(61c) Breaking the Rules for Selecting Protein-Resistant Surfaces

Both rational and trial-and-error methods have been used to search for low protein adhesive
(fouling) surfaces for marine, medical, separations technology and other applications. Although
these approaches to-date have produced some successes, we still do not fully understand how to
rationally choose a protein-resistant surface. Unfortunately, surface science has not yet
developed to the point that allows prediction of the surface or functional characteristics needed to
minimize undesirable interactions with solution components, and thus to control fouling.

About 14 years ago, George Whitesides and his research group listed a set of rules that, if
followed, constitute protein-resistant surfaces. The chemistry of the surface needs to (i) be
hydrophilic (wettable), (ii) contain hydrogen bond acceptors, (iii) lack hydrogen bond donors,
and (iv) be electrically neutral (Ostuni et al. (2001) Langmuir, 17 (18) 5605-5620).

Over the past five years we have screened monomer libraries and discovered a series of
protein-resistant monomers using an inexpensive, fast, reproducible and scalable high throughput
method. Both photo-oxidation with vacuum and atmospheric plasma without vacuum are used to
graft-polymerize commercially available and combinatorially produced monomers onto light
sensitive poly(ether sulfone) synthetic membranes. In addition to protein-resistant surfaces
identified by the Whitesides group and others such as polyethylene glycol and zwitterionic
monomers, the high throughput method selected a series of new monomers such as amines,
mixed polar/apolar and chiral compounds. Using a membrane filtration assay as a surrogate
measure for protein adhesion, and analyzing these new protein-resistant materials in light of the
Whitesides et al’s rules, we propose new modified rules.