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使用带有等离子体纳米涂层的倾斜光纤光栅传感器对尿液蛋白变化进行高灵敏度检测。

Highly sensitive detection of urinary protein variations using tilted fiber grating sensors with plasmonic nanocoatings.

机构信息

Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communications, Institute of Photonics Technology, Jinan University, Guangzhou 510632, China.

Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.

出版信息

Biosens Bioelectron. 2016 Apr 15;78:221-228. doi: 10.1016/j.bios.2015.11.047. Epub 2015 Nov 17.

Abstract

Surface plasmon resonance (SPR) optical fiber biosensors can be used as a cost-effective and relatively simple-to-implement alternative to well established bulky prism configurations for high sensitivity biological sample measurements. The miniaturized size and remote operation ability offer them a multitude of opportunities for single-point sensing in hard-to-reach spaces, even possibly in vivo. The biosensor configuration reported in this work uses a tilted fiber Bragg grating (TFBG) in a commercial single mode fiber coated with a nanometer scale silver film. The key point is that by reducing the silver film thickness to around 20-30 nm (rather than 50 nm for optimal SPR excitation), different modes of the TFBG spectrum present very high but opposite sensitivities to refractive index (RI) changes around the TFBG. Experimental results obtained with the coated TFBG embedded inside a microfluidic channel show an amplitude sensitivity greater than 8000 dB/RIU (Refractive Index Unit) and a limit of detection of 10(-5)RIU. Using this device, the effect of different concentrations of protein in rat urine was clearly differentiated between healthy samples, nephropatic samples and samples from individuals under treatment, with a protein concentration sensitivity of 5.5 dB/(mg/ml) and a limit of detection of 1.5 × 10(-3)mg/ml. Those results show a clear relationship between protein outflow and variations in the RI of the urine samples between 1.3400 and 1.3408, pointing the way to the evaluation and development of new drugs for nephropathy treatments. The integration of TFBGs with microfluidic channels enables precise measurement control over samples with sub-microliter volumes and does not require accurate temperature control because of the elimination of the temperature cross-sensitivity inherent in TFBG devices. Integration of the TFBG with a hypodermic needle on the other hand would allow similar measurements in vivo. The proposed optical fiber/microfluidic plasmonic biosensor represents an appealing solution for rapid, low consumption and highly sensitive detection of analytes at low concentrations in medicine as well as in chemical and environmental monitoring.

摘要

表面等离子体共振(SPR)光纤生物传感器可以作为一种经济高效且相对易于实现的替代方案,替代已建立的庞大棱镜配置,用于高灵敏度生物样品测量。其小型化尺寸和远程操作能力为单点感应提供了多种机会,即使在难以到达的空间,甚至可能在体内。本工作中报告的生物传感器配置使用涂有纳米级银膜的商用单模光纤中的倾斜光纤布拉格光栅(TFBG)。关键是通过将银膜厚度降低到约 20-30nm(而不是最佳 SPR 激发所需的 50nm),TFBG 光谱的不同模式对 TFBG 周围的折射率(RI)变化表现出非常高但相反的灵敏度。将涂覆的 TFBG 嵌入微流道内获得的实验结果表明,振幅灵敏度大于 8000 dB/RIU(折射率单位),检测限为 10(-5)RIU。使用该装置,明显区分了健康样本、肾病样本和接受治疗的个体样本中不同浓度的蛋白质,蛋白质浓度灵敏度为 5.5dB/(mg/ml),检测限为 1.5×10(-3)mg/ml。这些结果表明,蛋白质流出与尿液样本 RI 之间的变化之间存在明显的关系,RI 范围为 1.3400 至 1.3408,为肾病治疗的新药评估和开发指明了方向。TFBG 与微流道的集成能够对亚微升体积的样品进行精确的测量控制,并且由于消除了 TFBG 器件固有的温度交叉灵敏度,因此不需要精确的温度控制。另一方面,将 TFBG 与皮下注射针集成在一起将允许在体内进行类似的测量。所提出的光纤/微流控等离子体生物传感器代表了一种有吸引力的解决方案,用于快速、低消耗和高灵敏度地检测医学以及化学和环境监测中低浓度的分析物。

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