572640B2 (en) * 2004-09-28 2009-08-11 Singulex, Inc. Method for highly sensitive detection of single protein molecules labeled with fluorescent moieties
WO2006098772A2 (en) * 2004-10-13 2006-09-21 U.S. Genomics, Inc. Systems and methods for measurement optimization
US20070128083A1 (en) * 2005-07-18 2007-06-07 U.S. Genomics, Inc. Microfluidic methods and apparatuses for sample preparation and analysis
WO2007041621A2 (en) * 2005-10-03 2007-04-12 Xingsheng Sean Ling Hybridization assisted nanopore sequencing
WO2007056250A2 (en) * 2005-11-04 2007-05-18 U.S. Genomics, Inc. Heterogeneous assay of analytes in solution using polymers
EP3168618B1 (en) 2006-04-04 2018-11-21 Singulex, Inc. Highly sensitive methods for analysis of troponin
US7838250B1 (en) 2006-04-04 2010-11-23 Singulex, Inc. Highly sensitive system and methods for analysis of troponin
US9061901B2 (en) 2006-07-19 2015-06-23 Bionano Genomics, Inc. Nanonozzle device arrays: their preparation and use for macromolecular analysis
KR100810297B1 (en) * 2006-10-31 2008-03-06 삼성전자주식회사 Wireless communication interface for portable wireless terminal
US8999636B2 (en) * 2007-01-08 2015-04-07 Toxic Report Llc Reaction chamber
US20090053690A1 (en) * 2007-02-02 2009-02-26 California Institute Of Technology Surface chemistry and deposition techniques
CN103305402A (en) 2007-03-28 2013-09-18 博纳基因技术有限公司 Method of macromolecular analysis using nanochannel arrays
US20100294665A1 (en) * 2007-07-12 2010-11-25 Richard Allen Method and system for transferring and/or concentrating a sample
US8278047B2 (en) 2007-10-01 2012-10-02 Nabsys, Inc. Biopolymer sequencing by hybridization of probes to form ternary complexes and variable range alignment
US7914734B2 (en) 2007-12-19 2011-03-29 Singulex, Inc. Scanning analyzer for single molecule detection and methods of use
AU2009267086B2 (en) 2008-06-30 2016-01-14 Bionano Genomics, Inc. Methods and devices for single-molecule whole genome analysis
US8644580B2 (en) * 2008-08-07 2014-02-04 Cambridge Research & Instrumentation, Inc. Detection of RNA in tissue samples
WO2010028140A2 (en) * 2008-09-03 2010-03-11 Nabsys, Inc. Use of longitudinally displaced nanoscale electrodes for voltage sensing of biomolecules and other analytes in fluidic channels
US8262879B2 (en) 2008-09-03 2012-09-11 Nabsys, Inc. Devices and methods for determining the length of biopolymers and distances between probes bound thereto
US9650668B2 (en) 2008-09-03 2017-05-16 Nabsys 2.0 Llc Use of longitudinally displaced nanoscale electrodes for voltage sensing of biomolecules and other analytes in fluidic channels
US8361716B2 (en) * 2008-10-03 2013-01-29 Pathogenetix, Inc. Focusing chamber
US8248609B2 (en) * 2008-11-04 2012-08-21 The Johns Hopkins University Cylindrical illumination confocal spectroscopy system
CN102292454B (en) 2008-11-18 2014-11-26 博纳基因技术有限公司 Polynucleotide mapping and sequencing
EP2387616A2 (en) 2009-01-16 2011-11-23 Cepheid Methods of detecting cervical cancer
CN102388149A (en) 2009-02-02 2012-03-21 西菲伊德公司 Methods of detecting sepsis
US20100233704A1 (en) 2009-02-25 2010-09-16 Cepheid Methods of detecting lung cancer
US8455260B2 (en) * 2009-03-27 2013-06-04 Massachusetts Institute Of Technology Tagged-fragment map assembly
US20100243449A1 (en) * 2009-03-27 2010-09-30 Oliver John S Devices and methods for analyzing biomolecules and probes bound thereto
