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Biosensors, Volume 10, Issue 9 (September 2020) – 28 articles

Cover Story (view full-size image): Cytokine IL-6 plays a major role in several inflammatory diseases, from rheumatoid arthritis to cancer, and more recently, in COVID-19 pneumonia. In the aim of producing highly sensitive and selective biosensors, we performed a virtual comparison among different IL-6 receptors, two Fabs, an aptamer, a clinical antibody as well as the natural receptors of this protein. The procedure requires translating the biomolecules (the protein alone and complexed with its receptors) into complex elec-trical networks, then allowing a flow of electrons to cross them, in such a way that the electron flux works like a probe exploring the network topology. The selected receptors were ranked accounting for their topological complementarity with IL-6. Two of the analyzed receptors are endorsed in a would-be electrochemical biosensor. View this pa-per.
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11 pages, 3159 KiB  
Article
Selective Coordination of Cu2+ and Subsequent Anion Detection Based on a Naphthalimide-Triazine-(DPA)2 Chemosensor
by Artur J. Moro, Miguel Santos, Mani Outis, Pedro Mateus and Pedro M. Pereira
Biosensors 2020, 10(9), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090129 - 22 Sep 2020
Cited by 7 | Viewed by 2753
Abstract
A new fluorescent chemosensor for copper (II) and subsequent anion sensing was designed and fully characterized. The sensor consisted of a 1,8-naphthalimide core, bearing two terminal dipicolylamine (DPA) receptor units for binding metal cations, and an ethoxyethanol moiety for enhanced water solubility. The [...] Read more.
A new fluorescent chemosensor for copper (II) and subsequent anion sensing was designed and fully characterized. The sensor consisted of a 1,8-naphthalimide core, bearing two terminal dipicolylamine (DPA) receptor units for binding metal cations, and an ethoxyethanol moiety for enhanced water solubility. The DPA units are connected to position 4 of the fluorophore via a triazine-ethylenediamine spacer. Fluorescence titration studies of the chemosensor revealed a high selectivity for Cu2+ over other divalent ions, the emissions were strongly quenched upon binding, and a stability constant of 5.52 log units was obtained. Given the distance from DPA chelating units and the fluorophore, quenching from the Cu2+ complexation suggests an electron transfer or an electronic energy transfer mechanism. Furthermore, the Cu2+-sensor complex proved to be capable of sensing anionic phosphate derivatives through the displacement of the Cu2+ cation, which translated into a full recovery of the luminescence from the naphthalimide. Super-resolution fluorescence microscopy studies performed in HeLa cells showed there was a high intracellular uptake of the chemosensor. Incubation in Cu2+ spiked media revealed a strong fluorescent signal from mitochondria and cell membranes, which is consistent with a high concentration of ATP at these intracellular sites. Full article
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10 pages, 1369 KiB  
Article
Short Bouts of Gait Data and Body-Worn Inertial Sensors Can Provide Reliable Measures of Spatiotemporal Gait Parameters from Bilateral Gait Data for Persons with Multiple Sclerosis
by Lilian Genaro Motti Ader, Barry R. Greene, Killian McManus, Niall Tubridy and Brian Caulfield
Biosensors 2020, 10(9), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090128 - 20 Sep 2020
Cited by 6 | Viewed by 3459
Abstract
Wearable devices equipped with inertial sensors enable objective gait assessment for persons with multiple sclerosis (MS), with potential use in ambulatory care or home and community-based assessments. However, gait data collected in non-controlled settings are often fragmented and may not provide enough information [...] Read more.
Wearable devices equipped with inertial sensors enable objective gait assessment for persons with multiple sclerosis (MS), with potential use in ambulatory care or home and community-based assessments. However, gait data collected in non-controlled settings are often fragmented and may not provide enough information for reliable measures. This paper evaluates a novel approach to (1) determine the effects of the length of the walking task on the reliability of calculated measures and (2) identify digital biomarkers for gait assessments from fragmented data. Thirty-seven participants (37) diagnosed with relapsing-remitting MS (EDSS range 0 to 4.5) executed two trials, walking 20 m each, with inertial sensors attached to their right and left shanks. Gait events were identified from the medio-lateral angular velocity, and short bouts of gait data were extracted from each trial, with lengths varying from 3 to 9 gait cycles. Intraclass correlation coefficients (ICCs) evaluate the degree of agreement between the two trials of each participant, according to the number of gait cycles included in the analysis. Results show that short bouts of gait data, including at least six gait cycles of bilateral data, can provide reliable gait measurements for persons with MS, opening new perspectives for gait assessment using fragmented data (e.g., wearable devices, community assessments). Stride time variability and asymmetry, as well as stride velocity variability and asymmetry, should be further explored as digital biomarkers to support the monitoring of symptoms of persons with neurological diseases. Full article
(This article belongs to the Special Issue Wearable Biosensors for Healthcare)
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23 pages, 3997 KiB  
Review
Recent Advances in Portable Biosensors for Biomarker Detection in Body Fluids
by Brian Senf, Woon-Hong Yeo and Jong-Hoon Kim
Biosensors 2020, 10(9), 127; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090127 - 18 Sep 2020
Cited by 61 | Viewed by 7833
Abstract
A recent development in portable biosensors allows rapid, accurate, and on-site detection of biomarkers, which helps to prevent disease spread by the control of sources. Less invasive sample collection is necessary to use portable biosensors in remote environments for accurate on-site diagnostics and [...] Read more.
