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: 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.

Abstract: The present teachings provide for systems, and components thereof, for detecting and/or analyzing light. These systems can include, among others, optical reference standards utilizing luminophores, such as nanocrystals, for calibrating, validating, and/or monitoring light-detection systems, before, during, and/or after sample analysis.

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 is 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: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with excitation beams generated by a light source. The light source can include an area light array of light emitting diodes, one or more solid state lasers, one or more micro-wire lasers, or a combination thereof. According to various embodiments, a Fresnel lens can be disposed along a beam bath between the light source and the reaction regions. Methods of analysis using the optical instrument are also provided.

Abstract: According to various embodiments, a method is provided that comprises washing an array of DNA-coated beads on a substrate, with a wash solution to remove stacked beads from the substrate. The wash solution can include inert solid beads in a carrier. The DNA-coated beads can have an average diameter and the solid beads in the wash solution can have an average diameter that is at least twice the diameter of the DNA-coated beads. The washing can form dislodged DNA-coated beads and a monolayer of DNA-coated beads. In some embodiments, first beads for forming an array are contacted with a poly(ethylene glycol) (PEG) solution comprising a PEG having a molecular weight of about 350 Da or less. In some embodiments, slides for forming bead arrays are provided as are systems for imaging the same.

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: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with excitation beams generated by a light source. The light source can include an area light array of light emitting diodes, one or more solid state lasers, one or more micro-wire lasers, or a combination thereof. According to various embodiments, a Fresnel lens can be disposed along a beam bath between the light source and the reaction regions. Methods of analysis using the optical instrument are also provided.

Abstract: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with excitation beams generated by a light source. The light source can include an area light array of light emitting diodes, one or more solid state lasers, one or more micro-wire lasers, or a combination thereof. According to various embodiments, a Fresnel lens can be disposed along a beam bath between the light source and the reaction regions. Methods of analysis using the optical instrument are also provided.

Abstract: The present teachings provide for systems, and components thereof, for detecting and/or analyzing light. These systems can include, among others, optical reference standards utilizing luminophores, such as nanocrystals, for calibrating, validating, and/or monitoring light-detection systems, before, during, and/or after sample analysis.

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: 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: An instrument is provided that can monitor nucleic acid sequence amplification reactions, for example, PCR amplification of DNA and DNA fragments. The instrument includes a multi-notch filter disposed along one or both of an excitation beam path and an emission beam path. Methods are also provided for monitoring nucleic acid sequence amplifications using an instrument that includes a multi-notch filter disposed along a beam path.

Abstract: An apparatus for detecting labeled beads is provided. The apparatus can include: one or more irradiation sources disposed for irradiating the one or more detection zones with radiation; at least one detector disposed for collecting charges corresponding to light signals emitted from labeled beads in the one or more detection zones, which have been excited by the radiation; and a system coupled to the at least one detector for effecting time delay integration of the charges by accumulating the charges before reading the charges at the output of the at least one detector.

Abstract: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with excitation beams generated by a light source. The light source can include an area light array of light emitting diodes, one or more solid state lasers, one or more micro-wire lasers, or a combination thereof. According to various embodiments, a Fresnel lens can be disposed along a beam bath between the light source and the reaction regions. Methods of analysis using the optical instrument are also provided.

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: 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: A system and method for measuring signals having a wide range of intensity components using detectors adapted for use in biological analysis devices. In certain biological analysis applications, signals emitted by a sample may have intensity components that vary over several orders of magnitude. Measurement of such a signal may yield an acceptable quality for one intensity component at the expense of another component. For example, a detector configured to measure a relatively weak intensity component may cause it to overflow when subjected to a relatively strong intensity component. The detector can be adapted to be operated at different configurations to allow measurements of different components of the signal, and the results can be combined to yield an accurate representation of the signal.

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: A camera alignment system that can enable alignment in at least one of three planes and about an axis of at least one of the planes. An alignment mount can mate to a camera and lens. The alignment mount can comprise a mechanism to adjust the camera relative to the lens to that an image plane of the camera aligns with an image plane of the lens in a predetermined orientation. One predetermined orientation can be that the image plane of the camera being parallel to the image plane of the lens.