Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

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 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.

Abstract: 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.

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: 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.

Abstract: 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.

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: 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.

Abstract: 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.

Abstract: 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.