The discovery of noble metal plasmonic nanoparticles (PNPs) has introduced surface-enhanced Raman scattering (SERS) as a highly sensitive and specific bioanalytical technique with greater potential in point-of-need disease diagnosis. This Tutorial provides an overview of the principles governing a gold PNP-based biosensor design for sensitive and reliable SERS-based detection of disease biomarkers. First, we will highlight the optical transducer properties of PNPs, the principles of SERS, the benefits of SERS detection, and the modes of SERS for biomarker detection. The analytical performance (sensitivity and specificity) and the reliability (accuracy and reproducibility) of a SERS biosensor are mainly dictated by (i) the chemical and optical transducer properties of PNPs, (ii) the functional nano interface, where the interaction(s) between PNPs and target biomolecules take place, and (iii) SERS data acquisition and evaluation metrics. Maintaining a balance between SERS signal enhancement and reproducibility is critical for advancing the field deployment of SERS technologies. However, the reproducibility of SERS biosensors is often overlooked in lieu of the assay sensitivity. Consequently, next, we will discuss the systematic optimization strategies for fabricating gold PNPs as SERS substrates and designing their functional interface to design SERS biosensors with sufficient sensitivity, specificity, and reproducibility. We will highlight the choice of PNPs and their integration into biosensing platforms depending on the mode of SERS detection. Last, we will discuss the SERS data acquisition and performance evaluation as an integral part of the SERS biosensors development workflow.

中文翻译：

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用于制造基于表面增强拉曼散射 (SERS) 的生物传感的等离子体金纳米材料的设计标准

贵金属等离子体纳米粒子 (PNP) 的发现引入了表面增强拉曼散射 (SERS) 作为一种高度敏感和特异性的生物分析技术，在即时疾病诊断中具有更大的潜力。本教程概述了基于金 PNP 的生物传感器设计的原则，用于灵敏且可靠的基于 SERS 的疾病生物标志物检测。首先，我们将重点介绍 PNP 的光学传感器特性、SERS 的原理、SERS 检测的优势以及 SERS 用于生物标志物检测的模式。SERS 生物传感器的分析性能（灵敏度和特异性）和可靠性（准确性和再现性）主要取决于 (i) PNP 的化学和光学传感器特性，(ii) 功能纳米界面，PNP 和目标生物分子之间发生相互作用的地方，以及 (iii) SERS 数据采集和评估指标。在 SERS 信号增强和再现性之间保持平衡对于推进 SERS 技术的现场部署至关重要。然而，SERS 生物传感器的重现性往往被忽视，而不是检测灵敏度。因此，接下来，我们将讨论制造金 PNP 作为 SERS 底物并设计其功能界面以设计具有足够灵敏度、特异性和重现性的 SERS 生物传感器的系统优化策略。我们将根据 SERS 检测模式重点介绍 PNP 的选择及其与生物传感平台的集成。最后的，