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

项目摘要 本项目的长期目标是开发一种低成本、用户友好、准确的葡萄糖传感解决方案 具有多传感器的可靠性，以使得能够在人工胰腺中使用闭环胰岛素输送。系统 由于尺寸小，传感器和相关电子器件非常接近， 具有低电容的小型化电极，以及薄且柔性的轮廓，导致与 周围组织和局部血管化。这可以实现自动闭环葡萄糖控制， 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性， 小尺寸和更好地与周围组织整合（详细信息可在研究策略中获得）。 IMS开发了一种新颖的、小型化的（比米粒还小）、完全无线的、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。这个装置可以感应到 葡萄糖，这归功于新颖的微电子设计和集成的片上电化学传感器。这 使用专有插入器将器械注射到皮下组织中， 将数据传输到外部可穿戴发射器，该发射器将数据中继到智能手机以实现数据可视化， 基于云的数据处理，以提供实时反馈。在加州理工学院，NIH和NSF的资助下，我们 在体外、大鼠和猪模型中证明传感器功能超过1个月。我们的结果 表明传感器非常准确（对于<210 mg/dl，MARD=6.2%，这是最重要的范围），并且可以 与目前的经皮CGM产品相比，工作时间更长（> 1个月）。而且 装置是用户可插入和可移除的， 其他无线CGM设备（例如Senseonics的eversense）要求的医生办公室。 我们在该提案中的目标是开发我们的葡萄糖传感平台的一个版本，其可用于 首次人体试验。拟议中的新微系统将适合使用一个较小的（29号）针头， 弹簧加载的插入器，以实现安全和准确的插入。它将被附加到一个小磁盘安全删除 传感器在其使用寿命后（例如> 1个月后）。该设备将使用三个芯片上的 传感器，以提高读数的可靠性。传感平台将在猪模型中进行测试， 与人体皮肤和新陈代谢相匹配。 这项研究意义重大，因为它将使同类产品中最小的（29号可插入）工厂校准， 用户可插入和可拆卸，CGM可长时间工作（>30天），提供冗余的可靠性 葡萄糖传感和快速响应，所有这些都可以实现安全和准确的闭环葡萄糖控制， 人工胰腺此外，由于半导体的设计，该系统提供了最低的商品成本 技术. 该项目团队包括来自加州理工学院的核心技术的原始发明者（Nazari博士，Rahman博士，Mr. Sencan），葡萄糖传感器技术领域经验丰富、备受尊敬的研究人员（Bill货车Antwerp），实验 外科和生物材料专家（加州大学欧文分校Jonathan Lakey博士）和商业化专家（Peter先生 MiniMed、Therasense和OptiScan的规则）。该公司正在与IVD技术公司合作，一个ISO 根据设施租赁协议，该公司是一家经认证、在林业发展局注册的生物技术公司。

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.