阅读说明：本技术 自动化显微扫描系统和方法 (Automated micro-scanning system and method ) 是由 马修·P·霍宁 胡黎明 肖恩·麦圭尔 克洛西·墨哈尼安 于 2020-02-03 设计创作，主要内容包括：实现了用于自动化显微扫描系统的工艺和技术,其中显微镜系统在扫描窗中的粗间隔位置执行“搜寻模式”操作直到获得可接受的质量扫描结果。然后系统在包含具有可接受的扫描结果的位置的网格单元内的所有视场上执行详细扫描。系统对整个网格单元的扫描结果执行另一次评估,如扫描结果总体上可接受,则系统进行到执行“扫描模式”操作。扫描模式操作包括从搜寻模式操作中扫描和评估与可接受的网格单元相邻的一或多个网格单元内的所有视场。系统可依次执行搜寻模式操作和扫描模式操作,编译关于扫描处理的方面的信息,直到满足一或多个终止标准为止。(Processes and techniques for an automated microscopic scanning system are implemented in which the microscope system performs a "seek mode" operation at coarsely spaced locations in the scanning window until acceptable quality scanning results are obtained. The system then performs a detailed scan over all fields of view within the grid cell containing locations with acceptable scan results. The system performs another evaluation of the scan results for the entire grid cell, and if the scan results are generally acceptable, the system proceeds to perform a "scan mode" operation. The scan mode operation includes scanning and evaluating all fields of view within one or more grid cells adjacent to an acceptable grid cell from the search mode operation. The system may perform a seek mode operation and a scan mode operation in sequence, compiling information about aspects of the scan process until one or more termination criteria are met.)

1. A microscope system, comprising:

a microscope assembly configured to obtain a microscopic scan of a field of view within a sample, the microscope assembly operable to perform operations comprising:

defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view;

defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell;

selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and is

Providing an indication of the compiled one or more aspects of the acceptable scan results if one or more criteria for terminating a scan operation are met.

2. The system of claim 1, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

3. The system of claim 1, wherein defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view comprises:

the scanning window is defined as a plurality of square grid cells, wherein each square grid cell includes an equal number of rows and columns of fields of view.

4. The system of claim 1, wherein performing the microscopic scan at the selected field of view within the selected ones of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

5. The system of claim 1, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

6. The system of claim 1, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarse-spaced grid pattern comprising a first coarse-spaced grid cell positioned proximate the scanning window center and a plurality of first non-adjacent grid cells located within a first non-adjacent perimeter disposed around and spaced apart from the first coarse-spaced grid cell.

7. The system of claim 6, wherein selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell comprises:

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of:

proceeding outward from the first coarse spaced grid cells to select first non-adjacent grid cells located within the first non-adjacent perimeter; or

Traversing from one of first non-adjacent grid cells to select another of the first non-adjacent grid cells that is located within the first non-adjacent perimeter.

8. The system of claim 6, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarsely-spaced grid pattern comprising a plurality of second non-adjacent grid cells located within a second non-adjacent perimeter disposed around and spaced apart from the first non-adjacent perimeter.

9. The system of claim 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the micro-scan at all fields of view within half of the adjacent grid cells within a perimeter of the grid cell adjacent to the selected coarse spaced grid cell that is acceptable.

10. The system of claim 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of a grid cell adjacent to and sharing a common boundary with the acceptable selected coarse spaced grid cell.

11. The system of claim 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to and sharing common corner points with the acceptable selected coarse spaced grid cells.

12. The system of claim 1, wherein performing scan mode operations further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

13. The system of claim 1, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

at least one of the following operations:

defining a coarse-spaced grid pattern comprising a plurality of non-adjacent grid cells;

defining a coarse-spaced grid pattern comprising a plurality of adjacent grid cells; or

A coarse-spaced grid pattern is defined that includes a plurality of non-adjacent grid cells and a plurality of adjacent grid cells.

14. A microscope system, comprising:

a microscope assembly configured to enable microscopic scanning of a field of view within a sample, the microscope assembly operable to:

defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, a portion of the plurality of grid cells being coarse spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell; and

returning to a seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

15. The system of claim 14, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

16. The system of claim 14, wherein performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the acceptable selected coarse-spaced grid cell comprises:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells.

17. The system of claim 14, wherein performing the microscopic scan at the selected field of view within the selected ones of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

18. The system of claim 14, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

19. The system of claim 14, wherein the microscope assembly is further operable to perform operations comprising:

if one or more criteria for terminating the scanning operation are not satisfied, selecting a next coarse-interval grid cell as the selected coarse-interval grid cell, and returning to perform a seek mode operation.

20. The system of claim 14, wherein the scan mode operation further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

21. A method of operating a microscope assembly configured for enabling microscopic scanning of a field of view within a sample, the method comprising:

defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, a portion of the plurality of grid cells being coarse spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell; and

returning to a seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

22. The method of claim 21, wherein the sample comprises at least one of a thick or thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

23. The method of claim 21, wherein performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the acceptable selected coarse-spaced grid cell comprises:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells.

24. The method of claim 21, wherein performing the microscopic scan at the selected field of view within the selected ones of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

25. The method of claim 21, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

26. The method of claim 21, wherein the microscope assembly is further operable to perform operations comprising:

if one or more criteria for terminating the scanning operation are not satisfied, selecting a next coarse-interval grid cell as the selected coarse-interval grid cell, and returning to perform a seek mode operation.

27. The method of claim 21, wherein the scan mode operation further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

Technical Field

The present disclosure relates generally to microscopy, and more particularly to automated microscopic scanning for improved analysis of samples.

Background

Microscopic analysis of biological samples is a core technology in many areas of health care and life sciences. One important area in which microscopy plays a critical role is the diagnosis and treatment of diseases such as malaria.

Current educational material of the world health organization describes a method for malaria microscopy that includes preparing a microscope slide with a blood sample and staining the blood sample with Giemsa dye to improve visibility. Traditionally, blood samples deposited on microscopic slides include thick and thin films. Thick membranes are thicker sections, containing more blood in a given area (e.g., about 10-20 red blood cells thick), and are commonly used for preliminary diagnosis and quantification of malaria parasites. The membrane is a relatively thin section (e.g., ideally a monolayer of red blood cells) and is commonly used to identify the species of malaria parasite.

Microscopic analysis of blood samples can be performed manually by qualified personnel, however, automated or semi-automated microscope systems have also been developed to provide valuable assistance to medical providers and researchers. Representative examples of commercially available automated microscope systems include macondiEas (g)The yScan Go system, and various other commercially available automated microscopy systems. Although very desirable results have been obtained using such prior art microscope systems, there is still room for further development and improvement.

Disclosure of Invention

The present disclosure teaches automated microscanning systems and methods for improved analysis of biological samples. In at least some implementations, techniques and processes according to the present disclosure can identify regions of a microscope slide containing a biological sample (e.g., blood), can identify various regions and sub-regions of the sample suitable for microscopic analysis, and can provide scanning strategies to ensure efficient and effective scanning of sufficiently high quality regions of the sample to provide proper analysis of the sample. In some implementations, such systems can identify thick and thin film regions and boundaries of thick and thin film regions of a slide using machine learning methods (e.g., deep learning or other region detection methods) based on an initial low magnification (or macro) image of the slide.

Briefly, in at least some implementations, a microscope system defines a scanning window over a portion of a sample, the scanning window including a plurality of grid cells, each grid cell containing a plurality of fields of view. The system then performs a "seek mode" operation at coarse granularity locations throughout the scan window. More specifically, a microscopic scan is performed at one location and evaluated to determine the quality of the scan results. The system continues to scan and evaluate the scan results at various coarse spaced locations throughout the sample until acceptable quality scan results are obtained. The system then performs a detailed scan over all fields of view within the grid cell containing locations with acceptable scan results. The system performs another evaluation of the scan results for the entire grid cell and proceeds to perform a "scan mode" operation if the scan results for the grid cell are generally acceptable. More specifically, the scan mode operation includes scanning and evaluating all fields of view within one or more grid cells adjacent to an acceptable grid cell from the seek mode operation. The system then performs additional seek mode operations and scan mode operations in sequence, compiling one or more aspects of the scan process until one or more termination criteria are met, at which point the scan process ends.

More specifically, in at least some implementations, a microscope system includes: a microscope assembly configured to obtain a microscopic scan of a field of view within a sample, the microscope assembly operable to perform operations comprising: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; and defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells. In at least some implementations, each coarse-spaced grid cell is not adjacent to other coarse-spaced grid cells.

The system then performs a seek mode operation, which includes: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; and if the quality of the scan result at the selected field of view is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, and returning to perform the microscopic scan and evaluate the quality of the scan result. The seek mode operation further comprises, if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceed to scan mode operation.

The microscope assembly then performs a scan mode operation comprising: performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell.

The microscope assembly then performs operations comprising: selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and if the one or more criteria for terminating a scan operation are met, providing an indication of the compiled one or more aspects of the acceptable scan results.

In at least some implementations, the sample includes at least one of a thick film or a thin film of the blood sample, and wherein the one or more criteria for terminating the scanning operation includes: one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

This summary is intended to provide an introduction to some exemplary aspects of implementations consistent with the present disclosure. It is not intended to provide an exhaustive explanation of all possible implementations and therefore should be construed as merely an introduction to the following disclosure and not a limitation.

Drawings

FIG. 1 is a schematic illustration of a microscopic environment in which processes and techniques according to the present disclosure may be implemented.

FIG. 2 is a side cross-sectional view of an automated microscope.

Fig. 3 illustrates an embodiment of a microscopy process according to the present disclosure.

Fig. 4 illustrates an embodiment of a set of images of a biological sample on a slide.

FIG. 5 illustrates a process for determining the suitability of a slide for analysis according to the present disclosure.

Fig. 6 illustrates a scanning and evaluation process according to the present disclosure.

Fig. 7 shows a schematic view of a scanning window over a thick film according to the present disclosure.

Fig. 8 shows representative scan results of the type obtained during a detailed scan of a thick film.

Fig. 9 shows an enlarged view of an acceptable grid cell with a total of twenty-five fields of view according to the present disclosure.

Fig. 10 shows an enlarged view of the perimeter around an acceptable grid cell and an adjacent grid cell according to the present disclosure.

FIG. 11 illustrates another scanning and evaluation process according to the present disclosure.

FIG. 12 shows a schematic view of a scanning window positioned over a thin film according to the present disclosure.

Fig. 13 shows representative scan results of the type obtained during a detailed scan of a thin film.

Fig. 14 illustrates an implementation of a scan window divided into grid cells and including grid cells determined to be acceptable during scan mode operation.

Fig. 15 and 16 show the scan window of fig. 14 after additional scan mode operation.

Fig. 17 shows another embodiment of a microscopy process according to the present disclosure.

FIG. 18 illustrates a schematic diagram of a computing system for implementing one or more aspects of the present disclosure.

Fig. 19 and 20 show alternative embodiments of coarse-spaced grid cells according to the present disclosure.

Detailed Description

Processes and techniques for an improved microscanning system for analysis of biological samples will now be disclosed. In the following description, numerous specific details of certain implementations are described and illustrated in the accompanying drawings. One skilled in the art will understand that the present disclosure may have other possible implementations, and that such other implementations may be practiced with or without some of the specific details set forth in the following description. Additionally, it should be appreciated that although various aspects may be described in a particular order or with respect to certain drawings or certain embodiments, it should be appreciated that these aspects may be combined or reordered in various ways to create alternative implementations that remain consistent with the scope of the present disclosure and the claims set forth below.

The present disclosure teaches automated microscopy processes and techniques for improving analysis of biological samples. More specifically, in at least some implementations, a system according to the present disclosure can autonomously identify regions of a microscope slide containing a biological sample (e.g., blood), can identify various regions and sub-regions of the sample suitable for microscopic analysis, and can provide an automated scanning strategy to ensure that sufficiently high quality regions of the sample are effectively and efficiently scanned to provide proper analysis of the sample. In some implementations, such systems can use machine learning methods (e.g., deep learning or other region detection methods) to identify thick and thin film regions of a slide based on an initial low magnification (or macroscopic) image of the slide.

In at least some implementations, a system according to the present disclosure can capture high magnification images at various fields of view within a region, and can follow a scanning strategy that takes into account an assessment of the suitability of each region for analysis. Based on the suitability assessment, the location captured within the sample (thick or thin film) for the next detailed scan is determined. Such a system may continue to automatically capture and analyze detailed high magnification scans until predetermined criteria (e.g., a criterion specifying a total number of white or red blood cells to capture for analysis, etc.) are met.

As described more fully below, processes and techniques according to the present disclosure may advantageously reduce scan time by: reducing the number of low quality fields of view scanned, reducing the time and effort required by the operator to select the appropriate area of the slide, and reducing the time required to reject poor quality slides. Such processes and techniques may be particularly valuable for batch imaging of many slides or for time-sensitive analysis of biological samples.

Fig. 1 is a schematic illustration of a microscopy environment 100 for implementing processes and techniques according to the present disclosure. In this implementation, microscopy environment 100 includes an automated microscope assembly 110, with automated microscope assembly 110 having a microscope 112 (shown in phantom) for viewing a sample on a microscope slide, and a stage 114 for supporting and positioning the slide for microscopic analysis. The automated microscope component 110 represents many types, models, and variations of microscope systems that may be configured and operated (or modified to operate) in accordance with the processes and techniques disclosed herein, and is described more fully below with respect to fig. 2.

As further shown in fig. 1, slide 120 (enlarged for clarity) includes a biological sample for microscopic examination. In this implementation, the slide 120 includes a blood sample deposited as thick and thin films 124 and 126 in a manner that is conventional for malaria microscopy. In this implementation, the slide 120 also includes an identifier portion 122, the identifier portion 122 providing identifying information associated with the blood sample (e.g., patient, sample type, date, source, provenance data, etc.). As noted above, the thick film 124 is desirably a thicker section containing more blood (e.g., about 10-20 red blood cells thick) per given area and is typically used for initial diagnosis and quantification of malaria parasites, while the thin film 126 is a relatively thinner section (e.g., desirably a monolayer of red blood cells) and is typically used to identify the species of the plasmodium parasite. Procedures for the proper preparation of slides carrying blood samples for malaria microscopy are generally known, for example as described in the "malaria microscopy standard procedures" of the world health organization (e.g., currently available at the website "apps. who. int/iris/handle/10665/274382"). There are also dedicated slide systems for this procedure. See, for example, U.S. patent No.9,453,996 to Delahunt et al.

