Abstract: The high toxicity, endocrine-disrupting effects and low (bio)degradability commonly attributed to phenolic compounds have promoted their recognition as priority toxic pollutants. For this reason, the monitoring of these compounds in industrial, domestic and agricultural streams is crucial to prevent and decrease their toxicity in our daily life. To confront this relevant environmental issue, we propose the use of a combi-electrosensor which combines singlet oxygen (1O2)-based photoelectrochemistry (PEC) with square wave voltammetry (SWV). The high sensitivity of the PEC sensor (being a faster alternative for traditional COD measurements) ensures the detection of nmol L−1 levels of phenolic compounds while the SWV measurements (being faster than the color test kits) allow the differentiation between phenolic compounds. Herein, we report on the development of such a combi-electrosensor for the sensitive and selective detection of phenol (PHOH) in the presence of related phenolic compounds such as hydroquinone (HQ), bisphenol A (BPA), resorcinol (RC) and catechol (CC). The PEC sensor was able to determine the concentration of PHOH in spiked river samples containing only PHOH with a recovery between 96% and 111%. The SWV measurements elucidated the presence of PHOH, HQ and CC in the spiked samples containing multiple phenol compounds. Finally, the practicality of the combi-electrosensor set-up with a dual SPE containing two working electrodes and shared reference and counter electrodes was demonstrated. As a result, the combination of the two techniques is a powerful and valuable tool in the analysis of phenolic samples, since each technique improves the general performance by overcoming the inherent drawbacks that they display independently.

Abstract: Illicit drugs continue to pose a serious threat to society and public health. Drug (ab)use is linked to organised crime and violence. Therefore, to fight the so-called war on drugs, police and law enforcement agencies need to be equipped with accurate and efficient sensors for the detection of illicit drugs and drug use. Even though colour tests (for powders) and lateral flow immunoassays (for biological samples) lack accuracy, they are relied upon for fast and easy on-site detection. Alternatively, in recent years, there has been an increasing interest in electrochemical sensors as a promising technique for the rapid and accurate on-site detection of illicit drugs. While a myriad of literature exists on the use of electrochemical sensors for drug powder analysis, literature on their use for the detection of drug use in biological samples is scarce. To this end, this review presents an overview of strategies for the electrochemical detection of illicit drugs in oral fluid. First, pharmacokinetics of drugs in oral fluid and the legal limit dilemma regarding the analytical cut-offs for roadside drug detection tests are elaborated to present the reader with the background knowledge required to develop such a test. Subsequently, an overview of electrochemical strategies developed for the detection of illicit drugs in oral fluid is given. Importantly, key challenges to address in the development of roadside tests are highlighted to improve the design of the next electrochemical devices and to bring them to the field. Overall, electrochemical sensors for illicit drugs detection in oral fluid show promise to disrupt current strategies for roadside testing.

Abstract: The illicit drug precursor market for the manufacture of amphetamine-type stimulants (ATS), mainly amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA), has emerged quickly in the last years. The evidence of a more complex and sophisticated drug market underlines the pressing need for new on-site methods to quickly detect precursors of synthetic drugs, with electrochemical analysis as a promising technique. Herein, the electrochemical fingerprints of ten common ATS precursors-3-oxo-2-phenylbutanenitrile (APAAN), 3-oxo-2-phenylbutanamide (APAA), methyl 3-oxo-2-phenylbutanoate (MAPA), benzyl methyl ketone (BMK), 1-(1,3-benzodioxol-5-yl)propan-2-one (PMK), ephedrine, pseudoephedrine, safrole, sassafras oil and piperonal- are reported for the first time. The electrochemical screening disclosed the redox inactivity of BMK, which is an essential starting material for the production of ATS. Therefore, the local derivatization of BMK at an electrode surface by reductive amination is presented as a feasible solution to enrich its electrochemical fingerprint. To prove that, the resulting mixture was analyzed using a set of chromatographic techniques to understand the reaction mechanism and to identify possible electrochemical active products. Two reaction products (i.e. methamphetamine and 1-phenylpropan-2-ol) were found and characterized using mass spectrometry and electrochemical methods. Subsequently, the optimization of the reaction parameters was carefully addressed to set the portable electrochemical sensing strategy. Ultimately, the analysis concept was validated for the qualitative identification of ATS precursors in seizures from a forensic institute. Overall, the electrochemical approach demonstrates to be a useful and affordable analytical tool for the early identification of ATS precursors to prevent trafficking and drug manufacture in clandestine laboratories.

