Assessing the performance of a robust multiparametric wearable patch integrating silicon-based sensors for real-time continuous monitoring of sweat biomarkers.

The development of wearable devices for sweat analysis has experienced significant growth in the last two decades, being the main focus the monitoring of athletes health during workouts. One of the main challenges of these approaches has been to attain the continuous monitoring of sweat for time periods over 1 h. This is the main challenge addressed in this work by designing an analytical platform that combines the high performance of potentiometric sensors and a fluidic structure made of a plastic fabric into a multiplexed wearable device. The platform comprises Ion-Sensitive Field-Effect Transistors (ISFETs) manufactured on silicon, a tailor-made solid-state reference electrode, and a temperature sensor integrated into a patch-like polymeric substrate, together with the component that easily collects and drives samples under continuous capillary flow to the sensor areas. ISFET sensors for measuring pH, sodium, and potassium ions were fully characterized in artificial sweat solutions, providing reproducible and stable responses. Then, the real-time and continuous monitoring of the biomarkers in sweat with the wearable platform was assessed by comparing the ISFETs responses recorded during an 85-min continuous exercise session with the concentration values measured using commercial Ion-Selective Electrodes (ISEs) in samples collected at certain times during the session. The developed sensing platform enables the continuous monitoring of biomarkers and facilitates the study of the effects of various real working conditions, such as cycling power and skin temperature, on the target biomarker concentration levels.

Multisensing Wearables for Real-Time Monitoring of Sweat Electrolyte Biomarkers During Exercise and Analysis on Their Correlation With Core Body Temperature.

Sweat secreted by the human eccrine sweat glands can provide valuable biomarker information during exercise. Real-time non-invasive biomarker recordings are therefore useful for evaluating the physiological conditions of an athlete such as their hydration status during endurance exercise. This work describes a wearable sweat biomonitoring patch incorporating printed electrochemical sensors into a plastic microfluidic sweat collector and data analysis that shows the real-time recorded sweat biomarkers can be used to predict a physiological biomarker. The system was placed on subjects carrying out an hour-long exercise session and results were compared to a wearable system using potentiometric robust silicon-based sensors and to commercially available HORIBA-LAQUAtwin devices. Both prototypes were applied to the real-time monitoring of sweat during cycling sessions and showed stable readings for around an hour. Analysis of the sweat biomarkers collected from the printed patch prototype shows that their real-time measurements correlate well (correlation coefficient ≥ 0.65) with other physiological biomarkers such as heart rate and regional sweat rate collected in the same session. We show for the first time, that the real-time sweat sodium and potassium concentration biomarker measurements from the printed sensors can be used to predict the core body temperature with root mean square error (RMSE) of 0.02 °C which is 71% lower compared to the use of only the physiological biomarkers. These results show that these wearable patch technologies are promising for real-time portable sweat monitoring analytical platforms, especially for athletes performing endurance exercise.

Real-Time Edge Neuromorphic Tasting From Chemical Microsensor Arrays.

Liquid analysis is key to track conformity with the strict process quality standards of sectors like food, beverage, and chemical manufacturing. In order to analyse product qualities online and at the very point of interest, automated monitoring systems must satisfy strong requirements in terms of miniaturization, energy autonomy, and real time operation. Toward this goal, we present the first implementation of artificial taste running on neuromorphic hardware for continuous edge monitoring applications. We used a solid-state electrochemical microsensor array to acquire multivariate, time-varying chemical measurements, employed temporal filtering to enhance sensor readout dynamics, and deployed a rate-based, deep convolutional spiking neural network to efficiently fuse the electrochemical sensor data. To evaluate performance we created MicroBeTa (Microsensor Beverage Tasting), a new dataset for beverage classification incorporating 7 h of temporal recordings performed over 3 days, including sensor drifts and sensor replacements. Our implementation of artificial taste is 15× more energy efficient on inference tasks than similar convolutional architectures running on other commercial, low power edge-AI inference devices, achieving over 178× lower latencies than the sampling period of the sensor readout, and high accuracy (97%) on a single Intel Loihi neuromorphic research processor included in a USB stick form factor.

