Plasma clearance of water soluble and albumin bound toxins using graphene oxide nanoengineered laminates

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Abstract Patients with end-stage kidney and liver disease as well as acute organ failure are unable to maintain the necessary clearance of toxins and require blood-purification techniques or organ transplant. Over 400,000 end-stage renal disease (ESRD) patients receive regular hemodialysis (HD) treatments in the United States. A smaller number receive artificial liver support therapy for detoxification and liver failure. These blood purification techniques place an extremely high financial burden on our medical system with sometimes questionable efficacy and relatively poor quality of life. ESRD treatment alone accounts for 7% of all Medicare spending ($31B). The membrane and adsorption technology behind these treatments has been slow to evolve over the last few decades, limiting the opportunity to make significant improvements. Graphene oxide (GO) has the potential to radically improve and change hemodialysis and liver support systems because GO bilayers are the thinnest possible molecular sieve and nanoscale-spaced GO stacks offer unparalleled adsorptive capacity. The scientific premise behind the use of GO nanoengineered laminates for the clearance of water-soluble and albumin- bound toxins is two-fold. First, prior work has demonstrated that the use of ultrathin nanoporous membranes enables the reduction of laboratory-scale dialyzers by two orders of magnitude compared to conventional polymeric membranes due to dramatically increased permeability, while maintaining size-selectivity. We hypothesize that GO nanoengineered laminate membranes will further reduce required membrane area by at least another order of magnitude based on thinness (<10nm) and increased permeability. Second, albumin-bound toxins have traditionally been removed using anion- exchange columns or porous matrices of activated carbon. Nanospaced GO laminates offer a theoretical limit on surface area within a fixed volume that is likely to exceed conventional adsorbent materials by orders of magnitude. The two aims in the proposal will test both hypotheses. Aim 1 will investigate use of GO to clear water-soluble toxins from plasma, while Aim 2 will investigate the clearance of albumin-bound toxins via albumin dialysis and adsorption to a GO laminate stack. Success in these aims will enable novel device design and treatment flexibility that may include wearable and more efficient therapies with higher quality of life for patients with kidney and liver disease.