As further depicted in fig. 1, in at least some implementations, the slide 120 can be secured to the slide tray 130 with other slides, and the slide tray 130 can be placed on the stage 114 of the automated microscope assembly 110. The stage 114 may be automated such that the automated microscope assembly 110 can controllably position the slide 120 for imaging, scanning, and analysis, as described more fully herein. The automated microscope assembly 110 may be operatively coupled to a computing system 140, the computing system 140 having a keyboard 142 for inputting user commands and a display 144 for displaying analysis results, such as high magnification images 146 of the thick and thin films 124, 126 on the slide 120.

Fig. 2 is a side cross-sectional schematic view of the automated microscope assembly 110 of fig. 1. It should be understood that the automated microscope assembly 110 shown in fig. 2 is merely one representative embodiment that may be used to implement processes and techniques according to the present disclosure, and that numerous alternative embodiments of microscope assemblies may be suitably employed. In this implementation, microscope assembly 110 includes a main controller 202 operatively coupled to a memory 204 and an input/output (I/O) port 206. The main controller 202 generally includes one or more processors and circuitry configured to receive and interpret instructions (e.g., instructions stored in memory 204, instructions provided through I/O port 206, etc.) for providing control signals to and receiving information back from other components of the automated microscope assembly 110 as required to perform the processes and techniques described herein. In alternative implementations, the main controller 202 may be configured to perform at least some of the operations described, while additional operations may be performed by one or more separate processing components (e.g., computing system 140 of fig. 1) operatively coupled to the microscope assembly 110 via the I/O ports 206.

As shown in fig. 2, the main controller 202 is operatively coupled to a stage controller 208 that controls a motorized stage 210 (e.g., the motorized stage 210 can be at least a portion of the stage 114 of fig. 1) to controllably position the slide 120 relative to the microscope 112. In this implementation, the microscope 112 generally includes an objective lens assembly 212 operatively coupled to a positioner 214. Positioner controller 216 is operably coupled to receive control signals from main controller 202 and provide signals to positioner 214 to controllably adjust the operation of objective lens assembly 212, such as to adjust magnification, position, or other operating parameters. In operation, the light source 218 is controlled by the main controller 202 to provide illumination light 220 via one or more illumination optics 222 to illuminate the blood sample (or other biological sample) on the slide 120. The camera 224 is operably coupled to receive light or other suitable signals from the microscope 112 and may be controlled by the master controller 202 to obtain an image of the sample on the slide 120, which may then be stored in the memory 204 or output to other devices (e.g., the computer system 140 of fig. 1) through the I/O port 206.

As previously mentioned, automated microscope assembly 110 is but one representative embodiment of a microscope assembly suitable for implementing processes and techniques according to the present disclosure. Other suitable automated microscope components generally include, but are not limited to, a removable from MacAdyCaisy Hebo TengThose commercially available, and disclosed in U.S. Pat. No.9,851,550 to Soenksen and U.S. Pat. No.6,049,421 to Raz et alOpen systems and system types. The micro-scanning system may also be used with an image analysis system such as described in U.S. patent nos. 9,836,839 and 10,061,972 to Champlin et al.

Fig. 3 illustrates an embodiment of a microscopy process 300 according to the present disclosure. In this embodiment, the microscopy process 300 includes positioning a slide for analysis at 310, such as placing the slide 120 on the motorized stage 210 of the automated microscope assembly 110, and operating the motorized stage 210 to position the slide 120 in position relative to the microscope 112. The process 300 also includes obtaining a "macro image" of the slide at 312, such as by using the camera 224 of the microscope assembly 110. As used herein, the term "macroscopic image" of a slide refers to an image of at least a portion of the slide that shows enough (e.g., all or substantially all) of the biological sample on the slide to enable determination of the location and extent of one or more regions of interest (e.g., thick film regions, thin film regions, etc.) on the slide.

For example, fig. 4 shows an embodiment of a set of images of a biological sample including a macro image 400 of a slide 420 of the type that may be obtained (at 312) by the microscopy process 300. In this embodiment, the slide 420 includes an identifier portion 422 that provides information about the biological sample (e.g., patient name, etc.), information about a thick film 424 of the patient's blood, and information about a thin film 426 of the patient's blood, wherein the thick film 424 and the thin film 426 are preferably suitable for detection and diagnosis of malaria. Fig. 4 also shows a set of six field of view (FOV) images (labeled with letters "a" through "f") representing magnified views of various portions of a film 426 of the type that may be obtained using the microscope 112 of the automated microscope assembly 110. From the perspective of microscopy process 300, the six FOV images may be classified as having unacceptable quality for analysis (e.g., FOV images "a", "b", and "f") or acceptable quality for analysis (e.g., FOV images "c", "d", and "e"). More specifically, in at least some embodiments, FOV images "a" and "b" may be considered to lack sufficient resolution and clarity of a single cell, while FOV image "f" may contain too few cells and poor cell resolution and, therefore, may be classified as unacceptable or unavailable for at least some implementations of microscopy process 300. Moreover, in at least some implementations, FOV images "c" through "e" may be considered to not suffer from these unacceptable features and thus may be classified as acceptable and usable in at least some implementations. It should be understood that similar FOV images may be obtained within the thick film 424 of the slide 420 with similar results, i.e., some FOV images within the thick film 424 may be considered acceptable for at least some implementations of the microscopy process 300, while others may be considered unacceptable, as described more fully below.

Referring again to fig. 3, the microscopy process 300 also includes analyzing the macroscopic image of the slide at 314 to determine the suitability of the slide for malaria analysis. For example, in at least some implementations, analyzing the macroscopic image of the slide (at 314) can include performing a suitability analysis process as shown in fig. 5.

In the embodiment shown in fig. 5, the process 500 of determining the suitability of a slide for analysis includes providing a macroscopic image of the slide for analysis at 502, and then performing an initial quality assessment of the slide at 510. It should be appreciated that the initial quality assessment (at 510) may involve one or more operations directed to initial screening of slides in order to determine the general suitability of the slides before proceeding to more detailed microscope operations. For example, in the implementation shown in fig. 5, performing (at 510) an initial quality assessment includes assessing one or more quality characteristics of the film based on the macroscopic image at 512. In at least some implementations, assessing (at 512) one or more quality characteristics of the film based on the macroscopic image of the slide includes determining one or more of: composition, exposure, focus, sharpness, brightness, or any other suitable characteristic. In further implementations, assessing one or more quality characteristics of the film based on the macroscopic image (at 512) can include assessing a feature commonly known as a "Brenner" score "(or" Brenner focus score "), such as disclosed in U.S. patent No.9,041,791 to Zahniser, for example.

At 514, the process 500 includes (at 512) determining whether the quality of the slide is initially acceptable based on the assessment of the one or more quality features. If (at 514) it is determined that the quality of the slide is not acceptable, the process 500 proceeds to provide an indication at 516 that the slide is not suitable for analysis. Alternatively, if (at 514) it is determined that the quality of the slide is acceptable, process 500 may include performing image recognition at 518 to determine that thick and thin films are present on the slide. In at least some implementations, performing image recognition (at 518) to determine the presence of thick and thin films on the slide may involve performing one or more machine learning operations using one or more image recognition models. Such image recognition models are well known and used in a variety of image recognition processes and techniques, for example, as described in "Deep Learning for general Object Detection: A surface" by Li Liu et al, arXiv:1809.02165[ cs.CV ],6Sept., 2018.

Briefly, in at least some implementations, the machine learning operation may include training one or more image recognition models using known good images of known objects, at 520. The one or more image recognition models may include, for example, a Convolutional Neural Network (CNN) model, a region with CNN (RCNN) model, a depth CNN (dcnn) model, a Single Shot Detection (SSD) model, or any other suitable image recognition model. In at least some implementations, the images provided for analysis can be processed to determine which regions of the image (box) contain (or do not contain) one or more objects (e.g., thick films, thin films, etc.). The determination is based on features extracted from the image portions within each region (or frame). Features are computed using one or more image recognition models, and the features are trained using known good images that contain known objects. The region is classified according to whether it contains one or more objects. More specifically, in at least some implementations, a region can be classified as containing either a thick film or a thin film. In this manner, in at least some implementations, image recognition can be performed using machine learning operations to determine the presence of thick and thin films on the slide (at 518).

The initial quality assessment of the slide shown in FIG. 5 (at 510) also includes determining whether the slide is suitable for further analysis at 522 (e.g., the slide includes both thick and thin films). If (at 522) it is determined that the slide is not suitable (e.g., does not include both thick and thin films), then the process 500 proceeds to provide an indication of the suitability of the slide for analysis at 516. In another implementation, a determination that the image does not include a thick film (whether or not a thin film is present) causes the process to proceed to provide an indication of non-suitability. In other implementations not specific to conventional malaria microscopy, determining that the image does not include other types of biological samples (e.g., tissue sections) causes the process to proceed to provide an indication of the unsuitability.

Alternatively, if (at 522) it is determined that the slide is suitable (e.g., includes both thick and thin films), process 500 may optionally include providing a macro image at 524 for future training of one or more recognition models. The suitability assessment process 500 then proceeds to provide an indication of the suitability of the slide for analysis at step 526. Finally, after providing the indication of suitability (at 526), or after providing the indication of unsuitability (at 516), the process 500 ends or continues with other operations at 528.

Returning again to fig. 3, after analyzing the macroscopic image of the slide (at 314), the microscopy process 300 also includes determining whether the slide is suitable for malaria analysis at 316 (e.g., based on the results from the suitability analysis process 500). If (at 316) it is determined that the slide is not suitable for malaria analysis, process 300 proceeds to determine if there are more slides available for analysis at 318, if so, process 300 returns to position a new slide for analysis at 310, and the above operations 310 through 316 are repeated for the new slide.

Alternatively, if (at 316) it is determined that the slide is suitable for malaria analysis, process 300 continues with analyzing the macroscopic image of the slide to determine thick films at 320And the boundaries of the film. Techniques for automatically detecting biological sample boundaries on microscope slides (e.g., thick film 424, thin film 426) using automated microscope assemblies are well known and include, but are not limited to, commercially available productsOr generally by the processes and techniques disclosed in U.S. patent No.7,151,246 to Fein et al, U.S. patent No.7,558,415 to McLaren et al, U.S. patent No.8,107,715 to Baumfalk et al, and U.S. patent No.10,093,957 to Pollak et al.

With continued reference to fig. 3, microscopy process 300 further includes performing a scanning and analysis operation on the thick film at 322. The scanning and analyzing operations performed on the thick film (at 322) may include many detailed operations that may be performed in various suitable implementations, and will be described more fully below with respect to the accompanying figures. Briefly, in at least some implementations, the scanning and analysis operations performed (at 322) on the thick film may include one or more preparation operations followed by a so-called "seek mode" operation that involves evaluating microscopic images at various locations that are relatively coarsely spaced across many different locations of a desired biological sample (e.g., thick film 424, thin film 426, etc.). Once an acceptable location that provides (or initially appears to provide) microscopic scan results of acceptable quality is identified using the seek mode operation, the operation (at 322) may then perform a so-called "scan mode" operation in which detailed scanning microscopic images are performed at relatively dense-spaced locations that are close to the acceptable location determined from the seek mode. After successfully performing the detailed scan mode operation, the operation (at 322) may return to seek mode operation, and may continue to iterate between seek mode operation and scan mode operation until one or more desired criteria are met. Additional details of various possible implementations of the scanning and analysis operations performed on the thick film are described more fully below (at 322).

In the implementation shown in FIG. 3, a microscopic examination departmentThe method 300 further includes determining whether a malaria parasite is present within the thick film at 324. The determination (at 324) may be based on (at 322) results of scanning and analyzing operations on the thick film, which may be generally directed to automated image recognition processes and techniques configured to detect and enumerate features present in the biological sample, including cells and malaria parasites that may be present in the blood sample. Such automated image recognition processes and techniques have been implemented in commercially available systems, including but not limited to those commercially availableImplemented in a system such as the EasyScan Go system.

If (at 324) it is determined that no malaria parasites (or a relatively small number of malaria parasites below a given threshold) are present in the thick membrane 424, the microscopy process 300 may include providing an indication that no parasites are detected (or an insufficient number of detected parasites) at 326, and then the microscopy process 300 may continue (at 318) to determine whether more slides are available for analysis. In some implementations, this process can be done after reading the thick film, regardless of whether a parasite is detected, thereby providing an indication of whether a parasite is detected.

On the other hand, if it is determined (at 324) that malaria parasites are present in thick film 424, then in certain implementations, microscopy process 300 proceeds to perform scanning and analysis operations on the thin film at 328. Again, it should be understood that the scanning and analyzing operations performed on the thin film (at 328) may include many detailed operations that may be performed in various suitable implementations, and will be described more fully below with reference to the accompanying drawings. Briefly, in at least some implementations, the scanning and analysis operations performed on the thin film (at 328) may follow a substantially similar approach to the scanning and analysis operations performed on the thick film (at 322), may include one or more preparation operations, followed by so-called "seek mode" operations at various locations that are relatively coarsely spaced, and then followed by one or more "scan mode" operations once an acceptable location is determined using the seek mode. Additional details of various possible implementations of the scanning and analysis operations performed on the thin film are described more fully below (at 328).

With continued reference to fig. 3, after performing the scanning and analysis operations on the film (at 328), the microscopy process 300 includes providing an indication of one or more parasite species and/or one or more other characteristics of the biological sample at 330. In at least some implementations, the microscopy process 300 then determines whether more slides are available for analysis at 318, and if so, the process 300 returns to locate a new slide for analysis at 310 and repeats the above operations 310-330 for the new slide. Finally, once it is determined (at 318) that no more slides are available for analysis, the microscopy process 300 ends at 332 or continues with other operations.