US8246799B2 (en) * 2009-05-28 2012-08-21 Nabsys, Inc. Devices and methods for analyzing biomolecules and probes bound thereto
JP5678045B2 (en) 2009-06-08 2015-02-25 シンギュレックス・インコーポレイテッド High sensitivity biomarker panel
CA2711985A1 (en) * 2009-07-31 2011-01-31 Yves St-Onge Recycling method using tagging
EP2462245B1 (en) * 2009-08-06 2016-10-05 Cornell University Device and methods for epigenetic analysis
US9207205B2 (en) * 2009-12-17 2015-12-08 The Curators Of The University Of Missouri Method and apparatus for cancer screening
WO2011140484A1 (en) 2010-05-06 2011-11-10 Singulex, Inc Methods for diagnosing, staging, predicting risk for developing and identifying treatment responders for rheumatoid arthritis
US8715933B2 (en) 2010-09-27 2014-05-06 Nabsys, Inc. Assay methods using nicking endonucleases
US8859201B2 (en) 2010-11-16 2014-10-14 Nabsys, Inc. Methods for sequencing a biomolecule by detecting relative positions of hybridized probes
US11274341B2 (en) 2011-02-11 2022-03-15 NABsys, 2.0 LLC Assay methods using DNA binding proteins
US8956815B2 (en) 2012-04-18 2015-02-17 Toxic Report Llc Intercalation methods and devices
US9028776B2 (en) 2012-04-18 2015-05-12 Toxic Report Llc Device for stretching a polymer in a fluid sample
US8685708B2 (en) 2012-04-18 2014-04-01 Pathogenetix, Inc. Device for preparing a sample
ES2619032T3 (en) 2012-04-20 2017-06-22 Cepheid Bladder Cancer Screening Methods
CA2889024C (en) 2012-10-23 2018-03-27 Koc Universitesi A method and an apparatus for the detection of a tagging material in fluids
US9914966B1 (en) 2012-12-20 2018-03-13 Nabsys 2.0 Llc Apparatus and methods for analysis of biomolecules using high frequency alternating current excitation
WO2014113557A1 (en) 2013-01-18 2014-07-24 Nabsys, Inc. Enhanced probe binding
EP2964786B1 (en) 2013-03-06 2018-12-19 Cepheid Methods of detecting bladder cancer
WO2014164480A1 (en) 2013-03-12 2014-10-09 Cepheid Methods of detecting cancer
EP2971103A1 (en) 2013-03-14 2016-01-20 Cepheid Methods of detecting lung cancer
EP3068900B1 (en) * 2013-11-17 2020-01-08 Quantum-Si Incorporated Active-source-pixel, integrated device for rapid analysis of biological and chemical speciments
WO2016010494A1 (en) * 2014-07-17 2016-01-21 Kuantag Nanoteknolojiler Geliştirme Ve Üretim A.Ş. A fluorescent substance detection system
CN108064315B (en) 2014-08-22 2022-01-18 西菲伊德公司 Method for detecting influenza
WO2016069853A2 (en) 2014-10-30 2016-05-06 Cepheid Methods of detecting ebola
US20160371704A1 (en) 2015-06-18 2016-12-22 Kuantag Nanoteknolojiler Gelistirme Ve Uretim A.S. Integrated fuel tracking system
US10908072B2 (en) 2016-12-15 2021-02-02 The Board Of Regents Of The University Of Texas System Total internal reflection and transmission illumination fluorescence microscopy imaging system with improved background suppression
CN108387519A (en) * 2018-05-03 2018-08-10 上海市质子重离子临床技术研发中心 Microscopic system is just set in up-conversion luminescence near-infrared and the multi-functional wide field of colour imaging
US20220017979A1 (en) 2020-06-26 2022-01-20 Cepheid Methods of detecting sars-cov-2, influenza, and rsv
US20240035016A1 (en) 2022-04-29 2024-02-01 Cepheid Nucleic acid extraction and isolation with heat labile silanes and chemically modified solid supports

