This work presents the performance of a semi-open electrochemical cell (SOEC) for potentiometric biosensing. In this design, the electrodes are vertically stacked, and a solid-state polyelectrolyte is used as separator. This paper-based device requires a minimal sample volume, as only the top working electrode contacts the solution while the reference electrode remains shielded in the bottom of the cell. Using a paper-based Pt working electrode, the system demonstrates high sensitivity to hydrogen peroxide with linear response below 10 mu M and a Tafel slope of 120 mV/decade at higher concentrations. Electrode area optimization enables tunable analytical performance by controlling sensitivity and linear ranges. The device exhibits exceptional stability, with a baseline noise level below 0.1 mV and low impedance, facilitating integration with simple operational amplifiers. This design achieves ultralow detection limits for hydrogen peroxide (similar to 1 picomole in terms of mass-sensitivity) using only 1 mu L sample volumes and maintains linearity up to 10 mM. When coupled with oxidase enzymes, the system enables rapid and versatile glucose testing in artificial serum and sweat using single sample drops, with absolute limits of detection in the mu M range. This compact, versatile paper-based platform offers promising opportunities for developing wearable, disposable biosensors for point-of-need applications.

A novel paper-based ion-selective organic electrochemical transistor (IS-OECT) for the detection of potassium and creatinine is presented. First, ion-selective membranes are cast onto thick-film transistor channels to create highly sensitive and selective ion sensors. Since optimum performance is obtained at 0 V gate voltage, several sensors can be used in parallel with a single gate connected to a common grounded source electrode. Then, to further demonstrate the detection capabilities, the IS-OECTs were integrated with a purposely designed differential amplifier. This allows the conversion of current signals into a voltage output, facilitating comparison with potentiometric systems and the use of low-cost commercial data acquisition platforms. The evaluation of the performance in artificial serum is performed in clinically relevant ranges, which comprise 2.4-5.75 mM for potassium and 30-140 μM for creatinine. These results highlight the potential of the IS-OECT framework as a cost-effective, portable, and reliable solution for point-of-care diagnostics.

Organic electronics have garnered important attention, as they offer alternatives to classic, more expensive electronic materials and great biocompatibility for building (bio)-chemical sensors. Among them, organic electrochemical transistors (OECTs) provide in situ signal amplification, which translates to excellent performance in electrochemical (bio)-sensing. This work presents a compact paper-based thick-film quasi-solid-state OECT (QSS-OECT) that integrates the gate and channel in a vertically stacked design. Electrochemical activation by pulsing the gate voltage allows reaching high transconductances of up to 12.4 mS. This system is applied to the detection of H2O2 with a sensitivity of 3.5 ± 0.3 mA/dec. The compact vertical configuration of the device allows for a drastic sample volume reduction, which can be performed with droplets of 1 μL as well as under the flow regime with an open cell configuration. The versatility and high transconductance of this device open new avenues for integration within low-cost sensors and biowearable platforms.

The development and optimization of a paper-based ion-selective organic electrochemical transistor (IS-OECT) with an outstanding analytical performance is presented. The combination of thick-film transistor technology with a suitable optimization of the ion-selective membrane composition and thickness allows reaching sensitivities of up to 2.50 mA/decade, which is more than one order of magnitude higher than other similar devices reported up to date. The system shows good selectivity, allowing the detection of low concentrations of potassium in high saline concentrations, and a linear range from 0.1 mM to 100 mM, which covers the relevant clinical range of K+ in blood. A calibration curve for K+ in artificial serum between 1 and 10 mM shows changes in concentrations down to 0.05 mM can be discriminated. Furthermore, the device can be made with a simple manufacturing process, such as drop casting, on low-cost substrate materials and can be operated with a gate voltage of 0 V. This IS-OCET offers promising avenues for developing ion-sensing platforms for the point of need.

