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: A filling apparatus for filling a microplate. The microplate can comprise a plurality of wells each sized to receive an assay. A substrate can comprise a first surface and an opposing second surface, a first assay input port for receiving the assay disposed on the first surface, a plurality of staging capillaries extending through the substrate, and a first plurality of microfluidic channels fluidly coupling the first assay input port with at least one of the plurality of staging capillaries. Each of the plurality of staging capillaries can comprise an inlet and an outlet and be sized to receive the assay.

Abstract: In a high-density sequence detection system, an apparatus for transporting a microplate. A control system provides a thermocycler control signal to regulate a desired thermal output of a thermocycler block. A frame has a first side, a second side, and an opening that extends through the first side and the second side. A window is positioned in the opening and a circumferential seal is positioned around a periphery of the opening at the second side. The seal has a peripheral lip that seals against the microplate. A clamp is adapted to engage and displace the frame from an unclamped position to a clamped position, wherein in the unclamped position, the microplate is displaced away from the thermocycler block and in the clamped position, the clamp urges the microplate against the thermocycler block. In some embodiments the peripheral lip is positioned radially inward of the periphery of the opening.

Abstract: A filling apparatus for filling a microplate. The microplate can comprise a plurality of wells each sized to receive an assay. A substrate can comprise a first surface and an opposing second surface, a first assay input port for receiving the assay disposed on the first surface, a plurality of staging capillaries extending through the substrate, and a first plurality of microfluidic channels fluidly coupling the first assay input port with at least one of the plurality of staging capillaries. Each of the plurality of staging capillaries can comprise an inlet and an outlet and be sized to receive the assay.

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: 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: Methods for normalizing output from an instrument employing a reference standard or non-fluorescing substance disposed within at least one of a plurality of reaction chambers. The method comprises collecting and analyzing a signal associated with the reference standard or non-fluorescing substance to determine a normalizing bias. The normalizing bias is then applied to the data signal collected from a remainder of the plurality of reaction chambers.

Abstract: A filling apparatus for filling a microplate. The microplate can comprise a plurality of wells each sized to receive an assay. A substrate can comprise a first surface and an opposing second surface, a first assay input port for receiving the assay disposed on the first surface, a plurality of staging capillaries extending through the substrate, and a first plurality of microfluidic channels fluidly coupling the first assay input port with at least one of the plurality of staging capillaries. Each of the plurality of staging capillaries can comprise an inlet and an outlet and be sized to receive the assay.

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: Methods for normalizing output from an instrument employing a reference standard or non-fluorescing substance disposed within at least one of a plurality of reaction chambers. The method comprises collecting and analyzing a signal associated with the reference standard or non-fluorescing substance to determine a normalizing bias. The normalizing bias is then applied to the data signal collected from a remainder of the plurality of reaction chambers.

Abstract: A filling apparatus for filling a microplate. The microplate having a plurality of wells each sized to receive an assay. The filling apparatus can comprise an output layer having a plurality of capillaries. Each of the plurality of capillaries can comprises an inlet and an outlet. A funnel assembly can comprise a funnel member sized to receive the assay. The funnel member can comprise an outlet for delivering a fluid bead of the assay along a top surface of the output layer and in fluid communication with each of the plurality of capillaries such that a portion of the fluid bead can be drawn within at least some of the plurality of capillaries in response to capillary force. The funnel assembly and the output layer can be moveable relative to each other between a first position and a second position to draw the fluid bead across the top surface.

Abstract: A filling apparatus for filling a microplate. The microplate can comprise a plurality of wells each sized to receive an assay. A substrate can comprise a first surface and an opposing second surface, a first assay input port for receiving the assay disposed on the first surface, a plurality of staging capillaries extending through the substrate, and a first plurality of microfluidic channels fluidly coupling the first assay input port with at least one of the plurality of staging capillaries. Each of the plurality of staging capillaries can comprise an inlet and an outlet and be sized to receive the assay.

