Classifying microbeads in near-field imaging

Patent metadata

Field	Value
Publication number	US-11112347-B2
Application number	US-202016889430-A
Country	US
Kind code	B2
Filing date	Jun 1, 2020
Priority date	Nov 28, 2017
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

Among other things, an imaging sensor includes a two-dimensional array of photosensitive elements and a surface to receive a sample within a near-field distance of the photosensitive elements. Electronics classify microbeads in the sample as belonging to different classes based on the effects of different absorption spectra of the different classes of microbeads on light received at the surface. In some examples, the number of different distinguishable classes of microbeads can be very large based on combinations of the effects on light received at the surface of the different absorption spectra together, spatial arrangements of colorants in the microbeads that impart the different absorption spectra, different sizes of microbeads, and different shapes of microbeads, among other things.

First claim

The invention claimed is:

1. A method comprising
placing a sample at a surface of an imaging sensor, the imaging sensor comprising a two-dimensional array of photosensitive elements,
the sample including (a) microbeads, at least some of which are attached to units in the sample, (b) and target elements, at least some of which are attached to the units attached to the microbeads,
holding the sample statically within a near-field distance of the photosensitive elements,
using the imaging sensor to capture a two-dimensional image of the statically-held sample including the microbeads,
counting the microbeads belonging to each of two different classes in the two-dimensional image, or identifying locations of the microbeads of each of the two different classes in the two-dimensional image, or both counting the microbeads belonging to each of the two different classes and identifying the locations of the microbeads of each of the two different classes, and
based on at least one of the count of the microbeads belonging to each of the two different classes and the locations of the microbeads of each of the two different classes, performing at least one of an assay, a count, a classification, and an analysis of the target elements in the sample.

2. The method of claim 1 in which the units comprise antigens of a pathogen.

3. The method of claim 2 in which the units comprise capsid proteins.

4. The method of claim 1 in which the sample includes fluorescent anti-immunoglobulin detection antibodies.

5. The method of claim 4 , in which the two-dimensional image comprises a first two-dimensional image, and in which the method comprises
capturing a second two-dimensional image of the statically-held sample, in which fluorescence from the fluorescent anti-immunoglobulin detection antibodies is visible in the second two-dimensional image; and
associating the microbeads in the first two-dimensional image with the fluorescence in the second two-dimensional image.

6. The method of claim 5 , comprising computationally overlaying the first two-dimensional image and the second two-dimensional image.

7. The method of claim 1 in which the units are directed against cluster-of-differentiation cell surface antigens.

8. The method of claim 1 in which the target elements comprise antibodies.

9. The method of claim 8 , in which the target elements comprise anti-HIV antibodies.

10. The method of claim 1 , in which the target elements comprise hormones.

11. The method of claim 1 , comprising forming a monolayer of the sample at the surface.

12. The method of claim 1 in which the two different classes of microbeads have different respective absorption spectra.

13. The method of claim 1 in which the two different classes of microbeads have different respective ratios of intensities of different colors.

14. The method of claim 1 in which the two different classes of microbeads have different respective sizes.

15. The method of claim 1 in which the two different classes of microbeads have different respective shapes.

16. The method of claim 1 in which colorings of the microbeads are distributed evenly within each of the microbeads.

17. The method of claim 1 in which colorings of the microbeads are distributed unevenly within each of the microbeads.

18. The method of claim 1 in which colorings of the microbeads are at least partially internal to each of the microbeads.

19. The method of claim 1 in which colorings of the microbeads are at least partially on a surface of each of the microbeads.

20. The method of claim 1 , in which the two-dimensional image comprises a first two-dimensional image captured while the sample is illuminated by light including a first wavelength of light, and in which the method comprises
capturing a second two-dimensional image of the sample while the sample is illuminated by light including a second wavelength of light, in which the first wavelength is different from the second wavelength.

Assignees

• Alentic Microscience Inc

Inventors

• Fine Alan Marc

Classifications

• G01N2015/1493

  Particle size · CPC title

• G01N2015/1472

  with colour · CPC title

• B82Y10/00

  Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic · CPC title

• G02B27/1013

  for colour or multispectral image sensors, e.g. splitting an image into monochromatic image components on respective sensors (spectral imaging systems G01J) · CPC title

• G02B27/46

  Systems using spatial filters · CPC title