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 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 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: There is disclosed a system for electrical charge detection comprising a nanoFET device. Also disclosed is a method of electrical charge detection for single molecule sequencing. The method includes attaching a macromolecule or assemblies thereof to a gate of a nanoFET device and flowing in a solution of charge tags, where a charge tag includes a nucleotide attached to a charge complex. The method also includes incorporating one charge tag into the macromolecule or assemblies thereof and cleaving the charge tags from the macromolecule or assemblies thereof. The method further includes detecting at least one of current and voltage from the nanoFET device.

Abstract: Exemplary embodiments provide microfluidic devices and methods for their use. The microfluidic device can include an array of M×N reaction sites formed by intersecting a first and second plurality of fluid channels of a flow layer. The flow layer can have a matrix design and/or a blind channel design to analyze a large number of samples under a limited number of conditions. The microfluidic device can also include a control layer including a valve system for regulating solution flow through fluid channels. In addition, by aligning the control layer with the fluid channels, the detection of the microfluidic devices, e.g., optical signal collection, can be improved by piping lights to/from the reaction sites. In an exemplary embodiment, guard channels can be included in the microfluidic device for thermal cycling and/or reducing evaporation from the reaction sites.

Abstract: A fluid processing device and methods are provided that can process one or many different fluid samples, detection for each of which can be multiplexed to detect the presence or absence of each of a panel of target sequences, for example 20 different target sequences. The device can comprise a substrate and one or more fluid processing pathways at least partially defined by the substrate. Each fluid processing pathway can comprise a pre-amplification region and two or more amplification regions disposed downstream from and in fluid communication with the pre-amplification region. A burstable valve can be disposed along each fluid processing pathway and the downstream regions can contain pre-loaded ammonia gas to draw an amplified sample downstream.

Abstract: A method for determining bias across two domains comprising gene expression data. The method can comprise (a) providing a first domain and a second domain; (b) obtaining information indicative of a bias within the first domain; (c) obtaining information indicative of a bias within the second domain; and (d) using the information indicative of the bias within the first domain and the information indicative of the bias within the second domain to produce an indication of bias across the two domains.

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: A method for determining bias across two domains comprising gene expression data. The method can comprise (a) providing a first domain and a second domain; (b) obtaining information indicative of a bias within the first domain; (c) obtaining information indicative of a bias within the second domain; and (d) using the information indicative of the bias within the first domain and the information indicative of the bias within the second domain to produce an indication of bias across the two domains.

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: 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: Exemplary embodiments provide microfludic devices and methods for their use. The microfluidic device can include an array of M×N reaction sites formed by intersecting a first and second plurality of fluid channels of a flow layer. The flow layer can have a matrix design and/or a blind channel design to analyze a large number of samples under a limited number of conditions. The microfluidic device can also include a control layer including a valve system for regulating solution flow through fluid channels. In addition, by aligning the control layer with the fluid channels, the detection of the microfluidic devices, e.g., optical signal collection, can be improved by piping lights to/from the reaction sites. In an exemplary embodiment, guard channels can be included in the microfluidic device for thermal cycling and/or reducing evaporation from the reaction sites.

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 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: 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: A scanning detection system is provided wherein emissions from locations in a flow cell are detected. In some embodiments, the system can comprise an excitation source, a photocleavage source, and modulating optics configured to cause an excitation beam generated by the excitation source to irradiate a first group of the fixed locations and to cause a photocleavage beam generated by the photocleavage source to irradiate a second group of the fixed locations, which is separate and apart from the first group of fixed locations. Methods of detecting sequencing reactions using such a system 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: A scanning detection system is provided in which emissions from locations in a flow cell are detected. In some embodiments, the system can include an excitation source, a photocleavage source, and modulating optics configured to cause an excitation beam generated by the excitation source to irradiate a first group of the fixed locations and to cause a photocleavage beam generated by the photocleavage source to irradiate a second group of the fixed locations, which is separate and apart from the first group of fixed locations. Methods of detecting sequencing reactions using such a system are also provided.

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: 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.