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Electrochemical fabrication integrating templating strategies have paved the way for creating mesoporous metal alloy films with distinctive pores and functionalities for electrocatalysis, fuel cells, and sensor (bio) development.

Biosensors are common analytical devices, capable of sensing a myriad of biological analytes, including cancer biomarkers. Although biosensors have different transducer types, electrochemical biosensors provide fast analysis time, high sensitivity, and the ability to perform complex measurements such as multiplexed analysis or screening tests for early diagnosis and prognosis of cancer. This chapter describes the background and theory of electrochemical sensors and introduces the main readout techniques. Innovative electrochemical biosensing strategies for analysis and quantification of important early cancer biomarkers, which include circulating nucleic acids (e.g., circulating tumour DNA, gene mutations, and microRNA) proteins, circulating tumour cells, and extracellular vesicles are discussed with the recent developments to provide an overview of the possible academic and clinical approaches

Controllable ternary Pt–Cu–Mn lamellar oxides with different amounts of Pt were synthesized using a facile and expeditious self-propagating flaming technique for catalytic oxidation of toluene. The surface structure, composition, and structure–performance relationship were investigated by combining X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) surface area, scanning electron microscopy (SEM), transmission electron microscopy (TEM), hydrogen temperature-programmed reduction (H2-TPR), and X-ray photoelectron spectroscopy (XPS). The catalytic performance of the as-produced catalysts toward the catalytic oxidation of toluene was investigated. Among the catalysts, the 0.5Pt-MnCu catalyst has shown 90% toluene removal at 228 °C with excellent cyclic stability, which is a significant achievement for MnCu binary nanosheet-like catalysts containing low amounts of Pt (0.5 wt %). This study has also inferred the degradation activity of modulated MnCu composite catalysts, which greatly hinges on the doping level of Pt. The lattice oxygen species are dominating according to the Mn–O bond strength, local environment, and reducibility. Moreover, Pt can increase the covalency of surface metal–oxygen bonds and electron affinity of surface metal-coordinated oxygen centers, thereby expediting the adsorption/activation of the gaseous oxygen molecules on oxide surfaces, which can step up the lattice oxygen as well as oxygen vacancy-involved reactions to invoke the Mars–van Krevelen and Langmuir–Hinshelwood mechanisms for boosting the overall toluene oxidation performance of PtCuMnOx catalytic materials. Based on the obtained results, this study proposes a vital insight into manipulating the nanoscale catalytic functions, which could also promise pivotal potential toward engineering the state-of-the-art transition-metal nanostructure for environmental catalysis.

Magnetic cellulose (MC) is prepared by hydrolysis of iron precursors in an aqueous dispersion of cellulose nanofibres. A thin, flexible film was then prepared by removing the water and drying the sample in a hot press at 110°C followed by the removal of the water. Structural analysis of MC was performed and correlated with the measurement of electromagnetic properties. The magnetic cellulose showed high magnetic saturation of 68 emu/g with characteristic superparamagnetic behaviour, and conductivity in a range of semiconductors, with an increase of DC conductivity with increasing temperature. Modification of cellulose with Fe3O4 has a positive effect on the DC conductivity and lower limit that needs to be exceeded to achieve a stable and sustainable conductivity in the range of ~5-20 ×10-9 (Ω cm)-1 @30 °C is 65 wt% of the Fe3O4 for studied MC composites. The surface roughness of the magnetic cellulose shows a dynamic change with increasing temperature, which is closely related to the enhancement of MC conductivity. A theoretical model of the conductivity is calculated based on continuous 2D percolation and shows an interesting agreement with the experimental results.

Wearable and implantable bioelectronics have experienced remarkable progress over the last decades. Bioelectronic devices provide seamless integration between electronics and biological tissue, offering unique functions for healthcare applications such as real-time and online monitoring and stimulation. Organic semiconductors and silicon-based flexible electronics have been dominantly used as materials for wearable and implantable devices. However, inherent drawbacks such as low electronic mobility, particularly in organic materials, instability, and narrow band gaps mainly limit their full potential for optogenetics and implantable applications. In this context, wide-band-gap (WBG) materials with excellent electrical and mechanical properties have emerged as promising candidates for flexible electronics. With a significant piezoelectric effect, direct band gap and optical transparency, and chemical inertness, these materials are expected to have practical applications in many sectors such as energy harvesting, optoelectronics, or electronic devices, where lasting and stable operation is highly desired. Recent advances in micro/nanomachining processes and synthesis methods for WBG materials led to their possible use in soft electronics. Considering the importance of WBG materials in this fast-growing field, the present paper provides a comprehensive Review on the most common WBG materials, including zinc oxide (ZnO) for II–VI compounds, gallium nitride (GaN) for III–V compounds, and silicon carbide (SiC) for IV–IV compounds. We first discuss the fundamental physical and chemical characteristics of these materials and their advantages for biosensing applications. We then summarize the fabrication techniques of wide-band-gap semiconductors, including how these materials can be transferred from rigid to stretchable and flexible substrates. Next, we provide a snapshot of the recent development of flexible WBG materials-based wearable and implantable devices. Finally, we conclude with perspectives on future research direction.

