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 system for monitoring a tissue-simulation device, comprising:
 a first microchannel having a first fluid therein;   a second microchannel having a second fluid therein;   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 the migration of at least one of cells, particulates, chemicals, molecules, fluids, liquids, and gases from the first type of cells to the second type of cells; and   an image sensing device that provides images of at least the first type of cells.   
     
     
         3 . The system of claim  49 , wherein the membrane is controllably stretchable in a desired direction while the first fluid is present in the first microchannel and the second fluid is present in the second microchannel. 
     
     
         4 . The system of claim  49 , wherein the membrane is at least partially optically transparent. 
     
     
         5 . The system of claim  49 , further including a body in which the first microchannel and the second microchannel are located, the image sensing device being integrated into the body. 
     
     
         6 . The system of claim  49 , wherein the image sensing device is a camera. 
     
     
         7 . The system of claim  49 , wherein the image sensing device uses at least one of the techniques selected from the group consisting of fluorescence microscopy, microfluorimetry, optical coherence tomography (OCT), confocal microscopy, and electron microscopy. 
     
     
         8 . The system of claim  49 , wherein at least one of the first fluid and the second fluid is a liquid fluid. 
     
     
         9 . The system of claim  49 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         10 . The system of claim  49 , wherein at least one of the first fluid and the second fluid is a gaseous fluid. 
     
     
         11 . A method of monitoring a simulated tissue function or response in a device having a membrane, a first side of the membrane facing a first microchannel and having a first type of cells adhered thereto, a second side of the membrane facing a second microchannel and having a second type of 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, the method comprising:
 moving a first fluid through the first microchannel;   moving a second fluid through the second microchannel; and   while the first fluid is adjacent to the first type of cells within the first microchannel, monitoring, via an image sensing device, at least one of the first type of cells and the second type of cells adhered to the membrane.   
     
     
         12 . The method of claim  58 , further including stretching the membrane in a first direction so as to apply a force to the first type of cells adhered to the first side of the membrane. 
     
     
         13 . The method of claim  58 , wherein the first microchannel and the second microchannel are located in a body having multiple components, and the image sensing device is integrated into the body. 
     
     
         14 . The method of claim  58 , wherein the monitoring includes at least one of the techniques selected from the group consisting of fluorescence microscopy, microfluorimetry, optical coherence tomography (OCT), confocal microscopy, and electron microscopy. 
     
     
         15 . The method of claim  61 , wherein the image sensing device is for identifying cell behavior, the cell behavior including at least one of cell secretion, cell signaling, cell-to-cell interactions, dynamic tissue construction, and cell remodeling. 
     
     
         16 . The method of claim  58 , wherein the image sensing device is a camera. 
     
     
         17 . The method of claim  58 , wherein the monitoring occurs while at least one of the first fluid and the second fluid is moving, respectively, in the first microchannel and the second microchannel. 
     
     
         18 . The method of claim  58 , wherein at least one of the first fluid and the second fluid is a liquid fluid. 
     
     
         19 . The method of claim  58 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         20 . The method of claim  58 , wherein at least one of the first fluid and the second fluid is a gaseous fluid. 
     
     
         21 . A system for monitoring a tissue-simulation device, comprising:
 a body having a first microchannel and a second microchannel;   a 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 first type of cells and the second type of cells being in cellular communication through the membrane; and   an image sensor that is integrated into the body for taking images of at least one of the first type of cells and the second type of cells.   
     
     
         22 . The system of claim  68 , wherein the body is comprised of multiple components or layers that partially define the first microchannel and the second microchannel. 
     
     
         23 . The system of claim  68 , wherein the image sensor is a camera. 
     
     
         24 . The system of claim  68 , wherein the membrane is controllably stretchable in a desired direction while a first fluid is present in the first microchannel and a second fluid is present in the second microchannel. 
     
     
         25 . A system for monitoring a tissue-simulation device, comprising:
 a body having a first microchannel with a first fluid therein and a second microchannel with a second fluid therein;   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 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; and   a first sensing device for monitoring a change in the first fluid.   
     
     
         26 . The system of claim  72 , wherein the change in the first fluid is at least one of (i) a change in pH of the first fluid, (ii) a presence of reactive oxygen species within the first fluid, (iii) a change in gene expression within the first fluid, and (iv) a change in a protein level within the first fluid. 
     
     
         27 . The system of claim  72 , wherein the first sensing device is integrated into the body and being in direct communication with the first microchannel. 
     
     
         28 . The system of claim  72 , wherein at least one of the first fluid and the second fluid is a liquid. 
     
     
         29 . The system of claim  72 , further including a second sensing device for monitoring a change in the second fluid. 
     
     
         30 . The system of claim  72 , wherein an agent is introduced into the first fluid and the change in the first fluid is caused by a cellular release or secretion from the first type of cells. 
     
     
         31 . The system of claim  77 , wherein the cellular release or secretion occurs while a force is applied on the first type of cells due to the controlled stretching of the membrane. 
     
     
         32 . The system of claim  72 , wherein the change in the first fluid is caused by a cellular response to a force applied to the first type of cells due to the controlled stretching of the membrane. 
     
     
         33 . The system of claim  72 , wherein the change in the first fluid is in response to an agent being added to the second fluid, thereby causing (i) cellular communication from the second type of cells to the first type of cells and (i) a cellular release or secretion from the first type of cells. 
     
     
         34 . The system of claim  72 , wherein the body is comprised of multiple components or layers. 
     
     
         35 . The system of claim  72 , wherein the first fluid and the second fluid are the same fluid. 
     
     
         36 . The system of claim  72 , wherein at least one of the first fluid and the second fluid is a gaseous fluid.