Fluidic device for quantifying the dynamic permeability and hydraulic conductivitiy of living tissue layers

Abstract

Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.

What is claimed is: 
     
         1 . A system for measuring hydraulic conductivity associated with a cell layer, the system comprising:
 a microfluidic device having a first microchannel, a second microchannel, and a barrier located at an interface region between the first microchannel and the second microchannel, the barrier including a first side facing toward the first microchannel and a second side facing toward the second microchannel, the first side having the cell layer adhered thereto, the first and second microchannel comprising an input and output;   a working-fluid reservoir having a working fluid that is fluidically coupled to the input of the first microchannel;   a first output line for delivering a first portion of a working fluid from the first microchannel to a first output-fluid reservoir;   a fluid-resistance element coupled to the first output line, the fluid-resistance element having a first fluidic resistance that causes a pressure drop across the fluid-resistance element; and   a second output line for delivering a second portion of the working fluid from the second microchannel to a second output-fluid reservoir,   wherein migration of the second portion of the working fluid from the first microchannel to the second microchannel through the cell layer is indicative of the hydraulic conductivity associated with the cells.   
     
     
         2 . The system of  claim 1 , wherein the fluid-resistance element can be adjusted or altered. 
     
     
         3 . The system of  claim 1 , wherein the working-fluid reservoir is positioned above the first microchannel for delivering the fluid to the first microchannel under a force of gravity. 
     
     
         4 . The system of  claim 1 , wherein working-fluid reservoir is coupled to a pump for delivering the fluid to the first microchannel under a force of pressure. 
     
     
         5 . The system of  claim 1 , further including an image-gathering device for gathering images of the fluid migrating through the cell layer and the barrier. 
     
     
         6 . A system for measuring hydraulic conductivity associated with cells, comprising:
 a microfluidic device having a first microchannel, a second microchannel, and a barrier located at an interface region between the first microchannel and the second microchannel, the barrier including a first side facing toward the first microchannel and a second side facing toward the second microchannel, at least one of the first side and the second side having a cell layer adhered thereto;   a first fluid path associated with the first microchannel for delivering a fluid to and from the first microchannel; and   a second fluid path associated with the second microchannel for delivering, from the second microchannel, the fluid that has migrated through the barrier and the cell layer;   wherein a flow rate of the fluid that is delivered from the second microchannel is indicative of the hydraulic conductivity associated with the cell layer.   
     
     
         7 . The system of  claim 6 , wherein the first fluid path comprises a fluid-resistance element downstream from the first microchannel to maintain a substantially constant fluid pressure along the cell layer adhered to the barrier. 
     
     
         8 . The system of  claim 7 , wherein the fluid-resistance element can be adjusted or altered. 
     
     
         9 . The system of  claim 1 , further comprising a fluid reservoir fluidically coupled to said first microchannel. 
     
     
         10 . The system of  claim 9 , wherein the fluid reservoir is positioned above the first microchannel for delivering the fluid to the first microchannel under a force of gravity. 
     
     
         11 . The system of  claim 9 , wherein fluid reservoir is coupled to a pump for delivering the fluid to the first microchannel under a force of pressure. 
     
     
         12 . The system of  claim 6 , further including an image-gathering device for gathering images of the fluid migrating through the cell layer and the barrier.