An accurate, fast, and miniaturized glucose sensor for closed-loop diabetes management

用于闭环糖尿病管理的准确、快速、小型葡萄糖传感器

• 批准号: 9898653
• 负责人: William Van Antwerp
• 金额: $ 78.69万
• 依托单位: INTEGRATED MEDICAL SENSORS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898653
• 关键词: Adoption; Affect; Agreement; Animal Testing; Animals; Artificial Pancreas; Biocompatible Materials; Biotechnology; Blood; Businesses; Calibration; Carbohydrates; Cellular Phone; Chronic; Data; Data Analyses; Development; Devices; Diabetes Mellitus; Disease; Electric Capacitance; Electronics; Emergency department visit; Engineering; Environment; Excision; Family suidae; Feedback; Foreign Bodies; Foreign-Body Reaction; Funding; Geometry; Glucose; Goals; Grain; Health; Health Professional; Human; Hypoglycemia; Implant; In Vitro; Infection; Insulin; Insulin Infusion Systems; Insurance Coverage; Kinetics; Longevity; Measurement; Measures; Metabolism; Microelectrodes; Modeling; Morbidity - disease rate; Needles; Noise; Operative Surgical Procedures; Patients; Phase; Population; Pump; Rattus; Reaction Time; Reader; Reading; Reporting; Research; Research Personnel; Rice; Safety; Seasons; Semiconductors; Site; Skin; Sleep; Small Business Innovation Research Grant; Speed; Subcutaneous Tissue; Surveys; System; Technology; Testing; Thinness; Time; Tissues; Training; United States National Institutes of Health; Vascularization; Wireless Technology; Work; blood glucose regulation; cloud based; commercialization; cost; data visualization; design; diabetes management; diabetic; experience; first-in-human; flexibility; glucose monitor; glucose sensor; glycemic control; improved; innovation; irritation; microsystems; millimeter; miniaturize; monitoring device; mortality; novel; quality assurance; response; sensor; sensor technology; smart watch; subcutaneous; success; user-friendly

PROJECT SUMMARY The long term ​goal of this project is to develop a low-cost, user-friendly, and accurate glucose sensing solution with multisensor reliability to enable the use of closed-loop insulin delivery in an artificial pancreas. The system demonstrates fast sensor kinetics owing to small size, close proximity of sensor and related electronics, miniaturized electrodes with low capacitance, and thin and flexible profile leading to better integration with the surrounding tissue and local vascularization. This can enable automatic closed-loop glucose control without meal announcements and carbohydrate counting. The system also has excellent hypoglycemia accuracy due to small size and better integration with surrounding tissue (details available in research strategy). IMS has developed a novel, miniaturized (smaller than rice grain), completely wireless, and extremely low-cost glucose sensor that consists solely of a single semiconductor device (microsystem). This device can sense glucose owing to a novel microelectronics design and an integrated on-chip electrochemical sensor. This device is injected in subcutaneous tissue using a proprietary inserter and wirelessly communicates the glucose data to an external wearable transmitter which relays it to a smartphone to enable data visualization and cloud-based data handling to provide real-time feedback. With help of Caltech, NIH, and NSF funding, we have demonstrated sensor functionality in-vitro, in rats, and ​in porcine model for more than 1 month​. Our results indicate the sensor is very accurate (MARD=6.2% for <210 mg/dl which is the most important range), and can work for longer time (> 1 month) when compared to current transcutaneous CGM products. Moreover, the device is user-insertable and removable and hence eliminates the requirement of surgical procedures at doctor’s office as required by other wireless CGM devices (e.g. eversense by Senseonics). Our ​objective in this proposal is to develop a version of our glucose sensing platform that ​can be used for First-In-Human testing​. The proposed new microsystem will fit in a smaller (29 gauge) needle using a spring-loaded inserter to enable safe and accurate insertion. It will be attached to a small disk for safe removal of the sensor after its lifetime (e.g. after > 1 month). The device will measure glucose using ​three on-chip sensors to ​increase the reliability of the readout. The sensing platform will be tested in porcine model as it matches well with human skin and metabolism. This research is ​significant as it will enable the smallest in class (29 gauge insertable) factory-calibrated, user-insertable and removable, CGM that can work for a long time (>30 days), provide reliability of redundant glucose sensing, and fast response that can all enable safe and accurate closed-loop glucose control in an artificial pancreas. Also, the system offers lowest cost of goods by design owing to the semiconductor technology. The project ​team ​includes original inventors of the core technology from Caltech (Dr. Nazari, Dr. Rahman, Mr. Sencan), seasoned and respected researcher in Glucose sensor technology (Bill Van Antwerp), experimental surgery and biomaterials expert (Dr. Jonathan Lakey of UC Irvine) and commercialization expert (Mr. Peter Rule from MiniMed, Therasense, and OptiScan). The company is working within IVD Technologies Inc., an ISO certified, FDA registered biotechnology company under a facilities rental agreement.