In recent years, organic electrochemical transistors (OECTs) have emerged as a promising tool to add to current analytical methods due to their high-amplification capacities, robust analytical performance, and versatility. The present work proposes a compact multi-analyte transistor array with outstanding analytical performance. The ion-selective organic electrochemical transistors (IS-OECTs) were developed by combining the thick-film technology with the optimum ion-selective membrane, resulting in highly sensitive and selective IS-OECTs. The system has then been simplified using only a power supply for each OECT and a single gate electrode. To prove these advantages, the IS-OECT array of sensors has been combined with multivariate models to simultaneously detect and quantify sodium, potassium and ammonium ions in human saliva. The results obtained have been validated against reference techniques, showing promising results and confirming the usefulness of the newly developed sensing array.

A novel electrochemical cell design in a vertically stacked configuration is presented. Through a layered structure using a top macroporous working electrode, a polyelectrolyte, and a bottom metallic conductor a standalone electrochemical cell with an internal reference electrode is built. This sensor allows monitoring an electrochemical property of an external solution with only one electrode in direct contact with the sample. Using paper-based platinum electrode for the porous top electrode and Nafion as polyelectrolyte material, the self-powered detection of hydrogen peroxide is performed. The system can be operated in multiple modes. In a capacitive way, the open circuit potential is measured. Alternatively, in a self-powered current mode, the system emulates a fuel cell. Additionally, a potential-current switched mode is also demonstrated. Because of this unique design and operational features this sensor is considered as an electrochemical pixel. To further demonstrate the advantages of this device, the detection of glucose is performed by building an array of sensors using a single back (reference) electrode and multiple working electrodes. These results lay the groundwork for the development of a new generation of simple and low cost biochemical sensors and electrochemical sensing arrays.

Systematic errors in the calix [4] pyrrole-based potentiometric detection of creatinine have been observed in heavy smokers. This work further characterizes the interactions between the nicotinium cation and the cavitand as well as the resulting interference produced during the potentiometric detection. It is found that the nicotinium cation binds the electronic rich aromatic cavity defined by the pyrrole rings of the receptor's cone conformation with an estimated binding constant higher than 10-4 M-1 in methylene chloride. On the other hand, the creatininium cation is preferentially included in the hydrophobic aromatic cavity of the ionophore by establishing hydrogen bond interactions with the pyrrole NHs groups. Potentiometric calibrations confirmed the detection of the nicotinium cation at neutral and acidic pH, respectively. Due to the lower pka of creatinine, a methodology to quantify creatinine in presence of nicotine by using an array of three sensors at two pH values is proposed. A partial least squares regression was performed and reported recoveries of 103% with a standard deviation of 20%. The improved determination of creatinine was therefore discussed. This approach represents a step forward in the development of effective approaches to improve the measurement of creatinine in decentralized settings.

A paper-based potentiometric sensor was constructed and characterized for the detection of glucose in saliva. Dilution of the samples was optimized to afford the optimum experimental conditions of measurements. The performance allows for detecting abnormal high glucose concentrations observed in diabetes patients. Repeatability data were presented and the performance of the sensor compared to literature examples showing suitable characteristics at a much lower cost. The validation in real saliva samples was performed against a commercial colorimetric kit showing that glucose could be effectively determined in the 4-10 mM range based on the comparison with a reference method.

Organic electrochemical transistors (OECTs) have attracted great interest in the last few years as biochemical sensors due to their outstanding analytical performance, versatility, stability, and e...

The role of hydrogen peroxide in a wide range of biological processes has led to a steady increase in research into hydrogen peroxide determination in recent years, and conducting polymers have attracted much interest in electrochemistry as promising materials in this area. We present an overview of electrochemical devices for hydrogen peroxide determination using conducting polymers, either as a target or as a byproduct of redox reactions. We describe different combinations of electrode modifications through the incorporation of conducting polymers as the main component along with other materials or nanomaterials. We critically compare the analytical performances cited and highlight some of the future challenges for the feasible application of such devices.

