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
  • G01N21/6408—Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
• • 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"
• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
  • G01N21/6454—Individual samples arranged in a regular 2D-array, e.g. multiwell plates using an integrated detector array
• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• • H—ELECTRICITY
  • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
  • H10F—INORGANIC SEMICONDUCTOR DEVICES SENSITIVE TO INFRARED RADIATION, LIGHT, ELECTROMAGNETIC RADIATION OF SHORTER WAVELENGTH OR CORPUSCULAR RADIATION
  • H10F39/00—Integrated devices, or assemblies of multiple devices, comprising at least one element covered by group H10F30/00, e.g. radiation detectors comprising photodiode arrays
  • H10F39/80—Constructional details of image sensors
  • H10F39/802—Geometry or disposition of elements in pixels, e.g. address-lines or gate electrodes
• • H—ELECTRICITY
  • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
  • H10F—INORGANIC SEMICONDUCTOR DEVICES SENSITIVE TO INFRARED RADIATION, LIGHT, ELECTROMAGNETIC RADIATION OF SHORTER WAVELENGTH OR CORPUSCULAR RADIATION
  • H10F39/00—Integrated devices, or assemblies of multiple devices, comprising at least one element covered by group H10F30/00, e.g. radiation detectors comprising photodiode arrays
  • H10F39/80—Constructional details of image sensors
  • H10F39/803—Pixels having integrated switching, control, storage or amplification elements
• • H—ELECTRICITY
  • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
  • H10F—INORGANIC SEMICONDUCTOR DEVICES SENSITIVE TO INFRARED RADIATION, LIGHT, ELECTROMAGNETIC RADIATION OF SHORTER WAVELENGTH OR CORPUSCULAR RADIATION
  • H10F39/00—Integrated devices, or assemblies of multiple devices, comprising at least one element covered by group H10F30/00, e.g. radiation detectors comprising photodiode arrays
  • H10F39/80—Constructional details of image sensors
  • H10F39/806—Optical elements or arrangements associated with the image sensors
• • 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
• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N2021/6463—Optics
• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N2021/6463—Optics
  • G01N2021/6471—Special filters, filter wheel

Definitions

• Some aspects of the disclosure relate to an integrated circuit, comprising: at least one photodetection region configured to generate charge carriers responsive to incident photons emitted from a sample; at least one charge storage region configured to receive the charge carriers from the photodetection region; and at least one component configured to obtain information about the incident photons, the information comprising at least four members selected from s group comprising wavelength information, luminescence lifetime information, intensity information, pulse duration information, and interpulse duration information.
• Some aspects of the disclosure relate to a method, comprising: exciting a sample with excitation light; determining interpulse duration characteristics of light emitted by the sample in response to the excitation light; and determining at least one member selected from a group comprising wavelength, intensity, lifetime, and pulse duration characteristics of the light emitted by the sample in response to the excitation light.
• time-gating techniques may be used to obtain measurements of fluorescence lifetime, pulse width/duration, and/or interpulse duration of an emission from a sample under analysis.
• one or more measurements for intensity of emission light are obtained by collecting and quantifying charge carriers generated by incident photons in one or more charge storage regions.
• the inventors have recognized that such fluorescence lifetime, pulse duration, interpulse duration, and/or intensity information may be used as degrees of discrimination in some embodiments of 2-D, 3-D, 4-D and/or 5-D discrimination sample analysis techniques in addition or alternative to wavelength information.
• FIG. 1-lC is a circuit diagram of pixel 1-112 of FIG. 1-lB, according to some embodiments.
• photodetection region PPD is coupled to multiple storage regions SDO and SD1.
• Storage region SD1 and transfer gate TGI may be configured in the manner described for storage region SDO and transfer gate TGO.
• Pixel 1-112 may be configured such that only one of storage regions SDO and SD1 receive charge carriers from photodetection region PPD at a given time.
• FIG. 1-2A plots two different fluorescent emission probability curves (A and B), which can be representative of fluorescent emission from two different fluorescent molecules, for example.
