Tailoring Surface Chemistry of Graphene Ink for Highly-Sensitive Electrochemical Detection of Dopamine Down to 50 Picomolar

Abstract

Rising populations and healthcare expenses have sparked a global interest in rapid, cost-effective, and simple-to-use diagnostics at the point-of-care (PoC). According to The World Health Organization, over half of the world’s population does not have access to “essential medical services”.1 Current techniques for dopamine detection include capillary electrophoresis,2 high-performance liquid chromatography,3 colorimetry,4 and enzyme linked immunosorbent assays (ELISA).5 These methods, although effective, can be expensive, cumbersome, and require highly-skilled operators. Additionally, these techniques can be difficult to scale to point-of-care and continuous monitoring applications. Owing to their low cost, portability, and ease of operation, electrochemical sensors provide a viable solution. In the case of dopamine (DA), a highly redox-active molecule involved in many cognitive and neurological processes, as well as a stress and fatigue indicator,6,7 electrochemical sensors are an innate choice for its detection.Herein, we have developed an electrochemical sensor for detection of DA down to ultralow concentrations of 50 picomolar (pM) by specifically tailoring the surface properties of commercially available graphene ink. Graphene ink is spin-coated and serves as an inexpensive, easily-processible, and biocompatible platform for sensitive and selective dopamine detection. As shown in Figure 1a, we have examined the effect of various annealing conditions on the surface chemistry and the sensor response to DA. It was found that the response varied as a function of annealing temperature, environment, and duration. Samples annealed at 300℃ for 30 minutes in Ar/H2 environment showed the strongest response, with a detection limit of ~ 50 pM in phosphate buffered solution using differential pulse voltammetry (DPV, shown in Figure 1b). It is worth noting that the DA level in plasma is ~ 780 pM,8 which indicates that the developed DA sensor can potentially be used for testing clinical samples. Importantly, the sensor shows selective response to DA compared to uric acid and ascorbic acid, two common interfering species. To the best of our knowledge, this is the lowest detection limit reported for DA sensors solely based on graphene and is among the lowest for all electrochemical DA sensors. We observe that the variation in the sensor response between different annealing conditions is due to the different decomposition profiles of the ink’s ethyl cellulose stabilizing polymer.9 X-ray photoelectron spectroscopic (XPS) measurements are employed to characterize the effect of annealing on the surface chemistry. Principal component analysis (PCA) indicates that the π-π interaction and oxygen-containing functional groups on the graphene surface are the primary contributors to the improved dopamine response. This is further verified by studying the non-Faradaic interaction of three amine-containing molecules (dopamine (DA), phenylethylamine (PEA), and propylamine (PA))10 with the graphene surface (shown in Figure 1c-e). No change is seen in the charge vs. time between the background and 5 µM PA solutions, indicating the inconsequential role of the amine group on adsorption. However, PEA and DA show a noticeable difference in charge accumulation between the background and 5 μM solution, indicating both the aromatic ring of dopamine and the -OH groups contribute to adsorption on the graphene surface, in agreement with computational reports of dopamine adsorption on graphene.11,12 Variation of the processing conditions of graphene ink films can offer an avenue for tuning the electrochemical response towards different target analytes. Here, graphene enables low-concentration detection of dopamine in the pM-regime. The easily-processible, low-cost graphene ink utilized here poses as a scalable sensor material for use in flexible PoC electronics. The planar nature of the graphene improves compatibility with established integrated circuit (IC) technology, which can enable large-scale fabrication of biocompatible, electrochemical sensor arrays for application in wearable electronics and PoC diagnostics. 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