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.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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.
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.
Doffonon) toward one or more types of amino acid ligands, which advantageously increases the amount of, or confidence in, structural information that may be derived from polypeptide analysis.
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.
H01L 23/373 - Cooling facilitated by selection of materials for the device
H01L 21/48 - Manufacture or treatment of parts, e.g. containers, prior to assembly of the devices, using processes not provided for in a single one of the groups
H05K 7/20 - Modifications to facilitate cooling, ventilating, or heating
F28F 3/04 - Elements or assemblies thereof with means for increasing heat-transfer area, e.g. with fins, with recesses, with corrugations the means being integral with the element
H01L 23/36 - Selection of materials, or shaping, to facilitate cooling or heating, e.g. heat sinks
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
F28C 3/00 - Other direct-contact heat-exchange apparatus
6.
CYCLOPROPENE PHOSPHORAMIDITES AND CONJUGATES THEREOF
Provided herein are cyclopropene phosphoramidites, which can be coupled to oligonucleotides to form cyclopropene-functionalized oligonucleotides. Also provided herein are methods of preparing cyclopropene phosphoramidites. Further provided herein are methods of functionalizing oligonucleotides by reaction with tetrazines, including fluorescently labeled tetrazines, providing oligonucleotide cycloadduct products labeled with cyanine, fluorescein, rhodamine, or BODIPY dyes.
C07C 13/04 - Monocyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with a three-membered ring
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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
C09K 11/07 - Luminescent, e.g. electroluminescent, chemiluminescent, materials containing organic luminescent materials having chemically-interreactive components, e.g. reactive chemiluminescent compositions
7.
METHODS AND COMPOSITIONS FOR PROTEIN FINGERPRINTING
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.
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), in some aspects, the disclosure provides methods and compositions to identify novel proteins or nucleic acids having specific properties, or nucleic acids coding for proteins having specific properties, based on single-molecule measurements. In some aspects, the disclosure provides methods and compositions to identify nucleic acids coding for polymerases having desired properties, based on single-molecule measurements.
Aspects of the application provide compounds of formula (I): or a salt thereof, provided that one of R1-R6 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, which may be useful as chromophores and/or fluorophores for labeling highly water-soluble biomolecules comprising primary amine moiety or sulfide moiety (e.g., proteins, polypeptides, nucleotides, or oligonucleotides).
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.
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
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.
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.
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Photodetectors are used to detect light in a variety of applications. Integrated photodetectors have been developed that produce an electrical signal indicative of the intensity of incident light. Integrated photodetectors for imaging applications include an array of pixels to detect the intensity of light received from across a scene. 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.
The aspects of this disclosure relate to luminescently labeled nucleic acid nanostructure as well as methods and compositions for the detection and/or sequencing of one or more target molecules derived from a sample. The invention may utilize ultrabright DNA for the purpose of improving signal-to-noise ratio and poor specificity of current single molecule sensing technology.
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
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 1/6834 - Enzymatic or biochemical coupling of nucleic acids to a solid phase
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
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.
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.
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. Specifically, the nucleic acid adaptor comprising: a double-stranded transposase recognition sequence; a first primer-binding sequence; and a pair of index primer-binding sequences comprising a first index primer-binding sequence and a second index primer-binding sequence.
C04B 40/06 - Inhibiting the setting, e.g. mortars of the deferred action type containing water in breakable containers
C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
19.
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 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. 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.
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.
G01J 11/00 - Measuring the characteristics of individual optical pulses or of optical pulse trains
H01S 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
22.
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
23.
PROTEIN-WIDE MODIFICATION OF ASPARTATES AND GLUTAMATES
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.
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.
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.
G06K 19/06 - Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
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.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
G01N 27/414 - Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
H01L 27/085 - Devices consisting of a plurality of semiconductor or other solid-state components formed in or on a common substrate including integrated passive circuit elements with at least one potential-jump barrier or surface barrier the substrate being a semiconductor body including only semiconductor components of a single kind including field-effect components only
28.