• curve A dashed line
• a probability pA(t) of a fluorescent emission from a first molecule may decay with time, as depicted.
• signals that are read out can provide a histogram of bins that are representative of the fluorescent emission decay characteristics, for example.
• An example process is illustrated in FIG. 1-2D and FIG. 1-2E, for which two charge-storage regions are used to acquire fluorescent emission from the reaction chambers.
• the histogram’s bins can indicate a number of photons detected during each time interval after excitation of the fluorophore(s) in a reaction chamber.
• signals for the bins will be accumulated following a large number of excitation pulses, as depicted in FIG. 1-2D.
• the excitation pulses can occur at times tei, t e 2, t e 3, ...
• a depth of charge storage region SDO and/or a depth of charge storage region SD1 may be configured such that each charge storage region predominantly collects incident photons having a particular wavelength and/or range of wavelengths.
• the difference in depth between charge storage region(s) SDO and/or SD1 and photodetection region PPD may be configured such that each charge storage region predominantly collects incident photons having a particular wavelength and/or range of wavelengths.
• the higher wavelength photons of the above example may have a wavelength greater than 600nm, and the lower wavelength photons may have a wavelength less than 600 nm. In some embodiments, the higher wavelength photons of the above example may have a wavelength greater than 600nm, and the lower wavelength photons may have a wavelength less than 550 nm. In some embodiments, the higher wavelength photons of the above example may have a wavelength greater than 550nm, and the lower wavelength photons may have a wavelength less than 550 nm. In some embodiments, pixels described herein may have an area less than or equal to 40 square microns.
• FIG. 2-2 is a side view of pixel 2-212, which may have a time-gated charge storage region and a direct-excitation charge storage region configured to receive incident photons from a light source via a photodetection region, according to some embodiments.
• Pixel 2-212 may be configured in the manner described for pixel 2-112. For instance, as shown in FIG. 2-2, pixel 2-212 includes photodetection region PPD, charge storage regions SD0 and SD1, and transfer gate TG0.
• FIG. 2-2 may alternatively or additionally include one or more barriers such as metal layer M0, and/or the barrier illustrated extending from metal layer M0 into the pixel.
• FIG. 2-4 is a side view of pixel 2-412 having two photodetection regions of different depths and two time-gated charge storage regions, according to some embodiments.
• Pixel 2-412 may be configured in the manner described for pixel 2-112 in connection with FIG. 2-1.
• pixel 2-412 includes photodetection region PPDO, charge storage regions SDO and SD1, and transfer gate TGO.
• pixel 2-412 may include regions of different depths.
• pixel 2-412 may include photodetection region PPD1 and transfer gate TGI, and photodetection regions PPDO and PPD1 are shown having different depths.
• one or more charge storage regions may be positioned between adjacent ones of the photodetection regions.
• pixel 2-512 may include one or more barriers 2-502 (e.g., p-doped barriers “Pwell”) positioned between adjacent photodetection regions PD.
• barriers 2-502 may be doped with an opposite conductivity type than photodetection regions PPDO, PPD1, PPD2, such as being p-type doped when photodetection regions PPDO, PPD1, and PPD2 are n-type doped.
• some (or all) of the photodetection regions may have a same depth.
• the charge storage regions may have different depths. By including more regions of different depths, such as illustrated in FIG. 2-5, more timing and/or spectral information of the incident light may be obtained for processing.
• charge storage regions SD2 and SD3 may have a same depth and may be configured to receive charge carriers from photodetection region PPD1 via charge transfer channels having a same depth.
• charge storage regions SDO and SD3 may be configured substantially identically to one another, and charge storage regions SD1 and SD2 may be configured substantially identically to one another.
• charge storage regions SDO and SD2 may be configured substantially identically to one another, and charge storage regions SD1 and SD3 may be configured substantially identically to one another. It should be appreciated that slight differences, such as due to inconsistencies in manufacturing pixel 3-112, may result in greater differences between substantially identically configured charge storage regions.
• charge storage regions of pixel 3-112 may be configured differently from one another, such has having different depths from one another.
