A Miniaturized and Integrated Continuous Metabolic Monitoring Platform

小型化集成连续代谢监测平台

• 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
• 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

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.).

项目总结 该项目的长期目标是开发一种可扩展的、用户友好的、持续的代谢 提高激素替代治疗效果和可靠性的监测(CMM)系统 为数以百万计的糖尿病患者。IMS已经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 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) 包括极高的小型化、多个传感器的片上集成、改进的信号到 噪声(SNR)比(从而提高低血糖准确度)、传感器电容和 膜厚(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减去其信号)，以及片上温度 校准(通过确认传感器在组织中并测量 正确的温度)。提议的CMM将使用户能够受益于有用的药物(例如，二甲双胍， SGLT2抑制剂)、锻炼和无需宣布进餐的自动胰岛素给药系统， 碳水化合物计数，以及不良副作用的风险。因此，该设计具有很高的创新性。 我们已经演示了第一代血糖连续监测平台的功能 (CGM)在人类中。连续乳酸监测(CLM)可以显著提高系统的价值 以检测当前CGM系统未注意到的即将发生的乳酸酸中毒。我们有 在动物身上演示了CLM，并在实验室中以建议的规模展示了多路CGM-CLM。 我们在这项计划中的目标是开发一种能够感知葡萄糖、乳酸和温度的CMM 在间质液体(ISF)中使用小于半个芝麻种子的单个无线传感器。小的 柔性(20微米厚，带聚合物涂层)传感器可将异物反应(FBR)降至最低。 这项研究具有重要意义，因为它将使第一个能够使用小而无痛的针头的CMM系统 可在工厂校准(无手指)的情况下长时间(&gt；30天)工作的插针(26号针) 棍子)。一旦证实，该系统可以扩展到包括其他重要的分析物(例如，酮， 胰岛素、高血糖素)，而不会增加其尺寸，这是由于芯片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 (纳扎里博士、拉赫曼博士、森坎先生)，电化学传感器领域经验丰富、受人尊敬的研究员 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，JD)、商业化专家(Peter先生 规则；前MiniMed总裁、Therasense董事长和OptiScan)、临床专家(Alan博士 马库斯，医学博士，前美敦力糖尿病首席医疗官)，以及植入式生物传感器和 乳酸盐监测专家(Natalie Wisniewski博士，博士，普鲁萨公司前首席技术官)。