Organomimetic devices and methods of use and manufacturing thereof

Abstract

An organomimetic device includes a microfluidic device that can be used to culture cells in its microfluidic channels. The organomimetic device can be part of dynamic system that can apply mechanical forces to the cells by modulating the microfluidic device and the flow of fluid through the microfluidic channels. The membrane in the organomimetic device can be modulated mechanically via pneumatic means and/or mechanical means. The organomimetic device can be manufactured by the fabrication of individual components separately, for example, as individual layers that can be subsequently laminated together.

1 - 106 . (canceled) 
     
     
         107 . A method of producing an organomimetic device comprising:
 i) providing at least one first body including a central channel therein along a first axis, wherein the central channel has a first wall portion;   ii) providing a membrane positioned within the central channel;   iii) providing a second body including a housing channel therein, wherein the second body comprises a rigid material and wherein the housing channel has a height that is substantially the same as or greater than the height of the first body and a width that is greater than the width of the first body; and   iv) placing the at least one first body within the housing channel of the second body such that at least one operating chamber forms adjacent to the first wall portion of the first body along the first axis, thereby forming at least one organomimetic device.   
     
     
         108 . The method of  claim 107 , wherein the membrane is substantially rigid. 
     
     
         109 . The method of  claim 107 , wherein the membrane is at least partially flexible. 
     
     
         110 . The method of  claim 107 , wherein at least a portion of the membrane is treated to enhance adhesion of cells to the membrane. 
     
     
         111 . The method of  claim 107 , wherein at least one surface of the membrane comprises cells of at least two cell types. 
     
     
         112 . The method of  claim 111 , wherein the cells are selected to create an in vitro model that mimics cell behavior of at least a portion of a tissue. 
     
     
         113 . The method of  claim 111 , wherein the cells display at least one characteristic corresponding to a pre-determined physiological endpoint. 
     
     
         114 . The method of  claim 113 , wherein the pre-determined physiological endpoint is selected from the group consisting of a mature state, a differentiated state, a precursor state, a stratified state, a pseudo-stratified state, a confluency state, an inflamed state, an infected state, a stimulated state, an activated state, an inhibitory state, a normal healthy state, a pre-disease state, a disease-specific state, a growth state, a migratory state, a metamorphosing state, or any combinations thereof. 
     
     
         115 . A method of producing a microfluidic device comprising:
 a) providing a first body including a central channel;   b) extruding a thin polymer film;   c) machining said thin polymer film to create a membrane; and   d) positioning the membrane within the central channel.   
     
     
         116 . The method of  claim 115 , wherein said thin polymer film is of uniform thickness. 
     
     
         117 . The method of  claim 115 , wherein said thin polymer film comprises SEBS. 
     
     
         118 . The method of  claim 117 , wherein said thin polymer film comprises SEBS mixed with about 10-30% polypropylene. 
     
     
         119 . The method of  claim 115 , wherein said machining of said thin polymer film is with a laser. 
     
     
         120 . The method of  claim 115 , wherein said thin polymer film is supported by a liner during said machining of step (c). 
     
     
         121 . The method of  claim 115 , wherein said machining comprises pore fabrication. 
     
     
         122 . The method of  claim 115 , wherein said membrane is positioned in step (d) so as to separate the central channel to form a first central microchannel and a second central microchannel. 
     
     
         123 . The method of  claim 115 , further comprising seeding cells on said membrane. 
     
     
         124 . The method of  claim 123 , further comprising flowing fluid over said seeded cells. 
     
     
         125 . The method of  claim 115 , wherein the central channel has a first wall portion and said membrane is attached to said first wall. 
     
     
         126 . The method of  claim 115 , wherein said thin polymer film comprises silicone or silicone-based polymers, liquid silicon rubber, polymethylmethacrylate, polyurethane, styrenic block copolymers, polytetrafluoroethylene, polysulfone, polyethylene, polycarbonate, polypropylene, polyamide, polyester, polylactic acid, polylactide, polyglycolic acid, poly(lactic-co-glycolic acid), and polyvinyl alcohol.