Semiconductor quantum dots in photoelectrochemical sensors from fabrication to biosensing applications.

Semiconductor quantum dots (QDs) are a promising class of nanomaterials for developing new photoelectrodes and photoelectrochemistry systems for energy storage, transfer, and biosensing applications. These materials have unique electronic and photophysical properties and can be used as optical nanoprobes in displays, biosensors, imaging, optoelectronics, energy storage and energy harvesting. Researchers have recently been exploring the use of QDs in photoelectrochemical (PEC) sensors, which involve exciting a QD-interfaced photoactive material with a flashlight source and generating a photoelectrical current as an output signal. The simple surface properties of QDs also make them suitable for addressing issues related to sensitivity, miniaturization, and cost-effectiveness. This technology has the potential to replace current laboratory practices and equipment, such as spectrophotometers, used for testing sample absorption and emission. Semiconductor QD-based PEC sensors offer simple, fast, and easily miniaturized sensors for analyzing a variety of analytes. This review summarizes the various strategies for interfacing QD nanoarchitectures for PEC sensing, as well as their signal amplification. PEC sensing devices, particularly those used for the detection of disease biomarkers, biomolecules (glucose, dopamine), drugs, and various pathogens, have the potential to revolutionize the biomedical field. This review discusses the advantages of semiconductor QD-based PEC biosensors and their fabrication methods, with a focus on disease diagnostics and the detection of various biomolecules. Finally, the review provides prospects and considerations for QD-based photoelectrochemical sensor systems in terms of their sensitivity, speed, and portability for biomedical applications.

Biosensors for detecting viral and bacterial infections using host biomarkers: a review.

Viral and bacterial infections commonly occur by their transmission through air, contaminated food, water, body fluids or physical contact from person to person. They rapidly spread among the population causing millions of deaths worldwide. One of the major challenges in the diagnosis of infection is differential diagnosis of viral from bacterial infections. Constant viral mutations, reassortment and recombination give rise to the emergence of new and diverse viral populations which makes the diagnosis difficult. Antibiotics prescribed for patients suffering from viral infections are ineffective and a contributing factor to bacterial antibiotic resistance. Evaluating the existing biosensing platforms for early diagnosis of the bacterial etiology of infections enables researchers and clinicians to differentially diagnose viral infections. Over the last decade, many biosensors have been developed to detect a wide range of bacterial and viral markers and reduce the costs for healthcare. There has been considerable interest in finding diagnostic and prognostic biomarkers that can be detected in blood and predict bacterial and viral infections. This review provides an overview on the existing biosensor technology platforms for host biomarker detection that can be applied for differential diagnosis of viral and bacterial infections, as well as recommended considerations and future prospects of viral/bacterial infection detection technology.

In vitro HER2 protein-induced affinity dissociation of carbon nanotube-wrapped anti-HER2 aptamers for HER2 protein detection.

A new in vitro assay was developed to detect human epidermal growth factor receptor 2 (HER2) protein, based on affinity dissociation of carbon nanotube (CNT)-wrapped anti-HER2 ssDNA aptamers. First, we selected an anti-HER2 ssDNA aptamer (H2) using an in vitro serial evolution of ligands by an exponential enrichment (SELEX) process. Then the fluorescently labelled H2 ssDNAs were tightly packed on CNTs that had previously been coupled with magnetic microbeads (MBs), forming MB-CNT-H2 hybrids. The loading capacity of these MB-CNTs heterostructures (2.8 × 10(8)) was determined to be 0.025 to 3.125 µM of H2. HER2 protein-induced H2 dissociation occurred from MB-CNT-H2 hybrids, which was specifically induced by the target HER2 protein, with a dissociation constant (Kd) of 270 nM. The stoichiometric affinity dissociation ratio with respect to H2-to-HER2 protein was shown to be approximately 1 : 1. Our results demonstrated that the developed assay can be an effective approach in detecting native forms of disease biomarkers in free solutions or in biological samples, for accurate diagnosis.

Biosensors for detection of airborne pathogenic fungal spores: a review.

