摘要
基于表面增强拉曼散射(SERS)的免疫层析检测技术是一种前沿研究技术,主要利用纳米材料制得的SERS标志材料取代传统的胶体金,综合了SERS高通量、高灵敏度和免疫层析简便、快速的双重优势,满足了定量检测的需求。其中,高性能纳米材料是SERS免疫层析技术实现高灵敏度检测的关键,研究人员通过设计和优化纳米材料的粒径、形态、结构等制备出具有强SERS增强性能的SERS基底,以提高检测灵敏度。本文首先介绍了SERS免疫层析技术的基本原理;然后,综述了用于SERS免疫层析技术的几种SERS基底以及SERS免疫层析技术在不同检测物质中的应用;最后,讨论并展望了SERS免疫层析技术未来发展趋势。
Significance Developing an early rapid and highly sensitive diagnostic technology is of great significance to the prevention and treatment of diseases.However,current detection methods require tedious steps,long analytical time,high cost,advanced instruments,and skillful personnel,even with high sensitivity and specificity.Immunochromatographic assay(ICA)is currently recognized as the most promising method for point of care testing(POCT)due to its portability,simple operation,low cost,and short detection time.However,traditional ICA is judged by the visual detection results produced by colloidal gold nanoparticles,and can merely achieve qualitative and semiquantitative detection.To overcome the disadvantages of low sensitivity and non-quantitative detection,researchers apply PCR,fluorescent probes,and surface-enhanced Raman scattering(SERS)to immunochromatographic systems,greatly improving the sensitivity and quantitative detection properties of ICA.SERS is an excellent analytical method with high sensitivity,against photobleaching,narrow bandwidth,and multi-channel detection.SERS-ICA is the research on cutting-edge technologies and has become a research hotspot in related fields recently,which combines the advantages of SERS including high throughput and sensitivity,and ICA featuring simpleness and rapid speed.SERS immuno-tags prepared by nanomaterials are employed to replace the traditional colloidal gold nanoparticles and can provide SERS signals for quantitative detection.SERS immuno-tags are mainly composed of three parts containing noble metal nanomaterials(e.g.,gold,silver),Raman report molecules,and specific recognition elements(e.g.,antibodies,aptamer,nucleic acids).Notably,Raman report molecules are adopted to provide the characteristic Raman signals,and their SERS signal intensities will be greatly enhanced while approaching the rough surface of the noble metal nanomaterials.Additionally,the specific recognition elements are applied to specifically recognize and capture the targets from the sample solutions.Quantitative detection of SERS-ICA is achieved by collecting and analyzing the SERS signals on the test line of the strips produced by the intercepted SERS immuno-tags.Progress High-performance SERS tags play a key role in SERS-ICA detection.Many studies concentrate on developing the nanomaterials with high density"hot spots",and improving the SERS signals by constructing multi-dimensional and high-density"hot spots"on the SERS substrates.To improve the detection sensitivity,in recent years,researchers have synthesized the SERS substrates with strong SERS enhanced performances by designing and optimizing the particle sizes,morphology and structures of the nanomaterials(Figs.2-5).Raman report molecules and antibodies are successively conjugated on the SERS substrates to prepare functionalized SERS immuno-tags.The as-prepared SERS immuno-tags can specifically capture the target antigen to form the immunocomplex of tags-antigen and migrate on the ICA strips by capillary action towards the absorbent pad.In addition,the detection antibodies precoated on the test line of the ICA strips can specifically identify the target antigen and capture the immunocomplex of tags-antigen.Therefore,visual band and SERS signals can be found on the test line due to the formation of antibody-antigen-antibody sandwich composite structure.Then,the SERS signals on the test line are collected by the Raman detector,and the calibration curves of the SERS signal intensities and the corresponding concentrations of target antigen are plotted for quantitative analysis of the unknown target concentration in the sample.For improving the detection efficiency of SERS-ICA,researchers have set up multiple testing lines or testing dots on one ICA strip(Figs.6-10).Meanwhile,based on the characteristic Raman fingerprint spectra,different Raman report molecules with uncrossed characteristic Raman shifts are modified on the SERS substrates to distinguish different targets on the same sites and this feature is applied to SERS-ICA(Figs.8-9).Moreover,the as-reported integrated multi-channel immunochromatography reaction column greatly improves the multiplexing and automation detection properties of SERS-ICA(Fig.10).Conclusions and Prospects We briefly introduce the basic principles of SERS and ICA and summarize several different SERS substrates for SERS-ICA and the application of SERS-ICA in different detection fields.It is of significance for increasing the detection sensitivity of SERS-ICA to improve the antigen-capture ability of the SERS tags and SERS enhanced properties of the SERS substrates.Finally,the future development trend of SERS-ICA detection technology is prospected.
作者
刘真真
刘晓娴
孙岩松
肖瑞
Liu Zhenzhen;Liu Xiaoxian;Sun Yansong;Xiao Rui(Beijing Institute of Microbiology and Epidemiology,Academy of Military Medicine,PLA Academy of Military Sciences,Beijing 100071,China)
出处
《光学学报》
EI
CAS
CSCD
北大核心
2023年第17期65-78,共14页
Acta Optica Sinica
基金
国家重点研发计划(2021YFC2301102)
国防科技卓越青年科学基金。
关键词
表面增强拉曼散射
免疫层析
现场快速检测
多重检测
surface-enhanced Raman scattering
immunochromatographic assay
point of care testing
multiplex detection
