A Smart Semiconductor based Integrated Continuous Diabetes Monitoring Platform

项目总结 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 (CDM)系统，将数百万糖尿病患者的糖尿病酮症酸中毒(DKA)风险降至最低， 尤其是那些I型糖尿病患者，在IMS中加入连续酮体监测(CKM) 连续血糖监测仪(CGM)。IMS已经开发出世界上最小的无线电化学 CGM采用了一种新型的半导体(CMOS)平台。这种设计提供了一些独特的优点， 到其智能传感器(与竞争对手设计中的被动传感器相比)，包括Extreme 小型化(系统小于半个芝麻)，多个传感器的片上集成， 信噪比的提高(从而提高了低血糖的准确性)，传感器的减少 电容和膜厚(从而提高响应速度)和芯片上温度 校准。该系统可以在不通知膳食的情况下实现自动闭环血糖控制 和碳水化合物计数，无需担心错过降糖事件；大大简化了 患者体验和提高安全性。 我们已经在实验室、动物和最近的人类身上展示了我们的CGM平台的功能。 CKM的加入可以显著提高系统对即将到来的DKA的检测价值 在当前的CGM系统中未被注意到，对高危患者造成重大伤害。 因此，我们在这项提案中的目标是开发一种能够检测到 使用单一设备检测间质液(ISF)中的葡萄糖和酮。传感平台将是 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)。 这项研究具有重要意义，因为它将使第一个CDM系统能够使用小的、无痛的针头- 插入(26号针头)，可长时间工作(&gt；30天)。一旦得到验证，这个系统就可以 扩展到包括其他重要的分析物(例如，胰岛素、高血糖素)，而不增加其大小或 复杂性，因为在单个微规模设备上集成了多个传感器。 该团队包括来自加州理工学院的核心技术的原始发明者。 纳扎里、拉赫曼博士、森坎先生)，在葡萄糖传感器技术方面经验丰富、受人尊敬的研究员 (比尔·范·安特卫普，美敦力MiniMed前CSO)，外科和生物材料专家(乔纳森博士 加州大学欧文分校的Lakey)、监管和知识产权专家(John Heithaus，JD)、商业化专家(Peter先生 规则；前MiniMed总裁、Therasense董事长和OptiScan)和临床专家(Dr。 艾伦·马库斯，医学博士，美敦力糖尿病公司前首席医疗官)。该项目得到了 像JDRF这样的患者权益倡导团体，以及安妮·彼得斯博士这样的执业内分泌学家。

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.