A recent development in portable biosensors allows rapid, accurate, and on-site detection of biomarkers, which helps to prevent disease spread by the control of sources. Less invasive sample collection is necessary to use portable biosensors in remote environments for accurate on-site diagnostics and testing. For non- or minimally invasive sampling, easily accessible body fluids, such as saliva, sweat, blood, or urine, have been utilized. It is also imperative to find accurate biomarkers to provide better clinical intervention and treatment at the onset of disease. At the same time, these reliable biomarkers can be utilized to monitor the progress of the disease. In this review, we summarize the most recent development of portable biosensors to detect various biomarkers accurately. In addition, we discuss ongoing issues and limitations of the existing systems and methods. Lastly, we present the key requirements of portable biosensors and discuss ideas for functional enhancements. Full article
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19 pages, 2386 KiB  
Article
Combining Electrostatic, Hindrance and Diffusive Effects for Predicting Particle Transport and Separation Efficiency in Deterministic Lateral Displacement Microfluidic Devices
by Valentina Biagioni, Giulia Balestrieri, Alessandra Adrover and Stefano Cerbelli
Biosensors 2020, 10(9), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090126 - 16 Sep 2020
Cited by 7 | Viewed by 2410
Abstract
Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible [...] Read more.
Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection–diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique. Full article
(This article belongs to the Collection Recent Developments in Microfluidics)
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17 pages, 2713 KiB  
Article
Screen-Printed Glucose Sensors Modified with Cellulose Nanocrystals (CNCs) for Cell Culture Monitoring
by Ye Tang, Konstantinos Petropoulos, Felix Kurth, Hui Gao, Davide Migliorelli, Olivier Guenat and Silvia Generelli
Biosensors 2020, 10(9), 125; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090125 - 13 Sep 2020
Cited by 22 | Viewed by 4212
Abstract
Glucose sensors are potentially useful tools for monitoring the glucose concentration in cell culture medium. Here, we present a new, low-cost, and reproducible sensor based on a cellulose-based material, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized-cellulose nanocrystals (CNCs). This novel biocompatible and inert nanomaterial is employed as [...] Read more.
Glucose sensors are potentially useful tools for monitoring the glucose concentration in cell culture medium. Here, we present a new, low-cost, and reproducible sensor based on a cellulose-based material, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized-cellulose nanocrystals (CNCs). This novel biocompatible and inert nanomaterial is employed as a polymeric matrix to immobilize and stabilize glucose oxidase in the fabrication of a reproducible, operationally stable, highly selective, cost-effective, screen-printed glucose sensor. The sensors have a linear range of 0.1–2 mM (R2 = 0.999) and a sensitivity of 5.7 ± 0.3 µA cm−2∙mM−1. The limit of detection is 0.004 mM, and the limit of quantification is 0.015 mM. The sensor maintains 92.3 % of the initial current response after 30 consecutive measurements in a 1 mM standard glucose solution, and has a shelf life of 1 month while maintaining high selectivity. We demonstrate the practical application of the sensor by monitoring the glucose consumption of a fibroblast cell culture over the course of several days. Full article
(This article belongs to the Special Issue Novel Materials for Electrochemical Biosensors)
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13 pages, 2352 KiB  
Article
Robust Single-Trial EEG-Based Authentication Achieved with a 2-Stage Classifier
by Uladzislau Barayeu, Nastassya Horlava, Arno Libert and Marc Van Hulle
Biosensors 2020, 10(9), 124; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090124 - 13 Sep 2020
Cited by 10 | Viewed by 3343
Abstract
The risk of personal data exposure through unauthorized access has never been as imminent as today. To counter this, biometric authentication has been proposed: the use of distinctive physiological and behavioral characteristics as a form of identification and access control. One of the [...] Read more.
The risk of personal data exposure through unauthorized access has never been as imminent as today. To counter this, biometric authentication has been proposed: the use of distinctive physiological and behavioral characteristics as a form of identification and access control. One of the recent developments is electroencephalography (EEG)-based authentication. It builds on the subject-specific nature of brain responses which are difficult to recreate artificially. We propose an authentication system based on EEG signals recorded in response to a simple motor paradigm. Authentication is achieved with a novel two-stage decoder. In the first stage, EEG signal features are extracted using an inception- and a VGG-like deep learning neural network (NN) both of which we compare with principal component analysis (PCA). In the second stage, a support vector machine (SVM) is used for binary classification to authenticate the subject based on the extracted features. All decoders are trained on EEG motor-movement data recorded from 105 subjects. We achieved with the VGG-like NN-SVM decoder a false-acceptance rate (FAR) of 2.55% with an overall accuracy of 88.29%, a FAR of 3.33% with an accuracy of 87.47%, and a FAR of 2.89% with an accuracy of 90.68% for 8, 16, and 64 channels, respectively. With the Inception-like NN-SVM decoder we achieved a false-acceptance rate (FAR) of 4.08% with an overall accuracy of 87.29%, a FAR of 3.53% with an accuracy of 85.31%, and a FAR of 1.27% with an accuracy of 93.40% for 8, 16, and 64 channels, respectively. The PCA-SVM decoder achieved accuracies of 92.09%, 92.36%, and 95.64% with FARs of 2.19%, 2.17%, and 1.26% for 8, 16, and 64 channels, respectively. Full article
(This article belongs to the Section Intelligent Biosensors and Bio-Signal Processing)
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8 pages, 2453 KiB  
Article
Screen-Printed Sensor for Low-Cost Chloride Analysis in Sweat for Rapid Diagnosis and Monitoring of Cystic Fibrosis
by Alicia Hauke, Susanne Oertel, Leona Knoke, Vanessa Fein, Christoph Maier, Folke Brinkmann and Michael P. M. Jank
Biosensors 2020, 10(9), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090123 - 11 Sep 2020
Cited by 12 | Viewed by 4213
Abstract
Analysis of sweat chloride levels in cystic fibrosis (CF) patients is essential not only for diagnosis but also for the monitoring of therapeutic responses to new drugs, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and potentiators. Using iontophoresis as the gold [...] Read more.
