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Volume 11, November

Biosensors, Volume 11, Issue 12 (December 2021) – 57 articles

Cover Story (view full-size image): A promising candidate biosensor for multiplexed analyses of prognostic biomarkers in non-invasive biological fluids (e.g., saliva) was developed. Exploiting paper patterning through a rapid (5 sec) and one-step CO2 laser fabrication, a monolithic and fully integrated device was realized. The multiplexed biosensor was designed with a central sample deposition zone and three identical arms, each containing a pre-treatment and test zone. In the detection zones, a target-induced reshaping of plasmonic multibranched gold nanoparticles allows a clear and sensitive colorimetric readout in 10 min, appreciable by both naked-eye and smartphone camera. View this paper
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Article
Maximizing the Surface Sensitivity of LSPR Biosensors through Plasmon Coupling—Interparticle Gap Optimization for Dimers Using Computational Simulations
Biosensors 2021, 11(12), 527; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120527 - 20 Dec 2021
Viewed by 353
Abstract
The bulk and surface refractive index sensitivities of LSPR biosensors, consisting of coupled plasmonic nanosphere and nano-ellipsoid dimers, were investigated by simulations using the boundary element method (BEM). The enhancement factor, defined as the ratio of plasmon extinction peak shift of multi-particle and [...] Read more.
The bulk and surface refractive index sensitivities of LSPR biosensors, consisting of coupled plasmonic nanosphere and nano-ellipsoid dimers, were investigated by simulations using the boundary element method (BEM). The enhancement factor, defined as the ratio of plasmon extinction peak shift of multi-particle and single-particle arrangements caused by changes in the refractive index of the environment, was used to quantify the effect of coupling on the increased sensitivity of the dimers. The bulk refractive index sensitivity (RIS) was obtained by changing the dielectric medium surrounding the nanoparticles, while the surface sensitivity was modeled by depositing dielectric layers on the nanoparticle in an increasing thickness. The results show that by optimizing the interparticle gaps for a given layer thickness, up to ~80% of the optical response range of the nanoparticles can be utilized by confining the plasmon field between the particles, which translates into an enhancement of ~3–4 times compared to uncoupled, single particles with the same shape and size. The results also show that in these cases, the surface sensitivity enhancement is significantly higher than the bulk RI sensitivity enhancement (e.g., 3.2 times vs. 1.8 times for nanospheres with a 70 nm diameter), and thus the sensors’ response for molecular interactions is higher than their RIS would indicate. These results underline the importance of plasmonic coupling in the optimization of nanoparticle arrangements for biosensor applications. The interparticle gap should be tailored with respect to the size of the used receptor/target molecules to maximize the molecular sensitivity, and the presented methodology can effectively aid the optimization of fabrication technologies. Full article
(This article belongs to the Special Issue Nanoparticles-Based Biosensors)
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Article
Pressure-Free Assembling of Poly(methyl methacrylate) Microdevices via Microwave-Assisted Solvent Bonding and Its Biomedical Applications
Biosensors 2021, 11(12), 526; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120526 - 20 Dec 2021
Viewed by 322
Abstract
Poly(methyl methacrylate) (PMMA) has become an appealing material for manufacturing microfluidic chips, particularly for biomedical applications, because of its transparency and biocompatibility, making the development of an appropriate bonding strategy critical. In our research, we used acetic acid as a solvent to create [...] Read more.
Poly(methyl methacrylate) (PMMA) has become an appealing material for manufacturing microfluidic chips, particularly for biomedical applications, because of its transparency and biocompatibility, making the development of an appropriate bonding strategy critical. In our research, we used acetic acid as a solvent to create a pressure-free assembly of PMMA microdevices. The acetic acid applied between the PMMA slabs was activated by microwave using a household microwave oven to tightly merge the substrates without external pressure such as clamps. The bonding performance was tested and a superior bond strength of 14.95 ± 0.77 MPa was achieved when 70% acetic acid was used. Over a long period, the assembled PMMA device with microchannels did not show any leakage. PMMA microdevices were also built as a serpentine 2D passive micromixer and cell culture platform to demonstrate their applicability. The results demonstrated that the bonding scheme allows for the easy assembly of PMMAs with a low risk of clogging and is highly biocompatible. This method provides for a simple but robust assembly of PMMA microdevices in a short time without requiring expensive instruments. Full article
(This article belongs to the Special Issue Device-on-Chip Application in Biomedical Engineering)
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Review
Improving Biosensors by the Use of Different Nanomaterials: Case Study with Microcystins as Target Analytes
Biosensors 2021, 11(12), 525; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120525 - 20 Dec 2021
Viewed by 395
Abstract
The eutrophication of lakes and rivers without adequate rainfall leads to excessive growth of cyanobacterial harmful algal blooms (CyanoHABs) that produce toxicants, green tides, and unpleasant odors. The rapid growth of CyanoHABs owing to global warming, climate change, and the development of rainforests [...] Read more.
The eutrophication of lakes and rivers without adequate rainfall leads to excessive growth of cyanobacterial harmful algal blooms (CyanoHABs) that produce toxicants, green tides, and unpleasant odors. The rapid growth of CyanoHABs owing to global warming, climate change, and the development of rainforests and dams without considering the environmental concern towards lakes and rivers is a serious issue. Humans and livestock consuming the toxicant-contaminated water that originated from CyanoHABs suffer severe health problems. Among the various toxicants produced by CyanoHABs, microcystins (MCs) are the most harmful. Excess accumulation of MC within living organisms can result in liver failure and hepatocirrhosis, eventually leading to death. Therefore, it is essential to precisely detect MCs in water samples. To date, the liquid chromatography–mass spectrometry (LC–MS) and enzyme-linked immunosorbent assay (ELISA) have been the standard methods for the detection of MC and provide precise results with high reliability. However, these methods require heavy instruments and complicated operation steps that could hamper the portability and field-readiness of the detection system. Therefore, in order for this goal to be achieved, the biosensor has been attracted to a powerful alternative for MC detection. Thus far, several types of MC biosensor have been proposed to detect MC in freshwater sample. The introduction of material is a useful option in order to improve the biosensor performance and construct new types of biosensors. Introducing nanomaterials to the biosensor interface provides new phenomena or enhances the sensitivity. In recent times, different types of nanomaterials, such as metallic, carbon-based, and transition metal dichalcogenide-based nanomaterials, have been developed and used to fabricate biosensors for MC detection. This study reviews the recent advancements in different nanomaterial-based MC biosensors. Full article
(This article belongs to the Special Issue Nano/Micro Biosensor for Biomedical Applications)
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Article
Covalent Immobilization of Antibodies through Tetrazine-TCO Reaction to Improve Sensitivity of ELISA Technique
Biosensors 2021, 11(12), 524; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120524 - 20 Dec 2021
Viewed by 330
Abstract
Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility of decreasing their mortality rate. Several methods have been carried out to improve the ELISA sensitivity through antibodies [...] Read more.
Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility of decreasing their mortality rate. Several methods have been carried out to improve the ELISA sensitivity through antibodies immobilization on the microtiter plates. Here, we have developed a strategy of antibodies immobilization to improve the ELISA sensitivity increasing the antibody density surface through the tetrazine (Tz)-trans-cyclooctene (TCO) reaction. For this, we prepared surfaces with tetrazine groups while the captured antibody was conjugated with TCO. The tetrazine surfaces were prepared in two different ways: (1) from aminated plates and (2) from Tz-BSA-coated plates. The surfaces were evaluated using two sandwich ELISA models, one of them using the low-affinity antibody anti-c-myc as a capture antibody to detect the c-myc-GST-IL8h recombinant protein, and the other one to detect the carcinoembryonic human protein (CEA). The sensitivity increased in both surfaces treated with tetrazine in comparison with the standard unmodified surface. The c-myc-GST-IL8h detection was around 10-fold more sensible on both tetrazine surfaces, while CEA ELISA detection increased 12-fold on surfaces coated with Tz-BSA. In conclusion, we show that it is possible to improve the ELISA sensitivity using this immobilization system, where capture antibodies bond covalently to surfaces. Full article
(This article belongs to the Section Biosensors and Healthcare)
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Article
Rapid and Highly Sensitive Detection of C-Reaction Protein Using Robust Self-Compensated Guided-Mode Resonance BioSensing System for Point-of-Care Applications
Biosensors 2021, 11(12), 523; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120523 - 20 Dec 2021
Viewed by 496
Abstract
The rapid and sensitive detection of human C-reactive protein (CRP) in a point-of-care (POC) may be conducive to the early diagnosis of various diseases. Biosensors have emerged as a new technology for rapid and accurate detection of CRP for POC applications. Here, we [...] Read more.
The rapid and sensitive detection of human C-reactive protein (CRP) in a point-of-care (POC) may be conducive to the early diagnosis of various diseases. Biosensors have emerged as a new technology for rapid and accurate detection of CRP for POC applications. Here, we propose a rapid and highly stable guided-mode resonance (GMR) optofluidic biosensing system based on intensity detection with self-compensation, which substantially reduces the instability caused by environmental factors for a long detection time. In addition, a low-cost LED serving as the light source and a photodetector are used for intensity detection and real-time biosensing, and the system compactness facilitates POC applications. Self-compensation relies on a polarizing beam splitter to separate the transverse-magnetic-polarized light and transverse-electric-polarized light from the light source. The transverse-electric-polarized light is used as a background signal for compensating noise, while the transverse-magnetic-polarized light is used as the light source for the GMR biosensor. After compensation, noise is drastically reduced, and both the stability and performance of the system are enhanced over a long period. Refractive index experiments revealed a resolution improvement by 181% when using the proposed system with compensation. In addition, the system was successfully applied to CRP detection, and an outstanding limit of detection of 1.95 × 10−8 g/mL was achieved, validating the proposed measurement system for biochemical reaction detection. The proposed GMR biosensing sensing system can provide a low-cost, compact, rapid, sensitive, and highly stable solution for a variety of point-of-care applications. Full article
(This article belongs to the Special Issue Plasmonic Waveguide Biosensors)
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Article
AI-Enabled, Ultrasound-Guided Handheld Robotic Device for Femoral Vascular Access
Biosensors 2021, 11(12), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120522 (registering DOI) - 18 Dec 2021
Viewed by 682
Abstract
Hemorrhage is a leading cause of trauma death, particularly in prehospital environments when evacuation is delayed. Obtaining central vascular access to a deep artery or vein is important for administration of emergency drugs and analgesics, and rapid replacement of blood volume, as well [...] Read more.
Hemorrhage is a leading cause of trauma death, particularly in prehospital environments when evacuation is delayed. Obtaining central vascular access to a deep artery or vein is important for administration of emergency drugs and analgesics, and rapid replacement of blood volume, as well as invasive sensing and emerging life-saving interventions. However, central access is normally performed by highly experienced critical care physicians in a hospital setting. We developed a handheld AI-enabled interventional device, AI-GUIDE (Artificial Intelligence Guided Ultrasound Interventional Device), capable of directing users with no ultrasound or interventional expertise to catheterize a deep blood vessel, with an initial focus on the femoral vein. AI-GUIDE integrates with widely available commercial portable ultrasound systems and guides a user in ultrasound probe localization, venous puncture-point localization, and needle insertion. The system performs vascular puncture robotically and incorporates a preloaded guidewire to facilitate the Seldinger technique of catheter insertion. Results from tissue-mimicking phantom and porcine studies under normotensive and hypotensive conditions provide evidence of the technique’s robustness, with key performance metrics in a live porcine model including: a mean time to acquire femoral vein insertion point of 53 ± 36 s (5 users with varying experience, in 20 trials), a total time to insert catheter of 80 ± 30 s (1 user, in 6 trials), and a mean number of 1.1 (normotensive, 39 trials) and 1.3 (hypotensive, 55 trials) needle insertion attempts (1 user). These performance metrics in a porcine model are consistent with those for experienced medical providers performing central vascular access on humans in a hospital. Full article
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Article
Enabling Continuous Wearable Reflectance Pulse Oximetry at the Sternum
Biosensors 2021, 11(12), 521; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120521 (registering DOI) - 17 Dec 2021
Viewed by 501
Abstract
In light of the recent Coronavirus disease (COVID-19) pandemic, peripheral oxygen saturation (SpO2) has shown to be amongst the vital signs most indicative of deterioration in persons with COVID-19. To allow for the continuous monitoring of SpO2, we attempted [...] Read more.
In light of the recent Coronavirus disease (COVID-19) pandemic, peripheral oxygen saturation (SpO2) has shown to be amongst the vital signs most indicative of deterioration in persons with COVID-19. To allow for the continuous monitoring of SpO2, we attempted to demonstrate accurate SpO2 estimation using our custom chest-based wearable patch biosensor, capable of measuring electrocardiogram (ECG) and photoplethysmogram (PPG) signals with high fidelity. Through a breath-hold protocol, we collected physiological data with a wide dynamic range of SpO2 from 20 subjects. The ratio of ratios (R) used in pulse oximetry to estimate SpO2 was robustly extracted from the red and infrared PPG signals during the breath-hold segments using novel feature extraction and PPGgreen-based outlier rejection algorithms. Through subject independent training, we achieved a low root-mean-square error (RMSE) of 2.64 ± 1.14% and a Pearson correlation coefficient (PCC) of 0.89. With subject-specific calibration, we further reduced the RMSE to 2.27 ± 0.76% and increased the PCC to 0.91. In addition, we showed that calibration is more efficiently accomplished by standardizing and focusing on the duration of breath-hold rather than the resulting range in SpO2. The accurate SpO2 estimation provided by our custom biosensor and the algorithms provide research opportunities for a wide range of disease and wellness monitoring applications. Full article
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Article
Real-Time Monitoring of the In Situ Microfluidic Synthesis of Ag Nanoparticles on Solid Substrate for Reliable SERS Detection
Biosensors 2021, 11(12), 520; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120520 - 16 Dec 2021
Viewed by 417
Abstract
A sharpened control over the parameters affecting the synthesis of plasmonic nanostructures is often crucial for their application in biosensing, which, if based on surface-enhanced Raman spectroscopy (SERS), requires well-defined optical properties of the substrate. In this work, a method for the microfluidic [...] Read more.
