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-12480938-B2
Publication Date
2025-11-25
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 provides a method for processing a plurality of biological analytes using a rotating substrate affixed to a chuck about a rotational axis. The substrate comprises a substantially planar surface with the plurality of biological analytes immobilized thereto, and a fluid outlet and an objective are positioned above the substantially planar surface at a first location and a second location, respectively, with neither in contact with the substrate.
A solution is dispensed to contact at least a subset of the plurality of biological analytes on the substantially planar surface using the fluid outlet at the first location. The solution disperses radially outwards from a location of dispense corresponding to the first location of the fluid outlet on the substantially planar surface relative to the rotational axis during or subsequent to rotation of the substrate.
After dispensing and contacting, the substantially planar surface of the substrate is imaged using the objective at the second location to detect one or more signals, or signal changes, or lack thereof, from the substrate. The imaging is used to process a biological analyte of the plurality of biological analytes based on the detected signals or signal changes.
The invention also addresses rotational optical imaging for smoothly rotating substrates by contrasting it with rectilinear motion imaging. It characterizes the imaging problem as tangential blur arising from polar-coordinate angular motion and rotational motion imaging, and provides tailored continuous area scanning using TDI/pseudo-TDI or co-added area imaging with multiple sensors and focal-plane region segmentation.
Claims Coverage
The partial content includes two independent claim themes, one directed to processing biological analytes on a rotating substantially planar substrate and one directed to rotational optical imaging. The inventive features below reflect the overlapping core elements explicitly stated across the inputs.
Rotating immobilized biological analyte planar substrate with non-contact fluid outlet and objective
A method that rotates a substrate affixed to a chuck about a rotational axis, where the substrate comprises a substantially planar surface with the plurality of biological analytes immobilized thereto, and where a fluid outlet and an objective are not in contact with the substrate and are disposed above the substantially planar surface at a first location and a second location, respectively.
Radial outward dispersion of dispensed solution during or after rotation
A method that dispenses a solution to the substantially planar surface using the fluid outlet at the first location to contact at least a subset of the plurality of biological analytes, wherein the solution disperses radially outwards from a location of dispense corresponding to the first location of the fluid outlet on the substantially planar surface relative to the rotational axis during or subsequent to rotation.
Imaging to detect signals, signal changes, or lack thereof
A method that images the substantially planar surface of the substrate using the objective at the second location to detect one or more signals or signal changes, or lack thereof, from the substrate to process a biological analyte of the plurality of biological analytes.
Tailored continuous area scanning for rotational imaging
A rotational optical imaging approach that uses tailored continuous area scanning using TDI/pseudo-TDI or co-added area imaging with multiple sensors and focal-plane region segmentation.
Independent clocking of focal-plane regions
A rotational imaging approach that includes independent clocking of focal-plane regions based on radial position and tangential velocity, using controller logic and timing that accounts for pseudo-TDI frame rate and duty cycle.
Optical correction with magnification gradients
A rotational imaging approach that provides optical correction via tailored optical distortions and magnification gradients, including adjustable lens and cylindrical lens anamorphic gradients with magnification scaling with radius.
The claim coverage centers on rotating a substantially planar substrate with immobilized biological analytes, dispensing a solution that disperses radially outward during or after rotation, and imaging from above to detect signals, signal changes, or lack thereof. It also includes rotational imaging features directed to continuous area scanning, focal-plane clocking, and optical correction with magnification gradients.
Stated Advantages
Tailored continuous area scanning supports rotational optical imaging for smoothly rotating substrates.
Independent clocking and timing account for pseudo-TDI frame rate and duty cycle.
Tailored optical distortions and magnification gradients provide optical correction.
Documented Applications
Sequencing at least part of a nucleic acid molecule based on imaging-detected signals, signal changes, or their absence.
Rotational optical imaging for smoothly rotating substrates.
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