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 for simulating a function or response of a tissue, comprising:
 a first microchannel;   a second microchannel; and   a membrane located at an interface region between the first microchannel and the second microchannel, the membrane including a first side facing toward the first microchannel and a second side facing toward the second microchannel, the first side having cells of a first type adhered thereto, the second side having cells of a second type adhered thereto, the membrane permitting the migration of at least one of cells, particulates, chemicals, molecules, fluids, liquids, and gases from the first side of the membrane to the second side of the membrane, the membrane being controllably stretchable in at least one desired direction while a first fluid is present in the first microchannel and a second fluid is present in the second microchannel.   
     
     
         3 . The device of  claim 2 , further including a body having a moveable wall adjacent to the first microchannel and the second microchannel, the moveable wall being coupled to the membrane and being moveable so as to permit the membrane to be controllably stretchable in the at least one desired direction. 
     
     
         4 . The device of  claim 3 , wherein the body further includes a first operating channel that is separated from at least one of the first microchannel and the second microchannel by the moveable wall, the moveable wall undergoing movement in response to a pressure differential between the first operating channel and the at least one of the first microchannel and the second microchannel. 
     
     
         5 . The device of  claim 2 , further including a motor coupled to the membrane to permit the membrane to be controllably stretchable. 
     
     
         6 . The device of  claim 2 , further including a mechanical actuator coupled to the membrane to permit the membrane to be controllably stretchable. 
     
     
         7 . The device of  claim 2 , wherein the first microchannel has a different cross-sectional size than the second microchannel. 
     
     
         8 . The device of  claim 7 , wherein the membrane divides a main channel within a body of the device into the first microchannel and the second microchannel, the membrane being vertically offset from a center of the main channel to create the different cross-sectional sizes. 
     
     
         9 . The device of  claim 2 , further including a body defined by at least an upper layer and a lower layer, the membrane being a membrane layer located between the upper layer and the lower layer, the first microchannel being at least partially defined by the upper layer and the membrane layer, the second microchannel being at least partially defined by the lower layer and the membrane layer. 
     
     
         10 . The device of  claim 9 , wherein the upper layer, the lower layer, and the membrane layer are coupled together through a bonding process. 
     
     
         11 . The device of  claim 2 , further including a body defined by an upper component and a lower component that are made by introducing material into a master that forms the first microchannel and the second microchannel in the upper component and the lower component, respectively. 
     
     
         12 . The device of  claim 2 , wherein the first microchannel has the same cross-sectional size as the second microchannel. 
     
     
         13 . The device of  claim 2 , wherein the first microchannel and the second microchannel are at least partially defined by curved walls. 
     
     
         14 . The device of  claim 2 , wherein the membrane controllably stretches in a manner so as to undergo a cyclic movement pattern. 
     
     
         15 . The device of  claim 2 , wherein the membrane controllably stretches in a manner so as to undergo an irregular movement pattern. 
     
     
         16 . The device of  claim 2 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         17 . The device of  claim 2 , wherein at least one of the first fluid and the second fluid is a gaseous fluid. 
     
     
         18 . The device of  claim 2 , wherein at least one of the first fluid and the second fluid is a liquid. 
     
     
         19 . A method of simulating a function or a response of a tissue in a device having a membrane located at an interface region between a first microchannel and a second microchannel, a first side of the membrane being exposed to the first microchannel and having a first type of cells adhered thereto, the method comprising:
 moving a first fluid through the first microchannel;   moving a second fluid through the second microchannel; and   while (i) the first fluid is adjacent to the first type of living cells within the first microchannel and (ii) the second fluid is within the second microchannel, stretching the membrane in a first direction so as to apply a force to the first type of living cells adhered to the first side of the membrane.   
     
     
         20 . The method of  claim 19 , wherein a second side of the membrane has a second type of living cells adhered thereto, the membrane permitting the migration of at least one of cells, particulates, chemicals, molecules, fluids, liquids, and gases between the first type of cells and the second type of cells. 
     
     
         21 . The method of  claim 19 , wherein the stretching includes moving a movable wall to which the membrane is coupled. 
     
     
         22 . The method of  claim 19 , wherein the stretching includes using a motor that causes the membrane to move. 
     
     
         23 . The method of  claim 19 , wherein the stretching includes using a mechanical actuator that causes the membrane to move. 
     
     
         24 . The method of  claim 9 , further including, after the stretching, allowing the membrane to retract so to relieve the force applied to the first type of living cells. 
     