The excessive presence of airborne fungal spores presents major concerns with potential adverse impacts on public health and food safety. These spores are recognized as pathogens and allergens prevalent in both outdoor and indoor environments, particularly in public spaces such as hospitals, schools, offices and hotels. Indoor environments pose a heightened risk of pulmonary diseases due to continuous exposure to airborne fungal spore particles through constant inhalation, especially in those individuals with weakened immunity and immunocompromised conditions. Detection methods for airborne fungal spores are often expensive, time-consuming, and lack sensitivity, making them unsuitable for indoor/outdoor monitoring. However, the emergence of micro-nano biosensor systems offers promising solutions with miniaturized designs, nanomaterial integration, and microfluidic systems. This review provides a comprehensive overview of recent advancements in bio-nano-sensor system technology for detecting airborne fungal spores, while also discussing future trends in biosensor device development aimed at achieving rapid and selective identification of pathogenic airborne fungi.

AuAgCu trimetallic nanoparticles based alloy: an advanced electrocatalyst for hydrogen evolution reaction in alkaline media.

Hydrogen production via cost-effective electrochemical water splitting is one of the most promising approaches to confront the energy crisis and to obtain clean fuels with high energy density. To address this concern, herein, we developed a simple one-step synthesis method for creating an AuAgCu trimetallic alloy using aspirin as a capping agent. This alloy shows potential for efficient electrocatalyst for hydrogen evolution reaction. The trimetallic nanoparticles based alloy exhibit an equiaxed grain-like morphology and a face-centred cubic phase. In HER experiments using a 1 M KOH electrolyte, the AuAgCu alloy shows nearly negligible overpotential compared to mono- and bimetallic catalysts, and the Tafel slope was 32.7 mV dec-1, which is the lowest ever achieved for alloy-based electrocatalysts and extremely close to a commercially available Pt/C with high stability for 21 days and no decrease in current density in alkaline media. Besides, with excellent HER activity and stability, the trimetallic AuAgCu-modified electrode possessed significant durability for over 1000 cycles in the selected range of potential from 0.5 to 0.8 V at different scan rates from 1 to 100 mV s-1. This simple, cost-effective and environmentally friendly methodology can pave the way for the exploitation of mixed metal alloy-based electrocatalysts not only for water splitting but also for other applications, such as fuel cells, lithium-ion batteries and supercapacitors.

Graphene-interfaced flexible and stretchable micro-nano electrodes: from fabrication to sweat glucose detection.

Flexible and stretchable wearable electronic devices have received tremendous attention for their non-invasive and personal health monitoring applications. These devices have been fabricated by integrating flexible substrates and graphene nanostructures for non-invasive detection of physiological risk biomarkers from human bodily fluids, such as sweat, and monitoring of human physical motion tracking parameters. The extraordinary properties of graphene nanostructures in fully integrated wearable devices have enabled improved sensitivity, electronic readouts, signal conditioning and communication, energy harvesting from power sources through electrode design and patterning, and graphene surface modification or treatment. This review explores advances made toward the fabrication of graphene-interfaced wearable sensors, flexible and stretchable conductive graphene electrodes, as well as their potential applications in electrochemical sensors and field-effect-transistors (FETs) with special emphasis on monitoring sweat biomarkers, mainly in glucose-sensing applications. The review emphasizes flexible wearable sweat sensors and provides various approaches thus far employed for the fabrication of graphene-enabled conductive and stretchable micro-nano electrodes, such as photolithography, electron-beam evaporation, laser-induced graphene designing, ink printing, chemical-synthesis and graphene surface modification. It further explores existing graphene-interfaced flexible wearable electronic devices utilized for sweat glucose sensing, and their technological potential for non-invasive health monitoring applications.

Electrophoretic Fabrication of ZnO/CuO and ZnO/CuO/rGO Heterostructures-based Thin Films as Environmental Benign Flexible Electrode for Supercapacitor.