• FIG. 4-2 is a side view of pixel 4-212, which may have an optical sorting element, two photodetection regions, and two time-gated charge storage regions, according to some embodiments.
• Pixel 4-212 may be configured in the manner described for pixel 4-112 in connection with FIG. 4-1.
• pixel 4-212 is shown in FIG. 4-2 having photodetection regions PPDO and PPD1, charge storage regions SDO and SD1, and transfer gates TG0 and TGI.
• pixel 4-212 includes one or more barriers positioned at least partially between photodetection regions PPDO and PPD1 and respective charge storage regions SDO and SD1. Also shown in FIG.
• a two-dimensional discrimination technique for identifying a sample of interest is based on wavelength information and lifetime information of emission light associated with the sample.
• a three-dimensional discrimination technique may identify a sample of interest based on information of any three of lifetime, wavelength, pulse duration, interpulse duration, and intensity of emission light associated with the sample.
• a three-dimensional discrimination technique for identifying a sample of interest is based on lifetime information, wavelength information, and intensity information of emission light associated with the sample.
• a three-dimensional discrimination technique for identifying a sample of interest is based on any two of wavelength information, lifetime information, and intensity information, and any one of pulse duration information and interpulse duration information of emission light associated with the sample.
• the excitation source 5-106 may be configured to provide excitation light to the integrated device 5-102. As illustrated schematically in FIG. 5-1A, the integrated device 5- 102 has a plurality of pixels 5-112, where at least a portion of pixels may perform independent analysis of a sample of interest. Such pixels 5-112 may be referred to as “passive source pixels” since a pixel receives excitation light from a source 5-106 separate from the pixel, where excitation light from the source excites some or all of the pixels 5-112. Excitation source 5-106 may be any suitable light source. Examples of suitable excitation sources are described in U.S. Pat. Application No.
• the output pulses 5-122 from a pulsed optical source can be coupled into one or more optical waveguides 5-312 on a bio-optoelectronic chip 5-140, for example.
• the optical pulses can be coupled to one or more waveguides via a grating coupler 5-310, though coupling to an end of one or more optical waveguides on the optoelectronic chip can be used in some embodiments.
• a quad detector 5-320 can be located on a semiconductor substrate 5-305 (e.g., a silicon substrate) for aiding in alignment of the beam of optical pulses 5-122 to a grating coupler 5-310.
• the one or more waveguides 5-312 and reaction chambers or reaction chambers 5-330 can be integrated on the same semiconductor substrate with intervening dielectric layers (e.g., silicon dioxide layers) between the substrate, waveguide, reaction chambers, and photodetectors 5-322.
• a second bin can accumulate carriers produced during an interval between times h and t 3
• a third bin can accumulate carriers produced during an interval between times t 3 and U.
• the relative positions of amino acids in a protein are determined using a series of amino acid labeling and cleavage steps.
• the multi dimensional discrimination techniques described herein may be implemented with the protein sequencing methods described in U.S. Pat. Application No. 16/686,028 titled “METHODS AND COMPOSITIONS FOR PROTEIN SEQUENCING,” filed November 15, 2019 under Attorney Docket No. R0708.70042US02 and PCT Application No. PCT/US 19/61831 titled “METHODS AND COMPOSITIONS FOR PROTEIN SEQUENCING,” filed November 15, 2019 under Attorney Docket No. R0708.70042WO00, both which are hereby incorporated by reference in their entireties
• the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements.
• This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.

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• Optical Measuring Cells (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)
• Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

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• 2021
  • 2021-03-02 TW TW110107318A patent/TW202147591A/zh unknown
  • 2021-03-02 EP EP21717265.9A patent/EP4111178A1/en not_active Withdrawn
  • 2021-03-02 US US17/190,331 patent/US11719639B2/en active Active
  • 2021-03-02 JP JP2022552603A patent/JP2023515682A/ja not_active Withdrawn
  • 2021-03-02 KR KR1020227034235A patent/KR20220148273A/ko not_active Withdrawn
  • 2021-03-02 WO PCT/US2021/020521 patent/WO2021178438A1/en not_active Ceased
• 2023
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