Toward Point-of-Care Drug Testing: A New Paradigm for On-Chip Chromatography Coupled with Surface-Enhanced Raman Scattering

迈向即时药物测试：片上色谱与表面增强拉曼散射相结合的新范例

• 批准号: 9298363
• 负责人: Alan X Wang
• 金额: $ 20.64万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9298363
• 关键词: Adsorption; Algae; Allergic; Ammonia; Bedside Testings; Binding; Biological; Biological Assay; Biological Markers; Blood; Caliber; Calorimetry; Care Technology Points; Chemistry; Chromatography; Clinical; Cocaine; Complex; Consumption; Coupled; Crime; Crystallization; Deposition; Detection; Diatomaceous Earth; Diatoms; Drug abuse; Ethanol; Film; Food Safety; Fossils; Gas Chromatography; Geology; Glass; Goals; Gold; Growth; High Pressure Liquid Chromatography; Hybrids; Illicit Drugs; In Situ; Investigation; Iodine; Label; Law Enforcement; Link; Liquid substance; Marijuana; Marijuana Abuse; Mass Spectrum Analysis; Measures; Methods; Microfluidics; Monitor; Morphology; Nanostructures; Performance; Pharmaceutical Preparations; Phase; Planet Earth; Plasma; Preparation; Process; Production; Property; Proteins; Public Health; Raman Spectrum Analysis; Reagent; Research; Saliva; Sampling; Signal Transduction; Site; Societies; Solvents; Specificity; Structure; Surface; Surface Properties; Techniques; Technology; Testing; Tetrahydrocannabinol; Thick; Thin Layer Chromatography; Thinness; Time; Urine; Variant; Violence; Water; base; clinical Diagnosis; cost; cost effective; density; drug testing; ethyl acetate; hydrophilicity; illicit drug use; improved; metallicity; monolayer; n-hexane; nanoparticle; nanopore; nanostructured; photonics; plasmonics; point of care; portability; screening; sensor; silochrome; small molecule; success; tool; water quality

Toward Point-of-Care Drug Testing: A New Paradigm for On-Chip Chromatography Coupled with Surface-Enhanced Raman Scattering PROJECT SUMMARY In principle, surface enhanced Raman spectroscopy (SERS) can provide unique identification to a target analyte, especially small molecules such as illicit drugs. In practice, however, this is not always true for real- world samples due to various forms of interference such as nonspecific binding from large biomolecules (proteins, DNAs, etc.) in complex biological samples to the surface of metallic nanoparticles (NPs). Therefore, a selective (e.g., assay) or separation (e.g., chromatography) process with certain specificity is needed to transform existing SERS technique from a lab analysis tool into clinical usage. One urgent need for such on- chip sensing technology is point-of-care (POC) drug testing due to the alarming spread in drug abuse, fuelled by the production of inexpensive, easy-to-manufacture drug variants. Existing testing methods, including gas chromatography with mass spectrometry (GC/MS) and high-performance liquid chromatography (HPLC), demand tedious sample preparation with expensive reagents and substantive operator expertise, and are ill- suited to clinical and law enforcement settings for POC testing. Diatomaceous earth, also known as diatomite, consists of fossilized remains of diatoms, a type of hard-shelled algae. As a type of abundant and cost-effective natural photonic biosilica from geological deposits, it has a variety of unique properties including highly porous micro- and nano-structures, excellent adsorption capacity, rich surface chemistry, and unique micro-fluidic properties. The objective of this R21 project is to develop a new on-chip chromatography technology coupled with SERS sensing using diatomaceous earth thin film, which can provide a portable, cost-effective solution to detect various illicit drugs in complex biological fluidic samples. Particularly in this project, we will apply this lab-on-chip technology for POC testing of cocaine and Marijuana. Briefly, we will spin coat ultra-thin (eventually down to monolayer around 5μm) diatomaceous earth on regular glass substrates, and integrate high-density plasmonic NPs through in-situ synthesis. This hybrid photonic-plasmonic nanostructured thin film will act simultaneously as a thin layer chromatography (TLC) to separate drug molecules from the complex biofluid and ultra-sensitive SERS substrates to probe the signature Raman peaks. Through the combination with commercially available portable Raman spectrometers, our diatomite TLC-SERS technology will enable rapid, multiplex POC sensing with high specificity. Compared with existing TLC-SERS methods based on silica gel plates, we expect our technology to achieve >100× enhanced sensitivity (down to <1ppm) due to the photonic crystal effect from diatom frustules and the ultra-small thickness of the multi-scale porous structure. Last but not the least, the wide availability and low cost (<$1/chip) of the multifunctional TLC-SERS substrates are perfectly suitable for POC drug testing of cocaine, marijuana, and other illicit drugs from urine, saliva and blood. We must point out that such TLC-SERS sensors can be readily applied for label-free sensing for many other applications such as food safety, water quality monitoring, and allergic biomarker detection.

迈向保健药物测试：用于片上色谱的新范式耦合 具有表面增强的拉曼散射 项目摘要 原则上，表面增强的拉曼光谱法（SER）可以为目标提供唯一的识别 分析物，尤其是小分子，例如非法药物。但是，在实践中，对于现实而言，这并不总是如此 世界样本由于各种形式的干扰，例如来自大型生物分子的非特异性结合 （蛋白质，DNA等）在具有金属纳米颗粒（NP）表面的复杂生物样品中。所以， 需要具有一定特异性的选择性（例如，测定）或分离（例如色谱）过程 将现有的SER技术从实验室分析工具转换为临床用法。迫切需要这样的on- 芯片传感技术是由于药物滥用的惊人蔓延而引起的，是护理点（POC）药物测试 通过生产廉价，易于制造的药物变体。现有的测试方法，包括气体 质谱法（GC/MS）和高性能液相色谱（HPLC）的色谱法， 需要繁琐的样品制备，并具有昂贵的试剂和实体操作员专业知识，并且是不良的 适合用于POC测试的临床和执法环境。 硅藻土，也称为硅藻土，由化石剩余的硅藻组成，一种硬壳 藻类。作为一种地质沉积物的一种绝对和成本效益的天然光子生物硅酸盐，它具有 各种独特的特性，包括高度多孔的微型和纳米结构，出色的吸附能力， 丰富的表面化学和独特的微富特性。该R21项目的目的是开发 新的片上色谱技术以及使用硅藻土薄膜的SERS感测 它可以提供一种便携式，具有成本效益的解决方案，以检测复杂生物流体中的各种非法药物 样品。尤其是在这个项目中，我们将应用这种实验室技术来用于可卡因和可卡因的POC测试 大麻。简而 在常规玻璃基板上，并通过原位合成整合了高密度的血浆NP。这个混合动力 光子质量纳米结构薄膜将同时用作薄层色谱（TLC） 与复合物生物流体和超敏感的SERS底物分开的药物分子以探测特征 拉曼峰。通过与市售的便携式拉曼光谱仪的结合，我们 硅藻土TLC-SERS技术将具有高特异性的快速，多个POC传感。与 现有的TLC-SERS方法基于硅胶板，我们希望我们的技术实现> 100×增强 由于硅藻冻结和超小型的光子晶体效应，灵敏度（降至<1ppm） 多尺度多孔结构的厚度。最后但并非最不重要的是，广泛的可用性和低成本 （<$ 1/芯片）多功能TLC-SERS底物非常适合可卡因的POC药物测试， 大麻，以及尿液，唾液和血液中的其他非法药物。我们必须指出这样的TLC-SERS传感器 可以轻松地用于用于许多其他应用的无标签感应，例如食品安全，水质 监测和过敏生物标志物检测。