System for and method of focusing in automated microscope systems

Abstract

The present disclosure includes systems and techniques relating to focusing in automated microscope systems. In general, in one implementation, the technique includes obtaining an image of at least a portion of a scan region, analyzing the image to find an area in the image representing a sample, determining a nature of the sample at a selected focus point location in the area in the image, selecting an automated focusing process for use at the selected focus point location based on the determined nature of the sample at the selected focus point location, and focusing using the selected automated focusing process. The selecting can include selecting different automated focusing processes for different focus point locations based on different tissue characteristics at the locations.

1 . A method comprising: 
 analyzing an image of at least a portion of a scan region to find an area in the image representing a sample;    determining a nature of the sample at a selected focus point location that falls in the area in the image;    selecting an automated focusing process for use at the selected focus point location, from among multiple automated focusing processes, based on the determined nature of the sample at the selected focus point location; and    focusing using the selected automated focusing process.    
     
     
         2 . The method of  claim 1 , wherein the determining comprises performing a cluster analysis of data from the area representing the sample in the image according to focus-ability.  
     
     
         3 . The method of  claim 1 , wherein the selecting comprises selecting multiple different automated focusing processes for use at multiple different selected focus point locations based on different tissue characteristics at the multiple different selected focus point locations.  
     
     
         4 . The method of  claim 3 , further comprising: 
 preparing a set of candidate focus points; and    selecting from the candidate focus points to obtain the selected focus point locations such that the selected focus point locations are distributed across the area representing the sample.    
     
     
         5 . The method of  claim 4 , wherein the preparing comprises collecting the set of candidate focus points, and trimming the set based on specified criteria that sets an upper limit on focus point locations.  
     
     
         6 . The method of  claim 4 , wherein the selecting from the candidate focus points comprises maximizing distance between selected points.  
     
     
         7 . The method of  claim 6 , wherein the maximizing comprises maximizing the distance among a first set of selected focus points, and the selecting from the candidate focus points further comprises minimizing a distance among a second set of selected focus points.  
     
     
         8 . The method of  claim 4 , wherein the selecting from the candidate focus points comprises jittering a focus point to eliminate collinearity with previous focus points.  
     
     
         9 . The method of  claim 3 , wherein the focusing comprises using the different automated focusing processes at the different selected focus point locations, respectively, to obtain multiple Z-axis points, the method further comprising: 
 setting a focal surface according to the Z-axis points; and    focusing at other locations according to the focal surface.    
     
     
         10 . The method of  claim 9 , wherein the setting comprises: 
 weighting the Z-axis points according to a confidence measure; and    fitting the focal surface to the weighted Z-axis points.    
     
     
         11 . The method of  claim 9 , further comprising removing one or more of the Z-axis points determined to be outliers before setting the focal surface.  
     
     
         12 . The method of  claim 1 , wherein the analyzing comprises performing a silhouette scan.  
     
     
         13 . The method of  claim 1 , further comprising obtaining the image by taking a first digital image of a microscope slide with a lower-magnification microscope objective that has a large depth of view, wherein the analyzing comprises analyzing the first digital image to find the area representing the sample, and the determining comprises: 
 acquiring a second digital image of the microscope slide at the selected focus point location with a higher-magnification microscope objective; and    evaluating the second digital image with respect to available automated focusing processes.    
     
     
         14 . The method of  claim 13 , wherein the available automated focusing processes comprise focusing processes previously selected based on an empirical analysis of focusing processes applied in a given test of a biological specimen.  
     
     
         15 . An article comprising a machine-readable medium storing instructions operable to cause one or more machines to perform operations comprising: 
 obtaining an image of at least a portion of a scan region;    analyzing the image to find an area in the image representing a sample;    determining a nature of the sample at a selected focus point location that falls in the area in the image;    selecting an automated focusing process for use at the selected focus point location, from among multiple automated focusing processes, based on the determined nature of the sample at the selected focus point location; and    focusing using the selected automated focusing process.    
     
     
         16 . The article of  claim 15 , wherein the determining comprises performing a cluster analysis of data from the area representing the sample in the image according to focus-ability.  
     
     
         17 . The article of  claim 15 , wherein the selecting comprises selecting multiple different automated focusing processes for use at multiple different selected focus point locations based on different tissue characteristics at the multiple different selected focus point locations.  
     
     
         18 . The article of  claim 17 , the operations further comprising: 
 preparing a set of candidate focus points; and    selecting from the candidate focus points to obtain the selected focus point locations such that the selected focus point locations are distributed across the area representing the sample.    
     
     
         19 . The article of  claim 17 , wherein the focusing comprises using the different automated focusing processes at the different selected focus point locations, respectively, to obtain multiple Z-axis points, the operations further comprising: 
 setting a focal surface according to the Z-axis points; and    focusing at other locations according to the focal surface.    
     
