Platforms and systems for automated cell culture

Abstract

Disclosed herein are platforms, systems, and methods including a cell culture system that includes a cell culture container comprising a cell culture, the cell culture receiving input cells, a cell imaging subsystem configured to acquire images of the cell culture, a computing subsystem configured to perform a cell culture process on the cell culture according to the images acquired by the cell imaging subsystem, and a cell editing subsystem configured to edit the cell culture to produce output cell products according to the cell culture process.

What is claimed is: 
     
         1 . A system comprising:
 one or more cell culture containers, wherein each of the one or more cell culture containers comprises one or more closed cell culture chambers, each of the one or more cell culture chambers comprising:
 a first transparent window and a second transparent window opposite the first transparent window, wherein the cell culture chamber is configured to be at least partially filled with liquid, and wherein the first transparent window is configured to allow one or more cells inside the cell culture chamber to adhere thereto; and 
   an imaging system shared by the one or more cell culture containers, the imaging system comprising:
 a light source configured to illuminate at least one closed cell culture chamber of each of the one or more cell culture containers; 
 an objective configured to capture light from the light source transmitted through or reflected from the at least one closed cell culture chamber of each of the one or more cell culture containers; 
 a sensor configured to acquire a plurality of images from the at least one closed cell culture chamber of each of the one or more cell culture containers based at least in part on the captured light; and 
 a computer processor programmed to generate quantitative phase images of the one or more cells based at least in part on the plurality of images. 
   
     
     
         2 . The system of  claim 1 , further comprising a laser source configured to manipulate the one or more cells based at least in part on the quantitative phase images. 
     
     
         3 . The system of  claim 2 , wherein manipulating the one or more cells comprises removing a subset of cells of the one or more cells from the first transparent window. 
     
     
         4 . The system of  claim 2 , wherein the objective is shared by the imaging system and the laser source. 
     
     
         5 . The system of  claim 2 , wherein the first transparent window further comprises a semi-transparent film configured to absorb energy from the laser source and direct the absorbed energy to the one or more cells. 
     
     
         6 . The system of  claim 5 , wherein the semi-transparent film further comprises a fiducial mark. 
     
     
         7 . The system of  claim 5 , wherein the semi-transparent film is further configured to transmit incident light from the light source within a first range of wavelengths and absorb incident light from the laser source within a second range of wavelengths. 
     
     
         8 . The system of  claim 1 , wherein each of the one or more cell culture containers is stationary while the plurality of images are acquired, and wherein the system further comprises an actuator configured to perform movement of the light source and the objective relative to each of the one or more cell culture containers. 
     
     
         9 . The system of  claim 8 , wherein the movement of the light source and the objective relative to each of the one or more cell culture containers allows the plurality of images to be acquired at each of a plurality of different focal planes along an axis perpendicular to a horizontal plane of the first transparent window. 
     
     
         10 . The system of  claim 9 , wherein the objective is tilted at an angle with respect to the axis. 
     
     
         11 . The system of  claim 8 , wherein the movement of the light source and the objective relative to each of the one or more cell culture containers allows the plurality of images to be acquired at each of a plurality of different illumination angles relative to the first transparent window. 
     
     
         12 . The system of  claim 11 , wherein the light source emits light at a plurality of different wavelengths, and wherein the plurality of different wavelengths illuminates the at least one closed cell culture chamber at a plurality of different angles. 
     
     
         13 . The system of  claim 1 , wherein the computer processor is further programmed to perform a machine learning analysis of the plurality of images or the quantitative phase images. 
     
     
         14 . The system of  claim 1 , wherein the imaging system is further configured to automatically acquire the plurality of images based on a schedule. 
     
     
         15 . The system of  claim 1 , wherein the one or more cell culture containers comprise a closed cassette. 
     
     
         16 . The system of  claim 1 , wherein the imaging system is further configured to acquire the plurality of images over a period of time. 
     
     
         17 . The system of  claim 16 , wherein the computer processor is further programmed to store, for the at least one closed cell culture chamber of each of the one or more cell culture containers, a set of time-series image data from the plurality of images or the quantitative phase images. 
     
     
         18 . The system of  claim 1 , wherein the light source is further configured to direct incident light onto the first transparent window. 
     
     
         19 . The system of  claim 1 , wherein the light source is further configured to direct incident light on the second transparent window.