Neurotransmitters as electrochemical signaling molecules are essential for proper brain function and their dysfunction is involved in several mental disorders. Therefore, the accurate detection and monitoring of these substances are crucial in brain studies. Neurotransmitters are present in the nervous system at very low concentrations, and they mixed with many other biochemical molecules and minerals, thus making their selective detection and measurement difficult. Although numerous techniques to do so have been proposed in the literature, neurotransmitter monitoring in the brain is still a challenge and the subject of ongoing research. This article reviews the current advances and trends in neurotransmitters detection techniques, including in vivo sampling and imaging techniques, electrochemical and nano-object sensing techniques for in vitro and in vivo detection, as well as spectrometric, analytical and derivatization-based methods mainly used for in vitro research. The document analyzes the strengths and weaknesses of each method, with the aim to offer selection guidelines for neuro-engineering research.

Electrochemistry is developed as a new chemical imaging modality for microfluidics. The technique is based on multipoint voltammetry using an embedded 20 × 10 miniature electrode array implemented on a customized printed circuit board. Electrode durability was enhanced by chemical modification of the electrode surfaces, which enabled continuous, stable use for over 2 months. A system-level approach enables automatic calibration, data acquisition and data processing through a graphical user interface. Following data processing, redox currents and peak positions are extracted from location-specific voltammograms and converted into pixels of an "electrochemical image". The system is validated by imaging steady-state and dynamic laminar flow patterns of flow-confined solutions of the redox pairs Fe(CN)6(3-/4-) or multi-redox environments that include coflowing Ru(NH3)6(2+/3+) solutions. The images obtained are compared with flow simulations and optical images for validation. A strategy to achieve measurements with spatial resolution smaller than the individual electrodes is also demonstrated as an avenue to enhance image spatial resolution. It is expected that this new approach to chemical imaging will expand the applicability of microfluidics in certain areas of chemistry and biology without requiring expertise in electrochemistry.

The rapid electrochemical identification and quantification of neurotransmitters being a challenge in the ever-growing field of neuroelectronics, we aimed to facilitate the electrochemical selective detection of dopamine by functionalizing commercially available electrodes through the deposition of a thin film containing pre-formed gold nanoparticles. The influence of different parameters and experimental conditions, such as buffer solution, fiber material, concentration, and cyclic voltammetry (CV) cycle number, were tested during neurotransmitter detection. In each case, without drastically changing the outcome of the functionalization process, the selectivity towards dopamine was improved. The detected oxidation current for dopamine was increased by 92%, while ascorbic acid and serotonin oxidation currents were lowered by 66% under the best conditions. Moreover, dopamine sensing was successfully achieved in tandem with home-made triple electrodes and an in-house built potentiostat at a high scan rate mode.

A novel fully differential difference CMOS potentiostat suitable for neurotransmitter sensing is presented. The described architecture relies on a fully differential difference amplifier (FDDA) circuit to detect a wide range of reduction-oxidation currents, while exhibiting low-power consumption and low-noise operation. This is made possible thanks to the fully differential feature of the FDDA, which allows to increase the source voltage swing without the need for additional dedicated circuitry. The FDDA also reduces the number of amplifiers and passive elements in the potentiostat design, which lowers the overall power consumption and noise. The proposed potentiostat was fabricated in 0.18 µm CMOS, with 1.8 V supply voltage. The device achieved 5 µA sensitivity and 0.99 linearity. The input-referred noise was 6.9 µVrms and the flicker noise was negligible. The total power consumption was under 55 µW. The complete system was assembled on a 20 mm × 20 mm platform that includes the potentiostat chip, the electrode terminals and an instrumentation amplifier for redox current buffering, once converted to a voltage by a series resistor. the chip dimensions were 1 mm × 0.5 mm and the other PCB components were off-chip resistors, capacitors and amplifiers for data acquisition. The system was successfully tested with ferricyanide, a stable electroactive compound, and validated with dopamine, a popular neurotransmitter.