Recently, there has been an upsurge in the extent to which electrochemiluminescence (ECL) working in synergy with bipolar electrochemistry (BPE) is being applied in simple biosensing devices, especially in a clinical setup. The key objective of this particular write-up is to present a consolidated review of ECL-BPE, providing a three-dimensional perspective incorporating its strengths, weaknesses, limitations, and potential applications as a biosensing technique. The review encapsulates critical insights into the latest and novel developments in the field of ECL-BPE, including innovative electrode designs and newly developed, novel luminophores and co-reactants employed in ECL-BPE systems, along with challenges, such as optimization of the interelectrode distance, electrode miniaturization and electrode surface modification for enhancing sensitivity and selectivity. Moreover, this consolidated review will provide an overview of the latest, novel applications and advances made in this field with a bias toward multiplex biosensing based on the past five years of research. The studies reviewed herein, indicate that the technology is rapidly advancing at an outstanding purse and has an immense potential to revolutionize the general field of biosensing. This perspective aims to stimulate innovative ideas and inspire researchers alike to incorporate some elements of ECL-BPE into their studies, thereby steering this field into previously unexplored domains that may lead to unexpected, interesting discoveries. For instance, the application of ECL-BPE in other challenging and complex sample matrices such as hair for bioanalytical purposes is currently an unexplored area. Of great significance, a substantial fraction of the content in this review article is based on content from research articles published between the years 2018 and 2023.

8-Hydroxydeoxyguanosine (8-OHdG) is the most widely used oxidative stress biomarker of the free radical-induced oxidative damage product of DNA, which may allow a premature assessment of various diseases. This paper designs a label-free, portable biosensor device to directly detect 8-OHdG by plasma-coupled electrochemistry on a transparent and conductive indium tin oxide (ITO) electrode. We reported a flexible printed ITO electrode made from particle-free silver and carbon inks. After inkjet printing, the working electrode was sequentially assembled by gold nanotriangles (AuNTAs) and platinum nanoparticles (PtNPs). This nanomaterial-modified portable biosensor showed excellent electrochemical performance for 8-OHdG detection from 10 μg/mL to 100 μg/mL by our self-developed constant voltage source integrated circuit system. This work demonstrated a portable biosensor for simultaneously integrating nanostructure, electroconductivity, and biocompatibility to construct advanced biosensors for oxidative damage biomarkers. The proposed nanomaterial-modified ITO-based electrochemical portable device was a potential biosensor to approach 8-OHdG point-of-care testing (POCT) in various biological fluid samples, such as saliva and urine samples.

A sensing platform based on nanocomposite materials composed of gold metal nanoparticles (AuNPs) and conducting polymer (CP) matrix has been developed for serotonin and epinephrine detection. The CP-AuNPs nanocomposite materials have been synthesized onto glassy carbon electrodes (GCE) by using novel electrochemical procedures based on sinusoidal currents (SC). The SC procedures ensured good control of the metal nanoparticles distribution, increased electrochemical surface area, and enhanced analytical performance. The proposed sensing platform displayed good analytical performance toward serotonin and epinephrine detection. A wide linear analytical response toward epinephrine in the range from 10 to 640 μM and a low detection limit of 1.4 μM epinephrine has been obtained. The sensing platform has also displayed a linear response toward serotonin in the range from 10 to 320 μM, with a detection limit of 5.7 μM serotonin. The sensing platform has been successfully applied in the analysis of epinephrine and serotonin in real samples of tap water and urine with good accuracy.

Single-entity electrochemistry, which employs electrolysis during the collision of single particles on ultramicroelectrodes, has witnessed significant advancements in recent years, enabling the observation and characterization of individual particles. Information on a single aqueous droplet (e.g., size) can also be studied based on the redox species contained therein. Dopamine, a redox-active neurotransmitter, is usually present in intracellular vesicles. Similarly, in the current study, the electrochemical properties of neurotransmitters in submicron droplets were investigated. Because dopamine oxidation is accompanied by proton transfer, unique electrochemical properties of dopamine were observed in the droplet. We also investigated the electrochemical properties of the adsorbed droplets containing DA and the detection of oxidized dopamine by the recollision phenomenon.

