Integration of 3D printed Mg2+ potentiometric sensors into microfluidic devices for bioanalysis.

Electrochemical sensors provide an affordable and reliable approach towards the detection and monitoring of important biological species ranging from simple ions to complex biomolecules. The ability to miniaturize electrochemical sensors, coupled with their affordability and simple equipment requirements for signal readout, permits the use of these sensors at the point-of-care where analysis using non-invasively obtainable biofluids is receiving growing interest by the research community. This paper describes the design, fabrication, and integration of a 3D printed Mg2+ potentiometric sensor into a 3D printed microfluidic device for the quantification of Mg2+ in low-sample volume biological fluids. The sensor employs a functionalized 3D printable photocurable methacrylate-based ion-selective membrane affixed to a carbon-mesh/epoxy solid-contact transducer for the selective determination of Mg2+ in sweat, saliva and urine. The 3D printed Mg2+ ion-selective electrode (3Dp-Mg2+-ISE) provided a Nernstian response of 27.5 mV per decade with a linear range of 10 mM to 39 µM, covering the normal physiological and clinically relevant levels of Mg2+ in biofluids. 3Dp-Mg2+-ISEs selectively measure Mg2+ over other biologically present cations - sodium, potassium, calcium, ammonium - as well as provide high stability in the analytical signal with a drift of just 13 µV h-1 over 10 hours. Comparison with poly(vinylchloride)-based Mg2+-ISEs showed distinct advantages to the use of 3Dp-Mg2+-ISEs, with respect to stability, resilience towards biofouling and importantly providing a streamlined and rapid approach towards mass production of selective and reliable sensors. The miniaturization capabilities of 3D printing coupled with the benefits of microfluidic analysis (i.e., low sample volumes, minimal reagent consumption, automation of multiple assays, etc.), provides exciting opportunities for the realization of the next-generation of point-of-care diagnostic devices.

A smartphone-based sensor for detection of iron and potassium in food and beverage samples.

A novel approach for simultaneous detection of iron and potassium via a smartphone-based potentiometric method is proposed in this study. The screen printed electrodes were modified with carbon black nanomaterial and ion selective membrane including zinc (II) phtalocyanine as the ionophore. The developed Fe3+-selective electrode and K+-selective electrode exhibited detection limits of 1.0 × 10-6 M and 1.0 × 10-5 M for Fe3+ and K+ ions, respectively. The electrodes were used to simultaneously detect Fe3+ and K+ ions in apple juice, skim milk, soybean and coconut water samples with recovery values between 90%-100.5%, and validated against inductively coupled plasma-optical emission spectrometry. Due to the advantageous characteristics of the sensors and the portability of Near Field Communication potentiometer supported with a smartphone application, the proposed method offers sensitive and selective detection of iron and potassium ions in food and beverage samples at the point of need.

Polymeric membrane potentiometric sensors based on template-removal-free imprinted receptors for determination of antibiotics.

Currently, Nernstian-response-based polymeric membrane potentiometric sensors using molecularly imprinted polymers (MIPs) as receptors have been successfully developed for determination of organic ionic species. However, the preparation of these MIP receptors usually involves tedious and time-consuming template-removal procedures. Herein, a template-removal-free MIP is proposed and used as a receptor for fabrication of a potentiometric sensor. The proposed methodology not only significantly shortens the preparation time of MIP-based potentiometric sensors but also improves the batch-to-batch reproducibility of these sensors. By using antibiotic vancomycin as a model, the new concept offers a linear concentration range of 1.0 × 10-7 to 1.0 × 10-4 mol L-1 with a detection limit of 2.51 × 10-8 mol L-1. It can be expected that the template-removal-free MIP-based sensing strategy could lay the foundation for simple fabrication of electrochemical sensors without the need for template removal such as potentiometric and capacitive sensors and ion-sensitive field-effect transistors.

Wireless wearable potentiometric sensor for simultaneous determination of pH, sodium and potassium in human sweat.

