Apparatus and methods for cell culture

Abstract

A bioreactor (1) for the culture of cells (C) comprising a stack of carriers (7) for cell (C) adherence and liquid medium (M) distribution. The carriers (7) are stacked so as to define levels (6) between adjacent carriers (7) for the flow of the liquid medium (M). Adjacent levels (6) are fluidly interconnected via open spaces (2) so that the liquid medium (M) can flow from one level (6) to an adjacent level (6). The open spaces (2) between a first and an adjacent second level (6′) do not overlap with the one or more open spaces (2) between the second level (6′) and an adjacent third level (6″). One or more of the carriers may also include an area adapted to prevent cell adhesion or growth, thereby allowing for the viewing of cell growth on adjacent carriers from a vantage point external to the bioreactor. Related methods are also disclosed.

1 .- 122 . (canceled) 
     
     
         123 . A bioreactor for use in culturing cells, comprising:
 a plurality of carriers, each of the plurality of carriers having a first area adapted for cell adherence, and at least one of the plurality of carriers having a second area adapted for preventing cell adherence; and   a piece of optically transparent material associated with each of the at least one of the plurality of carriers having the second area, the piece of optically transparent material positioned in a space between adjacent carriers such that the space is completely filled to provide a substantially continuous optical path from an external vantage point through the plurality of carriers to a desired area of cell growth in one of the plurality of carriers.   
     
     
         124 . The bioreactor according to  claim 123 , further comprising a second piece of optically transparent material associated with each of the at least one of the plurality of carriers having the second area, the piece of optically transparent material positioned in a space between adjacent carriers such that the space is completely filled to provide a second substantially continuous optical path is created to a second desired area of cell growth in one of the plurality of carriers. 
     
     
         125 . The bioreactor according to  claim 123 , wherein the second area adapted for preventing cell adherence is hydrophobic. 
     
     
         126 . The bioreactor according to  claim 123 , further including a single housing for receiving the plurality of carriers. 
     
     
         127 . The bioreactor according to  claim 123 , wherein the plurality of carriers include stackable trays or cubes. 
     
     
         128 . The bioreactor according to  claim 123 , wherein the second area for preventing cell adherence constitutes a window. 
     
     
         129 . The bioreactor according to  claim 123 , wherein each of the plurality of carriers includes a separate inlet. 
     
     
         130 . The bioreactor according to  claim 123 , wherein each of the plurality of carriers includes open spaces configured to ensure the most desirable flow of fluid, oxygen, and nutrients to layers of cells formed on the plurality of carriers. 
     
     
         131 . A bioreactor comprising a stack of carriers and an optically transparent solid material positioned in a space between adjacent carriers and completely filling said space such that an optically transparent path is created from a vantage point external to the bioreactor through at least one carrier to one or more inner carriers. 
     
     
         132 . The bioreactor according to  claim 131 , wherein a cell growth area is on a surface of the one or more inner carriers. 
     
     
         133 . The bioreactor according to  claim 132 , wherein the optically transparent solid material is associated with each of the at least one carrier stacked on top of the one or more inner carriers, but not the one or more inner carriers. 
     
     
         134 . The bioreactor according to  claim 133 , wherein the optically transparent solid material prevents cell growth on an area of each of the at least one carrier for which said material is associated. 
     
     
         135 . The bioreactor according to  claim 131 , wherein the stack is vertical. 
     
     
         136 . A method for viewing growth of cells in a cell culture device from an external vantage point, comprising:
 providing a stack of carriers C a  . . . C n  forming the cell culture device;   generating a surface area on each carrier C a  . . . C n−1  wherein cells do not grow;   creating an optically transparent line of sight from the external vantage point to carrier C n  through carriers C a  . . . C n−1 ; and   viewing an area of cell growth on carrier C n .   
     
     
         137 . The method according to  claim 136 , wherein the cell culture device is a bioreactor. 
     
     
         138 . The method according to  claim 136 , wherein the viewing step includes utilizing a microscope. 
     
     
         139 . The method according to  claim 136 , wherein the generating step includes utilizing a chemical treatment to prevent cell adherence or growth on the surface area of each carrier C a  . . . C n−1 . 
     
     
         140 . The method according to  claim 136 , wherein the generating step includes utilizing an optically transparent material associated with each carrier C a  . . . C n−1  but not carrier C n . 
     
     
         141 . The method according to  claim 140 , wherein the utilizing step includes completely filling a space between adjacent carriers with the optically transparent material. 
     
     
         142 . The method according to  claim 136 , further including the steps of:
 generating a second surface area on each carrier C a  . . . C n−3  wherein cells do not grow;   creating a second optically transparent line of sight from another external vantage point to carrier C n−2  through carriers C a  . . . C n−3 ; and   viewing a second area of cell growth on carrier C n−2.