Low-cost, thin-film, mass-manufacturable carbon electrodes for detection of the neurotransmitter dopamine

Highlights

• A flexible, thin-film carbon electrode developed for detection of dopamine.

• The electrode was electrochemically characterised to assess its sensitivity.

• The electrode provided a dopamine limit of detection of ~50 pM.

• Good selectivity shown between dopamine and key interferent, ascorbic acid.

Abstract

A flexible, thin-film carbon electrode is reported for detection of the key neurotransmitter dopamine using standard electroanalytical techniques of cyclic voltammetry, differential pulse voltammetry and square wave voltammetry. The thin-film electrode has been explored as a possible low-cost solution to detect low concentrations of dopamine and its performance has been compared with a commercially available screen printed carbon electrode. It was found that the thin-film electrode is more sensitive than the screen printed electrode, and can faithfully detect dopamine between 50 pM and 1 mM concentrations. The electrode provides a limit of detection of ~50 pM, displays good selectivity between dopamine and ascorbic acid, and is able to show a level of differentiation between the two compounds in terms of peak currents as well as oxidative potentials at physiologically relevant concentrations. This is in contrast to the screen printed electrode which is unable to discriminate between dopamine and ascorbic acid at the same concentrations. The key advantages of the presented electrode system are its low-cost, flexible substrate, and the ability to achieve very low levels of dopamine detection without requiring any electrode surface modification steps, a key factor in reducing fabrication costs and overall device complexity.

Introduction

Dopamine (DA) is a highly important neurotransmitter, produced in the ventral tegmental area, substantia nigra and hypothalamus areas of the brain [1]. DA is a catecholamine which plays a significant role in the function of various biological systems including renal [2], cardiovascular [3], hormonal [4] and central nervous [5] systems of mammals. DA can behave as both an excitatory or inhibitory neurotransmitter and acts as the brain’s ‘feel good’ neurotransmitter. However, abnormal levels of DA play a role in different neurological disorders including depression [6], Parkinson’s [7] and schizophrenia [8]. There exists a link between high DA levels and patients displaying symptoms of anxiety, aggression, mood swings, ADHD etc., whereas a lack of DA can lead to cognitive problems such as lack of energy, lack of motivation, poor concentration and difficulty in completing tasks [9]. Therefore, to be able to accurately diagnose conditions associated with DA dysfunction, effective and sensitive DA detection is critical, and is becoming an increasingly significant research area within the wider field of medicine and healthcare [10], [11]. To date, a range of DA detection methods have been investigated, to varying degrees of success. Molecular imaging is one of the most commonly tested methods in the literature, and whilst it can be highly sensitive [12], it is also very expensive to implement and has the difficulty of being able to accurately separate DA from other key biological interferents such as ascorbic acid. On the other hand, electrochemical techniques have proven to be more cost-effective, sensitive, selective, and easier to implement into point of care systems [13], [14], [15], [16], [17], [18]. The key parameters for a useful DA biosensor are high sensitivity and selectivity. It is well understood that the biomolecule ascorbic acid (AA) coexists in relatively high concentration in biological samples such as blood and urine, meaning that any detection method must be both sensitive and selective to DA and AA. AA is also known more commonly as vitamin C, and is found in various foods and dietary supplements. However, DA and AA oxidise at similar potentials resulting in interference in the electrochemical response. Therefore, there is a need for the development of a low-cost, sensitive, and highly selective sensor to DA using electrochemical techniques. Previously, many methods have been adopted to try to detect DA using electrochemical approaches, with varying degrees of success. Often, electrodes are modified using a number of different materials to improve sensitivity and selectively compared to unmodified working electrodes. To avoid AA interference, overoxidised polypyrrole/graphene modified glassy carbon electrodes were fabricated [19]. The sensor displayed a linear response across a DA concentration range of 25 µM – 1 mM with a detection limit of 0.1 µM. Another electrode used to detect DA in the presence of AA and uric acid (UA) based on vanadium-substituted polyoxometalates, copper oxide and chitosan-palladium found good electrocatalytic activity toward DA oxidation, and displayed a limit of detection (LoD) of 45 pM [20]. A silver nanoparticle modified electrode covered by graphene oxide has been used to electrochemically detect low concentrations of DA and produced a detection limit of 0.2 µM [21]. Despite the enhancement in sensitivity and selectivity afforded by these modified electrodes compared to the majority of bare electrodes, there is still room for improvement, particularly in terms of detection limit for DA, cost-effectiveness and ease of fabrication, with many of the reported electrode modifications being too impractical for manufacture. One approach explored previously to detect DA is to use screen-printed electrodes (SPEs) to exploit their many advantages over more traditional electrodes such as simple fabrication and cleaning procedures, low cost, rapid time to result, reliability, and repeatability of measurements. They are also suitable for mass production, and large numbers of electrodes can be produced at reduced cost compared to traditional macro or microelectrodes [22]. However, the drawback of SPEs often lies in their ability to selectively detect DA alongside interferents such as AA, therefore they often require modification of the electrode surface, which adds additional complexity and cost to the fabrication process [23]. Our approach involves the use of a thin-film carbon-based flexible electrode (TFCE) defined by a dielectric which represents a relatively flat but disordered carbon surface, capable of detecting DA to low concentrations, as well as differentiating between DA and AA in solution, without the need for electrode surface modification. Having surveyed the literature, to the best of our knowledge this is the first report of DA detection in the presence of AA, without electrode surface modification, ultimately leading to a low cost and more manufacturable device suitable for mass production. Electrochemical techniques including cyclic voltammetry (CV) and differential pulse voltammetry (DPV) are used to characterise the electrodes as a function of DA concentration and to attempt to differentiate between DA and the common interferent AA. The electrode performance is also compared with a commercially available carbon SPE to evaluate the best electrode configuration for sensitive and selective DA detection and to aid with design requirements for future TFCEs.