This paper reports on the development of a flexible-wearable potentiometric sensor for real-time monitoring of sodium ion (Na+), potassium ion (K+), and pH in human sweat. Na0.44MnO2, polyaniline, and K2Co[Fe(CN)6] were used as sensing materials for Na+, H+ and K+ monitoring, respectively. The simultaneous potentiometric Na+, K+, and pH sensing were carried out by the developed sensor, which enables signal collection and transmission in real-time to the smartphone via a Wi-Fi access point. Then, the potentiometric responses were evaluated by a designed android application. Na+, K+, and pH sensors illustrated high sensitivity (59.7 ± 0.8 mV/decade for Na+, 57.8 ± 0.9 mV/decade for K+, and 54.7 ± 0.6 mV/pH for pH), excellent stability, and good batch-to-batch reproducibility. The results of on-body experiments demonstrated that the proposed platform is capable of real-time monitoring of the investigated ions.

A novel potentiometric screen-printed electrode based on crown ethers/nano manganese oxide/Nafion composite for trace level determination of copper ion in biological fluids.

Copper levels in biological fluids are associated with Wilson's, Alzheimer's, Menke's, and Parkinson's diseases, making them good biochemical markers for these diseases. This study introduces a miniaturized screen-printed electrode (SPE) for the potentiometric determination of copper(II) in some biological fluids. Manganese(III) oxide nanoparticles (Mn2O3-NPs), dispersed in Nafion, are drop-casted onto a graphite/PET substrate, serving as the ion-to-electron transducer material. The solid-contact material is then covered by a selective polyvinyl chloride (PVC) membrane incorporated with 18-crown-6 as a neutral ion carrier for the selective determination of copper(II) ions. The proposed electrode exhibits a Nernstian response with a slope of 30.2 ± 0.3 mV/decade (R2 = 0.999) over the linear concentration range 5.2 × 10-9 - 6.2 × 10-3 mol/l and a detection limit of 1.1 × 10-9 mol/l (69.9 ng/l). Short-term potential stability is evaluated using constant current chronopotentiometry (CP) and electrochemical impedance spectroscopy (EIS). A significant improvement in the electrode capacitance (91.5 µF) is displayed due to the use of Mn2O3-NPs as a solid contact. The presence of Nafion, with its high hydrophobicity properties, eliminates the formation of the thin water layer, facilitating the ion-to-electron transduction between the sensing membrane and the conducting substrate. Additionally, it enhances the adhesion of the polymeric sensing membrane to the solid-contact material, preventing membrane delamination and increasing the electrode's lifespan. The high selectivity, sensitivity, and potential stability of the proposed miniaturized electrode suggests its use for the determination of copper(II) ions in human blood serum and milk samples. The results obtained agree fairly well with data obtained by flameless atomic absorption spectrometry.

Functionalized orthopaedic implant as pH electrochemical sensing tool for smart diagnosis of hardware infection.

In the orthopaedic surgery field, the use of medical implants to treat a patient's bone fracture is nowadays a common practice, nevertheless, it is associated with possible cases of infection. The consequent hardware infection can lead to implant failure and systemic infections, with prolonged hospitalization, time-consuming rehabilitation treatments, and extended antibiotic therapy. Hardware infections are strictly related to bacterial adhesion to the implant, leading to infection occurrence and consequent pH decreasing from physiological level to acid pH. Here, we demonstrate the new strategy to use an orthopaedic implant functionalized with iridium oxide film as the working electrode for the potentiometric monitoring of pH in hardware infection diagnosis. A functional investigation was focused on selecting the implant material, namely titanium, titanium alloy, and stainless steel, and the component, namely screws and implants. After selecting the titanium-based implant as the working electrode and a silver wire as the reference electrode in the final configuration of the smart sensing orthopaedic implant, a calibration curve was performed in standard solutions. An equation equal to y = (0.76 ± 0.02) - (0.068 ± 0.002) x, R2 = 0.996, was obtained in the pH range of 4-8. Subsequently, hysteresis, interference, matrix effect, recovery study, and storage stability were investigated to test the overall performance of the sensing device, demonstrating the tremendous potential of electrochemical sensors to deliver the next generation of smart orthopaedic implants.

Single-cell calcium monitoring of Caco-2 cell co-cultured with intestinal microbiome through carbon fiber based potentiometric microelectrode.