Abstract: Phenols are considered as toxic pollutants and their discharge into the environment by industries is regulated by a concentration limit. As these limits are in the low mg L−1 to µg L−1-range, sensitive methods are necessary to detect these phenols. Here, aqueous industrial phenolic samples throughout a cleaning process were analyzed by two novel electrochemical sensors. Both the photoelectrochemical (PEC) sensor and the square wave voltammetric (SWV) sensor could successfully follow the decrease of the concentration of phenols along the industrial cleaning process. The discharge sample (μg L−1) could only be analyzed by the PEC sensor and not by the SWV sensor, as the phenolic concentration was close to the LOD of the latter. With HPLC-diode array detector (DAD) measurements, classical phenols such as phenol (PHOH), hydroquinone, resorcinol and o-cresol could be identified in the industrial samples, and their presence could be linked to the electrochemical responses. At last, the performance of the PEC and SWV sensors were compared with commercial colorimetric and chemical oxygen demand (COD) test kits. This comparison demonstrated the high sensitivity of the PEC sensor in the μg L−1 concentrated phenolic samples. Together with the identification of the redox peaks through HPLC-DAD analysis, the SWV sensor can be a powerful tool in the qualitative analysis of mg L−1 concentrated phenolic samples due to its speed, simplicity and absence of laborious sample pre-treatment steps.

Abstract: The increasing illicit production, distribution and abuse of amphetamine (AMP) poses a challenge for law enforcement worldwide. To effectively combat this issue, fast and portable tools for the on-site screening of suspicious samples are required. Electrochemical profile (EP)-based sensing of illicit drugs has proven to be a viable option for this purpose as it allows rapid voltammetric measurements via the use of disposable and low-cost graphite screen-printed electrodes (SPEs). In this work, a highly practical paraformaldehyde (PFA)-coated sensor, which unlocks the detectability of primary amines through derivatization, is developed for the on-site detection of AMP in seized drug samples. A potential interval was defined at the sole AMP peak (which is used for identification of the target analyte) to account for potential shifts due to fluctuations in concentration and temperature, which are relevant factors for on-site use. Importantly, it was found that AMP detection was not hindered by the presence of common diluents and adulterants such as caffeine, even when present in high amounts. When inter-drug differentiation is desired, a simultaneous second test with the same solution on an unmodified electrode is introduced to provide the required additional electrochemical information. Finally, the concept was validated by analyzing 30 seized AMP samples (reaching a sensitivity of 96.7 %) and comparing its performance to that of commercially available Raman and Fourier Transform Infrared (FTIR) devices.

Abstract: This work presents the results of a novel application for the fast on-site screening of cocaine and its main cutting agents in suspicious and confiscated samples. The methodology behind the novel application consists of portable electrochemical detection coupled with a peak-recognition algorithm for automated result output generation, validated both in laboratory and field settings. Currently used field tests, predominantly colorimetric tests, are lacking accuracy, often giving false positive or negative results. This presses the need for alternative approaches to field testing. By combining portable electrochemical approaches with peak-recognition algorithms, an accuracy of 98.4% concerning the detection of cocaine was achieved on a set of 374 powder samples. In addition, the approach was tested on multiple 'smuggled', colored cocaine powders and cocaine mixtures in solid and liquid states, typically in matrices such as charcoal, syrup and clothing. Despite these attempts to hide cocaine, our approach succeeded in detecting cocaine during on-site screening scenarios. This feature presents an advantage over colorimetric and optical detection techniques, which can fail with colored sample matrices. This enhanced accuracy on smuggled samples will lead to increased efficiency in confiscation procedures in the field, thus significantly reducing societal economic and safety concerns and highlighting the potential for electrochemical approaches in on-the-spot identification of drugs of abuse.

Abstract: Photoelectrochemical (PEC) sensing of phenolic compounds using singlet oxygen (1O2)-generating photocatalysts has emerged as a powerful detection tool. However, it is currently not known how experimental parameters, such as pH and applied potential, influence the generation of reactive oxygen species (ROS) and their photocurrents. In this article, the PEC response was studied over the 6 to 10 pH range using a rotating (ring) disk (R(R)DE) set-up in combination with quenchers, to identify the ROS formed upon illumination of a supported photosensitizer, F64PcZn. The photocurrents magnitude depended on the applied potential and the pH of the buffer solution. The anodic responses were caused by the oxidation of O2.−, generated due to the quenching of 1O2 with −OH and the reaction of 3O2 with [F64Pc(3-)Zn]. The cathodic responses were assigned to the reduction of 1O2 and O2.−, yielding H2O2. These insights may benefit 1O2 – based PEC sensing applications.

