Application of Single-particle Light Scattering Microscopic Technique in Biochemical and Medicine Analysis
  
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KeyWord:plasmonic nanoparticles  dark-field imaging  single particle spectroscopy  counting method  RGB color analysis
  
AuthorInstitution
CHENG Ru,LI Meng-xiao,HUANG Cheng-zhi,WANG Jian 1.Key Laboratory of Luminescence Analysis and Molecular SensingSouthwest University,Ministry of Education,College of Pharmaceutical Sciences,Southwest University,Chongqing,China;2.Key Laboratory of Luminescent and Real-Time Analytical SystemSouthwest University,Chongqing Science and Technology Bureau,College of Chemistry and Chemical Engineering,Southwest University,Chongqing,China
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Abstract:
      Plasmonic nanoparticles(PNPs) have been widely used in the fields of biochemical sensing,bioimaging,disease diagnosis,cancer therapy and materials science,etc due to their advantages of small size,easy surface modification,good biocompatibility and low toxicity.The light-scattering optical properties of plasmonic nanoparticles could be controllably adjusted by tuning their size,composition,morphology and microenvironment,which could be developed for biochemical and pharmaceutical analysis.In addition,with the help of unique local surface plasmon resonance(LSPR) characteristics of plasmonic nanoparticles,a single-particle light scattering microscopy equiped with high spatial resolution and sensitivity could be used to obtain real-time image at a single particle level.Then,a variety of microscopic imaging analysis methods have been developed according to the signal variation resulting from changes of the size,composition,morphology,microenvironment or coupling,which could be mainly classified into four kinds of methods,including wavelength shift of scattering spectrum,change of single-particle scattering intensity,high-throughput RGB analysis and counting method.The method based on the change of wavelength shift of nanoparticles LSPR scattering spectra is accurate and sensitive,but it requires an expensive single-particle scattering spectrophotometer and a complex operation.The method based on the change of scattering intensity is simple and feasible,but it is easily affected by various factors such as the nanoparticles size and exposure time.High-throughput RGB analysis method has high accuracy and low cost,but it is not applicable for the analysis of single particle whose color change is not obvious,and whats more the reproducibility of this method is poor.The method of single particle counting is highly sensitive,but sometimes the particle will not distribute evenly and the interference coming from the background impurities limits the accuracy of the method.Therefore,these four quantitative methods have their own advantages and disadvantages.In addition,some new quantitative methods have been gradually developed in recent years.For example,the researchers have developed new quantitative methods for time-resolved analysis,combining the dark field microscopy with optical devices such as polarizers and filters to eliminate background interference,as well as instruments such as electrochemistry and Raman to expand the scope of application.Furthermore,in order to improve the accuracy and sensitivity of analytical methods,combinations of the dark-field microscopy with some modern computer science technologies,such as deep learning,cloud computing and artificial intelligence,have become more and more popular.Based on the above reasons,this mini review focuses on the application of single-particle light scattering microscopy in the field of biochemical and pharmaceutical analysis,then the recent new research progress is summarized,and several main quantitative methods of single-particle light scattering microscopy in quantitative analysis are discussed,and finally their future development trends are put forward.It is expected that the review could provide a certain academic reference for the new comer.
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