Family Cites Families (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4573796A (en) * 1984-01-06 1986-03-04 The United States Of America As Represented By The United States Department Of Energy Apparatus for eliminating background interference in fluorescence measurements
US4833332A (en) * 1987-06-12 1989-05-23 E. I. Du Pont De Nemours And Company Scanning fluorescent detection system
US5270214A (en) * 1990-05-30 1993-12-14 The United States Of America As Represented By The United States Department Of Energy Method for sequencing DNA base pairs
JP3123249B2 (en) 1991-09-10 2001-01-09 株式会社日立製作所 DNA molecule length measuring method and measuring device
WO1994016104A1 (en) 1993-01-08 1994-07-21 Ctrc Research Foundation Color imaging system for use in molecular biology
US5538613A (en) * 1993-10-26 1996-07-23 Genesys Technologies, Inc. Electrophoresis analyzer
US5556790A (en) * 1994-12-05 1996-09-17 Pettit; John W. Method for Automated DNA sequencing
US5784157A (en) * 1995-11-21 1998-07-21 The Research Foundation Of State University Of New York Method and apparatus for identifying fluorophores
AU3829197A (en) 1996-09-03 1998-03-26 Pioneer Hi-Bred International, Inc. Method and apparatus for single molecule two color fluorescent detection and molecular weight and concentration determination
US5880473A (en) * 1997-07-28 1999-03-09 Applied Imaging, Inc. Multifluor-fluorescence in-situ hybridization (M-FISH) imaging techniques using multiple multiband filters with image registration
DE69825601T2 (en) 1997-02-12 2005-04-28 Chan, Eugene Y, Brookline METHOD FOR THE ANALYSIS OF POLYMERS
US6403311B1 (en) 1997-02-12 2002-06-11 Us Genomics Methods of analyzing polymers using ordered label strategies
WO1998049344A1 (en) * 1997-04-28 1998-11-05 Lockheed Martin Energy Research Corporation Method and apparatus for analyzing nucleic acids
US6139800A (en) * 1997-06-23 2000-10-31 Luminex Corporation Interlaced lasers for multiple fluorescence measurement
US6369893B1 (en) * 1998-05-19 2002-04-09 Cepheid Multi-channel optical detection system
US6038023A (en) * 1998-07-31 2000-03-14 The Research Foundation Of State University Of New York Sensors for detection and spectroscopy
AU5560699A (en) 1998-08-13 2000-03-06 U.S. Genomics, Inc. Optically characterizing polymers
US6210896B1 (en) 1998-08-13 2001-04-03 Us Genomics Molecular motors
US6790671B1 (en) 1998-08-13 2004-09-14 Princeton University Optically characterizing polymers
US6263286B1 (en) 1998-08-13 2001-07-17 U.S. Genomics, Inc. Methods of analyzing polymers using a spatial network of fluorophores and fluorescence resonance energy transfer
US6245507B1 (en) * 1998-08-18 2001-06-12 Orchid Biosciences, Inc. In-line complete hyperspectral fluorescent imaging of nucleic acid molecules
EP1123524A2 (en) * 1998-09-30 2001-08-16 Trellis Bioinformatics Inc. High throughput microscopy
US6232075B1 (en) 1998-12-14 2001-05-15 Li-Cor, Inc. Heterogeneous assay for pyrophosphate detection
US6635163B1 (en) 1999-06-01 2003-10-21 Cornell Research Foundation, Inc. Entropic trapping and sieving of molecules
US6927065B2 (en) 1999-08-13 2005-08-09 U.S. Genomics, Inc. Methods and apparatus for characterization of single polymers
US6762059B2 (en) 1999-08-13 2004-07-13 U.S. Genomics, Inc. Methods and apparatuses for characterization of single polymers