     
         25 . The method of  claim 24 , further including, repeating (i) the stretching the membrane and (ii) the allowing the membrane to retract so as to apply repeated forces to the first type of living cells. 
     
     
         26 . The method of  claim 25 , wherein the repeated forces are applied in a cyclical pattern. 
     
     
         27 . The method of  claim 25 , wherein the repeated forces are applied in a non-uniform pattern. 
     
     
         28 . The method of  claim 25 , wherein the repeated forces are of different durations. 
     
     
         29 . The method of  claim 19 , wherein at least one of the first fluid and the second fluid is a gaseous fluid. 
     
     
         30 . The method of  claim 19 , wherein the moving the first fluid further includes controlling a flow and content of the first fluid within the first microchannel. 
     
     
         31 . The method of  claim 30 , further including introducing an agent into the first fluid within the first microchannel and measuring a response of the first type of living cells to the agent. 
     
     
         32 . The method of  claim 31 , wherein the measuring the response of the first type of living cells to the agent occurs while the force is applied. 
     
     
         33 . The method of  claim 19 , further including while the first fluid is adjacent to the first type of living cells within the first microchannel, stretching the membrane in a second direction so as to apply a different force to the first type of living cells adhered to the first side of the membrane, the first direction being different from the second direction. 
     
     
         34 . The method of  claim 19 , wherein at least one of the first fluid and the second fluid is a liquid fluid. 
     
     
         35 . The method of  claim 19 , wherein the stretching occurs while the least one of the first fluid and the second fluid is moving, respectively, in the first microchannel and the second microchannel. 
     
     
         36 . The method of  claim 19 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         37 . A device for simulating a function or response of a tissue, comprising:
 a body having a main microchannel and a membrane-mounting region; and   a membrane extending generally within a plane across at least a portion of the main microchannel and separating the main microchannel into a first microchannel and a second microchannel, the membrane being coupled to the body at the membrane-mounting region, the membrane including a first side facing toward the first microchannel and a second side facing toward the second microchannel, the first side having cells of a first type adhered thereto;   wherein the membrane is controllably stretchable and retractable in at least a first direction along the plane while a first fluid is present in the first microchannel and a second fluid is present in the second microchannel.   
     
     
         38 . The device of  claim 37 , wherein the body includes a moveable wall adjacent to the main microchannel, the moveable wall including the membrane-mounting region and being coupled to the membrane, the movable wall causing the membrane to be controllably stretched and retracted in the first direction. 
     
     
         39 . The device of  claim 38 , wherein the moveable wall separates a first operating channel from the main microchannel, the moveable wall undergoing movement in response to a pressure differential between the first operating channel and the main microchannel. 
     
     
         40 . The device of  claim 37 , further including a motor that allows the membrane to be controllably stretched and retracted in the first direction. 
     
     
         41 . The device of  claim 37 , further including a mechanical actuator that allows the membrane to be controllably stretched and retracted in the first direction. 
     
     
         42 . The device of  claim 37 , wherein the second side of the membrane has a second type of living cells adhered thereto, the membrane permitting the migration of at least one of cells, particulates, chemicals, molecules, fluids and gases between the first type of cells and the second type of cells. 
     
     
         43 . The device of  claim 37 , wherein at least one of the first fluid and the second fluid is a liquid fluid. 
     
     
         44 . The device of  claim 37 , wherein at least one of the first fluid and the second fluid is a gaseous fluid. 
     
     
         45 . The device of  claim 37 , wherein the stretching and retracting occurs while the least one of the first fluid and the second fluid is moving, respectively, in the first microchannel and the second microchannel. 
     
     
         46 . The device of  claim 37 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         47 . A device for simulating a function or response of a tissue, comprising:
 a body having a first microchannel and a second microchannel, the first microchannel having a first fluid therein and the second microchannel having a second fluid therein; and   a membrane located at an interface region between the first microchannel and the second microchannel, the membrane including a first side facing toward the first microchannel and a second side facing toward the second microchannel, the first side having cells of at least a first type adhered thereto, the second side having cells of at least a second type adhered thereto, the membrane permitting cellular communication between the first type of cells and the second type of cells, the membrane being controllably stretchable while the first fluid is present in the first microchannel and the second fluid is present in the second microchannel.   
     
     
         48 . The device of  claim 47 , further including a motor that allows the membrane to be controllably stretched in a first direction. 
     
     
         49 . The device of  claim 47 , wherein at least one of the first fluid and the second fluid is a liquid fluid. 
     
     
         50 . The device of  claim 47 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         51 . The device of  claim 47 , wherein at least one of the first fluid and the second fluid is a gaseous fluid.