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Biosensors, Volume 10, Issue 10 (October 2020) – 21 articles

Cover Story (view full-size image): We report a novel diffraction-based leaky waveguide (LW) biosensor with an array of alternate strips with and without recognition elements created by selective removal of a photocleavable linker using 365 nm light. The photocleavable linker consisted of a N-hydroxysuccinimide carbonate ester with a photoactive nitrobenzene moiety, which in turn was linked through a polyethylene glycol spacer to biotin. The linker was coupled to the amine groups of a chitosan hydrogel layer that acted as a LW. We measured analyte concentration while removing the effects of temperature and sample composition by differential measurements between the alternate strips. The effect of temperature and sample composition changes caused by non-adsorbing and adsorbing species was reduced by ~98%, ~99%, and ~97%, respectively, compared to the absolute measurements. View this paper.
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15 pages, 1105 KiB  
Article
Development of a Novel SPR Assay to Study CXCR4–Ligand Interactions
by Arnaud Boonen, Abhimanyu K. Singh, Anneleen Van Hout, Kalyan Das, Tom Van Loy, Sam Noppen and Dominique Schols
Biosensors 2020, 10(10), 150; https://doi.org/10.3390/bios10100150 - 21 Oct 2020
Cited by 8 | Viewed by 5123
Abstract
G protein-coupled receptors (GPCRs) are involved in a plethora of different diseases. Consequently, these proteins are considered as an important class of drug targets. Measuring detailed kinetic information on these types of proteins has been challenging. Surface plasmon resonance (SPR) can provide this [...] Read more.
G protein-coupled receptors (GPCRs) are involved in a plethora of different diseases. Consequently, these proteins are considered as an important class of drug targets. Measuring detailed kinetic information on these types of proteins has been challenging. Surface plasmon resonance (SPR) can provide this information, however, the use of SPR on GPCRs remains a complex issue. Here, we report an SPR assay to investigate the interactions between the full-length chemokine receptor CXCR4 and nanobody-Fc (Nb-Fc) ligands. Nb-Fcs consist of two monovalent VHH domains fused with an Fc domain of a human IgG molecule. The CXCR4 protein used in this assay was produced with a C-terminal 10x-histidine tag and was immobilized on a nitrilotriacetic acid chip. In order to verify the sensitivity and effectiveness of this assay, the results were compared to data obtained from cellular assays as well as from another SPR assay using CXCR4 virus-like particles (VLPs). CXCR4 remained intact and stable for at least 12 h, and the kinetic results correlated well with both the cellular assays and the VLP SPR assay results. Apart from determining the binding kinetics of Nb-Fc with CXCR4, our results contributed to understanding CXCR4 interaction dynamics. In conclusion, this assay provides a viable experimental platform that has high potential to be expanded for studying other molecules as well as other histidine-tagged GPCRs. Full article
(This article belongs to the Section Biosensors and Healthcare)
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11 pages, 1140 KiB  
Article
Serum Analysis of Women with Early-Stage Breast Cancer Using a Mini-Array of Tumor-Associated Antigens
by Alma Rosa Oaxaca-Camacho, Oscar René Ochoa-Mojica, Adriana Aguilar-Lemarroy, Luis F. Jave-Suárez, José Francisco Muñoz-Valle, Eduardo Padilla-Camberos, Juan Antonio Núñez-Hernández, Sara E. Herrera-Rodríguez, Moisés Martínez-Velázquez, Ahtziri Socorro Carranza-Aranda, José Alfonso Cruz-Ramos, Abel Gutiérrez-Ortega and Rodolfo Hernández-Gutiérrez
Biosensors 2020, 10(10), 149; https://doi.org/10.3390/bios10100149 - 21 Oct 2020
Cited by 6 | Viewed by 2774
Abstract
Background: Several studies have shown that patients with cancer have antibodies in serum that react with cellular autoantigens, known as Tumor-Associated Antigens (TAA). The present work aimed to determine whether a mini-array comprising four recombinant TAA increases the detection of specific serum antibodies [...] Read more.
