Development of a miniaturized single-port automated insulin delivery system utilizing a glucose sensing catheter, ultra-concentrated insulin, and an optimized control algorithm

摘要 重要性：美国有超过500万人患有胰岛素治疗的糖尿病， 在2370亿美元的直接医疗费用中，糖尿病占了不成比例的大部分。使用 连续葡萄糖监测（CGM）已被证明可以降低HbA 1c水平，这是一种已被证明的健康预测指标 该人群的结局，当CGM与 持续皮下胰岛素输注（CSII）。CGM和胰岛素泵的最新融合 启用了第一代自动胰岛素输送（AID）系统，有望改善血糖 胰岛素治疗的糖尿病的控制。然而，当前的AID系统复杂、笨重且昂贵 因为他们需要在身体上佩戴多个设备：葡萄糖传感器，胰岛素 泵和胰岛素输送导管。我们开发了一种葡萄糖传感导管， 皮下组件的数量从两个减少到一个，显著减少了这些组件的尺寸和复杂性。 系统.我们建议在本研究中商业化的PDT可互操作传感套管组件 第2阶段SBIR将允许任何胰岛素贴片泵制造商快速将CGM直接集成到胰岛素上 输送套管，从而使贴片泵使用者的T1 D患者能够毫不费力地使用CGM 通过一个皮下注射点重要的是，该平台还将提高AID系统的可靠性 将CGM与泵控制器之间的无线通信替换为直接有线通信， 连接.由此导致的系统尺寸、复杂性和成本的降低将提高泵的采用率 使用者和使用AID的人，帮助提高依从性，降低HbA 1c水平，改善健康结果 1型糖尿病患者中。初步数据：PDT最近证明， 在葡萄糖感测的位置处，可以使用获得专利的基于氧化还原介体的感测套管。然而，在这方面， 我们还表明，在输注一剂胰岛素后立即出现稀释伪影 通过套管。我们已经表明，这种伪影是独立的胰岛素或生理盐水是输送。 在本SBIR的第1阶段，我们在猪研究中证明了该伪影与推注的大小有关。 我们进一步证明，通过使用更高浓度的胰岛素， 最终通过使用复杂的预测信号处理方法来消除。具体目标：第二阶段 在这个项目中，我们将使用第一阶段的产品来采取下一个逻辑步骤，集成我们的传感器 套管插入双功能贴片泵平台。在具体目标1中，我们将进一步描述和评估 PDT传感套管在人体研究中的准确性。在具体目标2中，我们将与商业合作 泵合作伙伴（EOFlow）开发和评估可互操作的传感套管组件（ISCA）， 设计用于快速集成到贴片泵中。ISCA将包括所需的电子、机械 组件和软件开发工具包，可快速集成到商业贴片泵中。 与OHSU的学术合作伙伴合作，我们将把伪影消除预测信号 处理算法，并将该算法移植到ISCA以用于实时操作。在具体目标3中，我们 将传感器组件集成到我们的商业合作伙伴的贴片泵中，并验证其性能， 猪研究中设计的准确性。在第二阶段结束时，我们将有一个双重功能的葡萄糖- 传感贴片泵在猪研究中得到验证，并准备进入临床研究。在第2B阶段，我们将 这些研究，并与我们的学术合作者和商业化合作伙伴合作， 将模型预测控制器应用到贴片泵中，以产生一体化的自动胰岛素输送解决方案。

ABSTRACT Significance: There are over 5 million people with insulin-treated diabetes in the United States who represent a disproportionately large share of the $237B in direct medical costs attributable to diabetes. The use of continuous glucose monitoring (CGM) has been shown to reduce HbA1c levels, a proven predictor of health outcomes within this population, with the greatest improvement achieved when CGM is coupled with continuous subcutaneous insulin infusion (CSII). The recent convergence of CGM and insulin pumps has enabled the first generation of automated insulin delivery (AID) systems, promising even better glycemic control for insulin-treated diabetes. However, current AID systems are complex, cumbersome, and expensive for the patient because they require multiple devices to be worn on the body: a glucose sensor, an insulin pump, and an insulin delivery catheter. We have developed a glucose sensing catheter that reduces the number of subcutaneous components from two to one, significantly reducing the size and complexity of these systems. The PDT interoperable sensing cannula assembly that we are proposing to commercialize in this phase 2 SBIR will allow any insulin patch pump manufacturer to rapidly integrate CGM directly on the insulin delivery cannula, thereby enabling people with T1D who are patch pump users to effortlessly utilize CGM through a single subcutaneous injection site. Importantly, this platform will also improve AID system reliability and security by replacing the wireless communication from CGM to pump controller with a direct wired connection. Resulting reductions in system size, complexity, and cost will increase adoption rates for pump user and people using AID, helping improve compliance, lower HbA1c levels, and improve health outcomes among people with type 1 diabetes. Preliminary Data: PDT has recently demonstrated that delivering insulin at the site of glucose sensing is possible using a patented redox mediator-based sensing cannula. However, we have also shown that there is a dilution artifact that occurs immediately after a dose of insulin is delivered through the cannula. We have shown that this artifact is independent of whether insulin or saline is delivered. In Phase 1 of this SBIR, we demonstrated in a swine study that this artifact is related to the size of the bolus. We further demonstrated that the artifact can be significantly reduced by using higher concentration insulin and ultimately eliminated by using sophisticated predictive signal processing methods. Specific Aims: In Phase 2 of this project, we will use the products of Phase 1 to take the next logical steps in integration of our sensing cannula into a dual function patch pump platform. In Specific Aim 1, we will further characterize and evaluate the accuracy of the PDT sensing cannula in a human study. In Specific Aim 2, we will work with a commercial pump partner (EOFlow) to develop and evaluate an interoperable sensing cannula assembly (ISCA) that is designed for rapid integration into a patch pump. The ISCA will include the required electronics, mechanical components, and a software development kit that will enable rapid integration into commercial patch pumps. Working with our academic partners at OHSU, we will transfer the artifact elimination predictive signal processing algorithm and port this algorithm to the ISCA for use in real-time operation. In Specific Aim 3, we will integrate the sensor assembly into our commercial partner’s patch pump and validate the performance and accuracy of the design in a swine study. At the conclusion of Phase 2, we will have a dual-function glucose- sensing patch pump validated in a swine study and poised to enter clinical study. In Phase 2B, we will conduct those studies, and work with our academic collaborators and commercialization partners to incorporate a model predictive controller into the patch pump to yield an all-in-one automated insulin delivery solution.