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Biosensors, Volume 10, Issue 11 (November 2020) – 38 articles

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Cover Story (view full-size image) The widespread adaptation of 3D printing in the microfluidic, bioelectronic, and Bio-MEMS [...] Read more.
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Open AccessArticle
Detection of Lethal Bronzing Disease in Cabbage Palms (Sabal palmetto) Using a Low-Cost Electronic Nose
Biosensors 2020, 10(11), 188; https://doi.org/10.3390/bios10110188 - 23 Nov 2020
Viewed by 185
Abstract
Lethal Bronzing Disease (LB) is a disease of palms caused by the 16SrIV-D phytoplasma. A low-cost electronic nose (eNose) prototype was trialed for its detection. It includes an array of eight Taguchi-type (MQ) sensors (MQ135, MQ2, MQ3, MQ4, MQ5, MQ9, MQ7, and MQ8) [...] Read more.
Lethal Bronzing Disease (LB) is a disease of palms caused by the 16SrIV-D phytoplasma. A low-cost electronic nose (eNose) prototype was trialed for its detection. It includes an array of eight Taguchi-type (MQ) sensors (MQ135, MQ2, MQ3, MQ4, MQ5, MQ9, MQ7, and MQ8) controlled by an Arduino NANO® microcontroller, using heater voltages that vary sinusoidally over a 2.5 min cycle. Samples of uninfected, early symptomatic, moderate symptomatic, and late symptomatic infected palm leaves of the cabbage palm were processed and analyzed. MQ sensor responses were subjected to a 256 element discrete Fourier transform (DFT), and harmonic component amplitudes were reviewed by principal component analysis (PCA). The experiment was repeated three times, each showing clear evidence of differences in sensor responses between the samples of uninfected leaves and those in the early stages of infection. Within each experiment, four groups of responses were identified, demonstrating the ability of the unit to repeatedly distinguish healthy leaves from diseased ones; however, detection of the severity of infection has not been demonstrated. By selecting appropriate coefficients (here demonstrated with plots of MQ5 Cos1 vs. MQ8 Sin3), it should be possible to build a ruleset classifier to identify healthy and unhealthy samples. Full article
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Open AccessArticle
Three-Dimensional Paper-Based Microfluidic Analysis Device for Simultaneous Detection of Multiple Biomarkers with a Smartphone
Biosensors 2020, 10(11), 187; https://doi.org/10.3390/bios10110187 - 21 Nov 2020
Viewed by 220
Abstract
Paper-based microfluidic analysis devices (μPADs) have attracted attention as a cost-effective platform for point-of-care testing (POCT), food safety, and environmental monitoring. Recently, three-dimensional (3D)-μPADs have been developed to improve the performance of μPADs. For accurate diagnosis of diseases, however, 3D-μPADs need to be [...] Read more.
Paper-based microfluidic analysis devices (μPADs) have attracted attention as a cost-effective platform for point-of-care testing (POCT), food safety, and environmental monitoring. Recently, three-dimensional (3D)-μPADs have been developed to improve the performance of μPADs. For accurate diagnosis of diseases, however, 3D-μPADs need to be developed to simultaneously detect multiple biomarkers. Here, we report a 3D-μPADs platform for the detection of multiple biomarkers that can be analyzed and diagnosed with a smartphone. The 3D-μPADs were fabricated using a 3D digital light processing printer and consisted of a sample reservoir (300 µL) connected to 24 detection zones (of 4 mm in diameter) through eight microchannels (of 2 mm in width). With the smartphone application, eight different biomarkers related to various diseases were detectable in concentrations ranging from normal to abnormal conditions: glucose (0–20 mmol/L), cholesterol (0–10 mmol/L), albumin (0–7 g/dL), alkaline phosphatase (0–800 U/L), creatinine (0–500 µmol/L), aspartate aminotransferase (0–800 U/L), alanine aminotransferase (0–1000 U/L), and urea nitrogen (0–7.2 mmol/L). These results suggest that 3D-µPADs can be used as a POCT platform for simultaneous detection of multiple biomarkers. Full article
(This article belongs to the Special Issue Biosensors for Point-of-Care Diagnostics)
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Open AccessReview
Electrochemical Biosensors for Detection of MicroRNA as a Cancer Biomarker: Pros and Cons
Biosensors 2020, 10(11), 186; https://doi.org/10.3390/bios10110186 - 20 Nov 2020
Viewed by 239
Abstract
Cancer is the second most fatal disease in the world and an early diagnosis is important for a successful treatment. Thus, it is necessary to develop fast, sensitive, simple, and inexpensive analytical tools for cancer biomarker detection. MicroRNA (miRNA) is an RNA cancer [...] Read more.
Cancer is the second most fatal disease in the world and an early diagnosis is important for a successful treatment. Thus, it is necessary to develop fast, sensitive, simple, and inexpensive analytical tools for cancer biomarker detection. MicroRNA (miRNA) is an RNA cancer biomarker where the expression level in body fluid is strongly correlated to cancer. Various biosensors involving the detection of miRNA for cancer diagnosis were developed. The present review offers a comprehensive overview of the recent developments in electrochemical biosensor for miRNA cancer marker detection from 2015 to 2020. The review focuses on the approaches to direct miRNA detection based on the electrochemical signal. It includes a RedOx-labeled probe with different designs, RedOx DNA-intercalating agents, various kinds of RedOx catalysts used to produce a signal response, and finally a free RedOx indicator. Furthermore, the advantages and drawbacks of these approaches are highlighted. Full article
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Open AccessReview
Recent Advances in MXene Nanocomposite-Based Biosensors
Biosensors 2020, 10(11), 185; https://doi.org/10.3390/bios10110185 - 20 Nov 2020
Viewed by 178
Abstract
The development of advanced biosensors with high sensitivity and selectivity is one of the most demanded concerns in the field of biosensors. To meet this requirement, up until now, numerous nanomaterials have been introduced to develop biosensors for achieving high sensitivity and selectivity. [...] Read more.
