A multiporous nanofiber (MPNFs) of SnO₂ and chitosan has been used for the immobilization of a redox protein, hemoglobin (Hb), onto the surface of glassy carbon electrode (GCE). The multiporous nanofiber of SnO₂ that has very high surface area is synthesized by using electrospinning technique through controlling the tin precursor concentration. Since the constructed MPNFs of SnO₂ exposes very high surface area, it increases the efficiency for biomolecule-loading. The morphology of fabricated electrodes is examined by SEM observation and the absorbance spectra of Hb/(MPNFs) of SnO₂ are studied by UV-Vis analysis. Cyclic Voltammetry and amperometry are employed to study and optimize the performance of the resulting fabricated electrode. After fabrication of the electrode with the Hb and MPNFs of SnO₂, a direct electron transfer between the protein's redox centre and the glassy carbon electrode was established. The modified electrode has showed a couple of redox peak located at -0.29 V and -0.18 V and found to be sensitive to H₂O₂. The fabricated electrode also exhibited an excellent electrocatalytic activity towards the reduction of H₂O₂. The catalysis currents increased linearly to the H₂O₂ concentration in a wide range of 5.0×10-6-1.5×10-4 M. Overall experimental results show that MPNFs of SnO₂ has a role towards the enhancement of the electroactivity of Hb at the electrode surface. Thus the MPNFs of SnO₂ is a very promising candidate for future biosensor applications.
The development of electrical biosensor towards device miniaturization in order to achieve better sensitivity with enhanced electrical signal has certain limitations especially complexity in fabrication process and costs. In this paper, an alternative technique with minor modification in the device structure is presented for signal amplification by implementing ambipolar conduction in the biosensor itself. We demonstrated the field-effect transistor (FET)-based biosensor coupled back-gate for attaining a higher sensitivity with the detection of lower target abundance. To utilize the coupled back-gate as a pre-amplifier, silicon-on-insulator wafer with thicknesses of top-silicon and buried oxide (BOX) layers of 70 nm and 145 nm, respectively were desired. Titanium dioxide (TiO2) nanomaterial was deposited using sol-gel method on the channel which acts as a transducer. Surface functionalization on TiO2 thin film allowed an effective immobilization of anti-cardiac troponin I antibody to interact cardiac troponin I (cTnI). Binding events at each step was validated by X-ray photoelectron spectroscopy (XPS) analysis. Further, electrical characterization (Id-Vd) confirms the potentiality of FET-based biosensor to detect cTnI (represents acute myocardial infarction disease) with the concentration ranges from 10 μg/ml down to 1 fg/ml. The sensitivity of 459.2 nA (g/ml)-1 and lower detection limit of 1 fg/ml were achieved at Vbg = -5 V and Vd = 5 V. The designed device demonstrates its ability to detect lower level of cTnI with pre-amplified electrical signal by back-gate biasing.
This study reports on the development of a novel impedimetric immunosensor design using plant-derived antigenic glycoprotein for the detection of dengue virus (DENV) IgG antibodies. The electrochemical immunosensor platform was constructed using screen-printed carbon electrode (SPCE) modified with graphene/titanium dioxide (G/TiO2) nanocomposite to improve the electrode in terms electrochemical performance and specific surface area. A plant-derived dengue envelope domain III (EDIII) protein was used as the antigenic probe protein in this immunosensing strategy. Under optimised sensing conditions, the immunosensor demonstrated high sensitivity towards DENV IgG in a wide linear working range (62.5-2000 ng/mL), with a limit of detection of 2.81 ng/mL. The immunosensor showed high specificity for discriminating DENV IgG against antibodies of other infectious disease, including the closely related Zika virus (ZIKV). The reliability of the immunosensor in serological diagnosis was verified by challenging the immunosensor against serum samples, compared to conventional enzyme-linked immunosorbent assay (ELISA). As shown by its remarkable performance throughout the study, the devised immunosensor is proposed as a reliable and practical diagnostic tool for the serological detection of dengue in realistic applications.
