A Smart Semiconductor based Integrated Continuous Diabetes Monitoring Platform

基于智能半导体的集成连续糖尿病监测平台

• 批准号: 10900360
• 负责人: Muhammad Mujeeb-U-Rahman
• 金额: $ 10万
• 依托单位: INTEGRATED MEDICAL SENSORS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10900360
• 关键词: Animals; Biocompatible Materials; Calibration; California; Carbohydrates; Chairperson; Chemistry; Clinical; Computer software; Continuous Glucose Monitor; Data; Development; Devices; Diabetes Mellitus; Diabetic Ketoacidosis; Electric Capacitance; Electrodes; Endocrinologist; Enzymes; Event; Fright; Glucagon; Glucose; Goals; Human; Hypoglycemia; Insulin; Insulin-Dependent Diabetes Mellitus; Intercellular Fluid; Ketones; Medical; Membrane; Miniaturization; Monitor; Needles; Noise; Operative Surgical Procedures; Pain Free; Pathway interactions; Patients; Reader; Research; Research Personnel; Risk; Safety; Seasons; Semiconductors; Sesame - dietary; Signal Transduction; Speed; System; Techniques; Technology; Temperature; Testing; Thick; Time; United States National Institutes of Health; Update; Work; blood glucose regulation; commercialization; design; experience; glucose sensor; improved; interest; novel; patient advocacy group; prevent; response; risk minimization; sensor; sensor technology; user-friendly; wireless

PROJECT SUMMARY The long-term goal of this project is to develop a scalable, user-friendly, continuous diabetes monitoring (CDM) system to minimize the risk of diabetic ketoacidosis (DKA) for millions of diabetes patients, especially those with type I diabetes by adding continuous ketone monitoring (CKM) to the IMS continuous glucose monitor (CGM). IMS has developed the world's smallest wireless electrochemical CGM using a novel semiconductor (CMOS) platform. This design offers some unique advantages due to its smart sensor (compared to passive sensors in competitor designs) including extreme miniaturization (system is smaller than half a sesame seed), on-chip integration of multiple sensors, improvement in signal-to-noise ratio (thus improving hypoglycemia accuracy), decrease in sensor capacitance and membrane thickness (thus improving response speed), and on-chip temperature calibration. This system can enable automatic closed-loop glucose control without meal announcements and carbohydrate counting and without the fear of missed hypoglycemic events; greatly simplifying patient experience and improving safety. We have demonstrated the function of our CGM platform in the lab, in animals, and recently in humans. The addition of CKM can significantly improve the value of the system to detect impending DKA that goes unnoticed with the current CGM systems, causing significant harm to the at-risk patients. Therefore, our objective in the original proposal was to develop a multi-analyte sensing platform that can sense both glucose and ketone in the interstitial fluid (ISF) using a single device. The sensing platform would be tested in the lab. This research is significant as it will enable the first CDM system with a small, pain-free needle- insertion (26-gauge needle) that can work for a long time (>30 days). Once proven, this system can be extended to include other important analytes (e.g., insulin, glucagon) without increasing its size or complexity, owing to on-chip integration of multiple sensors on a single microscale device. During our work, we discovered an unforeseen issue with the ketones sensing chemistry that prevents long-term stability. We have discovered a potential solution to that by using a conjugated enzyme. We need additional support via this supplement to enable us to test this solution. The team includes original inventors of the core technology from California Institute of Technology (Dr. Nazari, Dr. Rahman, Mr. Sencan), seasoned and respected researcher in Glucose sensor technology (Bill Van Antwerp, former CSO of Medtronic MiniMed), surgery and biomaterials expert (Dr. Jonathan Lakey of UC Irvine), regulatory and IP expert (John Heithaus, JD), commercialization expert (Mr. Peter Rule; former President of MiniMed, Chairman of Therasense, and OptiScan), and clinical expert (Dr. Alan Marcus, MD; former Chief Medical Officer of Medtronic Diabetes). The project is supported by patient advocacy groups like JDRF and practicing endocrinologists like Dr. Anne Peters.

项目摘要 该项目的长期目标是开发可扩展，用户友好的连续糖尿病监测 （CDM）系统以最大程度地减少数百万糖尿病患者的糖尿病性酮症酸中毒（DKA）的风险， 特别是那些通过向IMS添加连续的酮监测（CKM）来添加连续的酮监测（CKM） 连续葡萄糖监测器（CGM）。 IMS开发了世界上最小的无线电化学 CGM使用新型半导体（CMOS）平台。此设计提供了一些独特的优势 与其智能传感器（与竞争者设计中的被动传感器相比），包括极端 微型化（系统小于半芝麻种子），多个传感器的片上整合， 信噪比的提高（从而提高了低血糖精度），传感器的降低 电容和膜厚度（从而提高响应速度）和片上温度 校准。该系统可以无需公告即可自动闭环葡萄糖控制 和碳水化合物计数，而不必担心错过降血糖事件；大大简化 患者经验和改善安全性。 我们已经证明了我们在实验室，动物和最近在人类中的CGM平台的功能。 CKM的添加可以显着提高系统的价值，以检测即将来临的DKA 目前的CGM系统没有引起注意，对高危患者造成了重大伤害。 因此，我们在原始建议中的目标是开发一个多分析物传感平台 使用单个设备可以感觉到间质流体（ISF）中的葡萄糖和酮。感应 平台将在实验室进行测试。 这项研究很重要，因为它将启用第一个CDM系统，该系统具有小的无痛针 - 可以长时间工作（> 30天）的插入（26规针）。一旦证明了这个系统 扩展到包括其他重要分析物（例如胰岛素，胰高血糖素），而无需增加其大小或 复杂性，由于单个显微镜设备上多个传感器的芯片集成。 在我们的工作中，我们发现了酮传感化学反应的一个不可预见的问题 长期稳定性。我们通过使用共轭酶发现了一种潜在的解决方案。 我们需要通过此补充剂提供额外的支持，以使我们能够测试该解决方案。 该团队包括加利福尼亚理工学院核心技术的原始发明家（Dr. 纳扎里（Nazari （Bill van Antwerp，Medtronic Minimed的前CSO），手术和生物材料专家（Jonathan博士 UC Irvine的Lakey），监管和IP专家（John Heithaus，JD），商业化专家（Peter先生 规则;前总裁最小化，Therasense和Optiscan董事长）和临床专家（博士 艾伦·马库斯（Alan Marcus），医学博士； Medtronic糖尿病的前首席医疗官）。该项目由 诸如JDRF之类的患者倡导团体以及安妮·彼得斯博士等内分泌学家。