Dosimeters including lensless imaging systems

Patent metadata

Field	Value
Publication number	US-10466457-B2
Application number	US-201816157671-A
Country	US
Kind code	B2
Filing date	Oct 11, 2018
Priority date	Dec 17, 2013
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

Among other things, a method comprises imaging a sample displaced between a sensor surface and a surface of a microscopy sample chamber to produce an image of at least a part of the sample. The image is produced using lensless optical microscopy, and the sample contains at least blood from a subject. The method also comprises automatically differentiating cells of different types in the image, generating a count of one or more cell types based on the automatic differentiation, and deriving a radiation dose the subject has absorbed based on the count.

First claim

What is claimed is:

1. A method comprising:
imaging a sample displaced between a sensor surface and a surface of a microscopy sample chamber to produce an image of at least a part of the sample, the image being produced using lensless optical microscopy, the sample containing at least blood from a subject;
automatically differentiating cells of different types in the image;
generating a count of one or more cell types based on the automatic differentiation; and
deriving a radiation dose the subject has absorbed based on the count.

2. The method of claim 1 , wherein generating a count of one or more cell types comprises generating a count of lymphocytes.

3. The method of claim 2 , comprising estimating lymphocyte depletion based on the count of lymphocytes.

4. The method of claim 2 , wherein the sample is a first sample taken at a first time from the subject and count for lymphocyte is a first count for lymphocyte, and the method comprises
imaging a second sample taken at a second, different time from the subject,
generating a second count of lymphocyte based on the second sample, and
estimating lymphocyte depletion based on the first and second counts of lymphocyte.

5. The method of claim 1 , wherein the sample contains fiduciary beads distributed among blood cells of the sample.

6. The method of claim 1 , wherein the cells of different types are differentiated based on one or more of color, size of cell, nuclear shape, and nuclear size.

7. The method of claim 1 , wherein the count of one or more cell types is generated with correction for a volume of the imaged sample.

8. The method of claim 1 , wherein the sample contains diluted blood from the subject, and the count of one or more cell types is generated with correction for dilution of the blood.

9. The method of claim 1 , wherein the sample contains one or more of anticoagulant, diluent, stain, antibody, erythrocyte lysing solution, and other reagents.

10. The method of claim 1 , wherein generating a count of one or more cell types comprises generating the count based on detection one or more surface antigens associated with the one or more cell types.

11. The method of claim 1 , wherein the imaging is performed without using a lens.

12. The method of claim 1 , wherein the imaging comprises imaging at a resolution of 1 mega pixels or higher.

13. The method of claim 1 , wherein the imaging comprises rapid remixing and resampling the displaced sample by raising and lowering the surface of a microscopy sample chamber.

14. The method of claim 1 , wherein the image contains information about cells distributed in no more than a monolayer layer in the sample.

15. The method of claim 1 , wherein automatically differentiating cells comprises automatically classifying different types of cells in the image.

16. The method of claim 1 , comprising automatically delivering the image to a machine to process information contained in the image and provide information about the radiation dosage.

17. The method of claim 1 , comprising connecting to a network through wire or wireless connections.

18. The method of claim 1 , comprising deriving the radiation dosage based on comparing a count of the one or more cell types to reference biodosimetry data for the one or more cell types.

19. The method of claim 1 , comprising estimating lymphocyte depletion based on one or more counts of lymphocytes.

20. The method of claim 1 , comprising determining a first count of a first type of cells within a first sample received within the chamber at a first time; determining a second count of the first type of cells within a second sample received within the chamber at a second time after the first time; and estimating the change in concentration of the first type of cells based on comparing the first count to the second count.

21. The method of claim 1 , comprising correcting the count of the cells of at least one type based on a volume of the sample.

22. The method of claim 1 , comprising obtaining the sample by a pin prick of the subject.

23. The method of claim 1 , comprising including in the sample microbeads coupled to other molecules to endow the microbeads with binding specificity.

24. The method of claim 1 , comprising including in the sample microbeads of two or more different sizes.

25. The method of claim 1 , comprising including in the sample microbeads of two or more different shapes.

26. The method of claim 1 , comprising including in the sample microbeads that are at least one of transparent, colored, fluorescent, and opaque.

27. The method of claim 1 , comprising moving a first surface of the chamber relative to the sensor surface.

28. The method of claim 27 , moving the first surface parallel to the sensor surface during at least part of the motion.

29. The method of claim 27 , comprising moving the first surface to a designated location toward the sensor surface such that when the first surface is moved to the designated location, the part of the sample that is included in the image includes cells distributed in no more than a monolayer in the sample.

30. The method of claim 1 , comprising generating the count of the cells of at least one type based on a volume of diluent within the sample.

31. The method of claim 1 , comprising generating the count of the cells of at least one type based on detecting one or more surface antigens associated with the cells of the least one type.

32. The method of claim 1 , comprising mixing a volume of the sample received on the sensor surface by raising and lowering a surface of the chamber.

33. The method of claim 1 , comprises determining a degree of change in concentration of the cells of the at least one type in the blood.

34. The method of claim 32 comprising, based on the degree of change in the concentration of the cells of the at least one type in the blood, displaying information associated with a radiation dose absorbed by the subject.

Assignees

• Alentic Microscience Inc

Inventors

• Fine Alan Marc

Classifications

• G02B21/0004

  specially adapted for specific applications · CPC title

• G01T1/02

  Dosimeters (G01T1/15 takes precedence) · CPC title

• Y10S435/808

  Optical sensing apparatus · CPC title

• G01N15/1434 Primary

  Optical arrangements · CPC title

• C12M41/36

  of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404) · CPC title