阅读说明：本技术 基于珠粒的样品分析 (Bead-based sample analysis ) 是由 A.M.法恩 于 2020-03-04 设计创作，主要内容包括：除其他外,引起两个或更多个不同抗体结合至样品中的化学组分的一个或多个单元。抗体的每一个附接至一个或多个珠粒(例如微珠粒)。样品位于图像传感器的表面上。在图像传感器处,接收源于珠粒以外的光源处的光。接收的光包括由珠粒反射、由珠粒折射或透射穿过珠粒的光。图像传感器捕获包括珠粒的样品的一个或多个图像。处理样品的图像的至少一个以单独计算个别珠粒和附接至两个或更多个抗体的珠粒中的两个或更多个的复合体,所述抗体与化学组分的单元结合。使用该处理的结果来鉴定样品中化学组分的存在或水平。(Among other things, causing two or more different antibodies to bind to one or more units of a chemical component in a sample. Each of the antibodies is attached to one or more beads (e.g., microbeads). The sample is located on the surface of the image sensor. At the image sensor, light originating at a light source other than the beads is received. The received light includes light reflected by the bead, refracted by the bead, or transmitted through the bead. The image sensor captures one or more images of the sample including the beads. Processing at least one of the images of the sample to separately calculate complexes of two or more of the individual beads and beads attached to two or more antibodies that bind to units of the chemical component. The results of this treatment are used to identify the presence or level of a chemical component in the sample.)

1. A method, comprising:

causing two or more different antibodies to bind to each of one or more units of a chemical component in a sample, each of the antibodies being attached to one or more beads;

positioning the sample on a surface of an image sensor;

receiving, at the image sensor, light originating at a light source other than the beads, the received light including light reflected by, refracted by, or transmitted through the beads,

the image sensor captures one or more images of the sample including the beads;

processing at least one of the images of the sample to separately calculate complexes of two or more of individual beads and beads attached to the two or more antibodies that bind to each unit of the chemical component, and

using the results of the treatment to identify the presence or level of the chemical component in the sample.

2. The method of claim 1, wherein the two or more different antibodies bind at different positions of the unit of the chemical component.

3. The method of claim 1 or 2, wherein the beads attached to at least two of the different antibodies have the same reflective, refractive and transmissive properties.

4. The method of any one of claims 1 to 3, wherein the beads attached to at least two of the different antibodies have different reflective, refractive or transmissive properties or a combination thereof for light originating at the light source.

5. The method of claim 4, wherein the different reflective, refractive or transmissive properties comprise the color of the beads.

6. The method of claim 4 or 5, wherein the different reflective, refractive or transmissive properties comprise the size of the beads.

7. The method of any one of claims 4 to 6, wherein the different reflective, refractive or transmissive properties comprise the shape of the beads.

8. The method of any one of claims 4 to 7, wherein the different reflective, refractive or transmissive properties comprise the birefringence of the beads.

9. The method of any one of claims 1 to 8, wherein positioning the sample on a surface of the image sensor comprises forming a monolayer of the sample on the surface.

10. The method of any one of claims 1 to 9, wherein the processing comprises determining the amount of the chemical component in the sample based on a comparison of (a) a determined relationship between the number of the individual beads and the number of the complexes of beads and (b) a known relationship between the number of the individual beads and the number of complexes of beads in other samples having known amounts of component.

11. The method of any one of claims 1 to 10, wherein the sample comprises whole blood of a human or animal.

12. The method of any one of claims 1 to 11, comprising:

processing at least one of the images to determine a count of one or more types of blood cells in the sample.

13. The method of any one of claims 1 to 12, comprising:

processing at least one of the images to determine a complete blood count of the sample.

14. The method of any one of claims 1 to 13, which is done at the point of care.

15. A device, comprising:

an image sensor having an array of photosensitive elements exposed at a surface of the image sensor, the surface configured to receive a sample containing units of chemical components, at least one of the units of chemical components having two or more different antibodies bound thereto, each of the different antibodies attached to a single type of bead having the same reflective, refractive and transmissive properties;

a light source configured to illuminate the sample,

the light sensitive component configured to receive light from the light source, the light comprising light reflected by the bead, refracted by the bead, or transmitted through the bead; and

a processor configured to (a) receive one or more images of the sample including direct indicator beads captured by an image sensor based on the received light; (b) processing at least one of the images to identify complexes of individual beads and two or more of the beads attached to the two or more antibodies that bind to units of the chemical component; and (c) using information representative of identifying complexes of the individual beads and two or more beads to determine the presence or amount or both of the chemical component in the sample.

16. A method, comprising:

causing two or more different antibodies, one or more of which are attached to one or more beads, to bind to one or more units of a chemical component in a sample, at least another one of which is attached at a location on a surface;

applying the sample on a surface of an image sensor;

receiving, at the image sensor, light originating from a light source and reflected by, refracted by, or transmitted through the one or more beads attached to the antibody,

the image sensor captures one or more images of the sample including the one or more beads;

processing at least one of the images of the sample comprising the one or more beads to identify locations on the surface where the antibodies are attached; and

using the location to determine the presence or level of the chemical component in the sample.

17. The method of claim 16, wherein the surface to which the antibody is attached comprises a surface of the image sensor.

18. The method of claim 16, wherein the surface to which the antibody is attached comprises a surface facing a surface of the image sensor.