Currently available DNA detection techniques frequently require compromises between simplicity, speed, accuracy, and cost. Here, we propose a simple, label-free, and cost-effective DNA detection platform developed at screen-printed carbon electrodes (SPCEs) modified with reduced graphene oxide (RGO) and gold nanoparticles (AuNPs). The preparation of the detection platform involved a two-step electrochemical procedure based on GO reduction onto SPCEs followed by the electrochemical reduction of HAuCl4 to facilitate the post-grafting reaction with AuNPs. The final sensor was fabricated by the simple physical adsorption of a single-stranded DNA (ssDNA) probe onto a AuNPs-RGO/SPCE electrode. Each preparation step was confirmed by morphological and structural characterization using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy, respectively. Furthermore, the electrochemical properties of the modified electrodes have been investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the introduction of AuNPs onto RGO/SPCEs led to an enhancement in surface conductivity, a characteristic that favored an increased sensitivity in detection. The detection process relied on the change in the electrochemical signal induced by the binding of target DNA to the bioreceptor and was particularly monitored by the change in the charge transfer resistance of a [Fe(CN)6]4-/3- redox couple added in the test solution.

Here, a sensitive voltametric electrochemical sensor probe was fabricated to reliably trace the detection of L-aspartic acid in phosphate-buffered medium using a glassy carbon electrode (GCE) layered with a film of wet-chemically prepared Ag2O-doped ZnO nanosheets (NSs). EDS, FESEM, XPS, and X-ray diffraction analyses were implemented as characterizing tools of prepared NSs to confirm the structural and compositional morphology, binding energies of existing atoms, and the crystallinity of synthesized NSs. The differential pulse voltammetry (DPV) was applied to the trace detection of L-aspartic acid, and exhibited a wide detection range of 15.0~105.0 µM, a limit of detection (3.5 ± 0.15 µM), and good sensitivity (0.2689 µA µM-1 cm-2). Besides these the precious reproducibility, stability, and efficient responses were perceived from the voltametric analysis of aspartic acid. Moreover, the proposed aspartic acid was subjected to experiments to potentially detect aspartic acid in real biological samples. Therefore, the development of an enzyme-free sensor by applying this method will be a smart technical approach in the near future.

A new spectroelectrochemical two-enzyme sensor system has been developed for the detection of acetaldehyde in wine. A combination of spectroscopy and electrochemistry improves the analytical features of the electrochemical sensor because the optical information collected with this system is only associated with acetaldehyde and avoids the interferents also present in wines as polyphenols. Spectroelectrochemical detection is achieved by the analysis of the optical properties of the K3[Fe(CN)6]/K4[Fe(CN)6] redox couple involved in the enzymatic process: aldehyde dehydrogenase catalyzes the aldehyde oxidation using β-nicotinamide adenine dinucleotide hydrate (NAD+) as a cofactor and, simultaneously, diaphorase reoxidizes the NADH formed in the first enzymatic process due to the presence of K3[Fe(CN)6]. An analysis of the characteristic UV-vis bands of K3[Fe(CN)6] at 310 and 420 nm allows the detection of acetaldehyde, since absorption bands are only related to the oxidation of this substrate, and avoids the contribution of other interferents.

Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L-1 and 1 to 50 mg L-1), low limit of detection (1 µg L-1), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.

We report the design of an electrochemical aptasensor for ampicillin detection, which is an antibiotic widely used in agriculture and considered to be a water contaminant. We studied the transducing potential of nanostructure composed of MoS2 nanosheets and conductive polypyrrole nanoparticles (PPyNPs) cast on a screen-printed electrode. Fine chemistry is developed to build the biosensors entirely based on robust covalent immobilizations of naphthoquinone as a redox marker and the aptamer. The structural and morphological properties of the nanocomposite were studied by SEM, AFM, and FT-IR. High-resolution XPS measurements demonstrated the formation of a binding between the two nanomaterials and energy transfer affording the formation of heterostructure. Cyclic voltammetry and electrochemical impedance spectroscopy were used to analyze their electrocatalytic properties. We demonstrated that the nanocomposite formed with PPyNPs and MoS2 nanosheets has electro-catalytic properties and conductivity leading to a synergetic effect on the electrochemical redox process of the redox marker. Thus, a highly sensitive redox process was obtained that could follow the recognition process between the apatamer and the target. An amperometric variation of the naphthoquinone response was obtained regarding the ampicillin concentration with a limit of detection (LOD) of 10 pg/L (0.28 pM). A high selectivity towards other contaminants was demonstrated with this biosensor and the analysis of real river water samples without any treatment showed good recovery results thanks to the antifouling properties. This biosensor can be considered a promising device for the detection of antibiotics in the environment as a point-of-use system.

