Unveiling Potassium and Sodium Ion Dynamics in Living Plants with an In-Planta Potentiometric Microneedle Sensor.

Potassium and sodium ions (K+ and Na+) play crucial roles in influencing plant growth and health status. Unfortunately, current strategies to determine the concentrations of such ions are destructive for the plants because it is necessary to collect/extract the sap for further analysis and produce either scattered or delayed results. Here, we introduce a new potentiometric dual microneedle sensor for nondestructive, real-time, and continuous monitoring of K+ and Na+ concentrations in living plants. The developed sensors show a response time <5 s, close-to-Nernstian slope (∼55 mV dec-1), resiliency to five insertions on the stem, good repeatability (max. %RSD = 0.3%) and reversibility (max. %RSD = 3%), appropriate continuous operation for 24 h, and linear range of responses that cover expected plant physiological levels (5-50 mM for Na+ and 50-120 mM for K+). Moreover, the accuracy was successfully investigated by comparing the results provided by the microneedle sensors to those obtained by a standard reference method (e.g., ion chromatography). Finally, we demonstrate that the developed analytical device is capable of tracking K+ and Na+ transportation from the hydroponic solution to the stem within 5-10 min. This research will contribute to establishing a new generation of analytical platforms for smart agriculture offering real-time information.

3D-Printed Transducers for Solid Contact Potentiometric Ion Sensors: Improving Reproducibility by Fabrication Automation.

3D printing technology has become attractive in the development of electrochemical sensors as it offers automation in fabrication, customization on-demand, and reproducibility, among other features. Nonetheless, to date, solid contact potentiometric ion sensors have remained overlooked using this technology. Thus, the novelty of this work relies on demonstrating for the first time the usefulness of the multimaterial 3D printing approach to manufacture potentiometric ion-selective electrodes. The significance is indeed twofold. First, we discovered that by using the polyethylene terephthalate glycol (PETg) and polylactic acid-carbon black (PLA-CB) filaments together with a rational electrode design containing a well to accommodate the ion-selective membrane, a tight seal among all of the sensing materials is obtained. Importantly, this has mainly impacted the electrode-to-electrode reproducibility (ERSD0 ± 3 mV). Second, 75 ready-to-use electrodes can be printed in less than 3.5 h in a completely automated manner at a cost of ∼0.32 €/sensor. This feature may positively impact the suitability of further scaled-up production as well as the possibility of application in low-resource contexts. Overall, the presented outcomes are expected to encourage certain research directions to adopt using multimaterial 3D-printing approaches for producing highly reproducible solid contact potentiometric ion-selective electrodes, but are not restricted to them.

Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Light-induced Delivery of Charged Species using Ion-selective Core-Shell Nanoparticles.

Controlled release systems have gained considerable attention owing to their potential to deliver molecules, including ions and drugs, in a customized manner. We present a light-induced ion-transfer platform consisting of a dispersion of nanoparticles (NPs, ~300 nm) with the conductive polymer poly(3-octylthiophene-2,5-diyl) (POT) in the core and a potassium (K+)-selective membrane in the shell. Owing to the photoactive nature of POT, POT NPs can be used for a dual purpose: as a host for positively charged species and as an actuator to trigger the subsequent release. POT0 and doped POT+ coexist in the core, allowing K+ encapsulation in the shell. As POT0 is photo-oxidized to POT+, K+ is released to the (aqueous) dispersion phase to preserve the neutrality of the NPs. This process is reversible and can be simultaneously assessed using the native fluorescence of POT0 and via potentiometric measurements. The NP structure and its mechanism of action were thoroughly studied with a series of control experiments and complementary techniques. Understanding the NP and its surrounding interactions will pave the way for other nanostructured systems, facilitating sophisticated applications. The delivery of ionic drugs and interference/pollutant catching for advanced sensing/restoration will be considered in future research.

Usefulness of the Distribution of Relaxation Time Method in Electroanalytical Systems: The Case of Voltammetric Ion-Selective Electrodes.

