Real-time Point of Care Insulin Monitoring Device for Improved Diabetes Managemen

用于改善糖尿病管理的实时护理点胰岛素监测装置

• 批准号: 8648542
• 负责人: Brian Scott Ferguson
• 金额: $ 22.38万
• 依托单位: APTITUDE MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648542
• 关键词: Accounting; Adult; Affinity; Artificial Pancreas; Binding; Biological; Biological Assay; Biological Neural Networks; Buffers; Caring; Cells; Charge; Child; Clinical; Cocaine; Collaborations; Complex; Data; Dependence; Detection; Development; Device or Instrument Development; Devices; Diabetes Mellitus; Diffusion; Dimensions; Dose; Doxorubicin; Drug Formulations; Drug Kinetics; Exposure to; Failure; Frequencies; Generations; Goals; Hospitals; Hour; Human; Hyperinsulinism; Hypoglycemia; In Vitro; Individual; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Kanamycin; Kinetics; Label; Liquid substance; Marketing; Measurement; Measures; Metabolism; Microfluidic Microchips; Microfluidics; Molecular Target; Monitor; Noise; Non-Insulin-Dependent Diabetes Mellitus; Outpatients; Output; Patient Self-Report; Patients; Performance; Pharmacodynamics; Phase; Physiological; Population; Prediabetes syndrome; Preparation; Process; Proteins; Publishing; Reagent; Research; Research Institute; Safety; Sampling; Signal Transduction; Simulate; Surface; System; Techniques; Technology; Testing; Therapeutic; Time; United States; Whole Blood; Work; absorption; aptamer; base; commercialization; design; diabetes management; diabetic; experience; falls; glucose monitor; glucose sensor; glycemic control; improved; in vivo; innovation; meetings; miniaturize; monitoring device; pharmacokinetic model; point of care; preclinical study; public health relevance; sensor; subcutaneous; success

DESCRIPTION (provided by applicant): In the United States, 25.8 million children and adults have diabetes and 79 million have pre-diabetes. Insulin therapy is critical in Type 1 Diabetes and now understood to be an inevitable therapeutic component for Type 2 Diabetes in order to achieve adequate glycemic control. However, none of the available commercial insulin preparations are able to simulate normal secretion. Continuous glucose monitoring and insulin pumps have enabled progress toward maintaining euglycemia. However, they cannot account for the insulin absorption variability within and between individuals, which can result in hypoglycemia and hyperinsulinemia. Real-time insulin measurement could overcome this limitation. However, despite extensive research and advancements in the design of glucose sensors, the development of an analogous insulin monitor has yet to be achieved. This is due to three critical performance requirements that an ideal insulin sensor must meet: (1) resolve rising and falling insulin concentrations at physiological time-scales and concentrations; (2) operate continuously, without batch processing or exogenous reagents (3) retain a stable quantitative signal through prolonged exposure to unprocessed biological fluids. We propose to unlock the first real-time insulin sensor, by creating a disposable microfluidic device, which overcomes the critical performance challenges. In Phase I we focus on a proof of concept device to demonstrate real-time measurement of insulin doped into human whole blood in vitro. Our aims include: (1) Create an aptamer-based electrochemical insulin probe for measurement in buffer. Here we will develop a self-reporting probe that responds to dynamic insulin concentrations in buffer. (2) Create a continuous flow diffusion filter to support sensing from complex media. We will develop a microfluidic diffusion filter to selectively permits the passage of high-diffusivity insulin from whole blood to the sensor surface while rejecting low-diffusivity proteins and cells. (3) Develop stabilized quantitative output via auto-correcting differential measurement. Here we will exploit the frequency dependence of our probe to enable a new form of differential measurement, which eliminates signal drift for sustained insulin quantification in whole blood. We have preliminary data supporting each aim and we anticipate achieving accurate measurement of doped insulin in whole blood for 10 hours. In Phase II, we will enhance the sensor performance to detect in vivo insulin levels by discovering pM affinity insulin aptamers. We will miniaturize and integrate the device with micropumps for subcutaneous measurement. In collaboration with the Sansum Diabetes Research Institute, we will perform human tests and compare real-time output to reference lab insulin assays. This work leverages our unique experience in microfluidic device development, aptamer-based real-time monitoring, and high-performance aptamer discovery, and the vast clinical expertise of our Phase II collaborators. We expect to form a product co- development partnership with leaders in the diabetes care device market for commercialization within five years.

描述(申请人提供)：在美国，2580万儿童和成人患有糖尿病，7900万人患有糖尿病前期。胰岛素治疗对1型糖尿病至关重要，现在被认为是实现适当血糖控制的2型糖尿病不可避免的治疗组成部分。然而，现有的商业胰岛素制剂都不能模拟正常的分泌。持续的血糖监测和胰岛素泵使维持正常血糖的工作取得了进展。然而，它们不能解释个体内和个体之间胰岛素吸收的可变性，这可能导致低血糖和高胰岛素血症。实时胰岛素测量可以克服这一限制。然而，尽管在葡萄糖传感器的设计方面有了广泛的研究和进步，但类似的胰岛素监测仪的开发还没有实现。这是因为理想的胰岛素传感器必须满足三个关键性能要求：(1)在生理时间尺度和浓度下分辨胰岛素浓度的上升和下降；(2)连续运行，无需批处理或外部试剂；(3)通过长期暴露在未经处理的生物液中，保持稳定的定量信号。我们建议解锁第一个实时胰岛素传感器，通过创造一个一次性微流控设备，克服关键的性能挑战。在第一阶段中，我们将重点放在一个概念验证设备上，以演示在体外实时测量人全血中掺入的胰岛素。我们的目标包括：(1)建立一种基于适配子的电化学胰岛素探针，用于缓冲液中的测量。在这里，我们将开发一种自我报告的探头，它可以响应缓冲区中动态的胰岛素浓度。(2)创建连续流扩散过滤器，以支持复杂介质的传感。我们将开发一种微流控扩散过滤器，以选择性地允许高扩散系数的通道 胰岛素从全血到传感器表面，同时拒绝低扩散系数的蛋白质和细胞。(3)通过自动校正差值测量，发展稳定的定量输出。在这里，我们将利用我们的探头的频率依赖性来实现一种新的差示测量形式，它消除了全血中持续胰岛素定量的信号漂移。我们有支持每个目标的初步数据，我们预计可以在10小时内实现全血中掺杂胰岛素的准确测量。在第二阶段，我们将通过发现PM亲和胰岛素适配子来增强传感器的性能，以检测体内的胰岛素水平。我们将把该装置微型化并与皮下测量的微泵集成在一起。与Sansum糖尿病研究所合作，我们将进行人体测试，并将实时输出的胰岛素与参考实验室的胰岛素分析进行比较。这项工作利用了我们在微流控设备开发、基于适配子的实时监测和高性能适配子发现方面的独特经验，以及我们第二阶段合作者丰富的临床专业知识。我们希望在五年内与糖尿病护理设备市场的领先者形成产品共同开发伙伴关系，实现商业化。