Hybrid Technologies Combining Solid-State Sensors and Paper/Fabric Fluidics for Wearable Analytical Devices.

The development of diagnostic tools for measuring a wide spectrum of target analytes, from biomarkers to other biochemical parameters in biological fluids, has experienced a significant growth in the last decades, with a good number of such tools entering the market. Recently, a clear focus has been put on miniaturized wearable devices, which offer powerful capabilities for real-time and continuous analysis of biofluids, mainly sweat, and can be used in athletics, consumer wellness, military, and healthcare applications. Sweat is an attractive biofluid in which different biomarkers could be noninvasively measured to provide rapid information about the physical state of an individual. Wearable devices reported so far often provide discrete (single) measurements of the target analytes, most of them in the form of a yes/no qualitative response. However, quantitative biomarker analysis over certain periods of time is highly demanded for many applications such as the practice of sports or the precise control of the patient status in hospital settings. For this, a feasible combination of fluidic elements and sensor architectures has been sought. In this regard, this paper shows a concise overview of analytical tools based on the use of capillary-driven fluidics taking place on paper or fabric devices integrated with solid-state sensors fabricated by thick film technologies. The main advantages and limitations of the current technologies are pointed out together with the progress towards the development of functional devices. Those approaches reported in the last decade are examined in detail.

Microanalytical flow system for the simultaneous determination of acetic acid and free sulfur dioxide in wines.

Free sulfur dioxide and volatile acidity are parameters related to the quality of wines. Traditional methods for their determination are tedious, time consuming and require analysis in decentralized laboratories, therefore corrective actions cannot be applied on time. This may be more complex in aging wine cellars, where hundreds of individual barrels containing almost finished wines should be monitored. To achieve this aim, a portable microanalytical flow system for the simultaneous detection of free SO2 and acetic acid during the ageing of wines is proposed in this work. The miniaturized system is based on the use of a gas-diffusion membrane and a pH-ISFET, and can be easily installed in barrels. The system was optimized in the range of 5-60 mg L-1 and 0.15-1.40 g L-1 for SO2 and acetic acid, respectively. It was validated with different sets of wine samples by comparing the results with standard methods, demonstrating a good agreement between methods.

Compact analytical flow system for the simultaneous determination of L-lactic and L-malic in red wines.

During the malolactic fermentation of red wines, L-malic acid is mainly converted to L-lactic acid. Both acids should be precisely measured during the entire process to guarantee the quality of the final wine, thus making real-time monitoring approaches of great importance in the winemaking industry. Traditional analytical methods based on laboratory procedures are currently applied and cannot be deployed on-site. In this work, we report on the design and development of a bi-parametric compact analytical flow system integrating two electrochemical biosensors that could be potentially applied in this scenario. The developed flow-system will allow for the first time the simultaneous measurement of both acids in real scenarios at the real-time and in remote way. Miniaturized thin-film platinum four-electrode chips are fabricated on silicon substrates by standard photolithographic techniques and further implemented in a polymeric fluidic structure. This includes a 15 µL flow cell together with the required fluidic channels for sample and reagent fluid management. The four-electrode chip includes counter and pseudo-reference electrodes together with two working electrodes. These are sequentially modified with electropolymerized polypyrrole membranes that entrap the specific receptors for selectively detecting both target analytes. The analytical performance of both biosensors is studied by chronoamperometry, showing a linear range from 5 × 10-6 to 1 × 10-4 M (LOD of 3.2 ± 0.3 × 10-6 M) and from 1 × 10-7 to 1 × 10-6 M (LOD of 6.7 ± 0.2 × 10-8 M) for the L-lactate and the L-malate, respectively. Both biosensors show long-term stability, retaining more than the 90% of their initial sensitivity after more than 30 days, this being a prerequisite for monitoring the whole process of the malolactic fermentation of the red wines (time between 20 and 40 days). The flow system performance is assessed with several wine samples collected during the malolactic fermentation process of three red wines, showing an excellent agreement with the results obtained with the standard method.

A self-calibrating and multiplexed electrochemical lab-on-a-chip for cell culture analysis and high-resolution imaging.

