Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive overview of bioanalytical SERS with the main focus on the reliability issue. We first introduce the mechanism of SERS to guide the design of reliable SERS experiments with high detection sensitivity. We then introduce the current understanding of the interaction of nanomaterials with biological systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. We further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomolecules, to pathogens, to living cells, and we discuss the potential interferences from experimental design, measurement conditions, and data analysis. In the end, we give an outlook of the key challenges in bioanalytical SERS, including reproducibility, sensitivity, and spatial and time resolution.

中文翻译：

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用于生物分析的表面增强拉曼光谱：可靠性和挑战

表面增强拉曼光谱（SERS）继承了拉曼光谱上丰富的化学指纹信息，并通过等离激元增强的激发和散射获得了灵敏度。特别是，大多数拉曼峰具有较窄的宽度，适合进行多重分析，并且可以在环境和水性条件下方便地进行测量。这些优点使SERS成为研究复杂生物系统的非常有前途的技术，并且SERS在生物相关分析中引起了越来越多的兴趣。然而，在它被生物相关团体广泛接受，回答有趣的生物学问题并解决致命的临床问题之前，仍然需要解决巨大的挑战。SERS在生物分析中的应用涉及等离子体纳米材料与生物系统及其环境之间的复杂相互作用。为了从SERS数据中提取有意义的信息，可靠性成为生物分析SERS的关键问题。这篇综述提供了生物分析性SERS的全面概述，主要侧重于可靠性问题。我们首先介绍SERS的机制，以指导具有高检测灵敏度的可靠SERS实验的设计。然后，我们介绍当前对纳米材料与生物系统（主要是活细胞）相互作用的理解，以指导功能化SERS纳米粒子用于目标检测的设计。我们进一步介绍了从生物分子到病原体到活细胞的无标记（直接）和标记（间接）SERS检测的当前状态，并讨论了实验设计，测量条件和数据分析的潜在干扰。到底，