Nanoparticle, Raman-based Fiber-optic Glucose Sensor

描述（由申请人提供）： NIH估计约有1700万美国人患有糖尿病，其中约1/10为1型糖尿病，其余被分类为2型、妊娠期糖尿病和其他糖尿病。该疾病的特征可以是涉及眼睛、肾脏、神经和血管的长期并发症，这些并发症是常见的，但受限于以接近正常的糖化血红蛋白为特征的严格血糖控制。提出的研究的目标是证明基于表面增强拉曼光谱（Sers）的传感器可以用于测量体内葡萄糖水平，具有足够的精度，用于胰岛素输送的反馈控制。我们建议开发基于光纤的传感器，在体外和体内测试传感器，并在体内获得足够的数据，以指定用于人体试验的系统要求。 在葡萄糖感测领域中的许多先前工作集中于测量血糖水平的微创手段;这样的系统将允许患者避免重复的疼痛的手指针刺，但是葡萄糖控制将仍然基于患者依赖的反馈控制。自1999年中期以来，植入式电化学传感器已获得FDA批准，但它们必须由医生植入，并且它们在实时葡萄糖控制中的使用受到限制。我们的初步Sers工作，基于贵金属纳米粒子已经显示了潜在的准确性和精度的Sers传感器葡萄糖。我们建议这种Sers传感器的高级版本可以通过皮肤进入皮下空间，以类似于放置基于胰岛素泵的导管的方式，每3天更换一次，这是胰岛素泵导管的当前标准。基于纳米颗粒的Sers系统提供了葡萄糖浓度的直接测量，可以连续监测葡萄糖水平，不基于消耗品（例如酶或底物），并且像所有基于拉曼的分析一样，对葡萄糖是特异性的，并且对混淆分析物相对不敏感。我们设想使用这些传感器通过使用葡萄糖的连续测量来关闭反馈回路以控制胰岛素水平，从而使患者免于重复测量、碳水化合物计数和胰岛素给药问题。

DESCRIPTION (provided by applicant): NIH estimates approximately 17 million Americans have diabetes mellitus, with approximately 1/10 of these being type 1 and the remaining being classified as type 2, gestational, and other. The disease can be characterized by long-term complications involving eyes, kidneys, nerves, and blood vessels are common but are limited with tight glycemic control characterized by near-normal glycosylated hemoglobin. The goal of the proposed research is to prove that a sensor based on Surface Enhanced Raman Spectroscopy (SERS) can be used to measure glucose levels in vivo with sufficient accuracy for feedback control of insulin delivery. We propose to develop the fiber-optic-based sensor, test the sensor in vitro and in vivo, and acquire sufficient data in vivo to specify the system requirements for use in human trials. Much of the previous work in the field of glucose sensing has focused on minimally invasive means of measuring blood glucose levels; such systems will allow patients to avoid repeated painful finger-pricks but glucose control would still be based on patient-dependant feedback control. Implanted electrochemical sensors have been FDA-cleared since mid-1999, but they must be physician implanted and their use in real-time glucose control has been limited. Our preliminary SERS work, based on noble metal nanoparticles has shown the potential accuracy and precision of a SERS sensor for glucose. We propose that an advanced version of this SERS sensor could be passed through the skin into the subcutaneous space, in a manner similar to the placement of insulin-pump-based catheters, and replaced every 3 days, which is the current norm for insulin-pump catheters. The nanoparticle-based SERS system provides a direct measure of glucose concentration, can monitor glucose levels continuously, is not based upon consumables (e.g. enzymes or substrates), and like all Raman-based analysis is specific to glucose and relatively insensitive to confounding analytes. We envision using these sensors to close the feedback loop by using the continuous measurement of glucose to control insulin levels, thus freeing the patient of repeated measurements, carbohydrate-counting, and insulin-dosing problems.