Background: Several studies have shown that patients with cancer have antibodies in serum that react with cellular autoantigens, known as Tumor-Associated Antigens (TAA). The present work aimed to determine whether a mini-array comprising four recombinant TAA increases the detection of specific serum antibodies for the diagnosis of early-stage breast cancer. Methods: The mini-array included Alpha 1-AntiTrypsin (A1AT), TriosePhosphate Isomerase 1 (TPI1), Peptidyl-Prolyl cis-trans Isomerase A (PPIA), and PeroxiReDoXin 2 (PRDX2) full-length recombinant proteins. The proteins were produced after gene cloning, expression, and purification, and were verified by Western blot assays. Then, Dot-Blot was performed to find antibodies against the four TAA in 12 sera from women with early-stage breast cancer (stage II) and 12 sera from healthy women. Results: Antibody detection against individual TAA in early-stage breast cancer sera ranged from 58.3% to 83.3%. However, evaluation of the four TAA showed that there was a positive antibody reaction reaching a sensitivity of 100% and a specificity of 85% in early-stage breast cancer, suggesting that this mini-array must be evaluated as a clinical diagnostic tool for early-stage breast cancer in a larger sample size. Conclusion: Our results suggest that TAA mini-arrays may provide a promising and powerful method for improving the detection of breast cancer in Mexican women. Full article
(This article belongs to the Section Biosensors and Healthcare)
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14 pages, 2882 KiB  
Article
Determination of the Empirical Electrokinetic Equilibrium Condition of Microorganisms in Microfluidic Devices
by Adriana Coll De Peña, Nicole Hill and Blanca H. Lapizco-Encinas
Biosensors 2020, 10(10), 148; https://doi.org/10.3390/bios10100148 - 19 Oct 2020
Cited by 11 | Viewed by 2741
Abstract
The increased concern regarding emerging pathogens and antibiotic resistance has drawn interest in the development of rapid and robust microfluidic techniques to analyze microorganisms. The novel parameter known as the electrokinetic equilibrium condition (EEEC) was presented in recent [...] Read more.
The increased concern regarding emerging pathogens and antibiotic resistance has drawn interest in the development of rapid and robust microfluidic techniques to analyze microorganisms. The novel parameter known as the electrokinetic equilibrium condition (EEEC) was presented in recent studies, providing an approach to analyze microparticles in microchannels employing unique electrokinetic (EK) signatures. While the EEEC shows great promise, current estimation approaches can be time-consuming or heavily user-dependent for accurate values. The present contribution aims to analyze existing approaches for estimating this parameter and modify the process into an accurate yet simple technique for estimating the EK behavior of microorganisms in insulator-based microfluidic devices. The technique presented here yields the parameter called the empirical electrokinetic equilibrium condition (eEEEC) which works well as a value for initial approximations of trapping conditions in insulator-based EK (iEK) microfluidic systems. A total of six types of microorganisms were analyzed in this study (three bacteria and three bacteriophages). The proposed approach estimated eEEEC values employing images of trapped microorganisms, yielding high reproducibility (SD 5.0–8.8%). Furthermore, stable trapping voltages (sTVs) were estimated from eEEEC values for distinct channel designs to test that this parameter is system-independent and good agreement was obtained when comparing estimated sTVs vs. experimental values (SD 0.3–19.6%). The encouraging results from this work were used to generate an EK library of data, available on our laboratory website. The data in this library can be used to design tailored iEK microfluidic devices for the analysis of microorganisms. Full article
(This article belongs to the Collection Recent Developments in Microfluidics)
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17 pages, 2248 KiB  
Article
Synthesis of Bamboo-like Multiwall Carbon Nanotube–Poly(Acrylic Acid-co-Itaconic Acid)/NaOH Composite Hydrogel and its Potential Application for Electrochemical Detection of Cadmium(II)
by Luis F. Chazaro-Ruiz, Miguel Olvera-Sosa, Gabriela Vidal, J. Rene Rangel-Mendez, Gabriela Palestino, Fatima Perez and Wei Zhang
Biosensors 2020, 10(10), 147; https://doi.org/10.3390/bios10100147 - 19 Oct 2020
Cited by 8 | Viewed by 2937
Abstract
A poly(acrylic acid-co-itaconic acid) (PAA-co-IA)/NaOH hydrogel containing bamboo-type multiwall carbon nanotubes (B-MWCNTs) doped with nitrogen (PAA-co-IA/NaOH/B-MWCNTs) was synthesized and characterized by SEM, absorption of water, point of zero charges, infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The possible use of the PAA-co-IA/NaOH/B-MWCNT [...] Read more.
A poly(acrylic acid-co-itaconic acid) (PAA-co-IA)/NaOH hydrogel containing bamboo-type multiwall carbon nanotubes (B-MWCNTs) doped with nitrogen (PAA-co-IA/NaOH/B-MWCNTs) was synthesized and characterized by SEM, absorption of water, point of zero charges, infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The possible use of the PAA-co-IA/NaOH/B-MWCNT hydrogel as an electrode modifier and pre-concentrator agent for Cd(II) sensing purposes was then evaluated using carbon paste electrodes via differential pulse voltammetry. The presence of the B-MWCNTs in the hydrogel matrix decreased its degree of swelling, stabilized the structure of the swollen gel, and favored the detection of 3 ppb Cd(II), which is comparable to the World Health Organization’s allowable maximum value in drinking water. A calibration curve was obtained in the concentration range of 2.67 × 10−8 to 6.23 × 10−7 M (i.e., 3 and 70 ppb) to determine a limit of detection (LOD) of 19.24 μgL−1 and a sensitivity of 0.15 μC ppb−1. Also, the Zn(II), Hg(II), Pb(II) and Cu(II) ions interfered moderately on the determination of Cd(II). Full article
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52 pages, 9499 KiB  
Review
Gold Nanorods for LSPR Biosensing: Synthesis, Coating by Silica, and Bioanalytical Applications
by Vincent Pellas, David Hu, Yacine Mazouzi, Yoan Mimoun, Juliette Blanchard, Clément Guibert, Michèle Salmain and Souhir Boujday
Biosensors 2020, 10(10), 146; https://doi.org/10.3390/bios10100146 - 17 Oct 2020
Cited by 53 | Viewed by 10692
Abstract
Nanoparticles made of coinage metals are well known to display unique optical properties stemming from the localized surface plasmon resonance (LSPR) phenomenon, allowing their use as transducers in various biosensing configurations. While most of the reports initially dealt with spherical gold nanoparticles owing [...] Read more.