INTEGRATED CIRCUIT WITH IMPROVED CHARGE TRANSFER EFFICIENCY AND ASSOCIATED TECHNIQUES
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.
G01N 21/00 - Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
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
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.
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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 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.
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
G01N 21/62 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
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.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
G01N 21/31 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
G01N 21/62 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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.
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 photo stability 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).
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.
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.
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 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 3/00 - Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
H01S 3/102 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling the active medium, e.g. by controlling the processes or apparatus for excitation
H01S 3/11 - Mode locking; Q-switching; Other giant-pulse techniques, e.g. cavity dumping
H01S 3/081 - Construction or shape of optical resonators or components thereof comprising three or more reflectors
H01S 3/08 - Construction or shape of optical resonators or components thereof
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.
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 (2-104) configured to couple with sample wells (2-102). Vertical extents of optical modes of individual waveguides may be modulated to adjust confinement of light within the waveguides (2-104). This modulation may enable more uniform distribution of excitation light to the sample wells (2-102), improve excitation efficiency, and prevent overpower on regions of the integrated device.
Disclosed herein are aspects of a pulsed laser light source (106) for producing excitation light (104) in an integrated bioanalytical system (101). The light source (106) comprises one or more laser diodes (102) that produces pulsed light signals (104) synchronized with a common clock source (130) for excitation of samples within reaction chambers (108) on at least one chip (101). The light source (106) 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.
Aspects of the application provide methods of preparing an enriched sample for polypeptide sequencing, and compositions, kits and devices useful for the same.
Methods of preparing a multiplexed sample for polypeptide sequencing using barcodes. Methods for multiplexed samples for polypeptide sequencing in which the polypeptide populations are physically separated. Kit comprising a population of barcodes and device for preparing a sample comprising a sample preparation module comprising barcodes and immobilised capture probes configured to interact with a cartridge comprising a reservoir.
Embodiments described herein generally relate to apparatuses, cartridges, and pumps for peristaltic pumping of fluids and associated methods, systems, and devices. The pumping of fluids is, in certain cases, an important aspect of a variety of applications, such as bioanalytical applications (e.g., biological sample analysis, sequencing, identification). The inventive features described herein may, in some embodiments, provide an ability to pump fluids in ways that combine certain advantages of robotic fluid handling systems (e.g., automation, programmability, configurability, flexibility) with certain advantages of microfluidics (e.g., small fluid volumes with high fluid resolution, precision, monolithic consumables, limiting of the wetting of components to consumables).
Embodiments described herein generally relate to apparatuses, cartridges, and pumps for peristaltic pumping of fluids and associated methods, systems, and devices. The pumping of fluids is, in certain cases, an important aspect of a variety of applications, such as bioanalytical applications (e.g., biological sample analysis, sequencing, identification). The inventive features described herein may, in some embodiments, provide an ability to pump fluids in ways that combine certain advantages of robotic fluid handling systems (e.g., automation, programmability, configurability, flexibility) with certain advantages of microfluidics (e.g., small fluid volumes with high fluid resolution, precision, monolithic consumables, limiting of the wetting of components to consumables).
Methods of polypeptide sequencing and/or nucleic acid sequencing which may be carried out on single cell samples and may use barcode components and which facilitate the direct sequencing without amplification. All proteins in the sample may be first labelled with one barcode, secondly the nucleic acids or metabolites are labelled with a second barcode. Also provided herein are compositions, kits and devices useful for the same.
Methods of single-polypeptide sequencing. The methods comprise providing an enriched sample comprising a population of polypeptides; splitting the enriched sample into two or more subsamples; contacting each of at least two of the subsamples with a different modifying agent, wherein the modifying agent comprises a cleaving agent, e.g. an exopeptidase, thereby generating polypeptide fragments having a combination of cleavage patterns; and sequencing, in parallel, the polypeptide fragments, thereby determining the amino acid sequences of the polypeptide fragments. The fragments may be aligned in order to reconstruct the polypeptide sequence. Also provided herein is a kit comprising a plurality of enrichment molecules, e.g. antibodies, aptamers or enzymes and a sample preparation device comprising barcodes and capture probes.
