Prussian Blue-Gold Nanohybrids Combined with Headspace Microextraction for Colorimetric/SERS Dual-Mode Sensing of Trimethylamine N-Oxide

In this study, we rationally combined target-induced nanoprobe deactivation with a static headspace microextraction strategy for highly selective and sensitive colorimetric/SERS dual-mode sensing of trimethylamine N-oxide (TMAO). Prussian blue–polyacrylic acid–gold (PB-PAA-Au) nanohybrids were elaborately constructed as excellent peroxidase-like and SERS-active nanoprobes owing to the synergistic effect between PB and Au nanoparticles, which, however, could be deactivated by trimethylamine (TMA), the reduction product of TMAO. Accordingly, the nonvolatile TMAO in sample solution was catalytically reduced to volatile TMA, which could be headspace extracted and in turn cause the deactivation of PB-PAA-Au in the extracting droplet. The deactivation degree was totally dependent on TMA concentration and could be indicated by the catalytic efficiency of PB-PAA-Au toward chromogenic reaction of H2O2–3,3′,5,5′-tetramethylbenzidine, as well as the SERS intensity of PB-PAA-Au. Thus, the quantitative determination of TMAO could be realized by tracking the changes in colorimetric and SERS signals. Under the optimal conditions, the proposed sensing strategy exhibited a limit of detection down to 1.57 μM in colorimetric mode and 5.33 μM in SERS mode. Furthermore, the dual-mode system was successfully applied for TMAO detection in real samples with satisfactory outcomes. This work provides an efficient strategy for clinical monitoring of TMAO and holds great promise for further evaluation of the impact of dietary and environmental factors on TMAO levels.