Abstract: According to the World Health Organization, about 422 million people worldwide have diabetes, with 1.5 million deaths directly attributed each year. Therefore, there is still a need to effectively monitor glucose in diabetic patients for proper management. Recently, wearable patches based on microneedle (MN) sensors provide minimally invasive analysis of glucose through the interstitial fluid (ISF) while exhibiting excellent correlation with blood glucose. Despite many advances in wearable electrochemical sensors, long-term stability and continuous monitoring remain unsolved challenges. Herein, we present a highly stable electrochemical biosensor based on a redox mediator bilayer consisting of Prussian blue and iron-nickel hexacyanoferrate to increase the long-term stability of the readout coupled with a hollow MN array as a sampling unit for ISF uptake. First, the enzymatic biosensor is developed by using affordable screen-printed electrodes (SPE) and optimized for long-term stability fitting the physiological range of glucose in ISF (i.e., 2.5–22.5 mM). In parallel, the MN array is assessed for minimally invasive piercing of the skin. Subsequently, the biosensor is integrated with the MN array leaving a microfluidic spacer that works as the electrochemical cell. Interestingly, a microfluidic channel connects the cell with an external syringe to actively and rapidly withdraw ISF toward the cell. Finally, the robust MN sensing patch is characterized during in vitro and ex vivo tests. Overall, affordable wearable MN-based patches for the continuous monitoring of glucose in ISF are providing an advent in wearable devices for rapid and life-threatening decision-making processes.

Abstract: Wearable electrochemical sensors are driven by the user-friendly capability of continuous monitoring of key biomarkers for diagnostic or therapeutic operations. Particularly, microneedle (MN)-based sensors can access the interstitial fluid (ISF) in the dermis layer of skin to carry out on-body transdermal detection of analytes. Interestingly, 3D-printing technology allows for rapid and versatile prototyping reaching micrometer resolution. Herein, for the first time, we explore 3D-printed hollow MN patches (1 mm height x 1 mm base with 0.3 mm hole) which are modified with conductive inks to develop a potentiometric sensor for pH monitoring. First, the piercing capability of 3D-printed MN patches is demonstrated by using the parafilm model and their insertion in porcine skin. Subsequently, the hollow MNs are filled with conductive inks to engineer a set of microelectrodes. Thereafter, the working and reference electrodes are properly modified with polyaniline and polyvinyl butyral, respectively, toward a highly stable potentiometric cell. A full in vitro characterization is performed within a broad range of pH (i.e. pH 4 to pH 9). Besides, the MN sensor is analytically assessed in phantom gel and pierced on porcine skin to evaluate the resilience of the MN sensor. Finally, the MN sensor is pierced on the forearm of a subject and tested for its on-body monitoring capability. Overall, 3D-printed MN-based potentiometric sensing brings a versatile and affordable technology to minimally-invasively monitor key physiological parameters in the body.

Abstract: The WHO estimates that 8–10% of couples are facing fertility problems, often due to inaccuracy in predicting the female's ovulation period controlled by four key hormones. The quantification and monitoring of such key hormones are crucial for the early identification of infertility, but also in improving therapeutic management associated with hormonal imbalance. In this review, we extensively summarize and discuss: i) drawbacks of laboratory methods for fertility testing (costly, invasive, complex) and commercially available point-of-care tests (measuring only one/two of the four key hormones), ii) the understanding of different biosensors for fertility monitoring, and iii) an in-depth classification and overview of aptamer-based sensing of the hormones of interest. This review provides insights on hormone detection strategies for fertility, with a focus on the classification of the current ‘aptasensing’ strategies, aiming to assist as a basic guide for the development of accurate fertility window monitoring tools based on aptamers.

Abstract: Methamphetamine (MAP) is a highly addictive and illegal stimulant drug that has a significant impact on the central nervous system. Its detection in biological and street samples is crucial for various organizations involved in forensic medicine, anti-drug efforts, and clinical diagnosis. In recent years, nanotechnology and nanomaterials have played a significant role in the development of analytical sensors for MAP detection. In this study, a fast, simple, and cost-effective electrochemical sensor is presented that is used for the sensitive detection of MAP in confiscated street samples with a complex matrix. The optimized screen-printed sensor based on a carbon working electrode modified with graphene demonstrated an excellent limit of detection, good sensitivity, and a wide dynamic range (1–500 μM) for the target illicit drug both for standard solutions and real samples (seized samples, tap water, and wastewater samples). It can detect MAP at concentrations as low as 300 nM in real samples. This limit of detection is suitable for the rapid preliminary screening of suspicious samples in customs, ports, airports, and on the street. Furthermore, the sensor exhibits a good recovery rate, indicating its reliability and repeatability. This quality is crucial for ensuring consistent and accurate results during screening processes.