As described above, the scanning and analyzing operations performed (at 322) on the thick film may include many detailed operations that may be performed in various suitable implementations. For example, in the implementation shown in FIG. 6, the scanning and analysis process 600 includes performing a preparation operation at 605. In at least some implementations, the preparation operation performed at 605 can include establishing a scanning window for scanning the biological sample at 610. Establishing (at 610) the scanning window may include determining a portion of the thick film 424 that may be subjected to detailed scanning operations using the automated microscope assembly 110. It should be appreciated that the scanning window established at 610 is preferably, but not necessarily, a relatively small portion of the thick film 424, and is preferably positioned to provide a relatively high quality field of view (FOV) image, such that the desired microscopic analysis is performed and the desired information is obtained while the operation of the automated microscope assembly 110 can be performed as little as practical. Although the following description of the scanning and analysis process 600 is described below with specific reference to performing operations on the thick film 424, it should be understood that in alternative implementations, the scanning and analysis process 600 may also be applied to the thin film 426 of the slide 420, or to various other suitable biological samples that may be subjected to automated microscopic analysis.

In at least some implementations, the establishment of the scanning window can be automatically determined (at 610) based on the boundary of the thick film 424 (determined at 320). In some implementations, the scan window can be established as a relatively small scan area centered at the approximate center of the thick film 424. Additionally, the scan window may be established (at 610) based on input received from an external device, such as input received from a user of automated microscope assembly 110 (e.g., a technician, a healthcare worker, etc.) or from a user of computing system 140 (e.g., using keyboard 142), or based on input received from another device (e.g., through I/O port 206). Further, for cases where the biological sample is relatively uniform, such as for relatively uniform thick films, the location of the scanning window may be located at the approximate center of the thick film 424, or at any other suitable location within the thick film.

In still other implementations, the position of the scanning window may be determined based on an automatic analysis of the macro image 400 of the thick film 424 and an automatic selection of positions with relatively improved probabilities of containing a suitable number of field of view (FOV) images that are to be classified as having acceptable analytical quality. For example, in some implementations, the location of the scanning window may be automatically determined (at 610) by: the macro image 400 of the thick film 424 is analyzed and the area of the thick film 424 is selected that avoids or minimizes the relatively dark portions of the thick film 424 that may provide a FOV image lacking sufficient resolution, and also avoids or minimizes the relatively bright portions of the thick film 424 that may provide a FOV image that may contain too few cells. Accordingly, establishing (at 610) a scan window may include an automated analysis of the thick film 424 to determine the location of the scan window that captures areas with a relatively high probability of providing an acceptable FOV image. For example, in at least some implementations, the location of the scanning window may be based on an analysis of the relative intensities of the possible FOV images within the possible scanning window regions, and regions of relatively modest darkness (e.g., regions having a greater number of possible FOV images with average light transmittance) may be selected such that the scanning window provides a relatively greater probability of containing a field of view image that is to be classified as having acceptable analytical quality.

It should be understood that the size and shape of the scanning window (established at 610) may be any suitable size and shape and may vary from slide to slide (or from membrane to membrane on the same slide) depending on the particular biological sample being analyzed (e.g., thick membrane 424, thin membrane 426, other non-blood samples, etc.). As mentioned above, the scanning window may preferably be a relatively small area that provides a relatively high quality FOV image such that the desired microscopic analysis and the desired information is performed with as little manipulation as is practical to perform the automated microscope assembly 110. Thus, the size and shape of the scanning window, which may facilitate, achieve, or increase, at least in part, the likelihood of meeting one or more of these goals, may vary depending on the characteristics of the thick film 424 or other scanned area on the slide.

In at least some implementations, the scanning window can be square (or rectangular) in shape. For example, fig. 7 shows a schematic diagram 700 of a scan window 710 with a square shape built (at 610) over a thick film 424. In this particular implementation, the scanning window 710 has a width W of 45 fields of view (e.g., 11.25mm) and a length L of 45 fields of view (e.g., 11.25 mm). It should be understood that the scanning window 710 may have other suitable dimensions in alternative embodiments. For example, in some embodiments, the biological sample (e.g., thin film 426) can span the entire width of the slide 420, and thus, the scanning window 710 can span the entire width of the slide 420 (e.g., typically 25 mm). In some embodiments, the size of the scanning window may be predetermined (e.g., 11.25mm x 11.25mm), or alternatively, may be dynamically determined (larger or smaller) based on one or more results of the analysis of the macroscopic image 400 of the thick film 424, with the goal of selecting a size to provide a scanning window having a greater probability of containing an appropriate number of field-of-view images that are acceptable for analysis.

As further shown in fig. 6, the scanning and analysis process 600 further includes dividing the scanning window at 612. It should be appreciated that dividing (at 612) the scanning window includes mathematically dividing or defining the scanning window into a plurality of smaller portions. More specifically, dividing (at 612) the scanning window may include dividing the scanning window 710 into a plurality of smaller portions, where the smaller portions (or sub-portions) are referred to herein as "grid cells. For example, in the embodiment shown in fig. 7, the scanning window 710 has been divided into a plurality of grid cells 712. In some implementations, each grid cell 712 may be square, while in other implementations, each grid cell 712 may be rectangular or other suitable shape. In the depicted implementation, the dimensions of each grid unit 712 are the width of five fields of view and the length and width of five fields of view (i.e., 5FOV by 5FOV), for a total of twenty-five fields of view per grid unit 712. In at least some implementations, a single field of view may have a rectangular shape, and thus, grid cells 712 may also have a rectangular shape. In the upper right portion of fig. 7, the grid cell 712 has been enlarged to show a single field of view (FOV)714 (e.g., of the microscope 112 of the automated microscope assembly 110), and in the depicted embodiment, the grid cell 712 includes 25 FOVs 714. Thus, in the embodiment shown in fig. 7, the scanning window 710 is divided into nine grid cells 712 in width and nine grid cells 712 in length, for a total of eighty-one grid cells 712. Of course, in alternative embodiments, various suitable partitioning arrangements may be contemplated in accordance with the scope and teachings of the present disclosure.

Referring again to FIG. 6, the scanning and analysis process 600 also includes performing a seek mode operation at 620. As described above, the seek mode operation (at 620) generally involves evaluating the quality of microscopic images at a plurality of different locations across the thick film 424 (or thin film 426 or other biological sample), the evaluation being based on a relatively coarse spacing of locations. More specifically, in at least some implementations, performing (at 620) the seek mode operation includes positioning the microscope at the desired grid cell location at 622. For example, as shown in fig. 7, microscope 112 may be initially positioned such that the field of view of objective lens 212 is at a central field of view (FOV)750 of a central grid element 752 of scanning window 710 (e.g., substantially at the center of thick film 424). In at least some implementations, positioning of the microscope (at 622) can also include one or more focusing or refocusing operations (e.g., using position controller 216, positioner 214, etc. of microscope assembly 110).

It should be understood that depending on the particular details of dividing (at 612) the scanning window, in some implementations, some grid cells may have a field of view (FOV) at the center of the grid cell, while their grid cells may not, and may only, have a FOV near the center of the grid cell. More specifically, in some implementations, those grid cells that have been divided into equal numbers of odd rows of FOVs and odd columns of FOVs will have a central FOV (e.g., 5 FOVs by 5 FOVs, 7 FOVs by 7 FOVs, 3 FOVs by 3 FOVs, etc.), while other dividing configurations (e.g., 4 FOVs by 5 FOVs, 4 FOVs by 4 FOVs, 6 FOVs by 6 FOVs, etc.) will not have a central FOV, but will have one or more FOVs that are near (e.g., adjacent) the center of the grid cell. Accordingly, it should be understood that references to a central FOV (or an approximately central FOV) in the following discussion should be understood to include alternative implementations having a FOV that is near (e.g., adjacent) the center of a grid cell, but that is not at the exact center of the grid cell. In further implementations, it is understood that the desired grid cell location (at 622) need not be the center FOV, and that other FOVs may be selected as the desired grid cell location (e.g., the upper left corner FOV of the grid cell, etc.), and indeed any other FOV of the grid cell may be selected as the desired grid cell location (at 622).

After positioning (at 622) the microscope, the scanning and analysis process 600 further includes performing a detailed scan of the microscope field of view at the desired grid cell location at 624. The detailed scanning of the microscope field of view (performed at 624) may be a conventional scanning process that is generally known and may be readily performed by an automated microscope assembly (e.g., microscope assembly 110), including automated microscope assemblies of the type referred to elsewhere herein. For example, fig. 8 shows representative scan results 800 of the type that may be obtained (at 624) during a detailed scan of a thick film. Additionally, in at least some implementations, the performance (at 624) of the detailed scan of the field of view may include one or more focusing or refocusing operations (e.g., using position controller 216, positioner 214, master controller 202, etc. of microscope assembly 110).

As further shown in fig. 6, the scanning and analysis process 600 also includes evaluating the results of the detailed scan of the field of view at 626. In at least some implementations, evaluating (at 626) the results of the detailed scan can include evaluating the suitability of the scan results. More specifically, the suitability of the scan results for thick films may be assessed based on one or more quality characteristics of the scan results, including but not limited to determining one or more of composition (i.e., whether FOV is empty. In at least some implementations, the evaluation of the results of the detailed scan (at 626) can include the use of known automatic image recognition processes and techniques, as described more fully above with reference to, for example, in "Deep Learning for general Object Detection: A surveyy" by Li Liu et al, arXiv:1809.02165[ cs.CV ],6Sept., 2018.

Additionally, in at least some implementations, the evaluation (at 626) of the results of the detailed scan of the field of view can include counting a number of features present or detectable within the field of view. More specifically, in at least some implementations, the assessment (at 626) can include counting Red Blood Cells (RBCs), White Blood Cells (WBCs), Malaria Parasites (MPs), or any other suitable feature within the field of view. In the representative thick film scan results 800 of fig. 8, a plurality of malaria parasites 802 are shown that can be easily detected and counted using known processes and techniques. It should be appreciated that the detection and counting of these features (e.g., RBCs, WBCs, MPs, etc.) can be readily accomplished using known automated image recognition processes and techniques, as described more fully above. In addition, such automated image recognition techniques have been implemented in commercially available systems for detecting and enumerating features present within biological samples (e.g., enumerating blood cells and malaria parasites), including but not limited to commercially available systemsA system (e.g., the easysscango system).

In at least some implementations, the evaluation (at 626) of the results of scanning the field of view can include providing a quality assessment of the scan results associated with the field of view. For example, the evaluation (at 626) may provide a quality assessment score or numerical designation. In some implementations, the quality assessment score may be provided as follows: 0 is good, 1 is fuzzy, 2 is empty and 3 is RBC clumping too much (or unclear). In this particular implementation, only a quality assessment score of zero is considered acceptable or of sufficiently high quality. In alternative implementations, the quality assessment may provide non-quantized results, such as "acceptable", "unacceptable", "high quality", "low quality", or any other suitable non-quantized descriptor.

Referring again to FIG. 6, after evaluating (at 626) the results of the detailed scan of the field of view, the scanning and analysis process 600 also includes determining whether the results of the detailed scan of the field of view are acceptable at 628. If the result of the detailed scan of the field of view is not acceptable (at 628) (e.g., blurred, empty, insufficient cells, etc.), then the scanning and analysis process 600 next determines at 630 whether the field of view just scanned is the last grid cell available for seek mode operation. If (at 630) it is determined that the field of view just scanned is the last grid cell available for seek mode operation, then the scanning and analysis process 600 proceeds to output a seek mode termination message at 632 and ends execution of the seek mode operation (at 620) by proceeding to end at 650 or to continue to other operations, such as returning to the appropriate operations of the microscopy process 300 of FIG. 3.

Alternatively, if (at 630) it is determined that the field of view just scanned is not the last grid cell available for performing the seek mode operation, then the scanning and analysis process 600 includes stepping to the location of the next desired grid cell at 632, execution of the seek mode operation (at 620) returns (at 622) to positioning the microscope at the next desired grid location, and the seek mode operations 622 through 628 described above are repeated for the new desired grid location.

It should be appreciated that the progression to the next desired grid cell location for continuous seek mode operation may be implemented (at 632) in various suitable ways. In at least some implementations, as schematically depicted in fig. 7, a progression to the next desired grid cell location can be achieved (at 632). More specifically, the next desired grid cell location may be selected by: the grid cells adjacent to the center grid cell 752 are skipped and moved outward to the center (or center FOV)754 (or other desired grid cell location) of the non-adjacent grid cell 756, and then the above described seek mode operation (622-. Although the search mode operation (622-.

As shown in fig. 7, in at least some implementations, non-adjacent grid cells 756 are part of a first set of non-adjacent grid cells 760, the first set of non-adjacent grid cells 760 forming a first non-adjacent perimeter (i.e., the perimeter of a grid cell spaced apart from the central grid cell 752 by a distance of one grid cell) around the central grid cell 752. Additionally, as further shown in fig. 7, a second set of non-adjacent grid cells 762 may be identified that form a second non-adjacent perimeter around the central grid cell 752 (the second non-adjacent perimeter being spaced one grid cell outward from the first non-adjacent perimeter). It should be understood that in alternative implementations, dividing the scanning window (at 612) to provide any desired number of grid cells, and thus providing a perimeter of any desired number of grid cells formed around the central grid cell 752, may be performed in a variety of ways.

In at least some implementations, as the seek mode operation 620 continues to repeat (at 632) progressing to the next desired grid cell location in an attempt (at 628) to locate a grid cell with acceptable quality, the next desired grid cell location may be selected (at 632) by: proceeding around the first non-adjacent perimeter (e.g., in a counterclockwise direction as shown in fig. 7), every other grid cell in the first set of non-adjacent grid cells 760 is selected (i.e., one grid cell is skipped and the next grid cell is selected). Then, the above-described operations 622 to 628 are performed at the center (or center field of view) of the next desired grid cell location. After completely bypassing the first non-adjacent perimeter, the next desired grid cell location may be determined (at 632) by: moving outward to a second set of non-adjacent grid cells 762 forming a second non-adjacent perimeter, proceeding around the second non-adjacent perimeter (e.g., in a counterclockwise direction as shown in fig. 7), every other grid cell in the second set of non-adjacent grid cells 762 is selected (i.e., one grid cell is skipped and the next grid cell is selected). Thus, in at least some implementations, the detailed scanning and analysis operations (at 622, 624) are performed on a relatively coarse set of FOV positions (i.e., the center FOV of every other grid cell) that are spaced apart by about two grid cell sizes (e.g., 2 × 5 FOV-10 FOV).

