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 . (canceled) 
     
     
         2 . A device, comprising:
 a body comprising a membrane positioned between a first microchannel and a second microchannel,   wherein a first fluid is applied through the first microchannel and a second fluid is applied through the second microchannel, wherein the first side of the membrane comprises an extracellular matrix composition and hepatocytes, and wherein the second side of the membrane comprises endothelial cells.   
     
     
         3 . The device of  claim 2 , wherein said extracellular matrix composition comprises collagen; or optionally fibronectin. 
     
     
         4 . The device of  claim 2 , wherein said hepatocytes are adhered on the extracellular matrix composition. 
     
     
         5 . A method for culturing cells, comprising:
 a) providing a device having a body comprising a membrane positioned between a first microchannel and a second microchannel,   b) culturing hepatocytes in said first microchannel and endothelial cells in said second microchannel; and   c) perfusing a fluid through at least one of the first and second microchannels.   
     
     
         6 . The method of  claim 5 , further comprising coating at least a region of said membrane with at least one extracellular matrix protein. 
     
     
         7 . The method of  claim 5 , wherein the cells are grown for at least 7 days. 
     
     
         8 . The method of  claim 5 , wherein said human hepatocytes are primary human hepatocytes. 
     
     
         9 . The method of  claim 5 , further comprising d) determining the level of expression of one or more cellular proteins. 
     
     
         10 . The method of  claim 9 , wherein prior to step d), a chemical or biological agent is added to the device. 
     
     
         11 . A method for determining an effect of at least one agent in a tissue system, the method comprising:
 selecting a device having a body, the body comprising a membrane positioned between a first microchannel and a second microchannel;   contacting a first side of the membrane with hepatocytes and a second side of the membrane with endothelial cells thereby forming a tissue structure comprising at least two different types of cells;   contacting the tissue structure comprising at least two different types of cells with the at least one agent;   perfusing a fluid through at least one of the first and second microchannels; and   measuring a response of the cells in the tissue structure to determine the effect of the at least one agent on the cells.   
     
     
         12 . The method of  claim 11 , wherein said hepatocytes are selected from the group consisting of mammalian and human hepatocytes.