In vitro analysis requires cell proliferation in conditions close to physiological ones. Lab-on-a-chip (LoC) devices simplify, miniaturize and automate traditional protocols, with the advantages of being less expensive and faster due to their shorter diffusion distances. The main limitation of current LoCs is still the control of the culture conditions. Most LoCs employ off-chip equipment to determine cell culture activity, which confers limited monitoring capacity. The few systems integrating transducers on-chip present important functional problems mostly associated with the attachment of biomolecules to the transducer surface (i.e., biofouling) and the impossibility of re-calibrating the sensors during cell culturing. This limitation is addressed in the present LoC containing a network of micro-channels and micro-chambers, which allows (i) cell seeding and cultivation, avoiding biofouling risk, (ii) multiplexed analysis of cell culture, reactivation and recalibration of the (bio)sensors without compromising cell viability, (iii) cell imaging and (iv) reference electrode compartmentalization to guarantee stability. The activity of the culture is monitored with four independent electrochemical micro-electrodes for glucose, hydrogen peroxide, conductivity and oxidation reduction potential. Electrochemical analysis is complemented with high-resolution confocal microscopy analysis. This paper demonstrates the suitability of the current configuration for cell culture monitoring and future applications in drug screening or organ-on-a-chip development.

Reconfigurable multiplexed point of Care System for monitoring type 1 diabetes patients.

At the point of care (POC), on-side clinical testing allows fast biomarkers determination even in resource-limited environments. Current POC systems rely on tests selective to a single analyte or complex multiplexed systems with important portability and performance limitations. Hence, there is a need for handheld POC devices enabling the detection of multiple analytes with accuracy and simplicity. Here we present a reconfigurable smartphone-interfaced electrochemical Lab-on-a-Chip (LoC) with two working electrodes for dual analyte determination enabling biomarkers' selection in situ and on-demand. Biomarkers selection was achieved by the use of electrodepositable alginate hydrogels. Alginate membranes containing either glucose oxidase (GOx) or lactate oxidase (LOx) were selectively electrodeposited on the surface of each working electrode in around 4 min, completing sample measurement in less than 1 min. Glucose and lactate determination was performed simultaneously and without cross-talk in buffer, fetal bovine serum (FBS) and whole blood samples, the latter being possible by the size-exclusion filtration capacity of the hydrogels. At optimal conditions, glucose and lactate were determined in a wide linear range (0-12 mM and 0-5 mM, respectively) and with high sensitivities (0.24 and 0.54 µA cm-2 mM-1, respectively), which allowed monitoring of Type-1 diabetic patients with a simple dual analysis system. After the measurement, membranes were removed by disaggregation with the calcium-chelator phosphate buffer. At this point, new membranes could be electrodeposited, this time being selective to the same or another analyte. This conferred the system with on-demand biomarkers' selection capacity. The versatility and flexibility of the current architecture is expected to impact in POC analysis in applications ranging from homecare to sanitary emergencies.

Organoleptic Analysis of Drinking Water Using an Electronic Tongue Based on Electrochemical Microsensors.

The standards that establish water's quality criteria for human consumption include organoleptic analysis. These analyses are performed by taste panels that are not available to all water supply companies with the required frequency. In this work, we propose the use of an electronic tongue to perform organoleptic tests in drinking water. The aim is to automate the whole process of these tests, making them more economical, simple, and accessible. The system is composed by an array of electrochemical microsensors and chemometric tools for multivariable processing to extract the useful chemical information. The array of sensors is composed of six Ion-Sensitive Field Effect Transistors (ISFET)-based sensors, one conductivity sensor, one redox potential sensor, and two amperometric electrodes, one gold microelectrode for chlorine detection, and one nanocomposite planar electrode for sensing electrochemical oxygen demand. A previous study addressed to classify water samples according to taste/smell descriptors (sweet, acidic, salty, bitter, medicinal, chlorinous, mouldy, and earthy) was performed. A second study comparing the results of two organoleptic tests (hedonic evaluation and ranking test) with the electronic tongue, using Partial Least Squares regression, was conducted. The results show that the proposed electronic tongue is capable of analyzing water samples according to their organoleptic characteristics, which can be used as an alternative method to the taste panel.