Analysis of sweat chloride levels in cystic fibrosis (CF) patients is essential not only for diagnosis but also for the monitoring of therapeutic responses to new drugs, such as cystic fibrosis transmembrane conductance regulator (CFTR) modulators and potentiators. Using iontophoresis as the gold standard can cause complications like burns, is uncomfortable, and requires repetitive hospital visits, which can be particularly problematic during a pandemic, where distancing and hygiene requirements are increased; therefore, it is necessary to develop fast and simple measures for the diagnosis and monitoring of CF. A screen-printed, low-cost chloride sensor was developed to remotely monitor CF patients. Using potentiometric measurements, the performance of the sensor was tested. It showed good sensitivity and a detection limit of 2.7 × 10−5 mol/L, which covered more than the complete concentration range of interest for CF diagnosis. Due to its fast response of 30 s, it competes well with standard sensor systems. It also offers significantly reduced costs and can be used as a portable device. The analysis of real sweat samples from healthy subjects, as well as CF patients, demonstrates a proper distinction using the screen-printed sensor. This approach presents an attractive remote measurement alternative for fast, simple, and low-cost CF diagnosis and monitoring Full article
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12 pages, 3669 KiB  
Article
Silver-Based SERS Pico-Molar Adenine Sensor
by Yonhua Tzeng and Bo-Yi Lin
Biosensors 2020, 10(9), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090122 - 11 Sep 2020
Cited by 9 | Viewed by 3413
Abstract
Adenine is an important molecule for biomedical and agricultural research and applications. The detection of low concentration adenine molecules is thus desirable. Surface-enhanced Raman scattering (SERS) is a promising label-free detection and fingerprinting technique for molecules of significance. A novel SERS sensor made [...] Read more.
Adenine is an important molecule for biomedical and agricultural research and applications. The detection of low concentration adenine molecules is thus desirable. Surface-enhanced Raman scattering (SERS) is a promising label-free detection and fingerprinting technique for molecules of significance. A novel SERS sensor made of clusters of silver nanostructures deposited on copper bumps in valleys of an etched silicon substrate was previously reported to exhibit a low and reproducible detection limit for a 10−11 M neutral adenine aqueous solution. Reflection of laser illumination from the silicon surface surrounding a valley provides additional directions of laser excitation to adenine molecules adsorbing on a silver surface for the generation of enhanced SERS signal strength leading to a low detection limit. This paper further reports a concentration dependent shift of the ring-breathing mode SERS adenine peak towards 760 cm−1 with decreasing concentration and its pH-dependent SERS signal strength. For applications, where the pH value can vary, reproducible detection of 10−12 M adenine in a pH 9 aqueous solution is feasible, making the novel SERS structure a desirable pico-molar adenine sensor. Full article
(This article belongs to the Special Issue Novel Plasmonic Biosensors)
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47 pages, 7385 KiB  
Review
Biomolecules and Electrochemical Tools in Chronic Non-Communicable Disease Surveillance: A Systematic Review
by Ana Lúcia Morais, Patrícia Rijo, María Belén Batanero Hernán and Marisa Nicolai
Biosensors 2020, 10(9), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090121 - 10 Sep 2020
Cited by 13 | Viewed by 3842
Abstract
Over recent three decades, the electrochemical techniques have become widely used in biological identification and detection, because it presents optimum features for efficient and sensitive molecular detection of organic compounds, being able to trace quantities with a minimum of reagents and sample manipulation. [...] Read more.
Over recent three decades, the electrochemical techniques have become widely used in biological identification and detection, because it presents optimum features for efficient and sensitive molecular detection of organic compounds, being able to trace quantities with a minimum of reagents and sample manipulation. Given these special features, electrochemical techniques are regularly exploited in disease diagnosis and monitoring. Specifically, amperometric electrochemical analysis has proven to be quite suitable for the detection of physiological biomarkers in monitoring health conditions, as well as toward the control of reactive oxygen species released in the course of oxidative burst during inflammatory events. Besides, electrochemical detection techniques involve a simple and swift assessment that provides a low detection-limit for most of the molecules enclosed biological fluids and related to non-transmittable morbidities. Full article
(This article belongs to the Special Issue Advanced Biosensing Technologies in Medical Applications)
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12 pages, 1396 KiB  
Article
LipiSensors: Exploiting Lipid Nanoemulsions to Fabricate Ionophore-Based Nanosensors
by Alexandra L. Dailey, Meredith D. Greer, Tyler Z. Sodia, Megan P. Jewell, Tabitha A. Kalin and Kevin J. Cash
Biosensors 2020, 10(9), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090120 - 10 Sep 2020
Cited by 8 | Viewed by 3673
Abstract
Ionophore-based nanosensors (IBNS) are tools that enable quantification of analytes in complex chemical and biological systems. IBNS methodology is adopted from that of bulk optodes where an ion exchange event is converted to a change in optical output. While valuable, an important aspect [...] Read more.
