Antibiotics quantification in a compact SERS-based centrifugal microfluidics platform: The case of Meropenem in ICU settings

Infections in intensive care units (ICU) require immediate and optimal antibiotic treatment with optimal monitoring of drug dosage. Existing analytical techniques to quantify antibiotics in biological fluids result in long waiting time for dose adjustments. Therefore, introducing novel techniques in clinical settings that provide quick results is essential. In this work we developed a novel approach that combines surface-enhanced Raman spectroscopy (SERS) with a centrifugal microfluidics setting (the D-SERS device) to improve label-free meropenem (MER) quantification in serum samples. The D-SERS device consists of a microfluidics disc cartridge integrated into a custom-made Raman spectrometer. A serum cleanup step, consisting of mono-spin solid-phase extraction (ms-SPE), was coupled with the D-SERS device for efficient MER separation. The MER label-free SERS detection was performed on-disc by rapid scanning of an Ag-nanopillar substrate integrated into the disc cartridge. The coupling of ms-SPE to the D-SERS device led to a significant improvement in signal-to-noise ratio and sensitivity. Furthermore, the implementation of chemometrics algorithms on a large data set, such as Partial Least Squares Regression (PLSR), allowed in LoD and LoQ values of 12.12 and 36.37 µM, respectively. The performance of the D-SERS device was compared with a commercial Raman system, demonstrating high efficiency and reliability. In summary, the presented D-SERS system is compact and easy to operate, and results are provided within 15-20 min., supporting its clinical feasibility for point-of-care therapeutic drug monitoring of antibiotics.