Analysis of free and total sulfur dioxide in wine by using a gas-diffusion analytical system with pH detection.

The use of sulfur dioxide as preservative in winemaking industry has a direct impact on wine quality. The standard methods to analyze this parameter require several processes and are time consuming. In this paper a simple and rapid analytical method for free and total sulfur dioxide detection is proposed. This method is based on the separation of the analyte from the sample with a permeable gas diffusion membrane and its indirect detection with a pH sensor. The system has been validated and optimized for free sulfur dioxide detection in the range of 1-60mgL-1 and for total sulfur dioxide in the range of 30-300mgL-1 with a limit of detection of 0.5mgL-1. Validation of the system has been carried out using a total of 70 samples of white and red wines and two standard methods, the Ripper and the Paul method. The obtained values have demonstrated a good agreement for both methods.

Robust l-malate bienzymatic biosensor to enable the on-site monitoring of malolactic fermentation of red wines.

Monitoring the malolactic fermentation process is strictly required to guarantee the sensorial quality and freshness of red wines. This could be achieved by in-field and real-time continuous measurements of l-malate concentration in the fermentation tanks. The potential of a miniaturized amperometric bienzymatic biosensor as an analytical tool to be applied in such scenario is described in this paper. The biosensor comprises a thin-film gold electrode as transducer, malate dehydrogenase (MDH) and diaphorase (DP) enzymes together with nicotinamide adenine dinucleotide (NAD+) cofactor as the selective receptor and an adequate redox mediator to record the corresponding amperometric signal. Three different biosensor architectures are studied, whose main differences lie in the immobilization of the different chemical components onto the electrode surface. In all cases a fast-electrosynthethized polypyrrole (PPy) membrane is generated for this purpose. The experimental conditions are optimized and the best architecture shows a sensitivity of 1365 ± 110 mA M-1 cm-2 and a detection limit of 6.3 × 10-8 M in a concentration range of 1 × 10-7 M - 1 × 10-6 M. The biosensor presents an excellent working stability as it retains above 90% of its sensitivity after 37 days, thus enabling the monitoring of the malolactic fermentation of three red wines. The obtained results show excellent agreement with the standard colorimetric method.

Portable Electronic Tongue Based on Microsensors for the Analysis of Cava Wines.

Cava is a quality sparkling wine produced in Spain. As a product with a designation of origin, Cava wine has to meet certain quality requirements throughout its production process; therefore, the analysis of several parameters is of great interest. In this work, a portable electronic tongue for the analysis of Cava wine is described. The system is comprised of compact and low-power-consumption electronic equipment and an array of microsensors formed by six ion-selective field effect transistors sensitive to pH, Na⁺, K⁺, Ca2+, Cl-, and CO32-, one conductivity sensor, one redox potential sensor, and two amperometric gold microelectrodes. This system, combined with chemometric tools, has been applied to the analysis of 78 Cava wine samples. Results demonstrate that the electronic tongue is able to classify the samples according to the aging time, with a percentage of correct prediction between 80% and 96%, by using linear discriminant analysis, as well as to quantify the total acidity, pH, volumetric alcoholic degree, potassium, conductivity, glycerol, and methanol parameters, with mean relative errors between 2.3% and 6.0%, by using partial least squares regressions.

Monitoring of malolactic fermentation in wine using an electrochemical bienzymatic biosensor for L-lactate with long term stability.

