Abstract: 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.

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 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: The disclosure relates, in part, to a method for detecting an analyte in a sample, comprising: contacting a substrate construct with a sample that may comprise the analyte, and using evanescent wave imaging to detect the analyte.

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: The disclosure is directed to a compound of formula III: wherein: X is a heteroatom; Base is a nucleobase; R1 and R2 are each independently selected from the group consisting of H, CF3, CN, a C1-C12 straight chain or branched alkyl, a C2-C12 straight chain or branched alkenyl or polyenyl, a C2-C12 straight chain or branched alkynyl or polyalkynyl, a C1-C12 ether, and an aromatic group (e.g., a phenyl, a naphthyl, a pyridine), with the proviso that at least one of R1 and R2 is CF3, CN, a C1-C12 straight chain or branched alkyl, a C2-C12 straight chain or branched alkenyl or polyenyl, a C2-C12 straight chain or branched alkynyl or polyalkynyl, a C1-C12 ether, or an aromatic group (e.g., a phenyl, a naphthyl, a pyridine); R3 is NO2; R4 is H; R5 comprises a C1-C12 alkyne, an amide, and/or an amine; R6 is OMe or S—C6H6; and R7 is H or NO2.

Abstract: The disclosure is directed to an imaging device comprising: a reservoir having an interior lower surface; a substrate arranged below the reservoir, wherein at least a portion of an upper surface of the substrate forms the interior lower surface of the reservoir; a first light source arranged proximate to the substrate and configured to direct light into the substrate; an image sensor arranged below the substrate and configured to receive emission light produced within the reservoir.

Abstract: The disclosure is directed to a method for nucleic acid sequencing, comprising: contacting a substrate polynucleotide immobilized to a substrate with a protected nucleotide and a sequencing primer in a presence of a polymerase such that the polymerase incorporates the protected nucleotide into the sequencing primer, wherein the protected nucleotide comprises a detectable moiety and a photocleavable terminating moiety; using evanescent wave imaging to identify the protected nucleotide incorporated into the sequencing primer; and using evanescent wave imaging to cleave the photocleavable terminating moiety of the protected nucleotide.

Abstract: The disclosure is directed to a method for nucleic acid sequencing, comprising: using evanescent wave imaging to identify a 3?-unblocked protected nucleotide incorporated into a sequencing primer.

Abstract: The disclosure is directed to (i) controlling a first light source to emit a first light into a substrate on which substrate polynucleotides are immobilized, wherein a plurality of substrate polynucleotides are each annealed to a sequencing primer and bound with a polymerase, wherein the substrate polynucleotides are in a presence of a pool of protected nucleotides, and wherein each protected nucleotide comprises a detectable moiety and a photocleavable terminating moiety; (ii) processing a fluorescence signal to identify protected nucleotides incorporated in the sequencing primers; (iii) controlling a second light source to emit a second light into the substrate to cleave the detectable moieties from the incorporated protected nucleotides; (iv) determining one of both of: a percentage of the sequencing primers that incorporated a protected nucleotide and a percentage of the detectable moieties cleaved from the incorporated protected nucleotides; and (v) modifying one or more parameters of a sequencing primer

Abstract: The disclosure is directed to a method for preparing a sample for evanescent wave imaging, comprising: isothermally amplifying a target nucleic acid present in the sample in a reservoir to produce one or more amplicons, wherein the one or more amplicons are immobilized to a bottom surface of the reservoir; and contacting the one or more amplicons with an aqueous solution comprising sequencing reagents comprising a pool of 3?-unblocked protected nucleotides.

Abstract: Aspects of the present disclosure provide improved techniques for imaging a subject's retina fundus. Some aspects relate to an imaging apparatus that may be substantially binocular shaped and/or may house multiple imaging devices configured to provide multiple corresponding modes of imaging the subject's retina fundus. Some aspects relate to techniques for imaging a subject's eye using white light, fluorescence, infrared (IR), optical coherence tomography (OCT), and/or other imaging modalities that may be employed by a single imaging apparatus. Some aspects relate to improvements in white light, fluorescence, IR, OCT, and/or other imaging technologies that may be employed alone or in combination with other techniques. Some aspects relate to multi-modal imaging techniques that enable determination of a subject's health status.

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: 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: 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: 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.

Abstract: Aspects of the present disclosure provide improved techniques for imaging a subject's retina fundus. Some aspects relate to an imaging apparatus that may be substantially binocular shaped and/or may house multiple imaging devices configured to provide multiple corresponding modes of imaging the subject's retina fundus. Some aspects relate to techniques for imaging a subject's eye using white light, fluorescence, infrared (IR), optical coherence tomography (OCT), and/or other imaging modalities that may be employed by a single imaging apparatus. Some aspects relate to improvements in white light, fluorescence, IR, OCT, and/or other imaging technologies that may be employed alone or in combination with other techniques. Some aspects relate to multi-modal imaging techniques that enable determination of a subject's health status.