Objective Surface-enhanced Raman spectroscopy (SERS) can provide fingerprint information on target molecules with high detection sensitivity without being affected by water, which makes it an attractive non-destructive analysis technology. The SERS active substrate is key part of inspection applications. Therefore, a significant research effort has been devoted to the development of a stable, uniform, and repeatable SERS substrate. Unlike rigid SERS substrate, flexible SERS substrate can be flexibly deformed, which is convenient for in situ detection on irregular curved surfaces and can even be used for wipe sampling detection directly. However, the characteristics of the flexible substrate itself significantly impact the SERS performance, and the commonly used sol drop casting method to prepare SERS active substrates is significantly affected by the "coffee ring" effect. Because the effect caused uneven distribution of nanoparticles, uniformity of the SERS signal is affected. In this paper, simulation analysis and experimental research on the reflectivity of the substrate are carried out, and optimization of the substrate is performed to suppress the "coffee ring" effect. A high-throughput and array-type flexible SERS chip with excellent performance is successfully fabricated, which has application potential in biomedicine, food safety, environmental pollution, and other detection fields. Methods To study the influence of substrate reflectivity on SERS performance, the Raman signal intensities of different substrates are compared and analyzed by simulation ( COMSOL Multiphysics) and experimental tests. To eliminate the "coffee ring" effect generated from the evaporation of nanoparticle suspensions, we control the solvent composition by adding a certain proportion of ethylene glycol in Ag sol, and use inward Marangoni flow induced by the surface tension gradient, which ensure uniform deposition of nanoparticles. The array detection unit of the SERS chip is fabricated on aluminum foil through laser printing. Then, Ag sol mixed liquid is dropped into the detection area and confined by the hydrophobic toner film. The SERS chip is formed after the droplets dried in a vacuum drying oven. Rhodamine 6G (R6G) is used as a probe molecule for the SERS test, and the performance of the SERS chip is evaluated by calculating the Raman enhancement factor and performing a signal uniformity test. Results and Discussions Simulation analysis results show that the greater the reflectivity of the substrate, the higher the intensity of the Raman signal. The Raman detection results for R6G molecules also show that the substrate with high reflectivity is helpful for Raman signal collection, which is consistent with the simulation results. Aluminum foil is chosen as the substrate because it has the strongest reflectivity under 532 nm excitation light among the several materials used, and the SERS chip is manufactured using the Ag sol drop casting method. After adding ethylene glycol to the Ag sol, a tension gradient is formed on the surface of the droplet, resulting in an inward Marangoni flow, which prevents the nanoparticles from gathering on the edge of the droplet, thereby suppressing the "coffee ring" effect. The experimental results show that when 200 mu L. of ethylene glycol is added to 1 mL of Ag sol, the "coffee ring" effect is eliminated, and the Ag nanoparticles are uniformly distributed on the substrate. The Raman test results indicate that the SERS chip exhibited a high Raman enhancement factor of up to 1.32 x 10(8) and a detection limit of down to 10 (11) mol for R6G molecules. Furthermore, the chip showes good signal uniformity. Conclusions Flexible SERS chips have many advantages in Raman detection applications. In this work, simulation analysis and experimental tests show that the high reflectivity of the substrate has a significant impact on improving the SERS performance of the chip. By adding a certain proportion of ethylene glycol solution to the Ag sol, the surface tension state of the solution can be changed, ensuring uniform distribution of silver nanoparticles on the chip, thereby eliminating the "coffee ring" effect generated during deposition of the nanoparticles. The flexible SERS chip shows good Raman detection performance. The array structure of the SERS chip enables it to achieve high-throughput, multiparameter detection. It has strong application potential in fields such as biomedicine, food safety, and environmental pollution.
