System and method for imaging and illumination for cell confluence measurement

Patent metadata

Field	Value
Publication number	US-11768194-B2
Application number	US-202117564465-A
Country	US
Kind code	B2
Filing date	Dec 29, 2021
Priority date	Nov 30, 2018
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

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.

First claim

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, the one or more optical imaging systems each comprising an imaging component and an illumination component that share an aperture of the one or more apertures disposed in the flat top surface;
wherein the illumination component is 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, wherein the surface reflecting the light is a bottom surface of a second cell culture vessel stacked on top of the cell culture vessel placed on the flat top surface of the housing; and
wherein the illumination component is 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.

2. The apparatus of claim 1 , 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.

3. The apparatus of claim 2 , 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.

4. The apparatus of claim 2 , 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.

5. The apparatus of claim 1 , 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.

6. The apparatus of claim 5 , 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.

7. The apparatus of claim 6 , the controller transmitting images from the one or more optical imaging systems via the communications interface.

8. The apparatus of claim 5 , further comprising:
an image processing component for processing of images collected from the one or more optical imaging systems.

9. The apparatus of claim 8 , 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.

10. The apparatus of claim 9 , the imaging processing component comprising one or more machine learning models trained to determine cell confluence from images.

11. The apparatus of claim 9 , the imaging process component configured to transmit the results of the image analysis via the communications interface.

12. A method for determining cell confluence of a cell culture in a cell culture vessel comprising:
providing one or more optical imaging systems, each optical imaging system comprising an imaging component and illumination component within a housing disposed below the cell culture vessel, wherein the illumination component is configured to direct light at an oblique angle through cell culture in the cell culture vessel such that the light is reflected off of a surface above the cell culture vessel such as to illuminate the cell culture from a side opposite the imaging component, wherein the surface reflecting the light is a bottom surface of a second cell culture vessel stacked on top of the cell culture vessel;
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; and
varying the oblique angle of the illumination component so as to illuminate cultures located in cell culture vessels stacked on the cell culture vessel placed directly on the top surface of the housing.

13. The method of claim 12 , further comprising collecting images of the cell culture from one or more of the optical imaging systems.

14. The method of claim 13 , further comprising transmitting the collected image via a communications interface.

15. The method of claim 13 , further comprising analyzing the collected images using an image processing component, the image processing component configured to detect cell confluence in the cell culture.

16. The method of claim 15 , further comprising transmitting the results of the image analysis via the communications interface.

Assignees

• Corning Inc

Inventors

• Cobb Joshua Monroe
• Martin Gregory Roger
• Raczkowski Robert Raymond
• Sanson Mark Christian
• Schreiber Horst
• Upton Todd Michael

Classifications

• G01N33/4833 Primary

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• C12M23/12

  Well or multiwell plates (C12M25/04 takes precedence) · CPC title

• C12M41/46 Primary

  of cellular or enzymatic activity or functionality, e.g. cell viability · CPC title

• G01N21/55

  Specular reflectivity · CPC title

• G01N33/5005

  involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025) · CPC title