Multidrug resistant Pseudomonas aeruginosa (P. aeruginosa) is known to be a problematic bacterium for being a major cause of opportunistic and nosocomial infections. In this study, reduced graphene oxide decorated with gold nanoparticles (AuNPs/rGO) was utilized as a new sensing material for a fast and direct electrochemical detection of pyocyanin as a biomarker of P. aeruginosa infections. Under optimal condition, the developed electrochemical pyocyanin sensor exhibited a good linear range for the determination of pyocyanin in phosphate-buffered saline (PBS), human saliva and urine at a clinically relevant concentration range of 1-100 μM, achieving a detection limit of 0.27 μM, 1.34 μM, and 2.3 μM, respectively. Our developed sensor demonstrated good selectivity towards pyocyanin in the presence of interfering molecule such as ascorbic acid, uric acid, NADH, glucose, and acetylsalicylic acid, which are commonly found in human fluids. Furthermore, the developed sensor was able to discriminate the signal with and without the presence of pyocyanin directly in P. aeruginosa culture. This proposed technique demonstrates its potential application in monitoring the presence of P. aeruginosa infection in patients.
Chan Ding training is beneficial to health and emotional wellbeing. More and more people have taken up this practice over the past few years. A major training method of Chan Ding is to focus on the ten Mailuns, i.e., energy points, and to maintain physical stillness. In this article, wireless wearable accelerometers were used to detect physical stillness, and the created physical stillness index (PSI) was also shown. Ninety college students participated in this study. Primarily, accelerometers used on the arms and chest were examined. The results showed that the PSI values on the arms were higher than that of the chest, when participants moved their bodies in three different ways, left-right, anterior-posterior, and hand, movements with natural breathing. Then, they were divided into three groups to practice Chan Ding for approximately thirty minutes. Participants without any Chan Ding experience were in Group I. Participants with one year of Chan Ding experience were in Group II, and participants with over three year of experience were in Group III. The Chinese Happiness Inventory (CHI) was also conducted. Results showed that the PSI of the three groups measured during 20-30 min were 0.123 ± 0.155, 0.012 ± 0.013, and 0.001 ± 0.0003, respectively (p < 0.001 ***). The averaged CHI scores of the three groups were 10.13, 17.17, and 25.53, respectively (p < 0.001 ***). Correlation coefficients between PSI and CHI of the three groups were -0.440, -0.369, and -0.537, respectively (p < 0.01 **). PSI value and the wearable accelerometer that are presently available on the market could be used to evaluate the quality of the physical stillness of the participants during Chan Ding practice.
A real-time ability to interpret the interaction between targeted biomolecules and the surface of semiconductors (metal transducers) into readable electrical signals, without biomolecular modification involving fluorescence dyes, redox enzymes, and radioactive labels, created by label-free biosensors has been extensively researched. Field-effect transistor (FET)- and capacitor-based biosensors are among the diverse electrical charge biosensing architectures that have drawn much attention for having charge transduction; thus, enabling the early and rapid diagnosis of the appropriate cardiac biomarkers at lower concentrations. These semiconducting material-based transducers are very suitable to be integrated with portable electronic devices for future online collection, transmission, reception, analysis, and reporting. This overview elucidates and clarifies two major electrical label-free systems (FET- and capacitor-based biosensors) with cardiac troponin (cTn) biomarker-mediated charge transduction for acute myocardial infarction (AMI) diagnosis. Advances in these systems are highlighted by their progression in bridging the laboratory and industry; the foremost technologies have made the transition from benchtop to bedside and beyond.
Early cancer diagnosis remains the holy-grail in the battle against cancers progression. Tainted with debates and medical challenges, current therapeutic approaches for prostate cancer (PCa) lack early preventive measures, rapid diagnostic capabilities, risk factors identification, and portability, i.e. the inherent attributes offered by the label-free biosensing devices. Electronic assisted immunosensing systems inherit the high sensitivity and specificity properties due to the predilection of the antigen-antibody affinity. Bioelectronic immunosensor for PCa has attracted much attentions among the researchers due to its high-performance, easy to prepare, rapid feedback, and possibility for miniaturization. This review explores the current advances on bioelectronic immunosensors for the detection of PCa biomarker revealed in the past decade. The research milestones and current trends of the immunosensors are reported to project the future visions in order to propel their "lab-to-market" realization.