Ionophore-based nanosensors (IBNS) are tools that enable quantification of analytes in complex chemical and biological systems. IBNS methodology is adopted from that of bulk optodes where an ion exchange event is converted to a change in optical output. While valuable, an important aspect for application is the ability to intentionally tune their size with simple approaches, and ensure that they contain compounds safe for application. Lipidots are a platform of size tunable lipid nanoemulsions with a hydrophobic lipid core typically used for imaging and drug delivery. Here, we present LipiSensors as size tunable IBNS by exploiting the Lipidot model as a hydrophobic structural support for the sensing moieties that are traditionally encased in plasticized PVC nanoparticles. The LipiSensors we demonstrate here are sensitive and selective for calcium, reversible, and have a lifetime of approximately one week. By changing the calcium sensing components inside the hydrophobic core of the LipiSensors to those sensitive for oxygen, they are also able to be used as ratiometric O2 sensitive nanosensors via a quenching-based mechanism. LipiSensors provide a versatile, general platform nanosensing with the ability to directly tune the size of the sensors while including biocompatible materials as the structural support by merging sensing approaches with the Lipidot platform. Full article
(This article belongs to the Special Issue Fluorescence Biosensors 2020)
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11 pages, 2532 KiB  
Article
Exploiting Laser-Ablation ICP-MS for the Characterization of Salt-Derived Bismuth Films on Screen-Printed Electrodes: A Preliminary Investigation
by Carlo Dossi, Gilberto Binda, Damiano Monticelli, Andrea Pozzi, Sandro Recchia and Davide Spanu
Biosensors 2020, 10(9), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090119 - 09 Sep 2020
Cited by 2 | Viewed by 2205
Abstract
The use of insoluble bismuth salts, typically BiPO4, is known to be a viable alternative to classical Bi3+ ion electrochemical reduction for the preparation of bismuth film electrodes (BiFE) on screen-printed electrodes. The freshly prepared electrodes are indefinitely stable, and [...] Read more.
The use of insoluble bismuth salts, typically BiPO4, is known to be a viable alternative to classical Bi3+ ion electrochemical reduction for the preparation of bismuth film electrodes (BiFE) on screen-printed electrodes. The freshly prepared electrodes are indefinitely stable, and the active bismuth film is simply formed by in situ reduction. Two aspects are still to be investigated, namely the bismuth distribution on the working electrode and the possible residual presence of the counteranion, namely phosphate. High-vacuum techniques such as electron microscopy or spectroscopy, which are commonly employed for this purpose, cannot be safely used: the bismuth surface is well-known to reconstruct and recrystallize under the electron beam in vacuum. Here, we demonstrate the suitability and the effectiveness of laser ablation ICP-MS (LA-ICP-MS, a technique that vaporizes and analyzes the surface material under flowing helium at atmospheric pressure) for the characterization of BiFE. Fast and stable measurements of bismuth and phosphorous distribution are achieved with the advantage of a minimum alteration of the sample surface, avoiding possible interferences. This investigation evidenced how, upon reductive activation, the bismuth film is distributed with a radial symmetry and the phosphate counteranion is completely absent on the working electrode surface. Full article
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39 pages, 4639 KiB  
Review
Electrochemiluminescence Biosensors Using Screen-Printed Electrodes
by Emiliano Martínez-Periñán, Cristina Gutiérrez-Sánchez, Tania García-Mendiola and Encarnación Lorenzo
Biosensors 2020, 10(9), 118; https://doi.org/10.3390/bios10090118 - 09 Sep 2020
Cited by 36 | Viewed by 7529
Abstract
Electrogenerated chemiluminescence (also called electrochemiluminescence (ECL)) has become a great focus of attention in different fields of analysis, mainly as a consequence of the potential remarkably high sensitivity and wide dynamic range. In the particular case of sensing applications, ECL biosensor unites the [...] Read more.
Electrogenerated chemiluminescence (also called electrochemiluminescence (ECL)) has become a great focus of attention in different fields of analysis, mainly as a consequence of the potential remarkably high sensitivity and wide dynamic range. In the particular case of sensing applications, ECL biosensor unites the benefits of the high selectivity of biological recognition elements and the high sensitivity of ECL analysis methods. Hence, it is a powerful analytical device for sensitive detection of different analytes of interest in medical prognosis and diagnosis, food control and environment. These wide range of applications are increased by the introduction of screen-printed electrodes (SPEs). Disposable SPE-based biosensors cover the need to perform in-situ measurements with portable devices quickly and accurately. In this review, we sum up the latest biosensing applications and current progress on ECL bioanalysis combined with disposable SPEs in the field of bio affinity ECL sensors including immunosensors, DNA analysis and catalytic ECL sensors. Furthermore, the integration of nanomaterials with particular physical and chemical properties in the ECL biosensing systems has improved tremendously their sensitivity and overall performance, being one of the most appropriates research fields for the development of highly sensitive ECL biosensor devices. Full article
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12 pages, 1965 KiB  
Article
Transient Effect at the Onset of Human Running
by Christian Weich, Manfred M. Vieten and Randall L. Jensen
Biosensors 2020, 10(9), 117; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090117 - 08 Sep 2020
Cited by 4 | Viewed by 2303
Abstract
While training and competing as a runner, athletes often sense an unsteady feeling during the first meters on the road. This sensation, termed as transient effect, disappears after a short period as the runners approach their individual running rhythm. The foundation of this [...] Read more.