Nanoparticles made of coinage metals are well known to display unique optical properties stemming from the localized surface plasmon resonance (LSPR) phenomenon, allowing their use as transducers in various biosensing configurations. While most of the reports initially dealt with spherical gold nanoparticles owing to their ease of synthesis, the interest in gold nanorods (AuNR) as plasmonic biosensors is rising steadily. These anisotropic nanoparticles exhibit, on top of the LSPR band in the blue range common with spherical nanoparticles, a longitudinal LSPR band, in all respects superior, and in particular in terms of sensitivity to the surrounding media and LSPR-biosensing. However, AuNRs synthesis and their further functionalization are less straightforward and require thorough processing. In this paper, we intend to give an up-to-date overview of gold nanorods in LSPR biosensing, starting from a critical review of the recent findings on AuNR synthesis and the main challenges related to it. We further highlight the various strategies set up to coat AuNR with a silica shell of controlled thickness and porosity compatible with LSPR-biosensing. Then, we provide a survey of the methods employed to attach various bioreceptors to AuNR. Finally, the most representative examples of AuNR-based LSPR biosensors are reviewed with a focus put on their analytical performances. Full article
(This article belongs to the Special Issue Surface Plasmon Resonance for Biosensing)
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13 pages, 1471 KiB  
Article
Allosteric Enzyme-Based Biosensors—Kinetic Behaviours of Immobilised L-Lysine-α-Oxidase from Trichoderma viride: pH Influence and Allosteric Properties
by Antonio Guerrieri, Rosanna Ciriello, Giuliana Bianco, Francesca De Gennaro and Silvio Frascaro
Biosensors 2020, 10(10), 145; https://doi.org/10.3390/bios10100145 - 17 Oct 2020
Cited by 6 | Viewed by 2583
Abstract
The present study describes the kinetics of L-lysine-α-oxidase (LO) from Trichoderma viride immobilised by co-crosslinking onto the surface of a Pt electrode. The resulting amperometric biosensor was able to analyse L-lysine, thus permitting a simple but thorough study of the kinetics of the [...] Read more.
The present study describes the kinetics of L-lysine-α-oxidase (LO) from Trichoderma viride immobilised by co-crosslinking onto the surface of a Pt electrode. The resulting amperometric biosensor was able to analyse L-lysine, thus permitting a simple but thorough study of the kinetics of the immobilised enzyme. The kinetic study evidenced that LO behaves in an allosteric fashion and that cooperativity is strongly pH-dependent. Not less important, experimental evidence shows that cooperativity is also dependent on substrate concentration at high pH and behaves as predicted by the Monod-Wyman-Changeux model for allosteric enzymes. According to this model, the existence of two different conformational states of the enzyme was postulated, which differ in Lys species landing on LO to form the enzyme–substrate complex. Considerations about the influence of the peculiar LO kinetics on biosensor operations and extracorporeal reactor devices will be discussed as well. Not less important, the present study also shows the effectiveness of using immobilised enzymes and amperometric biosensors not only for substrate analysis, but also as a convenient tool for enzyme kinetic studies. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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20 pages, 2812 KiB  
Article
Integrated Experimental and Theoretical Studies on an Electrochemical Immunosensor
by Neda Rafat, Paul Satoh, Scott Calabrese Barton and Robert Mark Worden
Biosensors 2020, 10(10), 144; https://doi.org/10.3390/bios10100144 - 17 Oct 2020
Cited by 4 | Viewed by 2463
Abstract
Electrochemical immunosensors (EIs) integrate biorecognition molecules (e.g., antibodies) with redox enzymes (e.g., horseradish peroxidase) to combine the advantages of immunoassays (high sensitivity and selectivity) with those of electrochemical biosensors (quantitative electrical signal). However, the complex network of mass-transfer, catalysis, and electrochemical reaction steps [...] Read more.