Despite the distribution of relaxation time (DRT) method providing clear insights about processes that go unnoticed by traditional electrochemical impedance spectroscopy (EIS) analysis, it has not yet been adopted to solve electroanalytical systems. As an illustration case, we apply the DRT method to deconvolve EIS data from solid-state voltammetric ion-selective electrodes (ISEs). The main aim is to shed light on the underlying working mechanism across the different materials and interfaces, specifically, the doping of a conducting polymer when covered with a very thin (ca. 230 nm) permselective membrane. Although frequency-dependent AC measurements in EIS allow the separation of processes that contribute to the electrical signal, interpretation of the data is challenging. DRT may overcome this inconvenience by revealing a series of peaks corresponding to the predominant electrochemical processes, without any preknowledge on those. To demonstrate our hypothesis, we examine the conducting polymer poly(3-octylthiophene) (POT) linked to a membrane with sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (Na+TFPB-) as the cation exchanger, in which the lipophilic anionic part (TFPB-) is responsible for the POT doping when it gets electrochemically oxidized (POT+). The investigation of EIS data obtained under different conditions with the DRT method showed the occurrence of several processes. We have attributed two of these to two different conformational changes in the POT film in connection with p-type charge-transfer doping. Indeed, the kinetics is found to follow a Butler-Volmer behavior, with average charge transfers of 0.5 and 0.3 mol of electrons for each peak. Overall, we demonstrate the utility of the EIS-DRT tandem to separately study charge-transfer events that interconnect along the same (interfacial segmented) system, which cannot be reached by using classical electrochemical approaches. These kinds of insights are necessary for a more efficient design and high-level exploitation of voltammetric ISEs but also other electrochemical systems such as catalysts, batteries, and photovoltaic cells.

Demonstrating the Analytical Potential of a Wearable Microneedle-Based Device for Intradermal CO2 Detection.

Monitoring of carbon dioxide (CO2) body levels is crucial under several clinical conditions (e.g., human intensive care and acid-base disorders). To date, painful and risky arterial blood punctures have been performed to obtain discrete CO2 measurements needed in clinical setups. Although noninvasive alternatives have been proposed to assess CO2, these are currently limited to benchtop devices, requiring trained personnel, being tedious, and providing punctual information, among other disadvantages. To the best of our knowledge, the literature and market lack a wearable device for real-time, on-body monitoring of CO2. Accordingly, we have developed a microneedle (MN)-based sensor array, labeled as CO2-MN, comprising a combination of potentiometric pH- and carbonate (CO32-)-selective electrodes together with the reference electrode. The CO2-MN is built on an epidermal patch that allows it to reach the stratum corneum of the skin, measuring pH and CO32- concentrations directly into the interstitial fluid (ISF). The levels for the pH-CO32- tandem are then used to estimate the PCO2 in the ISF. Assessing the response of each individual MN, we found adequate response time (t95 < 5s), sensitivity (50.4 and -24.6 mV dec-1 for pH and CO32-, respectively), and stability (1.6 mV h-1 for pH and 2.1 mV h-1 for CO32-). We validated the intradermal measurements of CO2 at the ex vivo level, using pieces of rat skin, and then, with in vivo assays in anesthetized rats, showing the suitability of the CO2-MN wearable device for on-body measurements. A good correlation between ISF and blood CO2 concentrations was observed, demonstrating the high potential of the developed MN sensing technology as an alternative to blood-based analysis in the near future. Moreover, these results open new horizons in the noninvasive, real-time monitoring of CO2 as well as other clinically relevant gases.

Voltammetric Ion-Selective Electrodes in Thin-Layer Samples: Absolute Detection of Ions Using Ultrathin Membranes.

Calibration-free sensors are generally understood as analytical tools with no need for calibration apart from the initial one (i.e., after its fabrication). However, an "ideal" and therefore "more restricted" definition of the concept considers that no calibration is necessary at all, with the sensor being capable of directly providing the analyte concentration in the sample. In the electroanalysis field, investigations have been directed to charge-based readouts (i.e., coulometry) that allow for concentration calculation via the Faraday Law: The sample volume must be precisely defined and the absoluteness of the electrochemical process in which the analyte is involved must be ensured (i.e., the analyte in the sample is ∼100% converted/transported). Herein, we report on the realization of calibration-free coulometric ISEs based on ultrathin ion-selective membranes, which is demonstrated for the detection of potassium ions (K+). In essence, the K+ transfer at the membrane-sample interface is modulated by the oxidation state of the conducting polymer underlying the membrane. The accumulation/release of K+ to/from the membrane is an absolute process owing to the confinement of the sample to a thin-layer domain (thickness of <100 µm). The capacity of the membrane expressed in charge is fixed to ca. 18 µC, and this dictates the detection of micromolar levels of K+ present in ca. 5 µL sample volume. The system is interrogated with cyclic voltammetry to obtain peaks related to the K+ transfer that can be treated charge-wise. The conceptual and technical innovative steps developed here made the calibration-free detection of K+ possible in artificial and real samples with acceptable accuracy (<10% difference compared with the results obtained from a current-based calibration and ion chromatography). The charge-based analysis does not depend on temperature and appeared to be repetitive, reproducible, and reversible in the concentration range from 1 to 37.5 µM, with an average coulometry efficiency of 96%.

Selective Deionization of Thin-Layer Samples Using Tandem Carbon Nanotubes-Polymeric Membranes.

Herein, we investigate the selective deionization (i.e., the removal of ions) in thin-layer samples (<100 µm in thickness) using carbon nanotubes (CNTs) covered with an ionophore-based ion-selective membrane (ISM), resulting in a CNT-ISM tandem actuator. The concept of selective deionization is based on a recent discovery by our group ( Anal. Chem. 2022, 94, 21, 7455-7459), where the activation of the CNT-ISM architecture is conceived on a mild potential step that charges the CNTs to ultimately generate the depletion of ions in a thin-layer sample. The role of the ISM is to selectively facilitate the transport of only one ion species to the CNT lattice. To estimate the deionization efficiency of such a process, a potentiometric sensor is placed less than 100 µm away from the CNT-ISM tandem, inside a microfluidic cell. This configuration helped to reveal that the selective uptake of ions increases with the capacitance of the CNTs and that the ISM requires a certain ion-exchanger capacity, but this does not further affect its efficiency. The versatility of the concept is demonstrated by comparing the selective uptake of five different ions (H+, Li+, Na+, K+, and Ca2+), suggesting the possibility to remove any cation from a sample by simply changing the ionophore in the ISM. Furthermore, ISMs based on two ionophores proved to achieve the simultaneous and selective deionization of two ion species using the same actuator. Importantly, the relative uptake between the two ions was found to be governed by the ion-ionophore binding constants, with the most strongly bound ion being favored over other ions. The CNT-ISM actuator concept is expected to contribute to the analytical sensing field in the sense that ionic interferents influencing the analytical signal can selectively be removed from samples to lower traditional limits of detection.

Imaging of CO2 and Dissolved Inorganic Carbon via Electrochemical Acidification-Optode Tandem.

Dissolved inorganic carbon (DIC) is a key component of the global carbon cycle and plays a critical role in ocean acidification and proliferation of phototrophs. Its quantification at a high spatial resolution is essential for understanding various biogeochemical processes. We present an analytical method for 2D chemical imaging of DIC by combining a conventional CO2 optode with localized electrochemical acidification from a polyaniline (PANI)-coated stainless-steel mesh electrode. Initially, the optode response is governed by local concentrations of free CO2 in the sample, corresponding to the established carbonate equilibrium at the (unmodified) sample pH. Upon applying a mild potential-based polarization to the PANI mesh, protons are released into the sample, shifting the carbonate equilibrium toward CO2 conversion (>99%), which corresponds to the sample DIC. It is herein demonstrated that the CO2 optode-PANI tandem enables the mapping of free CO2 (before PANI activation) and DIC (after PANI activation) in complex samples, providing high 2D spatial resolution (approx. 400 µm). The significance of this method was proven by inspecting the carbonate chemistry of complex environmental systems, including the freshwater plant Vallisneria spiralis and lime-amended waterlogged soil. This work is expected to pave the way for new analytical strategies that combine chemical imaging with electrochemical actuators, aiming to enhance classical sensing approaches via in situ (and reagentless) sample treatment. Such tools may provide a better understanding of environmentally relevant pH-dependent analytes related to the carbon, nitrogen, and sulfur cycles.

Fully Integrated Wearable Device for Continuous Sweat Lactate Monitoring in Sports.

The chemical digitalization of sweat using wearable sensing interfaces is an attractive alternative to traditional blood-based protocols in sports. Although sweat lactate has been claimed to be a relevant biomarker in sports, an analytically validated wearable system to prove that has not yet been developed. We present a fully integrated sweat lactate sensing system applicable to in situ perspiration analysis. The device can be conveniently worn in the skin to monitor real-time sweat lactate during sports, such as cycling and kayaking. The novelty of the system is threefold: advanced microfluidics design for sweat collection and analysis, an analytically validated lactate biosensor based on a rational design of an outer diffusion-limiting membrane, and an integrated circuit for signal processing with a custom smartphone application. The sensor covering the range expected for lactate in sweat (1-20 mM), with appropriate sensitivity (-12.5 ± 0.53 nA mM-1), shows an acceptable response time (<90 s), and the influence of changes in pH, temperature, and flow rate are neglectable. Also, the sensor is analytically suitable with regard to reversibility, resilience, and reproducibility. The sensing device is validated through a relatively high number of on-body tests performed with elite athletes cycling and kayaking in controlled environments. Correlation outcomes between sweat lactate and other physiological indicators typically accessible in sports laboratories (blood lactate, perceived exhaustion, heart rate, blood glucose, respiratory quotient) are also presented and discussed in relation to the sport performance monitoring capability of continuous sweat lactate.

Electrochemical lateral-flow device for rapid COVID-19 antigen-diagnostic testing.

Antigen test kits (ATK) are extensively utilized for screening and diagnosing COVID-19 because they are easy to operate. However, ATKs exhibit poor sensitivity and cannot detect low concentrations of SARS-CoV-2. Herein, we present a new, highly sensitive, and selective device obtained by combining the principle of ATKs with electrochemical detection for COVID-19 diagnosis, which can be quantitatively assessed using a smartphone. An electrochemical test strip (E-test strip) was constructed by attaching a screen-printed electrode inside a lateral-flow device to exploit the remarkable binding affinity of SARS-CoV-2 antigen to ACE2. The ferrocene carboxylic acid attached to SARS-CoV-2 antibody acts as an electroactive species when it binds to SARS-CoV-2 antigen in the sample before it flows continuously to the ACE2-immobilization region on the electrode. Electrochemical-assay signal intensity on smartphones increased proportionally to the concentration of SARS-CoV-2 antigen (LOD = 2.98 pg/mL, under 12 min). Additionally, the application of the single-step E-test strip for COVID-19 screening was demonstrated using nasopharyngeal samples, and the results were consistent with those obtained using the gold standard (RT-PCR). Therefore, the sensor demonstrated excellent performance in assessing and screening COVID-19, and it can be used professionally to accurately verify diagnostic data while remaining rapid, simple, and inexpensive.

Portable All-in-One Electrochemical Actuator-Sensor System for the Detection of Dissolved Inorganic Phosphorus in Seawater.

We present a methodology for the detection of dissolved inorganic phosphorous (DIP) in seawater using an electrochemically driven actuator-sensor system. The motivation for this work stems from the lack of tangible solutions for the in situ monitoring of nutrients in water systems. It does not require the addition of any reagents to the sample and works under mild polarization conditions, with the sample confined to a thin-layer compartment. Subsequent steps include the oxidation of polyaniline to lower the pH, the delivery of molybdate via a molybdenum electrode, and the formation of an electroactive phosphomolybdate complex from DIP species. The phosphomolybdate complex is ultimately detected by either cyclic voltammetry (CV) or square wave voltammetry (SWV). The combined release of protons and molybdate consistently results in a sample pH < 2 as well as a sufficient excess of molybdate, fulfilling the conditions required for the stoichiometric detection of DIP. The current of the voltammetric peak was found to be linearly related to DIP concentrations between 1 and 20 µM for CV and 0.1 and 20 µM for SWV, while also being selective against common silicate interference. The analytical application of the system was demonstrated by the validated characterization of five seawater samples, revealing an acceptable degree of difference compared to chromatography measurements. This work paves the way for the future DIP digitalization in environmental waters by in situ electrochemical probes with unprecedented spatial and temporal resolution. It is expected to provide real-time data on anthropogenic nutrient discharges as well as the improved monitoring of seawater restoration actions.

