Abstract: A system and method for characterizing contributions to signal noise associated with charge-coupled devices adapted for use in biological analysis. Dark current contribution, readout offset contribution, photo response non-uniformity, and spurious charge contribution can be determined by the methods of the present teachings and used for signal correction by systems of the present teachings.

Abstract: An apparatus and method are provided for differentiating multiple detectable signals by excitation wavelength. The apparatus can include a light source that can emit respective excitation light wavelengths or wavelength ranges towards a sample in a sample retaining region, for example, in a well. The sample can contain two or more detectable markers, for example, fluorescent dyes, each of which can be capable of generating increased detectable emissions when excited in the presence of a target component. The detectable markers can have excitation wavelength ranges and/or emission wavelength ranges that overlap with the ranges of the other detectable markers. A detector can be arranged for detecting an emission wavelength or wavelength range emitted from a first marker within the overlapping wavelength range of at least one of the other markers.

Abstract: Systems and methods for multiple analyte detection include a system for distribution of a biological sample that includes a substrate, wherein the substrate includes a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber. The system may further include a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate and a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber. The substrate can be constructed of detection-compatible and assay-compatible materials.

Abstract: Aspects of the invention include methods for improving the accuracy and read length of sequencing reactions by utilizing unlabeled unincorporable nucleotides, or by rephasing colony based sequencing reactions. Other aspects include systems and devices for improved measurement of biological reactions associated with bead which may be removed, utilizing current measurement methods through the counter ions associated with said beads due to the presence of reactants bound or associated with said bead, wherein electrodes for generating and measuring said current may be within the Debye length of said bead. Other aspects of the invention include methods for determining concentrations of input samples, means for reuse of an array, methods and apparatus for separating beads with different charge levels from each other.

Abstract: In some embodiments, an analyte detection system is provided that includes a nanochannel, an electrode arrangement, and a plurality of nanoFET devices disposed in the nanochannel. A plurality of nucleic acid base detection components can be used that include a plurality of nanopores, a plurality of nanochannels, a plurality of hybridization probes, combinations thereof, and the like. According to other embodiments of the present teachings, different coded molecules are hybridized to a target DNA molecule and used to detect the presence of various sequences along the target molecule. A kit including mixtures of coded molecules is also provided. In some embodiments, devices including nanochannels, nanopores, and the like, are used for manipulating movement of DNA molecules, for example, in preparation for a DNA sequencing detection. Nanopore structures and methods of making the same are also provided as are methods of nucleic acid sequencing using the nanopore structures.

Abstract: The present disclosure provides apparatus, systems and method for detecting separately and substantially simultaneously light emissions from a plurality of localized light-emitting analytes. A system according to exemplary embodiments of the present disclosure comprises a sample holder having structures formed thereon for spatially separating and constraining a plurality of light-emitting analytes each having a single nucleic acid molecule or a single nucleic acid polymerizing enzyme, a light source configured to illuminate the sample holder, an optical assembly configured to collect and detect separately and substantially simultaneously light emissions associated with the plurality of light emitting analytes. The system may further include a computer system configured to analyze the light emissions to determine the structures or properties of a target nucleic acid molecule associated with each analyte.

Abstract: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with an excitation beam generated by a light source. A collimating lens can be disposed along a beam path between the light source and the reaction regions to form bundles of collimated excitation beams, wherein each bundle corresponds to a respective reaction region. Methods of analysis using the optical instrument are also provided.

Abstract: The present disclosure provides apparatus, systems and method for detecting separately and substantially simultaneously light emissions from a plurality of localized light-emitting analytes. A system according to exemplary embodiments of the present disclosure comprises a sample holder having structures formed thereon for spatially separating and constraining a plurality of light-emitting analytes each having a single nucleic acid molecule or a single nucleic acid polymerizing enzyme, a light source configured to illuminate the sample holder, an optical assembly configured to collect and detect separately and substantially simultaneously light emissions associated with the plurality of light emitting analytes. The system may further include a computer system configured to analyze the light emissions to determine the structures or properties of a target nucleic acid molecule associated with each analyte.

Abstract: Lateral flow test strips, systems, and methods are provided for measuring the presence and levels of analytes in samples in which the analyte may be complexed, for example within an analyte-antibody complex. Test strips are provided that can decomplex the analyte from the analyte-antibody complex during the lateral flow assay, resulting in high quality assays without the need for a decomplexation pre-treatment step. Various systems and methods for improving the performance of lateral flow assays are described, which include minimization of the Prozone effect, improved dynamic range, improving sensitivity by disrupting complexation of target antigens. The resulting lateral flow system has improved sensitivity and improved dynamic range, and may utilize fluorescence. The illumination system utilizes an LED, plastic lenses and plastic and colored glass filters for the excitation and emission light.

Abstract: A vacuum assist apparatus can comprise a microplate. The microplate can comprise a first surface and an opposing second surface. A plurality of wells can be formed in the first surface of the microplate. Each of the plurality of wells can be sized to receive an assay therein. A support base can comprise a fluid passage. The microplate can be positioned adjacent and in contact with the support base. A pressure device, in fluid communication with the fluid passage, can exert a vacuum within the fluid passage to actively retain the microplate in the contact with the support base.