Electrochemical immunosensors (EIs) integrate biorecognition molecules (e.g., antibodies) with redox enzymes (e.g., horseradish peroxidase) to combine the advantages of immunoassays (high sensitivity and selectivity) with those of electrochemical biosensors (quantitative electrical signal). However, the complex network of mass-transfer, catalysis, and electrochemical reaction steps that produce the electrical signal makes the design and optimization of EI systems challenging. This paper presents an integrated experimental and modeling framework to address this challenge. The framework includes (1) a mechanistic mathematical model that describes the rate of key mass-transfer and reaction steps; (2) a statistical-design-of-experiments study to optimize operating conditions and validate the mechanistic model; and (3) a novel dimensional analysis to assess the degree to which individual mass-transfer and reaction steps limit the EI’s signal amplitude and sensitivity. The validated mechanistic model was able to predict the effect of four independent variables (working electrode overpotential, pH, and concentrations of catechol and hydrogen peroxide) on the EI’s signal magnitude. The model was then used to calculate dimensionless groups, including Damkohler numbers, novel current-control coefficients, and sensitivity-control coefficients that indicated the extent to which the individual mass-transfer or reaction steps limited the EI’s signal amplitude and sensitivity. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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15 pages, 5531 KiB  
Article
Fabrication and Characterization of Simple Structure Fluidic-Based Memristor for Immunosensing of NS1 Protein Application
by Nor Shahanim Mohamad Hadis, Asrulnizam Abd Manaf, Mohamad Faizal Abd Rahman, Siti Hawa Ngalim, Thean Hock Tang, Marimuthu Citartan, Aziah Ismail and Sukreen Hana Herman
Biosensors 2020, 10(10), 143; https://doi.org/10.3390/bios10100143 - 16 Oct 2020
Cited by 4 | Viewed by 2332
Abstract
Non-structural protein 1 (NS1 protein) is becoming a commonplace biomarker for the diagnostic of early detection of dengue. In this study, we sought to use a label-free approach of detecting NS1 protein by harnessing fluidic-based memristor sensor. The sensor was fabricated using sol-gel [...] Read more.
Non-structural protein 1 (NS1 protein) is becoming a commonplace biomarker for the diagnostic of early detection of dengue. In this study, we sought to use a label-free approach of detecting NS1 protein by harnessing fluidic-based memristor sensor. The sensor was fabricated using sol-gel spin coating technique, by which TiO2 thin film is coated on the surface of Indium tin oxide (ITO) and a glass substrate. The sensor was then functionalized with glycidoxypropyl-trimethoxysilane (GPTS), acting as antibody for NS1. The addition of the target NS1 formed an antibody-antigen complex which altered the physical and electrical properties in sensing region. Sensing of the sensor is incumbent upon the measurement of Off-On resistance ratio. Imaging with Field Emission Scanning Electron Microscope (FESEM) evinced the successful immobilization of the antibody and the subsequent capture of the NS1 protein by the immobilized antibody. The detection limit actualized by the developed sensor was 52 nM and the diameter of 2 mm gives the most optimal measurement. The developed sensor demonstrated an immense potential towards the development of label-free diagnostic of early dengue infection. Full article
(This article belongs to the Section Biosensor Materials)
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15 pages, 4017 KiB  
Review
Plasmonic Sensors for Monitoring Biological and Chemical Threat Agents
by Yeşeren Saylan, Semra Akgönüllü and Adil Denizli
Biosensors 2020, 10(10), 142; https://doi.org/10.3390/bios10100142 - 15 Oct 2020
Cited by 32 | Viewed by 4933
Abstract
Sensors are excellent options owing to their ability to figure out a large number of problems and challenges in several areas, including homeland security, defense, medicine, pharmacology, industry, environment, agriculture, food safety, and so on. Plasmonic sensors are used as detection devices that [...] Read more.
Sensors are excellent options owing to their ability to figure out a large number of problems and challenges in several areas, including homeland security, defense, medicine, pharmacology, industry, environment, agriculture, food safety, and so on. Plasmonic sensors are used as detection devices that have important properties, such as rapid recognition, real-time analysis, no need labels, sensitive and selective sensing, portability, and, more importantly, simplicity in identifying target analytes. This review summarizes the state-of-art molecular recognition of biological and chemical threat agents. For this purpose, the principle of the plasmonic sensor is briefly explained and then the use of plasmonic sensors in the monitoring of a broad range of biological and chemical threat agents is extensively discussed with different types of threats according to the latest literature. A conclusion and future perspectives are added at the end of the review. Full article
(This article belongs to the Special Issue Novel Plasmonic Biosensors)
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12 pages, 1319 KiB  
Article
Development of a Novel ssDNA Sequence for a Glycated Human Serum Albumin and Construction of a Simple Aptasensor System Based on Reduced Graphene Oxide (rGO)
by A-Ru Kim, Yeongmi Choi, Sang-Heon Kim, Hyun-Seok Moon, Jae-Ho Ko and Moon-Young Yoon
Biosensors 2020, 10(10), 141; https://doi.org/10.3390/bios10100141 - 14 Oct 2020
Cited by 8 | Viewed by 1899
Abstract
Diabetes is one of the top 10 global causes of death. About one in 11 global adults have diabetes. As the disease progresses, the mortality rate increases, and complications can develop. Thus, early detection and effective management of diabetes are especially important. Herein, [...] Read more.
