Department of Bioengineering, Stanford University School of Medicine and School of Engineering, Stanford, California 94305, USA.
Department of Mechanical Engineering, Stanford University School of Engineering, Stanford, California 94305, USA.
J Chem Phys. 2020 Jun 28;152(24):240902. doi: 10.1063/1.5142767.
In a pandemic era, rapid infectious disease diagnosis is essential. Surface-enhanced Raman spectroscopy (SERS) promises sensitive and specific diagnosis including rapid point-of-care detection and drug susceptibility testing. SERS utilizes inelastic light scattering arising from the interaction of incident photons with molecular vibrations, enhanced by orders of magnitude with resonant metallic or dielectric nanostructures. While SERS provides a spectral fingerprint of the sample, clinical translation is lagged due to challenges in consistency of spectral enhancement, complexity in spectral interpretation, insufficient specificity and sensitivity, and inefficient workflow from patient sample collection to spectral acquisition. Here, we highlight the recent, complementary advances that address these shortcomings, including (1) design of label-free SERS substrates and data processing algorithms that improve spectral signal and interpretability, essential for broad pathogen screening assays; (2) development of new capture and affinity agents, such as aptamers and polymers, critical for determining the presence or absence of particular pathogens; and (3) microfluidic and bioprinting platforms for efficient clinical sample processing. We also describe the development of low-cost, point-of-care, optical SERS hardware. Our paper focuses on SERS for viral and bacterial detection, in hopes of accelerating infectious disease diagnosis, monitoring, and vaccine development. With advances in SERS substrates, machine learning, and microfluidics and bioprinting, the specificity, sensitivity, and speed of SERS can be readily translated from laboratory bench to patient bedside, accelerating point-of-care diagnosis, personalized medicine, and precision health.
在大流行时代，快速传染病诊断至关重要。表面增强拉曼光谱（SERS）有望实现敏感和特异性诊断，包括快速即时检测和药敏试验。SERS 利用与分子振动相互作用产生的非弹性光散射，通过共振金属或介电纳米结构的数量级增强。虽然 SERS 提供了样品的光谱指纹，但由于光谱增强一致性、光谱解释复杂性、特异性和灵敏度不足以及从患者样本采集到光谱采集的工作流程效率低下等挑战，其临床转化仍存在滞后。在这里，我们重点介绍了最近的互补进展，这些进展解决了这些缺点，包括（1）设计无标记 SERS 基底和数据处理算法，可提高光谱信号和可解释性，这对于广泛的病原体筛选分析至关重要；（2）开发新的捕获和亲和试剂，如适体和聚合物，对于确定特定病原体的存在或不存在至关重要；（3）用于有效临床样本处理的微流控和生物打印平台。我们还描述了低成本、即时护理、光学 SERS 硬件的开发。我们的论文重点介绍了用于病毒和细菌检测的 SERS，希望能加速传染病诊断、监测和疫苗开发。随着 SERS 基底、机器学习以及微流控和生物打印技术的进步，SERS 的特异性、灵敏度和速度可以很容易地从实验室工作台转化为患者床边，从而加速即时护理诊断、个性化医疗和精准健康。
