OPTICAL SYSTEM AND ASSAY CHIP FOR PROBING, DETECTING AND ANALYZING MOLECULE
First Claim
1. An instrument configured to interface with an assay chip comprising a plurality of sample wells, each sample well of the plurality of sample wells configured to receive a sample, the instrument comprising:
- at least one pulsed excitation light source configured to excite the sample of at least a portion of the plurality of sample wells;
a plurality of sensors, each sensor of the plurality of sensors corresponding to a sample well of the plurality of sample wells, wherein each sensor of the plurality of sensors is configured to detect emission energy from the sample in a respective sample well, wherein each sensor of the plurality of sensors is capable of detecting the detection time of the emission energy; and
at least one optical element configured to direct the emission energy from each sample well of the plurality of sample wells towards a respective sensor of the plurality of sensors.
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Accused Products
Abstract
Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.
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Citations
62 Claims
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1. An instrument configured to interface with an assay chip comprising a plurality of sample wells, each sample well of the plurality of sample wells configured to receive a sample, the instrument comprising:
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at least one pulsed excitation light source configured to excite the sample of at least a portion of the plurality of sample wells; a plurality of sensors, each sensor of the plurality of sensors corresponding to a sample well of the plurality of sample wells, wherein each sensor of the plurality of sensors is configured to detect emission energy from the sample in a respective sample well, wherein each sensor of the plurality of sensors is capable of detecting the detection time of the emission energy; and at least one optical element configured to direct the emission energy from each sample well of the plurality of sample wells towards a respective sensor of the plurality of sensors. - View Dependent Claims (2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13)
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14. An apparatus comprising:
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an assay chip comprising a plurality of pixels, each of the plurality of pixels comprising; a sample well configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction, wherein the at least one element is selected from the group consisting of a refractive element, a diffractive element, a plasmonic element and a resonator; and a light path along which the emission energy travels from the sample well toward a sensor; and an instrument configured to interface with the assay chip, the instrument comprising; at least one pulsed excitation light source configured to excite the sample in each sample well; a plurality of sensors, each sensor of the plurality of sensors corresponding to a respective sample well, wherein each sensor of the plurality of sensors is configured to detect emission energy from the sample in the respective sample well, wherein each sensor of the plurality of sensors is capable of detecting the detection time of the emission energy; and at least one optical element configured to direct the emission energy from each sample well towards a respective sensor of the plurality of sensors. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 23, 26, 27)
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24. The apparatus of claim 22, wherein the at least one wavelength dependent element is a diffractive optical element.
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25. The apparatus of claim 22, wherein the at least one wavelength dependent element is a spectral filter.
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28. A method of analyzing a specimen, the method comprising:
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providing the specimen on the top surface of an assay chip comprising a plurality of sample wells; aligning the chip with an instrument comprising at least one excitation light source and at least one sensor; exciting a sample from the specimen in at least one of the plurality of sample wells with pulsed excitation light from the at least one pulsed excitation light source; and detecting, with the at least one sensor, emission energy generated by the sample in the at least one sample well in response to excitation by the excitation light, wherein the at least one sensor is capable of determining the lifetime of the emission energy generated by the sample. - View Dependent Claims (29, 30, 31, 32, 33)
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34. A method for sequencing a target nucleic acid molecule, comprising:
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(a) providing a chip adjacent to an instrument that includes a pulsed excitation source and a sensor capable of detecting at least one temporal property of light, wherein said chip includes at least one well that is operatively coupled to said excitation source and said sensor when said chip is at a sensing position of said instrument, and wherein said well contains said target nucleic acid molecule, a polymerizing enzyme and a plurality of types of nucleotides or nucleotide analogs; (b) with said chip at said sensing position, performing an extension reaction at a priming location of said target nucleic acid molecule in the presence of said polymerizing enzyme to sequentially incorporate said nucleotides or nucleotide analogs into a growing strand that is complementary to said target nucleic acid molecule, wherein upon incorporation and excitation by excitation energy from said excitation source, said nucleotides or nucleotides analogs emit signals in said well; (c) using said sensor to detect spatial and/or temporal distribution patterns of said signals that are distinguishable for said plurality of types of nucleotides or nucleotide analogs; and (d) identifying said nucleotides or nucleotide analogs based on said spatial and/or temporal distribution patterns of said signals, thereby sequencing said target nucleic acid molecule. - View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)
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51. A method for nucleic acid sequencing, comprising:
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(a) providing a chip adjacent to an instrument, wherein said chip includes a plurality of wells that are each operatively coupled to (i) a pulsed excitation source and (ii) a sensor of said instrument when said chip is at a sensing position of said instrument, and wherein an individual well of said plurality contains said target nucleic acid molecule, a polymerizing enzyme and a plurality of types of nucleotides or nucleotide analogs; (b) with said chip at said sensing position, subjecting said target nucleic acid molecule to a polymerization reaction to yield a growing strand that is complementary to said target nucleic acid molecule in the presence of said nucleotides or nucleotide analogs and said polymerizing enzyme, wherein said nucleotides or nucleotides analogs emit signals in said individual well upon excitation by excitation energy from said excitation source during incorporation; (c) using said sensor to detect temporal distribution patterns of said signals that are distinguishable for said plurality of types of nucleotides or nucleotide analogs; and (d) identifying a sequence of said target nucleic acid molecule based on said spatial and/or temporal distribution patterns of said signals. - View Dependent Claims (52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62)
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Specification