It should be appreciated that in alternative implementations, the seek mode operation (at 620) may be repeatedly (at 632) stepped up to the next desired grid location by surrounding any number (e.g., 3, 4, etc.) of non-adjacent grid perimeters. Similarly, in an alternative implementation, the seek mode operation (at 620) may be repeatedly stepped up (at 632) to the next desired grid location by: proceeding in any desired direction (e.g., clockwise) around the first and second non-adjacent perimeters 760, 762, or alternately proceeding in a first direction (e.g., clockwise) around one of the perimeters (e.g., the first perimeter) and then proceeding in an opposite direction (e.g., counterclockwise) around the other perimeter.

As noted above, the coarsely spaced grid cells used during search mode operation need not be non-adjacent, and in alternative implementations may be adjacent grid cells, or a combination of adjacent and non-adjacent grid cells. Thus, a reference to a coarsely spaced grid cell may even include the desired FOVs (e.g., the central FOVs) of some neighboring grid cells. For example, fig. 19 shows one embodiment of a coarsely spaced grid cell 1900 with adjacent grid cells 1912 according to the present disclosure. In at least some implementations, the progression (at 632) to the next desired grid cell location may be done as schematically depicted in fig. 19. More specifically, after analyzing the desired FOV (e.g., central FOV)1950 of the central grid cell 1952, the progression (at 632) may continue to the next desired FOV (e.g., central FOV)1954 of the first grid cell 1956, and then the above-described seek mode operation (622-.

Alternatively, fig. 20 shows one embodiment of a coarsely spaced grid cell 2000 with some adjacent grid cells and some non-adjacent grid cells in accordance with the present disclosure. In at least some implementations, the progression (at 632) to the next desired grid cell location may be done as schematically depicted in fig. 20. More specifically, after analyzing the desired FOV (e.g., central FOV)2050 of the central grid cell 2052, the progression (at 632) may proceed to the next desired FOV (e.g., central FOV)2054 of the first adjacent grid cell 2056, then the above-described seek mode operation (622-. After proceeding around the entire perimeter of the adjacent grid cells, the progression may proceed outward to the outer perimeter of the non-adjacent grid cells, starting with the desired FOV2060 of the first non-adjacent grid cell 2062, and then proceed incrementally to the next desired FOV2064 of the next non-adjacent grid cell 2066, proceeding around the second perimeter (counterclockwise or clockwise), as shown by the arrows in fig. 20.

Referring again to FIG. 6, when it is determined (at 628) that the results of the detailed scan of the central field of view of the desired grid cell are acceptable, and therefore an acceptable grid cell has been located, then the scanning and analysis process 600 proceeds from the seek mode operation (at 620) to performing a "scan mode" operation at 640. In at least some implementations, the scan mode operation (at 640) includes performing a detailed scan and evaluation of all fields of view within an acceptable grid cell at 642. In at least some implementations, the detailed scan (at 642) may be substantially similar to the detailed scan performed (at 624) during the seek mode operation described above, and the evaluation (at 642) may be substantially similar to the evaluation performed during the seek mode operation (at 626) described above. Thus, in at least some implementations, each individual FOV of an acceptable grid cell may be evaluated and designated (at 642) as having acceptable or unacceptable quality during the performance of the detailed scan and evaluation. Similarly, detailed scanning and evaluation (at 642) may also include counting a number of features (e.g., RBCs, WBCs, MPs, etc.) present or detectable within the field of view using known processes and techniques.

For example, fig. 9 shows an enlarged view of an acceptable grid cell 900 divided into a total of twenty-five fields of view (i.e., 5 FOVs by 5 FOVs). In this implementation, the central FOV 902 is pre-scanned and evaluated and determined to be acceptable during seek mode operation (at 620). Thus, upon entering scan mode operation (at 640), all remaining fields of view of the acceptable grid cell 900 are scanned and evaluated (at 642). In the implementation shown in fig. 9, FOVs designated as being of acceptable quality (i.e., 21 acceptable FOVs) are shown visibly in relatively light shading, while FOVs designated as being of unacceptable quality (i.e., 4 unacceptable FOVs) are shown in relatively darker shading.

As further shown in fig. 6, performing (at 640) the scan mode operation also includes determining (at 642) whether acceptable grid cells remain acceptable based on the detailed scan and evaluation of all fields of view. In at least some implementations, determining (at 644) whether an acceptable grid cell remains acceptable includes comparing the number of acceptable FOVs to the number of unacceptable FOVs. For example, in some implementations, it may be determined (at 644) that the acceptable grid cell 900 remains acceptable when the number of acceptable FOVs is greater than the number of unacceptable FOVs. Alternatively, in some implementations, it may be determined (at 644) that the acceptable grid cell 900 remains acceptable when the number of acceptable FOVs reaches a suitable threshold, such as a predetermined percentage (e.g., 55%, 60%, 65%, etc.) of the total number of FOVs in the grid cell. For example, in the particular implementation shown in fig. 9, when the number of acceptable FOVs reaches or exceeds 15 FOVs (i.e., reaches or exceeds 60%) of the total 25 FOVs in grid cell 900, it may be determined that grid cell 900 remains acceptable (at 644). Under this criteria, since the acceptable grid cell 900 shown in FIG. 9 includes 21 acceptable FOVs, it will be determined (at 644) that the acceptable grid cell 900 remains acceptable.

If it is determined (at 644) that the grid cell has not remained acceptable based on the scanning and evaluating (at 642) all FOVs of the grid cell, then the scanning and analysis process 600 returns to the seek mode operation (at 620). More specifically, if (at 644) it is determined that the grid cells have not remained acceptable, process 600 returns (at 630) to determining whether the search mode operation has reached the last available grid cell of the coarse grid cells for the search mode operation. The scanning and analysis process 600 then proceeds from the determination (at 630) as described above, and additional seek mode operations may be performed (at 620) until another acceptable grid cell is found (at 628), at which point the process 600 may return (at 640) to the scan mode operation.

In the embodiment shown in fig. 6, after determining (at 644) that the grid cell is acceptable, the scan mode operation (at 640) further includes performing detailed scanning and evaluation of one or more grid cells adjacent to the acceptable grid cell at 646. More specifically, fig. 10 shows an enlarged view 1000 of an acceptable grid cell 900 and the surrounding perimeter of an adjacent grid cell 1010. It should be understood that in the implementation shown in fig. 10, there are eight adjacent grid cells in the perimeter of adjacent grid cells 1010, and four adjacent grid cells (i.e., half) have been scanned and evaluated at 644. In at least some implementations, the detailed scanning and evaluating (at 646) of one or more grid cells adjacent to the acceptable grid cell may include scanning and evaluating one or more adjacent grid cells that share a common edge (or common boundary) with the acceptable grid cell 900 (see fig. 10), however, in at least some alternative implementations, any other set or subset of perimeters of adjacent grid cells (e.g., four adjacent corner grid cells adjacent to four corners of the acceptable grid cell 900) may be selected for scanning and evaluating (at 646). For example, although the embodiment shown in fig. 10 depicts half of the grid cells adjacent to the acceptable grid cells being scanned and evaluated (at 646), in alternative embodiments, the scanning and evaluating may be performed (at 646) on any suitable number or percentage (e.g., 25%, 50%, 75%, etc.) of grid cells adjacent to the acceptable grid cells.

Again, in at least some implementations, the detailed scanning and evaluating of one or more adjacent grid cells (at 646) may be substantially similar to the scanning and evaluating performed during the seek mode operation (at 624, 626) described above, and may include specifying the quality of each FOV (e.g., acceptable or unacceptable), and may also include counting one or more features (e.g., RBCs, WBCs, MPs, etc.) present in each FOV, or determining one or more other features using known processes and techniques. For example, in the particular example shown in fig. 10, a first adjacent grid cell 1012 includes 24 acceptable FOVs and 1 unacceptable FOV, a second adjacent grid cell 1014 includes 22 acceptable FOVs and 3 unacceptable FOVs, a third adjacent grid cell 1016 includes 6 acceptable FOVs and 19 unacceptable FOVs, and a fourth adjacent grid cell 1018 includes 25 unacceptable FOVs.

With continued reference to fig. 6, after detailed scanning and evaluation of one or more grid cells adjacent to an acceptable grid cell (at 646), the scan mode operation (at 640) continues to determine whether one or more criteria for ending the scan and evaluation process 600 have been met at 648. In at least some implementations, the criteria for ending the scanning and evaluation process 600 can be established based on the total number of features that have been counted during the evaluation operation. More specifically, the criteria for ending the process 600 may be established based on: the total number of acceptable FOVs that have been scanned and evaluated (e.g., terminated if acceptable FOV >60, terminated if acceptable FOV > four full grid cell FOVs, terminated if acceptable FOV > three full grid cell FOVs, etc.), the number of white blood cells counted (e.g., terminated if WBC >1500, 1000, 2500, etc.), the number of red blood cells counted, the number of parasites counted, the amount of time elapsed in the execution of the scanning and evaluation process 600 (e.g., terminated if time >15 minutes, 10 minutes, 20 minutes, etc.), or any other desired criteria. In at least some implementations, the thick film scan results (e.g., fig. 8) can generally provide detailed information about the number of White Blood Cells (WBCs) and the number of Malaria Parasites (MPs), and thus, in at least some implementations, the one or more criteria can include one or more of the number of WBCs or the number of Malaria Parasites (MPs).

If (at 648) it is determined that one or more criteria for ending the scanning and evaluation process 600 have not been met, then the process 600 returns (at 630) from the scan mode operation (at 640) to the search mode operation (at 620), and more particularly to determining whether the search mode operation has reached the last available grid cell in the coarse grid cells for the search mode operation. The scanning and analysis process 600 then proceeds from the determination (at 630) as described above, and additional seek mode operations may be performed (at 620) until another acceptable grid cell is located (at 628), at which point the process 600 may return to the scan mode operation (at 640). Finally, the scanning and analysis process 600 will determine (at 648) that one or more criteria for ending the scanning and evaluation process 600 have been met, and then the process 600 proceeds to end at 650 or continue with other operations, such as returning to the appropriate operation of the microscopy process 300 shown in FIG. 3.

The foregoing description of the scanning and evaluation process 600 shown in fig. 6 may be described with particular reference to scanning and analysis operations (e.g., operation 322 of fig. 3) performed on thick film 424. In at least some implementations, the scanning and evaluation process 600 shown in fig. 6 can also be applied to scanning and analysis operations (e.g., operation 328 of fig. 3) performed on the thin film 426. However, it should be understood that in alternative implementations, one or more different details of the scanning and evaluation process 600 may be adjusted or changed when analyzing different biological samples (e.g., thin film 426).

For example, fig. 11 illustrates another scanning and evaluation process 1100 according to the present disclosure. At least some operations of scanning and evaluation process 1100 (fig. 11) are substantially similar to operations of scanning and evaluation process 600 (fig. 6) described above. Thus, the following description of the scanning and evaluation process 1100 will focus on the description of one or more particular operations that may desirably be adapted for scanning and analysis of the thin film 426 (or other biological sample).

In the implementation shown in fig. 11, the scanning and analysis process 1100 includes performing a preparation operation at 1105, which may include establishing a scanning window at 1110 for scanning the thin film 426 (or other biological sample). Establishing (at 1110) the scanning window may include determining a portion of the film 426 that may be subjected to detailed scanning operations to provide a relatively high quality field of view (FOV) image to enable performance of the desired microscopic analysis.

Fig. 12 shows a schematic 1200 (at 1110) with a scanning window 1210 having a rectangular shape established on the film 426. In this particular embodiment, the scanning window 1210 has a width W of 75 fields of view (e.g., 18.75mm) and a length L of 60 fields of view (e.g., 15 mm). It will be appreciated that in alternative embodiments, the scanning window 1210 may have other suitable dimensions or may be dynamically determined based on one or more results of the analysis performed on the macroscopic image 400 of the thin film 426.

The scanning and analysis process 1100 may further include dividing the scanning window at 1112. In the embodiment shown in fig. 12, the scanning window 1210 has been divided into a plurality of grid cells 1212, where each grid cell 1212 is a square having a size of 5FOV by 5FOV, for a total of 25 FOVs per grid 1212. Thus, in the embodiment shown in fig. 12, the scanning window 1210 is divided into a total of one hundred and eighty grid cells 1212, 15 grid cells wide and 12 grid cells long. Of course, in alternative embodiments, various suitable partitioning arrangements may be contemplated in accordance with the scope and teachings of the present disclosure.

In at least some implementations, dividing (at 1112) the scanning window further includes grouping at least some of the grid cells 1212 into a plurality of groups to facilitate subsequent scanning operations. For example, in the embodiment shown in fig. 12, some grid cells (e.g., 20 grid cells) are assigned to a first grid group 1214 (represented by darkest shading), while other grid cells (e.g., 20 grid cells) are assigned to a second grid group 1216 (represented by medium shading), and other grid cells (e.g., 20 grid cells) are assigned to a third grid group 1218 (represented by lightest shading). In at least some implementations, the grid cells of the three grid groups 1214, 1216, 1218 may be relatively evenly distributed throughout the scanning window 1210, and the grid cells of each group may be spaced apart from other grid cells of the same group, as shown in fig. 12. More specifically, in the particular embodiment shown in fig. 12, the center points (or center FOVs) of the grid cells of the first grid set 1214 are spaced three grid cells (15 FOVs) from the center points of the other members of the first grid set 1214. Similarly, the center points (or central FOVs) of the grid cells of second grid group 1216 are spaced at least three grid cells (15 FOVs) from the center points of the other members of second grid group 1216, and the center points (or central FOVs) of the grid cells of third grid group 1218 are spaced at least three grid cells (15 FOVs) from the center points of the other members of third grid group 1218. It should be understood that according to the embodiment shown in fig. 12, some grid cells may not be included in the grouping of grid cells (at 1112) and these grid cells remain unshaded in fig. 12. While such ungrouped grid cells may not be usable as coarse grid cells for search mode operation, they may be scanned during scan mode operation after being located to a suitable grid cell during search mode operation, as described more fully below.