The development of advanced biosensors with high sensitivity and selectivity is one of the most demanded concerns in the field of biosensors. To meet this requirement, up until now, numerous nanomaterials have been introduced to develop biosensors for achieving high sensitivity and selectivity. Among the latest nanomaterials attracting attention, MXene is one of the best materials for the development of biosensors because of its various superior properties. MXenes are two-dimensional inorganic compounds with few atomic layers that possess excellent characteristics including high conductivity and superior fluorescent, optical, and plasmonic properties. In this review, advanced biosensors developed on the basis of the MXene nanocomposite are discussed with the selective overview of recently reported studies. For this, introduction of the MXene including the definition, synthesis methods, and its properties are discussed. Next, MXene-based electrochemical biosensors and MXene-based fluorescent/optical biosensors are provided, which are developed on the basis of the exceptional properties of the MXene nanocomposite. This review will suggest the direction for use of the Mxene nanocomposite to develop advanced biosensors with high sensitivity and selectivity. Full article
(This article belongs to the Special Issue Last Advances in Optical Biosensors)
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Open AccessArticle
Drug-Based Gold Nanoparticles Overgrowth for Enhanced SPR Biosensing of Doxycycline
Biosensors 2020, 10(11), 184; https://doi.org/10.3390/bios10110184 - 19 Nov 2020
Viewed by 192
Abstract
In clinical chemistry, frequent monitoring of drug levels in patients has gained considerable importance because of the benefits of drug monitoring on human health, such as the avoidance of high risk of over dosage or increased therapeutic efficacy. In this work, we demonstrate [...] Read more.
In clinical chemistry, frequent monitoring of drug levels in patients has gained considerable importance because of the benefits of drug monitoring on human health, such as the avoidance of high risk of over dosage or increased therapeutic efficacy. In this work, we demonstrate that the drug doxycycline can act as an Au nanoparticle (doxy-AuNP) growth and capping agent to enhance the response of a surface plasmon resonance (SPR) biosensor for this drug. SPR analysis revealed the high sensitivity of doxy-AuNPs towards the detection of free doxycycline. More specifically, doxy-AuNPs bound with protease-activated receptor-1 (PAR-1) immobilized on the SPR sensing surface yield the response in SPR, which was enhanced following the addition of free doxy (analyte) to the solution of doxy-AuNPs. This biosensor allowed for doxycycline detection at concentrations as low as 7 pM. The study also examined the role of colloidal stability and growth of doxy-AuNPs in relation to the response-enhancement strategy based on doxy-AuNPs. Thus, the doxy-AuNPs-based SPR biosensor is an excellent platform for the detection of doxycycline and demonstrates a new biosensing scheme where the analyte can provide enhancement. Full article
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Open AccessReview
Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences
Biosensors 2020, 10(11), 183; https://doi.org/10.3390/bios10110183 - 19 Nov 2020
Viewed by 123
Abstract
Whilst it is universally accepted that the energy support of the brain is glucose, the form in which the glucose is taken up by neurones is the topic of intense debate. In the last few decades, the concept of lactate shuttling between glial [...] Read more.
Whilst it is universally accepted that the energy support of the brain is glucose, the form in which the glucose is taken up by neurones is the topic of intense debate. In the last few decades, the concept of lactate shuttling between glial elements and neural elements has emerged in which the glial cells glycolytically metabolise glucose/glycogen to lactate, which is shuttled to the neural elements via the extracellular fluid. The process occurs during periods of compromised glucose availability where glycogen stored in astrocytes provides lactate to the neurones, and is an integral part of the formation of learning and memory where the energy intensive process of learning requires neuronal lactate uptake provided by astrocytes. More recently sleep, myelination and motor end plate integrity have been shown to involve lactate shuttling. The sequential aspect of lactate production in the astrocyte followed by transport to the neurones is vulnerable to interruption and it is reported that such disparate pathological conditions as Alzheimer’s disease, amyotrophic lateral sclerosis, depression and schizophrenia show disrupted lactate signalling between glial cells and neurones. Full article
(This article belongs to the Special Issue Novel Sensing System for Biomedical Applications)
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Open AccessReview
Surface Modification Techniques for Endothelial Cell Seeding in PDMS Microfluidic Devices
Biosensors 2020, 10(11), 182; https://doi.org/10.3390/bios10110182 - 19 Nov 2020
Viewed by 181
Abstract
Microfluidic lab-on-a-chip cell culture techniques have been gaining popularity by offering the possibility of reducing the amount of samples and reagents and greater control over cellular microenvironment. Polydimethylsiloxane (PDMS) is the commonly used polymer for microfluidic cell culture devices because of the cheap [...] Read more.
Microfluidic lab-on-a-chip cell culture techniques have been gaining popularity by offering the possibility of reducing the amount of samples and reagents and greater control over cellular microenvironment. Polydimethylsiloxane (PDMS) is the commonly used polymer for microfluidic cell culture devices because of the cheap and easy fabrication techniques, non-toxicity, biocompatibility, high gas permeability, and optical transparency. However, the intrinsic hydrophobic nature of PDMS makes cell seeding challenging when applied on PDMS surface. The hydrophobicity of the PDMS surface also allows the non-specific absorption/adsorption of small molecules and biomolecules that might affect the cellular behaviour and functions. Hydrophilic modification of PDMS surface is indispensable for successful cell seeding. This review collates different techniques with their advantages and disadvantages that have been used to improve PDMS hydrophilicity to facilitate endothelial cells seeding in PDMS devices. Full article
(This article belongs to the Special Issue Recent Developments in Microfluidics)
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Open AccessArticle
Developing Rapid Antimicrobial Susceptibility Testing for Motile/Non-Motile Bacteria Treated with Antibiotics Covering Five Bactericidal Mechanisms on the Basis of Bead-Based Optical Diffusometry
Biosensors 2020, 10(11), 181; https://doi.org/10.3390/bios10110181 - 19 Nov 2020
Viewed by 192
Abstract
Rapid antimicrobial susceptibility testing (AST) is an effective measure in the treatment of infections and the prevention of bacterial drug resistance. However, diverse antibiotic types and bacterial characteristics have formed complicated barriers to rapid diagnosis. To counteract these limitations, we investigated the interactions [...] Read more.