A sharpened control over the parameters affecting the synthesis of plasmonic nanostructures is often crucial for their application in biosensing, which, if based on surface-enhanced Raman spectroscopy (SERS), requires well-defined optical properties of the substrate. In this work, a method for the microfluidic synthesis of Ag nanoparticles (NPs) on porous silicon (pSi) was developed, focusing on achieving a fine control over the morphological characteristics and spatial distribution of the produced nanostructures to be used as SERS substrates. To this end, a pSi membrane was integrated in a microfluidic chamber in which the silver precursor solution was injected, allowing for the real-time monitoring of the reaction by UV–Vis spectroscopy. The synthesis parameters, such as the concentration of the silver precursor, the temperature, and the flow rate, were varied in order to study their effects on the final silver NPs’ morphology. Variations in the flow rate affected the size distribution of the NPs, whereas both the temperature and the concentration of the silver precursor strongly influenced the rate of the reaction and the particle size. Consistently with the described trends, SERS tests using 4-MBA as a probe showed how the flow rate variation affected the SERS enhancement uniformity, and how the production of larger NPs, as a result of an increase in temperature or of the concentration of the Ag precursor, led to an increased SERS efficiency. Full article
(This article belongs to the Special Issue Surface Enhanced Raman Spectroscopy Based Sensors and Biosensors)
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Article
Development, Optimization, Characterization, and Application of Electrochemical Biosensors for Detecting Nickel Ions in Food
Biosensors 2021, 11(12), 519; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120519 - 16 Dec 2021
Viewed by 455
Abstract
Nickel is naturally present in drinking water and many dietary items, which expose the general population to nickel ingestion. This heavy metal can have a variety of harmful health effects, causing allergies and skin disorders (i.e., dermatitis), lung, cardiovascular, and kidney diseases, and [...] Read more.
Nickel is naturally present in drinking water and many dietary items, which expose the general population to nickel ingestion. This heavy metal can have a variety of harmful health effects, causing allergies and skin disorders (i.e., dermatitis), lung, cardiovascular, and kidney diseases, and even certain cancers; therefore, nickel detection is important for public health. Recent innovations in the development of biosensors have demonstrated they offer a powerful new approach over conventional analytical techniques for the identification and quantification of user-defined compounds, including heavy metals such as nickel. We optimized five candidate nickel-biosensing receptors, and tested each for efficiency of binding to immobilization elements on screen-printed electrodes (SPEs). We characterized the application of nickel-detecting biosensors with four different cultivated vegetables. We analyzed the efficiency of each nickel-detecting biosensor by potentiostat and atomic absorption spectrometry and compared the results from the sample analytes. We then analyzed the performance characteristics and responses of assembled biosensors, and show they are very effective at measuring nickel ions in food, especially with the urease-alginate biosensor affixed to silver SPEs, measured by cyclic voltammetry (sensitivity—2.1921 µA Mm−1 cm−2 and LOD—0.005 mg/L). Given the many advantages of biosensors, we describe an optimization pipeline approach to the application of different nickel-binding biosensors for public health, nutrition, and consumer safety, which are very promising. Full article
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Review
Exosomes as Powerful Engines in Cancer: Isolation, Characterization and Detection Techniques
Biosensors 2021, 11(12), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120518 - 16 Dec 2021
Viewed by 556
Abstract
Exosomes, powerful extracellular nanovesicles released from almost all types of living cells, are considered the communication engines (messengers) that control and reprogram physiological pathways inside target cells within a community or between different communities. The cell-like structure of these extracellular vesicles provides a [...] Read more.
Exosomes, powerful extracellular nanovesicles released from almost all types of living cells, are considered the communication engines (messengers) that control and reprogram physiological pathways inside target cells within a community or between different communities. The cell-like structure of these extracellular vesicles provides a protective environment for their proteins and DNA/RNA cargos, which serve as biomarkers for many malicious diseases, including infectious diseases and cancers. Cancer-derived exosomes control cancer metastasis, prognosis, and development. In addition to the unique structure of exosomes, their nanometer size and tendency of interacting with cells makes them a viable novel drug delivery solution. In recent years, numerous research efforts have been made to quantify and characterize disease-derived exosomes for diagnosis, monitoring, and therapeutic purposes. This review aims to (1) relate exosome biomarkers to their origins, (2) focus on current isolation and detection methods, (3) discuss and evaluate the proposed technologies deriving from exosome research for cancer treatment, and (4) form a conclusion about the prospects of the current exosome research. Full article
(This article belongs to the Special Issue Fluorescent and Luminescent Biosensors: Development and Applications)
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Article
Bacterial Lighthouses—Real-Time Detection of Yersinia enterocolitica by Quorum Sensing
Biosensors 2021, 11(12), 517; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120517 - 16 Dec 2021
Viewed by 450
Abstract
Foodborne zoonotic pathogens have a severe impact on food safety. The demand for animal-based food products (meat, milk, and eggs) is increasing, and therefore faster methods are necessary to detect infected animals or contaminated food before products enter the market. However, conventional detection [...] Read more.
Foodborne zoonotic pathogens have a severe impact on food safety. The demand for animal-based food products (meat, milk, and eggs) is increasing, and therefore faster methods are necessary to detect infected animals or contaminated food before products enter the market. However, conventional detection is based on time-consuming microbial cultivation methods. Here, the establishment of a quorum sensing-based method for detection of foodborne pathogens as Yersinia enterocolitica in a co-cultivation approach using a bacterial biosensor carrying a special sensor plasmid is described. We combined selective enrichment with the simultaneous detection of pathogens by recording autoinducer-1-induced bioluminescent response of the biosensor. This new approach enables real-time detection with a calculated sensitivity of one initial cell in a sample after 15.3 h of co-cultivation, while higher levels of initial contamination can be detected within less than half of the time. Our new method is substantially faster than conventional microbial cultivation and should be transferrable to other zoonotic foodborne pathogens. As we could demonstrate, quorum sensing is a promising platform for the development of sensitive assays in the area of food quality, safety, and hygiene. Full article
(This article belongs to the Special Issue Bioassays and Biosensors for Rapid Detection and Analysis)
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Article
On-Site Biolayer Interferometry-Based Biosensing of Carbamazepine in Whole Blood of Epileptic Patients
Biosensors 2021, 11(12), 516; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120516 - 15 Dec 2021
Viewed by 443
Abstract
On-site monitoring of carbamazepine (CBZ) that allows rapid, sensitive, automatic, and high-throughput detection directly from whole blood is of urgent demand in current clinical practice for precision medicine. Herein, we developed two types (being indirect vs. direct) of fiber-optic biolayer interferometry (FO-BLI) biosensors [...] Read more.