While training and competing as a runner, athletes often sense an unsteady feeling during the first meters on the road. This sensation, termed as transient effect, disappears after a short period as the runners approach their individual running rhythm. The foundation of this work focuses on the detection and quantification of this phenomenon. Thirty athletes ran two sessions over 60 min on a treadmill at moderate speed. Three-dimensional acceleration data were collected using two MEMS sensors attached to the lower limbs. By using the attractor method and Fourier transforms, the transient effect was isolated from noise and further components of human cyclic motion. A substantial transient effect was detected in 81% of all measured runs. On average, the transient effect lasted 5.25 min with a range of less than one minute to a maximum of 31 min. A link to performance data such as running level, experience and weekly training hours could not be found. The presented work provides the methodological basis to detect and quantify the transient effect at moderate running speeds. The acquisition of further physical or metabolic performance data could provide more detailed information about the impact of the transient effect on athletic performance. Full article
(This article belongs to the Special Issue Advanced Applications in Wearable Biosensors)
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11 pages, 1500 KiB  
Article
Impedimetric Sensing of Factor V Leiden Mutation by Zip Nucleic Acid Probe and Electrochemical Array
by Arzum Erdem and Ece Eksin
Biosensors 2020, 10(9), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090116 - 07 Sep 2020
Cited by 5 | Viewed by 2854
Abstract
A carbon nanofiber enriched 8-channel screen-printed electrochemical array was used for the impedimetric detection of SNP related to Factor V Leiden (FV Leiden) mutation, which is the most common inherited form of thrombophilia. FV Leiden mutation sensing was carried out in three steps: [...] Read more.
A carbon nanofiber enriched 8-channel screen-printed electrochemical array was used for the impedimetric detection of SNP related to Factor V Leiden (FV Leiden) mutation, which is the most common inherited form of thrombophilia. FV Leiden mutation sensing was carried out in three steps: solution-phase nucleic acid hybridization between zip nucleic acid probe (Z-probe) and mutant type DNA target, followed by the immobilization of the hybrid on the working electrode area of array, and measurement by electrochemical impedance spectroscopy (EIS). The selectivity of the assay was tested against mutation-free DNA sequences and synthetic polymerase chain reaction (PCR) samples. The developed biosensor was a trustful assay for FV Leiden mutation diagnosis, which can effectively discriminate wild type and mutant type even in PCR samples. Full article
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27 pages, 6273 KiB  
Review
Printed Electrodes in Microfluidic Arrays for Cancer Biomarker Protein Detection
by Lasangi Dhanapala, Colleen E. Krause, Abby L. Jones and James F. Rusling
Biosensors 2020, 10(9), 115; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090115 - 07 Sep 2020
Cited by 19 | Viewed by 5729
Abstract
Medical diagnostics is trending towards a more personalized future approach in which multiple tests can be digitized into patient records. In cancer diagnostics, patients can be tested for individual protein and genomic biomarkers that detect cancers at very early stages and also be [...] Read more.
Medical diagnostics is trending towards a more personalized future approach in which multiple tests can be digitized into patient records. In cancer diagnostics, patients can be tested for individual protein and genomic biomarkers that detect cancers at very early stages and also be used to monitor cancer progression or remission during therapy. These data can then be incorporated into patient records that could be easily accessed on a cell phone by a health care professional or the patients themselves on demand. Data on protein biomarkers have a large potential to be measured in point-of-care devices, particularly diagnostic panels that could provide a continually updated, personalized record of a disease like cancer. Electrochemical immunoassays have been popular among protein detection methods due to their inherent high sensitivity and ease of coupling with screen-printed and inkjet-printed electrodes. Integrated chips featuring these kinds of electrodes can be built at low cost and designed for ease of automation. Enzyme-linked immunosorbent assay (ELISA) features are adopted in most of these ultrasensitive detection systems, with microfluidics allowing easy manipulation and good fluid dynamics to deliver reagents and detect the desired proteins. Several of these ultrasensitive systems have detected biomarker panels ranging from four to eight proteins, which in many cases when a specific cancer is suspected may be sufficient. However, a grand challenge lies in engineering microfluidic-printed electrode devices for the simultaneous detection of larger protein panels (e.g., 50–100) that could be used to test for many types of cancers, as well as other diseases for truly personalized care. Full article
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8 pages, 1292 KiB  
Article
A Self-Powered Biosensor for the Detection of Glutathione
by Brandon G. Roy, Julia L. Rutherford, Anna E. Weaver, Kevin Beaver and Michelle Rasmussen
Biosensors 2020, 10(9), 114; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090114 - 03 Sep 2020
Cited by 10 | Viewed by 4638
Abstract
Glutathione is an important biological molecule which can be an indicator of numerous diseases. A method for self-powered detection of glutathione levels in solution has been developed using an enzymatic biofuel cell. The device consists of a glucose oxidase anode and a bilirubin [...] Read more.
Glutathione is an important biological molecule which can be an indicator of numerous diseases. A method for self-powered detection of glutathione levels in solution has been developed using an enzymatic biofuel cell. The device consists of a glucose oxidase anode and a bilirubin oxidase cathode. For the detection of glutathione, the inhibition of bilirubin oxidase leads to a measurable decrease in current and power output. The reported method has a detection limit of 0.043 mM and a linear range up to 1.7 mM. Being able to detect a range of concentrations can be useful in evaluating a patient’s health. This method has the potential to be implemented as a quick, low-cost alternative to previously reported methods. Full article
(This article belongs to the Special Issue Biofuel and Biosolar Cells as Biosensing Systems)
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10 pages, 1573 KiB  
Article
Enhancement of the Peroxidase-Like Activity of Iodine-Capped Gold Nanoparticles for the Colorimetric Detection of Biothiols
by Chia-Chen Chang, Tsz-Lian Hsu, Chie-Pein Chen and Chen-Yu Chen
Biosensors 2020, 10(9), 113; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090113 - 01 Sep 2020
Cited by 10 | Viewed by 4043
Abstract
A colorimetric assay was developed for the detection of biothiols, based on the peroxidase-like activity of iodine-capped gold nanoparticles (AuNPs). These AuNPs show a synergetic effect in the form of peroxidase-mimicking activity at the interface of AuNPs, while free AuNPs and iodine alone [...] Read more.
