Compositions useful for the detection of single molecules in a sample are provided. In some aspects, the disclosure provides a nucleotide connected to a nucleic acid comprising a FRET label comprising at least three luminescent molecules. In some embodiments, the nucleic acids described herein comprise one or more structural features that provide enhanced fluorescence intensity. In some aspects, methods of sequencing using the labeled nucleotides of the disclosure are provided.
Aspects of the disclosure relate to methods and compositions for identifying, isolating, and/or sequencing a target protein or peptide from a sample of proteins or peptides.
Disclosed herein are embodiments of a sensor chip package that comprises a cap that engages the sensor chip and serving as a helmet that covers some or all of a top surface of the sensor chip. Aspects of the present disclosure provide a cap design that has an optical component to deflect an excitation light signal towards the top surface of sensor chip to excite samples within the sample wells. In some embodiments, the optical component may be a mirror or prism that provides a right angle coupling of excitation light signal to the sensor chip. Some embodiments are directed to a cap design in which a mirror is supported by multiple support surfaces of the cap body such that a mirror of a different length will provide a different tilt angle when supported by the same support surfaces.
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region and a drain region electrically coupled to the photodetection region, and the photodetection region may be configured to induce an intrinsic electric field in a direction from the photodetection region to the drain region(s). In some embodiments, a charge storage region and the drain region may be positioned on a same side of the photodetection region. In some embodiments, at least one drain layer may be configured to receive incident photons and/or charge carriers via the photodetection region. In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in the plurality of pixels.
In some embodiments, an integrated circuit includes multiple charge storage regions configured to receive charge carriers from a photodetection region in response to a single excitation of a sample. In some embodiments, an integrated circuit includes first and second charge transfer paths configured to electrically couple a photodetection region to first and second charge storage regions, with the second charge transfer path bypassing the first charge storage region. In some embodiments, an integrated circuit includes a photodetection region configured to induce an intrinsic electric field having a vector component in at least three substantially perpendicular directions. In some embodiments, an integrated circuit includes multiple transfer gates configured to control charge carrier transfer out of a photodetection region in different directions. In some embodiments, an integrated circuit includes a photodetection region and multiple transfer gates configured to control charge carrier transfer from the photodetection region to one or more drain regions.
Apparatus and methods for producing ultrashort optical pulses are described. A high-power, solid-state, passively mode-locked laser can be manufactured in a compact module that can be incorporated into a portable instrument. The mode-locked laser can produce sub-50-ps optical pulses at a repetition rates between 200 MHz and 50 MHz, rates suitable for massively parallel data-acquisition. The optical pulses can be used to generate a reference clock signal for synchronizing data-acquisition and signal-processing electronics of the portable instrument.
H01S 3/08 - Construction or shape of optical resonators or components thereof
H01S 3/081 - Construction or shape of optical resonators or components thereof comprising three or more reflectors
H01S 3/0941 - Processes or apparatus for excitation, e.g. pumping using optical pumping by coherent light of a semiconductor laser, e.g. of a laser diode
Compositions useful for the detection of single molecules in a sample are provided. In some aspects, the disclosure provides a nucleic acid connected to a nucleotide and two or more luminescent labels. In some embodiments, the nucleic acids described herein comprise one or more structural features that provide enhanced fluorescence intensity. In some aspects, methods of sequencing using the labeled nucleotides of the disclosure are provided.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C07H 19/073 - Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
C07H 19/173 - Purine radicals with 2-deoxyribosyl as the saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6816 - Hybridisation assays characterised by the detection means
8.
DATA ACQUISITION CONTROL FOR ADVANCED ANALYTIC INSTRUMENTS HAVING PULSED OPTICAL SOURCES
Instrument control and data acquisition in advanced analytic systems that utilize optical pulses for sample analysis are described. Clocking signals for data acquisition, data processing, communication, and/or other data handling functionalities can be derived from an on-board pulsed optical source, such as a passively mode-locked laser. The derived clocking signals can operate in combination with one or more clocking signals from a stable oscillator, so that instrument operation and data handling can tolerate interruptions in operation of the pulsed optical source.
The present disclosure provides improvements to adjustable optical mounts that increase the stability of the optical mount alignment while providing for the alignment to be easy adjusted. Various aspects of the present disclosure related to an optical mount for adjusting the position of an optical component, the optical mount comprising: a front plate comprising a front surface, a back surface, and a shaft, wherein the front surface is configured to support the optical component, and the shaft extends from the back surface of the front plate; and a base comprising a bore, wherein the bore is configured to receive the shaft of the front plate such that the front plate is configured to rotate around an axis of rotation of the front plate that is aligned with the shaft.
G02B 7/182 - Mountings, adjusting means, or light-tight connections, for optical elements for mirrors for mirrors
G02B 7/198 - Mountings, adjusting means, or light-tight connections, for optical elements for mirrors for mirrors with means for adjusting the mirror relative to its support
10.
INTEGRATED CIRCUIT WITH SEQUENTIALLY-COUPLED CHARGE STORAGE AND ASSOCIATED TECHNIQUES
Described herein are techniques that improve the collection and readout of charge carriers in an integrated circuit. Some aspects of the present disclosure relate to integrated circuits having pixels with a plurality of charge storage regions. Some aspects of the present disclosure relate to integrated circuits configured to substantially simultaneously collect and read out charge carriers, at least in part. Some aspects of the present disclosure relate to integrated circuits having a plurality of pixels configured to transfer charge carriers between charge storage regions within each pixel substantially at the same time. Some aspects of the present disclosure relate to integrated circuits having three or more sequentially coupled charge storage regions. Some aspects of the present disclosure relate to integrated circuits capable of increased charge transfer rates. Some aspects of the present disclosure relate to techniques for manufacturing and operating integrated circuits according to the other techniques described herein.
