Biofilm formation leads to a 1000 times increase in antibiotic tolerance compared with planktonic bacteria and is associated with 80% of hospital acquired infections, resulting in $3.0 billion in excess health-care costs each year in the U.S alone. Thus, new materials that prevent biofilm formation would offer enormous benefits to the health industry and improve patient welfare. However, the limited understanding of bacteria-material interactions restricts the rational design of such materials. Polymer microarrays are emerging as a key enabling technology for the discovery of new biomaterials[1] and have been utilised to identify novel polymers that resist bacterial attachment.

Polymer microarrays were formed as previously described.[2] This platform enabled a large combinatorial space to be rapidly screened by a biological assay to identify new materials that fulfil a given performance criterion.[3] In the present study a bacterial attachment assay was developed using green fluorescing protein (GFP) tagged bacterial strains (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli) where the attachment of bacteria to each material was quantified by measuring the fluorescnce after incubation for 72 h.

Due to the large combinatorial chemical space available to the polymer micoarray format a strategy was devised to rapidly identify the optimal polymer composition that resists bacterial adhesion. This utilised a multi-generation microarray approach where the ‘hits’ from one array feed into the design of a subsequent array. Initially, an array was formed from 22 monomers with varied chemistry that were mixed to form 488 unique material compositions. Hit compositions were chosen from this array to produce a focussed second generation array containing unique materials where the hit compositions were varied incrementally. The resulting hit compositions were all amphiphilic containing both hydrophobic and hydrophilic moieties.

A methodology has been developed to screen the vast combinatorial chemical space within polymer chemistry for optimised compositions that produce novel materials with inherent resistance to bacterial adhesion. Key to this approach was the use of multi-generation microarrays.

[1] Hook AL, Anderson DG, Langer R, Williams P, Davies MC, Alexander MR. Biomaterials 2010;31:187-198.

[2] Anderson DG, Levenberg S, Langer R. Nature Biotechnology 2004;22:863-866.

[3] Mei Y, Saha K, Bogatyrev SR, Yang J, Hook AL, Kalcioglu ZI, Cho SW, Mitalipova M, Pyzocha N, Rojas F, Van Vliet KJ, Davies MC, Alexander MR, Langer R, Jaenisch R, Anderson DG. Nature Materials 2010;9:768-778.