A colorimetric assay was developed for the detection of biothiols, based on the peroxidase-like activity of iodine-capped gold nanoparticles (AuNPs). These AuNPs show a synergetic effect in the form of peroxidase-mimicking activity at the interface of AuNPs, while free AuNPs and iodine alone have weak catalytic properties. Thus, iodine-capped AuNPs possess good intrinsic enzymatic activity and trigger the oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB), leading to a change in color from colorless to yellow. When added to solution, biothiols, such as cysteine, strongly bind to the interface of AuNPs via gold-thiol bonds, inhibiting the catalytic activity of AuNPs, resulting in a decrease in oxidized TMB. Using this strategy, cysteine could be linearly determined, at a wide range of concentrations (0.5 to 20 μM), with a detection limit of 0.5 μM using UV-Vis spectroscopy. This method was applied for the detection of cysteine in diluted human urine. Full article
(This article belongs to the Special Issue Biomimetic Sensors and Their Applications)
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19 pages, 3848 KiB  
Review
Biosensors for Antioxidants Detection: Trends and Perspectives
by Melinda David, Monica Florescu and Camelia Bala
Biosensors 2020, 10(9), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090112 - 01 Sep 2020
Cited by 12 | Viewed by 3736
Abstract
Herein we review the recent advances in biosensors for antioxidants detection underlying principles particularly emphasizing advantages along with limitations regarding the ability to discriminate between the specific antioxidant or total content. Recent advances in both direct detection of antioxidants, but also on indirect [...] Read more.
Herein we review the recent advances in biosensors for antioxidants detection underlying principles particularly emphasizing advantages along with limitations regarding the ability to discriminate between the specific antioxidant or total content. Recent advances in both direct detection of antioxidants, but also on indirect detection, measuring the induced damage on DNA-based biosensors are critically analysed. Additionally, latest developments on (bio)electronic tongues are also presented. Full article
(This article belongs to the Special Issue Biosensors: 10th Anniversary Feature Papers)
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10 pages, 4556 KiB  
Article
Selective Nonenzymatic Amperometric Detection of Lactic Acid in Human Sweat Utilizing a Multi-Walled Carbon Nanotube (MWCNT)-Polypyrrole Core-Shell Nanowire
by Young Min Choi, Hana Lim, Ho-Nyun Lee, Young Min Park, Jin-Seong Park and Hyun-Jong Kim
Biosensors 2020, 10(9), 111; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090111 - 28 Aug 2020
Cited by 24 | Viewed by 4158
Abstract
Lactic acid plays an important role as a biochemical indicator for sports medicine and clinical diagnosis. The detection of lactic acid in sweat is a promising technique without any intrusive inconvenience or risk of infection. In this study, we present a selective nonenzymatic [...] Read more.
Lactic acid plays an important role as a biochemical indicator for sports medicine and clinical diagnosis. The detection of lactic acid in sweat is a promising technique without any intrusive inconvenience or risk of infection. In this study, we present a selective nonenzymatic amperometric detection method for lactic acid in human sweat utilizing a multi-wall carbon nanotube (MWCNT)-polypyrrole core-shell nanowire. Because polypyrrole is a p-type conducting polymer, onto which anions are exclusively doped, leading to charge transfer, it offers selective detection for lactate anions at a specific potential, while being inert to the neutral and cationic species contained in human sweat. A chronoamperometric study reveals good sensing performance for lactic acid with a high sensitivity of 2.9 μA mM−1 cm−2 and detection limit of 51 μM. Furthermore, the MWCNT-polypyrrole nanowire exhibits excellent selectivity for lactic acid over interfering species, such as sodium chloride, glucose, urea, and riboflavin, which coexist with lactic acid in sweat. Finally, a nonenzymatic amperometric sensor for the selective detection of lactic acid in human sweat is demonstrated on commercial flexible electrodes. The results demonstrate the potential applications of the MWCNT-polypyrrole core-shell nanowire as a nonenzymatic amperometric lactate sensor. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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35 pages, 6609 KiB  
Review
Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems
by Erika Ferrari, Cecilia Palma, Simone Vesentini, Paola Occhetta and Marco Rasponi
Biosensors 2020, 10(9), 110; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090110 - 28 Aug 2020
Cited by 64 | Viewed by 7779
Abstract
Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering [...] Read more.
Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed. Full article
(This article belongs to the Special Issue Organ-on-a-Chip for Biosensing)
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18 pages, 3977 KiB  
Article
Gait Phase Recognition Using Deep Convolutional Neural Network with Inertial Measurement Units
by Binbin Su, Christian Smith and Elena Gutierrez Farewik
Biosensors 2020, 10(9), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090109 - 27 Aug 2020
Cited by 26 | Viewed by 4677
Abstract
Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user’s current gait phase must [...] Read more.
Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user’s current gait phase must first be identified accurately. Gait phase recognition can potentially be achieved through input from wearable sensors. Deep convolutional neural networks (DCNN) is a machine learning approach that is widely used in image recognition. User kinematics, measured from inertial measurement unit (IMU) output, can be considered as an ‘image’ since it exhibits some local ‘spatial’ pattern when the sensor data is arranged in sequence. We propose a specialized DCNN to distinguish five phases in a gait cycle, based on IMU data and classified with foot switch information. The DCNN showed approximately 97% accuracy during an offline evaluation of gait phase recognition. Accuracy was highest in the swing phase and lowest in terminal stance. Full article
(This article belongs to the Special Issue Advanced Applications in Wearable Biosensors)
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19 pages, 1184 KiB  
Review
Aptasensors for Point-of-Care Detection of Small Molecules
by Marc Prante, Ester Segal, Thomas Scheper, Janina Bahnemann and Johanna Walter
Biosensors 2020, 10(9), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090108 - 26 Aug 2020
Cited by 51 | Viewed by 6181
Abstract
Aptamers, a group of nucleic acids which can specifically bind to a target molecule, have drawn extensive interest over the past few decades. For analytics, aptamers represent a viable alternative to gold-standard antibodies due to their oligonucleic nature combined with advantageous properties, including [...] Read more.
