System and method for imaging and illumination for cell confluence measurement

Abstract

A cell monitoring plate comprises a flat surface on which multiple cell culturing vessels may be stacked. The flats surface has multiple optical imaging systems embedded therein to fully image a cell culture vessels stacked on the plate. Each one of the multiple optical imaging systems provides both illumination and imaging through a single aperture in the surface of the monitoring plate.

What is claimed is: 
     
         1 . An apparatus comprising:
 a housing having a flat top surface;   one or more apertures disposed in the flat top surface;   one or more optical imaging systems disposed within the housing and configured to image a culture in a cell culture vessel placed on the flat top surface of the housing.   
     
     
         2 . The apparatus of  claim 1 , the one or more optical imaging systems each comprising:
 an imaging component; and   an illumination component.   
     
     
         3 . The apparatus of  claim 2 , the illumination component configured to direct light at an oblique angle to a surface above the culture in the cell culture vessel such that the light is reflected off of the surface such as to illuminate the culture from a side opposite the imaging component. 
     
     
         4 . The apparatus of  claim 3 , wherein the surface reflecting the light is the bottom surface of the cell culture vessels stacked on top of the cell culture vessel placed on the flat top surface of the housing. 
     
     
         5 . The apparatus of  claim 2 , the imaging component being disposed in the housing offset from one of the apertures in the top surface of the housing, further comprising:
 a mirror located directly underneath the aperture and angled to direct light from the culture to the imaging component.   
     
     
         6 . The apparatus of  claim 5 , the imaging component having a focal length fixed to image the culture in the cell culture vessel placed directly on the top surface of the housing. 
     
     
         7 . The apparatus of  claim 5 , the imaging component having a movable focal length which may be adjusted to image cultures located in cell culture vessels stacked on the cell culture vessel placed directly on the top surface of the housing. 
     
     
         8 . The apparatus of  claim 2 , the illumination component configured to vary the oblique angle such as to illuminate cultures located in cell culture vessels stacked on the cell culture vessel placed directly on the top surface of the housing. 
     
     
         9 . The apparatus of  claim 2 , further comprising:
 a communications interface;   a controller; and   a power source for powering communications interface, the controller, and the one or more optical imaging systems.   
     
     
         10 . The apparatus of  claim 9 , the controller receiving commands via the communication interface to image cultures located in one or more cell culture vessels stacked on the top surface of the housing. 
     
     
         11 . The apparatus of  claim 10 , the computer controller transmitting images from the one or more optical imaging systems via the communications interface. 
     
     
         12 . The apparatus of  claim 9 , further comprising:
 an image processing component for processing of images collected from the one or more optical imaging systems.   
     
     
         13 . The apparatus of  claim 12 , the imaging processing component analyzing images collected from the one or more optical imaging systems to determine confluence of cell cultures located in one or more cell culture vessels stacked on the top surface of the housing. 
     
     
         14 . The apparatus of  claim 13 , imaging processing component comprising one or more machine learning models trained to determine cell confluence from images. 
     
     
         15 . The apparatus of  claim 13 , the imaging process component configured to transmit the results of the image analysis via the communications interface. 
     
     
         16 . A method for determining cell confluence in a cell culture comprising:
 providing one or more optical imaging systems, each optical imaging system comprising an imaging component and illumination component below the cell culture;   directing light from the illumination component at an oblique angle to a reflective surface above the cell culture such that the cell culture is illuminated from a side opposite the imaging component;   capturing an image of the illuminated cell culture with the imaging component.   
     
     
         17 . The method of  claim 16 , further comprising
 collecting images of the cell culture from one or more of the optical imaging systems.   
     
     
         18 . The method of  claim 17 , further comprising transmitting the collected image via a communications interface. 
     
     
         19 . The method of  claim 17 , further comprising analyzing the collected images using an image processing component, the image processing component configured to detect cell confluence in the cell culture. 
     
     
         20 . The method of  claim 19 , further comprising transmitting the results of the image analysis via the communications interface. 
     
     
         21 . An apparatus comprising:
 a cell culture vessel having a top surface and a bottom surface;   a housing having a flat top surface wherein the bottom surface of the cell culture vessel is disposed on top of the flat top surface;   one or more apertures disposed in the flat top surface;   one or more optical imaging systems disposed within the housing and configured to image a culture in the cell culture vessel placed on the flat top surface of the housing.   
     
     
         22 . The apparatus of  claim 21 , the one or more optical imaging systems each comprising:
 an imaging component; and   an illumination component.   
     
     
         23 . The apparatus of  claim 22 , the illumination component configured to direct light at an oblique angle to the top surface of the culture vessel such that the light is reflected off of the top surface such as to illuminate the culture from a side opposite the imaging component. 
     
     
         24 . The apparatus of  claim 22 , further comprising a second cell culture vessel having a second bottom surface and a second top surface, wherein the second bottom surface of the second cell culture vessel is disposed adjacent the top surface of the cell culture surface. 
     
     
         25 . The apparatus of  claim 24 , the illumination component configured to direct light at an oblique angle to through the culture vessel such that the light is reflected off of the second bottom surface of the second cell culture vessel such as to illuminate the culture in the cell culture vessel from a side opposite the imaging component. 
     
     
         26 . The apparatus of  claim 22 , the imaging component being disposed in the housing offset from one of the apertures in the top surface of the housing, further comprising:
 a mirror located directly underneath the aperture and angled to direct light from the culture to the imaging component.   
     
     
         27 . The apparatus of  claim 26 , the imaging component having a focal length fixed to image the culture in the cell culture vessel placed directly on the top surface of the housing. 
     
     
         28 . The apparatus of  claim 26 , the imaging component having a movable focal length which may be adjusted to image cultures located in the second cell vessel stacked on the cell culture vessel placed directly on the top surface of the housing. 
     
     
         29 . The apparatus of  claim 22 , the illumination component configured to vary the oblique angle such as to illuminate cultures located in the second cell culture vessel stacked on the cell culture vessel placed directly on the top surface of the housing. 
     
     
         30 . The apparatus of  claim 22 , further comprising:
 a communications interface;   a controller; and   a power source for powering communications interface, the controller, and the one or more optical imaging systems.   
     
     
         31 . The apparatus of  claim 30 , the controller receiving commands via the communication interface to image cultures located in one or more cell culture vessels stacked on the top surface of the housing. 
     
     
         32 . The apparatus of  claim 31 , the computer controller transmitting images from the one or more optical imaging systems via the communications interface. 
     
     
         33 . The apparatus of  claim 30 , further comprising:
 an image processing component for processing of images collected from the one or more optical imaging systems.   
     
     
         34 . The apparatus of  claim 33 , the imaging processing component analyzing images collected from the one or more optical imaging systems to determine confluence of cell cultures located in one or more cell culture vessels stacked on the top surface of the housing. 
     
     
         35 . The apparatus of  claim 34 , imaging processing component comprising one or more machine learning models trained to determine cell confluence from images. 
     
     
         36 . The apparatus of  claim 34 , the imaging process component configured to transmit the results of the image analysis via the communications interface.