The Caco-2 cells were used as intestinal epithelial cell model to illustrate the hyperuricemia (HUA) mechanism under the co-culture of the imbalanced intestinal microbiome in this work. The uric acid (UA) concentration in the HUA process was monitored, and could be up to 425 µmol/L at 8 h co-cultured with the imbalanced intestinal microbiome. Single-cell potentiometry based on ion-selective microelectrode was used to study extracellular calcium change, which is hypothesized to play an important role in the UA excretion. The potential signal of the calcium in the extremely limited microenvironment around single Caco-2 cell was recorded through the single-cell analysis platform. The potential signal of sharp decrease and slow increase followed within a few seconds indicates the sudden uptake and gradually excretion process of calcium through the cell membrane. Moreover, the value of the potential decrease increases with the increase of the time co-cultured with the imbalanced intestinal microbiome ranging from 0 to 8 h. The Ca2+ concentration around the cell membrane could decrease from 1.3 mM to 0.4 mM according to the potential decrease of 27.0 mV at the co-culture time of 8 h. The apoptosis ratio of the Caco-2 cells also exhibits time dependent with the co-culture of the imbalanced intestinal microbiome, and was 39.1 ± 3.6 % at the co-culture time of 8 h, which is much higher than the Caco-2 cells without any treatment (3.9 ± 2.9 %). These results firstly provide the links between the UA excretion with the apoptosis of the intestinal epithelial cell under the interaction of the imbalanced intestinal microbiome. Moreover, the apoptosis could be triggered by the calcium signaling.

Aptamer-Based Potentiometric Sensor Enables Highly Selective and Neurocompatible Neurochemical Sensing in Rat Brain.

Selective and nondisruptive in vivo neurochemical monitoring within the central nervous system has long been a challenging endeavor. We introduce a new sensing approach that integrates neurocompatible galvanic redox potentiometry (GRP) with customizable phosphorothioate aptamers to specifically probe dopamine (DA) dynamics in live rat brains. The aptamer-functionalized GRP (aptGRP) sensor demonstrates nanomolar sensitivity and over a 10-fold selectivity for DA, even amidst physiological levels of major interfering species. Notably, conventional sensors without the aptamer modification exhibit negligible reactivity to DA concentrations exceeding 20 µM. Critically, the aptGRP sensor operates without altering neuronal activity, thereby permitting real-time, concurrent recordings of both DA flux and electrical signaling in vivo. This breakthrough establishes aptGRP as a viable and promising framework for the development of high-fidelity sensors, offering novel insights into neurotransmission dynamics in a live setting.

Locust bean gum hydrogels are bioadhesive and improve indole-3-carbinol cutaneous permeation: influence of the polysaccharide concentration

Abstract The locust bean gum (LBG) is a polysaccharide with thickening, stabilizing and gelling properties and it has been used in the preparation of pharmaceutical formulations. Hydrogels (HGs) are obtained from natural or synthetic materials that present interesting properties for skin application. This study aimed to develop HGs from LBG using indole-3-carbinol (I3C) as an asset model for cutaneous application. HGs were prepared by dispersing LBG (2%, 3% and 4% w/v) directly in cold water. The formulations showed content close to 0.5 mg/g (HPLC) and pH ranging from 7.25 to 7.41 (potentiometry). The spreadability factor (parallel plate method) was inversely proportional to LBG concentration. The rheological evaluation (rotational viscometer) demonstrated a non-Newtonian pseudoplastic flow behavior (Ostwald De Weale model), which is interesting for cutaneous application. The HET-CAM evaluation showed the non-irritating characteristic of the formulations. The bioadhesive potential demonstrated bioadhesion in a concentration-dependent manner. Permeation in human skin using Franz cells showed that the highest LBG concentration improved the skin distribution profile with greater I3C amounts in the viable skin layers. The present study demonstrated the feasibility of preparing HGs with LBG and the formulation with the highest polymer concentration was the most promising to transport active ingredients through the skin.

TBISTAT: An open-source, wireless portable, electrochemical impedance spectroscopy capable potentiostat for the point-of-care detection of S100B in plasma samples.

