Development of biomedical devices for the extracorporeal real-time monitoring and perfusion of transplant organs

Abstract

The goal of this Thesis is to develop a range of technologies that could enable a paradigm shift in organ preservation for renal transplantation, transitioning from static cold storage to warm normothermic blood perfusion. This transition could enable the development of novel pre-implantation therapies, and even serve as the foundation for a global donor pool. A low-hæmolysis pump was developed, based on a design first proposed by Nikola Tesla in 1913. Simulations demonstrated the theoretical superiority of this design over existing centrifugal pumps for blood recirculation, and provided insights for future avenues of research into this technology. A miniature, battery-powered, multimodal sensor suite for the in-line monitoring of a blood perfusion circuit was designed and implemented. This was named the ‘SmartPipe’, and proved capable of simultaneously monitoring temperature, pressure and blood oxygen saturations over the biologically-relevant ranges of each modality. Finally, the Thesis details the successful implementation and optimisation of a combined microfluidic and microdialysis system for the real-time quantitation of creatinine in blood or urine through amperometric sensing, to act as a live renal function monitor. The range of detection was 4.3μM – 500μM, with the possibility of extending this in both directions. This work also details and explores a novel methodology for functional monitoring in closed-loop systems which avoids the need for sensor calibration, and potentially overcomes the problems of sensor drift and desensitisation.