Ferritin is a clinically important biomarker which reflects the state of iron in the body and is directly involved with anemia. Current methods available for ferritin estimation are generally not portable or they do not provide a fast response. To combat these issues, an attempt was made for lab-on-a-chip-based electrochemical detection of ferritin, developed with an integrated electrochemically active screen-printed electrode (SPE), combining nanotechnology, microfluidics, and electrochemistry. The SPE surface was modified with amine-functionalized graphene oxide to facilitate the binding of ferritin antibodies on the electrode surface. The functionalized SPE was embedded in the microfluidic flow cell with a simple magnetic clamping mechanism to allow continuous electrochemical detection of ferritin. Ferritin detection was accomplished via cyclic voltammetry with a dynamic linear range from 7.81 to 500 ng·mL-1 and an LOD of 0.413 ng·mL-1. The sensor performance was verified with spiked human serum samples. Furthermore, the sensor was validated by comparing its response with the response of the conventional ELISA method. The current method of microfluidic flow cell-based electrochemical ferritin detection demonstrated promising sensitivity and selectivity. This confirmed the plausibility of using the reported technique in point-of-care testing applications at a much faster rate than conventional techniques.

Alkaline phosphatase (ALP) is one of the main biomarkers that is clinically detected in bone and liver disorders using optical assays. The electrochemical principle is important because point-of-care testing is increasing dramatically and absorbance techniques hardly compete with the medical revolution that is occurring. The detection of ALP using electrochemical detection is contributing to the integration systems field, and hence enhancing the detection of biological targets for pharmaceutical research and design systems. Moreover, in vitro electrochemical measurements use cost effective materials and simple techniques. Graphite screen-printed electrodes and linear sweep voltammetry were used to optimize the electrochemistry of the enzymatic product p-aminophenol using the enzyme kinetic assay. ALP release from embryonic and cancer cells was determined from adhesion cell culture. Additionally, capillary electrophoresis and colorimetric methods were applied for comparison assays. The resulting assays showed a dynamic range of ALP ranging from 1.5 to 1500 U/L, and limit of detection of 0.043 U/L. This was achieved by using 70 μL of the sample and an incubation time of 10 min at an optimal substrate concentration of 9.6 mM of p-aminophenol phosphate. A significant difference (p < 0.05) was measured between the absorbance assays. This paper demonstrates the advantages of the electrochemical assay for ALP release from cells, which is in line with recent trends in gene expression systems using microelectrode array technologies and devices for monitoring electrophysiological activity.

Azithromycin (AZY) is a well-known top-prioritized antibiotic and is used by humans in strong concentrations. However, the side effects of the AZY antibiotic may cause some serious and significant damage to humans and the environment. Thus, there is a need to develop effective and sensitive sensors to monitor accurate concentrations of AZY. In the last decade, electrochemistry-based sensors have received enormous attention from the scientific community because of their high sensitivity, selectivity, cost-effectiveness, fast response, rapid detection response, simple fabrication, and working principle. It is important to mention that electrochemical sensors rely on the properties of electrode modifiers. Hence, the selection of electrode materials is of great significance when designing and developing efficient and robust electrochemical sensors. In this study, we fabricated an AZY sensor by utilizing a molybdenum disulfide/titanium aluminum carbide (MoS2@Ti3AlC2) composite as the electrode material. The MoS2@Ti3AlC2 composite was synthesized via a simple sonication process. The synthesized MoS2@Ti3AlC2 composite was characterized using a powder X-ray diffraction (XRD) method to examine the phase purity and formation of the MoS2@Ti3AlC2 composite. Scanning electron microscopy (SEM) was used to study the surface morphological features of the prepared MoS2@Ti3AlC2 composite, whereas energy dispersive X-ray spectroscopy (EDAX) was adopted to determine the elemental composition of the prepared MoS2@Ti3AlC2 composite. The glassy carbon (GC) electrode was modified with the prepared MoS2@Ti3AlC2 composite and applied as the AZY sensor. The sensing performance of the MoS2@Ti3AlC2 composite-modified GC electrode was studied using linear sweep voltammetry. The sensor demonstrated excellent performance when determining AZY and showed a good detection limit of 0.009 µM with a sensitivity of 6.77 µA/µM.cm2.