Nanoparticle, Raman-based Fiber-optic Glucose Sensor

描述(由申请人提供)： NIH估计大约有1700万美国人患有糖尿病，其中约1/10是1型糖尿病，其余的被归类为2型糖尿病、妊娠期糖尿病和其他糖尿病。这种疾病的特点是涉及眼睛、肾脏、神经和血管的长期并发症是常见的，但仅限于严格的血糖控制，特征是糖化血红蛋白接近正常。这项研究的目的是证明基于表面增强拉曼光谱(SERS)的传感器可以用来测量体内的血糖水平，并具有足够的精度来反馈控制胰岛素的给药。我们建议开发基于光纤的传感器，在体外和体内测试该传感器，并在体内获得足够的数据，以明确用于人体试验的系统要求。 以前在血糖传感领域的大部分工作都集中在测量血糖水平的微创方法上；这样的系统将允许患者避免反复疼痛的手指刺痛，但血糖控制仍将基于患者依赖的反馈控制。自1999年年中以来，植入的电化学传感器已经通过了FDA的审批，但它们必须由医生植入，而且它们在实时血糖控制中的使用受到了限制。我们基于贵金属纳米颗粒的SERS初步工作显示了葡萄糖SERS传感器的潜在准确性和精密度。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，方式类似于放置基于胰岛素泵的导管，并每3天更换一次，这是目前胰岛素泵导管的标准。基于纳米颗粒的SERS系统提供了葡萄糖浓度的直接测量，可以连续监测血糖水平，不基于消耗品(例如酶或底物)，并且像所有基于拉曼的分析是特定于葡萄糖的，对混杂分析物相对不敏感。我们设想使用这些传感器通过连续测量血糖来控制胰岛素水平，从而关闭反馈回路，从而使患者摆脱重复测量、碳水化合物计数和胰岛素剂量的问题。

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.