The integration of nanoarchitectonics and hydrogel into conventional biosensing platforms offers the opportunities to design physically and chemically controlled and optimized soft structures with superior biocompatibility, better immobilization of biomolecules, and specific and sensitive biosensor design. The physical and chemical properties of 3D hydrogel structures can be modified by integrating with nanostructures. Such modifications can enhance their responsiveness to mechanical, optical, thermal, magnetic, and electric stimuli, which in turn can enhance the practicality of biosensors in clinical settings. This review describes the synthesis and kinetics of gel networks and exploitation of nanostructure-integrated hydrogels in biosensing. With an emphasis on different integration strategies of hydrogel with nanostructures, this review highlights the importance of hydrogel nanostructures as one of the most favorable candidates for developing ultrasensitive biosensors. Moreover, hydrogel nanoarchitectonics are also portrayed as a promising candidate for fabricating next-generation robust biosensors.

Dysregulated microRNA associated pathways contribute to the pathology of neurological disorders, hence presenting themselves as a potential candidate for motor neuron disease (MND) diagnosis. Herein, we reported an enzymatic amplification‐free approach for the electrochemical detection of exosomal microRNA (miR‐338‐3p) from preconditioned media of motor neurons obtained from amyotrophic lateral sclerosis (ALS) patients and healthy controls. Our assay utilizes a three‐step strategy that involves i) initial isolation and purification of exosomal miR‐338‐3p from patients and healthy controls using biotinylated complementary capture probe followed by heat‐release of the specific target, ii) direct adsorption of target miR‐338‐3p onto the gold‐loaded ferric oxide nanocatalyst (AuNP‐Fe2O3NC) through affinity interaction between microRNA and exposed gold surfaces within the AuNP‐Fe2O3NC, and iii) gold nanocatalyst‐induced electrocatalytic signal amplification through methylene blue‐ferricyanide redox cycling (MB/[Fe(CN)6]3−). The electrocatalytic signal is monitored by using chronocoulometry at the AuNP–Fe2O3NC‐modified screen‐printed carbon electrode (AuNP‐Fe2O3NC/SPCE). We demonstrated the detection of miR‐338‐3p as low as 100 aM in spiked buffer samples with a relative standard deviation of (%RSD)

Protein phosphorylation is a post-translational modification of kinase proteins that changes a protein's conformation to regulate crucial biological functions. However, the phosphorylation of protein is significantly altered during cancer progression which triggers abnormal cellular pathways and this phosphorylation can serve as an emergent diagnostic and prognostic biomarker for cancer. Herein, we develop a nanostructured mesoporous gold electrode (NMGE)-based biosensor that enables a highly sensitive detection of protein phosphorylation with electrochemical signal amplification. The biosensor comprises nanostructured mesoporous gold electrodes whose electro-conductive framework is superior to that of the nonporous electrodes. We characterize our developed nano/mesoporous gold electrode with various electrochemical methods in the presence of the [Fe(CN)6]3-/4- redox system. We find that the mesoporous gold electrode catalyzes both the oxidation and reduction processes of the [Fe(CN)6]3-/4- system and generates a current signal that is 3 times higher than that of the nonporous gold electrode. This superior signal transduction of our nano/mesoporous gold electrode is enabled through a pore-induced (i) high electrochemically active surface area and (ii) reduced impedance with a high signal to noise ratio. The assay utilizes direct adsorption of an immunoprecipitated purified BRAF protein towards the mesoporous gold electrode and thus avoids the cumbersome sensor surface functionalization. Our developed biosensor detects the phosphorylated BRAF protein with a 2.5-fold increase in sensitivity and an ≈10-fold increase in the limit of detection (LOD) in comparison with the nonporous gold electrodes. The assay also works on a wide dynamic range from 0.5 to 20 ng μL-1 of the protein which further shows its potential for clinical application. We envisage that this nanostructured mesoporous gold biosensor will be of high interest for clinical application.

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm

Although porous materials based on coordination compounds, including metal-organic frameworks (MOFs) and porous coordination polymers (PCPs), have well-defined pore structures and promising propert...

Most of the current exosome-analysis strategies are time-consuming and largely dependent on commercial extraction kit-based preisolation step, which requires extensive sample manipulations, costly isolation kits, reagents, tedious procedures, and sophisticated equipment and is prone to bias/artifacts. Herein we introduce a simple method for direct isolation and subsequent detection of a specific population of exosomes using an engineered superparamagnetic material with multifunctional properties, namely, gold-loaded ferric oxide nanocubes (Au-NPFe2O3NC). In this method, the Au-NPFe2O3NC were initially functionalized with a generic tetraspanin (exosomes-associated) antibody (i.e., CD63) and dispersed in sample fluids where they work as “dispersible nanocarriers” to capture the bulk population of exosomes. After magnetic collection and purification, Au-NPFe2O3NC-bound exosomes were transferred to the tissue-specific, antibody-modified, screen-printed electrode. As a proof of principle, we used a specific pl...