Methods and devices for isolating or enriching target molecules from a sample using lysis, fragmentation and affinity purification, e.g., using scodaphoresis, are provided herein. In particular embodiments, a device for enriching a target molecule from a biological sample is characterized in that the device comprises an automated sample preparation module comprising a cartridge housing that is configured to receive a removable cartridge. In some embodiments, methods and devices further involve detection, analysis and/or sequencing of a target molecule.
Methods and devices for enriching and analyzing target molecules from a sample are provided herein. In some embodiments, methods and devices using cartridges involve enrichment of target molecules (e.g., using SCODA) and detection and analysis using sequencing. The method may employ lysing of cells, fragmentation of target in the sample preparation module and enriching the target in the module and moving the target to the sequencing module.
Some embodiments relate to an integrated circuit, comprising: a pixel, comprising: a photodetection region; and a drain configured to discard charge carriers from within a semiconductor region of the pixel outside of the photodetection region. Some embodiments relate to an integrated circuit, comprising: a pixel, comprising: a photodetection region; and a drain configured to discard charge carriers from the photodetection region, wherein the drain comprises a semiconductor region and the semiconductor region is contacted by a metal contact. Some embodiments relate to an integrated circuit, comprising: a pixel, comprising: a photodetection region; and a drain configured to discard charge carriers from the photodetection region, wherein the drain comprises a semiconductor region that to which electrical contact is made through a conductive path that does not include a polysilicon electrode.
Aspects of the application provide methods of producing substrates having modified surfaces. In some aspects, methods of surface modification involve treating a surface of a substrate with an organic reagent in vapor phase to form an organic layer over the surface. In some aspects, methods of forming a stable surface coating on an oxidized surface are provided. Organic phosphoryl halide is used.
C23C 16/02 - Pretreatment of the material to be coated
C23C 16/00 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition (CVD) processes
B05D 1/00 - Processes for applying liquids or other fluent materials
C23C 16/455 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition (CVD) processes characterised by the method of coating characterised by the method used for introducing gases into the reaction chamber or for modifying gas flows in the reaction chamber
C23C 16/04 - Coating on selected surface areas, e.g. using masks
54.
INCREASED EMISSION COLLECTION EFFICIENCY IN INTEGRATED OPTICAL DEVICES
Apparatus and methods for improving optical signal collection in an integrated device are described. A microdisk (1-605) can be formed in an integrated device and increase collection and/or concentration of radiation incident on the microdisk (1-605) and re-radiated by the microdisk (1-605). An example integrated device that can include a microdisk (1-605) may be used for analyte detection and/or analysis. Such an integrated device may include a plurality of pixels, each having a reaction chamber (1-130) for receiving a sample to be analyzed, an optical microdisk (1-605), and an optical sensor (1-122) configured to detect optical emission from the reaction chamber (1-130). The microdisk (1-605) can comprise a dielectric material having a first index of refraction that is embedded in one or more surrounding materials (1-610) having one or more different refractive index values.
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
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.
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.
Apparatus and methods relating to photonic bandgap optical nanostructures are described. Such optical nanostructures may exhibit prohibited photonic bandgaps or allowed photonic bands, and may be used to reject (e.g., block or attenuate) radiation at a first wavelength while allowing transmission of radiation at a second wavelength. Examples of photonic bandgap optical nanostructures includes periodic and quasi-periodic structures, with periodicity or quasi-periodicity in one, two, or three dimensions and structural variations in at least two dimensions. Such photonic bandgap optical nanostructures may be formed in integrated devices that include photodiodes and CMOS circuitry arranged to analyze radiation received by the photodiodes.
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
G02B 1/00 - Optical elements characterised by the material of which they are made; Optical coatings for optical elements
Apparatus and methods relating to coupling radiation from an incident beam (1-122) into a plurality of waveguides (1-, 2-, 3-212a...e) with a grating coupler (1-, 2-, 3-210) are described. A grating coupler (1-, 2-, 3-210) can have offset receiving regions and grating portions with offset periodicity to improve sensitivity of the grating coupler (1-, 2-, 3-210) to misalignment of the incident beam (1-122).