Rapid antimicrobial susceptibility testing (AST) is an effective measure in the treatment of infections and the prevention of bacterial drug resistance. However, diverse antibiotic types and bacterial characteristics have formed complicated barriers to rapid diagnosis. To counteract these limitations, we investigated the interactions between antibiotic-treated bacteria and functionalized microbeads in optical diffusometry. The conjugation with bacteria increased the effective microbead complex size, thereby resulting in a temporal diffusivity change. The yielded data were sorted and analyzed to delineate a pattern for the prediction of antimicrobial susceptibility. The outcome showed that a completed rapid AST based on the trend of microbead diffusivity could provide results within 3 h (2 h measurement + 1 h computation). In this research, we studied four bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, and six antibiotics. Despite the different inhibitory effects caused by various antibiotics, similar trends in diffusivity alteration for all susceptible and resistant cases in the last 40 min of the 2-h measurement period were deduced. In addition, the AST results obtained using optical diffusometry showed good agreement with those acquired from the commercial instrument and conventional culture methods. Finally, we conducted a single-blinded clinical test, and the sensitivity, specificity, and accuracy of the system reached 92.9%, 91.4%, and 91.8%, respectively. Overall, the developed optical diffusometry showcased rapid AST with a small sample volume (20 μL) and low initial bacterial count (105 CFU/mL). This technique provided a promising way to achieve early therapy against microbial diseases in the future. Full article
(This article belongs to the Special Issue Advanced Biosensing Technologies in Medical Applications)
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Open AccessArticle
Dual-Channel Stopped-Flow Apparatus for Simultaneous Fluorescence, Anisotropy, and FRET Kinetic Data Acquisition for Binary and Ternary Biological Complexes
Biosensors 2020, 10(11), 180; https://doi.org/10.3390/bios10110180 - 19 Nov 2020
Viewed by 512
Abstract
The Stopped-Flow apparatus (SF) tracks molecular events by mixing the reactants in sub-millisecond regimes. The reaction of intrinsically or extrinsically labeled biomolecules can be monitored by recording the fluorescence, F(t), anisotropy, r(t), polarization, p(t), [...] Read more.
The Stopped-Flow apparatus (SF) tracks molecular events by mixing the reactants in sub-millisecond regimes. The reaction of intrinsically or extrinsically labeled biomolecules can be monitored by recording the fluorescence, F(t), anisotropy, r(t), polarization, p(t), or FRET, F(t)FRET, traces at nanomolar concentrations. These kinetic measurements are critical to elucidate reaction mechanisms, structural information, and even thermodynamics. In a single detector SF, or L-configuration, the r(t), p(t), and F(t) traces are acquired by switching the orientation of the emission polarizer to collect the IVV and IVH signals however it requires two-shot experiments. In a two-detector SF, or T-configuration, these traces are collected in a single-shot experiment, but it increases the apparatus’ complexity and price. Herein, we present a single-detector dual-channel SF to obtain the F(t) and r(t) traces simultaneously, in which a photo-elastic modulator oscillates by 90° the excitation light plane at a 50 kHz frequency, and the emission signal is processed by a set of electronic filters that split it into the r(t) and F(t) analog signals that are digitized and stored into separated spreadsheets by a custom-tailored instrument control software. We evaluated the association kinetics of binary and ternary biological complexes acquired with our dual-channel SF and the traditional methods; such as a single polarizer at the magic angle to acquire F(t), a set of polarizers to track F(t), and r(t), and by energy transfer quenching, F(t)FRET. Our dual-channel SF economized labeled material and yielded rate constants in excellent agreement with the traditional methods. Full article
(This article belongs to the Special Issue Nanobiosensors Based on Energy Transfer)
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Open AccessReview
State-of-the-Art Optical Microfiber Coupler Sensors for Physical and Biochemical Sensing Applications
Biosensors 2020, 10(11), 179; https://doi.org/10.3390/bios10110179 - 18 Nov 2020
Viewed by 200
Abstract
An optical fiber coupler is a simple and fundamental component for fiber optic technologies that works by reducing the fiber diameter to hundred nanometers or several micrometers. The microfiber coupler (MFC) has regained interest in optical fiber sensing in recent years. The subwavelength [...] Read more.
An optical fiber coupler is a simple and fundamental component for fiber optic technologies that works by reducing the fiber diameter to hundred nanometers or several micrometers. The microfiber coupler (MFC) has regained interest in optical fiber sensing in recent years. The subwavelength diameter rationales vast refractive index (RI) contrast between microfiber “core” and surrounding “cladding”, a large portion of energy transmits in the form of an evanescent wave over the fiber surface that determines the MFC ultrasensitive to local environmental changes. Consequently, MFC has the potential to develop as a sensor. With the merits of easy fabrication, low cost and compact size, numerous researches have been carried out on different microfiber coupler configurations for various sensing applications, such as refractive index (RI), temperature, humidity, magnetic field, gas, biomolecule, and so on. In this manuscript, the fabrication and operation principle of an MFC are elaborated and recent advances of MFC-based sensors for scientific and technological applications are comprehensively reviewed. Full article
(This article belongs to the Special Issue Recent Advances in Photonic Biosensors)
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Open AccessArticle
Newly Developed System for the Robust Detection of Listeria monocytogenes Based on a Bioelectric Cell Biosensor
Biosensors 2020, 10(11), 178; https://doi.org/10.3390/bios10110178 - 17 Nov 2020
Viewed by 322
Abstract
Human food-borne diseases caused by pathogenic bacteria have been significantly increased in the last few decades causing numerous deaths worldwide. The standard analyses used for their detection have significant limitations regarding cost, special facilities and equipment, highly trained staff, and a long procedural [...] Read more.
