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Biosensors, Volume 8, Issue 1 (March 2018) – 26 articles

Cover Story (view full-size image): As competitors of neurotransmitters like dopamine (DA), antipsychotic drugs (APD) bind to the receptor sites in neurons and block the biological responses in vivo. Currently available in vitro APD screening platforms are developed on the basis of drug-receptor interaction monitoring with fluorescent or radioactive methods that require lengthy and troublesome labelling steps. In this work, we unraveled the unique potentials of label-free electrochemical and optical biosensors for cost-efficient and simpler APD screening. Specifically, we demonstrate the utility of electrochemical impedance spectroscopy and nanoplasmonic sensing for rapid analysis and identification of APD candidates via drug-receptor in vitro assays. View this paper
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11 pages, 2872 KiB  
Article
Fabrication of SrTiO3 Layer on Pt Electrode for Label-Free Capacitive Biosensors
by Francesca Malvano, Luigi Maritato, Giovanni Carapella, Pasquale Orgiani, Roberto Pilloton, Marisa Di Matteo and Donatella Albanese
Biosensors 2018, 8(1), 26; https://doi.org/10.3390/bios8010026 - 16 Mar 2018
Cited by 15 | Viewed by 5772
Abstract
Due to their interesting ferroelectric, conductive and dielectric properties, in recent years, perovskite-structured materials have begun to attract increasing interest in the biosensing field. In this study, a strontium titanate perovskite layer (SrTiO3) has been synthesized on a platinum electrode and [...] Read more.
Due to their interesting ferroelectric, conductive and dielectric properties, in recent years, perovskite-structured materials have begun to attract increasing interest in the biosensing field. In this study, a strontium titanate perovskite layer (SrTiO3) has been synthesized on a platinum electrode and exploited for the development of an impedimetric label-free immunosensor for Escherichia coli O157:H7 detection. The electrochemical characterization of the perovskite-modified electrode during the construction of the immunosensor, as well as after the interaction with different E. coli O157:H7 concentrations, showed a reproducible decrease of the total capacitance of the system that was used for the analytical characterization of the immunosensor. Under optimized conditions, the capacitive immunosensor showed a linear relationship from to 1 to 7 log cfu/mL with a low detection limit of 1 log cfu/mL. Moreover, the atomic force microscopy (AFM) technique underlined the increase in roughness of the SrTiO3-modified electrode surface after antibody immobilization, as well as the effective presence of cells with the typical size of E. coli. Full article
(This article belongs to the Special Issue Label-free Biosensing)
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9 pages, 238 KiB  
Article
The Use of Biosensors to Explore the Potential of Probiotic Strains to Reduce the SOS Response and Mutagenesis in Bacteria
by Vladimir Anatolievich Chistyakov, Evgeniya Valer’evna Prazdnova, Maria Sergeevna Mazanko and Anzhelica Borisovna Bren
Biosensors 2018, 8(1), 25; https://doi.org/10.3390/bios8010025 - 16 Mar 2018
Cited by 15 | Viewed by 5000
Abstract
A model system based on the Escherichia coli MG1655 (pRecA-lux) Lux-biosensor was used to evaluate the ability of the fermentates of eight probiotic strains to reduce the SOS response stimulated by ciprofloxacin in bacteria and mutagenesis mediated by it. Preliminary attempts to estimate [...] Read more.
A model system based on the Escherichia coli MG1655 (pRecA-lux) Lux-biosensor was used to evaluate the ability of the fermentates of eight probiotic strains to reduce the SOS response stimulated by ciprofloxacin in bacteria and mutagenesis mediated by it. Preliminary attempts to estimate the chemical nature of active components of the fermentates were conducted. Full article
(This article belongs to the Special Issue Micro and Nanoscale Biosensors)
17 pages, 3617 KiB  
Review
Calibration of Minimally Invasive Continuous Glucose Monitoring Sensors: State-of-The-Art and Current Perspectives
by Giada Acciaroli, Martina Vettoretti, Andrea Facchinetti and Giovanni Sparacino
Biosensors 2018, 8(1), 24; https://doi.org/10.3390/bios8010024 - 13 Mar 2018
Cited by 71 | Viewed by 11333
Abstract
Minimally invasive continuous glucose monitoring (CGM) sensors are wearable medical devices that provide real-time measurement of subcutaneous glucose concentration. This can be of great help in the daily management of diabetes. Most of the commercially available CGM devices have a wire-based sensor, usually [...] Read more.