Diabetes is one of the top 10 global causes of death. About one in 11 global adults have diabetes. As the disease progresses, the mortality rate increases, and complications can develop. Thus, early detection and effective management of diabetes are especially important. Herein, we present a novel glycated human serum albumin (GHSA) aptamer, i.e., GABAS-01, which has high affinity and specificity. The aptamer was selected by reduced graphene oxide-based systematic evolution of ligands by exponential enrichement (rGO-based SELEX) against GHSA. After five rounds of selection through gradually harsher conditions, GABAS-01 with high affinity and specificity for the target was obtained. GABAS-01 was labeled by FAM at the 5′-end and characterized by measuring the recovery of a fluorescence signal that is the result of fluorescence quenching effect of rGO. As a result, GABAS-01 had low-nanomolar Kd values of 1.748 ± 0.227 nM and showed a low limit of detection of 16.40 μg/mL against GHSA. This result shows the potential application of GABAS-01 as an effective on-site detection probe of GHSA. In addition, these properties of GABAS-01 are expected to contribute to detection of GHSA in diagnostic fields. Full article
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13 pages, 4022 KiB  
Article
Machine Learning to Improve the Sensing of Biomolecules by Conical Track-Etched Nanopore
by Nathan Meyer, Jean-Marc Janot, Mathilde Lepoitevin, Michaël Smietana, Jean-Jacques Vasseur, Joan Torrent and Sébastien Balme
Biosensors 2020, 10(10), 140; https://doi.org/10.3390/bios10100140 - 05 Oct 2020
Cited by 21 | Viewed by 4137
Abstract
Single nanopore is a powerful platform to detect, discriminate and identify biomacromolecules. Among the different devices, the conical nanopores obtained by the track-etched technique on a polymer film are stable and easy to functionalize. However, these advantages are hampered by their high aspect [...] Read more.
Single nanopore is a powerful platform to detect, discriminate and identify biomacromolecules. Among the different devices, the conical nanopores obtained by the track-etched technique on a polymer film are stable and easy to functionalize. However, these advantages are hampered by their high aspect ratio that avoids the discrimination of similar samples. Using machine learning, we demonstrate an improved resolution so that it can identify short single- and double-stranded DNA (10- and 40-mers). We have characterized each current blockade event by the relative intensity, dwell time, surface area and both the right and left slope. We show an overlap of the relative current blockade amplitudes and dwell time distributions that prevents their identification. We define the different parameters that characterize the events as features and the type of DNA sample as the target. By applying support-vector machines to discriminate each sample, we show accuracy between 50% and 72% by using two features that distinctly classify the data points. Finally, we achieved an increased accuracy (up to 82%) when five features were implemented. Full article
(This article belongs to the Special Issue Micro- and Nanopore Biosensors)
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26 pages, 4776 KiB  
Review
Screen-Printed Electrode-Based Sensors for Food Spoilage Control: Bacteria and Biogenic Amines Detection
by Ricarda Torre, Estefanía Costa-Rama, Henri P. A. Nouws and Cristina Delerue-Matos
Biosensors 2020, 10(10), 139; https://doi.org/10.3390/bios10100139 - 30 Sep 2020
Cited by 48 | Viewed by 7003
Abstract
Food spoilage is caused by the development of microorganisms, biogenic amines, and other harmful substances, which, when consumed, can lead to different health problems. Foodborne diseases can be avoided by assessing the safety and freshness of food along the production and supply chains. [...] Read more.
Food spoilage is caused by the development of microorganisms, biogenic amines, and other harmful substances, which, when consumed, can lead to different health problems. Foodborne diseases can be avoided by assessing the safety and freshness of food along the production and supply chains. The routine methods for food analysis usually involve long analysis times and complex instrumentation and are performed in centralized laboratories. In this context, sensors based on screen-printed electrodes (SPEs) have gained increasing importance because of their advantageous characteristics, such as ease of use and portability, which allow fast analysis in point-of-need scenarios. This review provides a comprehensive overview of SPE-based sensors for the evaluation of food safety and freshness, focusing on the determination of bacteria and biogenic amines. After discussing the characteristics of SPEs as transducers, the main bacteria, and biogenic amines responsible for important and common foodborne diseases are described. Then, SPE-based sensors for the analysis of these bacteria and biogenic amines in food samples are discussed, comparing several parameters, such as limit of detection, analysis time, and sample type. Full article
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12 pages, 1036 KiB  
Article
Accuracy of the Dexcom G6 Glucose Sensor during Aerobic, Resistance, and Interval Exercise in Adults with Type 1 Diabetes
by Florian H. Guillot, Peter G. Jacobs, Leah M. Wilson, Joseph El Youssef, Virginia B. Gabo, Deborah L. Branigan, Nichole S. Tyler, Katrina Ramsey, Michael C. Riddell and Jessica R. Castle
Biosensors 2020, 10(10), 138; https://doi.org/10.3390/bios10100138 - 29 Sep 2020
Cited by 23 | Viewed by 5492
Abstract
The accuracy of continuous glucose monitoring (CGM) sensors may be significantly impacted by exercise. We evaluated the impact of three different types of exercise on the accuracy of the Dexcom G6 sensor. Twenty-four adults with type 1 diabetes on multiple daily injections wore [...] Read more.
