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.

项目摘要糖尿病（DM）仍然是一种无法治愈的疾病，在未来二十年中有望增加。 DM的管理主要是由胰岛素治疗介导的，胰岛素治疗取决于患者监测血液葡萄糖水平。但是，由于缺乏患者依从性，脱衣传感器不准确以及无法测试在睡眠期间，患者长期存在高血糖发作。连续的来自留置传感器的葡萄糖监测具有封闭环胰岛素输送系统的承诺。尽管传感器设计和整体准确性的显着改善，长期成功的障碍保留此类传感器的应用。这些包括需要小型化以最大程度地减少组织损伤敏感性/准确性，生物污染和异物反应（FBR）而不会丧失。改进的方法传感器功能包括传递组织修饰符以调节炎症反应。但是，迄今为止留置传感器的寿命限制为3-14天，并且将生物制剂纳入传感器很复杂制造并产生其他监管负担。因此，一种基于生物材料的方法调节FBR并改善传感器功能代表一个有吸引力的解决方案。在此应用程序中，我们提出基于块状金属玻璃（BMG）的新型葡萄糖传感器涂料的产生。 BMG是具有无定形原子结构的金属合金，结合了高腐蚀性和聚合物样加工性。具体而言，我们建议系统地评估铂或锆基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的是：1）筛选BMG库的理想材料属性，并生物反应； 2）识别BMG地形特征，能够在体内调节回应； 3）集成BMG地形特征以增强传感器功能。这样的生物保护表面可用于将几乎任何生物医学植入物免于不良生物反应，从而屏蔽任何生物医学植入物改善植入物功能和寿命。