Surface-Enhanced Raman Glucose Sensor

大约有2000万美国人患有糖尿病，是全世界糖尿病患者的十倍。 这种疾病是一种慢性疾病，需要在严格的限制内仔细调节血糖水平，以便 预防严重的继发性并发症，涉及患者的眼睛、肾脏、神经和血管。 我们小组最近的研究表明，表面增强拉曼光谱(SERS)是一种 解决这一重要公共卫生问题的新方法，提供了作为衡量手段的重要前景 实时、活体血糖水平。这个项目开始时设想的许多潜在问题，如 因为：(1)SERS从未测量过血糖；(2)时间稳定性；(3)可逆性；(4)实时 反应；(5)对蛋白质干扰的抵抗力；(6)干扰小分子分析物的并发症 已经被证明是不存在的或已经被克服了。 这里提出的研究重点是剩余的基本科学和技术挑战 与开发体内SERS作为生物体液中葡萄糖的坚固、便携式生物传感器平台有关。 为实现这一目标而设计的四个具体目标是：(1)合成和优化新的隔层， 减少与目标分析物的光谱重叠，提高灵敏度，延长体内工作寿命；(2) 改进用于从原料中提取葡萄糖水平的化学计量数据分析和校准方法 (3)开发光纤和自由空间激发/收集方法以实现经皮表面增强拉曼散射；以及 (4)使用大鼠模型来量化不受限制的、未麻醉的动物的血糖水平，最长可达5 几天。新的隔层将通过合成化学来创建，以最大限度地减少光谱重叠。这个 使用一种基于原子的新方法，隔层的工作寿命将显著增加 层沉积消除了弱的Ag-S键或Au-S键。校准将通过测量 使用高效液相色谱和稳健的内部拉曼标准确定葡萄糖分配系数 (钻石)。将进行经皮SERS研究，以证明自由空间激光的可行性 激发和收集。给出的初步结果表明，这是可能的。在体内的SERS将是 使用植入式电化学传感器(MiniMed)和体外血糖监测的交叉验证 液-质联用联用。

Approximately 20 million Americans and ten times that many persons worldwide have diabetes mellitus. This disease is a chronic disorder that requires careful regulation of glucose levels within tight limits in order to prevent severe secondary complications involving the patient's eyes, kidneys, nerves, and blood vessels. Recent research from our group has demonstrated that surface-enhanced Raman spectroscopy (SERS) is a new approach to this important public health problem that offers significant promise as a means to measure real-time, in vivo glucose levels. Many of the potential problems envisioned at the outset of this project such as: (1) glucose had never been measured by SERS; (2) temporal stability; (3) reversibility; (4) real-time response; (5) resistance to protein interference; and (6) complications from interfering small molecule analytes have been demonstrated to be non-existent or have been overcome. The research proposed herein is focused on the remaining fundamental scientific and technical challenges associated with developing in vivo SERS as robust, portable biosensor platform for glucose in biological fluids. Four specific aims to designed to achieve this goal are: (1) synthesize and optimize new partition layers that reduce spectral overlap with target analytes, increase sensitivity, and increase in vivo operating lifetime; (2) improve the chemometric data analysis and calibration methods used to extract the glucose level from the raw signal ; (3) develop both fiber optic and free-space excitation/collection approaches to transdermal SERS; and (4) use a rat model to quantify glucose levels in unrestrained, unanaesthetized animals for periods up to 5 days. New partition layers will be created through synthetic chemistry to minimize spectral overlap. The operating lifetime of the partition layer will be dramatically increased using a novel approach based on atomic layer deposition to eliminate the weak Ag-S or Au-S bond. Calibration will be improved by measuring the glucose partition coefficient using liquid chromatography and by using a robust internal Raman standard (diamond). Transdermal SERS studies will be carried out to demonstrate the viability of free-space laser excitation and collection. Preliminary results are presented indicating that this is possible. In vivo SERS will be cross-validated using an implanted electrochemical sensor (MiniMed) and ex vivo monitoring of glucose by liquid chromatography/mass spectrometry.