Aptamers, a group of nucleic acids which can specifically bind to a target molecule, have drawn extensive interest over the past few decades. For analytics, aptamers represent a viable alternative to gold-standard antibodies due to their oligonucleic nature combined with advantageous properties, including higher stability in harsh environments and longer shelf-life. Indeed, over the last decade, aptamers have been used in numerous bioanalytical assays and in various point-of-care testing (POCT) platforms. The latter allows for rapid on-site testing and can be performed outside a laboratory by unskilled labor. Aptamer technology for POCT is not limited just to medical diagnostics; it can be used for a range of applications, including environmental monitoring and quality control. In this review, we critically examine the use of aptamers in POCT with an emphasis on their advantages and limitations. We also examine the recent success of aptasensor technology and how these findings pave the way for the analysis of small molecules in POCT and other health-related applications. Finally, the current major limitations of aptamers are discussed, and possible approaches for overcoming these challenges are presented. Full article
(This article belongs to the Special Issue Aptamers to Replace Antibodies for in vitro Diagnostics)
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21 pages, 1349 KiB  
Review
B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor
by Dorin Harpaz, Raymond C. S. Seet, Robert S. Marks and Alfred I. Y. Tok
Biosensors 2020, 10(9), 107; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090107 - 26 Aug 2020
Cited by 11 | Viewed by 4711
Abstract
Stroke is a widespread condition that causes 7 million deaths globally. Survivors suffer from a range of disabilities that affect their everyday life. It is a complex condition and there is a need to monitor the different signals that are associated with it. [...] Read more.
Stroke is a widespread condition that causes 7 million deaths globally. Survivors suffer from a range of disabilities that affect their everyday life. It is a complex condition and there is a need to monitor the different signals that are associated with it. Stroke patients need to be rapidly diagnosed in the emergency department in order to allow the admission of the time-limited treatment of tissue plasminogen activator (tPA). Stroke diagnostics show the use of sophisticated technologies; however, they still contain limitations. The hidden information and technological advancements behind the utilization of biomarkers for stroke triaging are significant. Stroke biomarkers can revolutionize the way stroke patients are diagnosed, monitored, and how they recover. Different biomarkers indicate different cascades and exhibit unique expression patterns which are connected to certain pathologies in the human body. Over the past decades, B-type natriuretic peptide (BNP) and its derivative N-terminal fragment (NT-proBNP) have been increasingly investigated and highlighted as significant cardiovascular biomarkers. This work reviews the recent studies that have reported on the usefulness of BNP and NT-proBNP for stroke triaging. Their classification association is also presented, with increased mortality in stroke, correlation with cardioembolic stroke, and an indication of a second stroke recurrence. Moreover, recent scientific efforts conducted for the technological advancement of a bedside point-of-care (POC) device for BNP and NT-proBNP measurements are discussed. The conclusions presented in this review may hopefully assist in the major efforts that are currently being conducted in order to improve the care of stroke patients. Full article
(This article belongs to the Section Biosensors and Healthcare)
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19 pages, 3310 KiB  
Article
Biosensing Cytokine IL-6: A Comparative Analysis of Natural and Synthetic Receptors
by Eleonora Alfinito, Matteo Beccaria and Mariangela Ciccarese
Biosensors 2020, 10(9), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090106 - 24 Aug 2020
Cited by 5 | Viewed by 3364
Abstract
Cytokines are a family of proteins which play a major role in the regulation of the immune system and the development of several diseases, from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being developed to improve therapy [...] Read more.
Cytokines are a family of proteins which play a major role in the regulation of the immune system and the development of several diseases, from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being developed to improve therapy and diagnosis, as well as to produce inhibitory drugs and biosensors for a rapid, minimally invasive, and effective detection. In this regard, even more efficient cytokine receptors are under investigation. In this paper we analyze a set of IL-6 cytokine receptors, investigating their topological features by means of a theoretical approach. Our results suggest a topological indicator that may help in the identification of those receptors having the highest complementarity with the protein, a feature expected to ensure a stable binding. Furthermore, we propose and discuss the use of these receptors in an idealized experimental setup. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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57 pages, 7388 KiB  
Review
Biosensors and Sensing Systems for Rapid Analysis of Phenolic Compounds from Plants: A Comprehensive Review
by Cristina Forzato, Veronica Vida and Federico Berti
Biosensors 2020, 10(9), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090105 - 24 Aug 2020
Cited by 22 | Viewed by 6101
Abstract
Phenolic compounds are secondary metabolites frequently found in plants that exhibit many different effects on human health. Because of the relevant bioactivity, their identification and quantification in agro-food matrices as well as in biological samples are a fundamental issue in the field of [...] Read more.
