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Bulk metallic glass nanomoulding for glucose sensors

用于葡萄糖传感器的块状金属玻璃纳米成型

基本信息

批准号：
10153766
负责人：
THEMIS R KYRIAKIDES
金额：
$ 41.78万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10153766
关键词：
Adhesives Adopted Alloys Architecture Biocompatible Materials Biological Biological Assay Blood Glucose Blood Vessels Cells Cellular Assay Chemistry Clinical Collagen Corrosion Diabetes Mellitus Diffusion Disease Edema Electrodes Encapsulated Engineering Evaluation Fibroblasts Foreign Bodies Foreign-Body Giant Cells Generations Geometry Glass Glucose Health Implant Infiltration Inflammation Inflammatory Inflammatory Response Insulin Intercellular Fluid Libraries Longevity Macrophage Activation Mediating Miniaturization Modification Monitor Morphology Patient Monitoring Patients Pattern Platinum Polymers Porosity Property Proteins Reaction Resistance Series Sleep Structure Surface System Testing Tissues Vascularization Zirconium base biomaterial compatibility capsule compliance behavior cytokine design diabetes management diabetic rat experience experimental study glucose monitor glucose sensor high throughput screening implantable device improved improved functioning in vivo learning materials macrophage metallicity nanopattern nanorod nanoscale neovascularization novel release factor response screening sensor tissue injury virtual

项目摘要

Project Summary Diabetes mellitus (DM) remains an incurable disease that is poised to increase in the next two decades. Management of DM is mediated primarily by insulin therapy, which depends on patients monitoring their blood glucose levels. However, due to lack of patient compliance, inaccuracies of strip sensors, and inability to test for long periods such as during sleep, patients experience hyper- and hypo-glycemic episodes. Continuous glucose monitoring from indwelling sensors holds the promise of a closed loop insulin delivery system. Despite significant improvements in sensor design and overall accuracy, obstacles towards the long-term successful application of such sensors remain. These include the need for miniaturization to minimize tissue injury without a loss in sensitivity/ accuracy, biofouling, and the foreign body response (FBR). Approaches to improve sensor function include delivery of tissue modifiers to modulate inflammatory responses. However, to date the longevity of indwelling sensors is limited to 3-14 days and the inclusion of biologics to sensors complicates manufacturing and creates additional regulatory burdens. Therefore, a biomaterial-based approach to modulate the FBR and improve sensor function represents an attractive solution. In this application, we propose the generation of a novel glucose sensor coating based on bulk metallic glass (BMG). BMGs are metallic alloys with an amorphous atomic structure that combine high corrosion resistance and polymer-like processability. Specifically, we propose to systematically evaluate Platinum or Zirconium based BMG chemistries and geometries to develop a bio-protective surface for an indwelling glucose sensor. Accordingly, the specific aims of this application are: 1) to screen BMG libraries for desirable material properties and biological responses; 2) to identify BMG topographical features capable of favorably modulating in vivo responses; and 3) to integrate BMG topographical features to enhance sensor function. Such bio-protective surfaces could be used to shield virtually any biomedical implant from adverse biological reactions, thereby improving implant function and lifespan.

项目概要糖尿病（DM）仍然是一种无法治愈的疾病，并且在未来二十年中将会增加。糖尿病的管理主要通过胰岛素治疗来介导，这取决于患者监测他们的血液血糖水平。然而，由于缺乏患者依从性、条形传感器不准确以及无法测试在长时间内，例如在睡眠期间，患者会经历高血糖和低血糖发作。连续的留置传感器的血糖监测有望实现闭环胰岛素输送系统。尽管传感器设计和整体精度的显着改进，是长期成功的障碍此类传感器的应用仍然存在。其中包括需要小型化以尽量减少组织损伤不会损失灵敏度/准确性、生物污垢和异物反应 (FBR)。改进方法传感器功能包括递送组织修饰剂以调节炎症反应。然而，迄今为止留置传感器的使用寿命仅限于 3-14 天，并且传感器中包含生物制剂使情况变得复杂制造并造成额外的监管负担。因此，基于生物材料的方法调节 FBR 并改善传感器功能是一种有吸引力的解决方案。在这个应用程序中，我们提出了一种基于块状金属玻璃（BMG）的新型葡萄糖传感器涂层。 BMG 是具有非晶原子结构的金属合金，结合了高耐腐蚀性和类聚合物可加工性。具体来说，我们建议系统地评估铂基或锆基 BMG 化学和几何形状为留置葡萄糖传感器开发生物保护表面。因此，该应用程序的具体目标是：1) 筛选 BMG 库以获取所需的材料特性和生物反应； 2) 识别能够在体内有利调节的 BMG 拓扑特征回应； 3）集成BMG地形特征以增强传感器功能。这样的生物防护表面可用于保护几乎任何生物医学植入物免受不良生物反应的影响，从而改善种植体功能和使用寿命。