Raman spectroscopy is a method to collect and analyze the inelastic scattering light generated by a substance excited by the incident light.Its advantages are rapid,accurate,and non-destructive.However,Raman scattering has low efficiency and the signal intensity was weak.Until the discovery of surface enhanced Raman scattering(SERS),the problem of low sensitivity of Raman spectroscopy was solved.However,most noble metals in SERS substrates have strong radiation loss at visible light and near-infrared wavelengths,which limits their enhancement effect in the near-field region.The Fano resonance generated by the mutual coupling between the plasmon resonance modes can be used to reduce the near-field radiation loss of noble metals in SERS and play a vital role in the enhancement of the Raman signal.In this article,we adopted numerical simulation together with experiment to design and fabricate a Raman sensor chip based on Fano resonance through self-assembly.Furthermore,the chip was used to test and analyze the serum of patients with colorectal cancer.First,we designed a Fano resonance based SERS substrate and performed a numerical simulation was used to calculate the Fano resonance of the SERS substrate.Through numerical simulation,scattering,absorption and extinction spectra,electromagnetic field distribution diagrams,charge distribution diagrams,electric displacement vector diagrams are obtained,and the principle of Fano resonance generation is explained.The results show that the Fano resonance is generated under the combined action of the strong resonance coupling between the nanosphere and the gold film and the mirror imaging field effect.By changing the diameter of the nanospheres,the distance between the spheres,and the thickness of the gold plating in the simulation structure,the Fano dip spectrum position and intensity control methods are studied.The results suggest that the thickness of the gold plating has a greater influence on the strength of the Fano resonance,the nanosphere diameter has a linear influence on the Fano dip,and the gap distance between the sphere and the film is the key factor that determines whether the Fano resonance occurs.Secondly,a Raman sensor substrate based on Fano resonance was fabricated through experiments.In the experiment,avidin and biotin were used to chemically connect the nanospheres and the gold film and formed a strong bonding.The SEM image shows that the prepared substrate has a large area,good uniformity,and uniform nanosphere surface.The Raman test results show that the prepared substrate has a stronger enhancement than the traditional SERS substrate.In the scattering test,the Fano dip appears near 785 nm,which is corresponded with the numerical value.Finally,the performance influencing factors of the substrate were tested.The distance between the nanospheres and the gold substrate was controlled by polyethylene glycol,the diameter of the silica nanospheres,and the thickness of the gold plating were changed.The final conclusion was the same as the simulation conclusion.Finally,the prepared Fano resonance based SERS substrate was used to detect the serum of colorectal cancer patients.The results showed that the main difference between the Raman spectra of colorectal cancer patients’serum and non-pathological serum was at 726cm-1.The serum samples were then divided into three components:hydrophilic small molecule,hydrophobic small molecule,and protein.Raman test shows that the Raman spectrum characteristic peak of hydrophilic small molecule is most similar to that of serum at 726 cm-1.Furthermore,the hydrophilic small molecules were separated,and Raman spectroscopy tests were performed on the separated 60samples,and it was obtained that numbers 14 and 15 had the same peak intensities as the serum at the characteristic peaks.The mass spectrometry of No.14 and No.15samples by mass spectrometry showed that the content of hypoxanthine was the highest.The results suggest that the levels of hypoxanthine in the serum of patients with colorectal cancer are significantly down-regulated. |