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Publication Number
US-11733239-B2
Publication Date
2023-08-22
Expiration Date
Abstract
A method includes attaching two or more beads 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-bead complex including two or more beads and the unit of the chemical component; placing the sample on a surface of an image sensor; at the image sensor, receiving light originating at a light source, the received light including light reflected by, refracted by, or transmitted through the beads of the multi-bead complexes; at the image sensor, capturing one or more images of the sample from the received light; and identifying, in at least one of the images of the sample, separate multi-bead complexes, the identifying of the separate multi-bead complexes including associating the two or more beads of each of the multi-bead complexes based on proximity to one another.
Core Innovation
The disclosed invention relates to a method for identifying and quantifying a chemical component in a sample using bead-based analysis and image sensing. The method binds a first attachment unit and a second attachment unit to a unit of a chemical component in a sample disposed on a first surface, where the first attachment unit is attached to a bead. The bead is configured as an identifiable element for imaging by causing light originating at a light source and reflected by, refracted by, or transmitted through the bead to be received at an image sensor and captured as one or more images including the bead.
The method identifies the bead in the captured images and identifies, in the images, the location at which the second attachment unit bound to the chemical component is attached on the first surface or on the second surface based on the identification of the bead. The presence or level of the chemical component is then determined based on a correspondence between the second attachment unit attached at the identified location and the chemical component. The disclosure further describes a multi-bead complex concept in which two or more indicator beads are attached to each unit of a chemical component and separate multi-bead complexes are identified by associating beads within each complex based on proximity.
Additional embodiments include antibody binding, including antibody binding to pathogen or virus capsid antigen targets, and beads differentiated by optical characteristics such as color, size, shape, or birefringence. The disclosure also describes forming a monolayer on the image sensor, optionally confining the sample with an opposite surface, and enumerating complexed beads for complexed-beads mode quantification with a standard curve. The description further includes point-of-care whole-blood analysis and contact CBC imaging via monolayer contact non-fluorescence imaging.
Claims Coverage
The independent claim provides a bead-addressed binding and imaging workflow that links bead identification to the attachment-unit binding location, and then to a presence or level determination. The inventive features center on dual attachment units on a chemical-component unit, image-sensor light capture through the bead, and spatial identification of where the second attachment unit is attached followed by correspondence-based presence/level determination. Dependent claims further specify antibody binding, placement of the second attachment unit on the sensor surface, monolayer constraints, and arraying multiple attachment-unit locations, with further narrowing to pathogen and virus embodiments.
Two attachment units bound to a unit of a chemical component using bead as identifiable marker
Binding a first attachment unit and a second attachment unit to a unit of a chemical component in a sample disposed on a first surface, the first attachment unit being attached to a bead, and the second attachment unit being attached at a location on the first surface or on a second surface, wherein the first attachment unit is configured to bind to the unit of the chemical component and the second attachment unit is configured to bind to the unit of the chemical component.
Image sensor captures bead-originated light to produce images including the bead
Receiving, at an image sensor, light originating at a light source and reflected by, refracted by, or transmitted through the bead, and capturing by the image sensor one or more images of the sample, the one or more images including the bead, where the bead is imaged via the reflected, refracted, or transmitted light.
Spatial identification of second attachment location based on bead identification
Identifying the bead in at least one image of the one or more images of the sample, and identifying, in the at least one image of the one or more images of the sample, the location at which the second attachment unit bound to the chemical component is attached on the first surface or on the second surface based on the identification of the bead.
Presence or level determination via correspondence between attachment location and chemical component
Determining, based on a correspondence between the second attachment unit attached at the identified location and the chemical component, a presence or a level of the chemical component in the sample.
Antibody-based attachment units
The first attachment unit and the second attachment unit include antibodies.
Pathogen antigen and antibody association
The first and second attachment units include pathogen antigens, and the unit of the chemical component includes an antibody to the pathogen.
Second attachment unit attached on the sensor surface of the image sensor
The second attachment unit is attached to the first surface, where the first surface includes a sensor surface of the image sensor.
Monolayer formation between top and sensor surfaces
Forming a monolayer of the sample between a top surface and the sensor surface of an image sensor.
Multiple attachment units arranged as an array on first and/or second surfaces
Attaching multiple attachment units, including a second attachment unit, at respective locations on either the first surface or the second surface to form an array.
Pathogen narrowing to virus
Further narrowing wherein the pathogen is a virus.
Across the independent claim and its dependents, the core claim coverage is the combination of bead-addressed dual attachment-unit binding to a chemical-component unit, image-sensor capture of light reflected, refracted, or transmitted through the bead, identification of the bead to infer the second attachment-unit binding location on a surface, and determination of presence or level based on correspondence to the chemical component. Dependent claims narrow the binding chemistry to antibody-based systems and pathogen-related, including virus, antigen/antibody pairs, constrain physical arrangement to the image-sensor sensor surface and monolayer formats, and extend to arrays and multi-location attachment configurations.
Stated Advantages
Determines a presence or a level of the chemical component based on correspondence between the second attachment-unit binding location and the chemical component.
Enables identification of separate multi-bead complexes by associating beads within each complex based on proximity.
Provides quantification using complexed-beads enumeration with a standard curve.
Compatible with point-of-care whole-blood analysis.
Compatible with contact CBC imaging via monolayer contact non-fluorescence imaging.
Documented Applications
Point-of-care whole-blood analysis.
Contact CBC imaging using monolayer contact non-fluorescence imaging.
Quantification using a standard curve in a complexed-beads enumeration mode.
Pathogen or virus capsid antigen detection using antibody binding embodiments.
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