Su Jiabin, Chen Kaixin, Zhou Ping, Li Nan
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Molecules. 2025 May 16;30(10):2188. doi: 10.3390/molecules30102188.
Due to its unique molecular fingerprinting capability and multiplex detection advantages, surface-enhanced Raman scattering (SERS) has shown great application potential in the field of biological analysis. However, the weak signal intensity and large background interference significantly limited the application of SERS in biosensing and bioimaging. Loading a large amount of Raman molecules with signal in the silent region on the hotspots of the electromagnetic field of the SERS substrate can effectively avoid severe background noise signals and significantly improve the signal intensity, making the sensitivity and specificity of SERS detection remarkably improved. To achieve this goal, a new SERS signal-amplification strategy is herein reported for background-free detection of Cu by using Raman-silent probes loaded on cabbage-like gold microparticles (AuMPs) with high enhancement capabilities and single-particle detection feasibility. In this work, carboxyl-modified AuMPs were used to enable Cu adsorption via electrostatic interactions, followed by ferricyanide coordination with Cu to introduce cyano groups, therefore generating a stable SERS signal with nearly zero background signals owing to the Raman-silent fingerprint of cyano at 2137 cm. Based on the signal intensity of cyano groups correlated with Cu concentration resulting from the specific coordination between Cu and cyanide, a novel SERS method for Cu detection with high sensitivity and selectivity is proposed. It is noted that benefiting from per ferricyanide possessing six cyano groups, the established method with the advantage of signal amplification can significantly enhance the sensing sensitivity beyond conventional approaches. Experimental results demonstrated this SERS sensor possesses significant merits towards the determination of Cu in terms of high selectivity, broad linear range from 1 nM to 1 mM, and low limit of detection (0.1 nM) superior to other reported colorimetric, fluorescence, and electrochemical methods. Moreover, algorithm data processing for optimization of SERS original data was further used to improve the SERS signal reliability. As the proof-of-concept demonstrations, this work paves the way for improving SERS sensing capability through the silent-range fingerprint and signal amplification strategy, and reveals SERS as an effective tool for trace detection in complex biological and environmental matrices.
由于其独特的分子指纹识别能力和多重检测优势，表面增强拉曼散射（SERS）在生物分析领域显示出巨大的应用潜力。然而，微弱的信号强度和较大的背景干扰显著限制了SERS在生物传感和生物成像中的应用。在SERS基底的电磁场热点上加载大量处于沉默区域的带信号拉曼分子，可以有效避免严重的背景噪声信号，并显著提高信号强度，从而使SERS检测的灵敏度和特异性得到显著提高。为实现这一目标，本文报道了一种新的SERS信号放大策略，用于通过负载在具有高增强能力和单颗粒检测可行性的白菜状金微粒（AuMPs）上的拉曼沉默探针进行无背景检测铜。在这项工作中，羧基修饰的AuMPs用于通过静电相互作用实现铜的吸附，随后铁氰化物与铜配位引入氰基，因此由于氰基在2137 cm处的拉曼沉默指纹而产生具有几乎零背景信号的稳定SERS信号。基于铜与氰化物之间的特定配位导致氰基信号强度与铜浓度相关，提出了一种具有高灵敏度和选择性的新型铜检测SERS方法。值得注意的是，得益于每个铁氰化物含有六个氰基，所建立的具有信号放大优势的方法可以显著提高传感灵敏度，超越传统方法。实验结果表明，该SERS传感器在测定铜方面具有显著优点，具有高选择性、1 nM至1 mM的宽线性范围以及优于其他报道的比色、荧光和电化学方法的低检测限（0.1 nM）。此外，进一步使用算法数据处理来优化SERS原始数据，以提高SERS信号的可靠性。作为概念验证演示，这项工作为通过沉默范围指纹和信号放大策略提高SERS传感能力铺平了道路，并揭示了SERS作为复杂生物和环境基质中痕量检测的有效工具。
