Abstract: 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.

Abstract: 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.

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: 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.

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. 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

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: 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.

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: 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.

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. 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.

Abstract: Apparatus and methods for coupling an optical beam from an optical source to a hi-tech system are described. A compact, low-cost beam-shaping and steering assembly may be located between the optical source and hi-tech system and provide automated adjustments to beam parameters such as beam position, beam rotation, and beam incident angles. The beam-shaping and steering assembly may be used to couple an elongated beam to a plurality of optical waveguides.

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.

Abstract: 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.

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: 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: 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.