New Approach for Making Standard the Development of Biosensing Devices by a Modular Multi-Purpose Design

The fast widening of biosensing applications, such as healthcare, drug delivery, food, and military industries, is increasing the need for generality and compatibility among different sensors. To address this challenge, we present here an innovative approach for the fast development of new electronic biosensing systems, linking a custom-designed front-end with a multi-purpose system. We envision an open tool to help designers to focus on the target molecule and related detection method instead of designing each time a dedicated electronic device. The architecture of the proposed system is based on a modular approach, where only the front-end and the software need to be custom re-designed according to the application. Considering current research and applying a rigorous definition of the technical requirements, the core of the system is designed to fit the highest number of biosensing methods. The flexibility of this approach is successfully demonstrated with three different types of biosensors, i.e., amperometric, ion-sensitive, and memristive

Semi-Automated Data Analysis for Ion-Selective Electrodes and Arrays Using the R Package ISEtools.

A new software package, ISEtools, is introduced for use within the popular open-source programming language R that allows Bayesian statistical data analysis techniques to be implemented in a straightforward manner. Incorporating all collected data simultaneously, this Bayesian approach naturally accommodates sensor arrays and provides improved limit of detection estimates, including providing appropriate uncertainty estimates. Utilising >1500 lines of code, ISEtools provides a set of three core functions-loadISEdata, describeISE, and analyseISE- for analysing ion-selective electrode data using the Nikolskii-Eisenman equation. The functions call, fit, and extract results from Bayesian models, automatically determining data structures, applying appropriate models, and returning results in an easily interpretable manner and with publication-ready figures. Importantly, while advanced statistical and computationally intensive methods are employed, the functions are designed to be accessible to non-specialists. Here we describe basic features of the package, demonstrated through a worked environmental application

Semi-Automated Data Analysis for Ion-Selective Electrodes and Arrays Using the R Package ISEtools.

A new software package, ISEtools, is introduced for use within the popular open-source programming language R that allows Bayesian statistical data analysis techniques to be implemented in a straightforward manner. Incorporating all collected data simultaneously, this Bayesian approach naturally accommodates sensor arrays and provides improved limit of detection estimates, including providing appropriate uncertainty estimates. Utilising >1500 lines of code, ISEtools provides a set of three core functions-loadISEdata, describeISE, and analyseISE- for analysing ion-selective electrode data using the Nikolskii-Eisenman equation. The functions call, fit, and extract results from Bayesian models, automatically determining data structures, applying appropriate models, and returning results in an easily interpretable manner and with publication-ready figures. Importantly, while advanced statistical and computationally intensive methods are employed, the functions are designed to be accessible to non-specialists. Here we describe basic features of the package, demonstrated through a worked environmental application

Why not glycine electrochemical biosensors?

Glycine monitoring is gaining importance as a biomarker in clinical analysis due to its involvement in multiple physiological functions, which results in glycine being one of the most analyzed biomolecules for diagnostics. This growing demand requires faster and more reliable, while affordable, analytical methods that can replace the current gold standard for glycine detection, which is based on sample extraction with subsequent use of liquid chromatography or fluorometric kits for its quantification in centralized laboratories. This work discusses electrochemical sensors and biosensors as an alternative option, focusing on their potential application for glycine determination in blood, urine, and cerebrospinal fluid, the three most widely used matrices for glycine analysis with clinical meaning. For electrochemical sensors, voltammetry/amperometry is the preferred readout (10 of the 13 papers collected in this review) and metal-based redox mediator modification is the predominant approach for electrode fabrication (11 of the 13 papers). However, none of the reported electrochemical sensors fulfill the requirements for direct analysis of biological fluids, most of them lacking appropriate selectivity, linear range of response, and/or capability of measuring at physiological conditions. Enhanced selectivity has been recently reported using biosensors (with an enzyme element in the electrode design), although this is still a very incipient approach. Currently, despite the benefits of electrochemistry, only optical biosensors have been successfully reported for glycine detection and, from all the inspected works, it is clear that bioengineering efforts will play a key role in the embellishment of selectivity and storage stability of the sensing element in the sensor

