Title: Clinical Assessment of a Novel Microprobe Array Continuous Glucose Monitor in Type 1 Diabetes
Funder: Department of Health (England)

Abstract: The Imperial microprobe array continuous glucose sensor consists of 64 microprobes perpendicular to the base plate and arranged 8x8. The microprobes are 700-1000µm long with a base of 500-600µm and tip diameter of 10-50µm. They are a polymer coated with metal and functionalized with a layer of glucose oxidase (GOx) to detect glucose electrochemically. The microprobes are finally coated with a membrane to extend the working range and increase resistance to interferents. The device allows painless, accurate continuous glucose monitoring and is the only microprobe array-based glucose sensor using a non-extractive technique, avoiding the limitations of interstitial fluid (ISF) extraction through hollow microneedles. The device has undergone functional validation in vitro and mechanical validation ex vivo using human skin samples. Insertion tests have demonstrated successful skin penetration using forces as low as 7N without fracture. Axial fracture tests using large forces (up to 400N) have demonstrated bending and height reduction only, while transverse fracture tests have demonstrated a high safety margin. Data demonstrate a functional device able to access interstitial fluid without mechanical failure, and the device can now be assessed in vivo. The clinical study will assess the safety and efficacy of the sensor for continuous monitoring of ISF glucose. Safety will be assessed by pain, skin inflammation, skin damage, and microprobe integrity. Studies will start over six hours, then over 24 hours in non-diabetic subjects, then over 24 hours in subjects with T1DM and finally, in an ambulatory situation. Efficacy will be assessed mechanically (by the ability to penetrate the stratum corneum) and functionally (by the ability to accurately sense ISF glucose). The measured glucose will be compared with simultaneous venous samples and with a commercially available CGM device. In the ambulatory study, the device will be applied for five days to assess optimum duration of performance. The device will undergo further technical development through further optimization of the functionalization protocols for the integrated multielectrode system. Partitioning of the array will be done by isolating the metallised layers using laser machining to allow for multiple glucose sensors, as well as forming a reference electrode. This allows redundancy for technical failure as a single malfunctioning sensor can be voted out on the basis of divergent results. Partitioning of microprobe arrays can also allow for continuous multi-analyte sensing by immobilization of different enzymes across multiple sensing areas sharing a common reference electrode. Milestones: A. Work Plan 1: 1. End Month 6: Safety, accuracy and reliability assessed in non-diabetic subjects in a controlled environment over 6 hours (WP1: phase 1). 2. End Year 1: Safety, accuracy and reliability assessed in non-diabetic subjects in a controlled environment over 24 hours (WP1: phase 2). 3. End Month 21: Accuracy, reliability and safety assessed in subjects with T1DM in a controlled environment over 24 hours (WP1: phase 3). 4. End Year 3: Complete ambulatory study over 5 days in subjects with T1DM to assess safety, reliability, accuracy and duration of optimum device’s performance (WP1: phase 4). B. Work Plan 2: 1. End Month 6: Prototype Applicator built and microprobes partitioned in to sensing, reference and counter electrode (WP2) 2. End Month 12: Automation of functionalisation completed (WP2) 3. End Year 2: Partitioning in multiple sensors and data processing (WP2) 4. End Year 3: Complete wireless integration. (WP2)


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: METABOLIC AND ENDOCRINE