Point-of-Care (POC) testing for biomarker detection demands techniques that are easy to use, readily available, low-cost, and with rapid response times. This paper describes the development of a fully open-source, modular, wireless, battery-powered, smartphone-controlled, low-cost potentiostat capable of conducting electrochemical impedance spectroscopy for the electrochemical detection of the S100B protein captured in an ANTI-S100B functionalized thin-film gold interdigitated electrode platform to support traumatic brain injury diagnosis and treatment. EIS results from the developed potentiostat were validated with a commercial benchtop potentiostat by comparing impedance magnitude and phase values along the EIS frequency range. In addition, an experimental design was performed for detecting S100B in spiked human plasma samples with S100B concentrations of clinical utility, and a calibration curve was found for quantifying S100B detection. No statistically significant differences were found between EIS results from the developed potentiostat and the commercial potentiostat. Statistically significant differences in the changes in charge transfer resistance signal between each tested S100B concentration (p < 0.05) were found, with a limit of detection of 35.73 pg/mL. The modularity of the proposed potentiostat allows easier component changes according to the application demands in power, frequency excitation ranges, wireless communication protocol, signal amplification and transduction, precision, and sampling frequency of ADC, among others, when compared to state-of-the-art open-source EIS potentiostats. In addition, the use of minimal, easy acquirable open-source hardware and software, high-level filtering, accurate ADC, Fast Fourier Transform with low spectral leakage, wireless communication, and the simple user interface provides a framework for facilitating EIS analysis and developing new affordable instrumentation for POC biosensors integrated systems.

Ionic contrast across a lipid membrane for Debye length extension: towards an ultimate bioelectronic transducer.

Despite technological advances in biomolecule detections, evaluation of molecular interactions via potentiometric devices under ion-enriched solutions has remained a long-standing problem. To avoid severe performance degradation of bioelectronics by ionic screening effects, we cover probe surfaces of field effect transistors with a single film of the supported lipid bilayer, and realize respectable potentiometric signals from receptor-ligand bindings irrespective of ionic strength of bulky solutions by placing an ion-free water layer underneath the supported lipid bilayer. High-energy X-ray reflectometry together with the circuit analysis and molecular dynamics simulation discovered biochemical findings that effective electrical signals dominantly originated from the sub-nanoscale conformational change of lipids in the course of receptor-ligand bindings. Beyond thorough analysis on the underlying mechanism at the molecular level, the proposed supported lipid bilayer-field effect transistor platform ensures the world-record level of sensitivity in molecular detection with excellent reproducibility regardless of molecular charges and environmental ionic conditions.

A fully screen-printed potentiometric chloride ion sensor employing a hydrogel-based touchpad for simple and non-invasive daily electrolyte analysis.

This is the first report demonstrating proof of concept for the passive, non-invasive extraction and in situ potentiometric detection of human sweat chloride ions (Cl- ions) using a stable printed planar liquid-junction reference electrode-integrated hydrogel-based touch-sensor pad without activities such as exercise to induce perspiration, environmental temperature control, or requiring cholinergic drug administration. The sensor pad was composed entirely of a screen-printed bare Ag/AgCl-based chloride ion-selective electrode and a planar liquid-junction Ag/AgCl reference electrode, which were fully covered by an agarose hydrogel in phosphate-buffered saline (PBS). When human skin contacted the hydrogel pad, sweat Cl- ions were continuously extracted into the gel, followed by in situ potentiometric detection. The planar liquid-junction Ag/AgCl reference electrode had a polymer-based KCl-saturated inner electrolyte layer to stabilize the potential of the Ag/AgCl electrode even with a substantial change in the chloride ion concentration in the hydrogel pad. We expect this fully screen-printed sensor to achieve the low-cost passive and non-invasive daily monitoring of human Cl- ions in sweat in the future.

Potentiometric Determination of Circulating Glycoproteins by Boronic Acid End-Functionalized Poly(ethylene glycol)-Modified Electrode.

