Distributed electrochemical sensors: recent advances and barriers to market adoption.

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.

A Million Turnover Molecular Anode for Catalytic Water Oxidation.

Molecular ruthenium-based water oxidation catalyst precursors of general formula [Ru(tda)(Li )2 ] (tda2- is [2,2':6',2''-terpyridine]-6,6''-dicarboxylato; L1 =4-(pyren-1-yl)-N-(pyridin-4-ylmethyl)butanamide, 1 b; L2 =4-(pyren-1-yl)pyridine), 1 c), have been prepared and thoroughly characterized. Both complexes contain a pyrene group allowing ready and efficiently anchoring via π interactions on multi-walled carbon nanotubes (MWCNT). These hybrid solid state materials are exceptionally stable molecular water-oxidation anodes capable of carrying out more than a million turnover numbers (TNs) at pH 7 with an Eapp =1.45 V vs. NHE without any sign of degradation. XAS spectroscopy analysis before, during, and after catalysis together with electrochemical techniques allow their unprecedented oxidative ruggedness to be monitored and verified.

Recognition and Sensing of Creatinine.

Current methods for creatinine quantification suffer from significant drawbacks when aiming to combine accuracy, simplicity, and affordability. Here, an unprecedented synthetic receptor, an aryl-substituted calix[4]pyrrole with a monophosphonate bridge, is reported that displays remarkable affinity for creatinine and the creatininium cation. The receptor works by including the guest in its deep and polar aromatic cavity and establishing directional interactions in three dimensions. When incorporated into a suitable polymeric membrane, this molecule acts as an ionophore. A highly sensitive and selective potentiometric sensor suitable for the determination of creatinine levels in biological fluids, such as urine or plasma, in an accurate, fast, simple, and cost-effective way has thus been developed.

Chloride-selective electrodes based on "two-wall" aryl-extended calix[4]pyrroles: combining hydrogen bonds and anion-π interactions to achieve optimum performance.

The performance of chloride-selective electrodes based on "two-wall" aryl-extended calix[4]pyrroles and multiwall carbon nanotubes is presented. The calix[4]pyrrole receptors bear two phenyl groups at opposite meso-positions. When the meso-phenyl groups are decorated with strong electron-withdrawing substituents, attractive anion-π interactions may exist between the receptor's aromatic walls and the sandwiched anion. These anion-π interactions are shown to significantly affect the selectivity of the electrodes. Calix[4]pyrrole, bearing a p-nitro withdrawing group on each of the meso-phenyl rings, afforded sensors that display anti-Hofmeister behavior against the lipophilic salicylate and nitrate anions. Based on the experimental data, a series of principles that help in predicting the suitability of synthetic receptors for use as anion-specific ionophores is discussed. Finally, the sensors deliver excellent results in the direct detection of chloride in bodily fluids.

Carbon nanotube-based aptasensors for the rapid and ultrasensitive detection of bacteria.

In this paper we present a new generation of potentiometric biosensors based on carbon nanotubes (transducer layer of the biosensor) and aptamers (sensing layer of the biosensor) for the ultralow and selective detection of microorganisms. We show that with these aptasensors we were able to detect a few CFU of the target bacteria almost in real-time, both in buffered and in real samples.

A paper-based organic electrochemical transistor array with a simplified configuration for simultaneous multi-ion detection.

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.

Electrochemical Pixels: Semi-open electrochemical cells with a vertically stacked design.

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.

A potassium sensor based on non-covalent functionalization of multi-walled carbon nanotubes.

Non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) by a pyrene based benzo-18-crown-6 ether 1 leads to nanostructure assemblies that play both the role of an ion-to-electron transducer and a selective recognition element in solid-contact ion-selective-electrodes (SC-ISEs). The high loading capacity (36 wt%) as well as the suitable dispersion character of the MWCNT hybrid in the ion-selective membrane (ISM) confirmed the benefit of this approach over the covalent one. The sensor has been applied successfully to the detection of potassium. Nernstian response (56.9 ± 0.9 mV per decade) was obtained (10(-5) and 10(-2) M K(+)) and the selectivity pattern was not altered by the immobilization of the ionophore on the MWCNTs. Leakage of the ionophore from the polymeric matrix is therefore avoided while the sensor construction was simplified and the analytical performances were maintained.

Potentiometric detection of creatinine in the presence of nicotine: Molecular recognition, sensing and quantification through multivariate regression.

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.

Disposable planar reference electrode based on carbon nanotubes and polyacrylate membrane.

In this technical note, we report a new all-solid-state planar reference electrode based on single-walled carbon nanotubes and photocured poly(n-butylacrylate) (poly(nBA)) membrane containing the Ag/AgCl/Cl(-) ion system. Single-walled carbon nanotubes functionalized with octadecylamide (SWCNT-ODA) and deposited by drop-casting onto a disposable screen-printed electrode are an excellent all-solid-state transducer. The novel potentiometric planar reference electrode shows low potential variability (calibration slopes inferior to 2 mV/dec) for a wide range of chemical species (i.e., ions, small molecules, proteins) in a wide calibration range, redox pairs, changes in pH, and changes in ambient light. Potentiometric medium-term signal stability (-0.9 ± 0.2 mV/h) and electrochemical impedance characterization confirm the correct solid contact between the SWCNT-ODA layer and photocured poly(nBA) membrane. Overall, the materials used and the simple fabrication by screen-printing and drop-casting enable a high throughput and highly parallel and cost-effective mass manufacture of the new disposable reference electrode. Moreover, the reference electrode has a long shelf life, a characteristic that can be of special interest in decentralized and multiplexing potentiometric analysis.

