Devices and Methods for Pharmacokinetic-Based Cell Culture System

Abstract

Devices, in vitro cell cultures, systems, and methods are provided for microscale cell culture analogous (CCA) device.

1 . A pharmacokinetic-based microscale culture device, comprising:
 a first microscale chamber containing a first type of cell under conditions where the first type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the first chamber comprises a first inlet and a first outlet for flow of culture medium;   a second microscale chamber containing a second type of cell under conditions where the second type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the second chamber comprises a second inlet and a second outlet for flow of culture medium;   and a microfluidic channel interconnecting the first and second chambers.   
     
     
         2 . The culture device of  claim 1 , further comprising one or more additional microscale chambers containing an additional type of cell under conditions where the additional cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the one or more additional chambers comprise an inlet and outlet for flow of culture medium. 
     
     
         3 . The culture device of  claim 1 , further comprising culture medium. 
     
     
         4 . The culture device of  claim 3 , wherein the culture medium flows through the chambers. 
     
     
         5 . The culture device of  claim 3 , wherein the culture medium flows re-circulated through the chambers. 
     
     
         6 . The culture device of  claim 3 , further comprising a pumping mechanism. 
     
     
         7 . The culture device of  claim 6 , wherein the pumping mechanism is integrated in the device. 
     
     
         8 . The culture device of  claim 6 , wherein the pumping mechanism is external to the device. 
     
     
         9 . The culture device of  claim 1 , further comprising a debubbler located within the microfluidic channel. 
     
     
         10 . The culture device of  claim 1 , further comprising a debubbler located externally to the device. 
     
     
         11 . The culture device of  claim 1 , wherein at least one of the pharmacokinetic parameters is a measurement of interaction between cells, liquid residence time, liquid to cell ratio, metabolism by cells, or shear stress. 
     
     
         12 . The culture device of  claim 1 , further comprising at least one sensor for obtaining signals from cultured cells. 
     
     
         13 . The culture device of  claim 12 , wherein the at least one sensor is a biosensor. 
     
     
         14 . The culture device of  claim 12 , wherein the at least one sensor comprises a waveguide. 
     
     
         15 . The culture device of  claim 1 , wherein the device is microfabricated. 
     
     
         16 . The culture device of  claim 1 , wherein the device is manufactured from a microfabricated master. 
     
     
         17 . The culture device of  claim 1 , wherein at least one of the chambers provides for three-dimensional growth of cells. 
     
     
         18 . The culture device of  claim 1 , wherein at least one of the chambers contains a plurality of cells. 
     
     
         19 . The culture device of  claim 1 , wherein at least one of the chambers contains a tissue biopsy. 
     
     
         20 . The culture device of  claim 1 , wherein at least one of the chambers contains a cross-section of a tissue. 
     
     
         21 - 178 . (canceled)