Minimally invasive continuous glucose monitoring (CGM) sensors are wearable medical devices that provide real-time measurement of subcutaneous glucose concentration. This can be of great help in the daily management of diabetes. Most of the commercially available CGM devices have a wire-based sensor, usually placed in the subcutaneous tissue, which measures a “raw” current signal via a glucose-oxidase electrochemical reaction. This electrical signal needs to be translated in real-time to glucose concentration through a calibration process. For such a scope, the first commercialized CGM sensors implemented simple linear regression techniques to fit reference glucose concentration measurements periodically collected by fingerprick. On the one hand, these simple linear techniques required several calibrations per day, with the consequent patient’s discomfort. On the other, only a limited accuracy was achieved. This stimulated researchers to propose, over the last decade, more sophisticated algorithms to calibrate CGM sensors, resorting to suitable signal processing, modelling, and machine-learning techniques. This review paper will first contextualize and describe the calibration problem and its implementation in the first generation of CGM sensors, and then present the most recently-proposed calibration algorithms, with a perspective on how these new techniques can influence future CGM products in terms of accuracy improvement and calibration reduction. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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34 pages, 8042 KiB  
Review
Biosensors for Sustainable Food Engineering: Challenges and Perspectives
by Suresh Neethirajan, Vasanth Ragavan, Xuan Weng and Rohit Chand
Biosensors 2018, 8(1), 23; https://doi.org/10.3390/bios8010023 - 12 Mar 2018
Cited by 133 | Viewed by 19938
Abstract
Current food production faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technology development supported by both governments and enterprises. Multiple attempts have been promoted [...] Read more.
Current food production faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technology development supported by both governments and enterprises. Multiple attempts have been promoted in tackling challenges and enhancing drivers in food production. Biosensors and biosensing technologies with their applications, are being widely applied to tackling top challenges in food production and its sustainability. Consequently, a growing demand in biosensing technologies exists in food sustainability. Microfluidics represents a technological system integrating multiple technologies. Nanomaterials, with its technology in biosensing, is thought to be the most promising tool in dealing with health, energy, and environmental issues closely related to world populations. The demand of point of care (POC) technologies in this area focus on rapid, simple, accurate, portable, and low-cost analytical instruments. This review provides current viewpoints from the literature on biosensing in food production, food processing, safety and security, food packaging and supply chain, food waste processing, food quality assurance, and food engineering. The current understanding of progress, solution, and future challenges, as well as the commercialization of biosensors are summarized. Full article
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8 pages, 925 KiB  
Article
Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus
by Lyvia Biagi, Arthur Bertachi, Carmen Quirós, Marga Giménez, Ignacio Conget, Jorge Bondia and Josep Vehí
Biosensors 2018, 8(1), 22; https://doi.org/10.3390/bios8010022 - 09 Mar 2018
Cited by 40 | Viewed by 8668
Abstract
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of [...] Read more.
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise (p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise (p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation (p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities (p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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13 pages, 2714 KiB  
Article
A Nanostructured Sensor Based on Gold Nanoparticles and Nafion for Determination of Uric Acid
by Natalia Stozhko, Maria Bukharinova, Leonid Galperin and Khiena Brainina
Biosensors 2018, 8(1), 21; https://doi.org/10.3390/bios8010021 - 06 Mar 2018
Cited by 37 | Viewed by 7128
Abstract
The paper discusses the mechanism of uric acid (UA) electrooxidation occurring on the surface of gold nanoparticles. It has been shown that the electrode process is purely electrochemical, uncomplicated with catalytic stages. The nanoeffects observed as the reduction of overvoltage and increased current [...] Read more.
The paper discusses the mechanism of uric acid (UA) electrooxidation occurring on the surface of gold nanoparticles. It has been shown that the electrode process is purely electrochemical, uncomplicated with catalytic stages. The nanoeffects observed as the reduction of overvoltage and increased current of UA oxidation have been described. These nanoeffects are determined by the size of particles and do not depend on the method of particle preparation (citrate and “green” synthesis). The findings of these studies have been used to select a modifier for carbon screen-printed electrode (CSPE). It has been stated that CSPE modified with gold nanoparticles (5 nm) and 2.5% Nafion (Nf) may serve as non-enzymatic sensor for UA determination. The combination of the properties of nanoparticles and Nafion as a molecular sieve at the selected pH 5 phosphate buffer solution has significantly improved the resolution of the sensor compared to unmodified CSPE. A nanostructured sensor has demonstrated good selectivity in determining UA in the presence of ascorbic acid. The detection limit of UA is 0.25 μM. A linear calibration curve has been obtained over a range of 0.5–600 μM. The 2.5%Nf/Au(5nm)/CSPE has been successfully applied to determining UA in blood serum and milk samples. The accuracy and reliability of the obtained results have been confirmed by a good correlation with the enzymatic spectrophotometric analysis (R2 = 0.9938) and the “added−found” technique (recovery close to 100%). Full article
(This article belongs to the Special Issue Electrochemical (Bio)sensors for Environmental and Food Analyses)
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11 pages, 1670 KiB  
Article
Amperometric Self-Referencing Ceramic Based Microelectrode Arrays for D-Serine Detection
by Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero and Lisa Marshall
Biosensors 2018, 8(1), 20; https://doi.org/10.3390/bios8010020 - 06 Mar 2018
Cited by 10 | Viewed by 7279
Abstract
D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, [...] Read more.