The accuracy of continuous glucose monitoring (CGM) sensors may be significantly impacted by exercise. We evaluated the impact of three different types of exercise on the accuracy of the Dexcom G6 sensor. Twenty-four adults with type 1 diabetes on multiple daily injections wore a G6 sensor. Participants were randomized to aerobic, resistance, or high intensity interval training (HIIT) exercise. Each participant completed two in-clinic 30-min exercise sessions. The sensors were applied on average 5.3 days prior to the in-clinic visits (range 0.6–9.9). Capillary blood glucose (CBG) measurements with a Contour Next meter were performed before and after exercise as well as every 10 min during exercise. No CGM calibrations were performed. The median absolute relative difference (MARD) and median relative difference (MRD) of the CGM as compared with the reference CBG did not differ significantly from the start of exercise to the end exercise across all exercise types (ranges for aerobic MARD: 8.9 to 13.9% and MRD: −6.4 to 0.5%, resistance MARD: 7.7 to 14.5% and MRD: −8.3 to −2.9%, HIIT MARD: 12.1 to 16.8% and MRD: −14.3 to −9.1%). The accuracy of the no-calibration Dexcom G6 CGM was not significantly impacted by aerobic, resistance, or HIIT exercise. Full article
(This article belongs to the Special Issue Design and Evaluation of Sensors in Diabetes)
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13 pages, 1447 KiB  
Review
Lyme Disease Biosensors: A Potential Solution to a Diagnostic Dilemma
by Connor Flynn and Anna Ignaszak
Biosensors 2020, 10(10), 137; https://doi.org/10.3390/bios10100137 - 28 Sep 2020
Cited by 5 | Viewed by 4122
Abstract
Over the past four decades, Lyme disease has remained a virulent and pervasive illness, persisting throughout North America and many other regions of the world. Recent increases in illness in many countries has sparked a renewed interest in improved Lyme diagnostics. While current [...] Read more.
Over the past four decades, Lyme disease has remained a virulent and pervasive illness, persisting throughout North America and many other regions of the world. Recent increases in illness in many countries has sparked a renewed interest in improved Lyme diagnostics. While current standards of diagnosis are acceptable for the late stages of the disease, it remains difficult to accurately diagnose early forms of the illness. In addition, current diagnostic methods tend to be relatively expensive and require a large degree of laboratory-based analysis. Biosensors represent the fusion of biological materials with chemical techniques to provide simple, inexpensive alternatives to traditional diagnostic methods. Lyme disease biosensors have the potential to better diagnose early stages of the illness and provide possible patients with an inexpensive, commercially available test. This review examines the current state of Lyme disease biosensing, with a focus on previous biosensor development and essential future considerations. Full article
(This article belongs to the Section Biosensors and Healthcare)
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12 pages, 2840 KiB  
Article
Dopamine and Striatal Neuron Firing Respond to Frequency-Dependent DBS Detected by Microelectrode Arrays in the Rat Model of Parkinson’s Disease
by Guihua Xiao, Yilin Song, Yu Zhang, Yu Xing, Shengwei Xu, Mixia Wang, Junbo Wang, Deyong Chen, Jian Chen and Xinxia Cai
Biosensors 2020, 10(10), 136; https://doi.org/10.3390/bios10100136 - 28 Sep 2020
Cited by 4 | Viewed by 2718
Abstract
(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified [...] Read more.
(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level. Full article
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12 pages, 10418 KiB  
Article
Nanofluidic Immobilization and Growth Detection of Escherichia coli in a Chip for Antibiotic Susceptibility Testing
by Jan F. Busche, Svenja Möller, Ann-Kathrin Klein, Matthias Stehr, Foelke Purr, Margherita Bassu, Thomas P. Burg and Andreas Dietzel
Biosensors 2020, 10(10), 135; https://doi.org/10.3390/bios10100135 - 25 Sep 2020
Cited by 4 | Viewed by 3456
Abstract
Infections with antimicrobial resistant bacteria are a rising threat for global healthcare as more and more antibiotics lose their effectiveness against bacterial pathogens. To guarantee the long-term effectiveness of broad-spectrum antibiotics, they may only be prescribed when inevitably required. In order to make [...] Read more.
