Dosimeters including lensless imaging systems

• US 11,061,031 B2
• Filed: 04/03/2020
• Issued: 07/13/2021
• Est. Priority Date: 12/17/2013
• Status: Active Grant

• Current Assignee: Alentic Microscience Inc.
• Original Assignee: Alentic Microscience Inc.
• Inventors: Fine, Alan Marc
• Primary Examiner(s): Gabel, Gailene
• Application Number:
  US16/839,752
• Publication Number:
  US 20200292801A1
• Time in Patent Office: 466 Days
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: G01B 9/02041 characterised by particular imaging or detection techniques
• CPC Class Codes: G01N 15/1429 Signal processing
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2011/008 optical properties
• CPC Class Codes: G01N 2015/011 with lysing, e.g. of erythrocytes
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2333/70535 Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
• CPC Class Codes: G01N 33/56972 White blood cells
• CPC Class Codes: G01N 33/80 involving blood groups or blood types or red blood cells white blood cells G01N33/56972
• CPC Class Codes: G01T 1/02 Dosimeters G01T1/15 takes precedence
• CPC Class Codes: G02B 21/00 Microscopes
• CPC Class Codes: G02B 21/0004 specially adapted for specific applications
• CPC Class Codes: G02B 21/0008 Microscopes having a simple construction, e.g. portable microscopes
• CPC Class Codes: G02B 21/361 Optical details, e.g. image relay to the camera or image sensor G02B21/364 takes precedence; illumination details G02B21/06 and subgroups
• CPC Class Codes: G02B 21/365 Control or image processing arrangements for digital or video microscopes G02B21/361, G02B21/362 take precedence
• CPC Class Codes: G03H 2001/005 in microscopy, e.g. digital holographic microscope [DHM] microscopes G02B21/00; digital holography G03H1/0866
• CPC Class Codes: G03H 2001/045 : Fourier or lensless Fourier arrangement
• CPC Class Codes: G06T 2207/10056 : Microscopic image
• CPC Class Codes: G06T 2207/30242 : Counting objects in image
• CPC Class Codes: G06T 7/0012 : Biomedical image inspection
• CPC Class Codes: G06V 20/69 : Microscopic objects, e.g. biological cells or cellular parts
• CPC Class Codes: G06V 20/698 : Matching; Classification
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus

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.

Claims

1. A method comprising:

adding labeled antibodies to a blood sample of a subject,

producing an image of the blood sample using lensless optical microscopy, the blood sample including the labeled antibodies;

detecting the labeled antibodies in the image, wherein the labeled antibodies are bound to cells of one or more different types in the image based on the labeled antibodies being directed against the cells of the one or more different types;

generating counts of the cells of the one or more different types in the image based on the labeled antibodies in the image; and

based on the counts, deriving a radiation dose of the subject.

2. The method of claim 1 in which the labeled antibodies are specific to surface antigens of lymphocytes in the blood sample.

3. The method of claim 2 in which the surface antigens comprise CD3 or CD19 or both.

4. The method of claim 2 in which the lymphocytes comprise T lymphocytes or B lymphocytes or both.

5. The method of claim 1 in which the labeled antibodies are fluorescent or microbead-labeled or both.

6. The method of claim 1 comprising transferring the blood sample from the subject using a pipette system that includes the labeled antibodies.

7. The method of claim 1 in which the generation of the counts is performed automatically.

8. The method of claim 1 in which the cells of the one or more different types comprise lymphocytes.

9. The method of claim 1, in which the blood sample comprises a first blood sample taken at a first time from the subject, and the method comprises

performing the adding, producing, detecting generating, and deriving activities for a second blood sample taken from the subject at a second, different time, and

estimating lymphocyte depletion based on the adding, producing, detecting, generating, and deriving of the first blood sample and the second blood sample.

10. The method of claim 1 comprising correcting the counts for a volume of the imaged blood sample.

11. The method of claim 1, in which the blood sample contains diluted blood, and the method comprises correcting the counts for dilution of the imaged blood sample.

12. The method of claim 1, in which producing the image comprises producing the image at a resolution of 1 mega pixels or higher.

13. The method of claim 1, comprising remixing and resampling the blood sample by raising and lowering a surface of a sample chamber in which the blood sample is disposed.

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

15. The method of claim 1, comprising including in the sample microbeads coupled to the labeled antibodies to endow the microbeads with binding specificity.

16. The method of claim 15, comprising including in the sample microbeads of two or more different sizes.

17. The method of claim 15, comprising including in the sample microbeads of two or more different shapes.

18. The method of claim 15, comprising including in the sample microbeads that are at least one of transparent, colored, fluorescent, and opaque.

19. The method of claim 1, comprising moving a first surface of a chamber relative to a sensor surface of an image sensor by which the image is captured.

20. The method of claim 19, comprising moving the first surface parallel to the sensor surface during at least part of motion of the first surface relative to the sensor surface.

21. The method of claim 1, comprising including the labeled antibodies in a pipette system.