Methods, devices, and systems for analyte detection and analysis

Inventors

Almogy, Gilad • Beckett, Nathan • WOLF, Jacob A. • Caswell, Nathan • Anthony, Joseph • SOSA, Jose Martin • Lee, Phillip • KUBECKA, Stephanie

Assignees

Ultima Genomics Inc

Abstract

Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate. The open substrate may be configured to rotate or otherwise move. The open substrate can comprise an array of individually addressable locations, with analytes immobilized thereto. The substrate may be spatially indexed to identify nucleic acid molecules from one or more sources, and/or sequences thereof, with the respective one or more sources. A solution comprising a plurality of probes may be directed across the array to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via scanning of the substrate while minimizing temperature fluctuations of the substrate or optical aberrations caused by bubbles.

Core Innovation

The invention describes a nucleic acid sample processing system in which a substrate has a first region and a second region that are different from one another, with each region comprising at least 10,000 indexed locations. Nucleic acid molecules are supplied from a first source to the first region and from a second source to the second region. The substrate regions thus hold different sets of nucleic acid molecules associated with different sources.

A detector is configured to detect signals from indexed locations that are indicative of at least one nucleotide having been incorporated into a growing nucleic acid strand that is complementary to a nucleic acid molecule of the first set. One or more processors receive the detector signals and associate each nucleic acid molecule of the first set of indexed locations with the first source and/or associate each nucleic acid molecule of the second set of indexed locations with the second source. This creates a source-resolved association between incorporation-indicative signals and nucleic acid molecules held in different substrate regions.

The first and second regions are separated by a barrier formed from a viscous solution, polyethylene glycol (PEG), an immiscible fluid relative to a loading solution, an air knife, an injection molded guide, or a hydrophobic region. Optical imaging detects signals from both regions to determine sequence sets of nucleic acid molecules at indexed locations in each region, enabling separate determination of first and second set sequence information within the same system.

Claims Coverage

The independent claim defines a nucleic acid sample processing system that resolves which source each indexed location’s nucleic acid molecule originates from. The inventive coverage includes region-differentiated substrates with indexed locations, source-specific loading, incorporation-signal detection, and processor-based source association.

Across the independent claim, the system’s core inventive function is achieved by combining a differentiated two-region, indexed substrate loaded from different nucleic acid sources, detecting incorporation-indicative detector signals, and using processors to associate detected indexed-location nucleic acid molecules with their corresponding sources.

Stated Advantages

Documented Applications