Abstract: A method of using a standard to correct for variability in sample handling, can comprise (a) adding a template of known concentration to an assay comprising a sample; (b) preamplifying the assay; (c) amplifying the assay; (d) collecting data during the amplifying; and (e) correcting the data using a comparison of data collected from the template to data collected from the sample.

Abstract: A filling apparatus for filling a microplate. The microplate can comprise a plurality of wells each sized to receive an assay. A substrate can comprise a first surface and an opposing second surface, a first assay input port for receiving the assay disposed on the first surface, a plurality of staging capillaries extending through the substrate, and a first plurality of microfluidic channels fluidly coupling the first assay input port with at least one of the plurality of staging capillaries. Each of the plurality of staging capillaries can comprise an inlet and an outlet and be sized to receive the assay.

Abstract: In a high-density sequence detection system, an apparatus for transporting a microplate. A control system provides a thermocycler control signal to regulate a desired thermal output of a thermocycler block. A frame has a first side, a second side, and an opening that extends through the first side and the second side. A window is positioned in the opening and a circumferential seal is positioned around a periphery of the opening at the second side. The seal has a peripheral lip that seals against the microplate. A clamp is adapted to engage and displace the frame from an unclamped position to a clamped position, wherein in the unclamped position, the microplate is displaced away from the thermocycler block and in the clamped position, the clamp urges the microplate against the thermocycler block. In some embodiments the peripheral lip is positioned radially inward of the periphery of the opening.

Abstract: Methods for normalizing output from an instrument employing a reference standard or non-fluorescing substance disposed within at least one of a plurality of reaction chambers. The method comprises collecting and analyzing a signal associated with the reference standard or non-fluorescing substance to determine a normalizing bias. The normalizing bias is then applied to the data signal collected from a remainder of the plurality of reaction chambers.

Abstract: A sealing cover roll for use in sealing a microplate comprising an elongated carrier liner having a first surface and a second surface. A plurality of sealing covers are releasably carried on the first surface of the elongated carrier liner. Each of the plurality of sealing covers comprises a base stock and an adhesive. The adhesive is operable to retain the base stock to the elongated carrier liner and permit release of the base stock and the adhesive from the elongated carrier liner. A roll core supports a rolled configuration of the elongated carrier liner such that the first surface of the elongated carrier liner faces toward the roll core when rolled.

Abstract: A filling apparatus for filling a microplate. The microplate having a plurality of wells each sized to receive an assay. The filling apparatus can comprise an assay input layer having a first surface and an opposing second surface. The assay input layer can comprise an assay input port extending from the first surface to the second surface and at least one pressure nodule extending from the second surface. An output layer can comprise a plurality of staging capillaries each having an inlet and an outlet. A intermediate layer can be disposed between the assay input layer and the output layer. The intermediate layer can be flexible and comprise a plurality of microfluidic channels and a flow aperture being in fluid communication with the assay input port and the plurality of microfluidic channels.

Abstract: A method for simultaneously determining a genetic expression profile for an individual member of a species relative to an entire standard genome for the species. The method can comprise distributing a liquid sample into an array of reaction chambers of a substrate. The array can comprise a primer set and a probe for each polynucleotide target along the entire standard genome. The liquid sample can comprise substantially all genetic material of the member. Each of the reaction chambers can comprise the primer set and the probe for at least one of the polynucleotide targets and a polymerase. The method can further comprise amplifying the liquid sample in the array, detecting a signal emitted by at least one of the probes, and identifying the genetic expression profile in response to the signal.

Abstract: An assay card and devices and methods for isolating chambers on the assay card are described. The assay card comprises a substrate formed of one or more materials, e.g., plastic, having a softening temperature, the substrate defining channels communicating with respective reaction chambers. The assay card may be heated in a region of the channels to at least the softening temperature. The softened plastic may be deformed, e.g., with a tool which may or may not also provide the heat for softening the substrate. In this manner, the plastic of the substrate may be caused to at least partially obstruct the channels, thereby isolating the reaction chambers. The invention also relates to a method of manufacturing a tool device that includes pins for heating and deforming an assay card.