Human food-borne diseases caused by pathogenic bacteria have been significantly increased in the last few decades causing numerous deaths worldwide. The standard analyses used for their detection have significant limitations regarding cost, special facilities and equipment, highly trained staff, and a long procedural time that can be crucial for foodborne pathogens with high hospitalization and mortality rates, such as Listeria monocytogenes. This study aimed to develop a biosensor that could detect L. monocytogenes rapidly and robustly. For this purpose, a cell-based biosensor technology based on the Bioelectric Recognition Assay (BERA) and a portable device developed by EMBIO Diagnostics, called B.EL.D (Bio Electric Diagnostics), were used. Membrane engineering was performed by electroinsertion of Listeria monocytogenes homologous antibodies into the membrane of African green monkey kidney (Vero) cells. The newly developed biosensor was able to detect the pathogen’s presence rapidly (3 min) at concentrations as low as 102 CFU mL−1, demonstrating a higher sensitivity than most existing biosensor-based methods. In addition, lack of cross-reactivity with other Listeria species, as well as with Escherichia coli, was shown, thus, indicating biosensor’s significant specificity against L. monocytogenes. Full article
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Open AccessCommunication
Microfluidic Packaging Integration with Electronic-Photonic Biosensors Using 3D Printed Transfer Molding
Biosensors 2020, 10(11), 177; https://doi.org/10.3390/bios10110177 - 14 Nov 2020
Viewed by 338
Abstract
Multiplexed sensing in integrated silicon electronic-photonic platforms requires microfluidics with both high density micro-scale channels and meso-scale features to accommodate for optical, electrical, and fluidic coupling in small, millimeter-scale areas. Three-dimensional (3D) printed transfer molding offers a facile and rapid method to create [...] Read more.
Multiplexed sensing in integrated silicon electronic-photonic platforms requires microfluidics with both high density micro-scale channels and meso-scale features to accommodate for optical, electrical, and fluidic coupling in small, millimeter-scale areas. Three-dimensional (3D) printed transfer molding offers a facile and rapid method to create both micro and meso-scale features in complex multilayer microfluidics in order to integrate with monolithic electronic-photonic system-on-chips with multiplexed rows of 5 μm radius micro-ring resonators (MRRs), allowing for simultaneous optical, electrical, and microfluidic coupling on chip. Here, we demonstrate this microfluidic packaging strategy on an integrated silicon photonic biosensor, setting the basis for highly multiplexed molecular sensing on-chip. Full article
(This article belongs to the Special Issue Photonic Biosensors: Detection, Analysis and Medical Diagnostics)
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Open AccessReview
High-Tech and Nature-Made Nanocomposites and Their Applications in the Field of Sensors and Biosensors for Gas Detection
Biosensors 2020, 10(11), 176; https://doi.org/10.3390/bios10110176 - 13 Nov 2020
Viewed by 171
Abstract
Gas sensors have been object of increasing attention by the scientific community in recent years. For the development of the sensing element, two major trends seem to have appeared. On one hand, the possibility of creating complex structures at the nanoscale level has [...] Read more.
Gas sensors have been object of increasing attention by the scientific community in recent years. For the development of the sensing element, two major trends seem to have appeared. On one hand, the possibility of creating complex structures at the nanoscale level has given rise to ever more sensitive sensors based on metal oxides and metal–polymer combinations. On the other hand, gas biosensors have started to be developed, thanks to their intrinsic ability to be selective for the target analyte. In this review, we analyze the recent progress in both areas and underline their strength, current problems, and future perspectives. Full article
(This article belongs to the Section Biosensor Materials)
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Open AccessArticle
Electrochemical Immunosensors Based on Screen-Printed Gold and Glassy Carbon Electrodes: Comparison of Performance for Respiratory Syncytial Virus Detection
Biosensors 2020, 10(11), 175; https://doi.org/10.3390/bios10110175 - 13 Nov 2020
Viewed by 219
Abstract
This paper presents the development and comparison of label-free electrochemical immunosensors based on screen-printed gold and glassy carbon (GC) disc electrodes for efficient and rapid detection of respiratory syncytial virus (RSV). Briefly, the antibody specific to the F protein of RSV was successfully [...] Read more.
This paper presents the development and comparison of label-free electrochemical immunosensors based on screen-printed gold and glassy carbon (GC) disc electrodes for efficient and rapid detection of respiratory syncytial virus (RSV). Briefly, the antibody specific to the F protein of RSV was successfully immobilized on modified electrodes. Antibody coupling on the Au surface was conducted via 4-aminothiophenol (4-ATP) and glutaraldehyde (GA). The GC surface was modified with poly-L-lysine (PLL) for direct anti-RSV conjugation after EDC/NHS (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide) activation. Electrochemical characterizations of the immunosensors were carried out by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). GC-based immunosensors show a dynamic range of antigen detection from 1.0 × 105 PFU/mL to 1.5×107 PFU/mL, more than 1.0 × 105 PFU/mL to 1.0 × 107 PFU/mL for the Au-based sensor. However, the GC platform is less sensitive and shows a higher detection limit (LOD) for RSV. The limit of detection of the Au immunosensor is 1.1 × 103 PFU/mL, three orders of magnitude lower than 2.85 × 106 PFU/mL for GC. Thus, the Au-based immunosensor has better analytical performance for virus detection than a carbon-based platform due to high sensitivity and very low RSV detection, obtained with good reproducibility. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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Open AccessArticle
Real-Time Optical Monitoring of Endotracheal Tube Displacement
Biosensors 2020, 10(11), 174; https://doi.org/10.3390/bios10110174 - 12 Nov 2020
Viewed by 368
Abstract
Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should [...] Read more.
Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system. Full article
(This article belongs to the Special Issue Optical Fiber Sensors for Environmental and Biomedical Applications)
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Open AccessArticle
Electromagnetic Piezoelectric Acoustic Sensor Detection of Extracellular Vesicles through Interaction with Detached Vesicle Proteins
Biosensors 2020, 10(11), 173; https://doi.org/10.3390/bios10110173 - 11 Nov 2020
Viewed by 273
Abstract
An electromagnetic piezoelectric acoustic sensor (EMPAS) was used to study the non-specific adsorption of human red blood cell-derived extracellular vesicle preparations. Vesicle storage history (temperature and duration) highly affected the obtained results: The signal change, namely the frequency decrease of the crystal measured [...] Read more.
An electromagnetic piezoelectric acoustic sensor (EMPAS) was used to study the non-specific adsorption of human red blood cell-derived extracellular vesicle preparations. Vesicle storage history (temperature and duration) highly affected the obtained results: The signal change, namely the frequency decrease of the crystal measured at 20 °C, was negligibly small (<1 s−2) when the vesicle solutions had previously been stored at 4 °C, and was in the order of 10 s−2 when the vesicle solutions had been stored at −30 °C. Moreover, the rate of frequency decrease increased exponentially with the storage time at −30 °C. Upon a 4 °C storage period following the −30 °C storage period of the same sample, the measured frequency decrease dropped, suggesting a partial relaxation of the system. The results are explained by the disintegration of the vesicles triggered by the freeze–thaw cycle, likely due to the detachment of proteins from the vesicle surface as was proved by size-exclusion chromatography. Surface modification of the sensor crystal provided the possibility of signal enhancement, as the maximum rate of the frequency change for the same vesicle concentrations was higher on hydrophobic, octadecyl trichlorosilane–modified quartz than on hydrophilic, bare quartz. The EMPAS signal has been associated with the amount of detached proteins, which in turn is proportional to the originating vesicle concentration. Full article
(This article belongs to the Special Issue Biosensors: 10th Anniversary Feature Papers)
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Open AccessArticle
Gas Crosstalk between PFPE–PEG–PFPE Triblock Copolymer Surfactant-Based Microdroplets and Monitoring Bacterial Gas Metabolism with Droplet-Based Microfluidics
Biosensors 2020, 10(11), 172; https://doi.org/10.3390/bios10110172 - 11 Nov 2020
Viewed by 342
Abstract
The PFPE–PEG–PFPE (Perfluoropolyether-polyethylene glycol-perfluoropolyether) surfactant has been used in droplet-based microfluidics and is known to provide high droplet stability and biocompatibility. Since this surfactant ensures the stability of droplets, droplet-based microfluidic systems have been widely used to encapsulate and analyze various biological components [...] Read more.
The PFPE–PEG–PFPE (Perfluoropolyether-polyethylene glycol-perfluoropolyether) surfactant has been used in droplet-based microfluidics and is known to provide high droplet stability and biocompatibility. Since this surfactant ensures the stability of droplets, droplet-based microfluidic systems have been widely used to encapsulate and analyze various biological components at the single-molecule scale, including viruses, bacteria, nucleic acids and proteins. In this study, we experimentally confirmed that gas crosstalk occurred between droplets formed by fluorinated oil and the PFPE–PEG–PFPE surfactant. E. coli K-12 bacterial cells were encapsulated with Luria–Bertani broth within droplets for the cultivation, and gas crosstalk was identified with neighboring droplets that contain phenol red. Since bacteria produce ammonia gas during its metabolism, penetration of ammonia gas initiates a color change of phenol red-containing droplets. Ammonia gas exchange was also confirmed by reacting ammonium chloride and sodium hydroxide within droplets that encapsulated. Herein, we demonstrate the gas crosstalk issue between droplets when it is formed using the PFPE–PEG–PFPE surfactant and also confirm that the density of droplet barrier has effects on gas crosstalk. Our results also suggest that droplet-based microfluidics can be used for the monitoring of living bacteria by the determination of bacterial metabolites during cultivation. Full article
(This article belongs to the Special Issue Microfluidic Bio-Sensors and Their Applications)
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Open AccessReview
The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease
Biosensors 2020, 10(11), 171; https://doi.org/10.3390/bios10110171 - 11 Nov 2020
Viewed by 426
Abstract
Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results. Full article
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Open AccessReview
Liquid Metal Based Flexible and Implantable Biosensors
Biosensors 2020, 10(11), 170; https://doi.org/10.3390/bios10110170 - 10 Nov 2020
Viewed by 319
Abstract
Biosensors are the core elements for obtaining significant physiological information from living organisms. To better sense life information, flexible biosensors and implantable sensors that are highly compatible with organisms are favored by researchers. Moreover, materials for preparing a new generation of flexible sensors [...] Read more.
Biosensors are the core elements for obtaining significant physiological information from living organisms. To better sense life information, flexible biosensors and implantable sensors that are highly compatible with organisms are favored by researchers. Moreover, materials for preparing a new generation of flexible sensors have also received attention. Liquid metal is a liquid-state metallic material with a low melting point at or around room temperature. Owing to its high electrical conductivity, low toxicity, and superior fluidity, liquid metal is emerging as a highly desirable candidate in biosensors. This paper is dedicated to reviewing state-of-the-art applications in biosensors that are expounded from seven aspects, including pressure sensor, strain sensor, gas sensor, temperature sensor, electrical sensor, optical sensor, and multifunctional sensor, respectively. The fundamental scientific and technological challenges lying behind these recommendations are outlined. Finally, the perspective of liquid metal-based biosensors is present, which stimulates the upcoming design of biosensors. Full article
(This article belongs to the Special Issue Liquid Metal Enabled Bio-Related Applications)
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Open AccessArticle
Yeast-Based Fluorescent Sensors for the Simultaneous Detection of Estrogenic and Androgenic Compounds, Coupled with High-Performance Thin Layer Chromatography
Biosensors 2020, 10(11), 169; https://doi.org/10.3390/bios10110169 - 08 Nov 2020
Viewed by 376
Abstract
The persistence of endocrine disrupting compounds (EDCs) throughout wastewater treatment processes poses a significant health threat to humans and to the environment. The analysis of EDCs in wastewater remains a challenge for several reasons, including (a) the multitude of bioactive but partially unknown [...] Read more.
The persistence of endocrine disrupting compounds (EDCs) throughout wastewater treatment processes poses a significant health threat to humans and to the environment. The analysis of EDCs in wastewater remains a challenge for several reasons, including (a) the multitude of bioactive but partially unknown compounds, (b) the complexity of the wastewater matrix, and (c) the required analytical sensitivity. By coupling biological assays with high-performance thin-layer chromatography (HPTLC), different samples can be screened simultaneously, highlighting their active components; these may then be identified by chemical analysis. To allow the multiparallel detection of diverse endocrine disruption activities, we have constructed Saccharomyces cerevisiae-based bioreporter strains, responding to compounds with either estrogenic or androgenic activity, by the expression of green (EGFP), red (mRuby), or blue (mTagBFP2) fluorescent proteins. We demonstrate the analytical potential inherent in combining chromatographic compound separation with a direct fluorescent signal detection of EDC activities. The applicability of the system is further demonstrated by separating influent samples of wastewater treatment plants, and simultaneously quantifying estrogenic and androgenic activities of their components. The combination of a chemical separation technique with an optical yeast-based bioassay presents a potentially valuable addition to our arsenal of environmental pollution monitoring tools. Full article
(This article belongs to the Special Issue Biosensors: 10th Anniversary Feature Papers)
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Open AccessCommunication
Single-Molecule FRET Detection of Sub-Nanometer Distance Changes in the Range below a 3-Nanometer Scale
Biosensors 2020, 10(11), 168; https://doi.org/10.3390/bios10110168 - 08 Nov 2020
Viewed by 489
Abstract
Single-molecule fluorescence energy transfer (FRET) detection has become a key technique to monitor intra- and intermolecular distance changes in biological processes. As the sensitive detection range of conventional FRET pairs is limited to 3–8 nm, complement probes are necessary for extending this typical [...] Read more.
Single-molecule fluorescence energy transfer (FRET) detection has become a key technique to monitor intra- and intermolecular distance changes in biological processes. As the sensitive detection range of conventional FRET pairs is limited to 3–8 nm, complement probes are necessary for extending this typical working range. Here, we realized a single-molecule FRET assay for a short distance range of below 3 nm by using a Cy2–Cy7 pair having extremely small spectral overlap. Using two DNA duplexes with a small difference in the labeling position, we demonstrated that our assay can observe subtle changes at a short distance range. High sensitivity in the range of 1–3 nm and compatibility with the conventional FRET assay make this approach useful for understanding dynamics at a short distance. Full article
(This article belongs to the Special Issue Nanobiosensors Based on Energy Transfer)
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Open AccessReview
Interfacing DNA with Gold Nanoparticles for Heavy Metal Detection
Biosensors 2020, 10(11), 167; https://doi.org/10.3390/bios10110167 - 06 Nov 2020
Viewed by 335
Abstract
The contamination of heavy metals (e.g., Hg, Pb, Cd and As) poses great risks to the environment and human health. Rapid and simple detection of heavy metals of considerable toxicity in low concentration levels is an important task in biological and environmental analysis. [...] Read more.
The contamination of heavy metals (e.g., Hg, Pb, Cd and As) poses great risks to the environment and human health. Rapid and simple detection of heavy metals of considerable toxicity in low concentration levels is an important task in biological and environmental analysis. Among the many convenient detection methods for heavy metals, DNA-inspired gold nanoparticles (DNA-AuNPs) have become a well-established approach, in which assembly/disassembly of AuNPs is used for colorimetric signaling of the recognition event between DNA and target heavy metals at the AuNP interface. This review focuses on the recent efforts of employing DNA to manipulate the interfacial properties of AuNPs, as well as the major advances in the colorimetric detection of heavy metals. Beginning with the introduction of the fundamental aspects of DNA and AuNPs, three main strategies of constructing DNA-AuNPs with DNA binding-responsive interface are discussed, namely, crosslinking, electrostatic interaction and base pair stacking. Then, recent achievements in colorimetric biosensing of heavy metals based on manipulation of the interface of DNA-AuNPs are surveyed and compared. Finally, perspectives on challenges and opportunities for future research in this field are provided. Full article
(This article belongs to the Special Issue Emerging Nanoplasmonic Technologies in Biosensors)
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Open AccessReview
Printed Electrochemical Biosensors: Opportunities and Metrological Challenges
Biosensors 2020, 10(11), 166; https://doi.org/10.3390/bios10110166 - 04 Nov 2020
Viewed by 356
Abstract
Printed electrochemical biosensors have recently gained increasing relevance in fields ranging from basic research to home-based point-of-care. Thus, they represent a unique opportunity to enable low-cost, fast, non-invasive and/or continuous monitoring of cells and biomolecules, exploiting their electrical properties. Printing technologies represent powerful [...] Read more.
Printed electrochemical biosensors have recently gained increasing relevance in fields ranging from basic research to home-based point-of-care. Thus, they represent a unique opportunity to enable low-cost, fast, non-invasive and/or continuous monitoring of cells and biomolecules, exploiting their electrical properties. Printing technologies represent powerful tools to combine simpler and more customizable fabrication of biosensors with high resolution, miniaturization and integration with more complex microfluidic and electronics systems. The metrological aspects of those biosensors, such as sensitivity, repeatability and stability, represent very challenging aspects that are required for the assessment of the sensor itself. This review provides an overview of the opportunities of printed electrochemical biosensors in terms of transducing principles, metrological characteristics and the enlargement of the application field. A critical discussion on metrological challenges is then provided, deepening our understanding of the most promising trends in order to overcome them: printed nanostructures to improve the limit of detection, sensitivity and repeatability; printing strategies to improve organic biosensor integration in biological environments; emerging printing methods for non-conventional substrates; microfluidic dispensing to improve repeatability. Finally, an up-to-date analysis of the most recent examples of printed electrochemical biosensors for the main classes of target analytes (live cells, nucleic acids, proteins, metabolites and electrolytes) is reported. Full article
(This article belongs to the Special Issue Electrical and Electro-Optical Biosensors for Protein Detection)
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Open AccessReview
Modular and Integrated Systems for Nanoparticle and Microparticle Synthesis—A Review
Biosensors 2020, 10(11), 165; https://doi.org/10.3390/bios10110165 - 03 Nov 2020
Viewed by 358
Abstract
Nanoparticles (NPs) and microparticles (MPs) have been widely used in different areas of research such as materials science, energy, and biotechnology. On-demand synthesis of NPs and MPs with desired chemical and physical properties is essential for different applications. However, most of the conventional [...] Read more.