Phenolic compounds are secondary metabolites frequently found in plants that exhibit many different effects on human health. Because of the relevant bioactivity, their identification and quantification in agro-food matrices as well as in biological samples are a fundamental issue in the field of quality control of food and food supplements, and clinical analysis. In this review, a critical selection of sensors and biosensors for rapid and selective detection of phenolic compounds is discussed. Sensors based on electrochemistry, photoelectrochemistry, fluorescence, and colorimetry are discussed including devices with or without specific recognition elements, such as biomolecules, enzymes and molecularly imprinted materials. Systems that have been tested on real matrices are prevalently considered but also techniques that show potential development in the field. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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15 pages, 2240 KiB  
Article
Poly(9H-carbazole) as a Organic Semiconductor for Enzymatic and Non-Enzymatic Glucose Sensors
by Gintautas Bagdžiūnas and Delianas Palinauskas
Biosensors 2020, 10(9), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090104 - 23 Aug 2020
Cited by 21 | Viewed by 3453
Abstract
Organic semiconductors and conducting polymers are the most promising next-generation conducting materials for electrochemical biosensors as the greener and cheaper alternative for electrodes based on transition metals or their oxides. Therefore, polycarbazole as the organic semiconducting polymer was electrochemically synthesized and deposited on [...] Read more.
Organic semiconductors and conducting polymers are the most promising next-generation conducting materials for electrochemical biosensors as the greener and cheaper alternative for electrodes based on transition metals or their oxides. Therefore, polycarbazole as the organic semiconducting polymer was electrochemically synthesized and deposited on working electrode. Structure and semiconducting properties of polycarbazole have theoretically and experimentally been analyzed and proved. For these electrochemical systems, a maximal sensitivity of 14 μA·cm−2·mM−1, a wide linear range of detection up to 5 mM, and a minimal limit of detection of around 0.2 mM were achieved. Moreover, Michaelis’s constant of these sensors depends not only on the enzyme but on the material of electrode and applied potential. The electrocatalytic mechanism and performance of the non- and enzymatic sensors based on this material as a conducting layer have been discussed by estimating pseudocapacitive and faradaic currents and by adding glucose as an analyte at the different applied potentials. In this work, the attention was focused on the electrochemical origin and mechanism involved in the non- and enzymatic oxidation and reduction of glucose. Full article
(This article belongs to the Section Biosensor Materials)
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20 pages, 3169 KiB  
Article
A French–Greek Cross-Site Comparison Study of the Use of Automatic Video Analyses for the Assessment of Autonomy in Dementia Patients
by Anastasios Karakostas, Alexandra König, Carlos Fernando Crispim-Junior, François Bremond, Alexandre Derreumaux, Ioulietta Lazarou, Ioannis Kompatsiaris, Magda Tsolaki and Philippe Robert
Biosensors 2020, 10(9), 103; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090103 - 21 Aug 2020
Cited by 6 | Viewed by 2859
Abstract
Background: At present, the assessment of autonomy in daily living activities, one of the key symptoms in Alzheimer’s disease (AD), involves clinical rating scales. Methods: In total, 109 participants were included. In particular, 11 participants during a pre-test in Nice, France, and 98 [...] Read more.
Background: At present, the assessment of autonomy in daily living activities, one of the key symptoms in Alzheimer’s disease (AD), involves clinical rating scales. Methods: In total, 109 participants were included. In particular, 11 participants during a pre-test in Nice, France, and 98 participants (27 AD, 38 mild cognitive impairment—MCI—and 33 healthy controls—HC) in Thessaloniki, Greece, carried out a standardized scenario consisting of several instrumental activities of daily living (IADLs), such as making a phone call or preparing a pillbox while being recorded. Data were processed by a platform of video signal analysis in order to extract kinematic parameters, detecting activities undertaken by the participant. Results: The video analysis data can be used to assess IADL task quality and provide clinicians with objective measurements of the patients’ performance. Furthermore, it reveals that the HC statistically significantly outperformed the MCI, which had better performance compared to the AD participants. Conclusions: Accurate activity recognition data for the analyses of the performance on IADL activities were obtained. Full article
(This article belongs to the Special Issue Mobile and Wearable Systems for Smarthealth)
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12 pages, 1368 KiB  
Article
Rapid Detection of Legionella pneumophila in Drinking Water, Based on Filter Immunoassay and Chronoamperometric Measurement
by Josune J. Ezenarro, Noemí Párraga-Niño, Miquel Sabrià, Fancisco Javier Del Campo, Francesc-Xavier Muñoz-Pascual, Jordi Mas and Naroa Uria
Biosensors 2020, 10(9), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/bios10090102 - 20 Aug 2020
Cited by 16 | Viewed by 4822
Abstract
Legionella is a pathogenic bacterium, ubiquitous in freshwater environments and able to colonise man-made water systems from which it can be transmitted to humans during outbreaks. The prevention of such outbreaks requires a fast, low cost, automated and often portable detection system. In [...] Read more.
Legionella is a pathogenic bacterium, ubiquitous in freshwater environments and able to colonise man-made water systems from which it can be transmitted to humans during outbreaks. The prevention of such outbreaks requires a fast, low cost, automated and often portable detection system. In this work, we present a combination of sample concentration, immunoassay detection, and measurement by chronoamperometry. A nitrocellulose microfiltration membrane is used as support for both the water sample concentration and the Legionella immunodetection. The horseradish peroxidase enzymatic label of the antibodies permits using the redox substrate 3,3′,5,5′-Tetramethylbenzidine to generate current changes proportional to the bacterial concentration present in drinking water. Carbon screen-printed electrodes are employed in the chronoamperometric measurements. Our system reduces the detection time: from the 10 days required by the conventional culture-based methods, to 2–3 h, which could be crucial to avoid outbreaks. Additionally, the system shows a linear response (R2 value of 0.99), being able to detect a range of Legionella concentrations between 101 and 104 cfu·mL−1 with a detection limit (LoD) of 4 cfu·mL−1. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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