title: Vertical-flow paper SERS system for therapeutic drug monitoring of flucytosine in serum.
abstract: A number of life-saving drugs require therapeutic drug monitoring (TDM) for safe and effective use. Currently, however, TDM is performed using sophisticated analytical techniques relegated to central labs, increasing the cost per test and time to answer. Here, using a novel vertical flow membrane system with inkjet-printed surface enhanced Raman sensors, along with a portable spectrometer, we demonstrate a low cost and easy to use device to quantify levels of flucytosine, an antifungal that requires TDM for effective patient care, from undiluted human serum. To our knowledge, this work represents the first report of a passive vertical flow sample cleanup method with surface enhanced Raman detection. We first investigated and optimized the parameters of the vertical flow system for the detection of flucytosine in spiked serum samples. Then, using an optimized vertical-flow system utilizing nitrocellulose membranes and a paper SERS sensor, we achieved detection of down to 10 μg mL-1flucytosine in undiluted serum, with quantitative detection across the entire therapeutic range. This system reduces the assay time to about 15 min, far quicker than the current gold standards. We anticipate that this novel system will enable near-patient therapeutic drug monitoring, leading to the safe and effective administration of a number of life-saving drugs. Furthermore, it will spawn the development of SERS detection systems capable of separating target analytes from real-world biological matrices.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Berger
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Restaino
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA. Electronic address: ianwhite@umd.edu.
authors.forename: Ian M
authors.initials: IM
authors.lastname: White
mesh_terms: D016903:Drug Monitoring; D005437:Flucytosine / Q000097:blood*; D006801:Humans; D010209:Paper; D013059:Spectrum Analysis, Raman
chemical_list: D005437:Flucytosine
keywords: Flucytosine; Paper sensors; Point-of-care; SERS; Surface enhanced Raman spectroscopy; Therapeutic drug monitoring; Vertical flow