Sustainable fabrication of flexible hybrid supercapacitor electrodes is extensively investigated during the current era to solve global energy problems. Herein, we used a cost-effective and efficient electrophoretic deposition (EPD) approach to fabricate a hybrid supercapacitor electrode. ZnO/CuO and ZnO/CuO/rGO heterostructure were prepared by sol-gel synthesis route and were electrophoretically deposited on indium tin oxide (ITO) substrate as a thin uniform layer using 1 V for 20 min at 50 mV/s. ZnO/CuO and ZnO/CuO/rGO heterostructure coated ITOs were then employed as the working electrode in a three-electrode setup for supercapacitor measurements. The fabricated electrodes have been investigated by Galvanostatic charge-discharge (GCD), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) to study their charge storage properties. ZnO/CuO revealed a specific capacitance of 1945 F g-1 at 2 mV/s and 999 F g-1 at 5 A g-1. However, an increased specific capacitance of 2305 F g-1 was measured for ZnO/CuO/rGO heterostructure at 2 mV/s and 1235 F g-1 at 5 A g-1. The lower internal resistance was observed for ZnO/CuO/rGO heterostructure, indicating good conductivity of the electrode material. Thus, the overall results of the current study suggest that EPD-assisted ZnO/CuO/rGO heterostructure hybrid electrode possess a substantial potential for energy storage as a supercapacitor.

Phyto-synthesized facile Pd/NiOPdO ternary nanocomposite for electrochemical supercapacitor applications.

Sustainable and effective electrochemical materials for supercapacitors are greatly needed for solving the global problems of energy storage. In this regard, a facile nanocomposite of Pd/NiOPdO was synthesized using foliar phyto eco-friendly agents and examined as an electrochemical electrode active material for supercapacitor application. The nanocomposite showed a mixed phase of a ternary nano metal oxide phase of rhombohedral NiO and tetragonal PdO confirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and XPS (X-rays photoelectron spectroscopy). The optical (direct) energy value of the synthesized nanocomposite was 3.14 eV. The phyto-functionalized nanocomposite was studied for electrochemical supercapacitor properties and revealed a specific capacitance of 88 F g-1 and low internal resistance of 0.8 Ω. The nanoscale and phyto organic species functionalized nanocomposite exhibited enhanced electrochemical properties for supercapacitor application.

Probing chemical induced cellular stress by non-Faradaic electrochemical impedance spectroscopy using an Escherichia coli capacitive biochip.

A new capacitive biochip was developed using carboxy-CNT activated gold interdigitated (GID) capacitors immobilized with E. coli cells for the detection of cellular stress caused by chemicals. Here, acetic acid, H(2)O(2) and NaCl were employed as model chemicals to test the biochip and monitored the responses under AC electrical field by non-Faradaic electrochemical impedance spectroscopy (nFEIS). The electrical properties of E. coli cells under different stresses were studied based on the change in surface capacitance as a function of applied frequency (300-600 MHz) in a label-free and noninvasive manner. The capacitive response of the E. coli biochip under normal conditions exhibited characteristic dispersion peaks at 463 and 582 MHz frequencies. Deformation of these signature peaks determined the toxicity of chemicals to E. coli on the capacitive biochip. The E. coli cells were sensitive to, and severely affected by 166-498 mM (1-3%) acetic acid with declined capacitance responses. The E. coli biochip exposed to H(2)O(2) exhibited adaptive responses at lower concentrations (<2%), while at a higher level (882 mM, 3%), the capacitance response declined due to oxidative toxicity in cells. However, E. coli cells were not severely affected by high NaCl levels (513-684 mM, 3-4%) as the cells tend to resist the salt stress. Our results demonstrated that the biochip response at a particular frequency enabled the determination of the severity of the stress imposed by chemicals and it can be potentially applied for monitoring unknown chemicals as an indicator of cytotoxicity.

Aptamers-in-liposomes for selective and multiplexed capture of small organic compounds.

Small, organic, toxic compounds are not well eliminated by water-treatment systems and eventually become concentrated in the human body. In this study, liposomes are employed to house aptamers with their own binding buffer. When small, organic, toxic compounds in water pass through a liposome barrier, only the target molecules are captured by the DNA aptamers inside the liposomes. The capture efficiency is not high when DNA aptamers are used in tap water. When DNA aptamers in liposomes are used, the capture efficiency increases more than 80%. The simultaneous and selective elimination of target toxicants is successfully performed for tap-water samples containing toxicant mixtures.

Iron oxide nanoparticles based magnetic luminescent quantum dots (MQDs) synthesis and biomedical/biological applications: A review.