Nanoparticles (NPs) and microparticles (MPs) have been widely used in different areas of research such as materials science, energy, and biotechnology. On-demand synthesis of NPs and MPs with desired chemical and physical properties is essential for different applications. However, most of the conventional methods for producing NPs/MPs require bulky and expensive equipment, which occupies large space and generally need complex operation with dedicated expertise and labour. These limitations hinder inexperienced researchers to harness the advantages of NPs and MPs in their fields of research. When problems individual researchers accumulate, the overall interdisciplinary innovations for unleashing a wider range of directions are undermined. In recent years, modular and integrated systems are developed for resolving the ongoing dilemma. In this review, we focus on the development of modular and integrated systems that assist the production of NPs and MPs. We categorise these systems into two major groups: systems for the synthesis of (1) NPs and (2) MPs; systems for producing NPs are further divided into two sections based on top-down and bottom-up approaches. The mechanisms of each synthesis method are explained, and the properties of produced NPs/MPs are compared. Finally, we discuss existing challenges and outline the potentials for the development of modular and integrated systems. Full article
(This article belongs to the Special Issue Microfluidics for Biosensing)
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Open AccessArticle
Detecting Vasodilation as Potential Diagnostic Biomarker in Breast Cancer Using Deep Learning-Driven Thermomics
Biosensors 2020, 10(11), 164; https://doi.org/10.3390/bios10110164 - 31 Oct 2020
Viewed by 467
Abstract
Breast cancer is the most common cancer in women. Early diagnosis improves outcome and survival, which is the cornerstone of breast cancer treatment. Thermography has been utilized as a complementary diagnostic technique in breast cancer detection. Artificial intelligence (AI) has the capacity to [...] Read more.
Breast cancer is the most common cancer in women. Early diagnosis improves outcome and survival, which is the cornerstone of breast cancer treatment. Thermography has been utilized as a complementary diagnostic technique in breast cancer detection. Artificial intelligence (AI) has the capacity to capture and analyze the entire concealed information in thermography. In this study, we propose a method to potentially detect the immunohistochemical response to breast cancer by finding thermal heterogeneous patterns in the targeted area. In this study for breast cancer screening 208 subjects participated and normal and abnormal (diagnosed by mammography or clinical diagnosis) conditions were analyzed. High-dimensional deep thermomic features were extracted from the ResNet-50 pre-trained model from low-rank thermal matrix approximation using sparse principal component analysis. Then, a sparse deep autoencoder designed and trained for such data decreases the dimensionality to 16 latent space thermomic features. A random forest model was used to classify the participants. The proposed method preserves thermal heterogeneity, which leads to successful classification between normal and abnormal subjects with an accuracy of 78.16% (73.3–81.07%). By non-invasively capturing a thermal map of the entire tumor, the proposed method can assist in screening and diagnosing this malignancy. These thermal signatures may preoperatively stratify the patients for personalized treatment planning and potentially monitor the patients during treatment. Full article
(This article belongs to the Special Issue Biosensors: 10th Anniversary Feature Papers)
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Open AccessArticle
Development of Surface-Enhanced Raman Scattering (SERS)-Based Surface-Corrugated Nanopillars for Biomolecular Detection of Colorectal Cancer
Biosensors 2020, 10(11), 163; https://doi.org/10.3390/bios10110163 - 31 Oct 2020
Viewed by 365
Abstract
In this paper, a nanobiosensor with surface-enhanced Raman scattering (SERS) capability is introduced for highly sensitive miRNA detection in colorectal cancer. This sensor was designed and fabricated by employing a nanoshielding mechanism from nanopolystyrene beads to resist reactive ion etching and allow anisotropic [...] Read more.
In this paper, a nanobiosensor with surface-enhanced Raman scattering (SERS) capability is introduced for highly sensitive miRNA detection in colorectal cancer. This sensor was designed and fabricated by employing a nanoshielding mechanism from nanopolystyrene beads to resist reactive ion etching and allow anisotropic electrochemical etching, producing high-aspect-ratio, surface-corrugated nanopillars (SiNPs) on a silicon wafer to create extensive hot spots along the nanopillars for improved SERS signals. SERS enhancements were correlated with nanorange roughness, indicating that hot spots along the pillars were the crucial factor to improve the SERS effect. We achieved the detection capability of a trace amount of R6G (10−8 M), and the SERS signal enhancement factor (EF) was close to 1.0 × 107 on surface-corrugated gold SiNPs. miRNA samples were also demonstrated on this sensor with good sensitivity and specificity. The target molecule miR-21-Cy5 was easily monitored through Raman spectrum variation with a PCR-comparable concentration at around 100 pM with clear nucleotide-specific Raman signals, which is also suitable for biomolecule sensing. Full article
(This article belongs to the Special Issue Biosensors Based on Nanoscale Components and Devices)
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Open AccessReview
Carbon-Based Quantum Dots for Electrochemical Detection of Monoamine Neurotransmitters—Review
Biosensors 2020, 10(11), 162; https://doi.org/10.3390/bios10110162 - 31 Oct 2020
Viewed by 303
Abstract
Imbalance in the levels of monoamine neurotransmitters have manifested in severe health issues. Electrochemical sensors have been designed for their determination, with good sensitivity recorded. Carbon-based quantum dots have proven to be an important component of electrochemical sensors due to their high conductivity, [...] Read more.