It should be understood that in alternative implementations, grid cells 1212 may be grouped into different numbers of groups. For example, in an alternative implementation, grid cells 1212 may be grouped into two groups (instead of three groups as shown in fig. 12) and may be distributed similar to the distribution shown in fig. 12, in which case the center points (or central FOVs) of the grid cells of the first grid group would be spaced apart by only two grid cells (instead of three grid cells). In general, in still further implementations, the grid cells may be grouped into N groups (e.g., 4 groups, 5 groups, etc.) and may be distributed similar to the distribution shown in fig. 12, such that the center points (or central FOVs) of any particular group of grid cells are spaced N grid cells from the center point (e.g., in the x-direction and/or in the y-direction) of the nearest grid cell of the same group.

Additionally, in the embodiment shown in fig. 12, the grid cells of the first, second and third grid groups 1214, 1216, 1218 are diagonally aligned such that the grid cells of a particular group are adjacent to grid cells of one or more other groups only at their respective corners. More specifically, the center points (or center FOVs) of the grid cells of second grid group 1216 are diagonally offset from the center points of the grid cells of first grid group 1214 (e.g., one grid cell down the-y direction and one grid cell in the x direction). Similarly, the center points (or center FOVs) of the grid cells of third grid group 1218 are diagonally offset from the center points of the grid cells of second grid group 1216 (e.g., one grid cell down the-y direction and one grid cell in the x direction). In further implementations, the grid cells of different grid sets may be reoriented such that they are diagonally aligned along one or more other possible diagonal directions (i.e., offset in the x and y directions, offset in the-x and y directions, or offset in the-x and y directions). Of course, in alternative implementations, a wide variety of suitable partitioning arrangements are contemplated in accordance with the scope and teachings of the present disclosure.

With continued reference to FIG. 11, the scan and analyze process 1100 further includes performing a seek mode operation at 1120. In at least some implementations, performing (at 1120) a seek mode operation includes positioning the microscope at the desired grid location at 1122. For example, as shown in fig. 12, the microscope 112 may first be positioned such that the field of view of the objective lens 212 is at the central FOV 1250 of the first grid cell 1252 of the scanning window 1210. As described above, in at least some implementations, positioning the microscope (at 1122) can also include one or more focusing or refocusing operations (e.g., using position controller 216, positioner 214, etc. of microscope assembly 110).

In the embodiment shown in FIG. 11, the scanning and analysis process 1100 further includes scanning 1124 the microscope field of view within the film in detail. For example, FIG. 13 shows a representative scan result 1300 of the type that may be obtained (at 1124) during a detailed scan of a thin film. In this example, the representative scan result 1300 includes a plurality of malaria parasites 1302 (indicated by dark spots) and a plurality of red blood cells 1304 (indicated by circles and dotted circles). Additionally, in at least some implementations, the representative scan 1300 of the thin film 426 can distinguish between a malaria parasite of the first species 1302A and a malaria parasite of the second species 1302B.

The scanning and analysis process 1100 also includes evaluating the results of detailed scanning of the field of view within the film at 1126. In at least some implementations, the evaluation of the results of the detailed scan can include determining one or more of composition (i.e., whether the FOV is empty. In at least some implementations, the evaluation (at 1126) of the results of the detailed scan can include using known automatic image recognition processes and techniques, as described more fully above. As further shown in FIG. 11, the scan and analyze process 1100 may next determine whether the results of the detailed scan are acceptable at 1128. If not, scanning and analysis process 1100 determines at 1130 whether the search mode operation is complete based on one or more criteria (e.g., total time in search mode, maximum number of coarse grid points scanned, etc.). If (at 1130) the seek mode operation is complete, process 1100 proceeds to end at 1152 or to continue with other operations (e.g., returning to the appropriate operations of microscopy process 300 of FIG. 3). Alternatively, if (at 1130) the search mode operation is not complete, then the scan and analyze process 1100 includes stepping to the next coarse grid cell location at 1132 and then repeating (at 1120) the search mode operation of 1128) above for the new coarse grid cell location.

More specifically, for the implementation shown in fig. 12, in at least some implementations, the seek mode operation may begin scanning at the center FOV 1252 of the first coarse grid cell 1250 (or other desired grid cell location) and may be performed (at 1120) 1128) incrementally across members of the first grid group 1214 (e.g., to the center FOV 1254, then to the center FOV 1256, etc.), then across members of the second grid group 1216, and then across members of the third grid group 1218, until it is determined (at 1130) that the seek mode operation is complete.

Referring again to fig. 11, once it is determined that the detailed scan results for the central FOV of the coarse grid cell are acceptable (at 1128), the scan and analysis process 1100 proceeds from the seek mode operation (at 1120) to the "scan mode" operation performed at 1140. More specifically, the scan mode operation (at 1140) includes performing a detailed scan and evaluation of all fields of view within an acceptable grid cell at 1142. Thus, the detailed scanning and evaluation (at 1142) may further include: known processes and techniques are used to calculate the number of features (e.g., RBCs, WBCs, MPs, etc.) that are present or detectable within the field of view. In at least some implementations, the thin film scan results (e.g., fig. 13) can generally provide detailed information about the number of Red Blood Cells (RBCs) and the number of Malaria Parasites (MPs) including different species of malaria parasites (e.g., 1302A, 1302B).

Similarly, each individual FOV of an acceptable grid cell may be evaluated and designated as having acceptable or unacceptable quality during performance of the detailed scan and evaluation (at 1142). For example, as previously described with reference to fig. 9, a grid cell deemed acceptable during the seek mode operation of 1140 has (at 1142) all remaining fields of view of the acceptable grid cell scanned and evaluated, and all individual FOVs of that grid cell are designated as being of acceptable quality (i.e., 21 acceptable FOVs) or of unacceptable quality (i.e., 4 unacceptable FOVs).

The scan mode operation (at 1140) further comprises: based on the detailed scan and evaluation of all fields of view (at 1142), it is determined at 1144 whether acceptable grid cells remain acceptable. Possible criteria for determining (at 1144) whether a grid cell remains an acceptable grid cell are more fully described above (with reference to operation 642 of fig. 6). If (at 1142) it is determined that the grid cells are not acceptable, then the scan and analysis process 1100 returns (at 1120) to the search mode operation, or more specifically, determines (at 1130) whether the search mode operation is complete.

Alternatively, if (at 1144) it is determined that the grid cell is acceptable, then the scan mode operation (at 1140) proceeds to perform a detailed scan and evaluation of one or more grid cells adjacent to the acceptable grid cell at 1146. For example, fig. 14 shows an implementation of a scan window 1400 that is divided into grid cells and includes (at 1142) grid cells 1410 that are determined to be acceptable during scan mode operation. In this implementation, the scanning window 1400 is 10 grid cells by 8 grid cells and includes three sets of grid cells (indicated by light, medium, and dark shading) distributed in a diagonal pattern.

Detailed scanning and evaluation (at 1146) of one or more grid cells adjacent to an acceptable grid cell may be performed in various suitable manners. In at least some implementations, the detailed scan and evaluation (at 1146) may be performed on four of the eight grid cells adjacent to the acceptable grid cell 1410 (e.g., as described above with reference to fig. 10). For example, fig. 15 shows (at 1146) exemplary results of a detailed scan and evaluation of four grid cells adjacent to an acceptable grid cell. In this representative example, first and second adjacent grid cells 1512, 1514 are determined to be acceptable (as indicated by the dark shading), while third and fourth adjacent grid cells 1516, 1518 are determined to be unacceptable (as indicated by the darkest shading). In alternative implementations, different configurations of adjacent grid cells may be scanned and evaluated (at 1146), including scanning and evaluating more, fewer, or different adjacent grid cells.

With continued reference to fig. 11, the scan mode operations (at 1140) of process 1100 further include performing, at 1148, a quadratic detailed scan and evaluation of one or more grid cells adjacent to an acceptable adjacent grid cell. More specifically, as described above and shown in fig. 10, during the scanning and evaluating (at 1146) of one or more grid cells adjacent to an acceptable grid cell, the first and second adjacent grid cells 1512, 1514 are determined to be acceptable. Thus, at 1148, a secondary scan and evaluation operation is performed on one or more grid cells adjacent to the first adjacent grid 1512, and also on one or more grids adjacent to the second adjacent grid 1514.

For example, fig. 16 shows exemplary results of a quadratic detailed scan and evaluation (at 1148) of four grid cells adjacent to an acceptable grid cell. In this representative example, of the three grid cells adjacent to the first adjacent grid cell 1512 that is scanned (at 1148), the first and second secondary adjacent grid cells 1612, 1614 are determined to be acceptable (as indicated by dark shading), while the third secondary adjacent grid cell 1616 is determined to be unacceptable (as indicated by the darkest shading). Further, of the two grid cells adjacent to second adjacent grid cell 1514 that are scanned (at 1148), the fourth secondary adjacent grid cell 1618 is determined to be acceptable (as indicated by dark shading) and the fifth secondary adjacent grid cell 1620 is determined to be unacceptable (as indicated by darkest shading). Again, in alternative implementations, different configurations of secondary neighboring grid cells may be scanned and evaluated (at 1148), including scanning and evaluating more, fewer, or different secondary neighboring grid cells.

Referring again to fig. 11, after performing a secondary detailed scan and evaluation of one or more grid cells adjacent to an acceptable grid cell (at 1148), the scan mode operation (at 1140) proceeds to determine whether one or more criteria for ending the scan and evaluation process 1100 have been met at 1150. As described above with reference to process 600, in at least some implementations, criteria for ending the scanning and evaluation process 1100 can be established based on various different aspects, including a total number of acceptable fields of view obtained during the scanning and evaluation operations (e.g., acceptable FOVs greater than 60, greater than four full grid cells 'FOVs, greater than three full grid cells' FOVs, etc.), a number of white blood cells calculated (e.g., terminated if WBC >1500, 1000, 2500, etc.), a number of red blood cells calculated (e.g., terminated if RBC >20,000, 15,000, 25,000, etc.), a number of parasites calculated or a single species of parasite, an elapsed time (e.g., terminated if time >15 minutes, 10 minutes, 20 minutes, etc.), or any other desired criteria. In at least some implementations, the thin film scan results (e.g., fig. 13) can generally provide detailed information about the number of Red Blood Cells (RBCs) and the number of Malaria Parasites (MPs), including a single species of parasite, and thus, in at least some implementations, the one or more criteria can include one or more of the number of RBCs or the number of Malaria Parasites (MPs).

If (at 1150) it is determined that one or more criteria for ending the scanning and evaluation process 1100 have not been met, then the process 1100 returns from the scan mode operation (at 1140) to the seek mode operation (at 1120), and more specifically to determining (at 1130) whether the seek mode operation is determined to be complete. The scanning and analysis process 1100 then continues from the determination (at 1130) as described above, and additional seek mode operations may be performed (at 1120) until another acceptable grid cell is found (at 1128), at which point the process 1100 may return to the scan mode operation (at 1140). Finally, the scanning and analysis process 1100 may determine (at 1150) that one or more criteria for ending the scanning and evaluation process 1100 have been met, and then the process 1100 may continue to end at 1152 or continue with other operations, such as returning to the appropriate operations of the microscopy process 300 shown in fig. 3.

Based on the foregoing, it should be appreciated that processes and techniques for automated microscopic analysis of biological samples according to the present disclosure may provide significant advantages over conventional processes and techniques. More specifically, in at least some implementations, a system according to the present disclosure can autonomously identify regions of a microscope slide containing a biological sample (e.g., blood), can identify various regions and sub-regions of the sample suitable for microscopic analysis, and can provide an automated scanning strategy to ensure efficient and effective scanning of sufficiently high quality regions of the sample to provide proper analysis of the sample. In at least some implementations, such systems can use machine learning methods (e.g., deep learning or other region detection methods) to identify thick and thin film regions of a slide based on an initial low magnification (or macroscopic) image of the slide.

In at least some implementations, a system according to the present disclosure can capture high magnification scans at various fields of view within a region, and can follow a scanning strategy that takes into account an assessment of the suitability of each FOV for analysis. Based on the suitability assessment, the location of the next high quality scan is determined for capture in the sample (thick or thin film). Such a system may continue to automatically capture and analyze detailed high magnification scans until predetermined criteria (e.g., criteria specifying an acceptable total number of FOVs, a total number of white or red blood cells captured for analysis, etc.) are met.

Processes and techniques according to the present disclosure may advantageously reduce scan time by: reducing the number of low quality fields of view scanned, reducing the time and effort required by the operator to select the appropriate area of the slide, and reducing the time required to reject a poor quality slide. Such processes and techniques may be particularly valuable for batch imaging of many slides or for performing time-sensitive analysis on biological samples.

Although the processes and techniques for an automated microscopy process have been described above with reference to the particular microscopy process 300 shown in fig. 3, it should be understood that such processes and techniques may also be suitably implemented in a wide variety of other microscopy processes. For example, in at least some implementations, scanning and analyzing of the thick film can be performed at least partially concurrently with scanning and analyzing of the thin film. In such implementations, if the scanning and analysis of one of the portions of the biological sample is completed and a negative result is obtained (e.g., no malaria parasites, insufficient number of acceptable FOVs, insufficient number of WBCs or RBCs, etc.), the scanning and analysis of the other portion of the biological sample can be terminated, thereby saving time or resources. In another example, in some implementations, the results of the analysis of one portion of the slide (e.g., a thick film) can affect the criteria required to end scanning another portion of the slide (e.g., a thin film). As a specific example, if the results for thick membranes are negative for malaria parasites, the acceptable field of view required or the number criteria for red blood cells detected for thin membranes will be lower than if the results for thick membranes are positive for malaria.

For example, fig. 17 shows another embodiment of a microscopy process 1700 according to the present disclosure. In this embodiment, the microscopy process 1700 includes positioning a slide for analysis at 1710, for example placing the slide 120 on the motorized stage 210 of the automated microscope assembly 110, and operating the motorized stage 210 to position the slide 120 in place with respect to the microscope 112. The process 300 also includes analyzing the macroscopic image of the slide to determine the boundaries of the thick and thin films at 1712. Techniques for automatically detecting the boundaries of biological samples (e.g., thick film 424, thin film 426) on a microscope slide using an automated microscope assembly are generally known as described above.