L-lactic acid is monitored during malolactic fermentation process of wine and its evolution is strongly related with the quality of the final product. The analysis of L-lactic acid is carried out off-line in a laboratory. Therefore, there is a clear demand for analytical tools that enabled real-time monitoring of this process in field and biosensors have positioned as a feasible alternative in this regard. The development of an amperometric biosensor for L-lactate determination showing long-term stability is reported in this work. The biosensor architecture includes a thin-film gold electrochemical transducer selectively modified with an enzymatic membrane, based on a three-dimensional matrix of polypyrrole (PPy) entrapping lactate oxidase (LOX) and horseradish peroxidase (HRP) enzymes. The experimental conditions of the biosensor fabrication regarding the pyrrole polymerization and the enzymes entrapment are optimized. The biosensor response to L-lactate is linear in a concentration range of 1 × 10(-6)-1 × 10(-4) M, with a detection limit of 5.2 × 10(-7) M and a sensitivity of - (13500 ± 600) µA M(-1) cm(-2). The biosensor shows an excellent working stability, retaining more than 90% of its original sensitivity after 40 days. This is the determining factor that allowed for the application of this biosensor to monitor the malolactic fermentation of three red wines, showing a good agreement with the standard colorimetric method.

Electrochemical nanocomposite-derived sensor for the analysis of chemical oxygen demand in urban wastewaters.

This work reports on the fabrication and comparative analytical assessment of electrochemical sensors applied to the rapid analysis of chemical oxygen demand (COD) in urban waste waters. These devices incorporate a carbon nanotube-polystyrene composite, containing different inorganic electrocatalysts, namely, Ni, NiCu alloy, CoO, and CuO/AgO nanoparticles. The sensor responses were initially evaluated using glucose as standard analyte and then by analyzing a set of real samples from urban wastewater treatment plants. The estimated COD values in the samples were compared with those provided by an accredited laboratory using the standard dichromate method. The sensor prepared with the CuO/AgO-based nanocomposite showed the best analytical performance. The recorded COD values of both the sensor and the standard method were overlapped, considering the 95% confidence intervals. In order to show the feasible application of this approach for the detection of COD online and in continuous mode, the CuO/AgO-based nanocomposite sensor was integrated in a compact flow system and applied to the detection of wastewater samples, showing again a good agreement with the values provided by the dichromate method.

A new device for simple and accurate urinary pH testing by the Stone-former patient.

PURPOSE: Urinary pH is an important factor linked to renal stone disease and a useful marker in the treatment of urolithiasis. Although the gold standard for measuring urinary pH utilizes a glass electrode and a pH meter, at present dipstick testing is largely used to estimate urinary pH. However, the accuracy and precision of this method may be insufficient for making clinical decisions in patients with lithiasis. The aim of this study is to describe a new device for urinary pH testing. METHODS: The device includes a pH sensor based on differential measurement of an ISFET-REFET pair. The drawbacks associated with this type of configuration, namely short lifetime and manual fabrication, have been overcome in the prototype. An automatic one point calibration is performed when turning on the system. Two buffer solutions were utilized to determine the intra- and inter-day precision of the device. The pH of 30 fresh human urine samples was measured using a pH-meter, a dipstick and the new electronic device. RESULTS: In some cases, dipstick measurements differed from those of the pH meter by more than 0.40 units, a clinically relevant discrepancy, whereas none of the measurements made with the new electronic device differed from the results of the pH-meter by more than 0.1 pH units. CONCLUSIONS: This new electronic device has the possibility to be used by stone-formers to control their urinary pH at home, increasing the tools available for stone prevention and prophylaxis.

Thin-film electrochemical sensor for diphenylamine detection using molecularly imprinted polymers.

This work reports on the development of a new voltammetric sensor for diphenylamine based on the use of a miniaturized gold electrode modified with a molecularly imprinted polymer recognition element. Molecularly imprinted particles were synthesized ex situ and further entrapped into a poly(3,4-ethylenedioxythiophene) polymer membrane, which was electropolymerized on the surface of the gold electrode. The thickness of the polymer layer was optimized in order to get an adequate diffusion of the target analyte and in turn to achieve an adequate charge transfer at the electrode surface. The resulting modified electrodes showed a selective response to diphenylamine and a high sensitivity compared with the bare gold electrode and the electrode modified with poly(3,4-ethylenedioxythiophene) and non-imprinted polymer particles. The sensor showed a linear range from 4.95 to 115 µM diphenylamine, a limit of detection of 3.9 µM and a good selectivity in the presence of other structurally related molecules. This sensor was successfully applied to the quantification of diphenylamine in spiked apple juice samples.