Abstract: The haem group is a promising redox probe for the design of albumin-based voltammetric sensors. Among the endogenous ligands carried by human serum albumin (hSA), haem is characterised by a reversible redox behaviour and its binding kinetics strongly depend on hSA’s conformation, which, in turn, depends on the presence of other ligands. In this work, the potential applicability of haem, especially hemin, as a redox probe was first tested in a proof-of-concept study using perfluorooctanoic acid (PFOA) as model analyte. PFOA is known to bind hSA by occupying Sudlow’s I site (FA7) which is spatially related to the haem-binding site (FA1). The latter undergoes a conformational change, which is expected to affect hemin’s binding kinetics. To verify this hypothesis, hemin:albumin complexes in the presence/absence of PFOA were first screened by UV–Vis spectroscopy. Once the complex formation was verified, haem was further characterised via electrochemical methods to estimate its electron transfer kinetics. The hemin:albumin:PFOA system was studied in solution, with the aim of describing the multiple equilibria at stake and designing an electrochemical assay for PFOA monitoring. This latter could be integrated with protein-based bioremediation approaches for the treatment of per- and polyfluoroalkyl substances polluted waters. Overall, our preliminary results show how hemin can be applied as a redox probe in albumin-based voltammetric sensing strategies.

Abstract: Methamphetamine (MA) is a synthetic psychoactive drug which is consumed both licitly and illicitly. In some countries it is prescribed for attention-deficit and hyperactivity disorder, and short-term treatment of obesity. More often though, it is abused for its psychostimulant properties. Unfortunately, the spread and abuse of this synthetic drug have increased globally, being reported as the most widely consumed synthetic psychoactive drug in the world in 2019. Attempting to overcome the shortcomings of the currently used on-site methods for MA detection in suspected cargos, the present study explores the potential of electrochemical identification of MA by means of square wave voltammetry on disposable graphite screen-printed electrodes. Hence, the analytical characterization of the method was evaluated under optimal conditions exhibiting a linear range between 50 mu M and 2.5 mM MA, a LOD of 16.7 mu M, a LOQ of 50.0 mu M and a sensitivity of 5.3 mu A mM-1. Interestingly, two zones in the potential window were identified for the detection of MA, depending on its concentration in solution. Furthermore, the oxidative pathway of MA was elucidated employing liquid chromatography – mass spectrometry to understand the change in the electrochemical profile. Thereafter, the selectivity of the method towards MA in mixtures with other drugs of abuse as well as common adulterants/cutting agents was evaluated. Finally, the described method was employed for the analysis of MA in confiscated samples and compared with forensic methods, displaying its potential as a fast and easy-to-use method for on-site analysis.

Abstract: A highly sensitive and portable electrochemical sensor based on molecularly imprinted nanoparticles (nanoMIPs) was developed. NanoMIPs were computationally designed for specific recognition of amphetamine, and then synthetized using solid phase synthesis. NanoMIPs were immobilized onto screen-printed carbon electrodes using a composite film comprising chitosan, nanoMIPs, and graphene oxide.Ferrocenylmethyl methacrylate was incorporated in nanoMIPs allowing electrochemical detection. The signal recorded for the electrochemical oxidation of ferrocene has proven to be dependent on the presence of amphetamine interacting with nanMIPs. The sensor was tested successfully with street samples, with high sensitivity and satisfactory recoveries (from 100.9% to 107.6%). These results were validated with UPL-MS/MS. The present technology is suitable for forensic applications in selective determination of amphetamine in street samples.

Abstract: Identifying and quantifying 3,4-methyl​enedioxy​methamphetamine (MDMA) on-site in suspected illicit drug samples, whether it be at recreational settings or manufacturing sites, is a major challenge for law enforcement agencies (LEAs). Various analytical techniques exist to fulfil this goal, e.g. colourimetry and portable spectroscopic techniques, each having its specific limitations (e.g. low accuracy, fluorescence, no quantification) and strengths (e.g. fast, easy to use). In this work, for the first time, an electrochemical MDMA sensor is presented to become a detection tool that can realistically be used on-site. More specifically, the use of a single buffer solution and an unmodified screen-printed electrode, along with the integration of a data analysis algorithm and mobile application permits the straightforward on-site identification and quantification of MDMA in suspicious samples. Multiple studies investigating different parameters, including pH, concentration, reproducibility, temperature and binary mixture analyses, were executed. To fully understand all the occurring redox processes, liquid chromatography coupled with high-resolution mass spectrometry analysis of partially electrolyzed MDMA samples was performed unravelling oxidation of the methylenedioxy group. Validation of the methodology was executed on 15 MDMA street samples analysed by gas chromatography coupled with mass spectrometry and compared with the performance of a commercial portable Raman and Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR) device. The novel methodology outperformed the spectroscopic techniques, correctly identifying all 15 street samples. Additionally, the electrochemical sensor predicted the purity of the tablets with a mean absolute error of 2.3%. Overall, this new, electrochemical detection strategy provides LEAs the rapid, low-cost, on-site detection and quantification of MDMA in suspicious samples, without requiring specialized training.