Abstract: 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.

Abstract: 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.

Abstract: 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.

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 relating to attenuating excitation radiation incident on a sensor in an integrated device that is used for sample analysis are described. At least one semiconductor film of a selected material and crystal morphology is located between a waveguide and a sensor in an integrated device that is formed on a substrate. Rejection ratios greater than 100 or more can be obtained for excitation and emission wavelengths that are 40 nm apart for a single layer of semiconductor material.

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: Disclosed herein are aspects of a pulsed laser light source for producing excitation light in an integrated bioanalytical system. In some embodiments, the light source comprises one or more laser diodes that produces pulsed light signals synchronized with a common clock source for excitation of samples within reaction chambers on at least one chip. The light source may be used to provide excitation for a system with a large sensor array with reduced cost, size and electrical power requirements.

Abstract: Systems and methods for optical power distribution within an integrated device, in a substantially uniform manner, to a large number of sample wells and/or other photonic elements. The integrated device and related instruments and systems may be used to analyze samples in parallel. The integrated device may include a grating coupler configured to receive light from an excitation source and optically couple with multiple waveguides configured to couple with sample wells. Vertical extents of optical modes of individual waveguides may be modulated to adjust confinement of light within the waveguides. This modulation may enable more uniform distribution of excitation light to the sample wells, improve excitation efficiency, and prevent overpower on regions of the integrated device.

Abstract: 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.

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, 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.

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 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 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: 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: Apparatus and methods relating to attenuating excitation radiation incident on a sensor in an integrated device that is used for sample analysis are described. At least one semiconductor film of a selected material and crystal morphology is located between a waveguide and a sensor in an integrated device that is formed on a substrate. Rejection ratios greater than 100 or more can be obtained for excitation and emission wavelengths that are 40 nm apart for a single layer of semiconductor material.

Abstract: 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.

Abstract: 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.

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: 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: Various embodiments of apparatuses, systems and methods are described herein for a spectrometer comprising at least two dispersive elements configured to receive at least one input optical signal and generate two or more pluralities of spatially separated spectral components, at least a portion of the at least two dispersive elements being implemented on a first substrate; and a single detector array coupled to the at least two dispersive elements and configured to receive and measure two or more pluralities of narrowband optical signals derived from the two or more pluralities of spatially separated spectral components, respectively.