On-site monitoring of carbamazepine (CBZ) that allows rapid, sensitive, automatic, and high-throughput detection directly from whole blood is of urgent demand in current clinical practice for precision medicine. Herein, we developed two types (being indirect vs. direct) of fiber-optic biolayer interferometry (FO-BLI) biosensors for on-site CBZ monitoring. The indirect FO-BLI biosensor preincubated samples with monoclonal antibodies towards CBZ (MA-CBZ), and the mixture competes with immobilized CBZ to bind towards MA-CBZ. The direct FO-BLI biosensor used sample CBZ and CBZ-horseradish peroxidase (CBZ-HRP) conjugate to directly compete for binding with immobilized MA-CBZ, followed by a metal precipitate 3,3′-diaminobenzidine to amplify the signals. Indirect FO-BLI detected CBZ within its therapeutic range and was regenerated up to 12 times with negligible baseline drift, but reported results in 25 min. However, Direct FO-BLI achieved CBZ detection in approximately 7.5 min, down to as low as 10 ng/mL, with good accuracy, specificity and negligible matric interference using a high-salt buffer. Validation of Direct FO-BLI using six paired sera and whole blood from epileptic patients showed excellent agreement with ultra-performance liquid chromatography. Being automated and able to achieve high throughput, Direct FO-BLI proved itself to be more effective for integration into the clinic by delivering CBZ values from whole blood within minutes. Full article
(This article belongs to the Special Issue Recent Progress of Optical Fiber Based Biosensors)
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Article
Resonance Energy Transfer to Track the Motion of Lanthanide Ions—What Drives the Intermixing in Core-Shell Upconverting Nanoparticles?
Biosensors 2021, 11(12), 515; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120515 - 14 Dec 2021
Viewed by 549
Abstract
The imagination of clearly separated core-shell structures is already outdated by the fact, that the nanoparticle core-shell structures remain in terms of efficiency behind their respective bulk material due to intermixing between core and shell dopant ions. In order to optimize the photoluminescence [...] Read more.
The imagination of clearly separated core-shell structures is already outdated by the fact, that the nanoparticle core-shell structures remain in terms of efficiency behind their respective bulk material due to intermixing between core and shell dopant ions. In order to optimize the photoluminescence of core-shell UCNP the intermixing should be as small as possible and therefore, key parameters of this process need to be identified. In the present work the Ln(III) ion migration in the host lattices NaYF4 and NaGdF4 was monitored. These investigations have been performed by laser spectroscopy with help of lanthanide resonance energy transfer (LRET) between Eu(III) as donor and Pr(III) or Nd(III) as acceptor. The LRET is evaluated based on the Förster theory. The findings corroborate the literature and point out the migration of ions in the host lattices. Based on the introduced LRET model, the acceptor concentration in the surrounding of one donor depends clearly on the design of the applied core-shell-shell nanoparticles. In general, thinner intermediate insulating shells lead to higher acceptor concentration, stronger quenching of the Eu(III) donor and subsequently stronger sensitization of the Pr(III) or the Nd(III) acceptors. The choice of the host lattice as well as of the synthesis temperature are parameters to be considered for the intermixing process. Full article
(This article belongs to the Special Issue Nanobiosensors Based on Energy Transfer)
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Article
Effect of Al2O3 Passive Layer on Stability and Doping of MoS2 Field-Effect Transistor (FET) Biosensors
Biosensors 2021, 11(12), 514; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120514 - 13 Dec 2021
Viewed by 454
Abstract
Molybdenum disulfide (MoS2) features a band gap of 1.3 eV (indirect) to 1.9 eV (direct). This tunable band gap renders MoS2 a suitable conducting channel for field-effect transistors (FETs). In addition, the highly sensitive surface potential in MoS2 layers [...] Read more.
Molybdenum disulfide (MoS2) features a band gap of 1.3 eV (indirect) to 1.9 eV (direct). This tunable band gap renders MoS2 a suitable conducting channel for field-effect transistors (FETs). In addition, the highly sensitive surface potential in MoS2 layers allows the feasibility of FET applications in biosensors, where direct immobilization and detection of biological molecules are conducted in wet conditions. In this work, we report, for the first time, the degradation of chemical vapor deposition (CVD) grown MoS2 FET-based sensors in the presence of phosphate buffer and water, which caused false positive response in detection. We conclude the degradation was originated by physical delamination of MoS2 thin films from the SiO2 substrate. The problem was alleviated by coating the sensors with a 30 nm thick aluminum oxide (Al2O3) layer using atomic layer deposition technique (ALD). This passive oxide thin film not only acted as a protecting layer against the device degradation but also induced a strong n-doping onto MoS2, which permitted a facile method of detection in MoS2 FET-based sensors using a low-power mode chemiresistive I-V measurement at zero gate voltage (Vgate = 0 V). Additionally, the oxide layer provided available sites for facile functionalization with bioreceptors. As immunoreaction plays a key role in clinical diagnosis and environmental analysis, our work presented a promising application using such enhanced Al2O3-coated MoS2 chemiresistive biosensors for detection of HIgG with high sensitivity and selectivity. The biosensor was successfully applied to detect HIgG in artificial urine, a complex matrix containing organics and salts. Full article
(This article belongs to the Special Issue Electrochemistry and Spectroscopy-Based Biosensors)
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Article
Monoclonal Antibody-Based Immunosensor for the Electrochemical Detection of Chlortoluron Herbicide in Groundwaters
Biosensors 2021, 11(12), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120513 - 13 Dec 2021
Viewed by 420
Abstract
Chlortoluron (3-(3-chloro-p-tolyl)-1,1-dimethyl urea) is an herbicide widely used in substitution to isoproturon to control grass weed in wheat and barley crops. Chlortoluron has been detected in groundwaters for more than 20 years; and dramatic increases in concentrations are observed after intense rain outbreaks. [...] Read more.
Chlortoluron (3-(3-chloro-p-tolyl)-1,1-dimethyl urea) is an herbicide widely used in substitution to isoproturon to control grass weed in wheat and barley crops. Chlortoluron has been detected in groundwaters for more than 20 years; and dramatic increases in concentrations are observed after intense rain outbreaks. In this context; we developed an immunosensor for the determination of chlortoluron based on competitive binding of specific monoclonal antibodies on chlortoluron and immobilized biotinylated chlortoluron; followed by electrochemical detection on screen-printed carbon electrodes. The optimized immunosensor exhibited a logarithmic response in the range 0.01–10 µg·L−1; with a calculated detection limit (LOD) of 22.4 ng·L−1; which is below the maximum levels allowed by the legislation (0.1 µg·L−1). The immunosensor was used for the determination of chlortoluron in natural groundwaters, showing the absence of matrix effects. Full article
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Review
Raman Scattering-Based Biosensing: New Prospects and Opportunities
Biosensors 2021, 11(12), 512; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120512 - 13 Dec 2021
Viewed by 640
Abstract
The growing interest in the development of new platforms for the application of Raman spectroscopy techniques in biosensor technologies is driven by the potential of these techniques in identifying chemical compounds, as well as structural and functional features of biomolecules. The effect of [...] Read more.