US6696022B1 (en) 1999-08-13 2004-02-24 U.S. Genomics, Inc. Methods and apparatuses for stretching polymers
WO2002014462A1 (en) * 2000-08-14 2002-02-21 The Regents Of The University Of California Biosensors and methods for their use
EP1402069A4 (en) 2001-06-08 2006-01-25 Us Genomics Inc Methods and products for analyzing nucleic acids using nick translation
WO2002101353A2 (en) 2001-06-08 2002-12-19 U.S. Genomics, Inc. Methods and products for analyzing nucleic acids based on methylation status
US6995841B2 (en) * 2001-08-28 2006-02-07 Rice University Pulsed-multiline excitation for color-blind fluorescence detection
JP2005504275A (en) 2001-09-18 2005-02-10 ユー．エス． ジェノミクス， インコーポレイテッド Differential tagging of polymers for high-resolution linear analysis
US8423294B2 (en) 2001-09-18 2013-04-16 Pathogenetix, Inc. High resolution linear analysis of polymers
EP1461606A4 (en) * 2001-12-05 2005-06-29 Univ Washington Microfluidic device and surface decoration process for solid phase affinity binding assays
US7101467B2 (en) * 2002-03-05 2006-09-05 Caliper Life Sciences, Inc. Mixed mode microfluidic systems
AU2003228649A1 (en) 2002-04-23 2003-11-10 U.S.Genomics, Inc. Compositions and methods related to two-arm nucleic acid probes
WO2004048514A2 (en) 2002-05-09 2004-06-10 U.S. Genomics, Inc. Methods for analyzing a nucleic acid
US7282330B2 (en) 2002-05-28 2007-10-16 U.S. Genomics, Inc. Methods and apparati using single polymer analysis
US7371520B2 (en) 2002-05-28 2008-05-13 U.S. Genomics, Inc. Methods and apparati using single polymer analysis
JP2005533256A (en) 2002-07-17 2005-11-04 ユー．エス． ジェノミクス， インコーポレイテッド Methods and compositions for analyzing polymers using chimeric tags
US20060211055A1 (en) * 2002-11-12 2006-09-21 Caliper Life Sciences, Inc. Capture and release assay system and method
US20050042639A1 (en) * 2002-12-20 2005-02-24 Caliper Life Sciences, Inc. Single molecule amplification and detection of DNA length
EP1586068B1 (en) 2003-01-23 2008-07-30 U.S. Genomics, Inc. Methods for analyzing polymer populations
WO2004077692A1 (en) 2003-02-25 2004-09-10 Roke Manor Research Limited Spread spectrum baseband signal processor with decimation filtering
JP2006522940A (en) 2003-04-10 2006-10-05 ユー．エス． ジェノミクス， インコーポレイテッド Manipulating polymers in microchannels
WO2005012575A1 (en) 2003-08-01 2005-02-10 U.S. Genomics, Inc. Methods and compositions related to the use of sequence-specific endonucleases for analyzing nucleic acids under non-cleaving conditions
WO2005017205A2 (en) 2003-08-04 2005-02-24 U. S. Genomics, Inc. Nucleic acid mapping using linear analysis
WO2005022162A1 (en) 2003-08-21 2005-03-10 U.S. Genomics, Inc. Quantum dots and methods of use thereof
US20050142595A1 (en) 2003-11-07 2005-06-30 U.S. Genomics, Inc. Intercalator FRET donors or acceptors
WO2005047471A2 (en) 2003-11-07 2005-05-26 U.S. Genomics, Inc. Improved fret efficiency methods
US20050123974A1 (en) 2003-11-17 2005-06-09 U.S. Genomics, Inc. Methods and compositions relating to single reactive center reagents
JP2007518107A (en) 2004-01-13 2007-07-05 ユー．エス． ジェノミクス， インコーポレイテッド Detection and quantification of analytes in solution using polymers
US20050196790A1 (en) 2004-02-05 2005-09-08 U.S. Genomics, Inc. Methods for detection and quantitation of minimum length polymers