Porous nanomaterials with superior peroxidase mimetic activity (nanozyme) at room temperature have gained increasing attention as potential alternatives to natural peroxidase enzymes. Herein, we report the application of porous iron oxide nanoflakes (IONFs), synthesized using the combination of solvothermal method and high-temperature calcination as peroxidase nanozyme for the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of HO. The four IONF catalysts possess porous structures with a wide pore size distribution between 2–30 nm and high specific surface areas around to 200 m g. The increase of calcination temperature of the IONFs from 250 °C to 400 °C resulted in a gradual decrease in their specific surface area and Michaelis-Menten constant (K) for TMB oxidation. The optimum IONF sample showed a much lower K at 0.24 mM (towards TMB) compared to natural enzyme horseradish peroxidase (HRP) at 0.434 mM, revealing the promising potential of the as-prepared IONFs as alternatives to HRP for biosensing applications.

International audience; This work presents crystalline SiC-on-glass as a transparent, robust, and optically stable electrode for simultaneous electrochemical characterization and optical microscope imaging. Experimental results show a large potential window, as well as excellent stability and repeatability over multiple cyclic voltammetric scans in common redox biomarkers such as ruthenium hexaammine and methylene blue. The high optical transmittance and biocompatibility of SiC-on-glass were also observed, enabling cell culture, electrical stimulation, and high resolution fluorescence imaging. This new platform opens exciting opportunities in multi-functional biosensing-probes and observation.

Nanozymes (nanoparticles with enzyme-like properties) have attracted considerable attention in recent years owing to their intrinsic enzyme-like properties and broad application in the fields of ELISA based immunoassay and biosensing. Herein, we systematically investigate the influence of crystal phases (γ-Fe2O3 and α-Fe2O3) of mesoporous iron oxide (IO) on their peroxidase mimetic activity. In addition, we have also demonstrated the applicability of these mesoporous IOs as nanozymes for detecting the glucose biomarker with a limit of detection (LOD) of 0.9 μM. Mesoporous γ-Fe2O3 shows high nanozyme activities (and magnetism) toward the catalytic oxidation of chromogenic substances, such as 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-ABTS, as well as for the colourimetric detection of glucose, compared to that of α-Fe2O3. We believe that this in-depth study of crystal structure based nanozyme activity will guide designing highly effective nanozymes based on iron oxide nanostructures for chemical sensing, biosensing and environmental remediation.

Extracellular vesicles (EVs) can transfer intercellular messages in various (patho)physiological processes and transport biomolecules to recipient cells. EVs possess the capacity to evade the immune system and remain stable over long periods, identifying them as natural carriers for drugs and biologics. However, the challenges associated with EVs isolation, heterogeneity, coexistence with homologous biomolecules, and lack of site-specific delivery, have impeded their potential. In recent years, the amalgamation of EVs with rationally engineered nanostructures has been proposed for achieving effective drug loading and site-specific delivery. With the advancement of nanotechnology and nanoarchitectonics, different nanostructures with tunable size, shapes, and surface properties can be integrated with EVs for drug loading, target binding, efficient delivery, and therapeutics. Such integration may enable improved cellular targeting and the protection of encapsulated drugs for enhanced and specific delivery to target cells. This review summarizes the recent development of nanostructure amalgamated EVs for drug delivery, therapeutics, and real-time monitoring of disease progression. With a specific focus on the exosomal cargo, diverse drug delivery system, and biomimetic nanostructures based on EVs for selective drug delivery, this review also chronicles the needs and challenges of EV-based biomimetic nanostructures and provides a future outlook on the strategies posed.

Continuing our previous research work on a drug delivery system based on combined AC/DC magnetic fields, we have developed a prototype AC/DC magnetic syringe device for stimulation of drug release from drug carriers, with the options of injecting/removing drug carriers. The porous Fe3O4 carrier, in a dose-dependent manner, causes acute oxidative damage and reduces the viability of differentiated SH-SY5Y human neuroblastoma cells, indicating the necessity for its removal once it reaches the therapeutic concentration at the target tissue. The working mechanism of the device consists of three simple steps. First, direct injection of the drug adsorbed on the surface of a carrier via a needle inserted into the targeted area. The second step is stimulation of drug release using a combination of AC magnetic field (a coil magnetised needle with AC current) and permanent magnets (DC magnetic lens outside of the body), and the third step is removal of the drug carriers from the injected area after the completion of drug release by magnetising the tip of the needle with DC current. Removing the drug carriers allows us to avoid possible acute and long term side effects of the drug carriers in the patient's body, as well as any potential response of the body to the drug carriers.

Iron nanoparticles are used as a targeted drug delivery system. The nanocarrier itself can be genotoxic, trigger oxidative stress or cell death. Therefore, we developed an AC/DC magnetic syringe for injecting, stimulating drug release and safe removing of the nanocarrier. Alongside we optimized the method for nanoparticles’ drug release kinetics and testing cytotoxicity in vitro.•This paper presents detailed instructions for construction of AC/DC magnetic syringe device for stimulated drug release, injection and ejection of magnetic nanoparticles; nanoparticles preparation; adsorbing methylene blue on nanoparticles; determination of drug release kinetics from nanocarriers on the example of methylene blue•Gomori´s Prussian blue reaction for differentiated SH-SY5Y human neuroblastoma cell line; MTT viability assay optimized for differentiated SH-SY5Y human neuroblastoma cell line and antioxidant enzymes activities assay and lipid peroxidation methods are optimized for cell analyses cell cultivation for nanoparticles cytotoxicity testing in vitro.•Those protocols are the first step toward further testing the effect of nanoparticles in vivo, on brain tissue., Graphical abstract Image, graphical abstract

