A Miniaturized and Integrated Continuous Metabolic Monitoring Platform

项目摘要 这个项目的长期目标是开发一个可扩展的，用户友好的，连续的代谢 监测（CMM）系统，以提高性能和可靠性的激素替代治疗 为数百万糖尿病患者。IMS开发了世界上最小的无线电化学 一种基于专用集成电路（ASIC）的分析物感测平台， 互补金属氧化物半导体（CMOS）技术。这种设计提供了一些独特的 有源数字传感器的优势（与竞争对手设计中的无源模拟传感器相比） 包括极端小型化、多个传感器的片上集成、信号到 噪声（SNR）比（从而提高低血糖准确性），传感器电容降低， 膜厚度（从而提高响应速度），通用干扰抑制（使用 背景参考传感器并从所有传感器中减去其信号）和片上温度 校准（通过确认传感器在组织中并测量 正确的温度）。拟议的中药将使用户受益于有用的药物（例如，二甲双胍， SGLT 2抑制剂）、运动和自动胰岛素给药系统（无进餐通知）， 碳水化合物计数和不良副作用的风险。因此，该设计具有很强的创新性。 我们已经展示了第一代平台的功能，用于动态血糖监测 (CGM)在人类身上。连续乳酸监测（CLM）可以显著提高系统的价值 检测当前CGM系统未注意到的即将发生的乳酸酸中毒。我们有 在动物中证明了CLM，并在实验室中以建议的尺寸规模证明了多重CGM-CLM。 我们的目标是在这个建议是开发一个坐标测量机，可以感应葡萄糖，乳酸，和温度 在组织液（ISF）中使用小于半个芝麻籽的单个无线传感器。小 和柔性（20 μ m厚的聚合物涂层）传感器最大限度地减少异物反应（FBR）。 这项研究是重要的，因为它将使第一坐标测量系统能够一个小，无痛针 插入（26号针头），可长时间工作（>30天），工厂校准（无手指 棒）。一旦被证明，该系统可以扩展到包括其他重要的分析物（例如，酮， 胰岛素、胰高血糖素）而不增加其尺寸，这是由于多个传感器的芯片上集成。 该团队包括来自加州理工学院的核心技术的原始发明者 (Dr. Nazari，Rahman博士，Sencan先生），一位经验丰富且受人尊敬的电化学传感器研究人员 技术（Bill货车Antwerp，Medtronic MiniMed前CSO），生物材料专家（Jonathan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董事长和OptiScan）、临床专家（Alan博士 Marcus，MD; Medtronic Diabetes的前首席医疗官）和植入式生物传感器， 乳酸盐监测专家（Natalie Wisniewski博士，Profusa，Inc.的前CTO）。

PROJECT SUMMARY The long-term goal of this project is to develop a scalable, user-friendly, continuous metabolic monitoring (CMM) system to improve the performance and reliability of hormone replacement therapy for millions of diabetes patients. IMS has developed the world's smallest wireless electrochemical analyte sensing platform based on an application-specific integrated circuit (ASIC) using Complementary Metal-Oxide Semiconductor (CMOS) technology. This design offers some unique advantages due to its active digital sensor (compared to passive analog sensors in competitor designs) including extreme miniaturization, on-chip integration of multiple sensors, improvement in signal-to- noise (SNR) ratio (thus improving hypoglycemia accuracy), decrease in sensor capacitance and membrane thickness (thus improving response speed), universal interference rejection (using a background reference sensor and subtracting its signal from all sensors), and on-chip temperature calibration (improve accuracy, reliability by confirming the sensor is in the tissue and measuring the correct temperature). The proposed CMM will enable users to benefit from useful drugs (e.g., metformin, SGLT2 inhibitors), exercise, and automated insulin delivery systems without meal announcements, carbohydrate counting, and the risk of adverse side effects. Hence, the design is highly innovative. We have demonstrated the function of the first-generation platform for continuous glucose monitoring (CGM) in humans. Continuous lactate monitoring (CLM) can significantly improve the system's value to detect impending Lactic Acidosis that goes unnoticed with the current CGM systems. We have demonstrated the CLM in animals and a multiplexed CGM-CLM at the proposed size scale in the lab. Our objective in this proposal is to develop a CMM that can sense glucose, lactate, and temperature in the interstitial fluid (ISF) using a single wireless sensor smaller than half a sesame seed. The small and flexible (20um thick with polymer coatings) sensor minimizes the foreign body response (FBR). This research is significant as it will enable the first CMM system capable of a small, pain-free needle insertion (26-gauge needle) that can work for a long time (>30 days) with factory calibration (no finger sticks). Once proven, this system can be extended to include other important analytes (e.g., ketones, insulin, glucagon) without increasing its size, owing to the on-chip integration of multiple sensors. The team includes original inventors of the core technology from the California Institute of Technology (Dr. Nazari, Dr. Rahman, Mr. Sencan), a seasoned and respected researcher in electrochemical sensor technology (Bill Van Antwerp, former CSO of Medtronic MiniMed), 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), clinical experts (Dr. Alan Marcus, MD; former Chief Medical Officer of Medtronic Diabetes), and implantable biosensors and lactate Monitoring expert (Dr. Natalie Wisniewski, Ph.D., former CTO of Profusa, Inc.).