US20050221408A1 (en) 2004-03-19 2005-10-06 U.S. Genomics, Inc. Compositions and methods for detection of single molecules
WO2006017274A2 (en) * 2004-07-13 2006-02-16 U.S. Genomics, Inc. Systems and methods for sample modification using fluidic chambers
US7351538B2 (en) 2004-08-23 2008-04-01 U.S. Genomics Systems and methods for detecting and analyzing polymers
WO2006098772A2 (en) * 2004-10-13 2006-09-21 U.S. Genomics, Inc. Systems and methods for measurement optimization
WO2006044728A2 (en) * 2004-10-18 2006-04-27 U.S.Genomics, Inc. Methods for isolation of nucleic acids from prokaryotic spores
US20060160231A1 (en) * 2004-11-24 2006-07-20 U.S. Genomics, Inc. Linear analysis of polymers
US20060134679A1 (en) * 2004-12-17 2006-06-22 U.S. Genomics, Inc. Methods and compositions for acquiring information from unstretched polymer conformations
US20060292617A1 (en) 2005-06-23 2006-12-28 U.S. Genomics, Inc. Methods and compositions for analysis of microRNA
US20060292616A1 (en) 2005-06-23 2006-12-28 U.S. Genomics, Inc. Single molecule miRNA-based disease diagnostic methods
US20070042406A1 (en) 2005-07-18 2007-02-22 U.S. Genomics, Inc. Diffusion mediated clean-up of a target carrier fluid
US20070128083A1 (en) 2005-07-18 2007-06-07 U.S. Genomics, Inc. Microfluidic methods and apparatuses for sample preparation and analysis

Also Published As

Publication number Publication date
EP1786932A4 (en) 2010-10-27
US20060078915A1 (en) 2006-04-13
US20080254549A1 (en) 2008-10-16
US7402422B2 (en) 2008-07-22
WO2006036388A2 (en) 2006-04-06
US20060228747A1 (en) 2006-10-12
WO2006036388A3 (en) 2006-10-19
US7351538B2 (en) 2008-04-01
EP1786932A2 (en) 2007-05-23

Similar Documents

Publication Publication Date Title
WO2006036388B1 (en) Systems and methods for detecting and analyzing polymers
JP6039717B2 (en) Detection system and method
US20210072141A1 (en) Radiation Carrier and Use Thereof in an Optical Sensor
CA2580589C (en) Microfluidic detection system
US9551030B2 (en) Filter architecture for analytical devices
US7842465B2 (en) Immunocytostaining methods for enhanced dye ratio discrimination in rare event detection
US10101321B2 (en) Detecting target molecules in a sample
AU2002336771C1 (en) Imaging of microarrays using fiber optic exciter
US7604981B1 (en) Excitable target marker detection
AU2002336771A1 (en) Imaging of microarrays using fiber optic exciter
JP2013511713A (en) Improved fluorescence detection and method
US20040023229A1 (en) Direct detection of individual molecules
US20240027325A1 (en) Method and apparatus for flow-based, single-particle and/or single-molecule analysis
KR100483706B1 (en) A Apparatus for the Detection of Laser-induced Epifluoresecne
US7545498B2 (en) System and method for removing auto-fluorescence through the use of multiple detection channels
KR101025770B1 (en) Bio chip scanner
GB2595520A (en) A diagnostic device and method
JP2005321347A (en) Photodetector
JP2009150665A (en) Single-molecule fluorescence/phosphorescence analysis method and device therefor
TW202238105A (en) Detection device for detecting biological particles
CN115786098A (en) Light path structure for array scanning type fluorescent quantitative PCR detection
JP2014071059A (en) Optical detector

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2005810258

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2005810258

Country of ref document: EP