Methods of sequencing molecules based on luminescence lifetimes and/or intensities are provided. In some aspects, methods of sequencing nucleic acids involve determining the luminescence lifetimes, and optionally luminescence intensities, of a series of luminescently labeled nucleotides incorporated during a nucleic acid sequencing reaction. In some aspects, the disclosure provides compositions comprising luminescently labeled nucleotides.
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C12Q 1/6816 - Hybridisation assays characterised by the detection means
12.
INTEGRATED PHOTODETECTOR WITH DIRECT BINNING PIXEL
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit includes at least one charge carrier storage region. The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers directly into the at least one charge carrier storage region based upon times at which the charge carriers are produced.
Heat transfer systems and methods are generally described. A bioanalytical instrument may employ a variety of heat-generating optoelectronic chips to perform biochemical assays. In some embodiments, the instrument may include a heat transfer system configured to cool the chips by thermally coupling them to a heat sink. The heat transfer system may include an elastically deformable flexible plate to conform to the differently-sized chips, withstand numerous cycles of chip insertion/removal, and respond to pressures exerted by supporting structures of the instrument. The heat transfer system may include a thermally conductive material indirectly but thermally coupled to the chip via the flexible plate, which may be positioned between the heat sink and the flexible plate.
Aspects of the disclosure provide methods and compositions for determining the identity of an analyte using molecular barcodes and single-molecule directed evolution of target biomolecules (e.g., proteins or aptamers).
Some aspects 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 controller configured to obtain information about the incident photons, the information comprising at least one member selected from the group comprising pulse duration and interpulse duration and at least one member selected from the group comprising wavelength information, luminescence lifetime information, and intensity information. In some embodiments, the information comprises at least three, four, and/or five members selected from the group comprising wavelength information, luminescence lifetime information, intensity information, pulse duration information, and interpulse duration information. In some embodiments, the information obtained may be used to identify the sample.
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit also includes at least one charge carrier storage region. The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers into the at least one charge carrier storage region based upon times at which the charge carriers are produced.
Aspects of the application provide compounds of formula (I):
Aspects of the application provide compounds of formula (I):
Aspects of the application provide compounds of formula (I):
or a salt thereof, which may be useful as chromophores and/or fluorophores for labeling highly water-soluble biomolecules (e.g., proteins, polypeptides, nucleotides, or oligonucleotides).
System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device may include multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes a surface having a trench region recessed from a portion of the surface and an array of sample wells, disposed in the trench region. The integrated device also includes a waveguide configured to couple excitation energy to at least one sample well in the array and positioned at a first distance from a surface of the trench region and at a second distance from the surface in a region separate from the trench region. The first distance is smaller than the second distance. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
19.
SLICED GRATING COUPLER WITH INCREASED BEAM ALIGNMENT SENSITIVITY
Apparatus and methods relating to coupling radiation from an incident beam into a plurality of waveguides with a grating coupler are described. A grating coupler can have offset receiving regions and grating portions with offset periodicity to improve sensitivity of the grating coupler to misalignment of the incident beam.
G02B 6/12 - Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
20.
INTEGRATED CIRCUIT WITH SEQUENTIALLY-COUPLED CHARGE STORAGE AND ASSOCIATED TECHNIQUES
Described herein are techniques that improve the collection and readout of charge carriers in an integrated circuit. Some aspects of the present disclosure relate to integrated circuits having pixels with a plurality of charge storage regions. Some aspects of the present disclosure relate to integrated circuits configured to substantially simultaneously collect and read out charge carriers, at least in part. Some aspects of the present disclosure relate to integrated circuits having a plurality of pixels configured to transfer charge carriers between charge storage regions within each pixel substantially at the same time. Some aspects of the present disclosure relate to integrated circuits having three or more sequentially coupled charge storage regions. Some aspects of the present disclosure relate to integrated circuits capable of increased charge transfer rates. Some aspects of the present disclosure relate to techniques for manufacturing and operating integrated circuits according to the other techniques described herein.
Optical waveguides and couplers for delivering light to an array of photonic elements in a photonic integrated device. The photonic integrated device and related instruments and systems may be used to analyze samples in parallel. The photonic integrated device may include a grating coupler configured to receive light from an external light source and optically couple with multiple waveguides configured to optically couple with sample wells of the photonic integrated device.
G02B 6/12 - Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
G02B 6/122 - Basic optical elements, e.g. light-guiding paths
G02B 6/124 - Geodesic lenses or integrated gratings
Aspects of this disclosure relate to luminescently labeled nucleic acid nanostructures and methods and compositions for the detection and/or sequencing of one or more target molecules derived from a sample.
System and methods for optical power distribution to a large numbers of sample wells within an integrated device that can analyze single molecules and perform nucleic acid sequencing are described. The integrated device may include a grating coupler configured to receive an optical beam from an optical source and optical splitters configured to divide optical power of the grating coupler to waveguides of the integrated device positioned to couple with the sample wells. Outputs of the grating coupler may vary in one or more dimensions to account for an optical intensity profile of the optical source.
G02B 6/12 - Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
G01N 21/25 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01M 11/00 - Testing of optical apparatus; Testing structures by optical methods not otherwise provided for
G02B 6/122 - Basic optical elements, e.g. light-guiding paths
G02B 6/293 - Optical coupling means having data bus means, i.e. plural waveguides interconnected and providing an inherently bidirectional system by mixing and splitting signals with wavelength selective means
G02B 6/30 - Optical coupling means for use between fibre and thin-film device
Described herein are techniques to reduce or remove the impact of secondary path photons and/or charge carriers on storage bins of an integrated device to improve noise performance, and thus, sample analysis. Some embodiments relate to optical rejection techniques such as including an optical barrier positioned to block at least some photons from reaching the storage bins. Some embodiments relate to electrical rejection techniques such as including an electrical barrier configured to block at least some charge carriers from reaching the storage bins along at least one secondary path. Some embodiments relate to an integrated device in which at least one storage bin is shaped and/or positioned relative to the photodetector to facilitate receipt of some charge carriers (e.g., fluorescent emission charge carriers) and/or photons and to impede receipt of other charge carriers (e.g., noise charge carriers) and/or photons.
