提出一种外泌体检测新方法，通过将表面增强拉曼散射（SERS）纳米探针固定在核酸适体（DNA）功能化水凝胶中，实现对肿瘤源性外泌体的高灵敏度光学检测。SERS纳米探针被用于识别肿瘤源性外泌体并产生指纹光学信号。SERS活性DNA功能化水凝胶（简称“SD水凝胶”）作为传感器，不仅提供了用于生物识别的三维反应位点，而且可放大SERS纳米探针的光学信号。选择性地与靶外泌体结合后，SERS纳米探针脱离SD水凝胶，导致SERS信号减弱，从而实现光学检测。通过SERS信号变化，SD水凝胶可以定量、灵敏地检测肿瘤源性外泌体，浓度检测限（LOD）约为22 μL^-1。该SD水凝胶将为临床癌症诊断提供一种新的技术手段。

由于微流控芯片具有优异的集成性和灵活的可操作性, 基于芯片上的检测方法被大量开发, 发展十分迅速。其中, 表面增强拉曼光谱(SERS)凭借其超高的灵敏度、独一无二的指纹谱和窄峰宽等特点成为一种广泛采用的检测手段。SERS微流控芯片集SERS检测技术与微流控芯片的优势于一体, 一方面为SERS检测方法的重复性和可靠性提供了一个高效平台, 另一方面推动了微流控芯片的功能拓展, 在生物分子探测、细胞捕获乃至组织模拟等领域具有广阔的应用前景。本文在简要介绍SERS的原理及其生物传感应用的基础上, 重点概述了SERS微流控芯片的构建及其在生物传感及检测中的应用, 最后探讨了该研究方向存在的问题及发展方向。

A novel drug carrier based on SiO2-coated silver nanoparticle aggregates and antitumor drug is successfully synthesized. The surface-enhanced Raman scattering (SERS) spectra of the antitumor drug in living cells are obtained. By using silver nano-aggregates as SERS substrates instead of dispersed silver particles, a great improvement of SERS signal intensity is achieved. It is found that the chemical stability of the drug carrier can also be increased with the existence of SiO2 shell. The adsorbing effect between antitumor drug 9-aminoacridine (9AA) and silver particles is investigated to optimize the SERS signal. The core/shell structure of the drug carrier is characterized by ultraviolet-visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM) pictures. The experimental results show that the drug carrier offers biocompatibility, stability, and high SERS activity, holding the potential for realizing the intracellular drug tracing.

A novel structure with high surface enhanced Raman scattering (SERS) activity and bio-specificity as a SERS-based immuno-sensor (named as Raman reporter-labeled immuno-Au aggregate) is demonstrated and employed for protein detection. In each fabrication process, the features of those aggregates are obtained and characterized by ultraviolet-visible (UV-Vis) extinction spectra, transmission electron microscopy (TEM) images, scanning electron microscopy (SEM) pictures, and SERS spectra. Experimental results indicate that proper amounts of the reporter molecules can result in the moderate aggregation morphologies of gold nanoparticles. Compared with the previously reported method using Raman reporterlabeled immuno-Au nanoparticles, more sensitive SERS-based protein detection is realized with this novel immuno-sensor.

Optical methods and MTT method are used to characterize the antiproliferation effect of antitumor drug 9-aminoacridine (9AA) with and without silver nanoparticles. Intracellular surface enhanced Raman scattering (SERS) spectra and fluorescent spectra of 9AA indicate the form of 9AA adsorbed on the surface of silver nanoparticles. Although both silver nanoparticles and antitumor drug can inhibit the growth of Hela cells, silver nanoparticles can slow down the antiproliferation effect on Hela cells at low concentration of antitumor drugs. Our experimental results suggest that silver nanoparticles may serve as slow-release drug carriers, which is important in antitumor drug delivery.