Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.