A filter paper sputtered with a layer of Pt and subsequently coated with a Nafion (R) membrane is used as working electrode. The mixed potential of the Pt electrode allows the detection of H2O2 generated by the oxidation of galactose in the presence of the galactose oxidase enzyme. This provides a simple and mediator-free approach method. The system shows sensitivity values of -62.8 +/- 9.4 mV/decade of galactose in the range from 0.3 to 31.6 mM, well within the clinical relevant range. MnO2 nanoparticles were added to decrease the interference from ascorbic acid so that validation of the sensor in whole blood samples was performed with good recovery.

A novel paper-based potentiometric platform for the simple and fast monitoring of water hardness is presented. First, potentiometric ion-selective electrodes for calcium and magnesium printed on a paper substrate were built and optimized. These sensors, which display near-Nernstian sensitivity, were used for the determination of the concentration of these cations and the calculation of the water hardness. Second, the incorporation of a solid-state reference electrode allowed building an integrated paper-based potentiometric cell for the determination of the hardness of artificial and real samples (mineral waters). The validation of the results shows good ability to predict hardness in the conventional scale. Truly decentralized measurements were demonstrated by integration of a miniaturized instrument and dedicated software in a portable device. The measurements were able to be performed in just under two minutes, including a two-point calibration. Since the method is simple to use and cost-effective, it can be implemented in domestic and industrial settings.

The role of hydrogen peroxide in a wide range of biological processes has led to a steady increase in research into hydrogen peroxide determination in recent years, and conducting polymers have attracted much interest in electrochemistry as promising materials in this area. We present an overview of electrochemical devices for hydrogen peroxide determination using conducting polymers, either as a target or as a byproduct of redox reactions. We describe different combinations of electrode modifications through the incorporation of conducting polymers as the main component along with other materials or nanomaterials. We critically compare the analytical performances cited and highlight some of the future challenges for the feasible application of such devices.

The use of a Pt electrode coated with a layer of Nafion has been described in previous works as an attractive way to perform the potentiometric detection of hydrogen peroxide. Despite of the attractive features of this approach, the nature of the non-Nernstian response of this system was not properly addressed. In this work, using a mixed potential model, the open circuit potential of the Pt electrode is shown to be under kinetic control of the oxygen reduction reaction (ORR). It is proposed that hydrogen peroxide acts as an oxygenated species that blocks free sites on the Pt surface, interfering with the ORR. Therefore, the effect of the polyelectrolyte coating can be understood in terms of the modulation of the factors that affects the kinetics of the ORR, such as an increase of the H+ concentration, minimization of the effect of the spectator species, etc. Because of the complexity and the lack of models that accurately describe systems with practical applications, this work is not intended to provide a mechanistic but rather a phenomenological view on problem. A general framework to understand the factors that affect the potentiometric response is provided. Experimental evidence showing that the use of polyelectrolyte coatings are a powerful way to control the mixed potential open new ways for the development of robust and simple potentiometric sensors.

Creatinine level in urine is a key factor to monitor kidney performance. The use of an alternative microfluidic platform based on cellulose substrates is an interesting option to integrate sample treatment, creatinine recognition by ionophore extraction chemistry and quantification by color measurement through consumer electronics imaging devices. The inclusion of ionophore extraction chemistry based on aryl-substituted calix[4] pyrrole synthetic receptor on 8.7mm long cotton thread permit the sample treatment, optical recognition of creatinine and their quantification by smartphone running app in unfiltered urine samples diluted 1:100 ratio. The device shows a short response time, 30 s, to creatinine over a wide dynamic range (from 1.6 x 10(-6) to 5 10(-2) M) with precision between 2.9-4.3%. The low interference level of representative species in urine is studied and justified by density functional theory (DFT) calculations.