Combination of quantum dots (QDs) and magnetic nanoparticles (MNPs) as magnetic quantum dots (MQDs) has a broad range of applications as multifunctional nanoscale devices in biological imaging, medical nano-diagnostics and nanomedicine. MQDs derived from iron oxide nanoparticles and QDs possess excellent superparamagnetic and fluorescent properties, respectively making them multifunctional nanoprobes because of their; (a) strong magnetic strength with tunable functionality, such as rapid and simple magnetic separation, (b) intense and stable fluorescence from QDs combined with tunable biological functionality upon QDs' bio-activation, and (c) imaging/visualization by simple ultraviolet light exposure. These excellent features of MQD nanoprobes enable them to be used for magnetic resonance imaging (MRI) as contrast agents, nano-diagnostic systems for Point-of-Care (PoC) disease diagnosis, theranostics nanorobots and in other bio-medical applications. Most of MQDs are derived from iron based MNPs because of their abundancy, superparamagnetic properties, low cost and easy to synthesize. In this review, we present different methods employed for chemical synthesis of MQDs derived from iron oxide MNPs, their major chemical compositions and important parameters, such as precursor compositions, quantum yield and magnetic properties. The review also summarizes the most frequently used MQDs in applications such as bio-imaging, drug delivery, biosensor platforms and finally ends with future prospects and considerations for MQDs in biomedical applications.

Graphene and carbon nanotubes interfaced electrochemical nanobiosensors for the detection of SARS-CoV-2 (COVID-19) and other respiratory viral infections: A review.

Recent COVID-19 pandemic has claimed millions of lives due to lack of a rapid diagnostic tool. Global scientific community is now making joint efforts on developing rapid and accurate diagnostic tools for early detection of viral infections to preventing future outbreaks. Conventional diagnostic methods for virus detection are expensive and time consuming. There is an immediate requirement for a sensitive, reliable, rapid and easy-to-use Point-of-Care (PoC) diagnostic technology. Electrochemical biosensors have the potential to fulfill these requirements, but they are less sensitive for sensing viruses/viral infections. However, sensitivity and performance of these electrochemical platforms can be improved by integrating carbon nanostructure, such as graphene and carbon nanotubes (CNTs). These nanostructures offer excellent electrical property, biocompatibility, chemical stability, mechanical strength and, large surface area that are most desired in developing PoC diagnostic tools for detecting viral infections with speed, sensitivity, and cost-effectiveness. This review summarizes recent advancements made toward integrating graphene/CNTs nanostructures and their surface modifications useful for developing new generation of electrochemical nanobiosensors for detecting viral infections. The review also provides prospects and considerations for extending the graphene/CNTs based electrochemical transducers into portable and wearable PoC tools that can be useful in preventing future outbreaks and pandemics.

Label-free RNA aptamer-based capacitive biosensor for the detection of C-reactive protein.

In this study, we report a novel aptamer-based capacitive label-free biosensor for monitoring transducing aptamer-protein recognition events, based on charge distribution under the applied frequency by non-Faradaic impedance spectroscopy (NFIS). This approach to capacitive biosensors is reported for the first time in this study, is reagent-less in processing and is developed using gold interdigitated (GID) capacitor arrays functionalized with synthetic RNA aptamers. The RNA atpamers served as biorecognition elements for C-reactive protein (CRP), a biomarker for cardiovascular disease risk (CVR). The signal is generated as a result of the change in relative capacitance occurring as a result of the formation of an RNA-CRP complex on GID capacitors with the applied AC electrical frequency (50-350 MHz). The dispersion peak of the capacitance curve was dependent on the CRP concentration and tends to shift toward lower frequencies, accompanied by the increase in relaxation time due to the increased size of the aptamer-CRP complex. The dissociation constant (K(d)) calculated from the non-linear regression analysis of the relative capacitance change with the applied frequency showed that strong binding of CRP occurred at 208 MHz (K(d) = 1.6 microM) followed by 150 MHz (K(d) = 4.2 microM) and 306 MHz (K(d) = 3.4 microM) frequencies. The dynamic detection range for CRP is determined to be within 100-500 pg ml(-1). Our results demonstrates the behavior of an RNA-protein complex on GID capacitors under an applied electric field, which can be extended to other pairs of affinity biomolecules as well as for the development of electrical biosensor systems for different applications, including the early diagnosis of diseases.

