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 flucytosine 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.

Point-of-Care Diagnostics: Recent Developments in a Connected Age

“…Finally, precision medicine also involves trends in grouping patients into different subtypes in order to more accurately monitor their individual responses to drugs. A vertical-flow paper-based POC assay was developed to be used with a low-cost, bench-top fluorometer for monitoring therapeutic response via surface enhanced Raman detection 113 . The device operated on undiluted serum and provided a result in under 15 minutes 113 .…”

“…A vertical-flow paper-based POC assay was developed to be used with a low-cost, bench-top fluorometer for monitoring therapeutic response via surface enhanced Raman detection 113 . The device operated on undiluted serum and provided a result in under 15 minutes 113 . Such near-patient devices hold potential in implementing precision medicine across a broad range of clinical settings.…”

Fabrication of flexible paper‐based Surface‐enhanced Raman scattering substrate from Au nanocubes monolayer for trace detection of crystal violet on shell

“…On the basis of excellent liquid conductivity and softness, various detection modes have been proposed, such as wiping type, lateral flow, and longitudinal flow . For instance, White et al proposed a low cost and easy device using a novel vertical flow membrance system with inkjet‐printed technique . Tian et al demonstrated a novel SERS substrate based on common filter paper together with Au nanorods, which allows conformal contact with real‐world surfaces, resulting in highly enhancing the sample collection efficiency compared with conventional substrates .…”

Time resolved and label free monitoring of extracellular metabolites by surface enhanced Raman spectroscopy

“…So far, this effect, called surface enhanced Raman scattering (SERS), has been widely explored for the analysis of biological samples for different purposes, i.e. classification of different bacterial species [37], gene expression estimation [38] and detection of drugs [39–40]. Unfortunately, these studies are limited to the analysis of few biomolecules.…”