Construction And Applications Of Single-Nanoparticle Sensors Based On Plasmon Coupling

Local Surface Plasmon Resonance(LSPR)is a unique optical property of noble metal nanomaterials.The special interaction between light and nanomaterials gives rise to the selective absorption,scattering and photothermy effect on metal nanornaterials.Thanks to the development of dark-field microscopy(DFM)technology and spectrum technology,single-particle imaging and spectroscopy can be obtained.Plasmolic nanostructures show high scattering intensity,excellent optical stability,nonblinking and nonbleching properties.Besides,the LSPR effect of metal nanomaterials is highly sensitive to their size,shape,composition,charge density,local dielectric environment,etc.Plasmon coupling effect is a special interaction between nearby metal nanoparticles,which will usually induce distinct changes of scattering light color,intensity and LSPR peaks.DLie to their unique optical properties,lots of functional nanonaterials have been successfully utilized in sensing and biomedical applications,bringing new insights into high performance disease diagnosis and treatment.In this dissertation,we focus on the plasmon coupling effect between letal nanomaterials,and several metal nanoasselnblics have becn constructed to rcalize the detection and imaging analysis of heavy metal ions,nucleic acids and enzymatic activity.The details are summarized as follows:1.Application of core-satellite AuNPs nanoassemblies in detection of trace amount of mercury ionMercury severely damages the environment and human health,particularly when it accumulates in the food chain.Methods for the colorimetric detection of Hg2+ have increasingly been developed over the past decade because of the progress in nanotechnology.However,the limits of detection(LODs)of these methods are mostly either comparable to or higher than the allowable maximum level(10nM)in drinking water set by the US Environmental Protection Agency.In this study,we report a strategy for highly sensitive detection of Hg2+ based on the nanoassemblying of AuNPs induced by Hg2+,forming a core-satellite AuNPs nanostructure.Core AuNPs bound to satellite AuNPs in the solution in the presence of Hg2+ because of oligonucleotide hybridization.This process was accompanied by a color change which can be easily recognized and captured under dark-field microscope.The LSPR shifts of changed color spots corresponded with Hg2+ concentration.The LOD was determined as 1 pM,which may help guard against mercury accumulation.2.Plasmonic Nano halo Optical Probes for Highly Sensitive Imaging Survivin mRNA in Living CellsPlasmon coupling holds great promise for the optical characterization of many biological processes in vitro and in vivo.Here,we designed a strategy for picomolar-level detection of tumor biomarker survivin mRNA based on Rayleigh light scattering spectroscopy of individual Au plasmonic core-satellite nanosensor that couples large gold nanoparticles(L-AuNPs,50nm)with small AuNPs(S-AuNPs,18nm)through the affinity interaction between streptavidin and biotin.We further applied this halo-like Au(nanohalo)plasmon rulers to the imaging of survivin mRNA in living cells,which provided an alternative way to in vivo studies of many biologically important DNA and RNA.3.miRNA-21 induced AuNPs nanoassembly and its application in intracellular miRNA-21 imagingmiRNA-21 is one of the most important cancer biomarkers.We designed a strategy,based on which,two different sized AuNPs could be assembled in the presence of miRNA-21,forming a core-satellite nanostructure,which could be applied to miRNA-21 targeted imaging under dark-field microscopy(DFM).AuNPs(50 nm)are functionalized with Cy5-marked molecular beacon(MB).The MB can be opened upon miRNA-21 triggered hybridization,accompanied by the recovery of the fluorescence of Cy5.Meanwhile,AuNPs(13 nm)functionalized with capture DNA(cDNA)can hybridize with the near end of MB after hybridization with miRNA-21,thus forming a core-satellite nanostructure,with high plasmon coupling effect and super strong scattering intensity under DFM,which is very suitable for intracellular molecule imaging study.Intracellular miRNA-21 imaging can be realized by encapsulating the probes in liposomes for cell delivery.This strategy can be expended to in vivo studies of many biologically important DNA and RNA.4.Single-molecule imaging of telomerase activity via linear plasmon rulersPlasmon rulers is well-known for its ability to measure interparticle distance changes.In this work,we designed a novel Ag plasmon rulers for dynamically monitoring the extension of telomerase primer(TSP).AgNPs were modified with TSP and anchor DNA(aDNA),respectively.TSP could hybridize with part of aDNA,based on which,the Ag plasmon rulers was formed.The 3' end of TSP could be extended in the presence of telomerase,the extended telomeric repeats could exactly hybridize with the rest single-strand part of aDNA,thus forming a rigid double-strand structure step by step,leading to the increase of interparticle distance between the two AgNPs.During this process,the plasmon coupling effect of the plasmon rulers will be weakened,accompanied by the changes in color and LSPR peak.This plasmon rulers can not only distinguish tumor cells from normal cells,but also monitor the telomerase activity changes in the presence of telomerase inhibitor,which provides a potential tool in telomerase-targeted drug screening.