Potentiometric strip cell based on carbon nanotubes as transducer layer: toward low-cost decentralized measurements.

In this study, we developed a potentiometric planar strip cell based on single-walled carbon nanotubes that aims to exploit the attributes of solid-contact ion-selective electrodes for decentralized measurements. That is, the ion-selective and reference electrodes have been simultaneously miniaturized onto a plastic planar substrate by screen-printing and drop-casting techniques, obtaining disposable strip cells with satisfactory performance characteristics (i.e., the sensitivity is 57.4 ± 1.3 mV/dec, the response time is ≤30 s within the linear range from log a(K+) = -5 to -2, and the limit of detection is -6.5), no need of maintenance during long dry storage, quick signal stabilization, and light insensitivity in short-term measurements. We also show how the new potentiometric strip cell makes it possible to perform decentralized and rapid determinations of ions in real samples, such as saliva or beverages.

Electronic interactions between "pea" and "pod": the case of oligothiophenes encapsulated in carbon nanotubes.

One of the most challenging strategies to achieve tunable nanophotonic devices is to build robust nanohybrids with variable emission in the visible spectral range, while keeping the merits of pristine single-walled carbon nanotubes (SWNTs). This goal is realized by filling SWNTs ("pods") with a series of oligothiophene molecules ("peas"). The physical properties of these peapods are depicted by using aberration-corrected high-resolution transmission electron microscopy, Raman spectroscopy, and other optical methods including steady-state and time-resolved measurements. Visible photoluminescence with quantum yields up to 30% is observed for all the hybrids. The underlying electronic structure is investigated by density functional theory calculations for a series of peapods with different molecular lengths and tube diameters, which demonstrate that van der Waals interactions are the bonding mechanism between the encapsulated molecule and the tube.

The Use of Conducting Polymers for Enhanced Electrochemical Determination of Hydrogen Peroxide.

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.

Modulating the mixed potential for developing biosensors: Direct potentiometric determination of glucose in whole, undiluted blood.

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.

Controlling the mixed potential of polyelectrolyte-coated platinum electrodes for the potentiometric detection of hydrogen peroxide.

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.

A Wearable Paper-Based Sweat Sensor for Human Perspiration Monitoring.

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.

Ionophore-Based Optical Sensor for Urine Creatinine Determination.

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.

A disposable, simple, fast and low-cost paper-based biosensor and its application to the determination of glucose in commercial orange juices.

A new biosensor for monitoring glucose levels in beverages is presented. The measurements are performed using potentiometric detection. Working electrodes are made using platinised paper as support and a biocompatible polymeric membrane made of a mixture of polyvinyl alcohol and chitosan containing glucose oxidase as the recognition layer. The system is based on the detection of the hydrogen peroxide generated by an enzymatic reaction performed in a highly sensitive, selective and simple way. The biosensors display suitable analytical performance (sensitivity -119.6 ±â€¯6.4 mV/dec in the 0.03-1.0 mM range with a limit of detection of 0.02 mM). Determination of glucose in commercial orange juices is presented. These results were validated against conventional standard methods, showing good accuracy and fast analytical response. The methodology presented herein does not require complex samples treatment, offering an alternative to conventional methods, particularly for determinations performed with minimal expertise and without a laboratory infrastructure.

A novel wireless paper-based potentiometric platform for monitoring glucose in blood.

A novel low-cost, compact and sensitive paper-based platform for the accurate monitoring of glucose in biological fluids is presented. Paper-based working and reference electrodes are combined to build a whole potentiometric cell, which also fits a sampling module for simple and fast determination of glucose in a single drop of blood. The working electrode is built using a platinized filter paper coated with a Nafion membrane that entraps the enzyme glucose oxidase; the reference electrode is made by casting a polyvinylbutyral-based membrane onto a conductive paper. The system works by detecting the hydrogen peroxide generated as a result of the enzymatic reaction. Selectivity is achieved due to the permselective behaviour of Nafion, while a significant enhancement of the sensitivity is reached by exploiting the Donnan-coupled formal potential. Under optimum conditions, a sensitivity of -95.9 ± 4.8 mV per decade in the 0.3-3 mM range is obtained. Validation of the measurements has been performed against standard methods in human serum and blood. Final integration with a wireless reader allows for truly in situ measurements with a less than 2 minute procedure including a two-point calibration, washing and measurement. This low-cost analytical device opens up new prospects for rapid diagnostic results in non-laboratory settings.

Characterization of a new ionophore-based ion-selective electrode for the potentiometric determination of creatinine in urine.

The optimization, analytical characterization and validation of a novel ion-selective electrode for the highly sensitive and selective determination of creatinine in urine is presented. A newly synthesized calix[4]pyrrole-based molecule is used as an ionophore for the enhanced recognition of creatininium cations. The calculation of the complex formation constants in the polymeric membrane with creatininium, potassium and sodium confirms the strong selective interactions between the ionophore and the target. The optimization of the potentiometric sensor presented here yields an outstanding analytical performance, with a linear range that spans from 1µM to 10mM and limit of detection of 10-6.2M. The calculation of the selectivity coefficients against most commonly found interferences also show significant improvements when compared to other sensors already reported. The performance of this novel sensor is tested by measuring creatinine in real urine samples (N=50) and comparing the values against the standard colorimetric approach (Jaffé's reaction). The results show that this sensor allows the fast and accurate determination of creatinine in real samples with minimal sample manipulation.