Organ Chips And Uses Thereof

Abstract

Disclosed herein are organ chips that can be individually used or integrated together to form different microphysiological systems, e.g., for use in cell culturing, drug screening, toxicity assays, personalized therapeutic treatment, scaffolding in tissue repair and/or replacement, and/or pharmacokinetic or pharmacodynamics studies.

1 . An in vitro microphysiological system comprising:
 a. at least two different organ chips, wherein said at least two different organ chips are selected from either one or both of the following:
 (i) a first organ chip comprising: a body comprising a central channel therein, and an at least partially porous and at least partially flexible first membrane positioned within the central channel and along a plane, wherein the first membrane is configured to separate the central channel to form two sub-channels, wherein one side of the first membrane is seeded with vascular endothelial cells, and the other side of the first membrane is seeded with at least one type of organ-specific parenchymal cells; 
 (ii) a second organ chip comprising: a body comprising a first chamber enclosing a plurality of muscular thin films adapted to measure contraction of muscle cells, and a second chamber comprising a layer of muscle cells on the bottom surface of the second chamber, wherein the bottom surface is embedded with an array of microelectrodes for recording of action potentials, and wherein the top surface of the second chamber is placed with at least a pair of electrodes for providing electric field stimulation to the muscle cells; or 
 (iii) a combination of the first organ chip and the second organ chip; and 
   b. at least one connecting means between said at least two different organ chips.   
     
     
         2 - 40 . (canceled) 
     
     
         41 . The system of  claim 1 , wherein the system comprises at least three organ chips. 
     
     
         42 . The system of  claim 1 , wherein the connecting means comprises a tubing that fluidically connects an outlet of one of the organ chips to an inlet of another organ chip. 
     
     
         43 . The system of  claim 1 , wherein the first organ chip is selected from the group consisting of a lung chip, a liver chip, a gut chip, a kidney chip, a skin chip, a brain chip, a testis chip, and any combinations thereof. 
     
     
         44 . The system of  claim 1 , wherein the second organ chip is selected from the group consisting of a heart chip, a skeletal muscle chip, a lung airway smooth muscle chip, a brain chip, and any combinations thereof. 
     
     
         45 . The system of  claim 1 , wherein the first organ chip further comprises at least a channel wall positioned adjacent to the two sub-channels, wherein the first membrane is mounted to the channel wall; and an operating channel adjacent to the two sub-channels on an opposing side of the channel wall, wherein a pressure differential applied between the operating channel and the two sub-channels causes the channel wall to flex in a desired direction to expand or contract along the plane within the two sub-channels. 
     
     
         46 . The system of  claim 1 , wherein the second organ chip further comprises an at least partially porous second membrane positioned within the first chamber to form a top chamber and a bottom chamber, wherein the bottom chamber comprises the plurality of muscular thin films on its bottom surface, and wherein the surface of the second membrane in contact with the top chamber is seeded with a layer of epithelial cells. 
     
     
         47 . The system of  claim 1 , wherein the system is adapted to determine at least one pharmacokinetic and/or pharmacodynamics parameter of an active agent. 
     
     
         48 . The system of  claim 47 , wherein the active agent is selected from the group consisting of cells, proteins, peptides, antigens, antibodies or portions thereof, antibody-like molecules, enzymes, nucleic acids, siRNA, shRNA, aptamers, small molecules, antibiotics, therapeutic agents, molecular toxins, nanomaterials, particulates, aerosols, environmental contaminants or pollutants, and any combinations thereof. 
     
     
         49 . A kit comprising:
 a. at least one in vitro microphysiological system of  claim 1 ; and   b. at least one agent.   
     
     
         50 . The kit of  claim 49 , wherein said at least one agent comprises a culture medium, an agent for calibration and/or validation of the system, or a combination thereof. 
     
     
         51 . The kit of  claim 49 , further comprising at least one vial of vascular endothelial cells. 
     
     
         52 . The kit of  claim 49 , further comprising at least one vial of organ-specific parenchymal cells. 
     
     
         53 . A method, comprising:
 a. providing a microfluidic device comprising one or more microchannels comprising fluid, said microfluidic device comprising a porous material used to construct the device; and   b. oxygenating said fluid through said porous material used in the construction of the device.   
     
     
         54 . The method of  claim 53 , wherein said microfluidic device further comprises a membrane. 
     
     
         55 . The method of  claim 54 , wherein said membrane is an at least partially porous membrane. 
     
     
         56 . The method of  claim 53 , wherein said membrane is positioned is said one or more microchannels. 
     
     
         57 . The method of  claim 53 , wherein said microfluidic device further comprises cells within said one or more microchannels. 
     
     
         58 . The method of  claim 53 , wherein said porous material comprises PDMS. 
     
     
         59 . A method for creating an oxygen gradient, comprising:
 a. providing a microfluidic device comprising first and second microchannels separated by a porous membrane; and   b. flowing oxygen at different concentrations through said first and second microchannels so as to create an oxygen gradient.   
     
     
         60 . The method of  claim 59 , wherein said membrane comprises PDMS. 
     
     
         61 . The method of  claim 59 , wherein said membrane comprises cells. 
     
     
         62 . The method of  claim 59 , wherein the membrane is coated with one or more cell layers. 
     
     
         63 . The method of  claim 61 , wherein said cells are liver cells. 
     
     
         64 . The method of  claim 59 , further comprising monitoring oxygen levels in at least one of said microchannels. 
     
     
         65 . A method, comprising:
 a. providing a microfluidic device comprising one or more microchannels comprising fluid; and   b. oxygenating said fluid using a gas exchange membrane.   
     
     
         66 . The method of  claim 65 , wherein said one or more microchannels comprise cells. 
     
     
         67 . The method of  claim 66 , wherein said cells are contacted with said fluid by flowing the fluid through the microchannel where the cells are cultured. 
     
     
         68 . The method of  claim 67 , wherein the fluid comprises cell culture medium.