Microfluidic proximial tubule kidney-on-chip

Abstract

The present invention relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions. Importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.

1 - 21 . (canceled) 
     
     
         22 . A method of measuring toxicity, comprising:
 a) providing a microfluidic device comprising a membrane, said membrane comprising a first surface and a second surface, said first surface comprising proximal tubule cells and said second surface comprising glomerular microvascular endothelial cells;   b) culturing said cells under continuous flow of media;   c) introducing an agent; and   d) detecting toxicity of said agent.   
     
     
         23 . The method of  claim 22 , wherein said detecting comprises measuring release of a compound from said cells. 
     
     
         24 . The method of  claim 23 , wherein said compound comprises Lactate dehydrogenase (LDH). 
     
     
         25 . The method of  claim 22 , wherein said agent is a drug or drug candidate. 
     
     
         26 . The method of  claim 22 , wherein said membrane contains pores. 
     
     
         27 . The method of  claim 22 , wherein said membrane comprises a semiporous barrier. 
     
     
         28 . The method of  claim 22 , wherein said proximal tubule cells are human primary proximal tubular epithelial cells. 
     
     
         29 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells are attached to the first surface of said membrane and said glomerular microvascular endothelial cells are attached to the opposite side of the same membrane. 
     
     
         30 . The method of  claim 22 , wherein said first surface of said membrane is part of a first microfluidic channel and said second surface of said membrane is part of a second microfluidic channel. 
     
     
         31 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells express tight junction protein ZO-1. 
     
     
         32 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells express beta-catenin. 
     
     
         33 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells express occludin. 
     
     
         34 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells express Na/K-ATPase. 
     
     
         35 . The method of  claim 28 , wherein said human primary proximal tubular epithelial cells comprise cilia.