Improving Meropenem Quantification in a Compact SERS-Based Centrifugal Microfluidic Platform: Toward TDM of

Martyna A Pytlarz1, Gohar Soufi1, Isidro Badillo-Ramírez1

  • 1Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, Lyngby, Kongens 2800, Denmark.

Analytical Chemistry
|March 25, 2025
PubMed

Insights

This study introduces a rapid, automated D-SERS device for measuring meropenem (MER) in patient serum. The novel system provides quick and reliable antibiotic drug monitoring, crucial for intensive care unit (ICU) treatment.

Area of Science:

  • Analytical Chemistry
  • Biomedical Engineering
  • Spectroscopy

Background:

  • Infections are a leading cause of death, particularly in ICUs, requiring precise antibiotic dosing and monitoring.
  • Current methods for measuring antibiotic levels in patients have long lag times, delaying necessary dose adjustments.
  • Rapid quantification of antibiotic levels is essential for effective patient treatment and improved outcomes.

Purpose of the Study:

  • To develop and validate a novel, automated centrifugal microfluidic device utilizing label-free surface-enhanced Raman spectroscopy (SERS) for meropenem (MER) quantification in serum.
  • To enhance the sensitivity and signal-to-noise ratio of MER detection through the integration of a solid-phase extraction (SPE) cleanup step.
  • To assess the clinical feasibility and performance of the developed D-SERS device for point-of-care therapeutic drug monitoring.

Main Methods:

  • Development of a D-SERS device integrating a microfluidic disc, spin motor, and Raman spectrometer.
  • Implementation of a serum cleanup step using a monospin solid-phase extraction (ms-SPE) column coupled to the D-SERS device.
  • Label-free MER detection via SERS scanning on an integrated silver nanopillar substrate, analyzed using chemometrics (PLSR).

Main Results:

  • The integrated ms-SPE and D-SERS system significantly improved signal-to-noise ratio and sensitivity for MER detection.
  • Achieved limits of detection (LoD) and quantification (LoQ) of 12.12 μM and 36.37 μM, respectively, using PLSR analysis.
  • The D-SERS device demonstrated good correlation (R² = 0.8, p < 0.05) with HPLC in ICU patient samples, with a bias of 14.3 μM overestimation.

Conclusions:

  • The D-SERS device offers a compact, user-friendly, and rapid method for antibiotic therapeutic drug monitoring.
  • Results obtained within 15-20 minutes support the clinical feasibility of the D-SERS system for point-of-care applications.
  • This automated SERS-based approach facilitates timely antibiotic dose adjustments, potentially improving patient outcomes in critical care settings.