A Miniaturized and Integrated Continuous Metabolic Monitoring Platform

小型化集成连续代谢监测平台

基本信息

批准号：
10721798
负责人：
Muhammad Mujeeb-U-Rahman
金额：
$ 35万
依托单位：
INTEGRATED MEDICAL SENSORS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10721798
关键词：
Acidosis Adhesives Adverse event Affect American Animals Artificial Pancreas Biocompatible Materials Biosensor Businesses Calibration California Carbohydrates Caring Cellular Phone Chairperson Clinical Clinical Trials Communication Continuous Glucose Monitor Cutaneous Data Data Analyses Development Devices Diabetes Mellitus Diet Disease Doctor of Philosophy Electric Capacitance Elements Endocrinologist Engineering Exercise FDA approved Family suidae Feasibility Studies Feedback Fingers Foreign Bodies Generations Glucagon Glucose Goals Hair Hormone replacement therapy Human Hypoglycemia Implant Infection Insulin Intercellular Fluid Ketones Lactic Acidosis Longevity Measurement Measures Medical Membrane Metabolic Metformin Methods Miniaturization Monitor Movement Needles Noise Pain Free Patients Performance Persons Pharmaceutical Preparations Phase Polymers Population Process Pump Rattus Reaction Time Reader Reference Standards Research Research Personnel Risk Safety Scheme Seasons Semiconductors Sesame - dietary Signal Transduction Site Speed Surface System Technology Temperature Testing Thick Thinness Time Tissues Training Work analog commercialization cost design diabetes management digital flexibility improved in vivo inhibitor innovation integrated circuit irritation metal oxide microsensor miniaturize multimodality novel operation response sensor sensor technology side effect smart watch subcutaneous time use tool user-friendly wireless wireless sensor

项目摘要

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.).

项目概要该项目的长期目标是开发一种可扩展的、用户友好的、连续的代谢监测（CMM）系统，以提高激素替代疗法的性能和可靠性为数百万糖尿病患者服务。 IMS开发出世界上最小的无线电化学基于专用集成电路 (ASIC) 的分析物传感平台，使用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由于其有源数字传感器而具有优势（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、信号到信号的改进噪声 (SNR) 比（从而提高低血糖准确度）、传感器电容降低和膜厚度（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（通过确认传感器位于组织中并测量正确的温度）。拟议的 CMM 将使用户能够从有用的药物（例如二甲双胍、 SGLT2 抑制剂）、锻炼和无需进餐通知的自动胰岛素输送系统，碳水化合物计数以及不良副作用的风险。因此，该设计具有很强的创新性。我们展示了第一代连续血糖监测平台的功能（CGM）在人类中。连续乳酸监测（CLM）可以显着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。我们有在实验室中展示了动物体内的 CLM 和按建议尺寸规模的多重 CGM-CLM。我们在本提案中的目标是开发一种可以感应葡萄糖、乳酸和温度的坐标测量机使用比半颗芝麻还小的单个无线传感器在间质液 (ISF) 中进行检测。小的柔性（20um 厚，带聚合物涂层）传感器可最大限度地减少异物响应 (FBR)。这项研究意义重大，因为它将实现第一个能够使用小型无痛针的 CMM 系统插入（26号针），可长期工作（>30天），并经过工厂校准（无手指棍子）。一旦得到证实，该系统可以扩展到包括其他重要的分析物（例如酮、由于片上集成了多个传感器，因此无需增加其尺寸。该团队包括来自加州理工学院的核心技术原始发明人（Nazari 博士、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员技术（Bill Van Antwerp，美敦力 MiniMed 前 CSO），生物材料专家（Jonathan 博士）加州大学欧文分校的 Lakey）、监管和知识产权专家（John Heithaus，法学博士）、商业化专家（Peter 先生）规则; MiniMed 前总裁、Therasense 和 OptiScan 董事长）、临床专家（Alan 博士）马库斯，医学博士；美敦力糖尿病公司前首席医疗官），以及植入式生物传感器和乳酸监测专家（Natalie Wisniewski 博士，Profusa, Inc. 前首席技术官）。