D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a mean sensitivity of 8.61 ± 0.83 pA/µM to D-serine, a limit of detection (LOD) of 0.17 ± 0.01 µM, and a selectivity ratio of 80:1 or greater for D-serine over ascorbic acid (mean ± SEM; n = 12) that can be used for freely moving studies. Full article
(This article belongs to the Special Issue Implantable Biosensors for in vivo Detection and Measurement)
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12 pages, 3840 KiB  
Article
A DNA-Based Assay for Digoxin Detection
by Michael V. Kjelstrup, Line D. F. Nielsen, Malthe Hansen-Bruhn and Kurt V. Gothelf
Biosensors 2018, 8(1), 19; https://doi.org/10.3390/bios8010019 - 06 Mar 2018
Cited by 7 | Viewed by 7638
Abstract
The most common method for quantifying small-molecule drugs in blood samples is by liquid chromatography in combination with mass spectrometry. Few immuno-based assays are available for the detection of small-molecule drugs in blood. Here we report on a homogeneous assay that enables detection [...] Read more.
The most common method for quantifying small-molecule drugs in blood samples is by liquid chromatography in combination with mass spectrometry. Few immuno-based assays are available for the detection of small-molecule drugs in blood. Here we report on a homogeneous assay that enables detection of the concentration of digoxin spiked into in a plasma sample. The assay is based on a shift in the equilibrium of a DNA strand displacement competition reaction, and can be performed in 30 min for concentrations above 10 nM. The equilibrium shift occurs upon binding of anti-digoxigenin antibody. As a model, the assay provides a potential alternative to current small-molecule detection methods used for therapeutic drug monitoring. Full article
(This article belongs to the Special Issue FRET-Based Biosensors)
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10 pages, 3262 KiB  
Article
A Real-Time Thermal Self-Elimination Method for Static Mode Operated Freestanding Piezoresistive Microcantilever-Based Biosensors
by Yu-Fu Ku, Long-Sun Huang and Yi-Kuang Yen
Biosensors 2018, 8(1), 18; https://doi.org/10.3390/bios8010018 - 28 Feb 2018
Cited by 11 | Viewed by 5629
Abstract
Here, we provide a method and apparatus for real-time compensation of the thermal effect of single free-standing piezoresistive microcantilever-based biosensors. The sensor chip contained an on-chip fixed piezoresistor that served as a temperature sensor, and a multilayer microcantilever with an embedded piezoresistor served [...] Read more.
Here, we provide a method and apparatus for real-time compensation of the thermal effect of single free-standing piezoresistive microcantilever-based biosensors. The sensor chip contained an on-chip fixed piezoresistor that served as a temperature sensor, and a multilayer microcantilever with an embedded piezoresistor served as a biomolecular sensor. This method employed the calibrated relationship between the resistance and the temperature of piezoresistors to eliminate the thermal effect on the sensor, including the temperature coefficient of resistance (TCR) and bimorph effect. From experimental results, the method was verified to reduce the signal of thermal effect from 25.6 μV/°C to 0.3 μV/°C, which was approximately two orders of magnitude less than that before the processing of the thermal elimination method. Furthermore, the proposed approach and system successfully demonstrated its effective real-time thermal self-elimination on biomolecular detection without any thermostat device to control the environmental temperature. This method realizes the miniaturization of an overall measurement system of the sensor, which can be used to develop portable medical devices and microarray analysis platforms. Full article
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30 pages, 7729 KiB  
Review
Simple Approaches to Minimally-Instrumented, Microfluidic-Based Point-of-Care Nucleic Acid Amplification Tests
by Michael G. Mauk, Jinzhao Song, Changchun Liu and Haim H. Bau
Biosensors 2018, 8(1), 17; https://doi.org/10.3390/bios8010017 - 26 Feb 2018
Cited by 67 | Viewed by 18739
Abstract
Designs and applications of microfluidics-based devices for molecular diagnostics (Nucleic Acid Amplification Tests, NAATs) in infectious disease testing are reviewed, with emphasis on minimally instrumented, point-of-care (POC) tests for resource-limited settings. Microfluidic cartridges (‘chips’) that combine solid-phase nucleic acid extraction; isothermal enzymatic nucleic [...] Read more.