Deoxynivalenol (DON), a cosmopolitan mycotoxin found in agricultural commodities causes serious health maladies to human and animals when accidently consumed even at a low quantity. It necessitates selective and sensitive devices to analyse DON as the conventional methods are complex and time-consuming. This study is focused on developing a selective biosensing system using iron nanoflorets graphene nickel (INFGN) as the transducer and a specific aptamer as the biorecognition element. 3D-graphene is incorporated using a low-pressure chemical vapour deposition followed by the decoration of iron nanoflorets using electrochemical deposition. INFGN enables a feasible bio-capturing due to its large surface area. The X-ray photoelectron spectroscopy analysis confirms the presence of the hydroxyl groups on the INFGN surface, which acts as the linker. Clear Fourier-transform infrared peak shifts affirm the changes with surface chemical modification and biomolecular assembly. The limit of detection attained is 2.11 pg mL-1 and displays high stability whereby it retains 30.65% of activity after 48 h. The designed INFGN demonstrates remarkable discrimination of DON against similar mycotoxins (zearalenone and ochratoxin A). Overall, the high-performance biosensor shown here is an excellent, simple and cost-effective alternative for detecting DON in food and feed samples.
Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol-ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0-160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined.
Prostate cancer is currently diagnosed using the conventional gold standard methods using prostate-specific antigen (PSA) as the selective biomarker. However, lack of precision in PSA screening has resulted in needless biopsies and delays the treatment of potentially fatal prostate cancer. Thus, identification of glycans as novel biomarkers for the early detection of prostate cancer has attracted considerable attention due to their reliable diagnostic platform compared with the current PSA systems. Therefore, biosensing technologies that provide point-of-care diagnostics have demonstrated the ability to detect various analytes, including glycosylated micro- and macro-molecules, thereby enabling versatile detection methodologies. This highlight article discusses recent advances in the biosensor-based detection of prostate cancer glycan biomarkers and the innovative strategies for the conjugation of nanomaterials adapted to biosensing platforms. Finally, the article is concluded with prospects and challenges of prostate cancer biosensors and recommendations to overcome the issues associated with prostate cancer diagnosis.
The importance of body area sensor networks (BASNs) is increasing day by day because of their increasing use in Internet of things (IoT)-enabled healthcare application services. They help humans in improving their quality of life by continuously monitoring various vital signs through biosensors strategically placed on the human body. However, BASNs face serious challenges, in terms of the short life span of their batteries and unreliable data transmission, because of the highly unstable and unpredictable channel conditions of tiny biosensors located on the human body. These factors may result in poor data gathering quality in BASNs. Therefore, a more reliable data transmission mechanism is greatly needed in order to gather quality data in BASN-based healthcare applications. Therefore, this study proposes a novel, multiobjective, lion mating optimization inspired routing protocol, called self-organizing multiobjective routing protocol (SARP), for BASN-based IoT healthcare applications. The proposed routing scheme significantly reduces local search problems and finds the best dynamic cluster-based routing solutions between the source and destination in BASNs. Thus, it significantly improves the overall packet delivery rate, residual energy, and throughput with reduced latency and packet error rates in BASNs. Extensive simulation results validate the performance of our proposed SARP scheme against the existing routing protocols in terms of the packet delivery ratio, latency, packet error rate, throughput, and energy efficiency for BASN-based health monitoring applications.
Aptamers are a group of synthetic single-stranded nucleic acids. They are generated from a random library of single-stranded DNA or RNA by a technology named systematic evolution of ligands by exponential enrichment (SELEX). SELEX is a repetitive process to select and identify suitable aptamers that show high affinity and specificity towards target cells. Great strides have been achieved in the design, construction, and use of aptamers up to this point. However, only a small number of aptamer-based applications have achieved widespread commercial and clinical acceptance. Additionally, finding more effective ways to acquire aptamers with high affinity remains a challenge. Therefore, it is crucial to thoroughly examine the existing dearth and advancement in aptamer-related technologies. This review focuses on aptamers that are generated by SELEX to detect pathogenic microorganisms and mammalian cells, as well as in cell-internalizing SELEX for diagnostic and therapeutic purposes. The development of novel aptamer-based biosensors using optical and electrical methods for microbial detection is reported. The applications and limitations of aptamers are also discussed.
