Parallel therapeutic drug monitoring of vancomycin and tobramycin using paper-based laser-induced graphene extended-gate field-effect transistor sensor

Abstract： The use of multiple antibiotics in combination therapy for bacterial infections has become routine in clinical practice, whereas the increasing demand for therapeutic drug monitoring (TDM) imposes stricter requirements on analytical methods. The combined administration of vancomycin (Van) and tobramycin (TOB) offers broader antimicrobial coverage across diverse pathogenic species. However, both antibiotics possess narrow therapeutic windows, making the parallel monitoring of their blood concentrations crucial for precise and safe dosing. In this study, an extended-gate field-effect transistor (EG-FET) sensor fabricated from gold-doped, paper-based laser-induced graphene (LIG) is presented. The sensor operates via an aptamer-based, label-free response mechanism, enabling the multiplexed and rapid therapeutic drug monitoring of Van and TOB. The incorporation of paper-based substrates not only simplifies device fabrication but also enhances the overall sensing sensitivity. The EG-FET sensor exhibits excellent linear responses toward Van and TOB over concentrations ranging from 0.1 nM to 100 μM, with detection limits as low as 6.89 pM for Van and 52.9 pM for TOB. To enable point-of-care TDM applications, a portable and wireless sensing platform was assembled. Additionally, our EG-FET sensors can accurately detect Van and TOB in actual blood samples (including human blood and mice serum). This work represents the first demonstration of an EG-FET sensing platform enabling parallel and multiplexed detection of vancomycin and tobramycin, providing a promising strategy for multi-analyte therapeutic drug monitoring of antibiotics with narrow therapeutic windows.