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region and a drain region electrically coupled to the photodetection region, and the photodetection region may be configured to induce an intrinsic electric field in a direction from the photodetection region to the drain region(s). In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in a plurality of time-binning pixels. In some embodiments, an optical component for optical rejection is provided in between a waveguide and the time-binning pixel and configured to block at least some excitation photons in a pulsed light stream from arriving at the photodetection region. In some embodiments, the time-binning pixel does not comprise a time-gated transistor for electronic rejection configured to block a transfer of charge carriers associated with excitation photons in the pulsed light stream.
H04N 25/771 - Pixel circuitry, e.g. memories, A/D converters, pixel amplifiers, shared circuits or shared components comprising storage means other than floating diffusion
H04N 25/59 - Control of the dynamic range by controlling the amount of charge storable in the pixel, e.g. modification of the charge conversion ratio of the floating node capacitance
Techniques for multi-dimensional signal analysis are described herein. The techniques may be used in one or more sequencing applications. For example, according to some aspects, there is provided a method comprising: determining information about a sample that emits emission light in response to excitation light based on at least one of pulse duration and interpulse duration and at least two of wavelength, intensity, and lifetime of the emission light, wherein the sample comprises a reagent configured to be coupled to a luminescent label, and wherein a shielding element is disposed between the reagent and the luminescent label.
Aspects of the disclosure provide methods of identifying and sequencing proteins, polypeptides, and amino acids, and compositions useful for the same. In some aspects, the disclosure provides amino acid recognition molecule compositions, such as amino acid binding proteins comprising different labels, and methods of polypeptide sequencing using such compositions.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
Aspects of the application relate to methods and systems for obtaining information regarding multiple amino acids in a polypeptide based on binding interactions between the polypeptide and one or more amino acid recognizers. Kinetic signature information may be obtained from a series of signal pulses indicative of a series of binding events between one or more amino acid recognizers and an amino acid of a polypeptide (e.g., a terminal amino acid, an internal amino acid). The kinetic signature information (e.g., pulse duration, interpulse duration, recognition segment (RS) duration, intersegment duration) may be used to determine one or more chemical characteristics (e.g., identity, modification) of multiple amino acids of the polypeptide.
A method includes obtaining, from one or more sequencing devices, raw data detected from luminescent labels associated with nucleotides during nucleotide incorporation events; and processing the raw data to perform a comparison of base calls produced by a learning enabled, automatic base calling module of the one or more sequencing devices with actual values associated with the raw data, wherein the base calls identify one or more individual nucleotides from the raw data. Based on the comparison, an update to the learning enabled, automatic base calling module is created using at least some of the obtained raw data, and the update is made available to the one or more sequencing devices.
The present disclosure relates to compounds and methods for selective C-terminal functionalization of peptides. In certain embodiments, the compounds have improved water-solubility, and are suitable for use in connection with peptide sequencing methodologies.
Provided herein, in some embodiments, are methods of loading an integrated device and/or chip for detection (e.g., sequencing) and methods of sequencing a target molecule.
Aspects of the present disclosure relate to techniques for reducing skew in an integrated device, such as a CMOS imaging device. In some aspects, multiple pixels of an integrated circuit may be configured to receive a same control signal and conduct charge carriers responsive to the control signal substantially at the same time. In some aspects, an integrated circuit may have modulated charge transfer channel voltage thresholds, such as by having different charge transfer channel lengths, and/or a doped portion configured to set a voltage threshold for charge transfer. In some aspects, an integrated circuit may have a via structure having a plurality of vias extending between continuous portions of at least two metal layers. In some aspects, an integrated circuit may include a row of pixels and a voltage source configured to provide a voltage to bias a semiconductor substrate of the integrated circuit along the row of pixels.
Compact optical sources and methods for producing short and ultrashort optical pulses are described. A semiconductor laser or LED may be driven with a bipolar waveform to generate optical pulses with FWHM durations as short as approximately 85 ps having suppressed tail emission. The pulsed optical sources may be used for fluorescent lifetime analysis of biological samples and time-of-flight imaging, among other applications.
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit includes a charge carrier storage region.
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit includes a charge carrier storage region.
The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers directly into the at least one charge carrier storage region based upon times at which the charge carriers are produced.
An integrated device, comprising a substrate having a first surface; and at least one pixel formed on or in the substrate. The at least one pixel comprising a reaction chamber configured to receive a sample, and a sensor configured to detect emission light emitted from the reaction chamber and at least one nanostructure disposed in a plane between a waveguide and the sensor, wherein the optical nanostructure is configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane. The waveguide is configured to couple excitation light to each pixel.
Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.
obtaining first input data for the first data modality; providing the first input data to the first encoder to generate a first feature vector; identifying a second feature vector using the joint-modality representation, the first modality embedding and the first feature vector; and generating a prediction for the prediction task using the predictor and the second feature vector.
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06N 3/084 - Backpropagation, e.g. using gradient descent
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G06F 18/214 - Generating training patterns; Bootstrap methods, e.g. bagging or boosting
G06F 18/2411 - Classification techniques relating to the classification model, e.g. parametric or non-parametric approaches based on the proximity to a decision surface, e.g. support vector machines
G06N 3/04 - Architecture, e.g. interconnection topology
G06N 3/044 - Recurrent networks, e.g. Hopfield networks
Apparatus and methods for improving optical signal collection in an integrated device are described. A microdisk can be formed in an integrated device and increase collection and/or concentration of radiation incident on the microdisk and re-radiated by the microdisk. An example integrated device that can include a microdisk may be used for analyte detection and/or analysis. Such an integrated device may include a plurality of pixels, each having a reaction chamber for receiving a sample to be analyzed, an optical microdisk, and an optical sensor configured to detect optical emission from the reaction chamber. The microdisk can comprise a dielectric material having a first index of refraction that is embedded in one or more surrounding materials having one or more different refractive index values.
