Described herein are systems and methods for extending the dynamic range of assay methods and systems used for determining the concentration of analyte molecules or particles in a fluid sample. In some embodiments, a method comprises spatially segregating a plurality of analyte molecules in a fluid sample into a plurality of locations. At least a portion of the locations may be addressed to determine the percentage of said locations containing at least one analyte molecule. Based at least in part on the percentage, a measure of the concentration of analyte molecules in the fluid sample may be determined using an analog, intensity-based detection/analysis method/system and/or a digital detection/analysis method/system. In some cases, the assay may comprise the use of a plurality of capture objects.

Two or more upconverting particles are attached to each unit of one or more units of a chemical component in a sample, to form, for each unit of the chemical component, a multi-particle complex including the unit of the chemical component and two or more corresponding upconverting particles. The sample is illuminated by input light having a first wavelength. Light is received at an imaging sensor, the received light including output light generated by at least a portion of the upconverting particles attached to the units of the chemical component, the output light having a second wavelength that is shorter than the first wavelength. One or more images of the sample are captured from the received light. Based on the captured one or more images, a presence or a level of the chemical component in the sample is determined.

An indicator of a first type and an indicator of a second type are attached to a unit of a chemical component in a sample to form a first multi-indicator complex. The first multi-indicator complex includes the unit of the chemical component, the indicator of the first type, and the indicator of the second type. The indicator of the first type and the indicator of the second type have different discernible characteristics. An image of the sample, including the first multi-indicator complex corresponding to the unit of the chemical component, is captured by an image sensor. Based on a first image of the sample, a count is generated of multi-indicator complexes that include an indicator of the first type and an indicator of the second type, including the first multi-indicator complex. Based on the count, a presence or a level of the chemical component in the sample is identified.

A method is provided for detecting one or more analytes in a sample. The method relies, in part, on the ability of functionalized particles added to the sample to partially or completely inhibit the transmission of electromagnetic radiation into and out of the sample through a detection surface in a reaction vessel containing the sample. In a microarray format, the invention can be used to screen millions, billions or more biological elements, such as an organism, cell, protein, nucleic acid, lipid, saccharide, metabolite, or small molecules. Methods, apparatuses and kits are described.

Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

In various embodiments methods detecting and/or quantifying a target analyte using immuno-PCR and optionally nucleic acid amplification are provided. In certain embodiments the methods utilize a cartridge for performing immuno-PCR to detect and/or quantify one or more target analytes, and optionally detecting and/or quantifying a nucleic acid, where the cartridge comprises a sample receiving chamber; a chamber comprising a matrix material that acts as a filter and/or a DNA binding agent; a temperature controlled channel or chamber; and a plurality of chambers containing reagents and/or buffers for performing immuno-PCR, where the plurality of chambers comprises a chamber containing a capture antibody that binds the analyte that is to be detected; the plurality of chambers comprises a chamber containing a detection antibody where said detection antibody is optionally attached directly or indirectly to a signal DNA; the plurality of chambers comprises a chamber containing a PCR master mix; the plurality of chambers comprises a chamber containing primers for amplifying all or a region of said signal DNA; and the plurality of chambers comprises a chamber containing a probe for detecting all or a region of said signal DNA.

Devices, kits, and methods related to embodiments of an improved liquid test sample injection device comprising a sample mixture that comprises at least one sample flag compound for detecting the presence or non-presence of a patient's liquid test sample upon being interrogated by a pre-determined wavelength of light.

The invention provides for the detection of a perturbed gene network, which includes highly expressed genes during fetal brain development, which is dysregulated in neuron models of autism spectrum disorder (ASD). High-confidence ASD risk genes are upstream regulators of the network modulating RAS/ERK, PI3K/AKT, and WNT//β-catenin signaling pathways. The invention demonstrates how the heterogeneous genetics of ASD can dysregulate a core network to influence brain development at prenatal and very early postnatal ages and, thereby, the severity of later ASD symptoms. The invention provides a model for diagnosis, prognosis determination, and optionally treatment and monitoring, for any disease by comparing molecular marker patterns in non-affected tissues in a subject with healthy controls to determine a dysregulated network in the subject based on a co-expression pattern of interacting genes.

The invention provides carriers and kits for use in the identification of ligands. Carriers of the invention are provided to which is attached a DNA encoding a peptide and a β2 microglobulin. Carriers of the invention are capable of identifying an epitope recognized by a T-cell receptor and/or an NK-cell receptor and/or an NKT-cell receptor. The invention also provides kits for screening for a T-cell epitope and/or an NK-cell epitope and/or an NKT-cell epitope, wherein the kits comprise a carrier of the invention.

Devices, systems and methods for affinity reagent and catalyst discovery employing a library on a bead HTS platform, each bead comprising affixed non-natural polymers of a distinct bioactive monomer with sequence pre-defined branching and folding in tertiary structures, and fiber-optic array scanning technology.