Herein, we report the preparation of mesoporous gold (Au)-silver (Ag) alloy films through the electrochemical micelle assembly process and their applications as microRNA (miRNA) sensors. Following electrochemical deposition and subsequent removal of the templates, the polymeric micelles can create uniformly sized mesoporous architectures with high surface areas. The resulting mesoporous Au-Ag alloy films show high current densities (electrocatalytic activities) towards the redox reaction between potassium ferrocyanide and potassium ferricyanide. Following magnetic isolation and purification, the target miRNA is adsorbed directly on the mesoporous Au-Ag film. Electrochemical detection is then enabled by differential pulse voltammetry (DPV) using the [Fe(CN)6]3-/4- redox system (the faradaic current for the miRNA-adsorbed Au-Ag film decreases compared to the bare film). The films demonstrate great advantages towards miRNA sensing platforms to enhance the detection limit down to attomolar levels of miR-21 (limit of detection (LOD) = 100 aM, s/n = 3). The developed enzymatic amplification-free miniaturized analytical sensor has promising potential for RNA-based diagnosis of diseases.

We report the nanoconfinement-mediated graphitic nanoporous carbon nitride (gNPCN) adsorbents with a high content of inbuilt basic nitrogen (N) (48%) by X-ray photoelectron spectroscopy (XPS) for efficient CO

The detection of disease-specific biomarkers such as proteins (particularly autoantibody) and microRNA (miRNA) are prerequisites to understanding their physiological and biological functions, early diagnosis, the prognosis of the disease and their treatment. Despite the numerous molecular biology and analytical techniques, their detection approaches are largely narrowed to laboratory-based molecular biology techniques. While the analytical performance and reliability of these approaches are admirable, most of these methods necessitate enzymatic amplification, cumbrous sample pre-treatment, multi-step assay protocol, sound technical personnel and expensive maintenance. The cutting-edge electrochemical and optical approaches are relatively simple and rapid and provide sensitive detection in a portable arrangement, however, target-specific transduction surface modification is vital to achieving the selectivity of a functional biosensor. With the progress of nanotechnology, nanostructured magnetic materials have aroused enormous interest in the arena of biosensing and biomedicine owing to their flexible and modular structure, nanosize, low toxicity, biocompatibility, intrinsic functionalities. Magnetic nanoparticles inimitably combined with the dimension of more modest size or the same size of molecular analytes and henceforth retain enormous potentiality in isolation and purification of target molecules, signal transduction, signal generation and signal enhancing steps in biosensing. Nonetheless, engineered multifunctional magnetic nanostructure-based diagnostics that could offer the advantages of excellent stability in a complex biomatrix, easy and alterable biorecognition of ligands, antibodies, and receptor molecules and unified point-of-care integration have yet to be achieved.This PhD project endeavours to engineer the nanostructure-based strategies for developing an inexpensive, specific, sensitive, and portable point-of-care diagnostic platform for clinics. This thesis intensively studies the bio-favourable nanostructure synthesis, their biofunctionalisation, intrinsic properties and cutting-edge nanostructure-based strategies for the detection of clinically-relevant biomarkers. Besides, the biogenesis, diagnostic, and prognostic potential of miRNA biomarkers followed by a comprehensive evaluation of recent progress in the development of nanostructure-based electrochemical miRNA biosensors are reviewed. I initially reported on the synthesis of mesoporous iron oxides with two different crystal phases named α- and γ-Fe2O3 to examine and understand the phase-dependent behaviours towards the magnetism and peroxidase mimetic activity. The cubic γ-Fe2O3 phase exhibited much higher activity and presented their superior aptness for biosensing. I have then designed and developed a new class of gold-loaded superparamagnetic mesoporous iron oxide nanocube, which superbly shows intrinsic nanozyme (peroxidase-mimetic) activity and electrocatalytic activity towards different redox molecules. Based on these promising activities, I have developed a set of biosensing platform (three novel readout scheme) that facilitates simple, rapid, and inexpensive analysis of autoantibody and miRNA biomarkers. First, considering the promising nanozyme activity of developed nanocube a specific and sensitive autoantibody sensor was developed for detecting different stages of ovarian cancer, where the nanozyme potentially replaces the natural enzyme (horseradish peroxidase-HRP). The nanocube is purposefully loaded with nanosized (~ 2 nm) gold so that the nanocube can achieve good biocompatibility, well dispersibility in body fluids and can easily immobilise reporter or capturing antibody. Besides, the nanocube can easily achieve miRNA capture through favourite gold-DNA/RNA affinity interactions. By employing this gold-RNA affinity interaction and the electrocatalytic activity of this nanocube, I have then developed an amplification-free electrochemical miRNA sensor for the detection of esophageal cancer-specific mRNA (miR-21). This forthright sensor enables the 10 pM level of detection by using the direct adsorption of magnetically isolated and purified miRNAs onto nanocube-modified disposable electrodes. Succeeding in advance of this proof-of-concept detection system, I endeavoured to address the growing thirst for detecting the ultralow levels of miRNAs from the complex biological sample through the development of another novel readout system. In this approach, the electrocatalytic activity of nanocube towards the redox reaction of methylene blue (MB) was coupled with [Fe(CN)6]3-/4- to form an MB/[Fe(CN)6]3-/4- electrocatalytic redox cycle. The combination of both electrocatalytic activity and redox cycling, the sensor achieved detection of 100 aM of miRNAs from motor neuron disease (MND) patient samples. In my final detection strategies, I prolonged the approach towards a translational- focused assay platform, where a mesoporous gold electrode was engineered which will be used for direct adsorption of magnetically isolated and purified miRNA followed by differential pulse voltammetric (DPV) interrogation.All of the reported readout systems have revealed admirable analytical performance with high specificity and sensitivity. The applicability of the assays was also established in complex biological samples (a cohort of cancer and MND patient samples) with high reproducibility. The analytical performance of all miRNA assays was validated using the standard RT-qPCR approach. I have faith in that our research efforts will lead to the design and development of a translational-focused point-of-care platform for clinically relevant autoantibody and miRNA analysis, which in sequence will hold the significant potential to improve the patient care in clinics as well as the outcomes may substantiate to be a venture of enormous commercial implications.

Circulating tumor nucleic acids (ctNAs) are promising biomarkers for minimally invasive cancer assessment. The FGFR2 : FAM76A fusion gene is one of the highly promising ovarian cancer biomarkers detectable in ctNAs. Herein, we introduce a new amplification-free electrochemical assay for the detection of FGFR2 : FAM76A fusion gene in ctNAs extracted from ovarian cancer patients. The assay relies on the electrocatalytic activity of a new class of superparamagnetic graphene-loaded iron oxide nanoparticles (GO-NPFeO). After isolation and purification, the target RNA was directly adsorbed onto the GO-NPFeO surface through graphene-RNA affinity interaction. The electrocatalytic signal was achieved by the reduction of surface-attached ruthenium hexaammine(III) chloride which was further amplified by using the ferricyanide redox system. Our assay depicted an excellent detection sensitivity down to 1.0 fM, high specificity and excellent reproducibility (% RSD=

We report the electrocatalytic activity of a new class of superparamagnetic nanoparticles, graphene-oxide-loaded iron oxide (GO/IO hybrid material), towards the reduction of ruthenium hexaammine(III) chloride (Ru(NH)], RuHex). Leveraging the electrocatalytic activity of the GO/IO hybrid material and the signal enhancement capacity of [Ru(NH)]/[Fe(CN)] in an electrocatalytic cycle, an ultrasensitive and specific electrochemical sensor was developed for the detection of cancer-related microRNA (miRNA). Using the direct affinity interaction between RNA and graphene oxide, magnetically isolated and purified target miRNA were directly adsorbed onto a screen-printed electrode modified with the GO/IO hybrid material. The detection was enabled by chronocoulometric (CC) readout of charge-compensating [Ru(NH3)] followed by an enhancement in CC charge display through the Ru(NH)]/[Fe(CN)] system. We demonstrate an excellent limit of detection of 1.0 fM by accurately detecting miR-21 in synthetic samples and showcase its clinical utility in ovarian cancer cell lines with high sensitivity (ten cells) and good reproducibility (% RSD=

A crucial issue in microRNA (miRNA) detection is the lack of sensitive method capable of detecting the low levels of miRNA in RNA samples. Herein, we present a sensitive and specific method for the electrocatalytic detection of miR-107 using gold-loaded nanoporous superparamagnetic iron oxide nanocubes (Au-NPFe2O3NC). The target miRNA was directly adsorbed onto the gold surfaces of Au-NPFe2O3NC via gold-RNA affinity interaction. The electrocatalytic activity of Au-NPFe2O3NC was then used for the reduction of ruthenium hexaammine(III) chloride (RuHex, [Ru(NH3)6]3+) bound with target miRNA. The catalytic signal was further amplified by using the ferri/ferrocyanide [Fe(CN)6]3-/4- system. These multiple signal enhancement steps enable our assay to achieve the detection limit of 100aM which is several orders of magnitudes better than most of the conventional miRNA sensors. The method was also successfully applied to detect miR-107 from cancer cell lines and a panel of tissue samples derived from patients with oesophageal squamous cell carcinoma with excellent reproducibility (% RSD = < 5%, for n = 3) and high specificity. The analytical accuracy of the method was validated with a standard RT-qPCR method. We believe that our method has the high translational potential for screening miRNAs in clinical samples.

Nanomaterials (nanozymes) with peroxidase-mimetic activity have been widely used in biosensing platforms as low-cost, relatively stable and prevailing alternatives to natural enzymes. Herein, we report on the synthesis and application of the peroxidase-mimetic activity of mesoporous iron oxide (MIO) for the detection of global DNA methylation in colorectal cancer cell lines. The target DNA was extracted and denatured to get ssDNA followed by direct adsorption onto the surface of a bare screen-printed gold electrode (SPGE). A 5-methylcytosine antibody (5mC) functionalized nanomaterial (MIO-5mC) was then used to recognise the methylcytosine groups present on the SPGE. The MIO-5mC conjugates catalyse the TMB solution in the presence of hydrogen peroxide to give the colorimetric (i.e., naked-eye observation) and electrochemical detection of DNA methylation. The assay could successfully detect as low as 10% difference in the global DNA methylation level in synthetic samples and cell lines with good reproducibility and specificity (%RSD =

DNA methylation is one of the key epigenetic modifications of DNA that results from the enzymatic addition of a methyl group at the fifth carbon of the cytosine base. It plays a crucial role in cellular development, genomic stability and gene expression. Aberrant DNA methylation is responsible for the pathogenesis of many diseases including cancers. Over the past several decades, many methodologies have been developed to detect DNA methylation. These methodologies range from classical molecular biology and optical approaches, such as bisulfite sequencing, microarrays, quantitative real-time PCR, colorimetry, Raman spectroscopy to the more recent electrochemical approaches. Among these, electrochemical approaches offer sensitive, simple, specific, rapid, and cost-effective analysis of DNA methylation. Additionally, electrochemical methods are highly amenable to miniaturization and possess the potential to be multiplexed. In recent years, several reviews have provided information on the detection strategies of DNA methylation. However, to date, there is no comprehensive evaluation of electrochemical DNA methylation detection strategies. Herein, we address the recent developments of electrochemical DNA methylation detection approaches. Furthermore, we highlight the major technical and biological challenges involved in these strategies and provide suggestions for the future direction of this important field.

Autoantibodies are produced against tumor associated antigens (TAAs) long before the appearance of any symptoms and thus can serve as promising, non-invasive biomarkers for early diagnosis of cancer. Current conventional methods for autoantibody detection are highly invasive and mostly provide diagnosis in the later stages of cancer. Herein we report a new electrochemical method for early detection of p53 autoantibodies against colon cancer using a strategy that combines the strength of gold-loaded nanoporous iron oxide nanocube (Au@NPFe2O3NC)-based capture and purification while incorporating the inherent simplicity, inexpensive, and portable nature of the electrochemical and naked-eye colorimetric readouts. After the functionalisation of Au@NPFe2O3NC with p53 antigens, our method utilises a two-step strategy that involves (i) magnetic capture and isolation of autoantibodies using p53/Au@NPFe2O3NC as ‘dispersible nanocapture agents’ in serum samples and (ii) subsequent detection of autoantibodies through a peroxidase-catalyzed reaction on a commercially available disposable screen-printed electrode or naked-eye detection in an Eppendorf tube. This method has demonstrated a good sensitivity (LOD = 0.02 U mL−1) and reproducibility (relative standard deviation, %RSD =

The detection of clinically relevant disease-specific biomolecules, including nucleic acids, circulating tumor cells, proteins, antibodies, and extracellular vesicles, has been indispensable to understand their functions in disease diagnosis and prognosis. Therefore, a biosensor for the robust, ultrasensitive, and selective detection of these low-abundant biomolecules in body fluids (blood, urine, and saliva) is emerging in current clinical research. In recent years, nanomaterials, especially superparamagnetic nanomaterials, have played essential roles in biosensing due to their intrinsic magnetic, electrochemical, and optical properties. However, engineered multicomponent magnetic nanoparticle-based current biosensors that offer the advantages of excellent stability in a complex biomatrix; easy and alterable biorecognition of ligands, antibodies, and receptor molecules; and unified point-of-care integration have yet to be achieved. This review introduces the recent advances in superparamagnetic nanostructures for electrochemical and optical biosensing for disease-specific biomarkers. This review emphasizes the synthesis, biofunctionalization, and intrinsic properties of nanomaterials essential for robust, ultrasensitive biosensing. With a particular emphasis on nanostructure-based electrochemical and optical detection of disease-specific biomarkers such as nucleic acids (DNA and RNA), proteins, autoantibodies, and cells, this review also chronicles the needs and challenges of nanoarchitecture-based detection. These summaries provide further insights for researchers to inspire their future work on the development of nanostructures for integrating into biosensing and devices for a broad field of applications in analytical sensing and in clinic.

Implantable electronics are of great interest owing to their capability for real-time and continuous recording of cellular–electrical activity. Nevertheless, as such systems involve direct interfaces with surrounding biofluidic environments, maintaining their long-term sustainable operation, without leakage currents or corrosion, is a daunting challenge. Herein, we present a thin, flexible semiconducting material system that offers attractive attributes in this context. The material consists of crystalline cubic silicon carbide nanomembranes grown on silicon wafers, released and then physically transferred to a final device substrate (e.g., polyimide). The experimental results demonstrate that SiC nanomembranes with thicknesses of 230 nm do not experience the hydrolysis process (i.e., the etching rate is 0 nm/day at 96 °C in phosphate-buffered saline (PBS)). There is no observable water permeability for at least 60 days in PBS at 96 °C and non-Na+ ion diffusion detected at a thickness of 50 nm after being soaked in 1× PBS for 12 days. These properties enable Faradaic interfaces between active electronics and biological tissues, as well as multimodal sensing of temperature, strain, and other properties without the need for additional encapsulating layers. These findings create important opportunities for use of flexible, wide band gap materials as essential components of long-lived neurological and cardiac electrophysiological device interfaces.

Mesoporous noble metals and their patterning techniques for obtaining unique patterned structures are highly attractive for electrocatalysis, photocatalysis, and optoelectronics device applications owing to their expedient properties such as high level of exposed active locations, cascade electrocatalytic sites, and large surface area. However, patterning techniques for mesoporous substrates are still limited to metal oxide and silica films, although there is growing demand for developing techniques related to patterning mesoporous metals. In this study, the first demonstration of mesoporous metal films on patterned gold (Au) substrates, prefabricated using photolithographic techniques, is reported. First, different growth rates of mesoporous Au metal films on patterned Au substrates are demonstrated by varying deposition times and voltages. In addition, mesoporous Au films are also fabricated on various patterns of Au substrates including stripe and mesh lines. An alternative fabrication method using a photoresist insulating mask also yields growth of mesoporous Au within the patterning. Moreover, patterned mesoporous films of palladium (Pd) and palladium-copper alloy (PdCu) are demonstrated on the same types of substrates to show versatility of this method. Patterned mesoporous Au films (PMGFs) show higher electrochemically active surface area (ECSA) and higher sensitivity toward glucose oxidation than nonpatterned mesoporous Au films (NMGF).

We report the nanoconfinement-mediated graphitic nanoporous carbon nitride (gNPCN) adsorbents with a high content of inbuilt basic nitrogen (N) (48%) by X-ray photoelectron spectroscopy (XPS) for efficient CO2 adsorption. The gNPCNs (gNPCN-150 and gNPCN-130) are synthesized using the mesoporous SBA-15 silica template and a single carbon-nitrogen (C–N) precursor (guanidine hydrochloride). The various adsorbents were utilized for investigating the influence of pore size (PS), surface area (SA), and type of adsorbent for CO2 adsorption performance. The capacity for CO2 capturing of gNPCN-150 reached 23.1 mmol/g at 0 °C under 30 bar pressure. This CO2 capturing capacity value was higher than the capacity gNPCN-130, SBA15, activated carbon (AC), and multiwalled carbon nanotube (MWCN) under identical conditions. The gNPCN materials exhibited superior CO2 adsorption ability that is ascribed to the presence of the highly organized mesoporosity, inbuilt high content of basic N site for adsorbing more CO2 through acid-base interaction, and tunable surface-structural properties. Moreover, the synthesis strategy is remarkably flexible in selecting C–N sources. This study features graphitic high-ordered nanoporous CN materials as a resourceful platform towards the efficient CO2 capture.

A series of organosulfur-functionalized trans-platinum(II) bis(alkenylarylalkynyl) complexes, having one tolylthio moiety in each alkenyl backbone with general formula trans-[(PEt3)2Pt{C C-Ar-CH CH(SC6H4 CH3)}2], (2a–2d), (where, Ar = phenylene, biphenylene, 2,5-dimethylphenylene, and 2,5-dimethoxyphenylene) were synthesized in good to excellent yields with good regioselectivity. As compared to the absorption band of trans-platinum(II) bis(alkynylarylalkynyl) complexes, we found that the position of the lowest energy absorption bands in the trans-platinum(II) bis(alkenylarylalkynyl) complexes were red-shifted, after the functionalization of the trans-platinum(II) bis(alkynylarylalkynyl) complexes with arylthiol. For all trans-platinum(II) complexes, the lowest energy absorption bands in the UV/Vis spectra, in chloroform solution, at room temperature, were observed in the range 362–394 nm, and under excitation at the wavelength of the absorption maximum exhibited the emission peak maximum at room temperature in the range 401–426 nm. The newly synthesized complexes are not exhibited phosphorescence at room temperature but are exhibited at low temperature, 77 K. All the new platinum(II) complexes have been fully characterized by spectroscopic analysis as well as elemental analysis, and the trans square-planar arrangement at the platinum centre has been confirmed by single-crystal X-ray diffraction study of complex 2a.

Two palladium(II) nitroaryl complexes trans-[bromo(p-nitrophenyl)bis(triphenylphosphine)palladium(II)] 1 and trans-[bromo(2,4-dinitrophenyl)bis(triphenylphosphine)palladium(II)] 2 have been synthesized. The complexes were characterized by FTIR and NMR (1H, 13C and 31P) spectroscopy and elemental analysis. The molecular structure of complex 2, as confirmed by X-ray crystallography, reveals that the Pd atom and its neighboring groups (two PPh3, Br and phenylene group) lie in a slightly distorted square plane. In the UV–Vis spectra of the complexes 1 and 2, the palladium to aryl charge transfer bands were observed. The emission peaks from the singlet excited states (S1 → S0) were observed in the photoluminescence spectra of the complexes. The thermal stability of the complexes has been studied by thermal gravimetric analysis (TGA). TGA data showed that both complexes are thermally stable up to 200 °C, and complex 1 is more stable than 2. The catalytic efficiency of the new palladium(II) complexes was studied as demonstrated using the Sonogashira coupling reactions with good yields. The experimental results suggest that the Sonogashira coupling reactions can be performed at moderate temperature (50 °C) using these new palladium(II) complexes as catalysts.

