BLOOD AND CELL ANALYSIS USING AN IMAGING FLOW CYTOMETER

• US 20100232675A1
• Filed: 12/04/2009
• Published: 09/16/2010
• Est. Priority Date: 01/25/1999
• Status: Active Grant

• Current Assignee: Cytek Biosciences Inc
• Original Assignee: Amnis Corporation (DiaSorin S.p.A.)
• Inventors: Hall, Brian, George, Thaddeus, Basiji, David, Zimmerman, Cathleen, Morrissey, Philip, Ortyn, William, Perry, David
• Granted Patent: US 8,406,498 B2
• Time in Patent Office: Days
• US Class Current: 382/134
• CPC Class Codes: A61B 1/00188 with focusing or zooming features
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/147 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1475 using image analysis for extracting features of the particle
• CPC Class Codes: G01N 2015/1488 Methods for deciding
• CPC Class Codes: G06V 20/695 Preprocessing, e.g. image segmentation

Abstract

Multimodal or multispectral images of cells comprising a population of cells are simultaneously collected. Photometric and/or morphometric image features identifiable in the images are used to identify differences between first and second populations of cells. The differences can include changes in a relative percentage of different cell types in each population, or a change in a first type of cell present in the first population of cells and the same type of cell in the second population of cells. The changes may be indicative of a disease state, indicative of a relative effectiveness of a therapy, or indicative of a health of the person from whom the cells populations were obtained.

Claims

1. An imaging system configured to acquire and analyze image data separately collected from a first and a second population of cells, where the image data for each population include a plurality of images of individual cells that are acquired simultaneously, to enable differences between the first and second populations to be quantified, comprising:

(a) a collection lens disposed so that light traveling from an individual cell passes through the collection lens and travels along a collection path;

(b) a light dispersing element disposed in the collection path so as to disperse the light that has passed through the collection lens into a plurality of light beams, thereby producing dispersed light;

(c) an imaging lens disposed to focus the dispersed light, producing focused dispersed light;

(d) a detector disposed to receive the focused dispersed light, such that the focused dispersed light incident on the detector simultaneously produces a plurality of images of the individual cell, the plurality of images comprising the image data; and

(e) a processor configured to analyze the image data for the plurality of images collected from individual cells in the first and second population of cells, to quantify at least one difference between the first population of cells and the second population of cells.

2. The imaging system of claim 1, wherein the plurality of images comprise at least one of the following two types of images:

(a) multispectral images; and

(b) multimodal images.

3. The imaging system of claim 1, wherein the processor is further configured to quantify a difference between a relative abundance of cell types in the first and the second population of cells.

4. The imaging system of claim 1, wherein the processor is further configured to quantify a difference relating to a first type of cell present in the first population of cells and the same type of cell present in the second population of cells.

5. The imaging system of claim 1, wherein the processor is further configured to identify at least one morphometric image feature that differs between the first and the second population of cells.

6. The imaging system of claim 1, wherein the processor is further configured to identify at least one photometric image feature that differs between the first and second population of cells.

7. The imaging system of claim 1, wherein the difference quantified between the first and second population of cells is a distribution of a molecule within the cells of each sample.

8. The imaging system of claim 1, wherein the processor is further configured to identify at least one cell type present in one of the first and the second population of cells, but not in the other of the first and the second population of cells.

9. A method for detecting at least one difference between a first and a second population of cells using image data collected separately for each population, where the image data include a plurality of images of individual cells that are acquired simultaneously, for the first population and for the second population, comprising the steps of:

(a) imaging the first population of cells and the second population of cells to collect the image data, such that a plurality of images for the cells are simultaneously collected for cells in the first population and for cells in the second population, the plurality of images comprising at least one of the following two types of images;

(i) multispectral images; and

(ii) multimodal images; and

(b) analyzing the image data collected to identify at least one difference between the image data collected for the first and the second population of cells.

10. The method of claim 9, further comprising the step of determining whether the difference between the first and second population of cells is indicative of a health of a person from which the first and second population of cells were obtained.

11. The method of claim 9, wherein the step of analyzing the image data collected to identify at least one difference between the first and the second population of cells comprises the step of identifying at least one morphometric image feature that differs between the first and the second population of cells.

12. The method of claim 9, wherein the step of analyzing the image data collected to identify at least one difference between the first and second population of cells comprises the step of identifying at least one photometric image feature that differs between the first and the second population of cells.

13. The method of claim 9, wherein the step of analyzing the image data collected to identify at least one difference between the first and second population of cells comprises the step of identifying at least one cell type present in one of the first and second population of cells, but not in the other of the first and the second population of cells.

14. The method of claim 9, wherein the step of analyzing the image data collected to identify at least one difference between the first and the second population of cells comprises the step of quantifying a difference between a distribution of cell types in the first and the second population of cells.

16. The method of claim 9, further comprising the step of adding a reagent to at least one of the first and the second population of cells before imaging that population of cells, wherein the reagent comprises at least one reagent selected from the group consisting of:

(a) a label that facilitates identification of one or more cellular biomolecules; and

(b) a stimulus likely to induce a change in the population of cells exposed to the stimulus.

17. The method of claim 9, wherein the step of imaging the first and the second population of cells to collect the image data comprises the step of simultaneously collecting at least two types of images for a cell, selected from a group consisting of the following types of images:

a bright field image, a dark field image, and a fluorescence image.

18. The method of claim 9, further comprising the step of acquiring the first population of cells from a person at a first time, and acquiring the second population of cells from the person at a later time.

19. The method of claim 9, further comprising the step of acquiring the first population of cells and the second population of cells from a person at the same time.

20. The method of claim 9, further comprising the step of exposing the second population of cells to a stimulus without exposing the first population of cells to the same stimulus, before collecting the image data for the second population of cells.

21. The method of claim 9, wherein the difference quantified between the first and second population of cells is a distribution of a molecule within the cells of each sample.

15. The method of claim wherein the step of analyzing the image data collected to identify at least one difference between the first and the second population of cells comprises the step of quantifying a difference between a first type of cell present in the first population of cells and the same type of cell present in the second population of cells.