Title: An Adsorbent Device to Promote Toxin Removal during Haemodialysis (ADEPT)
Funder: Department of Health (England)

Abstract: The project will be carried out in four work packages (WPs). WP 1 (month 1-8) will be a material optimisation programme in which the miniaturized monoliths tested in previous studies will be scaled up to a clinically scaled carbon monolith adsorption device called the ADEPT system. The WP will be carried out by MAST Carbon International (MCI) and the University of Brighton (UB). Small prototype monoliths previously shown to be non-cytotoxic and non-activating with significant capacity to remove uraemic toxins will be prepared as part of WP 1 in sufficient quantity for full haemocompatibility assessment in WP2. The carbon monoliths contain a high level of mesoporosity and macroporosity in the 2 to 200nm range and it is these pores which significantly augment the adsorptive capacity of the monoliths for protein bound and high molecular weight proteins poorly removed by current haemodialysis. The monoliths will be scaled up using technology available at MCI. Porosity, macrostructure and flow will be assessed at UB using scanning electron microscopy (SEM), nitrogen gas and mercury porosimetry and in vitro assays for protein removal from plasma. Milestone M1: Small and large adsorbent monolith prototypes prepared for assessment in WP 2 and 3 respectively. Deliverable D1: Small and large adsorbent monolith prototypes prepared with appropriate porosity, structural integrity and adsorptive capacity. WP 2 (month 6-14) will involve assessment of prototype haemocompatibility according to the International Standards directive for selection of tests for interactions with blood (ISO 10993-4:2002(E)) in preparation for CE marking. A healthy donor blood study will be carried out by UB, The Sussex Kidney Unit and Clinical Investigation and Research Unit (CIRU) at Brighton and Sussex University Hospitals NHS Trust (BSUH) for assessment of platelet activation, coagulation, complement activation, leukocyte activation and haemolysis following blood filtration through the carbon monoliths using standard flow cytommetry, coagulometry and ELISA based assays, in addition to measurement of changes in blood biochemistry (urea and electrolytes, whole blood counts). M2:Full haemocompatibility profiling carried out according to ISO testing criteria. D2:Small adsorbent monoliths are shown to be haemocompatible in a prototype testing model using healthy donor blood samples. WP3 (month 14-24) will be carried out by UB, BSUH and the Royal Free Hospital (RFH). The scaled up ADEPT system will be assessed within an adult standard haemodialyzer circuit using a blood flow rate of 300 ml/min and using fresh bovine blood. Assessment will be made of pressure drop across the system and additional free volume of blood within the adsorbent cartridge will be compared with hypothesised values. SEM will be carried out post filtration on fixed adsorbent sections to assess maintained macroporous structure. Whole blood studies will be used to assess maintained capacity for removal of marker inflammatory molecules and uraemic toxins from spiked fresh bovine blood. Haemocompatibility at high flow rates will also be assessed using unspiked fresh bovine blood, measuring haemolysis, clotting, blood cell activation and removal. M3:Clinically scaled ADEPT prototype tested within a haemodialyzer system at high flow rates. D3: Clinically scaled ADEPT prototypes remove marker uraemic toxins and maintain haemocompatibility in scale up. WP 4 (month 22-24) will involve data analysis, preparation of the final report and consideration of further seed funding applications or investment routes for the in vivo studies. A business plan for commercial development of the device will also be prepared. M4:The ADEPT prototype fully characterised for progression to in vivo studies and commercial progression routes identified. D4:??Final report complete, further application for in vivo studies initiated, business plan for commercial development complete.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL