We present the synthesis of a new adamantane derivative containing Os(II) centers and investigate its function as a dissolved redox mediator in thin-layer ion-selective membranes for voltammetric ion sensing. The pronounced lipophilicity of the designed compound, herein termed as adamantane Os(II), ensures exceptional compatibility with the thin-layer membrane and its constituents (cation exchanger, ionophore, plasticizer, polymer), presenting complete dissolution at elevated concentrations (160 mmol/kg), absence of leaching into the sample during membrane electrode polarization, and reversible electrochemical behavior. The electrochemistry of the adamantane Os(II) is thoroughly characterized in organic medium, with variations in the counter ions of the background electrolyte and 19 distinct membrane compositions, which include control compositions, various plasticizers (DOS, o-NPOE) and polymeric matrix (PVC, PU) as well as sodium ion ionophore. The membrane composition is refined considering three interrogation strategies (namely thin-layer, diffusion, and accumulation regimes) to quantify sodium ion concentrations across several ranges (from micromolar to millimolar) in environmental samples. The accuracy of the methodology was experimentally validated using ion chromatography as the gold standard, revealing a discrepancy of < 3 % between them. Furthermore, a comprehensive theory for ionophore-based thin-layer membranes is established and supplemented by relevant numerical simulations for the three operational modes; successfully, the empirical data align closely with the proposed theoretical hypothesis. The advancement of novel lipophilic and reversible metallic-based redox mediators may create new prospects for the detection of ions and biomolecules.

As global demand for food rises and agricultural systems face unprecedented stress from environmental challenges, understanding the role of ions (i.e., key nutrient components) in crop productivity has never been more critical. Unfortunately, current tools for ion analysis in plants rely on destructive sap collection that fails to capture the dynamic changes in ionic concentrations. On the other hand, noninvasive optical methods lack practicality for field applications due to their reliance on expensive equipment and complex operational procedures. Recent advancements in microneedle (MN) sensing technology have demonstrated significant potential for real-time monitoring of plants' health by enabling the direct detection of various important biomarkers, including but not limited to ions. By offering a minimally invasive approach, MN sensors allow continuous in-planta monitoring with precise penetration into plant tissues, ensuring natural growth remains undisturbed. However, the application of MN sensors, especially for in vivo ion measurement, is still in its very early stage. Herein, we delve into the technological potential and application avenues of plant MN sensors, with a focus on tailoring sensor designs to meet the specific requirements of various plant growth environments and analytical performances for ion detection. This perspective paper also introduces the essential relevance of ion levels in plants, provides a comprehensive assessment of existing ion detection methods, and identifies key challenges associated with achieving effective in planta monitoring. Notably, we highlight the potential of MN sensors as a transformative approach for unveiling plant stress responses, optimizing crop yields, and fulfilling diverse roles that bridge the fields of precision agriculture and plant science research.

Ascorbic Acid (AA) has been the center of controversial dialogues and studies when it comes to cancer research, though recently it has gained interest as an anti-tumor agent. Here, we present an electroanalytical concept to determine AA based on a new fundamental finding: the reversible interaction of AA with carbon nanotubes (CNTs) under zero-current measurements (potentiometry). This interaction is systemically studied under several experimental conditions, aiming to provide specificity with the combination of a thin film of CNTs with a nanometer-sized plasticized polymeric membrane (ca. 300 nm in thickness). The resulting sensor shows a consistent sensitivity to AA of –33.53 ± 2.57 mV/decade (n = 17), presenting a linear range of response that includes from normal physiological to pharmacological AA concentrations (10–200 μM and 0.2–1 mM, respectively). Importantly, interferences such as uric acid (UA), sodium ion and lactate have a limited influence on the potentiometric response, in contrast to previously published sensors. In addition to the experimental evidence, computational simulations on the interactions of AA and UA with a graphene-based model were performed to provide insights in describing the very distinct experimental responses that were observed. Thus, the formulated hypothesis is supported by both experimental data and simulations, which has not been reported before, to the best of our knowledge. Furthermore, we demonstrate the suitability of the developed sensor for real sample analysis (undiluted human serum, saliva and urine). The significance of the developed sensor is three-fold: 1) analytical performance addressing several applications, 2) enhanced selectivity, specially towards UA, 3) simplicity of the concept in terms of materials and preparation that makes it compatible with micro- and nano-electrodes for further analytical applications never explored until now (e.g., intracellular measurements, nanoelectrochemistry, etc.)

We present a novel drug delivery nanocarrier consisting of 300 nm-sized POT/Fe<inf>3</inf>O<inf>4</inf>/TRZ⁺TPB⁻ nanoparticles (NPs). The mechanism is based on the (photo)oxidation of poly(3-octylthiophene-2,5-diyl) (POT) (from POT⁰ to POT⁺), which facilitates the release of the positively charged drug trazodone (TRZ⁺) encapsulated in the NPs. The primary factor guiding the overall process is the maintenance of the electroneutrality condition in each NP. The incorporation of a Fe<inf>3</inf>O<inf>4</inf> element enables the formation of an organic-inorganic heterojunction (Fe<inf>3</inf>O<inf>4</inf>/POT) in the core of the NP. This heterojunction permits us to utilize visible light to induce the POT photooxidation to trigger the release of TRZ⁺, unlike other platforms based on a more energetic illumination requirement. The developed nanocarrier allows for a controlled drug release, achieving doses of 3.5 µg mL⁻¹ of TRZ under 530 nm irradiation, 2.4 µg mL⁻¹ at 625 nm, and 1.6 µg mL⁻¹ at 470 nm within 1 h. The delivery is tested in undiluted blood serum, achieving an efficiency exceeding 90%. Overall, the integration of magnetic properties with a conductive polymer along with the adjustment of the band gap to enhance photooxidation performance in the visible range, constitute the conceptual innovation behind the controlled drug delivery system here presented, with TRZ as a model.

Nanopipettes with carbon-coated inner surfaces (carbon nanopipettes, CNPs) have attracted considerable attention due to their exceptional sensitivity and potential in electroanalytical applications. The nanoconfinement of the sample solution within the CNP facilitates a thin-layer electrochemical regime, in which ion and electron transferences are inherently coupled. This feature allows exhaustive oxidation/reduction of certain analytes within typical electroanalytical time scales, offering unprecedented opportunities for nanoscale sensing. Despite this promising advantage, a detailed understanding of how measurement dimensions and experimental conditions influence key electrochemical responses remains significantly underexplored. Effectively, conventional electrochemical methods frequently struggle with decoupling ionic and redox contributions, which are critical for understanding the performance toward optimal exploitation. For the first time, cyclic voltammetry (CV), numerical simulations, and electrochemical impedance spectroscopy (EIS) are combined to systematically investigate the interplay between ion transport and electron transfer in the electrochemical behavior of CNPs. CV experiments were used to assess essential parameters under varying electrolyte compositions, solution depths, and scan rates, achieving signal-to-noise ratio enhancements of over 10-fold and submicromolar detection of the redox couple at the rationalized conditions. Complementarily, it is demonstrated that EIS can resolve the nanofluidic behavior by deconvoluting iontronic and electronic contributions, opening an option to be investigated more extensively in future research. The present study not only provides insights into the unique thin-layer electrochemical behavior of CNPs but also establishes the feasibility of simultaneously obtaining iontronic and electronic information with a single setup. This dual capability is poised to advance both related applications, e.g., sensing, (bio)catalysis, imaging, and fundamental directions in nanoelectrochemistry.

Epidermal wearable sensing is a revolutionary concept with the potential of accomplishing a genuine digital transformation in research fields, such as sports physiology, clinical diagnostics, and health monitoring. The first wearable sweat sensor was reported 15 years ago, and despite the remarkable progress along this period, substantial challenges remain open concerning the complex nature of the manufacturing process. The recent democratization and extensive application of 3D printing technologies have made the automated fabrication of electrochemical sensors feasible, including their integration into complex structures such as microfluidic devices. Nevertheless, to the best of our knowledge, there is no evidence of full 3D printing automation (i.e., all fabrication steps) of an entirely functional epidermal wearable. In this context, we aim to contribute to the community by introducing the concept of “click-and-run” 3D printing, which refers to the complete printing of an epidermal wearable sensor (but not limited to) by just a “click” followed by a “run”. The run refers to the fact that after the click, you “run” away so that no other operations need to be performed, but it also indicates that you can go directly to “run” the experiments after the click. Evidently, this new concept cannot be materialized with traditional 3D printers. Therefore, we share herein how we envision a new generation of 3D printers specifically designed for overcoming the actual issues related to the manufacturing process of wearable sensors. Accordingly, this perspective article is organized as follows: (i) an overview of the advantages of ubiquitous desktop 3D printers and their potential to facilitate click-and-run printing, (ii) a tutorial revision of the main desktop 3D printing techniques and their relationship to manufacture electrochemical sensors, (iii) the rationalization of the required parts for a wearable sensor, (iv) a review of the recent advances and achievements in 3D-printed wearable sensors, and (v) our own description of the new generation of “click-and-run” 3D printers.

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 (E_RSD⁰ ± 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.

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. 

Sweat rate magnitude is a desired outcome for any wearable sensing patch dedicated to sweat analysis. Indeed, sweat rate values can be used two-fold: self-diagnosis of dehydration and correction/normalization of other physiological metrics, such as Borg scale, VO2, and different chemical species concentrations. Herein, a reliable sweat rate belt device for sweat rate monitoring was developed. The device measures sweat rates in the range from 1.0 to 5.0 µL min−1 (2 to 10 µL min−1 cm−2), which covers typical values for humans. The working mechanism is based on a new direct current (DC) step protocol activating a series of differential resistance measurements (spatially separated by 800 µm) that is gradually initiated by the action of sweat, which flows along a customized microfluidic track (~600 µm in width, 10 mm in length, and 235 µm in thickness). The device has a volumetric capacity of ~16 µL and an acquisition frequency between 0.010 and 0.043 Hz within the measured sweat rate range. Importantly, instead of using a typical and rather complex AC signal interrogation and acquisition, we put forward the DC approach, offering several benefits, such as simplified circuit design for easier fabrication and lower costs, as well as reduced power consumption and suitability for wearable applications. For the validation, either the commercial sweat collector (colorimetric) or the developed device was performed. In five on-body tests, an acceptable variation of ca. 10% was obtained. Overall, this study demonstrates the potential of the DC-based device for the monitoring of sweat rate and also its potential for implementation in any wearable sweat platform.

Polymeric membranes with ion-exchange properties have found numerous applications in water treatment, dialysis, energy storage, chemical sensors, and bio-interfaces, among others. Notably, it is common to operate under non-equilibrium conditions while pursuing specific features (e.g., current generation) through an electron-to-ion mechanism. To maximize the final performance, it is crucial to understand the role of each interface within the system, which becomes complex when the device is tailored with several materials and films. This is the case for ion sensors based on thin membranes in backside contact with a redox active conducting polymer. Herein, we investigate such a system operating under a charge transfer mechanism, which features electroneutrality maintenance as the main driving force upon application of a linear sweep potential. This potential is modeled as being unequally distributed among the various system interfaces. Our results demonstrate and quantify the existence of a transient membrane potential at the membrane-electrolyte interface, owing to the implementation of a strategical measurement point on the buried membrane side and connected to a built-in electrometer for the exclusive acquisition of the potential difference at such an interface. The transient membrane potential was found to be <1 % of the total applied potential, meaning that the ion-transfer process at the electrolyte-membrane interface is less energetically costly that the electron transfer and doping processes occurring at the conducting polymer side. This small contribution can be potentiated by increasing the ion-exchange capacity of the membrane, which indirectly enlarges the system current and serves as a strategy for increasing the efficiency of the device.