Therapeutic Drug Monitoring of Flucytosine in Serum using a SERS-active Membrane System

A need exists for near real-time therapeutic drug monitoring (TDM), in particular for antibiotics and antifungals in patient samples at the point-of-care. To truly fit the point-of-care need, techniques must be rapid and easy to use. Here we report a membrane system utilizing inkjet-fabricated surface enhanced Raman spectroscopy (SERS) sensors that allows sensitive and specific analysis; furthermore, it eliminates sophisticated chromatography equipment, expensive analytical instruments, and other systems relegated to the central lab. Utilizing inkjet-fabricated paper SERS sensors as substrates for 5FC detection, we leverage the natural wicking ability and filtering properties of microporous membranes to separate flucytosine spiked in whole blood and detect it. We investigate the use of microporous membranes in the vertical flow assay to allow separation of the flucytosine from whole blood. The passive vertical flow assay serves as a valuable method for physical separation of target analytes from complex biological matrices. This work further establishes a platform for easy, sensitive, and specific TDM of 5FC from whole blood.