The growing interest in the development of new platforms for the application of Raman spectroscopy techniques in biosensor technologies is driven by the potential of these techniques in identifying chemical compounds, as well as structural and functional features of biomolecules. The effect of Raman scattering is a result of inelastic light scattering processes, which lead to the emission of scattered light with a different frequency associated with molecular vibrations of the identified molecule. Spontaneous Raman scattering is usually weak, resulting in complexities with the separation of weak inelastically scattered light and intense Rayleigh scattering. These limitations have led to the development of various techniques for enhancing Raman scattering, including resonance Raman spectroscopy (RRS) and nonlinear Raman spectroscopy (coherent anti-Stokes Raman spectroscopy and stimulated Raman spectroscopy). Furthermore, the discovery of the phenomenon of enhanced Raman scattering near metallic nanostructures gave impetus to the development of the surface-enhanced Raman spectroscopy (SERS) as well as its combination with resonance Raman spectroscopy and nonlinear Raman spectroscopic techniques. The combination of nonlinear and resonant optical effects with metal substrates or nanoparticles can be used to increase speed, spatial resolution, and signal amplification in Raman spectroscopy, making these techniques promising for the analysis and characterization of biological samples. This review provides the main provisions of the listed Raman techniques and the advantages and limitations present when applied to life sciences research. The recent advances in SERS and SERS-combined techniques are summarized, such as SERRS, SE-CARS, and SE-SRS for bioimaging and the biosensing of molecules, which form the basis for potential future applications of these techniques in biosensor technology. In addition, an overview is given of the main tools for success in the development of biosensors based on Raman spectroscopy techniques, which can be achieved by choosing one or a combination of the following approaches: (i) fabrication of a reproducible SERS substrate, (ii) synthesis of the SERS nanotag, and (iii) implementation of new platforms for on-site testing. Full article
(This article belongs to the Special Issue Surface Enhanced Raman Spectroscopy Based Sensors and Biosensors)
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Article
One-Step Fabrication of Stimuli-Responsive Chitosan-Platinum Brushes for Listeria monocytogenes Detection
Biosensors 2021, 11(12), 511; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120511 - 13 Dec 2021
Viewed by 438
Abstract
Bacterial contamination in food-processing facilities is a critical issue that leads to outbreaks compromising the integrity of the food supply and public health. We developed a label-free and rapid electrochemical biosensor for Listeria monocytogenes detection using a new one-step simultaneous sonoelectrodeposition of platinum [...] Read more.
Bacterial contamination in food-processing facilities is a critical issue that leads to outbreaks compromising the integrity of the food supply and public health. We developed a label-free and rapid electrochemical biosensor for Listeria monocytogenes detection using a new one-step simultaneous sonoelectrodeposition of platinum and chitosan (CHI/Pt) to create a biomimetic nanostructure that actuates under pH changes. The XPS analysis shows the effective co-deposition of chitosan and platinum on the electrode surface. This deposition was optimized to enhance the electroactive surface area by 11 times compared with a bare platinum–iridium electrode (p < 0.05). Electrochemical behavior during chitosan actuation (pH-stimulated osmotic swelling) was characterized with three different redox probes (positive, neutral, and negative charge) above and below the isoelectric point of chitosan. These results showed that using a negatively charged redox probe led to the highest electroactive surface area, corroborating previous studies of stimulus–response polymers on metal electrodes. Following this material characterization, CHI/Pt brushes were functionalized with aptamers selective for L. monocytogenes capture. These aptasensors were functional at concentrations up to 106 CFU/mL with no preconcentration nor extraneous reagent addition. Selectivity was assessed in the presence of other Gram-positive bacteria (Staphylococcus aureus) and with a food product (chicken broth). Actuation led to improved L. monocytogenes detection with a low limit of detection (33 CFU/10 mL in chicken broth). The aptasensor developed herein offers a simple fabrication procedure with only one-step deposition followed by functionalization and rapid L. monocytogenes detection, with 15 min bacteria capture and 2 min sensing. Full article
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Article
Lateral Flow Immunoassay of SARS-CoV-2 Antigen with SERS-Based Registration: Development and Comparison with Traditional Immunoassays
Biosensors 2021, 11(12), 510; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120510 - 10 Dec 2021
Viewed by 551
Abstract
The current COVID-19 pandemic has increased the demand for pathogen detection methods that combine low detection limits with rapid results. Despite the significant progress in methods and devices for nucleic acid amplification, immunochemical methods are still preferred for mass testing without specialized laboratories [...] Read more.
The current COVID-19 pandemic has increased the demand for pathogen detection methods that combine low detection limits with rapid results. Despite the significant progress in methods and devices for nucleic acid amplification, immunochemical methods are still preferred for mass testing without specialized laboratories and highly qualified personnel. The most widely used immunoassays are microplate enzyme-linked immunosorbent assay (ELISA) with photometric detection and lateral flow immunoassay (LFIA) with visual results assessment. However, the disadvantage of ELISA is its considerable duration, and that of LFIA is its low sensitivity. In this study, the modified LFIA of a specific antigen of the causative agent of COVID-19, spike receptor-binding domain, was developed and characterized. This modified LFIA includes the use of gold nanoparticles with immobilized antibodies and 4-mercaptobenzoic acid as surface-enhanced Raman scattering (SERS) nanotag and registration of the nanotag binding by SERS spectrometry. To enhance the sensitivity of LFIA-SERS analysis, we determined the optimal compositions of SERS nanotags and membranes used in LFIA. For benchmark comparison, ELISA and conventional colorimetric LFIA were used with the same immune reagents. The proposed method combines a low detection limit of 0.1 ng/mL (at 0.4 ng/mL for ELISA and 1 ng/mL for qualitative LFIA) with a short assay time equal to 20 min (at 3.5 h for ELISA and 15 min for LFIA). The results obtained demonstrate the promise of using the SERS effects in membrane immuno-analytical systems. Full article
(This article belongs to the Special Issue Fundamentals of SARS-CoV-2 Biosensors)
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Article
A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array
Biosensors 2021, 11(12), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120509 - 10 Dec 2021
Viewed by 603
Abstract
Incorporation of extracellular matrix (ECM) and hydrogel in microfluidic 3D cell culture platforms is important to create a physiological microenvironment for cell morphogenesis and to establish 3D co-culture models by hydrogel compartmentalization. Here, we describe a simple and scalable ECM patterning method for [...] Read more.