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a plurality of photodetection regions and one or more intermediate regions between the photodetection regions. In some embodiments, the intermediate regions may comprise bulk semiconductor material that facilitates a transfer of noise charge carriers from the intermediate regions to drain regions associated with each photodetection region. In some embodiments, a drain device may be configured with a gate controlling the flow of charge carriers from the intermediate regions and photodetection regions to drain regions. In some embodiments, an integrated circuit may comprise an array of pixels and a control circuit configured to control a transfer of charge carriers in the array of pixels.
Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An integrated device includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits radiation; at least one element for directing the emission radiation in a particular direction; and a light path along which the emission radiation travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the integrated device. Each sensor may detect emission radiation from a sample in a respective sample well. The instrument includes an excitation light source for exciting the sample in each sample well.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
Methods and compositions for preparing nucleic acid libraries for nucleic acid sequencing are provided. In some embodiments, disclosed herein is a universal nucleic acid adaptor and methods of using same.
System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device may include multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes a surface having a trench region recessed from a portion of the surface and an array of sample wells, disposed in the trench region. The integrated device also includes a waveguide configured to couple excitation energy to at least one sample well in the array and positioned at a first distance from a surface of the trench region and at a second distance from the surface in a region separate from the trench region. The first distance is smaller than the second distance. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
43.
DEVICES AND METHODS FOR LOADING OF FLUIDIC RECEPTACLES
Aspects of this disclosure relate to systems, devices, and methods for the transfer of fluid to fluidic receptacles. In some embodiments, the fluid contains one or more molecules (e.g., one or more peptides, proteins, and/or nucleic acids) of interest, and the fluidic receptacle includes an integrated device. In certain embodiments, the one or more molecules can be immobilized on the integrated device for subsequent analysis (e.g., sequencing). Certain aspects of the present disclosure are directed towards systems and methods that can, in some instances, enhance the immobilization of the one or more molecules on the integrated device, e.g., by improving a rate of sample interaction with the integrated device. Through the use of systems, devices, and methods of the instant disclosure, target molecules may be more readily sequenced or prepared for sequencing. For example, in some embodiments, systems, devices, and methods of the instant disclosure allow automated loading of the fluidic receptacle using a fluidic device.
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region, an auxiliary region electrically coupled to the photodetection region by a first semiconductor device, and a drain region electrically coupled to the auxiliary region via a second semiconductor device. In some embodiments, a drain device may be configured with a gate controlling the flow of charge carriers to the drain region. In some embodiments, the flow of charge carriers to the drain region may occur via the second device. In some embodiments, the second device may be a diode-connected transistor. In some embodiments, the first and second semiconductor devices may advantageously decouple properties of the drain region from properties of the auxiliary region. In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in the plurality of pixels.
Aspects of this disclosure relate to systems, devices, and methods for the transfer of fluid to fluidic receptacles. In some embodiments, the fluid contains one or more molecules (e.g., one or more peptides, proteins, and/or nucleic acids) of interest, and the fluidic receptacle includes an integrated device. In certain embodiments, the one or more molecules can be immobilized on the integrated device for subsequent analysis (e.g., sequencing). Certain aspects of the present disclosure are directed towards systems and methods that can, in some instances, enhance the immobilization of the one or more molecules on the integrated device, e.g., by improving a rate of sample interaction with the integrated device. Through the use of systems, devices, and methods of the instant disclosure, target molecules may be more readily sequenced or prepared for sequencing. For example, in some embodiments, systems, devices, and methods of the instant disclosure allow automated loading of the fluidic receptacle using a fluidic device.
The present disclosure is related to peptides comprising modified aspartic acid and glutamic acid moieties, methods of making such peptides, and methods of using such modified peptides to selectively direct cleavage of peptide bonds. Selective peptide bond cleavage is advantageous in peptide sequencing applications, such as automated peptide sequencing applications.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07K 1/02 - General processes for the preparation of peptides in solution
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
47.
INTEGRATED CIRCUIT HAVING MIRRORED PIXEL CONFIGURATION
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some aspects, an integrated circuit described herein may include a first pixel and a second pixel, wherein the first pixel is proximate the second pixel in a mirrored configuration. In some aspects, an integrated circuit described herein may include a first pixel and a second pixel that is proximate to the first pixel along a row direction, and a conductive line extending along a column direction that intersects with the row direction, wherein the conductive line is in electrical communication with a first component of the first pixel and a second component of the second pixel.
H04N 5/3745 - Addressed sensors, e.g. MOS or CMOS sensors having additional components embedded within a pixel or connected to a group of pixels within a sensor matrix, e.g. memories, A/D converters, pixel amplifiers, shared circuits or shared components
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some aspects, an integrated circuit described herein may include a first pixel and a second pixel, wherein the first pixel is proximate the second pixel in a mirrored configuration. In some aspects, an integrated circuit described herein may include a first pixel and a second pixel that is proximate to the first pixel along a row direction, and a conductive line extending along a column direction that intersects with the row direction, wherein the conductive line is in electrical communication with a first component of the first pixel and a second component of the second pixel.
Disclosed herein are aspects of an optical pulse stretcher for temporally stretching a short duration pulsed light signal to reduce its peak power, thus reducing the risk of causing damage to components that receives the pulsed light signal. Some embodiments are directed to a molecule sequencing system, in which photochemical damage caused by laser pulses having high peak power may be mitigated by the optical pulse stretcher. In one embodiment, the optical pulse stretcher comprises a polarizing beam splitter, a quarter-wave plate and a single etalon disposed in series. In another embodiments, an optical pulse stretcher splits a pulsed light signal along multiple delay lines before combining the split signals together to form a stretched light signal.
