Methods and systems for analyte detection and analysis
Inventors
Barbee, Kristopher • Beckett, Nathan • Pristinski, Denis • Schulte, Derek • BARTOV, AVISHAI • Sullivan, Jamie • Brinza, Dumitru • Lakdawalla, Abizar • Menchen, Steven • Almogy, Gilad • Pratt, Mark
Assignees
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Publication Number
US-12188924-B2
Publication Date
2025-01-07
Expiration Date
Abstract
Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate configured to rotate. The open substrate can comprise an array of immobilized analytes. A solution comprising a plurality of probes may be directed, via centrifugal force, across the array during rotation of the substrate, 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 continuous rotational area scanning of the substrate.
Core Innovation
The invention relates to processing a biological analyte using a substrate that includes a plurality of biological analytes immobilized thereto. The substrate is moved between a first processing station and a second processing station located at different locations, using a moving arm, and at the second processing station a first solution comprising a plurality of probes is dispensed to contact the immobilized analytes without substrate contact.
After contacting, one or more signals or signal changes, or lack thereof, are detected from the substrate to process the biological analyte. The description includes continuous scanning with an optical imaging objective during relative motion at least for the detecting stage, together with an optical/anamorphic magnification gradient across the scanned field, a segmented focal plane, and independent clocking of detector regions.
Additional refinements include biological analytes immobilized at very large numbers of individually addressable locations, coupling the biological analyte to a bead that is immobilized on the substrate, and probes made of nucleotides or nucleotide analogs used in primer extension to incorporate into a growing strand hybridized and complementary to a target nucleic acid molecule. The document also discloses engineered solution-layer thickness and broad applicability to rotating planar arrays with immobilized analytes and signal detection.
Claims Coverage
The partial content includes one independent claim. Across the claim family, seven inventive features are specified for immobilization format, probe composition, dispensing configuration, and detection/scanning.
Moving substrate between processing stations with non-contact probe dispensing
Moving the substrate from the first processing station to a second processing station located at different locations using a moving arm, and dispensing a first solution via a first fluid outlet port not in contact with the substrate so that the first solution contacts the plurality of biological analytes, wherein the first solution comprises a plurality of probes.
Detecting signal or lack thereof from immobilized analytes to process biological analyte
Detecting one or more signals or signal changes, or lack thereof, from the substrate to process the biological analyte.
Immobilizing analytes at individually addressable locations
A plurality of biological analytes immobilized at least 1,000,000,000 individually addressable locations on the substrate.
Bead-based immobilization of biological analytes
Coupling the biological analyte to a bead that is immobilized on the substrate.
Nucleotide and nucleotide-analog probes for primer extension incorporation into a growing strand
Using a set of probes made of nucleotides or nucleotide analogs and incorporating at least one of those nucleotides or nucleotide analogs into a primer-extended growing strand hybridized and complementary to a target nucleic acid molecule.
Continuous scanning during detection with an optical imaging objective
Continuously scanning the substrate while moving it relative to an optical imaging objective during detecting.
Engineered solution layer with predetermined thickness
Engineering a layer of the solution to have a predetermined thickness.
The claim set centers on moving a substrate between spatially separated processing stations, dispensing a probe-containing solution to non-contactly contact immobilized biological analytes at the second station, and processing based on detected signals or signal changes from the substrate, with dependent refinements emphasizing large-scale immobilization, specific probe chemistry for primer extension, and continuous optical scanning during detection.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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