19. A device, comprising:

an array of photosensitive elements exposed at a surface of an image sensor, the surface configured to receive a sample containing one or more units of a chemical component, at least one of the one or more units of the chemical component having two or more different antibodies bound thereto, at least one of the antibodies being coupled to one or more beads, at least another of the antibodies being attached at a location on the surface,

a light source configured to illuminate the sample,

the photosensitive component configured to receive light originating from the source and reflected by, refracted by, or transmitted through the one or more beads; and

a processor configured to (a) receive one or more images captured by the image sensor based on the received light, (b) process at least one of the one or more images to identify a location where the bead-coupled antibody is attached to the surface, and (c) use the location to determine the presence or level of the chemical component in the sample.

20. A method, comprising:

associating a visible identifying mark with a unit of a chemical component of the sample;

capturing one or more images of the sample including the visible authentication mark while the sample is in contact with a surface of an image sensor that exposes an array of photosensitive elements; and

determining the presence or level of one or more types of chemical components based on the captured image.

21. A device, comprising:

a sample comprising units of a plurality of types of chemical components of the sample and a visible identifying mark associated with the units;

an array of photosensitive elements exposed at a surface of an image sensor configured to capture one or more images of the sample including the visible identification indicia while the sample is at the surface; and

a processor configured to determine a presence or level of one or more of the chemical components based on the captured image.

22. A method, comprising:

both a complete blood count and a chemical analysis of a whole blood sample are performed on a surface of an image sensor exposing an array of photosensitive elements, the complete blood count and the chemical analysis based on light originating from a light source external to the sample and reflected, refracted, or transmitted by the sample to the surface of the image sensor.

23. A device, comprising:

an array of photosensitive elements exposed at a surface of an image sensor, the surface configured to receive a whole blood sample;

a light source configured to illuminate the sample,

the photosensitive component configured to receive light originating from the source and reflected by, refracted by, or transmitted through the sample; and

a processor configured to perform both a complete blood count and a chemical analysis of the whole blood sample based on light originating from the light source and reflected by the sample, refracted by the sample, or transmitted through the sample to the surface of the image sensor.

Background

The specification pertains to bead-based sample analysis.

To obtain all useful information in a patient's whole blood sample for diagnostic purposes, for example, not only is the Complete Blood Count (CBC) of the various types of blood cells in the blood sample and their hemoglobin content required, but also chemical analysis of other components in the non-cellular fraction of the blood (e.g., plasma) is required. Such other components may include various kinds of molecules and ions.

Typically, both CBC and chemical analysis of blood are performed in laboratories on large, expensive machines using venous vessels obtained by venotomy. It may take hours or days to complete the chemical analysis and return the results.

SUMMARY

In general, in one aspect, two or more different antibodies are caused to bind to each of one or more units of a chemical component in a sample. Each of the antibodies is attached to one or more beads (e.g., microbeads). The sample is located on the surface of the image sensor. At the image sensor, light originating from a light source other than the beads is received. The received light includes light reflected by the bead, refracted by the bead, or transmitted through the bead. The image sensor captures one or more images of the sample including the beads. Processing at least one of the images of the sample to separately calculate complexes of two or more of the individual beads and beads attached to two or more antibodies that bind to each unit of the chemical component. The results of the treatment are used to identify the presence or level of a chemical component in the sample.

Embodiments may include one or a combination of two or more of the following features. Two or more different antibodies are bound to the unit of chemical component at different locations. In some cases, the beads attached to at least two of the different antibodies have the same reflective, refractive, and transmissive properties. In some cases, the beads attached to at least two of the different antibodies have different reflective, refractive, or transmissive properties, or a combination thereof, for light originating at the light source. The different reflective, refractive or transmissive properties include the color of the beads. The different reflective, refractive or transmissive properties include the size of the beads. The different reflective, refractive or transmissive properties include the shape of the beads. The different reflective, refractive or transmissive properties include the birefringence of the beads. Positioning the sample on the surface of the image sensor includes forming a monolayer of the sample on the surface. The processing includes determining the amount of the chemical component in the sample based on a comparison of (a) the determined relationship between the number of individual beads and the number of bead complexes and (b) the known relationship between the number of individual beads and the number of bead complexes in other samples having known amounts of the component. The sample comprises whole human or animal blood. Processing at least one of the images to determine a count of one or more types of blood cells in the sample. At least one of the images is processed to determine a complete blood count of the sample. The method is completed at the point of care.

In general, in one aspect, an image sensor has an array of photosensitive elements exposed at a surface of the image sensor. The surface is configured to receive a sample of a unit containing a chemical component. At least one of the units of the chemical component has two or more different antibodies bound thereto. Each of the different antibodies is attached to a single type of bead with the same reflective, refractive and transmissive properties. The light source is configured to illuminate the sample. The photosensitive component is configured to receive light from a light source, the light comprising light reflected by the beads, refracted by the beads, or transmitted through the beads. The processor is configured to (a) receive one or more images of a sample including direct indicator beads captured by the image sensor based on the received light, (b) process at least one of the images to identify complexes of two or more of the individual beads and beads attached to two or more antibodies that bind to units of the chemical component, and (c) determine the presence or amount or both of the chemical component in the sample using information representative of the identified complexes of the individual beads and the two or more beads.

In general, in one aspect, two or more antibodies are caused to bind to one or more units of a chemical component in a sample. One or more of the antibodies are attached to one or more beads. At least another one of the antibodies is attached at a location on the surface. At the image sensor, the sample is applied on the surface of the image sensor. Receiving light originating from a light source and reflected by, refracted by, or transmitted through one or more beads attached to the antibody. The image sensor captures one or more images of a sample comprising one or more beads. Processing at least one of the images of the sample comprising the one or more beads to identify the location of the antibody attached to the surface, and using the location to determine the presence or level of the chemical component in the sample.