Methods of preparing surfaces of sample wells are provided. In some aspects, methods of preparing a sample well surface involve contacting the sample well with a block copolymer to form an antifouling overlay over a metal oxide surface of the sample well. In some aspects, methods of passivating and/or selectively functionalizing a sample well surface are provided.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C09D 187/00 - Coating compositions based on unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
Apparatus and methods for producing ultrashort optical pulses are described. A high-power, solid-state, passively mode-locked laser can be manufactured in a compact module that can be incorporated into a portable instrument for biological or chemical analyses. The pulsed laser may produce sub-100-ps optical pulses at a repetition rate commensurate with electronic data-acquisition rates. The optical pulses may excite samples in reaction chambers of the instrument, and be used to generate a reference clock for operating signal-acquisition and signal-processing electronics of the instrument.
H01S 3/00 - Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
H01S 3/081 - Construction or shape of optical resonators or components thereof comprising three or more reflectors
H01S 3/0941 - Processes or apparatus for excitation, e.g. pumping using optical pumping by coherent light of a semiconductor laser, e.g. of a laser diode
H01S 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
H01S 3/101 - Lasers provided with means to change the location from which, or the direction in which, laser radiation is emitted
H01S 3/105 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling the mutual position or the reflecting properties of the reflectors of the cavity
H01S 3/11 - Mode locking; Q-switching; Other giant-pulse techniques, e.g. cavity dumping
H01S 3/13 - Stabilisation of laser output parameters, e.g. frequency or amplitude
Methods of forming an integrated device, and in particular forming one or more sample wells in an integrated device, are described. The methods may involve forming a metal stack over a cladding layer, forming an aperture in the metal stack, forming first spacer material within the aperture, and forming a sample well by removing some of the cladding layer to extend a depth of the aperture into the cladding layer. In the resulting sample well, at least one portion of the first spacer material is in contact with at least one layer of the metal stack.
Aspects of this disclosure related to methods, articles, kits, and/or systems for the preparation and/or study of one or more target molecules in a sample. In some embodiments, a target molecule is a peptide, a protein, or a fragment or derivative thereof. Through the use of methods, articles, kits, and/or systems of the instant disclosure, target molecules may, in some embodiment, be more readily sequenced or prepared for sequencing.
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.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
Apparatus and methods for producing ultrashort optical pulses are described. A high-power, solid-state, passively mode-locked laser can be manufactured in a compact module that can be incorporated into a portable instrument. The mode-locked laser can produce sub-50-ps optical pulses at a repetition rates between 200 MHz and 50 MHz, rates suitable for massively parallel data-acquisition. The optical pulses can be used to generate a reference clock signal for synchronizing data-acquisition and signal-processing electronics of the portable instrument.
H01S 3/0941 - Processes or apparatus for excitation, e.g. pumping using optical pumping by coherent light of a semiconductor laser, e.g. of a laser diode
H01S 3/00 - Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
H01S 3/1115 - Passive mode locking using intracavity saturable absorbers
H01S 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
Aspects of the disclosure provide methods of determining molecular barcode content based on binding interactions between a barcode recognition molecule and a molecular barcode. In some aspects, the disclosure relates to methods comprising contacting a molecular barcode with a barcode recognition molecule that binds to one or more sites on the molecular barcode, detecting a series of signal pulses, and determining the barcode content based on a barcode-specific pattern in the series of signal pulses.
The present disclosure provides techniques for improving the rate and efficiency of charge transfer within an integrated circuit configured to receive incident photons. Some aspects of the present disclosure relate to integrated circuits that are configured to induce one or more intrinsic electric fields that increase the rate and efficiency of charge transfer within the integrated circuits. Some aspects of the present disclosure relate to integrated circuits configured to induce a charge carrier depletion in the photodetection region(s) of the integrated circuits. In some embodiments, the charge carrier depletion in the photodetection region(s) may be intrinsic, in that the depletion is induced even in the absence of external electric fields applied to the integrated circuit. Some aspects of the present disclosure relate to processes for operating and/or manufacturing integrated devices as described herein.
The present disclosure provides techniques for improving the rate and efficiency of charge transfer within an integrated circuit configured to receive incident photons. Some aspects of the present disclosure relate to integrated circuits that are configured to induce one or more intrinsic electric fields that increase the rate and efficiency of charge transfer within the integrated circuits. Some aspects of the present disclosure relate to integrated circuits configured to induce a charge carrier depletion in the photodetection region(s) of the integrated circuits. In some embodiments, the charge carrier depletion in the photodetection region(s) may be intrinsic, in that the depletion is induced even in the absence of external electric fields applied to the integrated circuit. Some aspects of the present disclosure relate to processes for operating and/or manufacturing integrated devices as described herein.
Aspects of the disclosure relate to methods and systems for regenerating a sensor chip surface, including techniques for reuse of a single sensor chip in multiple sampling cycles by regenerating a surface of the sensor chip between successive sampling cycles. A method is provided for reusing an integrated device to process a sample, the sample being divided into a plurality of aliquots, the method comprising: loading a first aliquot of the plurality of aliquots into at least some of a plurality of chambers of the integrated device; sampling analytes of the first aliquot while the analytes are present in the at least some of the plurality of chambers; removing the first aliquot from the at least some of the plurality of chambers of the integrated device; and loading a second aliquot of the plurality of aliquots into the at least some of the plurality of chambers of the integrated device.
Methods and devices for ultrasensitive detection of target molecules (e.g., target nucleic acids or target proteins) from a biological sample are provided herein. In some embodiments, methods and devices enable ultrasensitive determination of the concentration of target molecules.
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.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit also includes at least one charge carrier storage region. The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers into the at least one charge carrier storage region based upon times at which the charge carriers are produced.