An aptasensor was developed on an interdigitated microelectrode (IDME) by current-volt sensing for the diagnosis of ulcerative colitis by detecting the biomarker lipocalin-2. Higher immobilization of the anti-lipocalin-2 aptamer as a probe was achieved by using sodium dodecyl benzenesulfonate-aided zeolite particles. FESEM and FETEM observations revealed that the size of the zeolite particles was <200 nm, and they displayed a uniform distribution and spherical shape. XPS analysis attested the occurrence of Si, Al, and O groups on the zeolite particles. Zeolite particles were immobilized on IDME by a (3-aminopropyl)-trimethoxysilane amine linker, and then, the aptamer as the probe was tethered on the zeolite particles through a biotin-streptavidin strategy assisted by a bifunctional aldehyde linker. Due to the high occupancy of the aptamer and the efficient electric transfer from zeolite particles, higher changes in current can be observed upon interaction of the aptamer with lipocalin-2. The lower detection of lipocalin-2 was noted as 10 pg/mL, with a linear range from 10 pg/mL to 1 μg/mL and a linear regression equation of y=8E-07x+8E-08; R² = 0.991. Control experiments with complementary aptamer and matrix metalloproteinase-9 indicate the specific detection of lipocalin-2. Furthermore, spiking lipocalin-2 in human serum does not interfere with the identification.
A label -free DNAzyme amplified biosensor is found to be highly selective and sensitive towards fluorescent detection of Pb2+ ions in aqueous media. The DNAzyme complex has designed by the hybridization of the enzyme and substrate strand. In the presence of Pb2+, the DNAzyme activated and cleaved the substrate strand of RNA site (rA) into two oligonucleotide fragments. Further, the free fragment was hybridized with a complementary strand on the surface of MBs. After magnetic separation, SYBER Green I was added and readily intercalate with the dsDNA to gives a bright fluorescence signal with intensity directly proportional to the concentration of Pb2+ions. A detection limit of 5 nM in Pb2+ the detection range 0 to 500 nM was obtained. This label- free fluorescent biosensor has been successfully applied to the determination of environmental water samples. Then results open up the possibility for real-time quantitative detection of Pb2+ with convenient potential applications in the biological and environmental field. Graphical Abstract.
Nanotechnology is the developing field, bringing the materials in the nanoscale level, has been applied in the interdisciplinary sciences. Different nanomaterials, such as gold, silver, zinc, copper and graphene are shown to have a wide range of applications. Among these, graphene is one of the faster upcoming two-dimensional nanomaterials utilized in various fields due to its positive features including the properties of thermal, electrical, strength and elasticity. Biomedical applications of graphene have been widely attested to be popular among academician and industrial partners for creating next generation medical systems and therapies. In this review, we selectively revealed the current applications of graphene in the interdisciplinary medical sciences.
A tri-enzyme system consisting of choline kinase/choline oxidase/horseradish peroxidase was used in the rapid and specific determination of the biomarker for bacterial sepsis infection, secretory phospholipase Group 2-IIA (sPLA2-IIA). These enzymes were individually immobilized onto the acrylic microspheres via succinimide groups for the preparation of an electrochemical biosensor. The reaction of sPLA2-IIA with its substrate initiated a cascading enzymatic reaction in the tri-enzyme system that led to the final production of hydrogen peroxide, which presence was indicated by the redox characteristics of potassium ferricyanide, K₃Fe(CN)₆. An amperometric biosensor based on enzyme conjugated acrylic microspheres and gold nanoparticles composite coated onto a carbon-paste screen printed electrode (SPE) was fabricated and the current measurement was performed at a low potential of 0.20 V. This enzymatic biosensor gave a linear range 0.01-100 ng/mL (R² = 0.98304) with a detection limit recorded at 5 × 10-3 ng/mL towards sPLA2-IIA. Moreover, the biosensor showed good reproducibility (relative standard deviation (RSD) of 3.04% (n = 5). The biosensor response was reliable up to 25 days of storage at 4 °C. Analysis of human serum samples for sPLA2-IIA indicated that the biosensor has potential for rapid bacterial sepsis diagnosis in hospital emergency department.
