MINIMALLY INVASIVE IN VIVO GLUCOSE MONITORING

定期监测血糖对糖尿病患者是必不可少的，并可能 将波动和/或高波动对健康的长期影响降至最低 血糖水平。目前监测血糖的方法有 不方便，需要采集血液样本，然后进行酶 血糖水平的测定。我们的目标是开发这项技术 需要一种低成本和便携式的光学血糖传感器。我们提出了一个 主要是无创监测血糖的方法，基于 植入型葡萄糖的透皮光学荧光测量 传感元件。虽然这种传感器可以显示组织葡萄糖，但它是 已知组织血糖与血糖之间只有一段时间 延迟。建议的方法利用了最近在 基于荧光寿命的传感，它能够实现定量 在散射和/或吸收介质中的测量。为了换取 血糖水平在寿命中的变化，我们建议使用 荧光共振能量转移现象，可以检测到 荧光供体标记的葡萄糖结合之间亲和力的变化 蛋白质和受体标记的葡萄糖类似物，如葡聚糖聚合物。 这允许在不需要任何消耗性试剂的情况下进行葡萄糖检测。 为了提供对血糖水平的实际监测， 他激发和检测到的荧光是必要的 仪器仪表。为此，我们建议发展葡萄糖测定法。 具有能够实现简单器械的供体-受体对。我们将使用 它不仅显示出长寿命的发光， 但也可以在红光区域的较长波长处被激发 频谱。这种方法的优点是人类皮肤是半透明的。 闯红灯。使用这种方法，这些探测器可以用一种 廉价的红色发光二极管激光器。 初步数据证明了该方法的可行性和实用性。 通过合理的皮肤厚度测量荧光衰减时间。 该项目的另一个组成部分将包括明智的选择 和葡萄糖渗透性植入材料及其测试 生物兼容性。我们将使用患糖尿病的BB/Wistar大鼠作为 测试我们传感器的系统。初步测试将在#年进行 生物反应器，以最大限度地减少使用。 这个项目的需求是复杂的和跨学科的。因此， 我们的团队包括生物、化学和电气工程方面的专家， 化学与兽医。

Regular monitoring of blood glucose is essential for diabetics and may minimize the long term health consequences of fluctuations and/or high levels of blood glucose. Present methods to monitor blood glucose are inconvenient, and require taking a blood sample followed by enzymatic determination of the glucose level. Our goal is to develop the technology needed for a low cost and portable optical glucose sensor. We propose a primarily non-invasive method for monitoring blood glucose, based on trans-dermal optical fluorescence measurement of an implantable glucose sensing element. While this sensor would reveal tissue glucose, it is known that tissue glucose follows blood glucose with only a modest time delay. The proposed method takes advantage of recent developments in fluorescence lifetime-based sensing, which enables quantitative measurements in scattering and/or absorbing media. In order to transduce the glucose level to a change in lifetime, we propose to use the phenomenon of fluorescence resonance energy transfer, which can detect changes in proximity between a fluorescent donor-labeled glucose binding protein and an acceptor-labeled glucose analog such as a dextran polymer. This permits glucose sensing without requiring any consumable reagents. In order to provide practical monitoring of the glucose level, it is necessary that the fluorescence he excited and detected with a simple instrumentation. Toward this end, we propose to develop the glucose assay with donor-acceptor pairs which enable simple instrumentation. We will use osmium-ligand complexes which not only display long-lived luminescence, but also can be excited at longer wavelengths in the red region of the spectrum. The advantage of this approach is that human skin is translucent to red light. With this approach, these probes can he excited with an inexpensive red-emitting diode laser. Preliminary data have demonstrated the possibility and practicality of measuring fluorescence decay times through reasonable thicknesses of skin. An additional component of this project will include judicious selection and testing of glucose permeable implant materials and their biocompatibility. We will use BB/Wistar rats which develop diabetes as test systems for our sensors. Preliminary tests will be conducted in bioreactors to minimize maximal use. The demands of this project are complex and interdisciplinary. Therefore, our team includes specialists in Bio, Chemical and Electrical Engineering, Chemistry and Veterinary Medicine.