Described herein are techniques that improve the collection and readout of charge carriers in an integrated circuit. Some aspects of the present disclosure relate to integrated circuits having pixels with a plurality of charge storage regions. Some aspects of the present disclosure relate to integrated circuits configured to substantially simultaneously collect and read out charge carriers, at least in part. Some aspects of the present disclosure relate to integrated circuits having a plurality of pixels configured to transfer charge carriers between charge storage regions within each pixel substantially at the same time. Some aspects of the present disclosure relate to integrated circuits having three or more sequentially coupled charge storage regions. Some aspects of the present disclosure relate to integrated circuits capable of increased charge transfer rates. Some aspects of the present disclosure relate to techniques for manufacturing and operating integrated circuits according to the other techniques described herein.
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
64.
Integrated circuit with sequentially-coupled charge storage and associated techniques comprising a photodetection region and charge storage regions to induce an intrinsic electric field
Described herein are techniques that improve the collection and readout of charge carriers in an integrated circuit. Some aspects of the present disclosure relate to integrated circuits having pixels with a plurality of charge storage regions. Some aspects of the present disclosure relate to integrated circuits configured to substantially simultaneously collect and read out charge carriers, at least in part. Some aspects of the present disclosure relate to integrated circuits having a plurality of pixels configured to transfer charge carriers between charge storage regions within each pixel substantially at the same time. Some aspects of the present disclosure relate to integrated circuits having three or more sequentially coupled charge storage regions. Some aspects of the present disclosure relate to integrated circuits capable of increased charge transfer rates. Some aspects of the present disclosure relate to techniques for manufacturing and operating integrated circuits according to the other techniques described herein.
Aspects of the present disclosure relate to methods and systems for increasing the number of samples that can be processed in parallel by an integrated device An integrated device is provided having at least two reaction chambers disposed above an active photodetection area of a single pixel, such that the pixel is sensitive to photons from each of the at least two reaction chambers. In some embodiments, an integrated device may have at least four or more reaction chambers per photodetector. Signals from multiple reaction chambers may be distinguished using any combination of multiplexing techniques including techniques for waveguide multiplexing, intensity multiplexing, and/or lifetime multiplexing. According to further aspects of the technology described herein, there is provided techniques for increasing the amount of sample that can be processed by a single device by reloading an integrated device repeated times to process an increased number of samples by a single device.
Aspects of the disclosure relate to techniques for determining a measure of quantitative loading of a sample in an integrated device. According to some embodiments, there is provided a method for determining a measure of quantitative loading of a sample in an integrated device, the method comprising exciting, with excitation light from at least one excitation source, one or more reference dye molecules that, during the exciting with the excitation light, are attached to respective biomolecules of the sample bound to a surface of a chamber of one or more chambers of the integrated device, obtaining a signal emitted by the one or more reference dye molecules in response to the excitation light, and determining, based on the signal emitted by the one or more reference dye molecules, the measure of quantitative loading of the sample.
Apparatus and methods for coupling an optical beam from an optical source to a hi-tech system are described. A compact, low-cost beam-shaping and steering assembly may be located between the optical source and hi-tech system and provide automated adjustments to beam parameters such as beam position, beam rotation, and beam incident angles. The beam-shaping and steering assembly may be used to couple an elongated beam to a plurality of optical waveguides.
Aspects of the present disclosure relate to techniques for calibrating a system comprising integrated device. According to some embodiments, there is provided a method for calibrating a system comprising an integrated device, the method comprising: exciting, with light from at least one excitation source, a reference dye molecule disposed in a chamber of the integrated device; obtaining a signal emitted by the reference dye molecule, the signal containing information representative of a bleaching time of the reference dye molecule; and adjusting one or more characteristics of the system based on the bleaching time of the reference dye molecule.
Aspects of the present disclosure relate to techniques for calibrating an integrated device. According to some embodiments, there is provided a method for calibrating an integrated device, the method comprising: exciting, with light from at least one excitation source, a reference dye molecule; obtaining a signal emitted by the reference dye molecule, the signal containing information representative of at least one characteristic of the reference dye molecule; and adjusting one or more subsequent measurements obtained from a sample based on the information obtained from the signal emitted by the reference dye molecule.
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.
An integrated device and related instruments and systems for analyzing samples in parallel are described. The integrated device may include sample wells arranged on a surface of where individual sample wells are configured to receive a sample labeled with at least one fluorescent marker configured to emit emission light in response to excitation light. The integrated device may further include photodetectors positioned in a layer of the integrated device, where one or more photodetectors are positioned to receive a photon of emission light emitted from a sample well. The integrated device further includes one or more photonic structures positioned between the sample wells and the photodetectors, where the one or more photonic structures are configured to attenuate the excitation light relative to the emission light such that a signal generated by the one or more photodetectors indicates detection of photons of emission light.
G02B 6/122 - Basic optical elements, e.g. light-guiding paths
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
H01L 25/16 - Assemblies consisting of a plurality of individual semiconductor or other solid state devices the devices being of types provided for in two or more different main groups of groups , or in a single subclass of , , e.g. forming hybrid circuits
Provided herein are methods and integrated devices for improved sequencing of nucleic acid and peptide biomolecules. The present disclosure relates to improved mechanisms for protecting a luminescent label from photo-induced damage through the use of quenching moieties. Further provided herein are methods for improved immobilization of quenching moieties and other molecules of interest through functionalization with chemical moieties, such as click chemistry handles, capable of participating in cross-linking reactions. Quenching moieties may be immobilized to the surface of a sample well in a sequencing substrate or apparatus in a manner that minimizes or eliminates photobleaching of the labeled molecule. The disclosed methods provide for minimized photodamage, increased sensitivity, accuracy and length of reads during nucleic acid and polypeptide sequencing.