In Vivo Transdermal Multi-Ion Monitoring with a Potentiometric Microneedle-Based Sensor Patch.

Microneedle sensor technology offers exciting opportunities for decentralized clinical analyses. A novel issue puts forward herein is to demonstrate the uniqueness of membrane-based microneedles to accomplish real-time, on-body monitoring of multiple ions simultaneously. The use of multi-ion detection is clinically relevant since it is expected to provide a more complete and reliable assessment of the clinical status of a subject concerning electrolyte disorders and others. We present a microneedle system for transdermal multiplexed tracing of pH, Na+, K+, Ca2+, Li+, and Cl-. The device consists of an array of seven solid microneedles externally modified to provide six indicator electrodes, each selective for a different ion, and a common reference electrode, all integrated into a wearable patch read in a potentiometric mode. We show in vitro measurements at the expected clinical levels, resulting in a fast response time, excellent reversibility and repeatability, and adequate selectivity. Close-to-Nernstian sensitivity, sufficient stability and resiliency to skin penetration guarantee the sensor's success in transdermal measurements, which we demonstrate through ex vivo (with pieces of rat skin) and in vivo (on-body measurements in rats) tests. Accuracy is evaluated by comparison with gold standard techniques to characterize collected dermal fluid, blood, and serum. In the past, interstitial fluid (ISF) analysis has been challenging due to difficult sample collection and analysis. For ions, this has resulted in extrapolations from blood concentrations (invasive tests) rather than pure measurements in ISF. The developed microneedle patch is a relevant analytical tool to address this information gap.

Imaging Sample Acidification Triggered by Electrochemically Activated Polyaniline.

In this letter, we demonstrate 2D acidification of samples at environmental and physiological pH with an electrochemically activated polyaniline (PANI) mesh. A novel sensor-actuator concept is conceived for such a purpose. The sample is sandwiched between the PANI (actuator) and a planar pH optode (sensor) placed at a very close distance (∼0.50 mm). Upon application of a mild potential to the mesh, in contrast to previously reported acidification approaches, PANI releases a significant number of protons, causing an acid-base titration in the sample. This process is monitored in time and space by the pH optode, providing chemical imaging of the pH decrease along the dynamic titration via photographic acquisition. Acidification of samples at varying buffer capacity has been investigated: the higher the buffer capacity, the more time (and therefore proton charge) was needed to reach a pH of 4.5 or even lower. Also, the ability to map spatial differences in buffer capacity within a sample during the acid-base titration was unprecedentedly proven. The sensor-actuator concept could be used for monitoring certain analytes in samples that specifically require acidification pretreatment. Particularly, in combination with different optodes, dynamic mapping of concentration gradients will be accessible in complex environmental samples ranging from roots and sediments to bacterial aggregates.

Intradermal Glycine Detection with a Wearable Microneedle Biosensor: The First In Vivo Assay.