Electrochemical aptasensor for tetracycline detection.

An electrochemical aptasensor was developed for the detection of tetracycline using ssDNA aptamer that selectively binds to tetracycline as recognition element. The aptamer was highly selective for tetracycline which distinguishes minor structural changes on other tetracycline derivatives. The biotinylated ssDNA aptamer was immobilized on a streptavidin-modified screen-printed gold electrode, and the binding of tetracycline to aptamer was analyzed by cyclic voltammetry and square wave voltammetry. Our results showed that the minimum detection limit of this sensor was 10 nM to micromolar range. The aptasensor showed high selectivity for tetracycline over the other structurally related tetracycline derivatives (oxytetracycline and doxycycline) in a mixture. The aptasensor developed in this study can potentially be used for detection of tetracycline in pharmaceutical preparations, contaminated food products, and drinking water.

Quercetin in the form of a nano-antioxidant (QTiO2) provides stabilization of quercetin and maximizes its antioxidant capacity in the mouse fibroblast model.

Living cells are constantly exposed to reactive oxygen species (ROS) causing them to rely on a constant supply of exogenous antioxidants. Quercetin (Q) is one of the potent exogenous antioxidants utilized in various antioxidant formulations. However, the potential application of Q is largely limited because of its poor water solubility. In this study, we employed titanium dioxide (TiO2) nanoparticles to maximize cellular penetration and antioxidant effect of Q on mouse fibroblast cells. To accomplish this, polyethylene glycol (PEG) modified TiO2-nanoparticle surfaces were utilized that exhibited better dispersion, with enhanced biocompatibility. Cell viability assays using Q and Q-conjugated TiO2-nanoparticles (QTiO2) were evaluated in terms of cell morphology as well as with an immunoblotting analysis to look for key biomarkers of apoptosis. In addition, cleavages of Cas 3 and PARP were obtained in cells treated with Q. Furthermore, antioxidant defence with QTiO2 was validated by means of the Nrf2 upregulation pathway. We also observed increased expressions of target enzymes; HO-1, NQO1 and SOD1 in QTiO2-treated cells. The antioxidant potency of the QTiO2 nano-antioxidant form was successfully tested in ROS and superoxide radicals induced cells. Our results demonstrated that the QTiO2 nano-antioxidant promoted a high quercetin bioavailability and stability, in cells with maximal antioxidant potency against ROS, with no signs of cytotoxicity.

ssDNA aptamers that recognize diclofenac and 2-anilinophenylacetic acid.

A series of 56 ssDNA aptamer variants that bind to diclofenac (DCF) were selected from an initial pool of 2.4x10(14) ssDNA molecules by Flu-Mag SELEX process. Sequence analysis of these aptamer variants showed three major groups based on sequence similarity in their random N40 sequences. Out of these, four aptamers designated as D10/DA24, D22, D16, and D3 showed high affinity to DCF with K(d) values 100.64, 166.34, 148.73, and 42.7 nM, respectively. Secondary structures of these aptamers showed highly distinct features with typical stem and loop structures. Specificity tests with these four aptamer variants showed that D3 aptamer had higher specificity to DCF followed by 2-anilinophenylacetic acid (2APA), a structural analog of DCF. Whereas aptamers D16 and D22 showed higher specificity to 2APA compared to DCF as target used during selection process. Further, the D10/DA24 aptamer showed high affinity but no specificity to DCF. The DCF aptamers selected can be potential candidates for drug-delivery systems, specific detection of DCF and its derivatives in pharmaceutical preparations and contaminants.

ssDNA aptamer-based surface plasmon resonance biosensor for the detection of retinol binding protein 4 for the early diagnosis of type 2 diabetes.

