Cellular obstruction of poly(dimethyl)siloxane (PDMS) catheters is one of the largest causes of hydrocephalic shunt failure with a 50% failure rate within two years of implantation. In cerebrospinal fluid most proteins maintain their native folded conformation. However, when they adsorb to the hydrophobic surface of PDMS they may unfold and lose their native structure. Making the PDMS surface more wettable and protein-like is expected to minimize protein adsorption and unfolding. This hypothesis was tested in a fluidic environment mimicking the physiological system by comparing binding of two proteins, fibronectin (Fn) and albumin (Alb) in a mixture, to hydrophobic PDMS and oxidized hydrophilic PDMS. A significant decline in adsorption of Fn (p<0.01) and Alb (p<0.05) was observed when proteins were exposed to oxidized hydrophilic PDMS. By adsorbing N-Acetyl-L-cysteine (NAC) onto PDMS, we increased surface wettability and decreased contact angle. When immersed in the combined Fn/Alb solution, a significantly lower protein adsorption pattern was found for both fibronectin (p<0.01) and albumin (p<0.05). While it is has been known that cell attachment can be inhibited by thiol-containing reagents, our results suggest that NAC modification of PDMS does so by inhibiting protein binding. Our future work will examine whether NAC can diminish adhesion of macrophages to PDMS. These results provide a better understanding of adsorption and lead to the identification of novel surface modification strategies to tissue obstruction in intracranial catheters.