     
         20 . The article of  claim 19 , wherein the setting comprises: 
 weighting the Z-axis points according to a confidence measure; and    fitting the focal surface to the weighted Z-axis points.    
     
     
         21 . The article of  claim 15 , wherein the obtaining comprises taking a first digital image of a microscope slide with a lower-magnification microscope objective that has a large depth of view, the analyzing comprises analyzing the first digital image to find the area representing the sample, and the determining comprises: 
 acquiring a second digital image of the microscope slide at the selected focus point location with a higher-magnification microscope objective; and    evaluating the second digital image with respect to available automated focusing processes.    
     
     
         22 . An automated imaging system comprising: 
 a microscope;    a controller coupled with the microscope; and    a display device coupled with the controller;    wherein the controller is configured to operate the microscope autonomously, to present image data on the display device, and to perform operations including:    analyzing an image of at least a portion of a scan region to find an area in the image representing a sample;    determining a nature of the sample at a selected focus point location that falls in the area in the image;    selecting an automated focusing process for use at the selected focus point location, from among multiple automated focusing processes, based on the determined nature of the sample at the selected focus point location; and    focusing using the selected automated focusing process.    
     
     
         23 . The system of  claim 22 , wherein the determining comprises performing a cluster analysis of data from the area representing the sample in the image according to focus-ability.  
     
     
         24 . The system of  claim 22 , wherein the selecting comprises selecting multiple different automated focusing processes for use at multiple different selected focus point locations based on different tissue characteristics at the multiple different selected focus point locations.  
     
     
         25 . The system of  claim 24 , wherein the operations further include: 
 preparing a set of candidate focus points; and    selecting from the candidate focus points to obtain the selected focus point locations such that the selected focus point locations are distributed across the area representing the sample.    
     
     
         26 . The system of  claim 25 , wherein the preparing comprises collecting the set of candidate focus points, and trimming the set based on specified criteria that sets an upper limit on focus point locations.  
     
     
         27 . The system of  claim 25 , wherein the selecting from the candidate focus points comprises maximizing distance between selected points.  
     
     
         28 . The system of  claim 24 , wherein the focusing comprises using the different automated focusing processes at the different selected focus point locations, respectively, to obtain multiple Z-axis points, and the operations further include: 
 setting a focal surface according to the Z-axis points; and    focusing at other locations according to the focal surface.    
     
     
         29 . The system of  claim 28 , wherein the setting comprises: 
 weighting the Z-axis points according to a confidence measure; and    fitting the focal surface to the weighted Z-axis points.    
     
     
         30 . The system of  claim 28 , the operations further including removing one or more of the Z-axis points determined to be outliers before setting the focal surface.  
     
     
         31 . The system of  claim 22 , the operations further comprising obtaining the image by taking a first digital image of a microscope slide with a lower-magnification microscope objective that has a large depth of view, wherein the analyzing comprises analyzing the first digital image to find the area representing the sample, and the determining comprises: 
 acquiring a second digital image of the microscope slide at the selected focus point location with a higher-magnification microscope objective; and    evaluating the second digital image with respect to available automated focusing processes.    
     
     
         32 . The system of  claim 31 , wherein the available automated focusing processes comprise focusing processes previously selected by an application designer based on an empirical analysis of focusing processes applied in a given test of a biological specimen.  
     
     
         33 . An apparatus comprising: 
 an interface configured to connect with a microscope; and    a controller configured to send signals through the interface to operate the microscope and to perform operations including:    analyzing an image of at least a portion of a scan region to find an area in the image representing a sample;    determining a nature of the sample at a selected focus point location that falls in the area in the image;    selecting an automated focusing process for use at the selected focus point location, from among multiple automated focusing processes, based on the determined nature of the sample at the selected focus point location; and    outputting a signal to cause focusing of the microscope using the selected automated focusing process.    
     
     
         34 . The apparatus of  claim 33 , wherein the determining comprises performing a cluster analysis of data from the area representing the sample in the image according to focus-ability.  
     
     
         35 . The apparatus of  claim 33 , wherein the selecting comprises selecting multiple different automated focusing processes for use at multiple different selected focus point locations based on different tissue characteristics at the multiple different selected focus point locations.  
     
     
         36 . The apparatus of  claim 35 , wherein the operations further include: 
 preparing a set of candidate focus points; and    selecting from the candidate focus points to obtain the selected focus point locations such that the selected focus point locations are distributed across the area representing the sample.    
     
     
         37 . The apparatus of  claim 36 , wherein the preparing comprises collecting the set of candidate focus points, and trimming the set based on specified criteria that sets an upper limit on focus point locations.  
     
     
         38 . The apparatus of  claim 36 , wherein the selecting from the candidate focus points comprises maximizing distance between selected points.