In vitro analysis of a hepatic device with intrinsic microvascular-based channels

• DOI: 10.1007/s10544-008-9194-3
• Publication Date: 2008-07-04T05:09:02Z
• Authors: Amedeo Carraro; Wen-Ming Hsu; Katherine M. Kulig; Wing S. Cheung; Mark L. Miller; Eli J. Weinberg; Eric F. Swart; Mohammad Kaazempu...; Jeffrey T. Borens...; Joseph P. Vacanti; Craig Neville
• Keywords: Male; 0301 basic medicine; Silicon; Cell Culture Techniques; Drug Evaluation, Preclinical; Membranes, Artificial; Microfluidic Analytical Techniques; Liver, Artificial; Rats; 03 medical and health sciences; Rats, Inbred Lew; Cell Line, Tumor; Hepatocytes; Animals; Humans; Animals; Cell Culture Techniques; Cell Line, Tumor; Drug Evaluation, Preclinical; Hepatocytes; Humans; Male; Microfluidic Analytical Techniques; Porosity; Rats; Rats, Inbred Lew; Silicon; Liver, Artificial; Membranes, Artificial; Porosity

A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.