Infections with antimicrobial resistant bacteria are a rising threat for global healthcare as more and more antibiotics lose their effectiveness against bacterial pathogens. To guarantee the long-term effectiveness of broad-spectrum antibiotics, they may only be prescribed when inevitably required. In order to make a reliable assessment of which antibiotics are effective, rapid point-of-care tests are needed. This can be achieved with fast phenotypic microfluidic tests, which can cope with low bacterial concentrations and work label-free. Here, we present a novel optofluidic chip with a cross-flow immobilization principle using a regular array of nanogaps to concentrate bacteria and detect their growth label-free under the influence of antibiotics. The interferometric measuring principle enabled the detection of the growth of Escherichia coli in under 4 h with a sample volume of 187.2 µL and a doubling time of 79 min. In proof-of-concept experiments, we could show that the method can distinguish between bacterial growth and its inhibition by antibiotics. The results indicate that the nanofluidic chip approach provides a very promising concept for future rapid and label-free antimicrobial susceptibility tests. Full article
(This article belongs to the Special Issue Recent Advances in Photonic Biosensors)
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17 pages, 16368 KiB  
Article
A Self-Referenced Diffraction-Based Optical Leaky Waveguide Biosensor Using Photofunctionalised Hydrogels
by Anil K. Pal, Nicholas J. Goddard, Hazel J. Dixon and Ruchi Gupta
Biosensors 2020, 10(10), 134; https://doi.org/10.3390/bios10100134 - 24 Sep 2020
Cited by 8 | Viewed by 3056
Abstract
We report a novel self-referenced diffraction-based leaky waveguide (LW) comprising a thin (~2 µm) film of a photofunctionalisable hydrogel created by covalent attachment of a biotinylated photocleavable linker to chitosan. Streptavidin attached to the chitosan via the photocleavable linker was selectively removed by [...] Read more.
We report a novel self-referenced diffraction-based leaky waveguide (LW) comprising a thin (~2 µm) film of a photofunctionalisable hydrogel created by covalent attachment of a biotinylated photocleavable linker to chitosan. Streptavidin attached to the chitosan via the photocleavable linker was selectively removed by shining 365 nm light through a photomask to create an array of strips with high and low loading of the protein, which served as sensor and reference regions respectively. The differential measurements between sensor and reference regions were used for measuring analytes (i.e., biotin protein A and IgG) while reducing environmental and non-specific effects. These include changes in temperature and sample composition caused by non-adsorbing and adsorbing species, leading to reduction in effects by ~98%, ~99%, and ~97% respectively compared to the absolute measurements. The novelty of this work lies in combining photofunctionalisable hydrogels with diffraction-based LWs for referencing. This is needed to realise the full potential of label-free optical biosensors to measure analyte concentrations in real samples that are complex mixtures, and to allow for sample analysis outside of laboratories where drifts and fluctuations in temperature are observed. Full article
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23 pages, 4439 KiB  
Review
Point of Care Diagnostics in Resource-Limited Settings: A Review of the Present and Future of PoC in Its Most Needed Environment
by Benjamin Heidt, Williane F. Siqueira, Kasper Eersels, Hanne Diliën, Bart van Grinsven, Ricardo T. Fujiwara and Thomas J. Cleij
Biosensors 2020, 10(10), 133; https://doi.org/10.3390/bios10100133 - 24 Sep 2020
Cited by 57 | Viewed by 8300
Abstract
Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can [...] Read more.
Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can be more a matter of convenience than necessity. However, in resource-limited settings such as low-income countries, PoC-diagnostics might be the only viable route, when the next laboratory is hours away. Therefore, it is especially important to focus research into novel diagnostics for these countries in order to alleviate suffering due to infectious disease. In this review, the current research describing the use of PoC diagnostics in resource-limited settings and the potential bottlenecks along the value chain that prevent their widespread application is summarized. To this end, we will look at literature that investigates different parts of the value chain, such as fundamental research and market economics, as well as actual use at healthcare providers. We aim to create an integrated picture of potential PoC barriers, from the first start of research at universities to patient treatment in the field. Results from the literature will be discussed with the aim to bring all important steps and aspects together in order to illustrate how effectively PoC is being used in low-income countries. In addition, we discuss what is needed to improve the situation further, in order to use this technology to its fullest advantage and avoid “leaks in the pipeline”, when a promising device fails to take the next step of the valorization pathway and is abandoned. Full article
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17 pages, 4422 KiB  
Communication
Tuning the Surface Charge of Self-Assembled Polydiacetylene Vesicles to Control Aggregation and Cell Binding
by Anthony David Nelson, Priyanka Shiveshwarkar, Butaek Lim, Gumaro Rojas, Izele Abure, Anura Shrestha and Justyn Jaworski
Biosensors 2020, 10(10), 132; https://doi.org/10.3390/bios10100132 - 24 Sep 2020
Cited by 4 | Viewed by 4048
Abstract
Polydiacetylene vesicles of various compositions were assembled using a two-part mixture of 10,12-pentacosadiynoic acid (PCDA) and ethylenedioxy-bis-ethylamine (EDEA)-labeled PCDA in order to control surface charge and stability within a desired pH range. Investigation of the interaction of the vesicles with mammalian cells as [...] Read more.
