Enhanced Superhydrophobic Substrate-Based 3D SERS Platform for a Portable Raman Spectrometer-Assisted Drug Detection in Plasma

In situ, fast, sensitive detection of drugs in blood is in great demand in many clinical scenarios. Surface-enhanced Raman spectroscopy (SERS) has shown great potential in drug analysis; however, achieving highly sensitive detection using a portable Raman instrument is still challenging. Herein, a superhydrophobic silver-film-assisted 3D SERS platform was proposed for sensitive detection of drugs in plasma. The superhydrophobic silver film was prepared through the self-assembly of silver nanoparticles (Ag NPs) at the liquid–liquid interface. Gold–silver core–shell (Au@Ag) nanoparticles (NPs), encoded with an internal standard signal, were mixed with the plasma sample. The mixture formed nanocomposites on the superhydrophobic silver film, creating abundant 3D hotspots that greatly enhanced the signal of the analytes. The 3D platform enabled the detection of crystal violet as low as 10 –13 M, and a relative standard deviation (RSD) of 13.4% using a research-grade Raman spectrometer. Furthermore, mitoxantrone and methylene blue drug analysis in plasma was performed by using a portable Raman spectrometer, which could be detected at as low as 8 × 10 –10 and 3 × 10 –8 M, respectively, with an improved signal repeatability (RSD 2.5%). Based on this technique, the pharmacokinetics of the two drugs postintravenous injection in mice was investigated. This work provided a facile and sensitive protocol for plasma drug analysis, showing great promise for the popularization of portable Raman spectroscopy in real clinical applications.