Designs and applications of microfluidics-based devices for molecular diagnostics (Nucleic Acid Amplification Tests, NAATs) in infectious disease testing are reviewed, with emphasis on minimally instrumented, point-of-care (POC) tests for resource-limited settings. Microfluidic cartridges (‘chips’) that combine solid-phase nucleic acid extraction; isothermal enzymatic nucleic acid amplification; pre-stored, paraffin-encapsulated lyophilized reagents; and real-time or endpoint optical detection are described. These chips can be used with a companion module for separating plasma from blood through a combined sedimentation-filtration effect. Three reporter types: Fluorescence, colorimetric dyes, and bioluminescence; and a new paradigm for end-point detection based on a diffusion-reaction column are compared. Multiplexing (parallel amplification and detection of multiple targets) is demonstrated. Low-cost detection and added functionality (data analysis, control, communication) can be realized using a cellphone platform with the chip. Some related and similar-purposed approaches by others are surveyed. Full article
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12 pages, 6319 KiB  
Article
Ultrasensitive Determination of Malathion Using Acetylcholinesterase Immobilized on Chitosan-Functionalized Magnetic Iron Nanoparticles
by Núbia Fernanda Marinho Rodrigues, Sakae Yotsumoto Neto, Rita De Cássia Silva Luz, Flávio Santos Damos and Hideko Yamanaka
Biosensors 2018, 8(1), 16; https://doi.org/10.3390/bios8010016 - 13 Feb 2018
Cited by 51 | Viewed by 6933
Abstract
A renewable, disposable, low cost, and sensitive sensor for the detection of organophosphorus pesticides was constructed by immobilizing the acetylcholinesterase enzyme (AChE), via glutaraldehyde, on magnetic iron nanoparticles (Fe3O4) previously synthesized and functionalized with chitosan (CS). The sensor was [...] Read more.
A renewable, disposable, low cost, and sensitive sensor for the detection of organophosphorus pesticides was constructed by immobilizing the acetylcholinesterase enzyme (AChE), via glutaraldehyde, on magnetic iron nanoparticles (Fe3O4) previously synthesized and functionalized with chitosan (CS). The sensor was denoted AChE/CS/Fe3O4. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. Acetylthiocholine (ATCh) was incubated with AChE/CS/Fe3O4 and attached to a screen-printed electrode using a magnet. The oxidation of thiocholine (from ATCh hydrolysis) was monitored at an applied potential of +0.5 V vs. Ag/AgCl(KClsat) in 0.1 mol L−1 phosphate buffer solution (pH 7.5) as the supporting electrolyte. A mixture of the pesticide malathion and ATCh was investigated using the same procedure, and the results were compared and expressed as inhibition percentages. For determination of malathion, the proposed sensor presented a linear response in the range from 0.5 to 20 nmol L−1 (R = 0.9942). The limits of detection (LOD) and quantification (LOQ) were 0.3 and 0.8 nmol L−1, respectively. Real samples were also investigated, with recovery values of 96.0% and 108.3% obtained for tomato and pond water samples, respectively. The proposed sensor is a feasible option for malathion detection, offering a linear response, good sensitivity, and a low detection limit. Full article
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12 pages, 2311 KiB  
Article
Probing Contaminant-Induced Alterations in Chlorophyll Fluorescence by AC-Dielectrophoresis-Based 2D-Algal Array
by Coralie Siebman, Orlin D. Velev and Vera I. Slaveykova
Biosensors 2018, 8(1), 15; https://doi.org/10.3390/bios8010015 - 11 Feb 2018
Cited by 6 | Viewed by 5107
Abstract
The investigation of contaminant impact on algae requires rapid and reliable cell collection and optical detection. The capability of alternative current (AC) dielectrophoresis (DEP) collection of whole cell arrays with combined fluorescence microscopy detection to follow the alterations of chlorophyll fluorescence during environmental [...] Read more.
The investigation of contaminant impact on algae requires rapid and reliable cell collection and optical detection. The capability of alternative current (AC) dielectrophoresis (DEP) collection of whole cell arrays with combined fluorescence microscopy detection to follow the alterations of chlorophyll fluorescence during environmental contaminant exposure was explored. The application of an AC-field of 100 V cm−1, 100 Hz for 30 min to capture and immobilize the cells of green alga Chlamydomonas reinhardtii in two-dimensional (2D) arrays does not induce changes in chlorophyll fluorescence. The results demonstrate that DEP-based 2D-arrays allow non-invasive detection of chlorophyll fluorescence change upon exposure to high concentrations of copper oxide nanoparticles and ionic copper. These results were in agreement with data obtained by flow cytometry used as a comparative method. The tool was also applied to follow the effect of a number of ubiquitous contaminants such as inorganic mercury, methylmercury, and diuron. However, a statistically significant short-term effect was observed only for mercury. Overall, DEP-based 2D-arrays of algal cells with fluorescence detection appear to be suitable for stain-free probing the effects on the photosynthetic microorganisms in highly polluted environment. Full article
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11 pages, 1970 KiB  
Communication
Self-Organized Nanostructure Modified Microelectrode for Sensitive Electrochemical Glutamate Detection in Stem Cells-Derived Brain Organoids
by Babak Nasr, Rachael Chatterton, Jason Hsien Ming Yong, Pegah Jamshidi, Giovanna Marisa D’Abaco, Andrew Robin Bjorksten, Omid Kavehei, Gursharan Chana, Mirella Dottori and Efstratios Skafidas
Biosensors 2018, 8(1), 14; https://doi.org/10.3390/bios8010014 - 05 Feb 2018
Cited by 30 | Viewed by 7712
Abstract
Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system [...] Read more.
Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system is highly advantageous for neurodevelopmental investigation. To address such challenges, we develop for the first time a convenient method to realize functionalized borosilicate glass capillaries with nanostructured texture as an electrochemical biosensor to detect glutamate release from cerebral organoids generated from human embryonic stem cells (hESC) that mimic various brain regions. The biosensor shows a clear catalytic activity toward the oxidation of glutamate with a sensitivity of 93 ± 9.5 nA·µM−1·cm−2. It was found that the enzyme-modified microelectrodes can detect glutamate in a wide linear range from 5 µM to 0.5 mM with a limit of detection (LOD) down to 5.6 ± 0.2 µM. Measurements were performed within the organoids at different time points and consistent results were obtained. This data demonstrates the reliability of the biosensor as well as its usefulness in measuring glutamate levels across time within the same culture system. Full article
(This article belongs to the Special Issue Micro and Nanoscale Biosensors)
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11 pages, 3501 KiB  
Article
Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure
by Paul Glogener, Michael Krause, Jens Katzer, Markus A. Schubert, Mario Birkholz, Olaf Bellmann, Claudia Kröger-Koch, Harald M. Hammon, Cornelia C. Metges, Christine Welsch, Roman Ruff and Klaus P. Hoffmann
Biosensors 2018, 8(1), 13; https://doi.org/10.3390/bios8010013 - 01 Feb 2018
Cited by 3 | Viewed by 7656
Abstract
A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed [...] Read more.
A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general. Full article
(This article belongs to the Special Issue Implantable Biosensors for in vivo Detection and Measurement)
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10 pages, 2523 KiB  
Article
Glucose Sensing Using Capacitive Biosensor Based on Polyvinylidene Fluoride Thin Film
by Ambran Hartono, Edi Sanjaya and Ramli Ramli
Biosensors 2018, 8(1), 12; https://doi.org/10.3390/bios8010012 - 30 Jan 2018
Cited by 27 | Viewed by 8588
Abstract
A polyvinylidene fluoride (PVDF) film-based capacitive biosensor was developed for glucose sensing. This device consists of a PVDF film sandwiched between two electrodes. A capacitive biosensor measures the dielectric properties of the dielectric layers at the interface between the electrolyte and the electrode. [...] Read more.
A polyvinylidene fluoride (PVDF) film-based capacitive biosensor was developed for glucose sensing. This device consists of a PVDF film sandwiched between two electrodes. A capacitive biosensor measures the dielectric properties of the dielectric layers at the interface between the electrolyte and the electrode. A glucose oxidase (GOx) enzyme was immobilized onto the electrode to oxidize glucose. In practice, the biochemical reaction of glucose with the GOx enzyme generates free electron carriers. Consequently, the potential difference between the electrodes is increased, resulting in a measurable voltage output of the biosensor. The device was tested for various glucose concentrations in the range of 0.013 to 5.85 M, and various GOx enzyme concentrations between 4882.8 and 2.5 million units/L. We found that the sensor output increased with increasing glucose concentration up to 5.85 M. These results indicate that the PVDF film-based capacitive biosensors can be properly applied to glucose sensing and provide opportunities for the low-cost fabrication of glucose-based biosensors based on PVDF materials. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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18 pages, 2400 KiB  
Review
Enzymatic Fuel Cells: Towards Self-Powered Implantable and Wearable Diagnostics
by Carla Gonzalez-Solino and Mirella Di Lorenzo
Biosensors 2018, 8(1), 11; https://doi.org/10.3390/bios8010011 - 29 Jan 2018
Cited by 99 | Viewed by 11601
Abstract
With the rapid progress in nanotechnology and microengineering, point-of-care and personalised healthcare, based on wearable and implantable diagnostics, is becoming a reality. Enzymatic fuel cells (EFCs) hold great potential as a sustainable means to power such devices by using physiological fluids as the [...] Read more.
