Bulk metallic glass nanomoulding for glucose sensors

项目摘要 糖尿病(DM)仍然是一种不治之症，在未来20年内有可能增加。 糖尿病的治疗主要是通过胰岛素治疗，这依赖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，试条传感器不准确，无法进行测试 在长时间内，如在睡眠中，患者会经历高血糖和低血糖发作。连续式 来自留置传感器的血糖监测有望建立一个闭合的胰岛素输送系统。尽管 传感器设计和总体精度的重大改进，阻碍了长期成功 这种传感器的应用仍然存在。这些措施包括需要微型化以将组织损伤降至最低 不会损失灵敏度/准确度、生物污垢和异物反应(FBR)。改进的方法 传感器的功能包括传递组织调节剂来调节炎症反应。然而，到目前为止 留置传感器的寿命被限制在3-14天，而将生物制品加入到传感器中使其复杂化。 并造成额外的监管负担。因此，以生物材料为基础的方法 对FBR进行调制，改善传感器性能是一种很有吸引力的解决方案。在此应用程序中，我们 提出了一种基于大块金属玻璃(BMG)的新型葡萄糖传感器涂层的制备方法。宝马是 具有非晶态原子结构的金属合金，它结合了高耐腐蚀性和类聚合物 加工性。具体地说，我们建议系统地评估铂或锆基BMG 为留置葡萄糖传感器开发生物保护表面的化学和几何结构。因此， 此应用程序的特定目标是：1)筛选BMG库以获得所需的材料属性和 生物学反应；2)确定在活体内能够有利调节的BMG地形图特征 响应；以及3)结合BMG地形特征以增强传感器功能。这样的生物保护 表面可以用来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 提高植入物的功能和寿命。

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.