Imbalance in the levels of monoamine neurotransmitters have manifested in severe health issues. Electrochemical sensors have been designed for their determination, with good sensitivity recorded. Carbon-based quantum dots have proven to be an important component of electrochemical sensors due to their high conductivity, low cytotoxicity and opto-electronic properties. The quest for more sensitive electrodes with cheaper materials led to the development of electrochemical sensors based on carbon-based quantum dots for the detection of neurotransmitters. The importance of monoamine neurotransmitters (NTs) and the good electrocatalytic activity of carbon and graphene quantum dots (CQDs and GQDs) make the review of the efforts made in the design of such sensors for monoamine NTs of huge necessity. The differences and the similarities between these two quantum dots are highlighted prior to a discussion of their application in electrochemical sensors over the last ten years. Compared to other monoamine NTs, dopamine (DA) was the most studied with GQDs and CQD-based electrochemical sensors. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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Open AccessArticle
A Rapid Immunochromatographic Method Based on a Secondary Antibody-Labelled Magnetic Nanoprobe for the Detection of Hepatitis B preS2 Surface Antigen
Biosensors 2020, 10(11), 161; https://doi.org/10.3390/bios10110161 - 31 Oct 2020
Viewed by 315
Abstract
Hepatitis B is a globally prevalent viral infectious disease caused by the hepatitis B virus (HBV). In this study, an immunochromatographic assay (ICA) for the rapid detection of hepatitis B preS2 antigen (preS2Ag) was established. The magnetic nanoparticles (MNPs) indirectly labelled with goat [...] Read more.
Hepatitis B is a globally prevalent viral infectious disease caused by the hepatitis B virus (HBV). In this study, an immunochromatographic assay (ICA) for the rapid detection of hepatitis B preS2 antigen (preS2Ag) was established. The magnetic nanoparticles (MNPs) indirectly labelled with goat anti-mouse (GAM) secondary antibody were applied as a nanoprobe for free preS2 antibody (preS2Ab) capturing and signal amplification. By employing sample pre-incubation processing as well, preS2Ag-preS2Ab was sufficiently caught by the GAM-MNPs probe in 5 min. A qualitative sensitivity of 625 ng/mL was obtained by naked-eye observation within 15–20 min. A standard curve (0–5000 ng/mL) was established, with a quantitative limit of detection (LOD) of 3.6 ng/mL, based on the stability and penetrability of the magnetic signal characteristics. The proposed method for preS2Ag was rapid (~25 min, cf. ELISA ~4 h) and had a good accuracy, which was verified using an ELISA kit (relative error < 15%). Large equipment and skilled technicians were not required. The sensitivity and specificity of the developed GAM-MNPs-ICA method were 93.3% and 90% in clinical serum samples (n = 25), respectively. A good detection consistency (84%) was observed between the developed ICA method and 2 types of commercial ELISA kits, indicating that the GAM-MNPs-ICA has a potential application in large-scale screening for and point-of-care diagnosis of hepatitis B or other infectious diseases. Full article
(This article belongs to the Section Nano- and Micro-Technologies in Biosensors)
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Open AccessBrief Report
High Sensitivity Protein Gel Electrophoresis Label Compatible with Mass-Spectrometry
Biosensors 2020, 10(11), 160; https://doi.org/10.3390/bios10110160 - 31 Oct 2020
Viewed by 388
Abstract
Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a widely utilized technique for macromolecule and protein analysis. While multiple methods exist to visualize the separated protein bands on gels, one of most popular methods of staining the proteins is with Coomassie dye. A [...] Read more.
Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a widely utilized technique for macromolecule and protein analysis. While multiple methods exist to visualize the separated protein bands on gels, one of most popular methods of staining the proteins is with Coomassie dye. A more recent approach is to use Bio-Rad stain-free technology for visualizing protein bands with UV light and achieve similar or greater sensitivity than that of Coomassie dye. Here, we developed a method to further amplify the sensitivity of stain-free gels using carboxyfluorescein succinimidyl ester (CFSE) staining. We compared our novel method using foetal bovine serum samples with Coomassie dye, standard stain-free gels, and silver staining. Our results show that while silver staining remains a gold-standard method in terms of sensitivity; CFSE staining of samples prior to use with stain-free gels results in a 10–100-fold increase in sensitivity over Coomassie staining and the standard stain-free method. Our method offers a sensitivity similar to that of silver staining which is compatible with downstream mass spectrometry, and therefore more advantageous for further retrieval and analysis of macromolecules in bands. Full article
(This article belongs to the Section Nano- and Micro-Technologies in Biosensors)
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Open AccessReview
Printed Circuit Board (PCB) Technology for Electrochemical Sensors and Sensing Platforms
Biosensors 2020, 10(11), 159; https://doi.org/10.3390/bios10110159 - 30 Oct 2020
Viewed by 459
Abstract
The development of various biosensors has revolutionized the healthcare industry by providing rapid and reliable detection capability. Printed circuit board (PCB) technology has a well-established industry widely available around the world. In addition to electronics, this technology has been utilized to fabricate electrical [...] Read more.
The development of various biosensors has revolutionized the healthcare industry by providing rapid and reliable detection capability. Printed circuit board (PCB) technology has a well-established industry widely available around the world. In addition to electronics, this technology has been utilized to fabricate electrical parts, including electrodes for different biological and chemical sensors. High reproducibility achieved through long-lasting standard processes and low-cost resulting from an abundance of competitive manufacturing services makes this fabrication method a prime candidate for patterning electrodes and electrical parts of biosensors. The adoption of this approach in the fabrication of sensing platforms facilitates the integration of electronics and microfluidics with biosensors. In this review paper, the underlying principles and advances of printed board circuit technology are discussed. In addition, an overview of recent advancements in the development of PCB-based biosensors is provided. Finally, the challenges and outlook of PCB-based sensors are elaborated. Full article
(This article belongs to the Special Issue Electrical and Electro-Optical Biosensors for Protein Detection)
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