Retinol binding protein 4 (RBP4) is a useful biomarker in the diagnosis of type 2 diabetes since its level in the serum is higher in insulin-resistant states. Accurate measurement of the serum RBP4 levels is hampered by conventional immunologic methods, such as enzyme-linked immunosorbent assay (ELISA). In this study, therefore, we have developed an aptamer-based surface plasmon resonance (SPR) biosensor that can be used to sense for RBP4 in serum samples. A single-stranded DNA (ssDNA) aptamer that showed high affinity (Kd = 0.2 +/- 0.03 microM) and specificity to RBP4 was selected. This RBP4-specific aptamer was immobilized on a gold chip and used in a label-free RBP4 detection using SPR. Analysis of RBP4 in artificial serum using SPR was compared with ELISA and Western blot analysis. Our results indicated that the RBP4-specific aptamer-based SPR biosensor gave better dose-dependent responses and was more sensitive than ELISA assays. As such, this RBP4 aptamer-based SPR biosensor can be potentially used to monitor the RBP4 levels within the serum as an indicator of type 2 diabetes.

Single-stranded DNA aptamers specific for antibiotics tetracyclines.

Tetracyclines (TCs) are a group of antibiotics comprising of a common tetracycline (TET) nucleus with variable X(1) and X(2) positions on 5 and 6 carbon atoms, such as oxytetracycline (OTC) and doxycycline (DOX). In this study, the tetracycline group specific (TGS) ssDNA aptamers were identified by modified SELEX method by employing tosylactivated magnetic beads (TMB) coated with OTC, TET, and DOX, respectively, as targets and counter targets. Twenty TGS-aptamers were selected, of which seven aptamers, designated as T7, T15, T19, T20, T22, T23, and T24, showed high affinity to the basic TET backbone (K(d)=63-483 nM). The specificity of these TGS-aptamers to structural analogues followed the order in which the TCs was employed during SELEX process (OTC>TET>DOX) except aptamer T22, which was highly specific to TET than OTC or DOX. Aptamers that were specific to one target molecule but fail to bind the other structurally related TCs were eliminated during counter selection steps. Three aptamers, T7, T19, and T23 contained palindromic consensus sequence motif GGTGTGG. The remaining TGS-aptamers showed many consensus sequences that are truncated forms of this palindrome forming mirror image or inverted sequences. For example, GTGG or its inverted form, GGTG motif was found in all TGS-aptamers. A consensus sequence motif TGTGCT or its truncated terminal T-residue was found in most TGS-aptamers, which is predicted to be essential for high affinity and group specificity. These TGS-aptamers have potential applications such as target drug delivery, and detection of TCs in pharmaceutical preparations and contaminated food products.

ssDNA aptamers that selectively bind oxytetracycline.

Single stranded DNA aptamers that bind with high affinity and specificity to the oxytetracycline (OTC) were identified by selection from an oligonucleotide library of 10(15) molecules. The binding affinities of four aptamers were in nanomolar range. The aptamers were highly selective in that, lack of -OH group at 5-position in tetracycline and -H group in place of -OH at 6-position in doxycycline determined the specificity of these aptamers to bind OTC. Three aptamers designated as No. 4, 5, and 20 shared strong affinities with K(d)=9.61, 12.08, and 56.84 nM, respectively, as well as selectivity to bind OTC (72-76%). Aptamer No. 4 had strong affinity among all with high selectivity, whereas No. 2 had relatively weak affinity (K(d)=121.1 nM) and moderate selectivity (52%). Our results indicated that the aptamers No. 4, 5, and 20 with variable 40-base oligonucleotides can be good candidates for selectively binding to OTC with high molecular discrimination over its analogs such as tetracycline and doxycycline.

Role of p53 circuitry in tumorigenesis: A brief review.

Maintenance of genome integrity under the stressed condition is paramount for normal functioning of cells in the multicellular organisms. Cells are programmed to protect their genome through specialized adaptive mechanisms which will help decide their fate under stressed conditions. These mechanisms are the outcome of activation of the intricate circuitries that are regulated by the p53 master protein. In this paper, we provided a comprehensive review on p53, p53 homologues and their isoforms, including a description about the ubiquitin-proteasome system emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an integral part of the ubiquitin-proteasome system. This review outlines the roles of important E3(Ub)-ligases and their splice variants in maintaining cellular p53 protein homeostasis. It also covers up-to-date and relevant information on small molecule Mdm2 inhibitors originated from different organizations. The review ends with a discussion on future prospects and investigation directives for the development of next-generation modulators as p53 therapeutics.