System and method for calculating focus variation for a digital microscope

• US 10,482,595 B2
• Filed: 08/27/2015
• Issued: 11/19/2019
• Est. Priority Date: 08/27/2014
• Status: Active Grant

• Current Assignee: S.D. Sight Diagnostics Ltd
• Original Assignee: S.D. Sight Diagnostics Ltd
• Inventors: Yorav-Raphael, Noam, Wolfovitz, Uri, Pollak, Joseph Joel
• Primary Examiner(s): Nakhjavan, Shervin K
• Application Number:
  US15/506,997
• Publication Number:
  US 20190087953A1
• Time in Patent Office: 1,545 Days
• Field of Search: None
• CPC Class Codes: G02B 21/244 using image analysis techniques
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/10061 from scanning electron microscope
• CPC Class Codes: G06T 2207/30072 Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 2207/30168 Image quality inspection
• CPC Class Codes: G06T 7/0002 Inspection of images, e.g. flaw detection
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G06T 7/90 Determination of colour characteristics

Abstract

A digital microscopy method, comprising: obtaining data representative of a series of images of at least a portion of a cell sample, the images being captured by performing a depth scan using a digital microscope, the series of images being associated with a series of depth levels of the cell sample, wherein the portion encompasses a mapping field, and the mapping field comprises a plurality of focus analysis regions; and calculating, using the images, a focus configuration for at least two of the focus analysis regions within the mapping field, giving rise to data indicative of focus variations within the mapping field.

Claims

1. A method, comprising:

obtaining, in a memory comprised in or operatively coupled to a digital microscope, data representative of at least one image of at least a portion of a cell sample, the at least one image acquired by a digital microscope, and the at least one image encompassing;

at least one mapping field, and

at least one diagnostic field, the at least one diagnostic field being different from the at least one mapping field;

using the obtained data, calculating data indicative of focus variation within the at least one mapping field;

capturing at least one image of the at least one diagnostic field; and

detecting an entity within the sample by analyzing the at least one captured image of the at least one diagnostic field,

the method comprising, using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing at least one action selected from the group consisting of;

(a) controlling the capturing of the at least one image of the at least one diagnostic field, and (b) analyzing the at least one captured image of the at least one diagnostic field.

2. The method according to claim 1, wherein obtaining the data representative of at least one image of at least the portion of the cell sample comprises obtaining the data representative of the at least one captured image.

3. The method according to claim 1, wherein obtaining the data representative of at least one image of at least the portion of the cell sample comprises obtaining data representative of at least one image of at least the portion of the cell sample, the at least one image being a different image from the at least one captured image.

4. The method according to claim 1, wherein obtaining the at least one image comprises obtaining the at least one image, the at least one diagnostic field differing from the at least one mapping field in at least one parameter selected from the group consisting of:

shape, size, and location.

5. The method according to claim 1, wherein the at least one diagnostic field is associated with at least one focus field, and wherein capturing at least one captured image of the at least one diagnostic field comprises using the focus field to calculate a focus configuration to be used for capturing the at least one image of the at least one diagnostic field.

6. The method according to claim 1, wherein using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action comprises using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting a parameter of the at least one diagnostic field selected from the group consisting of:

a size of the at least one diagnostic field, and a shape of the at least one diagnostic field.

7. The method according to claim 1, wherein using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action comprises using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting to capture a plurality of images of the at least one diagnostic field.

8. The method according to claim 1, wherein using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action comprises using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting to capture a plurality of images of the at least one diagnostic field, each of the plurality of images being acquired at a respective, different focus configuration.

9. The method according to claim 1, wherein the at least one mapping field encompasses a plurality of focus analysis regions, and wherein calculating data indicative of focus variation within the at least one mapping field comprises calculating data indicative of focus variation between respective focus analysis regions.

10. The method according to claim 9, wherein using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action comprises using the calculated data that are indicative of focus variation within the at least one mapping field as an input for calculating focus confidence scores indicative of levels of confidence in focus configurations calculated for respective focus analysis regions.

11. The method according to claim 10, wherein detecting an entity within the sample by analyzing the at least one image of the at least one diagnostic field comprises using a classification algorithm to classify the sample, and generating a classification confidence score associated with the classification of the sample, using the focus confidence scores as inputs.

12. The method according to claim 10, wherein detecting an entity within the sample by analyzing the at least one image of the at least one diagnostic field comprises:

detecting a candidate of the entity within the sample that is associated with a focus confidence score that is lower than a threshold; and

in response thereto, reimaging the candidate using different imaging parameters to those previously used to image the candidate.

