Dosimeters including lensless imaging systems

Patent metadata

Field	Value
Publication number	US-9910254-B2
Application number	US-201414572164-A
Country	US
Kind code	B2
Filing date	Dec 16, 2014
Priority date	Dec 17, 2013
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

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. An apparatus comprising:
a lensless imaging system comprising
an array of sensors exposed at a common sensor surface, and
a microscopy sample chamber to receive a sample for imaging; and

a processor configured to
receive a microscopy image of at least a part of the sample in the chamber generated by the array of sensors of the lensless imaging system, the at least part of the sample containing blood removed from a subject, the blood having absorbed a dose of radiation before being removed from the subject;
from the received microscopy image determine a count of cells of at least one type in the blood in the at least part of the sample,
determine if the cells of the at least one type are non-uniformly distributed within the part of the sample of the received image; and
correct the count of the cells of the at least one type if the cells of the at least one type are non-uniformly distributed within the part of the sample of the received image.

2. The apparatus of claim 1 , wherein the array of sensors is formed in a CMOS chip.

3. The apparatus of claim 1 , wherein each sensor of the array of sensors has a size of about 2 μm by 2 μm or smaller.

4. The apparatus of claim 1 , wherein the processor is configured to automatically analyze data contained in the image.

5. The apparatus of claim 4 , wherein automatically analyzing the data comprises classifying different types of cells in the image.

6. The apparatus of claim 1 , wherein the processor is configured to derive the radiation dose the subject has absorbed based on the count.

7. The apparatus of claim 1 , wherein the processor is configured to automatically deliver the received image to a machine external to the apparatus for the machine to process information contained in the image and provide information about the radiation dosage.

8. The apparatus of claim 1 , comprising a network interface for connecting the apparatus to a network through wire or wireless connections.

9. The apparatus of claim 1 , wherein the apparatus comprises a handheld device.

10. The apparatus of claim 1 , wherein the sensors comprise digital image sensors capable of lensless optical microscopy.

11. The apparatus of claim 1 , comprising a computer-readable storage medium that stores reference hematological bio-dosimetry data for one or more cell types.

12. The apparatus of claim 11 , wherein the processor is configured to derive the radiation dosage the subject has absorbed based on comparing a count of one or more cell types to the reference biodosimetry data for the one or more cell types.

13. The apparatus of claim 1 , wherein the processor is configured to estimate lymphocyte depletion based on one or more counts of lymphocytes.

14. The apparatus of claim 1 , wherein the processor is configured to:
determine a first count of a first type of cells within a first sample received within the chamber at a first time;
determine 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
estimate the change in concentration of the first type of cells based on comparing the first count to the second count.

15. The apparatus of claim 1 , wherein the processor is configured to correct the count of the cells of the at least one type based on a volume of the sample.

16. The apparatus of claim 1 , comprising a sample delivery component for preparing and delivering the sample onto the sensor surface.

17. The apparatus of claim 1 , wherein the sample is to contain capillary blood obtained by a pin prick of the subject.

18. The apparatus of claim 1 , wherein the sample is to contain microbeads coupled to other molecules to endow the microbeads with binding specificity.

19. The apparatus of claim 18 , wherein the microbeads are to comprise microbeads of two or more different sizes.

20. The apparatus of claim 18 , wherein the microbeads are to comprise microbeads of two or more different shapes.

21. The apparatus of claim 18 , wherein the microbeads are to comprise microbeads that are at least one of transparent, colored, fluorescent, and opaque.

22. The apparatus of claim 1 , comprising a mechanism configured to move a first surface of the chamber relative to the sensor surface.

23. The apparatus of claim 22 , wherein the mechanism is configured to move the first surface parallel to the-sensor surface during at least part of the motion.

24. The apparatus of claim 22 , wherein the mechanism is configured to move 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.

25. The apparatus of claim 1 , wherein the sample received on the sensor surface of the chamber comprises one or more of anticoagulant, diluent, stain, antibody, erythrocyte lysing solution, and other reagents.

26. The apparatus of claim 1 , wherein the processor is configured to generate the count of the cells of the at least one type based on a volume of diluent within the sample.

27. The apparatus of claim 1 , wherein the processor is configured to generate the count of the cells of the at least one type based on detecting one or more surface antigens associated with the cells of the at least one type.

28. The apparatus of claim 1 , wherein the array of sensors comprises 1 megapixel or higher sensors.

29. The apparatus of claim 1 , wherein the chamber comprises one or more components to mix a volume of the sample received on the sensor surface by raising and lowering a surface of the chamber.

30. The apparatus of claim 1 , wherein the chamber has a height to accommodate no more than a monolayer of blood cells in the sample.

31. The apparatus of claim 1 in which the sample is in contact with the sensor surface.

32. The apparatus of claim 1 in which the sample has a predetermined volume.

33. The apparatus of claim 1 in which the cells of the at least one type comprise lymphocytes.

34. The apparatus of claim 1 in which the change in concentration comprises depletion.

35. The apparatus of claim 1 in which the processor is configured to, based on the count, determine a degree of change in concentration of the cells of the at least one type in the blood.

36. The apparatus of claim 35 in which the processor is configured to, based on the degree of change in the concentration of the cells of the at least one type in the blood, display information associated with a radiation dose absorbed by the subject.

37. An apparatus comprising:
a lensless imaging system comprising
an array of sensors exposed at a sensor surface, and
a chamber to receive a sample containing blood having absorbed a dose of radiation before being removed from a subject; and

a processor configured to
receive a microscopy image of at least a part of the sample in the chamber generated by the array of sensors,
from the received microscopy image determine a count of cells of at least one type in the blood in the at least part of the sample, and
correct the count of the cells of the at least one type to account for a n

Assignees

• Alentic Microscience Inc

Inventors

• Fine Alan Marc

Classifications

• G01N15/1429

  Signal processing · CPC title

• G02B21/0004

  specially adapted for specific applications · CPC title

• G01T1/02

  Dosimeters (G01T1/15 takes precedence) · 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

• G03H2001/005

  in microscopy, e.g. digital holographic microscope [DHM] · CPC title