The growing demand for tools to generate chemical information in decentralized settings is creating a vast range of opportunities for potentiometric sensors, since their combination of robustness, simplicity of operation and cost can hardly be rivalled by any other technique. In previous works, we have shown that the mixed potential of a Pt electrode can be controlled with analytical purposes using a coating of Nafion, thus providing a way to develop a potentiometric biosensor for glucose. Unfortunately, the linear range of this device did not match the relevant clinical range for glucose in blood. This work presents a novel strategy to control the mixed potential that allows the development of a potentiometric biosensor for the direct detection of glucose in whole, undiluted blood without any sample pretreatment. By changing the ionomer, the analytical response can be tuned, shifting the linear range while keeping the sensitivity. Aquivion, a polyelectrolyte from the same family as Nafion, is used to stabilize the mixed potential of a platinized paper-based electrode, to entrap the enzyme and to reduce the interference from negatively charged species. Factors affecting the generation of the signal and the principle of detection are discussed. Optimization of the biosensor composition was achieved with particular focus on the characterization of the linear range and sensitivity. The accurate measurement of blood sugar levels in a single drop of whole blood with excellent recovery is presented.

Creatinine is a metabolite present in urine, and its concentration is used to diagnose and monitor kidney performance. For that reason, the development of new sensors to analyze this metabolite and obtain accurate results in a short period of time is necessary. An optical disposable sensor for monitoring creatinine levels in urine is described. The system, based on a new aryl-substituted calix[4]pyrrole synthetic receptor, has an unusual coextraction scheme. Due to the low p Ka values of creatininium (p Ka 4.8), a careful selection of a lipophilic pH indicator that works in acid medium is required. The sensor components were optimized, and the new sensor displays a good response time to creatinine (approximately 3 min) over a wide dynamic range (from 1 × 10-5 to 1 × 10-2 M). Moreover, the optical selectivity coefficients obtained for creatinine over common cations present in urine meet the requirements for real sample measurements. With a good sensor-to-sensor reproducibility (RSD, 5.1-6.9% in the middle of the range), this method provides a simple, quick, cost-effective, and selective alternative to the conventional methodology based on Jaffé's reaction.

The fabrication and performance of a wearable paper-based chemiresistor for monitoring perspiration dynamics (sweat rate and sweat loss) are detailed. A novel approach is introduced to measure the amount of aqueous solution in the order of microliters delivered to the sensor by monitoring a linear change in resistance along a conducting paper. The wearable sensor is based on a single-walled carbon nanotubes and surfactant (sodium dodecylbenzenesulfonate) nanocomposite integrated within cellulose fibers of a conventional filter paper. The analytical performance and the sensing mechanism are presented. Monitoring sweat loss in the human body while exercising is demonstrated using the integration of a wireless reader and a user-friendly interface. By addressing the barriers of cost, simplicity, and the truly in situ demanding measurements, this unique wearable sensor is expected to serve in the future in many different applications involving the on-body detection of biofluids, such as a monitoring tool of dehydration levels for athletes as well as a tool for enhancing the sport performance by providing an accurate recovery of the hydration status in daily exercises.

Despite predictions of their widespread application in healthcare and environmental monitoring, electrochemical sensors are yet to be distributed at scale, instead remaining largely confined to R&D labs. This contrasts sharply with the situation for physical sensors, which are now ubiquitous and seamlessly embedded in the mature ecosystem provided by electronics and connectivity protocols. Although chemical sensors could be integrated into the same ecosystem, there are fundamental issues with these sensors in the three key areas of analytical performance, usability, and affordability. Nevertheless, advances are being made in each of these fields, leading to hope that the deployment of automated and user-friendly low-cost electrochemical sensors is on the horizon. Here, we present a brief survey of key challenges and advances in the development of distributed electrochemical sensors for liquid samples, geared towards applications in healthcare and wellbeing, environmental monitoring, and homeland security. As will be seen, in many cases the analytical performance of the sensor is acceptable; it is usability that is the major barrier to commercial viability at this moment. Were this to be overcome, the issue of affordability could be addressed. Graphical Abstract ᅟ