Polydiacetylene vesicles of various compositions were assembled using a two-part mixture of 10,12-pentacosadiynoic acid (PCDA) and ethylenedioxy-bis-ethylamine (EDEA)-labeled PCDA in order to control surface charge and stability within a desired pH range. Investigation of the interaction of the vesicles with mammalian cells as a function of surface charge was carried out and identified a clear correlation in cell–vesicle association and corresponding cell death for vesicles with positive surface charge. The binding behavior of the vesicles was found to be tunable by regulating the proportion of anionic PCDA relative to cationic PCDA–EDEA content within vesicles as to control the surface charge as a function of pH. Association of vesicles with cells thus depended on the corresponding charge of the vesicles and cell surface. The prospect of this work may serve as a step toward future vesicle designs to allow triggered uptake of vesicles locally within low pH tumor microenvironments. Full article
(This article belongs to the Section Biosensor Materials)
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17 pages, 2865 KiB  
Article
One-Pot, In-Situ Synthesis of 8-Armed Poly(Ethylene Glycol)-Coated Ag Nanoclusters as a Fluorescent Sensor for Selective Detection of Cu2+
by Xiaoyuan Zhang, Guanghua Zhang, Gang Wei and Zhiqiang Su
Biosensors 2020, 10(10), 131; https://doi.org/10.3390/bios10100131 - 23 Sep 2020
Cited by 11 | Viewed by 2615
Abstract
Fluorescent nanomaterials, such as quantum dots, have developed rapidly in recent years and have been significantly developed. Herein, we demonstrate a facile, one-pot, and in-situ synthesis strategy to obtain fluorescent silver nanoclusters (AgNCs) coated with eight-armed poly (ethylene glycol) polymers (8PEG-AgNCs) via a [...] Read more.
Fluorescent nanomaterials, such as quantum dots, have developed rapidly in recent years and have been significantly developed. Herein, we demonstrate a facile, one-pot, and in-situ synthesis strategy to obtain fluorescent silver nanoclusters (AgNCs) coated with eight-armed poly (ethylene glycol) polymers (8PEG-AgNCs) via a direct gel-mediated process. During the synthesis, ammonium (NH3) served as the crosslinker for the gel formation via a amine-type Michael addition reaction. This hydrogel can be used as a template to synthesize AgNCs using its volume-limiting effect. The in-situ generation of AgNCs takes place inside the nanocages of the formed gels, which guarantees the homogenous distribution of AgNCs in the gel matrix, as well as the efficient coating of PEG on the nanoclusters. After the degradation of gels, the released 8PEG-AgNCs nanohybrids showed strong blue fluorescence and exhibited long-term stability in aqueous solution for nearly one year. Results showed that the fabricated sensor revealed excellent fluorescent sensitivity for the selective detection of Cu2+ with a detection limit of 50 nM and a wide linear detection range of 5–100 μM. It is proposed that the greater cross-linking density leads to smaller gel pores and allows the synthesis of AgNCs with fluorescent properties. These results indicate that this novel hydrogel with certain biodegradation has the potential to be applied as a fluorescent sensor for catalytic synthesis, fluorescence tracing in cells, and fluorescence detection fields. Meanwhile, the novel design principle has a certain versatility to accelerate the development and application of other kinds of metal nanoclusters and quantum dots. Full article
(This article belongs to the Special Issue Nanoparticles-Based Biosensors)
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14 pages, 3001 KiB  
Article
Colorimetric Diagnostic Capillary Enabled by Size Sieving in a Porous Hydrogel
by John Mello Camille C. Guzman, Sheng-Min Hsu and Han-Sheng Chuang
Biosensors 2020, 10(10), 130; https://doi.org/10.3390/bios10100130 - 23 Sep 2020
Cited by 7 | Viewed by 3169
Abstract
Handy and disposable point-of-care diagnostics facilitate the early screening of severe diseases in resource-limited areas. To address urgent needs in inconvenient sites, a simple colorimetric diagnostic device equipped with a capillary tube with porous hydrogel and immunocomplex particles was developed for the rapid [...] Read more.
Handy and disposable point-of-care diagnostics facilitate the early screening of severe diseases in resource-limited areas. To address urgent needs in inconvenient sites, a simple colorimetric diagnostic device equipped with a capillary tube with porous hydrogel and immunocomplex particles was developed for the rapid detection of biomarkers (16 min). In this device, probe particles attach to capture particles (dp = 40 µm) and form sandwiched immunocomplexes in the presence of target biomarkers, and a red color progressively emerges when the sandwiched immunocomplex particles are blocked by the porous hydrogel embedded inside the glass capillary. Colorimetric aggregation was recorded using a smartphone and analyzed with imaging software. The limit of detection reached 1 ng/mL and showed a maximum of 79% accuracy compared with that obtained through a conventional spectrophotometric technique. The level of a diabetic retinopathy (DR) biomarker, lipocalin-1 (LCN-1), was measured in 1 µL of a human tear sample and used in testing the practicability of the proposed device. All healthy subjects showed lower intensity levels than the other diabetic counterparts (proliferative DR or nonproliferative DR patients), implying the potential of this device in clinical applications. Overall, the diagnostic device facilitates point-of-care-testing and provides a low-cost (~1 USD), compact, and reliable tool for early diagnosis in resource-limited areas. Full article
(This article belongs to the Special Issue Advanced Biosensing Technologies in Medical Applications)
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