With the rapid progress in nanotechnology and microengineering, point-of-care and personalised healthcare, based on wearable and implantable diagnostics, is becoming a reality. Enzymatic fuel cells (EFCs) hold great potential as a sustainable means to power such devices by using physiological fluids as the fuel. This review summarises the fundamental operation of EFCs and discusses the most recent advances for their use as implantable and wearable self-powered sensors. Full article
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10 pages, 16108 KiB  
Article
Regenerative, Highly-Sensitive, Non-Enzymatic Dopamine Sensor and Impact of Different Buffer Systems in Dopamine Sensing
by Saumya Joshi, Vijay Deep Bhatt, Andreas Märtl, Markus Becherer and Paolo Lugli
Biosensors 2018, 8(1), 9; https://doi.org/10.3390/bios8010009 - 24 Jan 2018
Cited by 18 | Viewed by 7915
Abstract
Carbon nanotube field-effect transistors are used extensively in ultra-sensitive biomolecule sensing applications. Along with high sensitivity, the possibility of regeneration is highly desired in bio-sensors. An important constituent of such bio-sensing systems is the buffer used to maintain pH and provide an ionic [...] Read more.
Carbon nanotube field-effect transistors are used extensively in ultra-sensitive biomolecule sensing applications. Along with high sensitivity, the possibility of regeneration is highly desired in bio-sensors. An important constituent of such bio-sensing systems is the buffer used to maintain pH and provide an ionic conducting medium, among its other properties. In this work, we demonstrate highly-sensitive regenerative dopamine sensors and the impact of varying buffer composition and type on the electrolyte gated field effect sensors. The role of the buffer system is an often ignored condition in the electrical characterization of sensors. Non-enzymatic dopamine sensors are fabricated and regenerated in hydrochloric acid (HCl) solution. The sensors are finally measured against four different buffer solutions. The impact of the nature and chemical structure of buffer molecules on the dopamine sensors is shown, and the appropriate buffer systems are demonstrated. Full article
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13 pages, 4563 KiB  
Article
Investigating Colorimetric Protein Array Assay Schemes for Detection of Recurrence of Bladder Cancer
by Selma Gogalic, Ursula Sauer, Sara Doppler and Claudia Preininger
Biosensors 2018, 8(1), 10; https://doi.org/10.3390/bios8010010 - 24 Jan 2018
Cited by 9 | Viewed by 6616
Abstract
A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick [...] Read more.
A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick therapy monitoring at doctors’ offices. The chip is based on the principle of a sandwich immunoassay and was optimized prior to multiplexing using IL8 as a model marker. Six different colorimetric assay formats were evaluated using a detection antibody (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III) oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin–carbon, (V) streptavidin (strp)–gold, and (VI) strp–horseradish peroxidase (HRP). Assay Format (III) worked best for NP-based detection and showed a low background while the enzymatic approach, using 3,3′,5,5′-tetramethylbenzidine (TMB) substrate, led to the most intense signals with good reproducibility. Both assay formats showed consistent spot morphology as well as detection limits lower than 15 ng/L IL8 and were thus applied for the multiplexed detection of IL8, DCN, and VEGF in synthetic urine. Colorimetric detection in urine (1:3) yields reaction signals and measurement ranges well comparable with detection in the assay buffer, as well as excellent data reproducibility as indicated by the coefficient of variation (CV 5–9%). Full article
(This article belongs to the Special Issue Biomarkers)
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16 pages, 5051 KiB  
Article
Antibody Biomimetic Material Made of Pyrrole for CA 15-3 and Its Application as Sensing Material in Ion-Selective Electrodes for Potentiometric Detection
by Alexandra R. T. Santos, Felismina T. C. Moreira, Luísa A. Helguero and M. Goreti F. Sales
Biosensors 2018, 8(1), 8; https://doi.org/10.3390/bios8010008 - 19 Jan 2018
Cited by 25 | Viewed by 6143
Abstract
This work reports a very simple approach for creating a synthetic antibody against any protein of interest and its application in potentiometric transduction. The selected protein was Breast Cancer Antigen (CA 15-3), which is implicated in breast cancer disease and used to follow-up [...] Read more.