Manipulation and injection of single nanosensors with high cell viability is an emerging field in cell analysis. We propose a new method using fluorescence nanosensors with a glass nanoprobe and optical control of the zeta potential. The nanosensor is fabricated by encapsulating a fluorescence polystyrene nanobead into a lipid layer with 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (SP), which is a photochromic material. The nanobead contains iron oxide nanoparticles and a temperature-sensitive fluorescent dye, Rhodamine B. The zeta potential of the nanosensor switches between negative and positive by photo-isomerization of SP with ultraviolet irradiation. The positively-charged nanosensor easily adheres to a negatively-charged glass nanoprobe, is transported to a target cell, and then adheres to the negatively-charged cell membrane. The nanosensor is then injected into the cytoplasm by heating with a near-infrared (NIR) laser. As a demonstration, a single 750 nm nanosensor was picked-up using a glass nanoprobe with optical control of the zeta potential. Then, the nanosensor was transported and immobilized onto a target cell membrane. Finally, it was injected into the cytoplasm using a NIR laser. The success rates of pick-up and cell immobilization of the nanosensor were 75% and 64%, respectively. Cell injection and cell survival rates were 80% and 100%, respectively.
The platinum(II) salphen complex N,N'-Bis-4-(hydroxysalicylidene)-phenylenediamine-platinum(II); (1) and its two derivatives containing hydroxyl functionalized side chains N,N'-bis-[4-[[1-(2-hydroxyethoxy)] salicylidene] phenylenediamine-platinum(II); (2) and N,N'-bis-[4-[[1-(3-hydroxypropoxy)] salicylidene] phenylenediamine-platinum(II); (3) were synthesized and characterized. The structures of the complexes were confirmed by 1H and 13C NMR spectroscopy, FTIR, ESI-MS and CHN elemental analyses. The effects of the hydroxyl substituent on the spectral properties and the DNA binding behaviors of the Pt(II) complexes were explored. The binding mode and interactions of these complexes with duplex DNA (calf thymus DNA and porcine DNA) and also single-stranded DNA were studied by UV-Vis and emission DNA titration. The complexes interact with DNA by intercalation binding mode with the binding constants in the order of magnitude (Kb = 104 M-1, CT-DNA) and (Kb = 105 M-1, porcine DNA). The intercalation of the complex in the DNA structure was proposed to happen by π-π stacking due to its square-planar geometry and aromatic rings structure. The phosphorescence emission spectral characteristics of Pt(II) complexes when interacted with DNA have been studied. Also, the application of the chosen hydroxypropoxy side chains complex (3) as an optical DNA biosensor, specifically for porcine DNA was investigated. These findings will be valuable for the potential use of the platinum(II) salphen complex as an optical DNA biosensor for the detection of porcine DNA in food products.
The emergence of coronavirus disease 2019 (COVID-19) motivates continuous efforts to develop robust and accurate diagnostic tests to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Detection of viral nucleic acids provides the highest sensitivity and selectivity for diagnosing early and asymptomatic infection because the human immune system may not be active at this stage. Therefore, this work aims to develop a label-free electrochemical DNA biosensor for SARS-CoV-2 detection using a printed circuit board-based gold substrate (PCBGE). The developed sensor used the nucleocapsid phosphoprotein (N) gene as a biomarker. The DNA sensor-based PCBGE was fabricated by self-assembling a thiolated single-stranded DNA (ssDNA) probe onto an Au surface, which performed as the working electrode (WE). The Au surface was then treated with 6-mercapto-1-hexanol (MCH) before detecting the target N gene to produce a well-oriented arrangement of the immobilized ssDNA chains. The successful fabrication of the biosensor was characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM). The DNA biosensor performances were evaluated using a synthetic SARS-CoV-2 genome and 20 clinical RNA samples from healthy and infected individuals through EIS. The developed DNA biosensor can detect as low as 1 copy per μL of the N gene within 5 minutes with a LOD of 0.50 μM. Interestingly, the proposed DNA sensor could distinguish the expression of SARS-CoV-2 RNA in a patient diagnosed with COVID-19 without any amplification technique. We believe that the proposed DNA sensor platform is a promising point-of-care (POC) device for COVID-19 viral infection since it offers a rapid detection time with a simple design and workflow detection system, as well as an affordable diagnostic assay.
Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands' roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.