Hospital acquired infections (HAIs) and the emergence of antibiotic resistant strains are major threats to human health. Copper is well known for its high antimicrobial efficacy, including the ability to kill superbugs and the notorious ESKAPE group of pathogens. We sought a material that maintains the antimicrobial efficacy of copper while minimizing the downsides – cost, appearance and metallic properties – that limit application. Here we describe a copper-glass ceramic powder as an additive for antimicrobial surfaces; its mechanism is based on the controlled release of copper (I) ions (Cu 1+ ) from cuprite nanocrystals that form in situ in the water labile phase of the biphasic glass ceramic. Latex paints containing copper-glass ceramic powder exhibit ≥99.9% reduction in S. aureus , P. aeruginosa, K. aerogenes and E. Coli colony counts when evaluated by the US EPA test method for efficacy of copper-alloy surfaces as sanitizer, approaching that of benchmark metallic copper.

The standard solution-depletion method is implemented with SDS-gel electrophoresis as a multiplexing, separation-and-quantification tool to measure competition between two proteins (i and j) for adsorption to the same hydrophobic adsorbent particles (either octyl sepharose or silanized glass) immersed in binary-protein solutions. Adsorption kinetics reveal an unanticipated slow protein-size-dependent competition that controls steady-state adsorption selectivity. Two sequential pseudo-steady-state adsorption regimes (State 1 and State 2) are frequently observed depending on i, j solution concentrations. State 1 and State 2 are connected by a smooth transition, giving rise to sigmoidally-shaped adsorption-kinetic profiles with a downward inflection near 60 minutes of solution/adsorbent contact. Mass ratio of adsorbed i, j proteins (m i m j ) remains nearly constant between States 1 and 2, even though both m i and m j decrease in the transition between states. State 2 is shown to be stable for 24 hours of continuous-adsorbent contact with stagnant solution whereas State 2 is eliminated by continuous mixing of adsorbent with solution. In sharp contrast to binarycompetition results, adsorption to hydrophobic adsorbent particles from single-protein solutions (pure i or j) exhibits no detectable kinetics within the timeframe of experiment from either stagnant or continuously-mixed solution, quickly achieving a single steady-state value in proportion to solution concentration. Comparison of binary competition between dissimilarly-sized protein pairs chosen to span a broad molecular-weight (MW) range demonstrates that selectivity between i and j scales with MW ratio that is proportional to protein-volume ratio (ubiquitin, Ub, MW = 10.7 kDa; human serum albumin, HSA, MW = 66.3 kDa; prothrombin, FII, 72 kDa; immunoglobulin G, IgG, MW = 160 kDa; fibrinogen, Fib, MW = 341 kDa). Results are interpreted in terms of a kinetic model of adsorption that has protein molecules rapidly diffusing into an inflating interphase that is spontaneously formed by bringing a protein solution into contact with a physical surface (State 1). State 2 follows by rearrangement of proteins within this interphase to achieve the maximum interphase concentration (dictated by energetics of interphase dehydration) within the thinnest (lowest volume) interphase possible by ejection of interphase water and initially-adsorbed proteins. Implications for understanding biocompatibility are discussed using a computational example relevant to the problem of blood-plasma coagulation.

Silanized-glass-particle adsorbent capacities are extracted from adsorption isotherms of human serum albumin (HSA, 66 kDa), immunoglobulin G (IgG, 160 kDa), fibrinogen (Fib, 341 kDa), and immunoglobulin M (IgM, 1000 kDa) for adsorbent surface energies sampling the observable range of water wettability. Adsorbent capacity expressed as either mass-or-moles per-unit-adsorbent-area increases with protein molecular weight (MW) in a manner that is quantitatively inconsistent with the idea that proteins adsorb as a monolayer at the solution-material interface in any physically-realizable configuration or state of denaturation. Capacity decreases monotonically with increasing adsorbent hydrophilicity to the limit-of-detection (LOD) near τo = 30 dyne/cm (θ~65o) for all protein/surface combinations studied (where τo≡γlvocosθ is the water adhesion tension, γlvo is the interfacial tension of pure-buffer solution, and θ is the buffer advancing contact angle). Experimental evidence thus shows that adsorbent capacity depends on both adsorbent surface energy and adsorbate size. Comparison of theory to experiment implies that proteins do not adsorb onto a two-dimensional (2D) interfacial plane as frequently depicted in the literature but rather partition from solution into a three-dimensional (3D) interphase region that separates the physical surface from bulk solution. This interphase has a finite volume related to the dimensions of hydrated protein in the adsorbed state (defining “layer” thickness). The interphase can be comprised of a number of adsorbed-protein layers depending on the solution concentration in which adsorbent is immersed, molecular volume of the adsorbing protein (proportional to MW), and adsorbent hydrophilicity. Multilayer adsorption accounts for adsorbent capacity over-and-above monolayer and is inconsistent with the idea that protein adsorbs to surfaces primarily through protein/surface interactions because proteins within second (or higher-order) layers are too distant from the adsorbent surface to be held surface bound by interaction forces in close proximity. Overall, results are consistent with the idea that protein adsorption is primarily controlled by water/surface interactions.

Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension in dyne/cm, where is water interfacial tension in dyne/cm and θ is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties dyne/cm (0° ≤ θ < 120°), falling sharply through a broad minimum within the dyne/cm (55° < θ < 75°) range over which activation yield (putatively FXIIa) rises just above detection limits. Activation is very rapid upon contact with all activators tested and did not significantly vary over 30 minutes of continuous FXII-procoagulant contact. Results suggest that materials falling within the dyne/cm surface-energy range should exhibit minimal activation of blood-plasma coagulation through the intrinsic pathway. Surface chemistries falling within this range are, however, a perplexingly difficult target for surface engineering because of the critical balance that must be struck between hydrophobicity and hydrophilicity. Results are interpreted within the context of blood plasma coagulation and the role of water and proteins at procoagulant surfaces.

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