This work reports a very simple approach for creating a synthetic antibody against any protein of interest and its application in potentiometric transduction. The selected protein was Breast Cancer Antigen (CA 15-3), which is implicated in breast cancer disease and used to follow-up breast cancer patients during treatment. The new material with antibody-like properties was obtained by molecular-imprinting technology, prepared by electropolymerizing pyrrol (Py, 5.0 × 10−3 mol/L) around Breast Cancer Antigen (CA 15-3) (100 U/mL) on a fluorine doped tin oxide (FTO) conductive glass support. Cyclic voltammetry was employed for this purpose. All solutions were prepared in 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, of pH 6.5. The biomarker was removed from the imprinted sites by chemical action of ethanol. The biomimetic material was then included in poly vinyl chloride (PVC) plasticized membranes to act as potentiometric ionophore, having or not a lipophilic ionic additive added. The corresponding selective electrodes were evaluated by calibration curves (in buffer and in synthetic serum) and by selectivity testing. The best analytical performance was obtained by selective electrodes including the plastic antibody and no lipophilic additive. The average limits of detection were 1.07 U/mL of CA 15-3, with a linear response from 1.44 to 13.2 U/mL and a cationic slope of 44.5 mV/decade. Overall, the lipophilic additives yielded no advantage to the overall potentiometric performance. The application of the MIP-based electrodes to the analysis of spiked synthetic serum showed precise and accurate results. Full article
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18 pages, 8241 KiB  
Article
A Low-Cost Inkjet-Printed Aptamer-Based Electrochemical Biosensor for the Selective Detection of Lysozyme
by Niazul Islam Khan, Alec G. Maddaus and Edward Song
Biosensors 2018, 8(1), 7; https://doi.org/10.3390/bios8010007 - 15 Jan 2018
Cited by 55 | Viewed by 13196
Abstract
Recently, inkjet-printing has gained increased popularity in applications such as flexible electronics and disposable sensors, as well as in wearable sensors because of its multifarious advantages. This work presents a novel, low-cost immobilization technique using inkjet-printing for the development of an aptamer-based biosensor [...] Read more.
Recently, inkjet-printing has gained increased popularity in applications such as flexible electronics and disposable sensors, as well as in wearable sensors because of its multifarious advantages. This work presents a novel, low-cost immobilization technique using inkjet-printing for the development of an aptamer-based biosensor for the detection of lysozyme, an important biomarker in various disease diagnosis. The strong affinity between the carbon nanotube (CNT) and the single-stranded DNA is exploited to immobilize the aptamers onto the working electrode by printing the ink containing the dispersion of CNT-aptamer complex. The inkjet-printing method enables aptamer density control, as well as high resolution patternability. Our developed sensor shows a detection limit of 90 ng/mL with high target selectivity against other proteins. The sensor also demonstrates a shelf-life for a reasonable period. This technology has potential for applications in developing low-cost point-of-care diagnostic testing kits for home healthcare. Full article
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14 pages, 4606 KiB  
Article
Mining the Potential of Label-Free Biosensors for In Vitro Antipsychotic Drug Screening
by Tugba Kilic, Maria Soler, Nafiseh Fahimi-Kashani, Hatice Altug and Sandro Carrara
Biosensors 2018, 8(1), 6; https://doi.org/10.3390/bios8010006 - 09 Jan 2018
Cited by 11 | Viewed by 9146
Abstract
The pharmaceutical industry is facing enormous challenges due to high drug attribution rates. For the past decades, novel methods have been developed for safety and efficacy testing, as well as for improving early development stages. In vitro screening methods for drug-receptor binding are [...] Read more.
The pharmaceutical industry is facing enormous challenges due to high drug attribution rates. For the past decades, novel methods have been developed for safety and efficacy testing, as well as for improving early development stages. In vitro screening methods for drug-receptor binding are considered to be good alternatives for decreasing costs in the identification of drug candidates. However, these methods require lengthy and troublesome labeling steps. Biosensors hold great promise due to the fact that label-free detection schemes can be designed in an easy and low-cost manner. In this paper, for the first time in the literature, we aimed to compare the potential of label-free optical and impedimetric electrochemical biosensors for the screening of antipsychotic drugs (APDs) based on their binding properties to dopamine receptors. Particularly, we have chosen a currently-used atypical antipsychotic drug (Buspirone) for investigating its dopamine D3 receptor (D3R) binding properties using an impedimetric biosensor and a nanoplasmonic biosensor. Both biosensors have been specifically functionalized and characterized for achieving a highly-sensitive and reliable analysis of drug-D3R binding. Our biosensor strategies allow for comparing different affinities against the D3R, which facilitates the identification of strong or weak dopamine antagonists via in vitro assays. This work demonstrates the unique potential of label-free biosensors for the implementation of cost-efficient and simpler analytical tools for the screening of antipsychotic drugs. Full article
(This article belongs to the Special Issue Label-free Biosensing)
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3 pages, 293 KiB  
Editorial
Acknowledgement to Reviewers of Biosensors in 2017
by Biosensors Editorial Office
Biosensors 2018, 8(1), 5; https://doi.org/10.3390/bios8010005 - 09 Jan 2018
Viewed by 4183
Abstract
Peer review is an essential part in the publication process, ensuring that Biosensors maintains high quality standards for its published papers.[...] Full article
13 pages, 4022 KiB  
Article
A Cuprous Oxide Thin Film Non-Enzymatic Glucose Sensor Using Differential Pulse Voltammetry and Other Voltammetry Methods and a Comparison to Different Thin Film Electrodes on the Detection of Glucose in an Alkaline Solution
by Yifan Dai, Alireza Molazemhosseini, Kevin Abbasi and Chung Chiun Liu
Biosensors 2018, 8(1), 4; https://doi.org/10.3390/bios8010004 - 06 Jan 2018
Cited by 29 | Viewed by 8540
Abstract
A cuprous oxide (Cu2O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50–200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study [...] Read more.