Described herein are systems and techniques for identifying polypeptides using data collected by a protein sequencing device. The protein sequencing device may collect data obtained from detected light emissions by luminescent labels during binding interactions of reagents with amino acids of the polypeptide. The light emissions may result from application of excitation energy to the luminescent labels. The device may provide the data as input to a trained machine learning model to obtain output that may be used to identify the polypeptide. The output may indicate, for each of a plurality of locations in the polypeptide, one or more likelihoods that one or more respective amino acids is present at the location. The output may be matched to an amino acid sequence that specifies a protein.
Apparatus and methods relating to attenuating excitation radiation incident on a sensor (1-122) in an integrated device that is used for sample analysis are described. At least one semiconductor film (1-336) of a selected material and crystal morphology is located between a waveguide (1-115) and a sensor (1-122) in an integrated device that is formed on a substrate (1-105). 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 (1-135).
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.
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
C12Q 1/6818 - Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
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.
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
63.
SAMPLE WELL FABRICATION TECHNIQUES AND STRUCTURES FOR INTEGRATED SENSOR DEVICES
A method of forming an integrated device includes forming a sample well within a cladding layer of a substrate; forming a sacrificial spacer layer over the substrate and into the sample well; performing a directional etch of the sacrificial spacer layer so as to form a sacrificial sidewall spacer on sidewalls of the sample well; forming, over the substrate and into the sample well, a functional layer that provides a location for attachment of a biomolecule; and removing the sacrificial spacer material.
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 methods of obtaining data during a degradation process of a polypeptide, and outputting a sequence representative of the polypeptide. In some aspects, the application provides amino acid recognition molecules comprising a shielding element that enhances photostability in polypeptide sequencing reactions.
Systems and methods for detecting lifetime of luminescent molecules using photodetectors configured to perform photon counting are described. The systems and methods may involve an array of photodetectors for detecting photons emitted from a sample, which may include the luminescent molecules, and detection circuitry associated with the array of photodetectors. The detection circuitry may be configured to count, during at least a first time period and a second time period, a quantity of incident photons at a photodetector in the array of photodetectors.
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.
Provided herein is a biomolecule comprising a fluorescent marker. The label is a Cy3B having formula (I) wherein, Q1and Q2 are independently monomeric or oligomeric biomolecules.
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
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
68.
INTEGRATED PHOTODETECTOR WITH CHARGE STORAGE BIN OF VARIED DETECTION TIME
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.
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
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.
Methods and apparatus for predicting an association between input data in a first modality and data in a second modality using a statistical model trained to represent interactions between data having a plurality of modalities including the first modality and the second modality, the statistical model comprising a plurality of encoders and decoders, each of which is trained to process data for one of the plurality of modalities, and a joint-modality representation coupling the plurality of encoders and decoders. The method comprises selecting, based on the first modality and the second modality, an encoder/decoder pair or a pair of encoders, from among the plurality of encoders and decoders, and processing the input data with the joint-modality representation and the selected encoder/decoder pair or pair of encoders to predict the association between the input data and the data in the second modality.
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
Described herein are machine learning techniques for generating biological polymer assemblies of macromolecules. For example, the system may use machine learning techniques to generate a genome assembly of an organism's DNA, a gene sequence of a portion of an organism's DNA, or an amino acid sequence of a protein. The system may access biological polymer sequences generated by a sequencing device and an assembly generated from the sequences. The system may generate input to a machine learning model using the sequences and the assembly. The system may provide the input to the machine learning model to obtain a corresponding output. The system may use the corresponding output to identify biological polymers at locations in the assembly, and then update the assembly to indicate the identified biological polymers at the locations in the assembly to obtain an updated assembly.
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.
A method and apparatus for characterizing an optical element. The optical element is part of a laser and is mounted on a translation stage to scan the optical element transverse to an intracavity laser beam. A performance characteristic of the laser is recorded as a function of position of the optical element.