Next, process 1700 includes performing a scanning and analyzing operation on the thick film at 1714 and performing a scanning and analyzing operation on the thin film at least partially simultaneously at 1716. It is to be understood that in at least some implementations, the scanning and analyzing operations (at 1714) on the thick film can be completed before the scanning and analyzing operations (at 1716) on the thin film. Of course, in alternative implementations, the thin film operation (at 1716) may be completed before the thick film operation (at 1714).

As further shown in fig. 17, microscopy process 1700 also includes determining whether the result of the thick film operation is negative (or unacceptable) at 1718 and whether the result of the thin film operation is negative (or unacceptable) at 1720. If (at 1718) the result of the thick film operation is determined to be negative (at 1718), or if (at 1720) the result of the thin film operation is determined to be negative, microscopy process 1700 proceeds to end at 1728 or to continue with other operations.

Alternatively, if the result of the thick film operation (at 1718) is not negative, the process 1700 includes providing an indication of whether a parasite is detected at 1722. Similarly, if the result of the membrane manipulation (at 1720) is not negative, then the process 1700 includes providing an indication of parasites and/or other characteristics of the sample at 1724. Next, once it is determined at 1726 that both the thick film operation and the thin film operation are complete, the microscopy process 1700 ends at 1728 or continues with other operations.

In some implementations, one or more aspects of the microscopy process described above may be implemented, at least in part, using a computing apparatus (e.g., computing apparatus 140, master controller 202, etc.). For example, fig. 18 is a schematic diagram of an exemplary computing device 1800 configured to operate in accordance with implementations of the present disclosure. As described below, the computing device 1800 may be configured to perform one or more of the functions and operations associated with one or more of the processes and techniques for automated microscopy processing disclosed herein.

As shown in fig. 18, in some implementations, the computing device 1800 may include one or more processors (or processing units) 1802, special purpose circuitry 1882, memory 1804, and a bus 1806 that couples various system components including the memory 1804 to the one or more processors 1802 and special purpose circuitry 1882. The bus 1806 represents one or more of any of several types of bus structures, including a memory bus or memory controller, a peripheral bus, an accelerated graphics port, and a processor or local bus using any of a variety of bus architectures. In this implementation, memory 1804 includes Read Only Memory (ROM)1808 and Random Access Memory (RAM) 1810. A basic input/output system (BIOS)1812, containing the basic routines that help to transfer information between elements within the computing device 1800, such as during start-up, is stored in ROM 1808.

Exemplary computing device 1800 also includes a hard disk drive 1814 for reading from and writing to a hard disk (not shown), and is connected to bus 1806 via a hard disk drive interface 1816, such as a SCSI, ATA, or other type of interface. A disk drive 1818 for reading from and writing to a removable disk 1820 is connected to the system bus 1806 by a disk drive interface 1822. Similarly, an optical disk drive 1824 for reading from or writing to a removable optical disk 1826 (such as a CD ROM, DVD, or other optical media) is connected to the bus 1806 by an optical drive interface 1828. The drives and their associated computer-readable media provide nonvolatile storage of computer-readable instructions, data structures, program modules and other data for the computing device 1800. Although the exemplary computing device 1800 described herein employs a hard disk, a removable magnetic disk 1820 and a removable optical disk 1826, it should be appreciated by those skilled in the art that other types of computer readable media which can store data that is accessible by a computer, such as magnetic cassettes, flash memory cards, digital video disks, Random Access Memories (RAMs) Read Only Memories (ROMs), and the like, may also be used.

As further shown in fig. 18, a number of program modules can be stored in memory 1804 (e.g., ROM1808 or RAM1810), memory 1804 including an operating system 1830, one or more application programs 1832, other program modules 1834, and program data 1836. Alternatively, these program modules may be stored on other computer-readable media, including on a hard disk, magnetic disk 1820, or optical disk 1826. For purposes of illustration, programs and other executable program components (e.g., operating system 1830) are illustrated in fig. 18 as discrete blocks, but it is recognized that such programs and components reside at various times in different storage components of the computing device 1800, and can be executed by the processor 1802 or specialized circuitry 1882 of the computing device 1800.

A user may enter commands and information into the computing device 1800 through input devices such as a keyboard 1838 and pointing device 1840. Other input devices (not shown) may include a microphone, joystick, game pad, satellite dish, scanner, or the like. These and other input devices are connected to the processing unit 1802 and specialized circuits 1882 through interfaces 1842 that are coupled to the system bus 1806. A monitor 1844 or other type of display device is also connected to the bus 1806 via an interface, such as a video adapter 1846. In addition to the monitor, computing device 1800 may include other peripheral output devices (not shown), such as speakers and printers.

The computing device 1800 may operate in a networked environment using logical connections to one or more remote computers (or servers) 1858. Such remote computer (or server) 1858 can be a personal computer, a server, a router, a network PC, a peer device or other common network node, (or the automated microscopy assembly 110 of FIG. 1), and can include many or all of the elements described above relative to the computing device 1800. The logical connections depicted in FIG. 18 may include one or more Local Area Networks (LAN)1848 and Wide Area Networks (WAN) 1850. Such networking environments are commonplace in offices, enterprise-wide computer networks, intranets and the Internet. In this embodiment, computing device 1800 also includes one or more broadcast tuners 1856. The broadcast tuner 1856 may receive broadcast signals directly (e.g., via analog or digital cable transmission fed directly to the tuner 1856) or via a receiving device (e.g., via an antenna, satellite dish, etc.).

When used in a LAN networking environment, the computing device 1800 may be connected to the local network 1848 through a network interface (or adapter) 1852. When used in a WAN networking environment, the computing device 1800 typically includes a modem 1854 or other means for establishing communications over the wide area network 1850, such as the Internet. The modem 1854, which can be internal or external, can be connected to the bus 1806 via the serial port interface 1842. Similarly, computing device 1800 may exchange (send or receive) wireless signals 1853 with one or more remote computers (or servers) 1858 (or with automated microscope assembly 110 of fig. 1) using a wireless interface 1855 coupled to a wireless communicator 1857 (e.g., an antenna, a satellite dish, a transmitter, a receiver, a transceiver, a photoreceptor, a photodiode, a transmitter, a receiver, etc.).

In a networked environment, program modules depicted relative to the computing device 1800, or portions thereof, can be stored in the memory 1804 or in remote memory storage devices. Program modules may be implemented using software, hardware, firmware, or any suitable combination thereof. In cooperation with other components of the computing device 1800, such as the processing unit 1802 or the dedicated circuitry 1882, the program modules may be operative to perform one or more implementations or aspects of processes in accordance with the present disclosure.

In general, application programs and program modules executing on the computing device 1800 can include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. These program modules and the like may be executed as native code or may be downloaded and executed, for example, in a virtual machine or other just-in-time compilation execution environment. Typically, the functionality of the program modules may be combined or distributed as desired in various implementations.

In view of the disclosure of the processes and techniques for automated microscopy systems and methods disclosed herein, some representative embodiments are summarized below. It should be understood that the representative embodiments described herein are not intended to be an exhaustive list of all possible embodiments, and that other embodiments may be readily conceived from the disclosure of the processes and techniques provided herein.

For example, in at least some implementations, a microscope system includes: a microscope assembly configured to obtain a microscopic scan of a field of view within a sample, the microscope assembly operable to perform operations comprising: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and if one or more criteria for terminating a scan operation are met, providing an indication of the compiled one or more aspects of the acceptable scan results.

In at least some implementations, the sample includes at least one of a thick film or a thin film of the blood sample, and wherein the one or more criteria for terminating the scanning operation includes: one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed. Similarly, in some implementations, defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, includes: the scanning window is defined as a plurality of square grid cells, wherein each square grid cell includes an equal number of rows and columns of fields of view. In further implementations, performing the microscopic scan at the selected field of view within the selected ones of the plurality of coarse-spaced grid cells includes: performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

Further, in at least some implementations, assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell includes: assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results. Similarly, in a further implementation, the threshold percentage is at least fifty percent.

In further implementations, defining a coarse-spaced grid pattern including a plurality of coarse-spaced grid cells includes: defining a coarse-spaced grid pattern comprising a first coarse-spaced grid cell positioned proximate the scanning window center and a plurality of first non-adjacent grid cells located within a first non-adjacent perimeter disposed about and spaced apart from the first coarse-spaced grid cell. Similarly, in at least some implementations, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell includes: selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of: proceeding outward from the first coarse spaced grid cells to select first non-adjacent grid cells located within the first non-adjacent perimeter; or laterally from one of the first non-adjacent grid cells to select another of the first non-adjacent grid cells located within the first non-adjacent perimeter. In further implementations, defining a coarse-spaced grid pattern including a plurality of coarse-spaced grid cells includes: a coarsely-spaced grid pattern is defined that includes a plurality of second non-adjacent grid cells located within a second non-adjacent perimeter disposed around and spaced apart from the first non-adjacent perimeter.

Further, in at least some implementations, defining a coarse-spaced grid pattern including a plurality of coarse-spaced grid cells includes: defining a coarse-spaced grid pattern comprising a first set of first non-adjacent grid cells and a second set of second non-adjacent grid cells, the first set of the first non-adjacent grid cells being distributed throughout the scanning window and each first non-adjacent grid cell being non-adjacent to other first non-adjacent grid cells, and each second non-adjacent grid cell being diagonally disposed proximate to at least one first non-adjacent grid cell and non-adjacent to other second non-adjacent grid cells. In still other implementations, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell includes: selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of: proceeding from one of the first set of the first non-adjacent grid cells to another of the first set of first non-adjacent grid cells; proceeding from one of the first set of the first non-adjacent grid cells to one of the second set of the second non-adjacent grid cells arranged diagonally proximate to the one of the first set of the first non-adjacent grid cells; or from one of the second set of the second non-adjacent grid cells to another of the second set of second non-adjacent grid cells. And, in other implementations, defining a coarse-spaced grid pattern including a plurality of coarse-spaced grid cells includes: a coarse-spaced grid pattern is defined that includes a third set of third non-adjacent grid cells, each third non-adjacent grid cell being arranged diagonally adjacent to at least one second non-adjacent grid cell and not adjacent to other third non-adjacent grid cells.

In at least some other implementations, performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell includes: performing the micro-scan at all fields of view within half of the adjacent grid cells within a perimeter of the grid cell adjacent to the selected coarse spaced grid cell that is acceptable. Similarly, in some implementations, performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell includes: performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of a grid cell adjacent to and sharing a common boundary with the acceptable selected coarse spaced grid cell. And in yet further implementations, performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid comprises: performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to and sharing common corner points with the acceptable selected coarse spaced grid cells.

In yet further implementations, performing the scan mode operation further comprises: for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell: performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and compiling, for each of the one or more secondary neighboring grid cells, one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell. Alternatively, in still other implementations, evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell includes: evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell based on one or more of sharpness, blur, or brightness. Similarly, in further implementations, evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell includes: assigning a quality assessment score based on a quality assessment of the scan results.

In further implementations, the microscope assembly is operable to perform operations comprising: obtaining a macroscopic image of at least a portion of the sample; and analyzing the macroscopic image to determine the suitability of the at least a portion of the sample for analysis. In some implementations, analyzing the macroscopic image to determine the suitability of the at least a portion of the sample for analysis includes: performing one or more machine learning operations using one or more image recognition models to determine suitability of the at least a portion of the sample for analysis. In yet other implementations, defining the scanning window over at least a portion of the sample as a plurality of grid cells comprises: obtaining a macroscopic image of at least a portion of the sample; analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample; and defining a position of the scanning window based on the one or more boundaries of the at least a portion of the sample. In still other implementations, analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample includes: performing one or more machine learning operations using one or more image recognition models to determine one or more boundaries of the at least a portion of the sample.

In yet further implementations, defining a coarse-spaced grid pattern including a plurality of coarse-spaced grid cells includes: at least one of the following operations: defining a coarse-spaced grid pattern comprising a plurality of non-adjacent grid cells; defining a coarse-spaced grid pattern comprising a plurality of adjacent grid cells; or a coarse-spaced grid pattern comprising a plurality of non-adjacent grid cells and a plurality of adjacent grid cells.

In at least some alternative implementations, a method of operating a microscope assembly configured for enabling microscopic scanning of a field of view within a sample includes: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of a plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and if one or more criteria for terminating a scan operation are met, providing an indication of the compiled one or more aspects of the acceptable scan results.

In yet further implementations, one or more non-transitory computer-readable media carrying instructions that, when executed by one or more processing devices, controllably operate a microscope component to perform operations comprising: defining a scanning window over at least a portion of a sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of a plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and for each of the one or more neighboring grid cells, compiling the acceptable scan result with one or more aspects of a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and if one or more criteria for terminating a scan operation are met, providing an indication of the compiled one or more aspects of the acceptable scan results.

Moreover, in still other implementations, a microscope system includes: a microscope assembly configured to enable microscopic scanning of a field of view within a sample, the microscope assembly operable to: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; a portion of the plurality of grid cells are coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and for each of the one or more neighboring grid cells, compiling the acceptable scan result with one or more aspects of a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; and returning to seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

In at least some alternative implementations, the sample includes at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating the scanning operation include: one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed. And, in still other implementations, performing the scanning and evaluating for all fields of view within one or more adjacent grid cells adjacent to the acceptable selected coarse-spaced grid cell comprises: performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and evaluating the quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells.