Development of Flexible Ion-Selective Electrodes for Saliva Sodium Detection

Saliva can be used for health monitoring with non-invasive wearable systems. Such devices, including electrochemical sensors, may provide a safe, fast, and cost-efficient way of detecting target ions. Although salivary ions are known to reflect those in blood, no available clinical device can detect essential ions directly from saliva. Here, we introduce an all-solid-state, flexible film sensor that allows highly accurate detection of sodium levels in saliva, comparable to those in blood. The wireless film sensor system can successfully measure sodium ions from a small volume of infants' saliva (<400 µL), demonstrating its potential as a continuous health monitor. This study includes the structural characterization and error analysis of a carbon/elastomer-based ion-selective electrode and a reference electrode to confirm the signal reliability. The sensor, composed of a pair of the electrodes, shows good sensitivity (58.9 mV/decade) and selectivity (log K = -2.68 for potassium), along with a broad detection range of 5 × 10-5 ≈ 1 M with a low detection limit of 4.27 × 10-5 M. The simultaneous comparison between the film sensor and a commercial electrochemical sensor demonstrates the accuracy of the flexible sensor and a positive correlation in saliva-to-blood sodium levels. Collectively, the presented study shows the potential of the wireless ion-selective sensor system for a non-invasive, early disease diagnosis with saliva.ope

Conceptualization and ideation of a wearable device to predict HE

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2020-2021. Directora: Anna Baiges. Tutor: Mario García.Hepatic encephalopathy (HE) is a pathology believed to be produced when the liver function is impaired and cannot adequately remove toxins from the blood, such as ammonia, which leads to a buildup of toxins in the bloodstream that can reach the brain and affect its function. Some patients that present cirrhosis may be eligible to have a TIPS (Transjugular Intrahepatic Portosystemic Shunt) implanted, which decreases the pressure in the portal vein and improves their liver condition. However, clinical evidences have shown that HE is more likely to appear in patients that have had a TIPS implanted. This work is a first stage of a project that aims to create a device able to predict the development of HE on patients that have an implanted TIPS and also study the causes of this pathology. Since ammonium is the only proven biomarker for HE, an initial study was performed to discuss which other ions or molecules could have a correlation with the development of HE. Additionally, since there is a correlation between the ammonium concentration in blood and sweat, a non-invasive sensor that measures the ammonium concentration in sweat was conceptualized and designed. Because this device is non-invasive, could be worn in daily life and it allows a simple maintenance that does not require a technician, it would present an advantage over the current diagnostic techniques since they are invasive or mainly based on psychological tests

Flexible Electrochemical Lactate Sensor

Lactic acid is a vital indicator for shock, trauma, stress, and exercise intolerance. It is a key biomarker for increases in stress levels and is the primary metabolically produced acid responsible for tissue acidosis that can lead to muscle fatigue and weakness. During intensive exercise, the muscles go through anerobic metabolism to produce energy. This leads to decreases in the blood flow of nutrients and oxygen to the muscles and increases in lactate production, which in turn cause lactic acidosis. Currently, changes in blood lactate concentrations are monitored by sensors that can be invasive via blood or wearable based sensors that use the enzyme lactate oxidase. Lactate oxidase produces hydrogen peroxide, which is a toxic byproduct and can foul the surface of the sensor. Here, we present the development of a noninvasive wearable electrochemical lactate biosensor for the detection of lactic acid. The bioelectrode was designed with buckypaper (BP), which is composed of a dense network of multi-walled carbon nanotubes. This material was chosen due to its low cost, high conductivity, flexibility, and high active surface area. D-Lactate dehydrogenase (D-LDH) was immobilized on the surface of the BP to facilitate the oxidation of lactic acid. The biosensor was then integrated into a polydimethylsiloxane (PDMS) flexible substrate platform. PDMS was chosen because of its lightweight, flexible, biocompatibility, and conformal properties. The sensor is designed to be placed on skin in order to measure the concentration of lactate in sweat. The concentration of lactate in sweat has been shown to be a good biomarker for evaluating the severity of peripheral occlusive arterial diseases and damage in soft tissue. The lactate biosensor developed in this work exhibited a dynamic linear range of 5 mM to 45 mM lactic acid with a good sensitivity of 1.388μA/mMcm2. It can measure higher than the average lactate concentration in sweat during exercise, which is 31mM. This electrochemical biosensor has the potential to be used for the real-time detection of lactic acid concentration in sweat, suggesting promising applications in clinical, biological and sports medicine fields

Sol-Gel Coating Membranes for Optical Fiber Sensors for Concrete Structures Monitoring