Classification and characterization of different white grape juices by using a hybrid electronic tongue.

A multisensor system combined with multivariate analysis is applied for the characterization and classification of white grape juices. The proposed system, known as hybrid electronic tongue, consists of an array of electrochemical microsensors and a colorimetric optofluidic system. A total of 25 white grape juices representing the large variability of vines grown in the Northwest Iberian Peninsula were studied. The data obtained were treated with Principal Component Analysis (PCA) and Soft Independent Modeling Class Analogy (SIMCA). The first tool was used to train the system with the reference genotypes -Albariño, Muscat à Petit Grains Blanc and Palomino- and the second to study the feasibility of the hybrid electronic tongue to distinguish between different grape juice varieties. The results show that the three reference genotypes are well differentiated in the PCA model and this can be used to interpolate the rest of varieties and predict their basic characteristics. Besides, using the SIMCA, the system demonstrates high potential for classifying and discriminating grape varieties.

Improving immunosensor performance through oriented immobilization of antibodies on carbon nanotube composite surfaces.

We report the straightforward oriented covalent attachment of antibodies (Abs) on the surface of carboxylated multiwalled carbon nanotube-polystyrene (MWCNT-PS) materials. The combination of this composite material, applied as a robust electrochemical transducer platform, and its covalent functionalization with Abs in a controlled way by means of a two-step process, could contribute to the development of highly sensitive immunosensor devices. Using the simple and versatile carbodiimide chemistry, Abs were attached to the carboxylic groups of the MWCNT-PS composite surfaces via their superficial amine groups. By taking into account the Ab isoelectric point and the net charge of the composite surface, we engineered an immobilization process to achieve the oriented binding of the Ab molecules by favoring an ionic pre-adsorption step before covalent binding occurred. Thus, the antigen binding capacity of the attached Abs was enhanced by up to 10 times with respect to the capacity estimated for a random spatial distribution of these molecules. The proposed strategy would also serve as a model for the efficient biofunctionalization of other carboxylated carbon-based polymer composite materials with potential applications in the biosensor field.

Determination of total polyphenol index in wines employing a voltammetric electronic tongue.

This work reports the application of a voltammetric electronic tongue system (ET) made from an array of modified graphite-epoxy composites plus a gold microelectrode in the qualitative and quantitative analysis of polyphenols found in wine. Wine samples were analyzed using cyclic voltammetry without any sample pretreatment. The obtained responses were preprocessed employing discrete wavelet transform (DWT) in order to compress and extract significant features from the voltammetric signals, and the obtained approximation coefficients fed a multivariate calibration method (artificial neural network-ANN-or partial least squares-PLS-) which accomplished the quantification of total polyphenol content. External test subset samples results were compared with the ones obtained with the Folin-Ciocalteu (FC) method and UV absorbance polyphenol index (I(280)) as reference values, with highly significant correlation coefficients of 0.979 and 0.963 in the range from 50 to 2400 mg L(-1) gallic acid equivalents, respectively. In a separate experiment, qualitative discrimination of different polyphenols found in wine was also assessed by principal component analysis (PCA).

Application of an e-tongue to the analysis of monovarietal and blends of white wines.

This work presents a multiparametric system capable of characterizing and classifying white wines according to the grape variety and geographical origin. Besides, it quantifies specific parameters of interest for quality control in wine. The system, known as a hybrid electronic tongue, consists of an array of electrochemical microsensors-six ISFET based sensors, a conductivity sensor, a redox potential sensor and two amperometric electrodes, a gold microelectrode and a microelectrode for sensing electrochemical oxygen demand--and a miniaturized optofluidic system. The test sample set comprised eighteen Catalan monovarietal white wines from four different grape varieties, two Croatian monovarietal white wines and seven bi- and trivarietal mixtures prepared from the Catalan varieties. Different chemometric tools were used to characterize (i.e., Principal Component Analysis), classify (i.e., Soft Independent Modeling Class Analogy) and quantify (i.e., Partial-Least Squares) some parameters of interest. The results demonstrate the usefulness of the multisensor system for analysis of wine.