The Study Of SERS Biosensor Based On Micro/Nano Materials

Surface-enhanced Raman spectroscopy?SERS?has been widely used in recent years for the characterization of materials and structures of substances,the analysis of artworks and cultural relics,as well as the analysis and detection of small molecules,proteins,DNA and other substances.Since it has many advantages,such as extremely strong Raman peak,high sensitivity,good specificity,and the detection needs a small number of samples,can do non-destructive analysis,small background interference,etc.However,the detection sensitivity of biosensors based on surface-enhanced Raman spectroscopy still needs to be improved.Therefore,we have designed different novel signal amplification strategies and micro-nanostructuresto increase the signal intensity of surface enhanced Raman spectroscopy biosensors for sensitively detecting biomolecules.The detalied research in this article is as follows:1.A SERS biosensor based on target triggered configuration change of DNA tetrahedron for sensitive SERS detection of microRNA.A surface-enhanced Raman scattering?SERS?biosensor was manufactured for sensitive detection of microRNA 122 based on conformational changes of DNA tetrahedron.Firstly,the DNA tetrahedron was self-assembled with one vertex labeled with toluidine blue?TB?.Then it was immobilized on the prepared porous Ni/SiO₂@PEI@Au as SERS platform.At this time,the DNA tetrahedron was contracted,so the TB is close to Au nanoparticles resulting in a high Raman signal.When target microRNA 122?miRNA 122?existed,with the nicking enzyme amplification strategy,a great deal of DNA signal chains?S1?was obtained,which can extend the contracted DNA tetrahedron and change it into a three-dimensional DNA tetrahedron.In this case,the TB was far from Au nanoparticles,resulting in a lower Raman signal.Due to the configuration change of DNA tetrahedron,the Raman signal can have a linear relationship with miRNA 122.This SERS biosensor has high sensitivity for miRNA 122 in detection range from 0.01 aM to 10 fM.This SERS strategy was designed based on the target triggered configuration change of DNA tetrahedron,which may give new insight for DNA structures in biological analysis.2.A SERS immunosensor combining porous magnetic Ni@C nanospheres and CaCO3microcapsule as SERS sensing platform for hypersensitive C-reactive protein detection.We have designed an efficient and rapid SERS immunosensor for supersensitive analysis of Hypersensitive C-reactive protein?hs-CRP?with label-free method by combining porous magnetic Ni@C nanospheres to aggregate together for simplifying the experiment operation and CaCO₃ microcapsule to encapsulate Rhodamine B as Raman signal.The final solution containing signal molecule was dropped on the Ag nanoparticle substrate.And the signal could be enhanced by Ag particles.Firstly,Rhodamine B was encapsulated in the CaCO₃microcapsule when it precipitated to form microcubes.Subsequently,the porous CaCO₃microcapsule was layer-by-layer assembled with poly?ether imide??PEI?and second antibody to obtain Rhodamine B@CaCO₃@PEI@Ab₂.Then functionalized magnetic Ni@C nanospheres were prepared to immobilize primary antibody?Ab₁?.Finally,the immunosensor was fabricated by the sandwiched antibody-antigen interactions.Compared to DNA hydrogel,the low-cost CaCO₃ microcapsule would be rapidly dissolved by EDTA and released Rhodamine B to produce a strong Raman signal for rapid and efficient detection of hs-CRP.With the hs-CRP concentration ranges from 0.1 pg mL-1 to 1?g mL-1,the SERS intensity of the platform have a liner relationship with the logarithm of hs-CRP concentration and the detection limit was 0.01 pg mL-1.By this smart design,this work can give a direction for rapid label free SERS analysis.3.Stimuli-Responsive DNA Microcapsules for SERS Sensing of Trace MicroRNAOne stimuli-responsive DNA microcapsule was designed to combine duplex-specific nuclease?DSN?amplification strategy and surface-enhanced Raman spectroscopy?SERS?technology for sensitive detection of microRNA 155?miRNA 155?.First,toluidine blue?TB?as Raman dye and CaCO₃ as core templates coprecipitated to form TB@CaCO₃ composite.Then,DNA networks were layer by layer constructed with oligonucleotide layers cross-linked by linker ssDNA L to lock TB@CaCO₃ inside.In the presence of ethylenediaminetetraacetic acid,the core CaCO₃ would be dissolved to form TB-loading DNA microcapsule.With target miRNA 155-induced DSN signal amplification,a large amount of simulative target ssDNA D was obtained,which can completely complement with the linker L on the DNA networks,destroying the microcapsule to release TB and obtain a strong Raman signal.So by this smart design,a SERS platform was fabricated on the basis of the stimuli-responsive DNA microcapsule to detect miRNA 155 from 1 fM to 10 nM with a detection limit of 0.67 fM.In the present study,the programmable property and rapid response speed of DNA microcapsule,which helped in fabrication of a new potential biosensing technology for miRNA detection that is anticipated to be applied for clinical diagnosis.