In further implementations, performing the microscopic scan at the selected field of view within the selected ones of the plurality of coarse-spaced grid cells includes: performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells. In still further implementations, assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell includes: assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

Similarly, in some other implementations, the microscope component is operable to perform operations including: if one or more criteria for terminating the scanning operation are not satisfied, selecting a next coarse-interval grid cell as the selected coarse-interval grid cell, and returning to perform a seek mode operation. In still other implementations, the scan mode operations further include: for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell: performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell; evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and compiling, for each of the one or more secondary neighboring grid cells, one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

In at least some further implementations, a method of operating a microscope assembly configured for enabling microscopic scanning of a field of view within a sample, the method comprising: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; a portion of the plurality of grid cells are coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; and returning to seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

In still other implementations, one or more non-transitory computer-readable media carrying instructions that, when executed by one or more processing devices, controllably operate a microscope component to perform operations comprising: defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view; a portion of the plurality of grid cells are coarse-spaced grid cells; performing a seek mode operation comprising: performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells; evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell; selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results; if the quality of the scan results at the selected field of view is acceptable: performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell; evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell; assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell; if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and if the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation; performing a scan mode operation comprising: performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the neighboring grid cell; and returning to seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

It should be understood that the specific embodiments of the processes described herein are merely possible implementations of the present disclosure, and that the present disclosure is not limited to the specific implementations described herein and shown in the accompanying drawings. In addition, in alternative implementations, certain actions need not be performed in the order described, but may be modified or combined, and/or may be omitted entirely, depending on the circumstances. Further, in various implementations, the described acts may be implemented by a computer, controller, processor, programmable device, or any other suitable device, and may be based on instructions stored on one or more computer-readable media or otherwise stored or programmed into such a device. Where a computer-readable medium is used, the computer-readable medium can be any available medium that can be accessed by a device to implement the instructions stored thereon.

Various methods, systems, and techniques have been described herein in the general context of computer-executable instructions, such as program modules, being executed by one or more processors or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically, the functionality of the program modules may be combined or distributed as desired in various alternative embodiments. Additionally, embodiments of these methods, systems, and techniques may be stored on or transmitted across some form of computer readable media.

The foregoing examples are meant to be illustrative only, and the omission of examples herein should not be construed as an intentional or unintentional disavowal of subject matter. At the end of this application, the scope of the invention herein set forth is defined only by the claims appended hereto.

In some cases, use of the system or method may occur in a region even if the component is located outside of the region. For example, in a distributed computing environment, use of a distributed computing system may occur in a region, but components of the system may be located outside of the region (e.g., relays, servers, processors, signal-bearing media, sending computers, receiving computers, etc. located outside of the region).

Likewise, the sale of a system or method may occur in a region even if components of the system or method are located and/or used outside of the region. Furthermore, the implementation of at least a portion of a system for performing a method in one region does not preclude the use of the system in another region.

In a general sense, those skilled in the art will also recognize that various aspects described herein, which may be implemented individually and/or collectively by a wide range of hardware, software, firmware, and/or any combination thereof, may be considered to comprise various types of "circuitry". Thus, "circuitry" as used herein includes, but is not limited to: a circuit having at least one discrete circuit, a circuit having at least one integrated circuit, a circuit having at least one application specific integrated circuit, a circuit forming a general purpose computing device configured by a computer program (e.g., a general purpose computer configured by a computer program that at least partially implements a process and/or apparatus described herein, or a microprocessor configured by a computer program that at least partially implements a process and/or apparatus described herein), a circuit forming a storage device (e.g., various forms of memory (e.g., random access memory, flash memory, read only memory, etc.), and/or a circuit forming a communication device (e.g., a modem, a communication switch, an optoelectronic device, etc.). Those skilled in the art will recognize that the subject matter described herein may be implemented in analog or digital fashion, or some combination thereof.

One skilled in the art will recognize that at least a portion of the devices and/or processes described herein may be integrated into a data processing system. Those skilled in the art will recognize that data processing systems typically include one or more of the following: a system unit housing, a video display device, a memory such as a volatile or non-volatile memory, a processor such as a microprocessor or digital signal processor, a computing entity such as an operating system, a driver, a graphical user interface, an application program, one or more interaction devices (e.g., a touch pad, a touch screen, an antenna, etc.), and/or a control system including a feedback loop and a control motor (e.g., a feedback for sensing position and/or velocity, a control motor for moving and/or adjusting a component and/or quantity). The data processing system may be implemented using suitable commercially available components such as those commonly found in data computing/communication and/or network computing/communication systems.

For purposes of this application, "cloud" computing may be understood as described in the cloud computing literature. For example, cloud computing may be a method and/or system for delivering computing power and/or storage power as a service. A "cloud" may refer to one or more hardware and/or software components that deliver or assist in delivering computing and/or storage capabilities, including but not limited to one or more of a client, an application, a platform, an infrastructure, and/or a server. A cloud may refer to any hardware and/or software associated with a client, application, platform, infrastructure, and/or server. For example, clouds and cloud computing may involve computers, processors, storage media, routers, switches, modems, virtual machines (e.g., virtual servers), data centers, operating systems, middleware, firmware, hardware back-ends, software back-ends, and/or software applications. A cloud may refer to a private cloud, a public cloud, a hybrid cloud, and/or a community cloud. A cloud may be a shared pool of configurable computing resources, which may be public, private, semi-private, distributable, scalable, flexible, temporary, virtual, and/or physical. The cloud or cloud services may be delivered over one or more types of networks (e.g., mobile communication networks) and the internet.

As used herein, a cloud or cloud service may include one or more of infrastructure as a service ("IaaS"), platform as a service ("PaaS"), software as a service ("SaaS"), and/or desktop as a service ("DaaS"). As a non-exclusive example, IaaS may include, for example, one or more virtual server instances that may start, stop, access, and/or configure virtual servers and/or storage centers (e.g., provide one or more processors, storage space, and/or network resources (e.g., EMC and Rackspace). PaaS may include, for example, one or more software and/or development tools hosted on an infrastructure (e.g., a computing platform and/or solution stack from which a client may create a software interface and an application, such as Microsoft Azure). For example, a user may be provided with a desktop, applications, data, and/or services over a network (e.g., providing a multi-application framework, applications in a framework, data associated with an application, and/or services related to applications and/or data over a network, such as Citrix). The foregoing is intended as an example of the type of system and/or method referred to herein as "cloud" or "cloud computing" and should not be taken as complete or exhaustive.

Those skilled in the art will recognize that the components (e.g., operations), devices, objects, and the discussion accompanying them described herein are used as examples for the sake of conceptual clarity, and that various configuration modifications are contemplated. Thus, as used herein, the specific examples set forth and the accompanying discussion are intended to be representative of their more general categories. In general, the use of any particular example is intended to be representative of its class, and the exclusion of particular components (e.g., operations), devices, and objects should not be considered limiting.

The subject matter described herein sometimes illustrates different components contained within, or connected with, different other components. It is to be understood that such depicted architectures are merely exemplary, and that in fact many other architectures can be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively "associated" such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality can be seen as "associated with" each other such that the desired functionality is achieved, irrespective of architectures or intermedial components. Likewise, any two components so associated can also be viewed as being "operably connected," or "operably coupled," to each other to achieve the desired functionality, and any two components capable of being so associated can also be viewed as being "operably couplable," to each other to achieve the desired functionality. Specific examples of operably couplable include but are not limited to physically mateable and/or physically interacting components, and/or wirelessly interactable and/or wirelessly interacting components, and/or logically interactable components.

To the extent there is a formal outline heading in this application, it is understood that the outline heading is for descriptive purposes and that different types of subject matter may be discussed throughout the application (e.g., devices/structures may be described under a process/operation heading and/or processes/operations may be discussed under a structure/process heading; and/or a description of a single subject matter may span two or more subject matter headings). Accordingly, any use of the formal outline headings in this application is for presentation purposes and is not intended to be limiting in any way.

Throughout this application, examples and lists are given, and these examples and/or lists may be depicted in parentheses, commas, abbreviations "e.g., (e.g.)" or some combination thereof. Unless expressly stated otherwise, these examples and lists are exemplary only and not exhaustive. In most cases, listing each example and each combination is difficult to achieve. Thus, using fewer illustrative lists and examples, emphasis is placed upon giving understanding of claim terms, rather than limiting the scope of such terms.

With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. For the sake of clarity, various singular/plural permutations are not explicitly set forth herein.

It will be appreciated by those of ordinary skill in the art that the components (e.g., operations), devices, objects, and the discussion that accompanies them described herein are used as examples for conceptual clarity, and that various configuration modifications are contemplated. Thus, as used herein, the specific examples set forth and the accompanying discussion are intended to represent a more general class thereof. In general, the use of any particular example is intended to represent its class, and the exclusion of particular components (e.g., operations), devices, and objects should not be viewed as limiting.

Although one or more users may be shown and/or described herein and elsewhere, as a single illustrated diagram, one skilled in the art will appreciate that one or more users may represent one or more human users, robotic users (e.g., computing entities), and/or substantially any combination thereof (e.g., one or more robotic agents may assist a user), unless context dictates otherwise. It will be understood by those skilled in the art that, in general, a "sender" and/or other entity-oriented is considered to be the same term as such term is used herein, unless the context indicates otherwise.

In some cases, one or more components may be referred to herein as "configured," "configured by …," "configurable," "operable/operational," "adapted/adaptable," "capable," "conformable/complying with," or the like. Those skilled in the art will recognize that such terms (e.g., "configured to") may generally include components in an active state and/or components in an inactive state and/or components in an on-standby state unless the context requires otherwise.

While particular aspects of the subject matter described herein have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from the subject matter described herein and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of the subject matter described herein. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.).

It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to claims containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and/or "an" should typically be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. Furthermore, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, typically means at least two recitations, or two or more recitations).

Further, in those instances where a convention analogous to "A, B, at least one of C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand (e.g., "a system having at least one of A, B and C" would include, but not be limited to, an A only system, a B only system, a C only system, both A and B systems, both A and C systems, both B and C systems, and/or both A, B and C systems, etc.). In those instances where a convention analogous to "A, B or at least one of C, etc." is used, in general such a construction is intended in the sense one having skill in the art would understand (e.g., "a system having at least one of A, B or C" would include but not be limited to systems having A alone, B alone, C alone, both A and B together, both A and C together, both B and C together, and/or both A, B and C together, etc.). It will also be understood by those within the art that in general, the words and/or phrases setting forth two or more alternative terms, whether in the specification, claims, or drawings, are to be understood as contemplating possibilities for one, either, or both, unless the context dictates otherwise. For example, the phrase "a or B" will generally be understood to include the possibility of "a" or "B" or "a and B".

Those of skill in the art will understand with respect to the claims that follow that the operations described therein can generally be performed in any order. Additionally, while the various operational flows are presented in a sequential order, it should be understood that the various operations may be performed in a different order than those set forth, or may be performed concurrently. Examples of such alternative orders may include overlapping, interleaved, interrupted, reordered, incremental, preliminary, supplemental, simultaneous, reverse, or other variant orders, unless the context dictates otherwise. Moreover, adjectives such as "responsive to," "related to … …," or other past tenses are generally not intended to exclude such variations, unless the context dictates otherwise.

The present application may refer to one or more trademarks such as words, letters, symbols, or devices employed by a manufacturer or merchant to identify and/or distinguish its product from other products. The trademark name used herein is set forth in language that clearly indicates its identity, distinguishes it from common descriptive terms having a fixed and definite meaning, or in many, if not all cases, appends other specific identifiers using terms not covered by the trademark. Additionally, the trade names used herein have meanings that are well known and defined in the literature or do not represent products or compounds that require knowledge of one or more trade secrets in order to understand their meanings. All trademarks referenced in this application are the property of their respective owners and the appearance of one or more trademarks in this application does not diminish or otherwise adversely affect the effectiveness of the one or more trademarks. It is assumed that all registered or unregistered trademarks appearing in this application contain the appropriate trademark symbol, such as circled R or brackets capitalization (e.g., [ brand name ]), even if the trademark symbol is not explicitly shown next to the trademark. To the extent that a trademark is used in a descriptive manner to refer to a product or process, the trademark should be interpreted as representing the corresponding product or process as of the filing date of this patent application.

In this application, the terms "in one embodiment," "in at least some embodiments," "in one embodiment," "in some embodiments," "in several embodiments," "in at least one embodiment," "in various embodiments," and the like may be used. Unless expressly stated otherwise, each of these terms, as well as all such similar terms, shall be interpreted as "in at least one embodiment, and possibly but not necessarily in all embodiments. In particular, phrases like these are intended to provide non-exclusive and non-limiting examples of implementations of the present invention unless expressly stated otherwise. The mere fact that one, some, or more embodiments include one or more things or have one or more features does not imply that all embodiments include one or more things or have one or more features, nor does it imply that such embodiments must be present. It is merely an indication of an example and should not be construed in other ways unless explicitly stated as such.

In this application, the terms "in an implementation," "in at least some implementations," "in one implementation," "in some implementations," "in several implementations," "in at least one implementation," "in various implementations," and so forth may be used. Unless expressly stated otherwise, each of these terms, as well as all such similar terms, should be interpreted as "in at least one implementation, and possibly but not necessarily in all implementations". In particular, phrases like these are intended to provide non-exclusive and non-limiting examples of implementations of the present invention unless expressly stated otherwise. The mere fact that one, some, or more implementations include one or more things or have one or more features does not mean that all implementations include one or more things or have one or more features, nor does it mean that such implementations must be present. It is merely an indication of an example and should not be construed in other ways unless explicitly stated as such.

Aspects of the subject matter described herein are described in the following numbered clauses:

1. a microscope system, comprising:

a microscope assembly configured to obtain a microscopic scan of a field of view within a sample, the microscope assembly operable to perform operations comprising:

defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view;

defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell;

selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and is

Providing an indication of the compiled one or more aspects of the acceptable scan results if one or more criteria for terminating a scan operation are met.

2. The system of clause 1, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

3. The system of clause 1, wherein defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, comprises:

the scanning window is defined as a plurality of square grid cells, wherein each square grid cell includes an equal number of rows and columns of fields of view.

4. The system of clause 1, wherein performing the microscopic scan at the selected field of view within the selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

5. The system of clause 1, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

6. The system of clause 5, wherein the threshold percentage is at least fifty percent.

7. The system of clause 1, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarse-spaced grid pattern comprising a first coarse-spaced grid cell positioned proximate the scanning window center and a plurality of first non-adjacent grid cells located within a first non-adjacent perimeter disposed about and spaced apart from the first coarse-spaced grid cell.

