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Publication Number
US-12241893-B2
Publication Date
2025-03-04
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 invention provides an apparatus with an image sensor having an array of light sensitive elements at a sensor surface and a first surface for receiving a sample. The sample comprises a unit of a chemical component bound to a first attachment unit and a second attachment unit, where the first attachment unit is attached to a bead and the second attachment unit is attached either on the first surface or on a second surface facing the first surface. The array of light sensitive elements is configured to capture one or more images based on light originating at a light source and reflected by, refracted by, or transmitted through the bead.
Image processing receives image sensor data, identifies the bead in at least one image, and identifies the location at which the second attachment unit is attached on the first surface or on the second surface based on the identification of the bead. The apparatus then bounds a presence or a level of the chemical component in the sample using the bound chemical component bound to the first attachment unit attached to the bead. The pixel spacing of the array of light sensitive elements is smaller than 5 μm.
In another aspect, the invention provides an apparatus configured to capture images of a sample that comprises a plurality of multi-bead complexes, where each multi-bead complex comprises two or more beads attached to a respective unit of a chemical component. The image sensor captures images based on light reflected by, refracted by, or transmitted through the beads of each multi-bead complex. The processors measure a proximity to one another of the beads of multi-bead complexes in at least one image and identify two or more separate multi-bead complexes based on the measured proximity.
Claims Coverage
The independent claims are directed to two apparatus architectures for bead-based sample analysis using an image sensor, with a pixel-spacing constraint smaller than 5 μm and image processing that associates beads and bead clusters to chemical-component units. The inventive features include bead imaging through reflected, refracted, or transmitted light, bead identification, proximity-based grouping, and determination of presence or level of the chemical component; refinements support enumeration of multi-bead complexes.
Bead-bound chemical component imaged to infer attachment-unit location and presence or level
An apparatus with an image sensor capturing one or more images of a sample, where the sample comprises a unit of a chemical component bound to a first attachment unit and a second attachment unit, the first attachment unit attached to a bead and the second attachment unit attached on the first surface or on a second surface facing the first surface; the array captures images based on light originating at a light source and reflected by, refracted by, or transmitted through the bead; the processors identify the bead, identify the location where the second attachment unit is attached based on bead identification, and bound a presence or a level of the chemical component in the sample.
Proximity-based identification of separate multi-bead complexes from bead images
An apparatus where the sample comprises a plurality of multi-bead complexes, each multi-bead complex comprising two or more respective beads attached to a respective unit of a chemical component; the array of light sensitive elements captures images based on light reflected by, refracted by, or transmitted through the two or more respective beads of each multi-bead complex; the processors measure, in at least one image, a proximity to one another of the two or more respective beads of at least two different multi-bead complexes and identify, in the at least one image, two or more separate multi-bead complexes based on the measured proximity to one another.
Overall, the claim coverage centers on image-sensor-based detection using bead optical interaction with light and image processing that associates beads or multi-bead complexes either to a second attachment-unit location and then bounds presence or level, or to proximity measurements that identify separate multi-bead complexes.
Stated Advantages
Enables determining a presence or a level of the chemical component in the sample.
Identifies two or more separate multi-bead complexes based on measured proximity to one another of beads.
Enables enumerating the number of the plurality of multi-bead complexes in a sample.
Documented Applications
Bead-based point-of-care sample analysis using a contact image sensor with a sample monolayer imaged by reflected, refracted, and/or transmitted light through beads.
Chemical analysis integrated with contact CBC using a shared sensor/light setup.
Use of direct indicator beads (non-fluorescent) for analysis.
Multiplexing using bead optical characteristics such as color, size, shape, or birefringence.
Serology-based detection including pathogen or virus serology using capture/detection antibody chemistries, including binding involving capsid proteins, antigens, and antibodies.
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