Incorporation of extracellular matrix (ECM) and hydrogel in microfluidic 3D cell culture platforms is important to create a physiological microenvironment for cell morphogenesis and to establish 3D co-culture models by hydrogel compartmentalization. Here, we describe a simple and scalable ECM patterning method for microfluidic cell cultures by achieving hydrogel confinement due to the geometrical expansion of channel heights (stepped height features) and capillary burst valve (CBV) effects. We first demonstrate a sequential “pillar-free” hydrogel patterning to form adjacent hydrogel lanes in enclosed microfluidic devices, which can be further multiplexed with one to two stepped height features. Next, we developed a novel “spheroid-in-gel” culture device that integrates (1) an on-chip hanging drop spheroid culture and (2) a single “press-on” hydrogel confinement step for rapid ECM patterning in an open-channel microarray format. The initial formation of breast cancer (MCF-7) spheroids was achieved by hanging a drop culture on a patterned polydimethylsiloxane (PDMS) substrate. Single spheroids were then directly encapsulated on-chip in individual hydrogel islands at the same positions, thus, eliminating any manual spheroid handling and transferring steps. As a proof-of-concept to perform a spheroid co-culture, endothelial cell layer (HUVEC) was formed surrounding the spheroid-containing ECM region for drug testing studies. Overall, this developed stepped height-based hydrogel patterning method is simple to use in either enclosed microchannels or open surfaces and can be readily adapted for in-gel cultures of larger 3D cellular spheroids or microtissues. Full article
(This article belongs to the Special Issue Bioinspired and Biobased Materials for Biosensor Applications)
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Article
Permittivity-Inspired Microwave Resonator-Based Biosensor Based on Integrated Passive Device Technology for Glucose Identification
Biosensors 2021, 11(12), 508; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120508 - 09 Dec 2021
Cited by 1 | Viewed by 567
Abstract
In this study, we propose a high-performance resonator-based biosensor for mediator-free glucose identification. The biosensor is characterized by an air-bridge capacitor and fabricated via integrated passive device technology on gallium arsenide (GaAs) substrate. The exterior design of the structure is a spiral inductor [...] Read more.
In this study, we propose a high-performance resonator-based biosensor for mediator-free glucose identification. The biosensor is characterized by an air-bridge capacitor and fabricated via integrated passive device technology on gallium arsenide (GaAs) substrate. The exterior design of the structure is a spiral inductor with the air-bridge providing a sensitive surface, whereas the internal capacitor improves indicator performance. The sensing relies on repolarization and rearrangement of surface molecules, which are excited by the dropped sample at the microcosmic level, and the resonance performance variation corresponds to the difference in glucose concentration at the macroscopic level. The air-bridge capacitor in the modeled RLC circuit serves as a bio-recognition element to glucose concentration (εglucoseC0), generating resonant frequency shifts at 0.874 GHz and 1.244 GHz for concentrations of 25 mg/dL and 300 mg/dL compared to DI water, respectively. The proposed biosensor exhibits excellent sensitivity at 1.38 MHz per mg/dL with a wide detection range for glucose concentrations of 25–300 mg/dL and a low detection limit of 24.59 mg/dL. Additionally, the frequency shift and concentration are highly linear with a coefficient of determination of 0.98823. The response time is less than 3 s. We performed multiple experiments to verify that the surface morphology reveals no deterioration and chemical binding, thus validating the reusability and reliability of the proposed biosensor. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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Article
A Dual Electrode Biosensor for Glucose and Lactate Measurement in Normal and Prolonged Obese Mice Using Single Drop of Whole Blood
Biosensors 2021, 11(12), 507; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120507 - 09 Dec 2021
Viewed by 471
Abstract
Understanding the levels of glucose (G) and lactate (L) in blood can help us regulate various chronic health conditions such as obesity. In this paper, we introduced an enzyme-based electrochemical biosensor adopting glucose oxidase and lactate oxidase on two working screen-printed carbon electrodes [...] Read more.
Understanding the levels of glucose (G) and lactate (L) in blood can help us regulate various chronic health conditions such as obesity. In this paper, we introduced an enzyme-based electrochemical biosensor adopting glucose oxidase and lactate oxidase on two working screen-printed carbon electrodes (SPCEs) to sequentially determine glucose and lactate concentrations in a single drop (~30 µL) of whole blood. We developed a diet-induced obesity (DIO) mouse model for 28 weeks and monitored the changes in blood glucose and lactate levels. A linear calibration curve for glucose and lactate concentrations in ranges from 0.5 to 35 mM and 0.5 to 25 mM was obtained with R-values of 0.99 and 0.97, respectively. A drastic increase in blood glucose and a small but significant increase in blood lactate were seen only in prolonged obese cases. The ratio of lactate concentration to glucose concentration (L/G) was calculated as the mouse’s gained weight. The results demonstrated that an L/G value of 0.59 could be used as a criterion to differentiate between normal and obesity conditions. With L/G and weight gain, we constructed a diagnostic plot that could categorize normal and obese health conditions into four different zones. The proposed dual electrode biosensor for glucose and lactate in mouse whole blood showed good stability, selectivity, sensitivity, and efficiency. Thus, we believe that this dual electrode biosensor and the diagnostic plot could be used as a sensitive analytical tool for diagnosing glucose and lactate biomarkers in clinics and for monitoring obesity. Full article
(This article belongs to the Special Issue Electrochemical Biosensors for Biomedical Applications)
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Article
Construction of a Fibroblast-Associated Tumor Spheroid Model Based on a Collagen Drop Array Chip
Biosensors 2021, 11(12), 506; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120506 - 09 Dec 2021
Viewed by 520
Abstract
Spheroid, a 3D aggregate of tumor cells in a spherical shape, has overcome the limitations of conventional 3D cell models to accurately mimic the in-vivo environment of a human body. The spheroids are cultured with other primary cells and embedded in collagen drops [...] Read more.
Spheroid, a 3D aggregate of tumor cells in a spherical shape, has overcome the limitations of conventional 3D cell models to accurately mimic the in-vivo environment of a human body. The spheroids are cultured with other primary cells and embedded in collagen drops using hang drop plates and low-attachment well plates to construct a spheroid–hydrogel model that better mimics the cell–cell and cell–extracellular matrix (ECM) interactions. However, the conventional methods of culturing and embedding spheroids into ECM have several shortcomings. The procedure of transferring a single spheroid at a time by manual pipetting results in well-to-well variation and even loss or damage of the spheroid. Based on the previously introduced droplet contact-based spheroid transfer technique, we present a poly(dimethylsiloxane) and resin-based drop array chip and a pillar array chip with alignment stoppers, which enhances the alignment between the chips for uniform placement of spheroids. This method allows the facile and stable transfer of the spheroid array and even eliminates the need for a stereomicroscope while handling the cell models. The novel platform demonstrates a homogeneous and time-efficient construction and diverse analysis of an array of fibroblast-associated glioblastoma multiforme spheroids that are embedded in collagen. Full article
(This article belongs to the Special Issue Biochip Technology: Cell-, Organ-, Body- and Disease-on-a-Chip)
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Review
FRET Ratiometric Nanoprobes for Nanoparticle Monitoring
Biosensors 2021, 11(12), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120505 - 09 Dec 2021
Viewed by 546
Abstract
Fluorescence labelling is often used for tracking nanoparticles, providing a convenient assay for monitoring nanoparticle drug delivery. However, it is difficult to be quantitative, as many factors affect the fluorescence intensity. Förster resonance energy transfer (FRET), taking advantage of the energy transfer from [...] Read more.
