Organ mimic device with microchannels and methods of use and manufacturing thereof

Abstract

System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.

1 - 48 . (canceled) 
     
     
         49 . A method of cell culture comprising:
 providing a microfluidic device comprising first and second microchannels, wherein said microchannels are fluidically connected by a membrane positioned between said microchannels, said membrane comprising first and second surfaces;   introducing first cells on said first membrane surface and second cells on said second membrane surface, wherein said first cells comprise epithelial cells and said second cells comprise endothelial cells;   flowing a fluid in at least one of said first and second microchannels; and   culturing said cells such that the cells in at least one of the first or second microchannel polarize.   
     
     
         50 . The method of  claim 49 , wherein said fluid is a cell culture medium. 
     
     
         51 . The method of  claim 49 , wherein the membrane comprises a plurality of pores, and said pores have a width in the range of 0.5 microns to 20 microns. 
     
     
         52 . The method of  claim 49 , wherein the membrane comprises a plurality of pores, and said pores have a width of about 10 microns. 
     
     
         53 . The method of  claim 49 , wherein said epithelial cells are lung epithelial cells. 
     
     
         54 . The method of  claim 53 , wherein said lung epithelial cells are alveolar epithelial cells. 
     
     
         55 . The method of  claim 49 , wherein the membrane comprises a plurality of pores, and said pores are coated or filled with one or more molecules associated with an extracellular matrix (ECM). 
     
     
         56 . The method of  claim 49 , wherein the membrane comprises a plurality of pores, and said pores are coated or filled with one or more of laminin, collagen, fibronectin, fibrin, and elastin. 
     
     
         57 . A method, comprising:
 providing a microfluidic device comprising first and second microchannels, wherein said microchannels are fluidically connected by a membrane positioned between said microchannels, said membrane comprising top and bottom surfaces;   introducing epithelial cells on said top surface of said membrane and endothelial cells on said bottom surface of said membrane;   flowing a fluid in at least one of said first and second microchannels; and   culturing said cells such that the cells in at least one of the first or second microchannel form an organized barrier.   
     
     
         58 . The method of  claim 57 , wherein said epithelial cells are lung epithelial cells and tissue layers of said lung epithelial cells and said endothelial cells mimic an interface between lung epithelium and endothelium in vivo. 
     
     
         59 . The method of  claim 57 , wherein the membrane comprises a plurality of pores, and the first and second microchannels are fluidically connected through the plurality of pores. 
     
     
         60 . The method of  claim 57 , wherein the membrane is flexible. 
     
     
         61 . The method of  claim 57 , wherein the membrane is elastic. 
     
     
         62 . The method of  claim 57 , wherein said cells remain viable for at least two weeks. 
     
     
         63 . The method of  claim 57 , wherein said membrane comprises a coating and said epithelial cells introduced into said first microchannel attach to said coating. 
     
     
         64 . The method of  claim 63 , wherein said coating is a gel. 
     
     
         65 . The method of  claim 49 , wherein the cells are alternatively introduced on a coating on said first surface and said second surface of said membrane. 
     
     
         66 . The method of  claim 65 , wherein said coating is a gel.