Despite tremendous complexity in glycan structure, sialic acid (SA) provides an analytically accessible index for glycosylation, owing to its uniquely anionic nature and glycan-chain terminal occupation. Taking advantage of boronic acid (BA) based SA-recognition chemistry, we here demonstrate a label-free, no enzymatic, potentiometric determination of fetuin, a blood-circulating glycoprotein implicated in physiological and various pathological states. A phenylboronic acid (PBA) ω-end-functionalized poly(ethylene glycol) (PEG) with an α-tethering unit bearing pendent alkyne groups was "grafted-to" a gold electrode modified with 11-azide-undecathiol by a copper-catalyzed azide-alkyne cycloaddition reaction. Using the electrode, fetuin was potentiometrically detectable with a µM-order-sensitivity that is comparable to what is found in blood-collected specimen. Our finding may have implications for developing a remarkably economic hemodiagnostic technology with ease of downsizing and mass production.

Wearable electrochemical biosensors in North America.

Tremendous research and commercialization efforts around the world are focused on developing novel wearable electrochemical biosensors that can noninvasively and continuously screen for biochemical markers in body fluids for the prognosis, diagnosis and management of diseases, as well as the monitoring of fitness. Researchers in North America are leading the development of innovative wearable platforms that can comfortably comply to the human body and efficiently sample fluids such as sweat, interstitial fluids, tear and saliva for the electrochemical detection of biomarkers through various sensing approaches such as potentiometric ion selective electrodes and amperometric enzymatic sensors. We start this review with a historical timeline overviewing the major milestones in the development of wearable electrochemical sensors by North American institutions. We then describe how such research efforts have led to pioneering developments and are driving the advancement and commercialization of wearable electrochemical sensors: from minimally invasive continuous glucose monitors for chronic disease management to non-invasive sweat electrolyte sensors for dehydration monitoring in fitness applications. While many countries across the globe have contributed significantly to this rapidly emerging field, their contributions are beyond the scope of this review. Furthermore, we share our perspective on the promising future of wearable electrochemical sensors in applications spanning from remote and personalized healthcare to wellness.

Potentiometric Sensors for the Determination of Anionic Surfactants - A Review.

Anionic surfactants are important components of many products used in everyday life in all households. They are also applied in various industrial fields at a very large scale. Since they have a negative influence on the environment, it is an imperative to monitor their concentration in aquatic ecosystems. Therefore, it is of great importance to develop new methods for the determination of a wide spectra of anionic surfactants in complex environmental samples in a short time. A comprehensive review of potentiometric sensors for the determination of anionic surfactants in the last 50 years is given with special concern to papers published since 2000, but noting some earlier published important papers. The latest development in use of new ionophores, polymer formulations, and nanomaterials is presented. Additionally, the application of new potentiometric sensors in batch mode or in miniaturized microfluidic methods is discussed.

Application of Potentiometric Sensors in Real Samples.

Potentiometry is one of the most important electrochemical methods and potentiometric based sensors have been extensively studied by researchers for many years. The fact that potentiometric sensors have several advantages over other analytical devices is another reason for intensive research on the topic. In this area, hundreds of different sensors have been developed till today and introduced into the literature. The successful use of the developed sensors, particularly in real sample analysis, has made potentiometric sensors the center of attention. In this review, we highlight the studies which have been successfully applied to the developed drug samples and also to many real samples, with high recovery rates.

Monitoring of total potassium in winemaking processes using a potentiometric analytical microsystem.

Innovation in products and processes, traceability, food security and quality control are inherent challenges in agri-food sector. Trends in wine production are focused on obtaining natural wines with less chemical intervention. Following this goal, a low cost miniaturized, easy-to-use and highly automated microanalyzer to monitor total potassium in winemaking processes is presented. The microsystem monolithically integrates microfluidics as well as a potentiometric detection system and does not require any sample pretreatment. The analytical features provided are a linear range from 250 to 4000 mg L-1 K+, covering all the concentrations expected in must and wine samples, a detection limit of 75 ± 12 mg L-1 K+, and an adequate reproducibility and repeatability. Sample throughput is calculated at 20 h-1 with a waste volume generation lower than 4 mL per analysis. The microsystem lifetime is at least 4 months. Different wine and grape juice samples have been analyzed reaching outstanding results.

A Single-Mode, Self-Adapting, and Self-Powered Mechanoreceptor Based on a Potentiometric-Triboelectric Hybridized Sensing Mechanism for Resolving Complex Stimuli.