H01S 3/00 - Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
H01S 3/11 - Mode locking; Q-switching; Other giant-pulse techniques, e.g. cavity dumping
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 3/08 - 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 3/086 - One or more reflectors having variable properties or positions for initial adjustment of the resonator
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 3/042 - Arrangements for thermal management for solid state lasers
H01S 3/131 - Stabilisation of laser output parameters, e.g. frequency or amplitude by controlling the active medium, e.g. by controlling the processes or apparatus for excitation
74.
MACHINE LEARNING ENABLED PULSE AND BASE CALLING FOR SEQUENCING DEVICES
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.
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.
A hand-held bioanalytic instrument is described that can perform massively parallel sample analysis including single-molecule gene sequencing. The instrument includes a pulsed optical source that produces ultrashort excitation pulses and a compact beam-steering assembly. The beam-steering assembly provides automated alignment of excitation pulses to an interchangeable bio-optoelectronic chip that contains tens of thousands of reaction chambers or more. The optical source, beam-steering assembly, bio-optoelectronic chip, and coupling optics register to an alignment structure in the instrument that can form at least one wall of an enclosure and dissipate heat.
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.
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.
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.
Methods of loading a molecule of interest into a sample well are provided. In some aspects, methods of loading a molecule of interest into a sample well involve loading a molecule of interest into a sample well in the presence of a crowding agent and/or a condensing agent. In some aspects, methods of loading a sequencing template into a sample well are provided.
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.
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 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 3/10 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating
Apparatus and methods for coupling an optical beam from an optical source to a hitech 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.
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.
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
86.
INTEGRATED DEVICE FOR DETECTING AND ANALYZING MOLECULES
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.
System and methods for identifying nucleotides based on data acquired from a sensor during sequencing of nucleic acids. The method may include obtaining characteristics of light detected from luminescent labels associated with the nucleotides during nucleotide incorporation events. The characteristics may include, for each nucleotide incorporation event, a temporal characteristic of the light and an intensity characteristic of the light. The temporal characteristic representing a speed of decay of a probability of photon emission by a luminescent label after excitation. The method may further include grouping points representing the characteristics of the nucleotide incorporation events into groups of points. The individual points may represent at least the temporal characteristic and the intensity characteristic for a corresponding nucleotide incorporation event. The method may further include assigning the groups of points to individual nucleotides.
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
88.
LABELED NUCLEOTIDE COMPOSITIONS AND METHODS FOR NUCLEIC ACID SEQUENCING
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 Iuminescently 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 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
Compact optical sources and methods for producing short and ultrashort optical pulses are described. A semiconductor laser or LED (2-423) 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.
Apparatus and methods for producing ultrashort optical pulses (1-110) are described. A high-power, solid-state, passively mode- locked laser (1-110) 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 5/06 - Arrangements for controlling the laser output parameters, e.g. by operating on the active medium
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
91.
METHOD OF DETERMINING THE SEQUENCE OF A NUCLEAR ACID USING TIME RESOLVED LUMINESCENCE
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.
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.
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.
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.
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.
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
96.
INTEGRATED DEVICE WITH EXTERNAL LIGHT SOURCE FOR PROBING DETECTING AND ANALYZING MOLECULES
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.
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
97.
ACTIVE-SOURCE-PIXEL, INTEGRATED DEVICE FOR RAPID ANALYSIS OF BIOLOGICAL AND CHEMICAL SPECIMENTS
An active- source -pixel, integrated device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, is described. An active pixel of the integrated device includes a sample well into which a sample to be analyzed may diffuse, an excitation source for providing excitation energy to the sample well, and a sensor configured to detect emission from the sample. The sensor may comprise two or more segments that produce a set of signals that are analyzed to differentiate between and identify tags that are attached to, or associated with, the sample. Tag differentiation may be spectral and/or temporal based. Identification of the tags may be used to detect, analyze, and/or sequence the biomolecule.
patents
