Preparation And Application Of LoC-SERS Chip With Tunable “Hot-Spots” Based On Induced Nanoparticle Aggregation Strategy

Surface-enhanced Raman Scattering（SERS）not only has the fingerprint property of Raman spectroscopy,but also has very high sensitivity.As an analytical technology,SERS has been widely applied in the fields of physics,chemistry,materials,biology,environment and so on.SERS enhancement is strongly dependent on the light-induced electromagnetic field on the surface of metal nanostructures.Aggregation of metal nanoparticles may be the simplest method to generate strong electromagnetic field enhancement,and can even be used for SERS detection of single molecule.Halogen ions are common aggregators,they can reduce the Zeta potential of nanoparticles which leads to unstable aggregation of nanoparticles.Also,halogen ions can replace the ligands on the surface of nanoparticles to reduce the interference from the intrinsic signals of the substrate.However,halogen-induced nanoparticle aggregation has the problem of uncontrollable aggregation,which will lead to poor signal uniformity and reproducibility,thus limit practical application.In this dissertation,we prepared uniform SERS chips with tunable"hot spots"based on induced nanoparticle aggregation with the help of an ultra-fast microfluidic mixer.We solved the problem of uncontrollable nanoparticle aggregation.The main research contents are as follows:（1）A SERS chip based on NaCl induced nanoparticle aggregation was prepared by combining ultrafast microfluidic mixing and layer by layer self-assembly.Taking R6G as the analyte,the concentration of NaCl for realizing the best SERS enhancement effect was explored.Compared with the solid SERS substrate induced by NaCl outside the microfluidic chip,the SERS active microfluidic chip has high signal uniformity.（2）The sensitivity of the prepared SERS active microfluidic chip based on NaCl-induced aggregation was characterized.It was pointed out that the high sensitivity of the SERS chip comes from two mechanisms:（1）the analyte was transported to the"hot spots"effectively;（2）NaCl decrease the distance between two nanoparticles and increase electromagnetic field enhancement.Substitution experiment was conducted to quantitatively studied the contribution of"hot spots".Experimental results shown that when 2 mM NaCl was used as the aggregator,the contribution of"hot spots"reached 82%.Based on the SERS detection strategy of NaCl induced nanoparticle aggregation in the microfluidic chip,the highly sensitive detection of cefazolin sodium was realized,and the linear detection range was 2×10^-6 M-2×10^-10 M.At the same time,this SERS substrate has good long-term stability,which overcomes the problem of timeliness of detection of nanoparticle aggregation.（3）Based on the same strategy,phosphoric acid,the reagent used in chemical reactions,was used as the aggregator to realize the detection of malondialdehyde（MDA）.The optimal phosphoric acid concentration for MDA detection was explored based on phosphoric acid induced aggregation strategy.Under the optimized phosphoric acid concentration,the linear detection range of this strategy for MDA detection was 3.3×10^-7 M-1.67×10^-10 M.Selectivity,uniformity,repeatability and real sample detection ability of this method were characterized and the potential of this method in practical application was investigated.