(26e) Super Protein-Resistant Membranes

Finding surfaces that repel proteins is extremely difficult because of the complex nature of protein binding, how water structure influences this process, and the heterogeneity of most industrial surfaces.  Since we do not fully understand non-specific binding, nor can we predict what chemistries would be the best for protein repulsion, we have in the past relied on empirical experimental results. Whitesides’ group, using a heuristic approach, has identified the following general features of surfaces having low affinity for proteins: (i) hydrophilic (wettable), (ii) contain hydrogen bond acceptors, (iii) lack hydrogen bond donors, and (iv) are electrically neutral.  Thus, hydrophilic (polar) surfaces have been mostly used to repel proteins and include polyethylene glycol (PEG) and zwitterionic functional groups.  Their mechanism of action is also unclear. 

Besides the heuristic approach, another methodology that copies evolutionary techniques, such as those used in chemistry (e.g. combinatorial spot/well analysis) and biology (e.g. phage display and SELEX) has been persued in our lab.  A high throughput platform (HTP) allows one to synthesize, screen and select desirable surfaces for any particular application.  This method is an inexpensive, fast, reproducible and scalable approach to synthesize and screen protein-resistant surfaces appropriate for a specific feed.  The method is illustrated here by combining a high throughput platform (HTP) approach together with our patented photo-induced graft polymerization (PGP) method developed for facile modification of commercial poly(aryl sulfone) membranes.  We demonstrate that the HTP–PGP approach to synthesize and screen fouling-resistant surfaces is general, and thus provides the capability to develop surfaces optimized for specific feeds.  Surfaces were prepared via graft polymerization onto poly(ether sulfone) (PES) membranes and were evaluated using a protein adsorption assay followed by pressure-driven filtration.  Using this method, we have employed the HTP–PGP approach to confirm previously reported successful monomers and to develop new anti-fouling surfaces from a library of 66 monomers for four different challenges of interest to the biotechnology community: hen egg-white lysozyme, supernatant from Chinese Hamster Ovary (CHO) cells in phosphate buffered saline (PBS) solution as a model cell suspension, and immunoglobulin G (IgG) precipitated in the absence and presence of bovine serum albumin (BSA) in high salt solution as a model precipitation process.