Fluorescence labelling is often used for tracking nanoparticles, providing a convenient assay for monitoring nanoparticle drug delivery. However, it is difficult to be quantitative, as many factors affect the fluorescence intensity. Förster resonance energy transfer (FRET), taking advantage of the energy transfer from a donor fluorophore to an acceptor fluorophore, provides a distance ruler to probe NP drug delivery. This article provides a review of different FRET approaches for the ratiometric monitoring of the self-assembly and formation of nanoparticles, their in vivo fate, integrity and drug release. We anticipate that the fundamental understanding gained from these ratiometric studies will offer new insights into the design of new nanoparticles with improved and better-controlled properties. Full article
(This article belongs to the Special Issue Nanomaterial-Based Biosensors for Biomedical Applications)
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Article
Objective Numerical Evaluation of Diffuse, Optically Reconstructed Images Using Structural Similarity Index
Biosensors 2021, 11(12), 504; https://doi.org/10.3390/bios11120504 - 08 Dec 2021
Viewed by 464
Abstract
Diffuse optical tomography is emerging as a non-invasive optical modality used to evaluate tissue information by obtaining the optical properties’ distribution. Two procedures are performed to produce reconstructed absorption and reduced scattering images, which provide structural information that can be used to locate [...] Read more.
Diffuse optical tomography is emerging as a non-invasive optical modality used to evaluate tissue information by obtaining the optical properties’ distribution. Two procedures are performed to produce reconstructed absorption and reduced scattering images, which provide structural information that can be used to locate inclusions within tissues with the assistance of a known light intensity around the boundary. These methods are referred to as a forward problem and an inverse solution. Once the reconstructed image is obtained, a subjective measurement is used as the conventional way to assess the image. Hence, in this study, we developed an algorithm designed to numerically assess reconstructed images to identify inclusions using the structural similarity (SSIM) index. We compared four SSIM algorithms with 168 simulated reconstructed images involving the same inclusion position with different contrast ratios and inclusion sizes. A multiscale, improved SSIM containing a sharpness parameter (MS-ISSIM-S) was proposed to represent the potential evaluation compared with the human visible perception. The results indicated that the proposed MS-ISSIM-S is suitable for human visual perception by demonstrating a reduction of similarity score related to various contrasts with a similar size of inclusion; thus, this metric is promising for the objective numerical assessment of diffuse, optically reconstructed images. Full article
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Article
Multisite Simultaneous Neural Recording of Motor Pathway in Free-Moving Rats
Biosensors 2021, 11(12), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120503 - 08 Dec 2021
Viewed by 548
Abstract
Neural interfaces typically focus on one or two sites in the motoneuron system simultaneously due to the limitation of the recording technique, which restricts the scope of observation and discovery of this system. Herein, we built a system with various electrodes capable of [...] Read more.
Neural interfaces typically focus on one or two sites in the motoneuron system simultaneously due to the limitation of the recording technique, which restricts the scope of observation and discovery of this system. Herein, we built a system with various electrodes capable of recording a large spectrum of electrophysiological signals from the cortex, spinal cord, peripheral nerves, and muscles of freely moving animals. The system integrates adjustable microarrays, floating microarrays, and microwires to a commercial connector and cuff electrode on a wireless transmitter. To illustrate the versatility of the system, we investigated its performance for the behavior of rodents during tethered treadmill walking, untethered wheel running, and open field exploration. The results indicate that the system is stable and applicable for multiple behavior conditions and can provide data to support previously inaccessible research of neural injury, rehabilitation, brain-inspired computing, and fundamental neuroscience. Full article
(This article belongs to the Section Intelligent Biosensors and Bio-Signal Processing)
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Review
Electrochemical Amino Acid Sensing: A Review on Challenges and Achievements
Biosensors 2021, 11(12), 502; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120502 - 07 Dec 2021
Viewed by 518
Abstract
The rapid growth of research in electrochemistry in the last decade has resulted in a significant advancement in exploiting electrochemical strategies for assessing biological substances. Among these, amino acids are of utmost interest due to their key role in human health. Indeed, an [...] Read more.
The rapid growth of research in electrochemistry in the last decade has resulted in a significant advancement in exploiting electrochemical strategies for assessing biological substances. Among these, amino acids are of utmost interest due to their key role in human health. Indeed, an unbalanced amino acid level is the origin of several metabolic and genetic diseases, which has led to a great need for effective and reliable evaluation methods. This review is an effort to summarize and present both challenges and achievements in electrochemical amino acid sensing from the last decade (from 2010 onwards) to show where limitations and advantages stem from. In this review, we place special emphasis on five well-known electroactive amino acids, namely cysteine, tyrosine, tryptophan, methionine and histidine. The recent research and achievements in this area and significant performance metrics of the proposed electrochemical sensors, including the limit of detection, sensitivity, stability, linear dynamic range(s) and applicability in real sample analysis, are summarized and presented in separate sections. More than 400 recent scientific studies were included in this review to portray a rich set of ideas and exemplify the capabilities of the electrochemical strategies to detect these essential biomolecules at trace and even ultra-trace levels. Finally, we discuss, in the last section, the remaining issues and the opportunities to push the boundaries of our knowledge in amino acid electrochemistry even further. Full article
(This article belongs to the Special Issue Feature Issue of Biosensor Materials Section)
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Article
Application of Tamm Plasmon Polaritons and Cavity Modes for Biosensing in the Combined Spectroscopic Ellipsometry and Quartz Crystal Microbalance Method
Biosensors 2021, 11(12), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120501 - 07 Dec 2021
Viewed by 484
Abstract
Low-cost 1D plasmonic photonic structures supporting Tamm plasmon polaritons and cavity modes were employed for optical signal enhancement, modifying the commercially available quartz crystal microbalance with dissipation (QCM-D) sensor chip in a combinatorial spectroscopic ellipsometry and quartz microbalance method. The Tamm plasmon optical [...] Read more.
