Biomedical Applications Of Plasmonic Nanoparticles

Multiplex bioassays have drawn more and more attention in the biomedical field due to its high sensitivity,large encoding capacity,high throughput and fast reaction speed.The suspension biochip technology based on self-encoded fluidic microcarriers is a commercially used method for multiplex bioassay.Recently,the suspension biochip is based on the optical coding of spectral technology.However,the most commonly used encoding elements are fluorescent dyes and quantum dots(QDs),which are not stable.And the encoding capacity of photonic crystals(PCs)in the visible region limits their applications.Surface-enhancement Raman scattering(SERS)technique has high sensitivity,no sample pretreatment,easy operation,fast detection speed,high accuracy and nondestructive testing of samples,which has been widely applied in chemical analysis,biomedical,food safety and environmental monitoring.Owing to the advantages of simple preparation and well enhancement effect,the plasma optical particles become commonly used materials for preparing SERS active substrates.However,the encoding capacity of SERS nanotags based on plasma optical particles is still limited.The combination of photonic crystal and SERS nanotags can effectively make up the above problems,which has very important practical significance.Therefore,we developed a study on dual encoding methods by photonic crystals and SERS nanotags and applied it to multiplex detection.The mainly contents and results were as follows:(1)Multiplex bioassay encoded by photonic crystal bead(PCB)and SERS nanotags based on gold nanoparticles(GNPs)was proposed.SERS nanotags and photonic crystal encoded bead formed standard sandwich immunocomplex.Multiple analytes could be deciphered by the reflection peaks of photonic crystals and Raman scattering peaks of SERS nanotags.A quantitative assay for mouse IgG detection was performed to evaluate the quantitative performance of dual encoding by PC and SERS,the quantitative range was from 100 ?g/mL down to 10 pg/mL,and the limit of detection(LOD)was 9.2 pg/mL,which is about six times lower than that of the previously reported binary encoding strategy with QDs and silica PCBs.For the simultaneous quantitative detection of two tumor markers,AFP and CEA,the LOD for AFP and CEA were calculated to be 4.8 pg/mL and 1.3 pg/mL.Moreover,the multiplex assay exhibited good reproducibility performance because the intra-assay and inter-assay coefficients of variation were 6.7%and 9.3%for 10 ng/mL AFP and 6.2%and 9.1%for 10 ng/mLCEA,respectively.The multiplex bioassay encoded by PC and SERS holds great promise in biomedical applications like protein biomarker analysis.(2)Multiplex bioassay encoded by photonic crystal bead(PCB)and SERS nanotags based on gold-silver core-shell nanoparticles(Au@Ag NPs)was proposed.The concentrations of RTs and silver nitrate(AgNO3)were optimized to get the maximum Raman intensity of SERS nanotags.The results showed that the concentrations of Nile Blue A(NBA)and AgNO3 were 2.0 ?M and 2.5 ?M,respectively,which had the best SERS effect.The LOD for mouse IgG detection by our dual encoding method was 672 fg/mL.For the detection of native human plasma C-reactive protein(CRP),the LOD was calculated to 478 fg/mL,which is much lower than that of the previously reported colorimetric method,the shift of UV-Vis absorption spectra and electrochemical detection method.The SERS enhancement of the gold-silver core-shell nanoparticles was significantly better than that of the gold nanoparticles.(3)Multiplex bioassay encoded by inverse opal photonic crystal hydrogel bead(IOPCB)and SERS nanotags based on Au@Ag NPs was proposed.First,reflection peaks of IOPCBs and exciting wavelengths of SERS were optimized to get the maximum near-field intensity.FDTD simulation was used for illustrating this selectivity.It is found that the photonic crystal hydrogel bead with reflection peak at 507 nm for analytes carry and the exciting wavelength of laser at 785 nm gave rise to the best detection sensitivity.The SERS enhancement of RT with IOPCB was 31.2 times higher than that of the non photonic crystal hydrogel bead.Meanwhile,we selected the optimal immunoreaction time and the concentration of SERS nanotags.The results demonstrated that they were 1 h and 75 pM,which have the best detection signals.For the quantitative detection of mouse IgG,the LOD was 3.1 fg/mL.Photonic crystal hydrogel bead supported two order of extra enhancement to the LSPR effect of SERS nanotags.For the multiplex detection of AFP and CEA at a photonic crystal hydrogel bead,the LOD for AFP and CEA were calculated to be 3.6 fg/mL and 1.9 fg/mL.The results of cross reaction showed that the coefficients of variation of Raman signals were 7.3%for AFP and 6.6%for CEA,respectively,indicating a stable and high sensitivity detection,as well as improve the efficiency of detection.Finally,we explored the enhancement effect of gold-silver core-shell nanoparticles with different parameters for SERS nanotags by FDTD simulation.It is found that the position of the absorption peak will more and more red-shift with the decrease of the gap sizes and the thicknesses of silver shell.We used the red-shift absorption peak as the wavelength of the excitation laser,the maximum ratio of near field intensity between the interior gap and outer silver shell was obtained.The results provide a theoretical basis for the further improvement of the sensitivity of the dual encoding method for multiplex detection,and it has important guiding value in practice.