Human skin is equipped with slow adapting (SA) and fast adapting (FA) capabilities simultaneously. To mimic such functionalities, elaborately designed devices have been explored by integrating multiple sensing elements or adopting multimode sensing principles. However, the complicated fabrication, signal mismatch of different modules, complex operation, and high power-consumption hinder their widespread applications. Here, a new type of single-mode and self-powered mechanoreceptor that can mimic both SA and FA via seamless fusion of complementary while compatible potentiometric and triboelectric sensing principles is reported. The resultant potentiometric-triboelectric hybridized mechanoreceptor exhibits distinctive features that are hard to achieve via currently existing methods, including single-mode output (only voltage signal), greatly simplified operation (single-measurement setup), ultralow power-consumption (<1 nW), self-adaptive response behavior, and good capability for resolving complex stimuli. Diverse mechanical characteristics, including magnitude, duration, frequency, applying and releasing speed, can be well interpreted with this single-mode and self-powered mechanoreceptor. Its promising application for monitoring object manipulations with a soft robotic gripper is explored. Furthermore, the versatility of the mechanoreceptor for resolving complex stimuli in diverse daily scenarios is demonstrated. This work presents a new design that will significantly simplify the fabrication/operation and meanwhile boost the functionality/energy-efficiency of future electronic devices and smart systems.

Portable electrochemical carbon cloth analysis device for differential pulse anodic stripping voltammetry determination of Pb2.

A novel electrochemical carbon cloth (CC) analysis device (eCAD) is proposed for the determination of Pb2+ in environmental water samples, which was assembled using a single-step functional CC as both the sensing and the substrate material. The modified CC was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectra, and electrochemical impedance spectroscopy. The increase in electrochemical activity is due to the increased defective extent and excellent electrochemical activity of CC. Under optimum conditions (viz. a pH value of 4.5, deposition time of 160 s), the sensor is capable of determining Pb2+ by differential pulse anodic stripping voltammetry (DPASV) at a typical working potential of - 1.0 V (vs. Ag/AgCl). Response is linear from 5.0 × 10-9 to 3.0 × 10-6 M Pb2+, and the detection limit is 4.8 nM (at S/N = 3). The sensor was successfully applied to the determination of Pb2+ in real samples, with apparent recoveries from 96.0 to 102.0% and a relative standard deviation of less than 3.4%. In addition, the integration of the sensor with signal collection components has enabled us to realize on-site analysis of Pb2+, which is highlighted as a new generation of electrode platform for the development of a portable analysis device.Graphical abstract.

Polymeric Membrane Electrodes Using Calix[4]pyrrole Bis/Tetra-Phosphonate Cavitands as Ionophores for Potentiometric Acetylcholine Sensing with High Selectivity.

A handful of bis/tetra-phosphonate calix[4]pyrroles with recognition sites embedding in hydrophobic cavitands were evaluated for the first time as ionophores for polymeric membrane Ach+-selective electrodes. Highly selective potentiometric Ach+ could be achieved over its analogues, especially for Ch+, which differs only by an acetate tail from Ach+. The superior performance of the proposed ISEs might be ascribed to a dual-site binding mode, in which the trimethylammonium head and acetate tail were accommodated by the phosphonate group-bridged aryl walls and the bowl-shaped aromatic cavity, through cation-π/charge-dipole interaction and the convergent four N-H···O hydrogen bonds, respectively. To gain more insight into the performance of the proposed ISEs, the cation-ionophore complex constants in the membrane phase were determined, and the binding affinity trend correlates well with the selectivity pattern. These results suggest that conformational preorganization of the ionophores and complementary weak interactions do change the selectivity of the ionophores. Studies on the influence of the sample solution pH demonstrated that the developed ISEs can be employed in a wide pH range of 4.0-9.6 with a fast response (<60 s), good reversibility, and long lifetime. Optimizing the membrane components, such as ionophores, lipophilic additives, and plasticizers, yielded ISEs, showing Nernstian responses to Ach+ with improved linear ranges and detection limits (a slope of -59.5 mV/dec in the linear range of 1 × 10-6-1 × 10-2 M with a detection limit of 3 × 10-7 M), which led to the success of the determination of Ach+ in spiked urine and milk samples.