System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes at least one waveguide configured to propagate excitation energy to the sample wells from a region of the integrated device configured to couple with an excitation energy source. A pixel may also include at least one element for directing the emission energy towards a sensor within the pixel. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device. One of multiple markers distinguishable by temporal parameters of the emission energy may label the sample and configuration of the sensor within a pixel may allow for detection of a temporal parameter associated with the marker labeling the sample.
Methods of sequencing molecules based on luminescence lifetimes and/or intensities are provided. In some aspects, methods of sequencing nucleic acids involve determining the luminescence lifetimes, and optionally luminescence intensities, of a series of luminescently labeled nucleotides incorporated during a nucleic acid sequencing reaction.
Techniques for evaluating change points in sequencing data during a sequencing reaction is described. The techniques may include obtaining data regarding light detected over time from luminescent labels associated with at least one molecule undergoing a sequencing reaction, evaluating candidate change points of the data within a time window of the data that varies over time, and outputting information identifying a set of change points based on evaluating the candidate change points. The set of change points may be used to determine pulse segments and individual nucleotides corresponding to at least some of the pulse segments.
The invention includes methods and apparatus for separating mutations, especially rare and unknown mutations, using heteroduplex binding proteins. Nucleic acids may optionally be nicked at or near the mutation in order to promote heteroduplex binding protein recognition and binding. In particular, using the disclosed methods, it is possible to separate heteroduplexed nucleic acid strand pair from homoduplexed nucleic acid strand pairs having similar sequences and being at a much higher concentration. Once the heteroduplexed nucleic acids are isolated and recovered, it is straightforward to analyze the sequences of the heteroduplexed nucleic acids, e.g., using sequencing or hybrid assays.
An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit includes at least one charge carrier storage region. The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers directly into the at least one charge carrier storage region based upon times at which the charge carriers are produced.
Apparatus and methods relating to attenuating excitation radiation incident on a sensor in an integrated device that is used for sample analysis are described. At least one semiconductor film of a selected material and crystal morphology is located between a waveguide and a sensor in an integrated device that is formed on a substrate. Rejection ratios greater than 100 or more can be obtained for excitation and emission wavelengths that are 40 nm apart for a single layer of semiconductor material.
Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.
Methods and devices for preparing target molecules (e.g., target nucleic acids or target proteins) from a biological sample are provided herein. In some embodiments, methods and devices involve sample lysis, sample fragmentation, enrichment of target molecule(s), and/or functionalization of target molecule(s).
Aspects of the application provide methods of identifying and sequencing proteins, polypeptides, and amino acids, and compositions useful for the same. In some aspects, the application provides amino acid recognition molecules, such as amino acid binding proteins and fusion polypeptides thereof. In some aspects, the application provides amino acid recognition molecules comprising a shielding element that enhances photostability in polypeptide sequencing reactions.
Methods and devices for preparing target molecules (e.g., target nucleic acids or target proteins) from a biological sample are provided herein. In some embodiments, methods and devices involve sample lysis, sample fragmentation, enrichment of target molecule(s), and/or functionalization of target molecule(s).
Methods and devices for preparing target molecules (e.g., target nucleic acids or target proteins) from a biological sample are provided herein. In some embodiments, methods and devices involve sample lysis, sample fragmentation, enrichment of target molecule(s), and/or functionalization of target molecule(s).
Aspects of the present disclosure relate to techniques for reducing skew in an integrated device, such as a CMOS imaging device. In some aspects, multiple pixels of an integrated circuit may be configured to receive a same control signal and conduct charge carriers responsive to the control signal substantially at the same time. In some aspects, an integrated circuit may have modulated charge transfer channel voltage thresholds, such as by having different charge transfer channel lengths, and/or a doped portion configured to set a voltage threshold for charge transfer. In some aspects, an integrated circuit may have a via structure having a plurality of vias extending between continuous portions of at least two metal layers. In some aspects, an integrated circuit may include a row of pixels and a voltage source configured to provide a voltage to bias a semiconductor substrate of the integrated circuit along the row of pixels.
Aspects of the present disclosure relate to techniques for reducing skew in an integrated device, such as a CMOS imaging device. In some aspects, multiple pixels of an integrated circuit may be configured to receive a same control signal and conduct charge carriers responsive to the control signal substantially at the same time. In some aspects, an integrated circuit may have modulated charge transfer channel voltage thresholds, such as by having different charge transfer channel lengths, and/or a doped portion configured to set a voltage threshold for charge transfer. In some aspects, an integrated circuit may have a via structure having a plurality of vias extending between continuous portions of at least two metal layers. In some aspects, an integrated circuit may include a row of pixels and a voltage source configured to provide a voltage to bias a semiconductor substrate of the integrated circuit along the row of pixels.
Apparatus and techniques for electrokinetic loading of samples of interest into sub-micron-scale reaction chambers are described. Embodiments include an integrated device and related apparatus for analyzing samples in parallel. The integrated device may include at least one reaction chamber formed through a surface of the integrated device and configured to receive a sample of interest, such as a molecule of nucleic acid. The integrated device may further include electrodes patterned adjacent to the reaction chamber that produce one or more electric fields that assist loading the sample into the reaction chamber. The apparatus may further include a sample reservoir having a fluid seal with the surface of the integrated device and configured to hold a suspension containing the samples.
Apparatus and methods for producing ultrashort optical pulses are described. A high-power, solid-state, passively mode-locked laser can be manufactured in a compact module that can be incorporated into a portable instrument for biological or chemical analyses. The pulsed laser may produce sub-100-ps optical pulses at a repetition rate commensurate with electronic data-acquisition rates. The optical pulses may excite samples in reaction chambers of the instrument, and be used to generate a reference clock for operating signal-acquisition and signal-processing electronics of the instrument.