A cuprous oxide (Cu2O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50–200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum was carried out. Neither ascorbic acid nor uric acid, even at a relatively high concentration level (100 mg/dL in serum), interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer-based glucose sensor. Chronoamperometry and single potential amperometric voltammetry were used to verify the measurements obtained by DPV, and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum, and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. The cuprous oxide (Cu2O) thin layer-based sensor showed the best sensitivity for glucose detection among the sensors evaluated. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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2813 KiB  
Review
Electronic Tongue—A Tool for All Tastes?
by Marta Podrażka, Ewa Bączyńska, Magdalena Kundys, Paulina S. Jeleń and Emilia Witkowska Nery
Biosensors 2018, 8(1), 3; https://doi.org/10.3390/bios8010003 - 31 Dec 2017
Cited by 142 | Viewed by 19190
Abstract
Electronic tongue systems are traditionally used to analyse: food products, water samples and taste masking technologies for pharmaceuticals. In principle, their applications are almost limitless, as they are able to almost completely reduce the impact of interferents and can be applied to distinguish [...] Read more.
Electronic tongue systems are traditionally used to analyse: food products, water samples and taste masking technologies for pharmaceuticals. In principle, their applications are almost limitless, as they are able to almost completely reduce the impact of interferents and can be applied to distinguish samples of extreme complexity as for example broths from different stages of fermentation. Nevertheless, their applications outside the three principal sample types are, in comparison, rather scarce. In this review, we would like to take a closer look on what are real capabilities of electronic tongue systems, what can be achieved using mixed sensor arrays and by introduction of biosensors or molecularly imprinted polymers in the matrix. We will discuss future directions both in the sense of applications as well as system development in the ever-growing trend of low cost analysis. Full article
(This article belongs to the Special Issue Electronic Noses and Tongues as Biosensors)
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1678 KiB  
Article
An FT-Raman, FT-IR, and Quantum Chemical Investigation of Stanozolol and Oxandrolone
by Tibebe Lemma, Fabiano De Barros Souza, Claudio A. Tellez Soto and Airton A. Martin
Biosensors 2018, 8(1), 2; https://doi.org/10.3390/bios8010002 - 26 Dec 2017
Cited by 8 | Viewed by 7267
Abstract
We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR [...] Read more.
We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR and FT-Raman spectra were collected in a solid phase. The consistency between the calculated and experimental FT-IR and FT-Raman data indicates that the B3LYP/6-31G (d, p) can generate reliable geometry and related properties of the title compounds. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution. The good agreement between the experimental and theoretical spectra allowed positive assignment of the observed vibrational absorption bands. Finally, the calculation results were applied to simulate the Raman and IR spectra of the title compounds, which show agreement with the observed spectra. Full article
(This article belongs to the Special Issue Raman and IR Spectroscopic Sensing)
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1622 KiB  
Article
Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors
by Rita La Spina, Valentina E. V. Ferrero, Venera Aiello, Mattia Pedotti, Luca Varani, Teresa Lettieri, Luigi Calzolai, Willem Haasnoot and Pascal Colpo
Biosensors 2018, 8(1), 1; https://doi.org/10.3390/bios8010001 - 22 Dec 2017
Cited by 18 | Viewed by 8129
Abstract
Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive [...] Read more.
Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive methods to detect EDCs, which are detrimental even at very low concentrations. In this work, we propose a label-free surface plasmon resonance (SPR) biosensor method to detect specific EDCs (17 β-estradiol (E2), ethinyl-estradiol, 4-nonylphenol, tamoxifen) through their binding to estrogen receptor alpha (ERα). We show that the use of rationally designed ERα (as bio-recognition element) in combination with conformation-sensitive peptides (as amplification agent, resulting in increased responses) enables the detection of low parts per billion (ppb) levels of E2. As a proof of concept, this bioassay was used to detect E2 in (spiked) real water samples from fish farms, rivers and the sea at low ppb levels after concentration by solid phase extraction. In addition, the present SPR assay that combines a conformation-sensitive peptide with an array of ERα mutants is very promising for the assessment of the risk of potential estrogenic activity for chemical substances. Full article
(This article belongs to the Special Issue Label-free Biosensing)
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