Surface-Enhanced Raman Glucose Sensor

表面增强拉曼血糖传感器

• 批准号: 7686651
• 负责人: RICHARD Palmer VAN DUYNE
• 金额: $ 26.8万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686651
• 关键词: Acute; Address; Adsorption; Algorithms; American; Anesthesia procedures; Animals; Architecture; Area; Ascorbic Acid; Behavior; Biological; Biological Neural Networks; Biological Preservation; Biosensor; Blood Vessels; Boronic Acids; Calibration; Chemistry; Chronic Disease; Class; Collection; Data; Data Analyses; Data Set; Deposition; Detection; Devices; Diabetes Mellitus; Diamond; Disease; Dose; Eye; Fiber Optics; Film; Glucose; Glycerol; Glycol; Goals; Hypoglycemia; Immunohistochemistry; Implant; Infiltration; Inflammation; Infusion procedures; Insulin; Intercellular Fluid; Invasive; Kidney; Lasers; Leukocytes; Liquid Chromatography; Liquid substance; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Methods; Modality; Modeling; Modification; Monitor; Nanosphere; Nerve; Object Attachment; Operative Surgical Procedures; Optics; Partition Coefficient; Patients; Performance; Persons; Polyethylene Glycols; Process; Proteins; Public Health; Raman Spectrum Analysis; Rattus; Reaction Time; Recovery; Research; Resistance; Sampling; Signal Transduction; Silicon Dioxide; Skin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrum Analysis; Sprague-Dawley Rats; Standards of Weights and Measures; Sterility; Surface; Surface Plasmon Resonance; Synthesis Chemistry; Techniques; Testing; Thick; Time; Tissues; Treatment Protocols; Urea; Validation; atomic layer deposition; awake; base; biomaterial compatibility; blood glucose regulation; boronic acid; carboxylate; day; design; glucose monitor; glucose sensor; implantation; improved; in vivo; liquid chromatography mass spectrometry; monolayer; nanoparticle; nanostructured; novel strategies; prevent; response; sensor; small molecule; subcutaneous; transmission process

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.

全世界许多人患有糖尿病，大约有2000万美国人和十倍。 该疾病是一种慢性疾病，需要在紧密范围内仔细调节葡萄糖水平，以便 防止涉及患者眼睛，肾脏，神经和血管的严重继发并发症。 我们小组的最新研究表明，表面增强的拉曼光谱法（SER）是 解决这个重要的公共卫生问题的新方法，该问题提供了重大希望作为衡量的手段 实时，体内葡萄糖水平。该项目一开始就设想了许多潜在的问题 AS：（1）SERS从未测量过葡萄糖； （2）时间稳定性； （3）可逆性； （4）实时 回复; （5）对蛋白质干扰的抗性； （6）干扰小分子分析物的并发症 已被证明是不存在的或已经克服了。 本文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SER作为生物流体中葡萄糖的稳健，便携式生物传感器平台相关。 旨在实现此目标的四个具体目标是：（1）合成并优化新的分区层 减少与目标分析物的光谱重叠，提高灵敏度并增加体内工作寿命； （2） 改善用于从RAW提取葡萄糖水平的化学数据分析和校准方法 信号 ; （3）为透皮SER开发光纤和自由空间激发/收集方法；和 （4）使用大鼠模型来定量未受约的，单虫的动物的葡萄糖水平，最高为5个 天。新的分区层将通过合成化学创建，以最大程度地减少光谱重叠。这 分区层的运行寿命将使用基于原子的新方法大大增加 层沉积以消除弱Ag-S或Au-S键。通过测量 使用液相色谱法和使用强大的内部拉曼标准 （钻石）。将进行透皮SERS研究以证明自由空间激光的生存能力 激发和收集。提出了初步结果，表明这是可能的。体内的sers会 使用植入的电化学传感器（最小化）和对葡萄糖的离体监测进行交叉验证 液相色谱/质谱法。