Abstract: Aspects of the invention include methods for improving the accuracy and read length of sequencing reactions by utilizing unlabeled unincorporable nucleotides, or by rephasing colony based sequencing reactions. Other aspects include systems and devices for improved measurement of biological reactions associated with bead which may be removed, utilizing current measurement methods through the counter ions associated with said beads due to the presence of reactants bound or associated with said bead, wherein electrodes for generating and measuring said current may be within the Debye length of said bead. Other aspects of the invention include methods for determining concentrations of input samples, means for reuse of an array, methods and apparatus for separating beads with different charge levels from each other.

Abstract: Various embodiments of the teachings relate to a system or method for sample preparation or analysis in biochemical or molecular biology procedures. The sample preparation can involve small volume processed in discrete portions or segments or slugs, herein referred to as discrete volumes. A molecular biology procedure can be nucleic acid analysis. Nucleic acid analysis can be an integrated DNA amplification/DNA sequencing procedure.

Abstract: Various embodiments relate to systems and/or methods for sample preparation that can be used for biochemical and/or molecular biology procedures involving small volumes, for example, micro volumes or smaller. Methods and systems that can reduce sample size requirements and increase the number of samples on a substrate are provided. Samples can be applied to a plate or other appropriate substrate and can be used for, inter alia, sequencing reactions. In some embodiments, apparatuses, systems, and/or methods for charged analyte collection are provided. Charged analytes in a sample can be electrokinetically collected or extracted from a conduit through a hole formed in a sidewall of the conduit, by application of an electric field that causes the charged analytes to migrate in a direction that is transverse to the conduit.

Abstract: Aspects of the invention include methods for improving the accuracy and read length of sequencing reactions by utilizing unlabeled unincorporable nucleotides, or by rephasing colony based sequencing reactions. Other aspects include systems and devices for improved measurement of biological reactions associated with bead which may be removed, utilizing current measurement methods through the counter ions associated with said beads due to the presence of reactants bound or associated with said bead, wherein electrodes for generating and measuring said current may be within the Debye length of said bead. Other aspects of the invention include methods for determining concentrations of input samples, means for reuse of an array, methods and apparatus for separating beads with different charge levels from each other.

Abstract: Systems and methods of manipulating discrete volumes of a first fluid in a second fluid are provided. In some embodiments, discrete volumes can be formed in a conduit. In other embodiments, addition fluid can be added to a discrete volume in a first conduit by injecting the addition fluid at a relatively higher pressure. In some embodiments, discrete volumes that normally would not coalesce can be manipulated to be merged together.

Abstract: A method comprises magnetically holding a bead carrying biological material (e.g., nucleic acid, which may be in the form of DNA fragments or amplified DNA) in a specific location of a substrate, and applying an electric field local to the bead to isolate the biological material or products or byproducts of reactions of the biological material. For example, the bead isolated from other beads having associated biological material. The electric field in various embodiments concentrates reagents for an amplification or sequencing reaction, and/or concentrates and isolates detectable reaction by-products. For example, by isolating nucleic acids around individual beads, the electric field can allow for clonal amplification, as an alternative to emulsion PCR. In other embodiments, the electric field isolates a nanosensor proximate to the bead, to facilitate detection of at least one of local pH change, local conductivity change, local charge concentration change and local heat.

Abstract: Various embodiments relate to systems and/or methods for sample preparation that can be used for biochemical and/or molecular biology procedures involving small volumes, for example, micro volumes or smaller. Methods and systems that can reduce sample size requirements and increase the number of samples on a substrate are provided. Samples can be applied to a plate or other appropriate substrate and can be used for, inter alia, sequencing reactions. In some embodiments, apparatuses, systems, and/or methods for charged analyte collection are provided. Charged analytes in a sample can be electrokinetically collected or extracted from a conduit through a hole formed in a sidewall of the conduit, by application of an electric field that causes the charged analytes to migrate in a direction that is transverse to the conduit.

Abstract: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with an excitation beam generated by a light source. A collimating lens can be disposed along a beam path between the light source and the reaction regions to form bundles of collimated excitation beams, wherein each bundle corresponds to a respective reaction region. Methods of analysis using the optical instrument are also provided.

Abstract: A plasmonic nanostructure for enhanced light excitation is disclosed. The plasmonic nanostructure includes a substrate, an adhesion layer disposed on top of the substrate, a surface plasmon resonance layer, and a cavity that extends into the surface plasmon resonance layer. The surface plasmon resonance layer is configured to concentrate an applied plasmon field to a bottom portion of the cavity.

Abstract: The invention relate to systems and methods for sequencing polynucleotides, as well as detecting reactions and binding events involving other biological molecules. The systems and methods may employ chamber-free devices and nanosensors to detect or characterize such reactions in high-throughput. Because the system in many embodiments is reusable, the system can be subject to more sophisticated and improved engineering, as compared to single use devices.