Development and evaluation of a novel microprobe array continuous glucose monitor for type 1 diabetes

Abstract

Despite the evidence demonstrating benefits of continuous glucose monitoring (CGM), the technology has not been widely implemented in routine management of type 1 diabetes due to several challenges. Our group has developed a novel sensor for CGM based on microprobe technology. The sensor consists of an array of solid microprobes, which are functionalised for in situ electrochemical measurement of dermal interstitial fluid glucose. The unique minimally-invasive non-extractive approach provides several avenues to enhance CGM accuracy. In this thesis, I describe the work carried out aiming to transfer this novel technology from bench side to bedside. To evaluate sensor’s ability to penetrate stratum corneum, human skin was utilised ex vivo to assess the force required for microprobes’ insertion compared to that required for their fracture. These studies guided a change in the fabrication technique and a modification in microprobes’ design. In vitro studies showed high sensitivity to glucose, providing the potential to enhance sensor accuracy. Further evaluation showed that neither skin insertion nor gamma ray sterilisation had impacted sensor performance. Clinical evaluation of sensor safety and proof of concept started with phase 1. The six-hour study demonstrated that sensor use was associated with barely noticeable skin reaction and minimal pain. The work also includes a mixed-method study aimed at capturing patients’ views in relation to CGM and describes the role of patient and public involvement in this project. These findings have important implications for the development of an accurate, cost-effective and user-friendly CGM system. This may help in widespread implementation of CGM technology and enhance compliance with CGM use with subsequent improvement in clinical effectiveness. Finally, a re-analysis of 448 glucose profiles from the Juvenile Diabetes Research Foundation CGM study is presented. This describes measures of glycaemic variability in type 1 diabetes and demonstrates the value of CGM in reducing these measures.