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年内有增加的趋势。 糖尿病的治疗主要是通过胰岛素治疗，这取决于患者监测他们的血液 葡萄糖水平然而，由于缺乏患者依从性，条带传感器不准确，以及无法测试 对于长时间，例如在睡眠期间，患者经历高血糖和低血糖发作。连续 来自留置传感器的葡萄糖监测具有闭环胰岛素输送系统的前景。尽管 传感器设计和整体精度的显著改进，长期成功的障碍 这种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 而不会损失灵敏度/准确度、生物污染和异物反应（FBR）。方法以改善 传感器功能包括递送组织改性剂以调节炎症反应。然而，迄今为止， 留置传感器的寿命限于3-14天， 制造业，并产生额外的监管负担。因此，基于生物材料的方法， 调制FBR和改善传感器功能代表了一种有吸引力的解决方案。在本申请中，我们 提出了一种基于块体金属玻璃（BMG）的新型葡萄糖传感器涂层的产生。BMG是 具有无定形原子结构的金属合金，其结合了联合收割机的高耐腐蚀性和聚合物状 加工性能具体而言，我们建议系统地评估铂或锆基BMG 化学性质和几何形状来开发用于留置葡萄糖传感器的生物保护表面。因此，委员会认为， 本申请的具体目的是：1）筛选BMG文库的所需材料性质， 生物学反应; 2）鉴定能够在体内有利地调节的BMG地形特征 响应;和3）整合BMG地形特征，以增强传感器功能。这种生物保护 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， 改善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.