8. The system of clause 7, wherein selecting the next coarse-spaced grid cell as the selected coarse-spaced grid cell comprises:

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of:

proceeding outward from the first coarse spaced grid cells to select first non-adjacent grid cells located within the first non-adjacent perimeter; or

Traversing from one of first non-adjacent grid cells to select another of the first non-adjacent grid cells that is located within the first non-adjacent perimeter.

9. The system of clause 7, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarsely-spaced grid pattern comprising a plurality of second non-adjacent grid cells located within a second non-adjacent perimeter disposed around and spaced apart from the first non-adjacent perimeter.

10. The system of clause 1, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarse-spaced grid pattern comprising a first set of first non-adjacent grid cells and a second set of second non-adjacent grid cells, the first set of the first non-adjacent grid cells being distributed throughout the scanning window and each first non-adjacent grid cell being non-adjacent to other first non-adjacent grid cells, and each second non-adjacent grid cell being diagonally disposed proximate to at least one first non-adjacent grid cell and non-adjacent to other second non-adjacent grid cells.

11. The system of clause 10, wherein selecting the next coarse-spaced grid cell as the selected coarse-spaced grid cell comprises:

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of:

proceeding from one of the first set of the first non-adjacent grid cells to another of the first set of first non-adjacent grid cells;

proceeding from one of the first set of the first non-adjacent grid cells to one of the second set of the second non-adjacent grid cells arranged diagonally proximate to the one of the first set of the first non-adjacent grid cells; or

Proceeding from one of the second set of the second non-adjacent grid cells to another of the second set of second non-adjacent grid cells.

12. The system of clause 10, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

a coarse-spaced grid pattern is defined that includes a third set of third non-adjacent grid cells, each third non-adjacent grid cell being arranged diagonally adjacent to at least one second non-adjacent grid cell and not adjacent to other third non-adjacent grid cells.

13. The system of clause 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the micro-scan at all fields of view within half of the adjacent grid cells within a perimeter of the grid cell adjacent to the selected coarse spaced grid cell that is acceptable.

14. The system of clause 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of a grid cell adjacent to and sharing a common boundary with the acceptable selected coarse spaced grid cell.

15. The system of clause 1, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to and sharing common corner points with the acceptable selected coarse spaced grid cells.

16. The system of clause 1, wherein performing scan mode operations further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

17. The system of clause 1, wherein evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell comprises:

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell based on one or more of sharpness, blur, or brightness.

18. The system of clause 1, wherein evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell comprises:

assigning a quality assessment score based on a quality assessment of the scan results.

19. The system of clause 1, wherein the microscope assembly is operable to perform operations comprising:

obtaining a macroscopic image of at least a portion of the sample; and

analyzing the macroscopic image to determine suitability of the at least a portion of the sample for analysis.

20. The system of clause 19, wherein analyzing the macroscopic image to determine the suitability of the at least a portion of the sample for analysis comprises:

performing one or more machine learning operations using one or more image recognition models to determine suitability of the at least a portion of the sample for analysis.

21. The system of clause 1, wherein defining the scanning window over at least a portion of the sample as a plurality of grid cells comprises:

obtaining a macroscopic image of at least a portion of the sample;

analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample; and

defining a position of the scanning window based on the one or more boundaries of the at least a portion of the sample.

22. The system of clause 21, wherein analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample comprises:

performing one or more machine learning operations using one or more image recognition models to determine one or more boundaries of the at least a portion of the sample.

23. The system of clause 1, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

at least one of the following operations:

defining a coarse-spaced grid pattern comprising a plurality of non-adjacent grid cells;

defining a coarse-spaced grid pattern comprising a plurality of adjacent grid cells; or

A coarse-spaced grid pattern is defined that includes a plurality of non-adjacent grid cells and a plurality of adjacent grid cells.

24. A method of operating a microscope assembly configured for enabling microscopic scanning of a field of view within a sample, the method comprising:

defining a scanning window over at least a portion of the sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view;

defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of a plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell;

selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and is

Providing an indication of the compiled one or more aspects of the acceptable scan results if one or more criteria for terminating a scan operation are met.

25. The method of clause 24, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

26. The method of clause 24, wherein defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, comprises:

the scanning window is defined as a plurality of square grid cells, wherein each square grid cell includes an equal number of rows and columns of fields of view.

27. The method of clause 24, wherein performing the microscopic scan at the selected field of view within the selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

28. The method of clause 24, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

29. The method of clause 28, wherein the threshold percentage is at least fifty percent.

30. The method of clause 24, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarse-spaced grid pattern comprising a first coarse-spaced grid cell positioned proximate the scanning window center and a plurality of first non-adjacent grid cells located within a first non-adjacent perimeter disposed about and spaced apart from the first coarse-spaced grid cell.

31. The method of clause 30, wherein selecting the next coarse-spaced grid cell as the selected coarse-spaced grid cell comprises:

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of:

proceeding outward from the first coarse spaced grid cells to select first non-adjacent grid cells located within the first non-adjacent perimeter; or

Traversing from one of first non-adjacent grid cells to select another of the first non-adjacent grid cells that is located within the first non-adjacent perimeter.

32. The method of clause 30, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarsely-spaced grid pattern comprising a plurality of second non-adjacent grid cells located within a second non-adjacent perimeter disposed around and spaced apart from the first non-adjacent perimeter.

33. The method of clause 24, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

defining a coarse-spaced grid pattern comprising a first set of first non-adjacent grid cells and a second set of second non-adjacent grid cells, the first set of the first non-adjacent grid cells being distributed throughout the scanning window and each first non-adjacent grid cell being non-adjacent to other first non-adjacent grid cells, and each second non-adjacent grid cell being diagonally disposed proximate to at least one first non-adjacent grid cell and non-adjacent to other second non-adjacent grid cells.

34. The method of clause 33, wherein selecting the next coarse-spaced grid cell as the selected coarse-spaced grid cell comprises:

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell, comprising at least one of:

proceeding from one of the first set of the first non-adjacent grid cells to another of the first set of first non-adjacent grid cells;

proceeding from one of the first set of the first non-adjacent grid cells to one of the second set of the second non-adjacent grid cells arranged diagonally proximate to the one of the first set of the first non-adjacent grid cells; or

Proceeding from one of the second set of the second non-adjacent grid cells to another of the second set of second non-adjacent grid cells.

35. The method of clause 33, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

a coarse-spaced grid pattern is defined that includes a third set of third non-adjacent grid cells, each third non-adjacent grid cell being arranged diagonally adjacent to at least one second non-adjacent grid cell and not adjacent to other third non-adjacent grid cells.

36. The method of clause 24, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the micro-scan at all fields of view within half of the adjacent grid cells within a perimeter of the grid cell adjacent to the selected coarse spaced grid cell that is acceptable.

37. The method of clause 24, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of a grid cell adjacent to and sharing a common boundary with the acceptable selected coarse spaced grid cell.

38. The method of clause 24, wherein performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the acceptable selected coarse spaced grid cell comprises:

performing the microscopic scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to and sharing common corner points with the acceptable selected coarse spaced grid cells.

39. The method of clause 24, wherein performing scan mode operations further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

40. The method of clause 24, wherein evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell comprises:

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell based on one or more of sharpness, blur, or brightness.

41. The method of clause 24, wherein evaluating the quality of the scan results from the microscopic scan within the selected coarse-spaced grid cell comprises:

assigning a quality assessment score based on a quality assessment of the scan results.

42. The method of clause 24, further comprising:

obtaining a macroscopic image of at least a portion of the sample; and

analyzing the macroscopic image to determine suitability of the at least a portion of the sample for analysis.

43. The method of clause 42, wherein analyzing the macroscopic image to determine the suitability of the at least a portion of the sample for analysis comprises:

performing one or more machine learning operations using one or more image recognition models to determine suitability of the at least a portion of the sample for analysis.

44. The method of clause 24, wherein defining the scanning window over at least a portion of the sample as a plurality of grid cells comprises:

obtaining a macroscopic image of at least a portion of the sample;

analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample; and

defining a position of the scanning window based on the one or more boundaries of the at least a portion of the sample.

45. The system of clause 44, wherein analyzing the macroscopic image to determine one or more boundaries of the at least a portion of the sample comprises:

performing one or more machine learning operations using one or more image recognition models to determine one or more boundaries of the at least a portion of the sample.

46. The method of clause 24, wherein defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells comprises:

at least one of the following operations:

defining a coarse-spaced grid pattern comprising a plurality of non-adjacent grid cells;

defining a coarse-spaced grid pattern comprising a plurality of adjacent grid cells; or

A coarse-spaced grid pattern is defined that includes a plurality of non-adjacent grid cells and a plurality of adjacent grid cells.

47. One or more non-transitory computer-readable media carrying instructions that, when executed by one or more processing devices, controllably operate a microscope assembly to:

defining a scanning window over at least a portion of a sample into a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view;

defining a coarse-spaced grid pattern comprising a plurality of coarse-spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of a plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell;

selecting a next coarse-interval grid cell as the selected coarse-interval grid cell if one or more criteria for terminating the scanning operation are not satisfied, and returning to perform a seek mode operation; and is

Providing an indication of the compiled one or more aspects of the acceptable scan results if one or more criteria for terminating a scan operation are met.

48. A microscope system, comprising:

a microscope assembly configured for enabling microscopic scanning of a field of view within a sample, the microscope assembly operable to:

defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, a portion of the plurality of grid cells being coarse spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell; and

returning to a seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

49. The system of clause 48, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

50. The system of clause 48, wherein performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the acceptable selected coarse-spaced grid cell comprises:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells.

51. The system of clause 48, wherein performing the microscopic scan at the selected field of view within the selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

52. The system of clause 48, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

53. The system of clause 48, wherein the microscope assembly is further operable to perform operations comprising:

if one or more criteria for terminating the scanning operation are not satisfied, selecting a next coarse-interval grid cell as the selected coarse-interval grid cell, and returning to perform a seek mode operation.

54. The system of clause 48, wherein the scan mode operation further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

55. A method of operating a microscope assembly configured for enabling microscopic scanning of a field of view within a sample, the method comprising:

defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, a portion of the plurality of grid cells being coarse spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell; and

returning to a seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

56. The method of clause 55, wherein the sample comprises at least one of a thick film or a thin film of a blood sample, and wherein the one or more criteria for terminating a scanning operation comprises:

one or more of a total number of acceptable fields of view scanned, a total number of white blood cells calculated, a total number of red blood cells calculated, a total number of malaria parasites calculated, an amount of time elapsed during seek mode operation, an amount of time elapsed during scan mode operation, or a total amount of time elapsed.

57. The method of clause 55, wherein performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the acceptable selected coarse-spaced grid cell comprises:

performing the micro-scan at all fields of view within one or more adjacent grid cells within a perimeter of grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more adjacent grid cells.

58. The method of clause 55, wherein performing the microscopic scan at the selected field of view within the selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells comprises:

performing the microscopic scan at a central field of view of a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells.

59. The method of clause 55, wherein assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell comprises:

assessing that the selected coarse spacing grid cell is acceptable when at least a threshold percentage of the field of view of the selected coarse spacing grid cell is evaluated to provide acceptable scan results.

60. The method of clause 55, wherein the microscope assembly is further operable to perform operations comprising:

if one or more criteria for terminating the scanning operation are not satisfied, selecting a next coarse-interval grid cell as the selected coarse-interval grid cell, and returning to perform a seek mode operation.

61. The method of clause 55, wherein the scan mode operation further comprises:

for each of the one or more neighboring grid cells, if the quality of the scan result is acceptable for the neighboring grid cell:

performing the micro-scan at all fields of view within one or more secondary neighboring grid cells within a perimeter of a grid cell neighboring the acceptable neighboring grid cell;

evaluating a quality of the scan results from the microscopic scans at all fields of view within the one or more secondary neighboring grid cells; and

for each of the one or more secondary neighboring grid cells, compiling one or more aspects of the acceptable scan result with a previous acceptable scan result if the quality of the scan result is acceptable for the secondary neighboring grid cell.

62. One or more non-transitory computer-readable media carrying instructions that, when executed by one or more processing devices, controllably operate a microscope assembly to:

defining a scanning window over at least a portion of the sample as a plurality of grid cells, wherein each grid cell of the plurality of grid cells is sized to include a plurality of fields of view, a portion of the plurality of grid cells being coarse spaced grid cells;

performing a seek mode operation comprising:

performing the microscopic scan at a selected field of view within a selected coarse-spaced grid cell of the plurality of coarse-spaced grid cells;

evaluating a quality of a scan result from the microscopic scan within the selected coarse-spaced grid cell;

selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell if the quality of the scan results at the selected field of view is not acceptable, and returning to perform the microscopic scan and evaluate the quality of the scan results;

if the quality of the scan results at the selected field of view is acceptable:

performing the microscopic scan of all remaining fields of view of the selected coarse-spaced grid cell;

evaluating the quality of the scan results from all remaining fields of view of the selected coarse-spaced grid cell;

assessing whether the selected coarse-spaced grid cell is acceptable based on the quality of the scan results from all fields of view of the selected coarse-spaced grid cell;

if the selected coarse-spaced grid cell is not acceptable, selecting a next coarse-spaced grid cell as the selected coarse-spaced grid cell and returning to perform the microscopic scan and evaluating the quality of the scan results; and is

If the selected coarse-spaced grid cell is acceptable, proceeding to a scan mode operation;

performing a scan mode operation comprising:

performing a scan and evaluation of all fields of view within one or more adjacent grid cells adjacent to the selected coarse spaced grid cell that are acceptable; and

for each of the one or more neighboring grid cells, compiling one or more aspects of the acceptable scan results with a previous acceptable scan result if the quality of the scan results is acceptable for the neighboring grid cell; and

returning to a seek mode operation if one or more criteria for terminating a scan operation are not satisfied, otherwise providing an indication of the compiled one or more aspects of the acceptable scan results.

It should be appreciated by those of skill in the art that the foregoing specific exemplary processes and/or devices and/or techniques represent more general processes and/or devices and/or techniques as taught elsewhere herein (e.g., in the claims filed herewith and/or elsewhere in the present application).