Low-cost 1D plasmonic photonic structures supporting Tamm plasmon polaritons and cavity modes were employed for optical signal enhancement, modifying the commercially available quartz crystal microbalance with dissipation (QCM-D) sensor chip in a combinatorial spectroscopic ellipsometry and quartz microbalance method. The Tamm plasmon optical state and cavity mode (CM) for the modified mQCM-D sample obtained sensitivity of ellipsometric parameters to RIU of ΨTPP = 126.78 RIU−1 and ΔTPP = 325 RIU−1, and ΨCM = 264 RIU−1 and ΔCM = 645 RIU−1, respectively. This study shows that Tamm plasmon and cavity modes exhibit about 23 and 49 times better performance of ellipsometric parameters, respectively, for refractive index sensing than standard spectroscopic ellipsometry on a QCM-D sensor chip. It should be noted that for the optical biosensing signal readout, the sensitivity of Tamm plasmon polaritons and cavity modes are comparable with and higher than the standard QCM-D sensor chip. The different origin of Tamm plasmon polaritons (TPP) and cavity mode (CM) provides further advances and can determine whether the surface (TPP) or bulk process (CM) is dominating. The dispersion relation feature of TPP, namely the direct excitation without an additional coupler, allows the possibility to enhance the optical signal on the sensing surface. To the best of our knowledge, this is the first study and application of the TPP and CM in the combinatorial SE-QCM-D method for the enhanced readout of ellipsometric parameters. Full article
(This article belongs to the Special Issue Photonic Sensors in Chemical and Biological Applications)
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Review
On Demand Biosensors for Early Diagnosis of Cancer and Immune Checkpoints Blockade Therapy Monitoring from Liquid Biopsy
Biosensors 2021, 11(12), 500; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120500 - 07 Dec 2021
Viewed by 533
Abstract
Recently, considerable interest has emerged in the development of biosensors to detect biomarkers and immune checkpoints to identify and measure cancer through liquid biopsies. The detection of cancer biomarkers from a small volume of blood is relatively fast compared to the gold standard [...] Read more.
Recently, considerable interest has emerged in the development of biosensors to detect biomarkers and immune checkpoints to identify and measure cancer through liquid biopsies. The detection of cancer biomarkers from a small volume of blood is relatively fast compared to the gold standard of tissue biopsies. Traditional immuno-histochemistry (IHC) requires tissue samples obtained using invasive procedures and specific expertise as well as sophisticated instruments. Furthermore, the turnaround for IHC assays is usually several days. To overcome these challenges, on-demand biosensor-based assays were developed to provide more immediate prognostic information for clinicians. Novel rapid, highly precise, and sensitive approaches have been under investigation using physical and biochemical methods to sense biomarkers. Additionally, interest in understanding immune checkpoints has facilitated the rapid detection of cancer prognosis from liquid biopsies. Typically, these devices combine various classes of detectors with digital outputs for the measurement of soluble cancer or immune checkpoint (IC) markers from liquid biopsy samples. These sensor devices have two key advantages: (a) a small volume of blood drawn from the patient is sufficient for analysis, and (b) it could aid physicians in quickly selecting and deciding the appropriate therapy regime for the patients (e.g., immune checkpoint blockade (ICB) therapy). In this review, we will provide updates on potential cancer markers, various biosensors in cancer diagnosis, and the corresponding limits of detection, while focusing on biosensor development for IC marker detection. Full article
(This article belongs to the Special Issue Biomarkers Used for the Diagnosis of Diseases)
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Article
Resting-State EEG Signal for Major Depressive Disorder Detection: A Systematic Validation on a Large and Diverse Dataset
Biosensors 2021, 11(12), 499; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120499 - 06 Dec 2021
Viewed by 853
Abstract
Major depressive disorder (MDD) is a global healthcare issue and one of the leading causes of disability. Machine learning combined with non-invasive electroencephalography (EEG) has recently been shown to have the potential to diagnose MDD. However, most of these studies analyzed small samples [...] Read more.
Major depressive disorder (MDD) is a global healthcare issue and one of the leading causes of disability. Machine learning combined with non-invasive electroencephalography (EEG) has recently been shown to have the potential to diagnose MDD. However, most of these studies analyzed small samples of participants recruited from a single source, raising serious concerns about the generalizability of these results in clinical practice. Thus, it has become critical to re-evaluate the efficacy of various common EEG features for MDD detection across large and diverse datasets. To address this issue, we collected resting-state EEG data from 400 participants across four medical centers and tested classification performance of four common EEG features: band power (BP), coherence, Higuchi’s fractal dimension, and Katz’s fractal dimension. Then, a sequential backward selection (SBS) method was used to determine the optimal subset. To overcome the large data variability due to an increased data size and multi-site EEG recordings, we introduced the conformal kernel (CK) transformation to further improve the MDD as compared with the healthy control (HC) classification performance of support vector machine (SVM). The results show that (1) coherence features account for 98% of the optimal feature subset; (2) the CK-SVM outperforms other classifiers such as K-nearest neighbors (K-NN), linear discriminant analysis (LDA), and SVM; (3) the combination of the optimal feature subset and CK-SVM achieves a high five-fold cross-validation accuracy of 91.07% on the training set (140 MDD and 140 HC) and 84.16% on the independent test set (60 MDD and 60 HC). The current results suggest that the coherence-based connectivity is a more reliable feature for achieving high and generalizable MDD detection performance in real-life clinical practice. Full article
(This article belongs to the Collection Wearable Biosensors for Healthcare Applications)
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Article
Can ECIS Biosensor Technology Be Used to Measure the Cellular Responses of Glioblastoma Stem Cells?
Biosensors 2021, 11(12), 498; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120498 - 06 Dec 2021
Viewed by 527
Abstract
Glioblastoma is considered the most aggressive and lethal form of brain cancer. Glioblastoma tumours are complex, comprising a spectrum of oncogenically transformed cells displaying distinct phenotypes. These can be generated in culture and are called differentiated-glioblastoma cells and glioblastoma stem cells. These cells [...] Read more.
Glioblastoma is considered the most aggressive and lethal form of brain cancer. Glioblastoma tumours are complex, comprising a spectrum of oncogenically transformed cells displaying distinct phenotypes. These can be generated in culture and are called differentiated-glioblastoma cells and glioblastoma stem cells. These cells are phenotypically and functionally distinct, where the stem-like glioblastoma cells give rise to and perpetuate the tumour. Electric cell-substrate impedance sensing (ECIS) is a real-time, label-free, impedance-based method for the analysis of cellular behaviour, based on cellular adhesion. Therefore, we asked the question of whether ECIS was suitable for, and capable of measuring the adhesion of glioblastoma cells. The goal was to identify whether ECIS was capable of measuring glioblastoma cell adhesion, with a particular focus on the glioblastoma stem cells. We reveal that ECIS reliably measures adhesion of the differentiated glioblastoma cells on various array types. We also demonstrate the ability of ECIS to measure the migratory behaviour of differentiated glioblastoma cells onto ECIS electrodes post-ablation. Although the glioblastoma stem cells are adherent, ECIS is substantially less capable at reliably measuring their adhesion, compared with the differentiated counterparts. This means that ECIS has applicability for some glioblastoma cultures but much less utility for weakly adherent stem cell counterparts. Full article
(This article belongs to the Section Biosensor and Bioelectronic Devices)
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