Glycine (GLY) is gaining importance in medical diagnoses due to its relationship with multiple physiological functions. Today, GLY is exclusively analyzed using instrumentation centralized in clinical labs, and a tangible point-of-care tool that gathers real-time data from the patient for effective and fast evaluations is lacking. Relevant clinical advances are expected as soon as the rapid provision of both punctual and continuous measurements is possible. In that context, this work presents a microneedle (MN)-based biosensor for intradermal GLY detection in interstitial fluid (ISF). The MN tip is externally tailored to detect GLY levels through the hydrogen peroxide formed in its reaction with a quinoprotein-based GLY oxidase enzyme. The analytical performance of the MN biosensor indicates a fast response time (<7 s); acceptable reversibility, reproducibility, and stability; as well as a wide linear range of response (25-600 µM) that covers the physiological levels of GLY in ISF. The MN biosensor conveniently exhibits high selectivity for GLY over other compounds commonly found in ISF, and the response is not influenced by temperature, pH, or skin insertions. Validated intradermal measurements of GLY were obtained at the in vitro (with pieces of rat skin), ex vivo (on-body tests of euthanized rats) and in vivo (on-body tests of anesthetized rats) levels, demonstrating its ability to produce accurate physiological data. The developed GLY MN biosensor is skin-wearable and provides reliable, real-time intradermal GLY measurements in ISF by means of a minimally invasive approach.

Spectroelectrochemistry with Ultrathin Ion-Selective Membranes: Three Distinct Ranges for Analytical Sensing.

We present spectroelectrochemical sensing of the potassium ion (K+) at three very distinct analytical ranges─nanomolar, micromolar, and millimolar─when using the same ion-selective electrode (ISE) but interrogated under various regimes. The ISE is conceived in the all-solid-state format: an ITO glass modified with the conducting polymer poly(3-octylethiophene) (POT) and an ultrathin potassium-selective membrane. The experimental setup is designed to apply a potential in a three-electrode electrochemical cell with the ISE as the working electrode, while dynamic spectral changes in the POT film are simultaneously registered. The POT film is gradually oxidized to POT+, and this process is ultimately linked to K+ transfer at the membrane-sample interface, attending to electroneutrality requirements. The spectroelectrochemistry experiment provides two signals: a voltammetric peak and a transient absorbance response, with the latter of special interest because of its correspondence with the generated charge in the POT and thus with the ionic charge expelled from the membrane. By modifying how the ion analyte (K+ but also others) is initially accumulated into the membrane, we found three ranges of response for the absorbance: 10-950 nM for an accumulation-stripping protocol, 0.5-10 µM in diffusion-controlled cyclic voltammetry, and 0.5-32 mM with thin-layer cyclic voltammetry. This wide response range is a unique feature, one that is rare to find for a sensor and indeed for any analytical technique. Accordingly, the developed sensor is highly appealing for many analytical applications, especially considering the versatility of samples and ion analytes that may be spotted.

Selective Ion Capturing via Carbon Nanotubes Charging.

We present a phenomenon consisting of the synergistic effects of a capacitive material, such as carbon nanotubes (CNTs), and an ion-selective, thin-layer membrane. CNTs can trigger a charge disbalance and propagate this effect into a thin-layer membrane domain under mildly polarization conditions. With the exceptional selectivity and the fast establishment of new concentration profiles provided by the thin-layer membrane, a selective ion capture from the solution is expected, which is necessarily linked to the charge generation on the CNTs lattice. As a proof-of-concept, we investigated an arrangement based on a layer of CNTs modified with a nanometer-sized, potassium-selective membrane to conform an actuator that is in contact with a thin-layer aqueous solution (thickness of 50 µm). The potassium ion content was fixed in the solution (0.1-10 mM range), and the system was operated for 120 s at -400 mV (with respect to the open circuit potential). A 10-fold decrease from the initial potassium concentration in the thin-layer solution was detected through either a potentiometric potassium-selective sensor or an optode confronted to the actuator system. This work is significant, because it provides empirical evidence for interconnected charge transfer processes in CNT-membrane systems (actuators) that result in controlled ion uptake from the solution, which is monitored by a sensor. One potential application of this concept is the removal of ionic interferences in a sample by means of the actuator to enhance precision of analytical assessments of a charged or neutral target in the sample with the sensor.

Potentiometric pH Nanosensor for Intracellular Measurements: Real-Time and Continuous Assessment of Local Gradients.

