An accurate, fast, and miniaturized glucose sensor for closed-loop diabetes management

PROJECT SUMMARY The long term ​goal of this project is to develop a low-cost, user-friendly, and accurate glucose sensing solution with multisensor reliability to enable the use of closed-loop insulin delivery in an artificial pancreas. The system demonstrates fast sensor kinetics owing to small size, close proximity of sensor and related electronics, miniaturized electrodes with low capacitance, and thin and flexible profile leading to better integration with the surrounding tissue and local vascularization. This can enable automatic closed-loop glucose control without meal announcements and carbohydrate counting. The system also has excellent hypoglycemia accuracy due to small size and better integration with surrounding tissue (details available in research strategy). IMS has developed a novel, miniaturized (smaller than rice grain), completely wireless, and extremely low-cost glucose sensor that consists solely of a single semiconductor device (microsystem). This device can sense glucose owing to a novel microelectronics design and an integrated on-chip electrochemical sensor. This device is injected in subcutaneous tissue using a proprietary inserter and wirelessly communicates the glucose data to an external wearable transmitter which relays it to a smartphone to enable data visualization and cloud-based data handling to provide real-time feedback. With help of Caltech, NIH, and NSF funding, we have demonstrated sensor functionality in-vitro, in rats, and ​in porcine model for more than 1 month​. Our results indicate the sensor is very accurate (MARD=6.2% for andlt;210 mg/dl which is the most important range), and can work for longer time (andgt; 1 month) when compared to current transcutaneous CGM products. Moreover, the device is user-insertable and removable and hence eliminates the requirement of surgical procedures at doctor’s office as required by other wireless CGM devices (e.g. eversense by Senseonics). Our ​objective in this proposal is to develop a version of our glucose sensing platform that ​can be used for First-In-Human testing​. The proposed new microsystem will fit in a smaller (29 gauge) needle using a spring-loaded inserter to enable safe and accurate insertion. It will be attached to a small disk for safe removal of the sensor after its lifetime (e.g. after andgt; 1 month). The device will measure glucose using ​three on-chip sensors to ​increase the reliability of the readout. The sensing platform will be tested in porcine model as it matches well with human skin and metabolism. This research is ​significant as it will enable the smallest in class (29 gauge insertable) factory-calibrated, user-insertable and removable, CGM that can work for a long time (andgt;30 days), provide reliability of redundant glucose sensing, and fast response that can all enable safe and accurate closed-loop glucose control in an artificial pancreas. Also, the system offers lowest cost of goods by design owing to the semiconductor technology. The project ​team ​includes original inventors of the core technology from Caltech (Dr. Nazari, Dr. Rahman, Mr. Sencan), seasoned and respected researcher in Glucose sensor technology (Bill Van Antwerp), experimental surgery and biomaterials expert (Dr. Jonathan Lakey of UC Irvine) and commercialization expert (Mr. Peter Rule from MiniMed, Therasense, and OptiScan). The company is working within IVD Technologies Inc., an ISO certified, FDA registered biotechnology company under a facilities rental agreement.Project Narrative Diabetes affects more than 425 million people worldwide,more than 30 million of whom live in the US. It costs more than $320 Billion and causes more than 14 million emergency room visits in the US. CGM is the technology of choice for diabetes management, by itself as well as in conjunction with insulin delivery devices (pumps, pens). However, both transcutaneous (due to tissue irritation owing hard anchor with a bulky and wired external transmitter) CGM devices and recently approved wireless CGM devices (due to large size) suffer from significantly large blood-ISF delay and adverse foreign body reaction. The artificial pancreas efforts will significantly benefit from a more accurate (especially in hypoglycemia), faster (especially at meal times), and more reliable CGM system. In this proposal, we intend to design a glucose sensor that integrates better with surrounding tissue due to its small size and thin profile. Also, it uses miniaturized microelectrodes in close proximity of integrated electronics, which improves its hypoglycemia accuracy. This can result in a sensor that provides faster kinetics as compared to bigger or wired devices, and can work for a long time (andgt;30 days) with better hypoglycemia accuracy. IMS has proven the feasibility of a wireless version of its sensor in lab bench (andgt;1 year), ​and in pigs for more than 1 month​. Our main goal in this proposal is to design a more human-friendly version of the sensor that provides all the benefits of current IMS design along with the ease of insertion and removal for safe and effective human testing. The above mentioned advantages along with low cost and potentially fast kinetics can enable the use of artificial pancreas for a diverse range of patients for whom glycemic control otherwise is difficult leading to both morbidity and mortality.