A Smart Semiconductor based Integrated Continuous Diabetes Monitoring Platform

项目摘要 该项目的长期目标是开发一种可扩展的、用户友好的、连续的糖尿病监测系统 (CDM)系统，以尽量减少糖尿病酮症酸中毒（DKA）的风险，为数百万糖尿病患者， 通过在IMS中添加连续酮监测（CKM），尤其是I型糖尿病患者 动态血糖监测仪（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。这种设计提供了一些独特的优势， 其智能传感器（与竞争对手设计中的无源传感器相比），包括极端 小型化（系统小于半个芝麻），多个传感器的片上集成， 信噪比改善（从而改善低血糖准确性），传感器减少 电容和膜厚度（从而提高响应速度），以及片上温度 校准。该系统可以实现自动闭环血糖控制，无需进餐通知 和碳水化合物计数，而不必担心错过低血糖事件;大大简化 患者体验和提高安全性。 我们已经在实验室、动物和最近的人类中证明了CGM平台的功能。 添加CKM可以显著提高系统检测即将发生的DKA的价值， 在当前CGM系统中未被注意到，对高危患者造成重大伤害。 因此，我们在本提案中的目标是开发一种可以检测的多分析物传感平台 使用单个器械测定组织液（ISF）中的葡萄糖和酮。传感平台将在 在实验室和猪模型中进行了测试（与人类皮肤和新陈代谢很好地匹配）。 这项研究是重要的，因为它将使第一个清洁发展机制系统与一个小，无痛针- 插入（26号针），可以工作很长时间（>30天）。一旦被证实，该系统可以 扩展到包括其它重要的分析物（例如，胰岛素、胰高血糖素）而不增加其大小，或 由于在单个微尺度器件上芯片上集成了多个传感器， 该团队包括核心技术的原始发明者，来自加州理工学院（博士。 Nazari、Rahman博士、Sencan先生），葡萄糖探头技术领域经验丰富、备受尊敬的研究人员 (Bill货车安特卫普，美敦力MiniMed前CSO），手术和生物材料专家（乔纳森博士 Lakey）、法规和知识产权专家（John Heithaus，JD）、商业化专家（Peter Rule; MiniMed前总裁、Therasense和OptiScan主席）和临床专家（Dr. Alan Marcus，MD; Medtronic Diabetes前首席医疗官）。该项目得到了 患者权益团体如JDRF和执业内分泌学家如Anne Peters博士。

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 this proposal is 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 will be tested both in the lab and in a porcine model (matches well with human skin and metabolism). 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. 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.