We present a pH nanosensor conceived for single intracellular measurements. The sensing architecture consisted of a two-electrode system evaluated in the potentiometric mode. We used solid-contact carbon nanopipette electrodes tailored to produce both the indicator (pH nanosensor) and reference electrodes. The indicator electrode was a membrane-based ion-selective electrode containing a receptor for hydrogen ions that provided a favorable selectivity for intracellular measurements. The analytical features of the pH nanosensor revealed a Nernstian response (slope of -59.5 mV/pH unit) with appropriate repeatability and reproducibility (variation coefficients of <2% for the calibration parameters), a fast response time (<5 s), adequate medium-term drift (0.7 mV h-1), and a linear range of response including physiological and abnormal cell pH levels (6.0-8.5). In addition, the position and configuration of the reference electrode were investigated in cell-based experiments to provide unbiased pH measurements, in which both the indicator and reference electrodes were located inside the same cell, each of them inside two neighboring cells, or the indicator electrode inside the cell and the reference electrode outside of (but nearby) the studied cell. Finally, the pH nanosensor was applied to two cases: (i) the tracing of the pH gradient from extra-to intracellular media over insertion into a single PC12 cell and (ii) the monitoring of variations in intracellular pH in response to exogenous administration of pharmaceuticals. It is anticipated that the developed pH nanosensor, which is a label-free analytical tool, has high potential to aid in the investigation of pathological states that manifest in cell pH misregulation, with no restriction in the type of targeted cells.

Reagentless Acid-Base Titration for Alkalinity Detection in Seawater.

Herein, we report on a reagentless electroanalytical methodology for automatized acid-base titrations of water samples that are confined into very thin spatial domains. The concept is based on the recent discovery from our group (Wiorek, A. Anal. Chem. 2019, 91, 14951-14959), in which polyaniline (PANI) films were found to be an excellent material to release a massive charge of protons in a short time, achieving hence the efficient (and controlled) acidification of a sample. We now demonstrate and validate the analytical usefulness of this approach with samples collected from the Baltic Sea: the titration protocol indeed acts as an alkalinity sensor via the calculation of the proton charge needed to reach pH 4.0 in the sample, as per the formal definition of the alkalinity parameter. In essence, the alkalinity sensor is based on the linear relationship found between the released charge from the PANI film and the bicarbonate concentration in the sample (i.e., the way to express alkalinity measurements). The observed alkalinity in the samples presented a good agreement with the values obtained by manual (classical) acid-base titrations (discrepancies <10%). Some crucial advantages of the new methodology are that titrations are completed in less than 1 min (end point), the PANI film can be reused at least 74 times over a 2 week period (<5% of decrease in the released charge), and the utility of the PANI film to even more decrease the final pH of the sample (pH ∼2) toward applications different from alkalinity detection. Furthermore, the acidification can be accomplished in a discrete or continuous mode depending on the application demands. The new methodology is expected to impact the future digitalization of in situ acid-base titrations to obtain high-resolution data on alkalinity in water resources.

Can Wearable Sweat Lactate Sensors Contribute to Sports Physiology?

The rise of wearable sensors to measure lactate content in human sweat during sports activities has attracted the attention of physiologists given the potential of these "analytical tools" to provide real-time information. Beyond the assessment of the sensing technology per se, which, in fact, has not rigorously been validated yet in controlled conditions, there are many open questions about the true usefulness of such wearable sensors in real scenarios. On the one hand, the evidence for the origin of sweat lactate (e.g., via the sweat gland, derivation from blood, or other alternative mechanisms), its high concentration (1-25 mM or even higher) compared to levels in the blood, and the possible correlation between different biofluids (particularly blood) is rather contradictory and generates vivid debate in the field. On the other hand, it is important to point out that accurate detection of sweat lactate is highly dependent on the procedure used to collect and/or reach the fluid, and this can likely explain the large discrepancies reported in the literature. In brief, this paper provides our vision of the current state of the field and a thoughtful evaluation of the possible reasons for present controversies, together with an analysis of the impact of wearable sweat lactate sensors in the physiological context. Finally, although there is not yet overwhelming scientific evidence to provide an unequivocal answer to whether wearable sweat lactate sensors can contribute to sports physiology, we still understand the importance to bring this challenging question up-front to create awareness and guidance in the development, validation, and implementation of wearable sensors.