Automated Cell Culture System with Heated, Angled Adapter and Method

Abstract

An automated method for culturing stem cells using a robotic liquid handling system including a translatable bed and a movable multi-channel pipette. The method includes the steps of: locating a first multi-well cell culture plate and a multi-trough plate on the bed; placing a suspension of stem cells in at least one trough of the multi-trough plate; using the multi-channel pipette, transferring a portion of the suspension of stem cells to each well of the first multi-well cell culture plate such that at least two of the wells of the first multi-well cell culture plate have different densities of stem cells; selecting a well of the first multi-well cell culture plate having a desired density of stem cells; locating a second multi-well cell culture plate on the bed; and using the multi-channel pipette, transferring the cells of the selected well to a plurality of wells of the second multi-well cell culture plate.

What is claimed is: 
     
         1 . An adapter comprising:
 a base;   a top surface configured to hold one or more multi-well plates at an angle relative to the base; and   a heating element configured to apply heat to a fluid media in one or more wells of the one or more multi-well plates.   
     
     
         2 . The adapter of  claim 1 , wherein the base of the adapter has a size and a shape configured to match a footprint of the one or more multi-well plates. 
     
     
         3 . The adapter of  claim 2 , wherein the size and the shape of the base are configured to fit in a holder designed to hold the one or more multi-well plates. 
     
     
         4 . The adapter of  claim 2 , wherein the size and the shape of the base are configured to fit in a position of a robotic liquid handling system configured to receive the one or more multi-well plates. 
     
     
         5 . The adapter of  claim 1 , wherein the adapter is configured to facilitate fluid recovery from each well of the one or more multi-well plates by holding the one or more multi-well plates at the angle relative to the base causing the fluid in each well to pool on one side of the well. 
     
     
         6 . The adapter of  claim 1 , wherein the adapter is configured to maintain the fluid media in the one or more multi-well plates at an elevated temperature while they are being treated with an enzyme to promote cell detachment. 
     
     
         7 . The adapter of  claim 1 , wherein the heating element includes a resistive heating element embedded in the adapter or positioned on the top surface of the adapter. 
     
     
         8 . The adapter of  claim 1 , wherein the heating element includes a fluid heating mechanism configured to circulate heated liquid or air inside the adapter. 
     
     
         9 . The adapter of  claim 1 , further comprising:
 a temperature measurement device configured to monitor a temperature of the adapter or a temperature of the multi-well plate; and   a controller configured to adjust a heat input of the heating element based on the monitored temperature in order to maintain a target temperature.   
     
     
         10 . The adapter of  claim 1 , wherein the controller is configured to adjust the heat input to maintain the fluid media at the target temperature of 37° C. 
     
     
         11 . An automated system for culturing stem cells, the system comprising:
 a robotic liquid handling system including a translatable bed and a movable multi-channel pipette, the translatable bed configured to selectively hold a first multi-well cell culture plate, a second multi-well cell culture plate, and a multi-trough plate; and   a controller in communication with the robotic liquid handling system, the controller configured to
 using the multi-channel pipette, transfer a portion of the suspension of stem cells from at least one trough of the multi-trough plate to each well of the first multi-well cell culture plate such that at least two of the wells of the first multi-well cell culture plate have different densities of stem cells; 
 obtain user input to select a well of the first multi-well cell culture plate having a desired density of stem cells after growth of cell colonies in the first multi-well cell culture plate; and 
 using the multi-channel pipette, transfer the cells of the selected well to a plurality of wells of the second multi-well cell culture plate. 
   
     
     
         12 . The system of  claim 11 , wherein the controller is further configured to translate the bed of the robotic liquid handling system to mix the suspension of stem cells in the multi-trough plate. 
     
     
         13 . The system of  claim 11 , wherein the controller is further configured to detach the stem cells from the first multi-well cell culture plate using one of an enzymatic method and a chemical method before transferring the cells of the selected well to the plurality of wells of the second multi-well cell culture plate. 
     
     
         14 . The system of  claim 13 , wherein the controller, to transfer the cells of the selected well to a plurality of wells of the second multi-well cell culture plate, is further configured to guide the multi-channel pipette such that a plurality of pipette tips of the multi-channel pipette are adjacent side walls of a plurality of the wells of the second multi-well cell culture plate. 
     
     
         15 . The system of  claim 11 , further comprising a heated, angled adapter selectively positionable on the translatable bed, wherein the heated, angled adapter is configured to hold a multi-well cell culture plate at an angle relative to a surface of the translatable bed. 
     
     
         16 . The system of  claim 15 , wherein the heated, angled adapter is configured to hold the multi-well cell culture plate at an angle of approximately 10° relative to the surface of the translatable bed. 
     
     
         17 . The system of  claim 15 , wherein the controller is further configured to feed the stem cells in at least one well of the multi-well cell culture plate positioned on the heated, angled adapter, wherein to feed the stem cells the controller is configured to remove cell culture media from the at least one well of the second multi-well cell culture plate and add new cell culture media to the at least one well of the second multi-well cell culture plate. 
     
     
         18 . The system of  claim 17 , wherein, to remove cell culture media from the at least one well of the multi-well cell culture plate positioned on the heated, angled adapter, the controller is further configured to guide the multi-channel pipette such that a plurality of pipette tips of the multi-channel pipette are located at or near a lowest point of a plurality of wells of the multi-well cell culture plate positioned on the heated, angled adapter. 
     
     
         19 . An automated method for culturing stem cells using a robotic liquid handling system including a translatable bed and a movable multi-channel pipette, the method comprising the steps of:
 locating a first multi-well cell culture plate and a multi-trough plate on the bed;   placing a suspension of stem cells in at least one trough of the multi-trough plate;   using the multi-channel pipette, transferring a portion of the suspension of stem cells to each well of the first multi-well cell culture plate such that at least two of the wells of the first multi-well cell culture plate have different densities of stem cells;   selecting a well of the first multi-well cell culture plate having a desired density of stem cells after growth of cell colonies in the first multi-well cell culture plate;   locating a second multi-well cell culture plate on the bed; and   using the multi-channel pipette, transferring the cells of the selected well to a plurality of wells of the second multi-well cell culture plate.