H01S 3/101 - Lasers provided with means to change the location from which, or the direction in which, laser radiation is emitted
H01S 3/13 - Stabilisation of laser output parameters, e.g. frequency or amplitude
H01S 3/105 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling the mutual position or the reflecting properties of the reflectors of the cavity
H01S 3/081 - Construction or shape of optical resonators or components thereof comprising three or more reflectors
H01S 3/11 - Mode locking; Q-switching; Other giant-pulse techniques, e.g. cavity dumping
H01S 3/0941 - Processes or apparatus for excitation, e.g. pumping using optical pumping by coherent light of a semiconductor laser, e.g. of a laser diode
H01S 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
H01S 3/00 - Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
88.
Integrated sensor for multi-dimensional signal analysis
Some aspects 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 controller configured to obtain information about the incident photons, the information comprising at least one member selected from the group comprising pulse duration and interpulse duration and at least one member selected from the group comprising wavelength information, luminescence lifetime information, and intensity information. In some embodiments, the information comprises at least three, four, and/or five members selected from the group comprising wavelength information, luminescence lifetime information, intensity information, pulse duration information, and interpulse duration information. In some embodiments, the information obtained may be used to identify the sample.
Methods and apparatus providing for the isolation of an unknown mutation from a sample comprising wild type nucleic acids and mutated nucleic acids through the application of time-varying driving fields and periodically varying mobility-altering fields to the sample within in an affinity matrix.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
B01D 29/05 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups ; Filtering elements therefor with flat filtering elements supported
B01D 35/027 - Filters adapted for location in special places, e.g. pipe-lines, pumps, stop-cocks rigidly mounted in or on tanks or reservoirs
B62D 5/06 - Power-assisted or power-driven steering fluid, i.e. using a pressurised fluid for most or all the force required for steering a vehicle
The present disclosure relates to compounds and methods for selective C-terminal functionalization of peptides. In certain embodiments, the compounds have improved water-solubility, and are suitable for use in connection with peptide sequencing methodologies.
Systems and methods for optical power distribution within an integrated device, in a substantially uniform manner, to a large number of sample wells and/or other photonic elements. The integrated device and related instruments and systems may be used to analyze samples in parallel. The integrated device may include a grating coupler configured to receive light from an excitation source and optically couple with multiple waveguides configured to couple with sample wells. Vertical extents of optical modes of individual waveguides may be modulated to adjust confinement of light within the waveguides. This modulation may enable more uniform distribution of excitation light to the sample wells, improve excitation efficiency, and prevent overpower on regions of the integrated device.
Systems and methods are described for producing an amplitude-modulated laser pulse train. The laser pulse train can be used to cause fluorescence in materials at which the pulse trains are directed. The parameters of the laser pulse train are selected to increase fluorescence relative to a constant-amplitude laser pulse train. The amplitude-modulated laser pulse trains produced using the teachings of this invention can be used to enable detection of specific molecules in applications such as gene or protein sequencing.
H01S 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
H01S 3/11 - Mode locking; Q-switching; Other giant-pulse techniques, e.g. cavity dumping
H01S 3/106 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling devices placed within the cavity
H01S 3/107 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling devices placed within the cavity using electro-optic devices, e.g. exhibiting Pockels or Kerr effect
Some aspects relate to integrated devices for obtaining timing and/or spectral information from incident light. In some embodiments, a pixel may include one or more charge storage regions configured to receive charge carriers generated responsive to incident photons from a light source, with charge carriers stored in the charge storage region(s) indicative of spectral and timing information. In some embodiments, a pixel may include regions having different depths, each configured to generate charge carriers responsive to incident photons. In some embodiments, a pixel may include multiple charge storage regions having different depths, and one or more of the charge storage regions may be configured to receive the incident photons and generate charge carriers therein. In some embodiments, a pixel may include an optical sorting element configured to direct at least some incident photons to one charge storage region and other incident photons to another charge storage region.
Disclosed herein are aspects of a pulsed laser light source for producing excitation light in an integrated bioanalytical system. In some embodiments, the light source comprises one or more laser diodes that produces pulsed light signals synchronized with a common clock source for excitation of samples within reaction chambers on at least one chip. The light source may be used to provide excitation for a system with a large sensor array with reduced cost, size and electrical power requirements.
Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region and a drain region electrically coupled to the photodetection region, and the photodetection region may be configured to induce an intrinsic electric field in a direction from the photodetection region to the drain region(s). In some embodiments, a charge storage region and the drain region may be positioned on a same side of the photodetection region. In some embodiments, at least one drain layer may be configured to receive incident photons and/or charge carriers via the photodetection region. In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in the plurality of pixels.
Techniques for performing a prediction task using a multi-modal statistical model configured to receive input data from multiple modalities including input data from a first modality and input data from a second modality different from the first modality. The techniques include: obtaining information specifying the multi-modal statistical model including values of parameters of each of multiple components of the multi-modal statistical model, the multiple components including first and second encoders for processing input data for the first and second modalities, respectively, first and second modality embeddings, a joint-modality representation, and a predictor; obtaining first input data for the first data modality; providing the first input data to the first encoder to generate a first feature vector; identifying a second feature vector using the joint-modality representation, the first modality embedding and the first feature vector; and generating a prediction for the prediction task using the predictor and the second feature vector.
G06K 9/62 - Methods or arrangements for recognition using electronic means
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
Aspects of the application provide methods of preparing a multiplexed sample for polypeptide sequencing, and compositions, kits and devices useful for the same.
Provided herein are methods of single-polypeptide sequencing and reconstruction. Also provided herein are compositions, kits and devices useful for the same.
System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device may include multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes a surface having a trench region recessed from a portion of the surface and an array of sample wells, disposed in the trench region. The integrated device also includes a waveguide configured to couple excitation energy to at least one sample well in the array and positioned at a first distance from a surface of the trench region and at a second distance from the surface in a region separate from the trench region. The first distance is smaller than the second distance. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
Provided herein are methods of single-cell polypeptide and/or polynucleic acid sequencing, which facilitate the direct sequencing of a single cell without amplification. Also provided herein are compositions, kits and devices useful for the same.
patents
