Utilizing Antifouling Coatings on Stencil-printed Electrodes for Sensitive Electrochemical Detection of the Epilepsy Therapy Drug Carbamazepine from Human Saliva

Introduction: Saliva has great promise for use in therapeutic drug monitoring for people with epilepsy. However, due to the complex composition of human saliva and the associated potential for signal interference, quantification of analytes in saliva can be challenging. Further, analyte concentration in saliva is often at substantially lower levels than in serum such that signal enhancement methods can be critical. In this study, we investigate the use of Nafion™, an ion-exchange polymer, as an electrode coating, in combination with sodium dodecyl sulfate (SDS) for signal enhancement, for the salivary detection of the anti-seizure drug carbamazepine (CBZ) using electrochemical detection.
Methods: Our system consisted of single-use polyester-based electrochemical sample cells with stencil-printed electrodes (carbon paste working and counter and Ag/AgCl reference). Human saliva was collected using an IRB-approved protocol and spiked with 15-μM CBZ, 0.4 mM SDS, and 0.1 M KCl (electrolyte). In select saliva samples, centrifugal filters with molecular weight cutoffs of 3, 30, and 100 kDa were used to remove larger species. Square-wave voltammetry was performed with a benchtop potentiostat and peak area was extracted as the signal.
Results: We demonstrated that Nafion™ coating the electrodes rescued the CBZ peak in saliva backgrounds which substantially masked the CBZ peak when using uncoated electrodes. Further, complementary saliva filtering experiments indicated that the molecular weight of the interfering species was in the approximate range of 3-30 kD. We identified the Nafion™ coating range that produced the highest CBZ signal across multiple saliva samples. Finally, our results showed that fabricating an SDS film on top of the Nafion™ coated electrode produced a greater signal than a composite SDS and Nafion™ film but was still inferior to the case of SDS in solution.