13. The method according to claim 10, wherein using the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action further comprises using the focus confidence scores as inputs for performing the at least one action selected from the group consisting of:

(a) controlling the capturing of the at least one image of the at least one diagnostic field, and (b) analyzing the at least one image of the at least one diagnostic field.

14. The method according to claim 13, wherein using the focus confidence scores as inputs for performing the at least one action comprises using the focus confidence scores as inputs for selecting a parameter of the at least one diagnostic field selected from the group consisting of:

a size of the at least one diagnostic field, and a shape of the at least one diagnostic field.

15. Apparatus comprising:

a digital microscope comprising;

a memory configured to obtain data representative of at least one image of at least a portion of a cell sample, wherein the portion encompasses at least one mapping field, and at least one diagnostic field, the at least one diagnostic field being different from the at least one mapping field; and

a computer processor configured to;

calculate, using the obtained data, data indicative of focus variation within the at least one mapping field,

capture at least one image of the at least one diagnostic field,

detect an entity within the sample by analyzing the at least one captured image of the at least one diagnostic field, and

use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing an action selected from the group consisting of;

(a) controlling the capturing of the at least one image of the at least one diagnostic field, and (b) analyzing the at least one captured image of the at least one diagnostic field.

16. The apparatus according to claim 15, wherein the memory is configured to obtain the data representative of at least one image by obtaining the at least one image, the at least one diagnostic field differing from the at least one mapping field in at least one parameter selected from the group consisting of:

shape, size, and location.

17. The apparatus according to claim 15, wherein the at least one diagnostic field is associated with at least one focus field, and wherein the computer processor is configured to capture the at least one image of the at least one diagnostic field by using the focus field to calculate a focus configuration to be used for capturing the at least one image of the at least one diagnostic field.

18. The apparatus according to claim 15, wherein the computer processor is configured to use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action by using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting a parameter of the at least one diagnostic field selected from the group consisting of:

a size of the at least one diagnostic field, and a shape of the at least one diagnostic field.

19. The apparatus according to claim 15, wherein the computer processor is configured to use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action by using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting to capture a plurality of images of the at least one diagnostic field.

20. The apparatus according to claim 15, wherein the computer processor is configured to use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action by using the calculated data that are indicative of focus variation within the at least one mapping field as an input for selecting to capture a plurality of images of the at least one diagnostic field, each of the plurality of images being acquired at a respective, different focus configuration.

21. The apparatus according to claim 15, wherein the at least one mapping field encompasses a plurality of focus analysis regions, and wherein the computer processor is configured to calculate data indicative of focus variation within the at least one mapping field by calculating data indicative of focus variation between respective focus analysis regions.

22. The apparatus according to claim 21, wherein the computer processor is configured to use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action by using the calculated data that are indicative of focus variation within the at least one mapping field as an input for calculating focus confidence scores indicative of levels of confidence in focus configurations calculated for respective focus analysis regions.

23. The apparatus according to claim 22, wherein the computer processor is configured to detect an entity within the sample by analyzing the at least one image of the at least one diagnostic field by using a classification algorithm to classify the sample, and generating a classification confidence score associated with the classification of the sample, using the focus confidence scores as inputs.

24. The apparatus according to claim 22, wherein the computer processor is configured to detect an entity within the sample by analyzing the at least one image of the at least one diagnostic field by:

detecting a candidate of the entity within the sample that is associated with a focus confidence score that is lower than a threshold; and

in response thereto, reimaging the candidate using different imaging parameters to those previously used to image the candidate.

25. The apparatus according to claim 22, wherein the computer processor is configured to use the calculated data that are indicative of focus variation within the at least one mapping field as an input for performing the at least one action by using the focus confidence scores as inputs for performing the at least one action selected from the group consisting of:

(a) controlling the capturing of the at least one image of the at least one diagnostic field, and (b) analyzing the at least one image of the at least one diagnostic field.

26. The apparatus according to claim 25, wherein the computer processor is configured to use the focus confidence scores as inputs for performing the at least one action by using the focus confidence scores as inputs for selecting a parameter of the at least one diagnostic field selected from the group consisting of:

a size of the at least one diagnostic field, and a shape of the at least one diagnostic field.

27. A method, comprising:

obtaining, in a memory comprised in or operatively coupled to a digital microscope, data representative of at least one image of at least a portion of a cell sample, the at least one image acquired by a digital microscope;

using the obtained data, calculating focus configurations to be used for acquiring images of the cell sample or parts thereof by the digital microscope;

determining that a calculated focus configuration exceeds a given threshold; and

in response thereto, generating an error message indicative of an error selected from the group consisting of;

an error in the microscope, an error in the sample carrier, an error in positioning of the sample carrier with respect to a portion of the microscope, and an error in the cell sample.