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In this work, we simultaneously detected and predicted the concentration levels of serotonin (SE) and dopamine (DA) neurotransmitters (NTs) for in vitro mixtures, with measurements obtained using conventional glassy carbon electrodes (CGCEs) and differential pulse voltammetry (DPV). The NTs were estimated by deconvolving the multiplexed signals of both NTs using Principal Component Analysis with Gaussian Process Regression (PCA-GPR) and Partial Least Squares with Gaussian Process Regression (PLS-GPR), both with exponential–isotropic kernels. The average testing accuracies of estimation using PCA-GPR for DA alone, SE alone and their mixture (DA–SE) were 87.6%, 88.1%, and 96.7%, respectively. Using PLS-GPR, the testing accuracies of estimation for DA alone, SE alone, and their mixture (DA–SE) were 87.3%, 83.8%, and 95.1%, respectively. Furthermore, we explored methods of reducing the procedural complexity in estimating the NTs by finding reduced subsets of features for accurately detecting and predicting their concentrations. The reduced subsets of features found in the oxidation potential windows of the NTs improved the testing accuracy of the estimation of DA–SE to 97.4%. We thus believe that reducing complexity has the potential to increase the detection and prediction accuracies of NT measurements for practical clinical uses such as deep brain stimulation. 

Reactive oxygen species (ROS) including the superoxide anion (O2•−) are typically studied in cell cultures using fluorescent dyes, which provide only discrete single-point measurements. These methods lack the capabilities for assessing O2•− kinetics and release in a quantitative manner over long monitoring times. Herein, we present the fabrication and application of an electrochemical biosensor that enables real-time continuous monitoring of O2•− release in cell cultures for extended periods (> 8 h) using an O2•− specific microelectrode. To achieve the sensitivity and selectivity requirements for cellular sensing, we developed a biohybrid system consisting of superoxide dismutase (SOD) and Ti3C2Tx MXenes, deposited on a gold microwire electrode (AuME) as O2•− specific materials with catalytic amplification through the synergistic action of the enzyme and the biomimetic MXenes-based structure. The biosensor demonstrated a sensitivity of 18.35 nA/μM with a linear range from 147 to 930 nM in a cell culture medium. To demonstrate its robustness and practicality, we applied the biosensor to monitor O2•− levels in human leukemia monocytic THP-1 cells upon stimulation with lipopolysaccharide (LPS). Using this strategy, we successfully monitored LPS-induced O2•− in THP-1 cells, as well as the quenching effect induced by the ROS scavenger N-acetyl-l-cysteine (NAC). The biosensor is generally useful for exploring the role of oxidative stress and longitudinally monitoring O2•− release in cell cultures, enabling studies of biochemical processes and associated oxidative stress mechanisms in cellular and other biological environments. 

Dopamine is an essential neurotransmitter for daily cognitive functions controlling many neurophysiological processes including memory, cognition, and physical control. Development of analytical methods and sensors to detect dopamine is important for health monitoring and neurological research. This review provides an overview of recent advances in the development of electrochemical catalytic biosensors based on enzyme and enzyme-mimetic materials and discusses their potential applications for measurements of dopamine in biological fluids. The first part of the review summarizes and critically assesses the different types of enzymes and enzyme mimetic materials that can be used to catalytically convert dopamine, followed by a discussion of the biosensor’s fabrication, key design parameters, and detection mechanism on various electrode platforms ranging from single-use screen-printed electrodes to microneedles and implantable microelectrodes. The second part provides examples of measurements of dopamine in biological samples, including saliva, urine, serum, cell cultures, and brain tissue. We conclude with a summary of advantages and limitations of these devices in the clinical field, and an outlook to future research towards the implementation and broader adoption of electrochemical biosensors in neurophysiology, pharmacology, and the clinical field. 

Electrochemical biosensors have the potential to provide rapid and inexpensive diagnostics while moving clinical testing from centralized labs to point-of-care (POC) applications. Conductive materials functionalized with bioreceptors that remain stable and functional for measurements in real-world conditions are essential for the fabrication of electrochemical biosensors, and carbon-based nanomaterials provide the electrical, chemical, structural, and mechanical features that make them suitable for POC devices. This review details the most recent developments in the use of carbon-based nanostructures, with a focus on one-dimensional carbon nanotubes, two-dimensional graphene, and graphene oxide, their interface with biological receptors, deposition on portable, flexible, and wearable substrates, and integration on low-cost platforms for detection of clinical biomarkers. The large-scale manufacturing and implementation of microneedles as implantable and electronic tattoos as wearable devices for on-skin diagnostics, and lab-on-mouth platforms as well as the interface with mobile technologies and their potential implementation for remote POC monitoring and decentralized healthcare through cloud processing and the internet of things (IoT) are discussed with examples of applications. The review concludes with an overview of the regulatory perspectives and future trends, challenges, and opportunities for commercialization and translation of these technologies from the research lab to practice, as useful diagnostic tools for remote monitoring of patient health conditions.