Measuring volume and constituents of cells

• US 9,588,033 B2
• Filed: 12/10/2014
• Issued: 03/07/2017
• Est. Priority Date: 04/15/2011
• Status: Active Grant

• Current Assignee: Roche Diagnostics Hematology Inc (Roche Holding AG)
• Original Assignee: Roche Diagnostics Hematology Inc (Roche Holding AG)
• Inventors: Zahniser, Michael, Zahniser, Russell
• Primary Examiner(s): Stock, Jr., Gordon J
• Application Number:
  US14/566,000
• Publication Number:
  US 20150092200A1
• Time in Patent Office: 818 Days
• US Class Current: 1/1
• CPC Class Codes: G01N 15/0227 using imaging; using holography
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/018 Platelets
• CPC Class Codes: G01N 2015/1472 with colour
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/30024 Cell structures in vitro; Tissue sections in vitro
• CPC Class Codes: G06T 7/62 of area, perimeter, diameter or volume
• CPC Class Codes: G06V 20/69 Microscopic objects, e.g. biological cells or cellular parts
• CPC Class Codes: G06V 20/695 Preprocessing, e.g. image segmentation

Abstract

A method for determining a mean cell volume for a blood sample includes: illuminating the sample with incident light at a plurality of illumination wavelengths and obtaining a two-dimensional image of the sample at each of the plurality of illumination wavelengths; identifying a plurality of cells that appear in each of the images; for each one of the plurality of cells, determining an integrated optical density corresponding to each of the plurality of illumination wavelengths; for each one of the plurality of cells, determining a cell volume based on the integrated optical densities corresponding to each of the plurality of illumination wavelengths; and determining the mean cell volume for the blood sample from the cell volumes for each one of the plurality of cells.

Claims

1. A method for assessing an operating condition of a blood analysis device, the method comprising:

for each one of a plurality of cells in a control composition, using an electronic processor of the blood analysis device to;

determine at least one optical density value corresponding to a wavelength of illumination radiation incident on the cell;

determine at least one cell volume value corresponding to the wavelength of the illumination radiation incident on the cell based on mean and maximum optical density values associated with the cell; and

determine a hemoglobin content value by combining the at least one optical density value and the at least one cell volume value;

using the electronic processor to determine a mean cell hemoglobin value for the control composition based on the hemoglobin content values of each one of the plurality of cells;

using the electronic processor to compare a reference mean cell hemoglobin value for the control composition to the determined mean cell hemoglobin value for the control composition by determining a difference between the determined and reference mean cell hemoglobin values for the control composition;

using the electronic processor to compare the difference to a threshold difference value; and

re-calibrating the device if the difference is beyond the threshold difference value.

2. The method of claim 1, comprising, for each one of the plurality of cells, using the electronic processor to:

determine an area of the cell; and

determine the at least one cell volume value based on the area of the cell and a mean optical density value for the cell.

3. The method of claim 2, comprising, for each one of the plurality of cells, using the electronic processor to determine the at least one optical density value based on the area of the cell and the mean optical density value for the cell.

4. The method of claim 2, comprising, for each one of the plurality of cells, using the electronic processor to determine the hemoglobin content value by combining the area of the cell, the at least one optical density value, and the at least one cell volume value.

5. The method of claim 4, wherein the combining comprises calculating the hemoglobin content value as a linear combination of the at least one optical density value and the at least one cell volume value.

6. The method of claim 2, comprising, for each one of the plurality of cells:

obtaining an image of the cell comprising a plurality of pixels; and

using the electronic processor to determine the area of the cell from the plurality of pixels.

7. The method of claim 6, comprising, for each one of the plurality of cells, using the electronic processor to:

determine a perimeter of the cell from the plurality of pixels; and

determine whether to exclude the cell from the plurality of cells used to determine the mean cell hemoglobin value based on the perimeter.

8. The method of claim 6, comprising, for each one of the plurality of cells, using the electronic processor to determine whether to exclude the cell from the plurality of cells used to determine the mean cell hemoglobin value by comparing the area of the cell to a range of area values.

9. The method of claim 1, comprising, for each one of the plurality of cells, using the electronic processor to determine one cell volume value, one optical density value, and one hemoglobin content value.

10. The method of claim 9, wherein the one cell volume value and the one optical density value correspond to one wavelength of illumination radiation.

11. The method of claim 1, comprising, for each one of the plurality of cells, using the electronic processor to determine multiple cell volume values, multiple optical density values, and multiple hemoglobin content values.

12. The method of claim 11, wherein the multiple cell volume values and the multiple optical density values correspond to multiple wavelengths of illumination radiation.

13. A system for determining a mean cell hemoglobin value, the system comprising:

an illumination source configured to direct illumination radiation to each one of a plurality of cells;

a detector configured to measure radiation from each one of the plurality of cells;

a display device; and

an electronic processor coupled to the detector and configured to;

receive measurement signals from the detector corresponding to the measured radiation;

for each one of the plurality of cells, determine;

at least one optical density value corresponding to a wavelength of the illumination radiation;

at least one cell volume value corresponding to the wavelength of the illumination radiation based on mean and maximum optical density values associated with the cell; and

a hemoglobin content value by combining the at least one optical density value and the at least one cell volume value;

determine the mean cell hemoglobin value based on the hemoglobin content values of each one of the plurality of cells;

display images of at least some of the plurality of cells on the display device; and

for each one of the images, display the mean cell hemoglobin value for the corresponding one of the plurality cells overlaid on the image on the display device.

14. The system of claim 13, wherein the electronic processor is configured, for each one of the plurality of cells, to:

determine an area of the cell; and

determine the at least one cell volume value based on the area of the cell and a mean optical density value for the cell.

15. The system of claim 14, wherein the electronic processor is configured, for each one of the plurality of cells, to determine the at least one optical density value based on the area of the cell and the mean optical density value for the cell.

16. The system of claim 14, wherein the electronic processor is configured, for each one of the plurality of cells, to determine the hemoglobin content value by combining the area of the cell, the at least one optical density value, and the at least one cell volume value.

17. The system of claim 16, wherein the combining comprises calculating the hemoglobin content value as a linear combination of the at least one optical density value and the at least one cell volume value.

18. The system of claim 13, wherein the electronic processor is configured to determine, for each one of the plurality of cells, one cell volume value, one optical density value, and one hemoglobin content value, and wherein the one cell volume value and the one optical density value correspond to one wavelength of the illumination radiation.