An acousto-assisted liquid-marble-based microreactor for quantitative SERS detection of alkaline phosphatase

Liquid-phase-based direct surface-enhanced Raman spectroscopy (SERS) has extensive applications in the field of (bio)chemical analyses. Yet, existing techniques are generally constrained by signal fluctuations caused by the evaporation effect. Liquid marbles, acting as enclosed microreactors, have been proposed to minimize the evaporation effect and have shown great application potentials in microfluidics and sensors. Herein, an acousto-assisted liquid-marble-based SERS platform was proposed to achieve non-destructive and rapid coalescence of liquid marbles and the subsequent high-sensitivity SERS detection. To evaluate the feasibility of our platform, alkaline phosphatase (ALP)—an important diagnostic indicator for specific human diseases (e.g., osteoporosis, lymphoma, leukemia, and hepatitis)—was selected. Our proposed method achieved a remarkable sensitivity of detecting the ALP activity, with a limit of detection of 0.33 UL−1. We also determined the ALP activity in ten complex human serum samples, showing excellent consistency with the ones obtained by the commercial ALP assay kit. We envision that our acousto-assisted liquid-marble-based SERS platform could be further applied as a versatile and reliable technique for liquid-phase biomedical and chemical applications, with the advantages of negligible evaporation and fully automatic mixing operations.