项目概要 该项目的长期目标是开发一种低成本、用户友好且准确的葡萄糖传感解决方案 具有多传感器可靠性，可在人工胰腺中使用闭环胰岛素输送。系统 由于传感器和相关电子设备尺寸小、距离近，因此展示了快速传感器动力学， 具有低电容、薄而灵活的外形的微型电极，可以更好地与 周围组织和局部血管化。这可以实现自动闭环葡萄糖控制，而无需 膳食通知和碳水化合物计数。该系统还具有出色的低血糖准确度 尺寸小并与周围组织更好地融合（详细信息请参阅研究策略）。 IMS开发了一种新型、小型化（比米粒还小）、完全无线、成本极低的 仅由单个半导体器件（微系统）组成的葡萄糖传感器。该设备可以感应 葡萄糖得益于新颖的微电子设计和集成的片上电化学传感器。这 使用专有的插入器将设备注射到皮下组织中，并无线传输葡萄糖 将数据传输到外部可穿戴发射器，该发射器将其转发到智能手机以实现数据可视化和 基于云的数据处理提供实时反馈。在加州理工学院、美国国立卫生研究院和美国国家科学基金会资助的帮助下，我们 在体外、大鼠和猪模型中展示了传感器功能超过 1 个月​。我们的成果 表明传感器非常准确（对于 <210 mg/dl，这是最重要的范围，MARD=6.2%），并且可以 与目前的经皮 CGM 产品相比，工作时间更长（> 1 个月）。此外， 该装置是用户可插入和可拆卸的，因此无需在现场进行外科手术 其他无线 CGM 设备（例如 Senseonics 的eversense）所要求的医生办公室。 我们在此提案中的目标是开发一个版本的葡萄糖传感平台，可用于 首次人体测试​。拟议的新微系统将使用一个更小的（29号）针头 弹簧加载插入器可实现安全、准确的插入。它将附加到一个小磁盘上以便安全删除 传感器在其使用寿命结束后（例如，> 1 个月后）。该设备将使用三个片上测量葡萄糖 传感器以提高读数的可靠性。该传感平台将在猪模型中进行测试，因为它 与人体皮肤和新陈代谢良好契合。 这项研究意义重大，因为它将实现同类中最小的（29 规格可插入）工厂校准， 用户可插拔，可长期工作（>30天）的CGM，提供冗余的可靠性 葡萄糖传感和快速响应都可以在一个系统中实现安全、准确的闭环葡萄糖控制 人工胰腺。此外，由于采用了半导体技术，该系统在设计上提供了最低的商品成本 技术。 项目团队​包括加州理工学院核心技术的原始发明人（Nazari 博士、Rahman 博士、Rahman 先生）。 Sencan），葡萄糖传感器技术领域经验丰富且受人尊敬的研究员（Bill Van Antwerp），实验 手术和生物材料专家（加州大学欧文分校的 Jonathan Lakey 博士）和商业化专家（Peter 先生） 来自 MiniMed、Therasense 和 OptiScan 的规则）。该公司隶属于 IVD Technologies Inc.（一家 ISO） 根据设施租赁协议，经过 FDA 认证、注册的生物技术公司。