Development of a paper-based SERS substrate for rapid on-site analysis

Portable detection of contamination in the food supply is highly desirable for the food industry and regulatory agencies, as current benchtop detection methods generally require samples to be transported to a dedicated analytical lab, which greatly increases the time needed to complete the analysis. Surface enhanced Raman spectroscopy (SERS) has emerged as a promising analytical technology for food analysis, as it is rapid, economical, and generally requires simpler sample preparation compared to gold standard methods. However, portable SERS detection is challenging due to poor laser focus control and low spectral resolution. Herein, we developed a simple, low-cost SERS substrate and compatible sample holder to overcome these limitations. The substrate consists of filter paper embedded with densely packed silver nanoparticles, where the nanoparticles were dispersed in acetone and pressed into the paper matrix to a depth of 50–100 µm. This three-dimensional distribution provides both enhanced signal intensity and focal depth buffering, which is critical for consistent performance with handheld Raman devices. The entire substrate can be fabricated in 30 seconds at a material cost of less than $0.10. A custom-designed sample holder enables easy alignment with the spectrometer and allows for one-time use liquid sample application. Erythrosine (FD&C Red 3) is a synthetic colorant that was banned in food products by the Food and Drug Administration in January 2025 because it was shown to cause cancer in laboratory rats. Monitoring Red 3 in food products is significant for the FDA to ensure that the food industry complies with its regulations. Traditional detection methods such as high-performance liquid chromatography requires expensive benchtop instrumentation and time-consuming sample preparation. Using the paper-based substrate and a handheld Raman spectrometer, Red 3 was successfully detected at both 10% and 50% adulteration levels (5 mg/L and 25 mg/L) in solutions of Red 40, carmine, and red radish extract. Additionally, Red 3 was identified in sprinkles and peppermint candy containing both Red 40 and Red 3. The method enables specific, rapid detection within 5 minutes of sample preparation in a low resource setting, offering a significant improvement over existing techniques and supporting enforcement of recent FDA regulations.