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基于微腔的微流控芯片的构建,用于同时对双生物标志物进行 SERS 定量分析,以实现阿尔茨海默病的早期诊断。

Construction of a microcavity-based microfluidic chip with simultaneous SERS quantification of dual biomarkers for early diagnosis of Alzheimer's disease.

机构信息

State Key Laboratory of Bioelectronics, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096, China.

State Key Laboratory of Bioelectronics, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096, China.

出版信息

Talanta. 2023 Aug 15;261:124677. doi: 10.1016/j.talanta.2023.124677. Epub 2023 May 16.

DOI:10.1016/j.talanta.2023.124677
PMID:37201340
Abstract

Since there is no effective Alzheimer's disease (AD)-modifying therapy available currently, early analysis of AD core biomarkers has become one of great significance and common concern in clinical diagnosis. Herein, we designed an Au-plasmonic shell attached polystyrene (PS) microsphere in a microfluidic chip for simultaneous detection of Aβ1-42 and p-Tau181 protein. The corresponding Raman reporters were identified in femto gram level by ultrasensitive surface enhanced Raman spectroscopy (SERS). Both of Raman experimental data and finite-difference time-domain modeling demonstrates the synergetic coupling between PS microcavity with the optical confinement property and the localized surface plasmon resonance (LSPR) of AuNPs, so leading to highly amplified electromagnetic fields at the 'hot spot'. Moreover, the microfluidic system is designed with multiplex testing and control channels in which the AD-related dual proteins were detected quantitatively with a lower limit of 100 fg mL. Thus, the proposed microcavity-based SERS strategy initiates a new way for accurately prediction of AD in human blood samples and provides the potential application for synchronous determination of multiple analytes in general disease assays.

摘要

由于目前尚无有效的阿尔茨海默病(AD)修饰疗法,因此对 AD 核心生物标志物的早期分析已成为临床诊断中具有重要意义和普遍关注的问题之一。在此,我们设计了一种在微流控芯片上附着金等离子体壳的聚苯乙烯(PS)微球,用于同时检测 Aβ1-42 和 p-Tau181 蛋白。通过超灵敏表面增强拉曼光谱(SERS),在皮克克级水平上鉴定出相应的拉曼报告分子。拉曼实验数据和有限差分时间域建模都表明 PS 微腔与光学限制特性和 AuNPs 的局域表面等离子体共振(LSPR)之间存在协同耦合,从而在“热点”处产生高度放大的电磁场。此外,该微流控系统设计具有多重测试和控制通道,可定量检测与 AD 相关的两种蛋白质,其检测下限为 100 fg mL。因此,基于微腔的 SERS 策略为准确预测人血液样本中的 AD 开辟了新途径,并为一般疾病分析中同步测定多种分析物提供了潜在的应用。

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