The blood brain barrier (BBB) plays a critical physiological role. Numerous studies have demonstrated that BBB function is impaired or altered in Alzheimer's disease (AD). There is significant interest in studing the BBB in AD because: 1) biomarker studies for AD often must begin with studies of cerebrospinal fluid protein expression rather than the study of blood, serum or plasma; and 2) pharmacological interventions that are administered intravenously must address the issue of treating pathological features in the brain. Thus, in vitro models for the BBB provide an opportunity to significantly help in the development of biomarker technologies and in the understanding of treatment paradigms.

We have designed and synthesized thin, optically clear membranes based on poly(hydroxy styrene) using a combination of lithography and self assembly. The membranes are about 1 μm thick, with pore diameters selectively ranging in size from 10 – 50 nm. The membranes are modified to be useful for cell culture by the attachment of various protein substrates. We successfully cultured primary astrocytes and endothelial cells on these membranes and demonstrated proliferative capability and morphologies that are indistinguishable from conventional membranes and surfaces used in cell culture and used in other BBB models. We have also co-cultured these cell lines on both the front and back of these membranes at the same time demonstrating the possibility of using our designed transwell-type device for BBB model testing. We have also used a conventional PET transwell apparatus to measure the TEER of the co-cultured primary astrocytes and endothelial cells and observed TEER values "better" than other published in vitro BBB model.

Gilda Shayan received her B.S. degree in Molecular Biology & Genetics from Cornell University ( Ithaca , NY ) in December, 2005 and is currently a Ph.D. graduate student in the Department of Biomedical Engineering at Cornell University , in the research laboratory of Dr. Kelvin Lee.