The use of advanced sensing devices for concrete and reinforced concrete structures (RCS) is considered a rational approach for the assessment of repair options and scheduling of inspection and maintenance strategies. The immediate benefits are cost reduction and a reliable prevention of unpredictable events. The use of optical fiber sensors (OFS) for such purposes has increased considerably in the last few years due to their intrinsic advantages. In most of the OFS, the chemical transducer consists of immobilized chemical reagents placed in the sensing region of the optical sensor by direct deposition or by encapsulation in a polymeric matrix. The choice of the support matrix impacts directly on the performance of the OFS. In the last two decades, the development of OFS functionalized with organic-inorganic hybrid (OIH) sol-gel membranes have been reported. Sol-gel route is considered a simple method that offers several advantages when compared to traditional synthesis processes, allowing to obtain versatile materials with unique chemical and physical properties, and is particularly valuable in the design of OIH materials. This review will provide an update of the current state-of-the-art of the OFS based on OIH sol-gel materials for concrete and RCS since 2016 until mid-2021. The main achievements in the synthesis of OIH membranes for deposition on OFS will be discussed. The challenges and future directions in this field will also be considered, as well as the main limitations of OFS for RCS monitoring. (c) 2021 by the authors. Licensee MDPI, Basel, Switzerland

Highly Reproducible Electrochemical Sensors towards Wearable Applications and Pharmaceutical Analysis

Ion-selective electrodes (ISEs) are widely used to monitor ions in various applications from environmental to clinical settings and pharmaceutical analysis. ISEs are a type of potentiometric sensor that provides a versatile, cost-effective, and efficient platform towards wearable sensing applications. Among the two different platforms of ISEs (solid-contact and liquid-contact), solid-contact ISEs are superior to ISEs with internal electrolytes (liquid-contact) since they are easy to be miniaturized, can be used in any environment and their portability is facilitated. Unfortunately, mass production and commercialization of such devices is often constrained by the requirement of sensor calibration. Thus, approaches for sensor manufacturing towards improving sensor to sensor reproducibility is a need, mainly for wearable sensors applications. This work discusses the development and characterization of calibration-free ISEs for the selective detection of different ions (Na+, K+ and Fluoxetine). The sensor response is measured using the NERNST equation that relates concentration with electromotive force (electrical potential). To obtain reproducible potentials from sensor to senor, different optimizations were performed such as components of the ion-selective membrane (ISM) and solid contact support. Effect of ion-selective membrane (ISM) solvent on ISE reproducibility was studied by comparing tetrahydrofuran (THF) (a typical solvent for membrane preparation) and cyclohexanone. In addition, a single-step integration of semiconducting/transducer polymer poly(3-octylthiophene) (POT) with single-walled carbon nanotubes (SWCNTs) into the ISEs substrate was introduced. Upon full optimization, highly reproducible paper-based ion-selective electrodes and wearable sensors for the measurement of sodium and potassium ions in aqueous solution and artificial sweat were fabricated. This technology was also applied for the development of a highly reproducible paper-based ion-selective electrode for the determination of fluoxetine

Plasma-Jet Printing and In Situ Sintering of Electronic Materials for Flexible Hybrid Electronic Applications

Additive manufacturing has become a promising method for the fabrication of inexpensive, green, flexible sensors and electronics. Printed electronics on low- temperature substrates are very appealing for the flexible hybrid electronics market for their use in disposable and biocompatible electronic applications and in areas like packaging, wearables, and consumer electronics. Plasma jet printing uses a dielectric barrier discharge plasma to focus aerosolized nanoparticles onto a target substrate. The same plasma can be used to change the properties of the printed material and even sinter in situ. The voltage of the plasma has a significant effect on the deposition of nanomaterials. The effect of the plasma on deposition and sintering mechanisms are observed and discussed as an exploration into the practicality of the printer to additively manufacture electronics. The technology can also be utilized in space and microgravity environments since the plasma-assisted deposition is independent of gravity. Since plasma-jet printing is a new technology, significant developments in optimizing the printer for many materials and applications were made. Plasma jet printing has advantages of self-sintering and gravity-independent deposition over other methods like inkjet and aerosol-jet printing. This dissertation explores the direct printing of thermoelectric generators with excellent flexibility and comparable thermoelectric properties. As printing and sintering of metallic nanomaterials are an important part of flexible hybrid electronics, we will also show the direct manufacturing of conductive gold structures on glass polymer, and low-temperature substrates without the need for thermal or photonic post-processing. The addition of polymer into the ink was explored, and increased adhesion of the printed gold was achieved. This advancement in gold deposition can be utilized in additive manufacturing for biocompatible, corrosion-resistant electronics on low-temperature substrates. This is shown in demonstrations of a functional plasma jet-printed heater and LED interconnects without thermal post-processing