Advances in nanoarchitectonics enable a wide variety of nanostructured electrodes with tunable shapes and surface for constructing sensitive biosensors. Herein we demonstrate the fabrication of a mesoporous gold (Au) biosensor for the specific and sensitive detection of miRNA in a relatively simple and portable manner. The electrocatalytic activity of the mesoporous Au electrode (MPGE) towards the redox reaction of Fe(CN)6]3-/4- expansively examined. Leveraging the electrocatalytic activity and signal enhancement capacity of the MPGE, an ultrasensitive and specific electrochemical sensor was developed for the detection of microRNA (miRNA). The target miRNA from spiked samples is selectively isolated and purified using magnetic bead-capture probe followed by the direct adsorption on the MPGE through direct affinity interaction between miRNA and mesoporous Au surface. The MPGE-bound miRNA is then quantified by differential pulse voltammetry (DPV) using [Fe(CN)6]4-/3- redox system (Faradaic current decrease with reference to the bare MPGE). This method evades the cumbersome PCR (polymerase chain reaction) and enzymatic amplification steps. This is a single-step assay building which can detect a wide dynamic linear range (100 aM to 1 nM) of miRNA with an ultra-low limit detection of 100 aM and present high translational potentiality for the development of high-performance detection tools for clinics.

Semiconductor nanowires are widely considered as the building blocks that revolutionized many areas of nanosciences and nanotechnologies. The unique features in nanowires, including high electron transport, excellent mechanical robustness, large surface area, and capability to engineer their intrinsic properties, enable new classes of nanoelectromechanical systems (NEMS). Wide bandgap (WBG) semiconductors in the form of nanowires are a hot spot of research owing to the tremendous possibilities in NEMS, particularly for environmental monitoring and energy harvesting. This article presents a comprehensive overview of the recent progress on the growth, properties and applications of silicon carbide (SiC), group III‐nitrides, and diamond nanowires as the materials of choice for NEMS. It begins with a snapshot on material developments and fabrication technologies, covering both bottom‐up and top‐down approaches. A discussion on the mechanical, electrical, optical, and thermal properties is provided detailing the fundamental physics of WBG nanowires along with their potential for NEMS. A series of sensing and electronic devices particularly for environmental monitoring is reviewed, which further extend the capability in industrial applications. The article concludes with the merits and shortcomings of environmental monitoring applications based on these classes of nanowires, providing a roadmap for future development in this fast‐emerging research field., Wide bandgap semiconductor nanowires with unique properties and advanced fabrication/integration technologies set a new class of nanosensing and electronic applications. Implementation of these smart devices such as gas sensors, photodetectors, wearable devices, strain sensors, and energy harvesters into environmental monitoring systems offers promising solutions for critical environmental challenges.

With revolutionary advances in next-generation sequencing, the human transcriptome has been comprehensively interrogated. These discoveries have highlighted the emerging functional and regulatory roles of a large fraction of RNAs suggesting the potential they might hold as stable and minimally invasive disease biomarkers. Although a plethora of molecular-biology- and biosensor-based RNA-detection strategies have been developed, clinical application of most of these is yet to be realized. Multifunctional nanomaterials coupled with sensitive and robust electrochemical readouts may prove useful in these applications. Here, we summarize the major contributions of engineered nanomaterials-based electrochemical biosensing strategies for the analysis of miRNAs. With special emphasis on nanostructure-based detection, this review also chronicles the needs and challenges of miRNA detection and provides a future perspective on the presented strategies.

The enzyme-mimicking activity of iron oxide based nanostructures has provided a significant advantage in developing advanced molecular sensors for biomedical and environmental applications. Herein, we introduce the horseradish peroxidase (HRP)-like activity of gold-loaded nanoporous ferric oxide nanocubes (Au–NPFe2O3NC) for the development of a molecular sensor with enhanced electrocatalytic and colorimetric (naked eye) detection of autoantibodies. The results showed that Au–NPFe2O3NC exhibits enhanced peroxidase-like activity toward the catalytic oxidation of 3,3′,5,5′-tertamethylbenzidine (TMB) in the presence of H2O2 at room temperature (25 °C) and follows the typical Michaelis–Menten kinetics. The autoantibody sensor based on this intrinsic property of Au–NPFe2O3NC resulted in excellent detection sensitivity [limit of detection (LOD) = 0.08 U/mL] and reproducibility [percent relative standard deviation (% RSD) =

This paper reports the development of a nonenzymatic, amplification-free, and sensitive platform for the detection of microRNA based on a new class of electrocatalytically active superparamagnetic gold-loaded nanoporous iron oxide nanocubes (Au@NPFe2O3NC). The assay showed an excellent detection sensitivity down to 100 fM and specificity towards the analysis of miR-21 in cell lines and tissue samples derived from patients with oesophageal squamous-cell carcinoma (ESCC).

Despite having reliable and excellent diagnostic performances, the currently available messenger RNA (mRNA) detection methods mostly use enzymatic amplification steps of the target mRNA which is generally affected by the sample manipulations, amplification bias and longer assay time. This paper reports an amplification-free electrochemical approach for the sensitive and selective detection of mRNA using a screen-printed gold electrode (SPE-Au). The target mRNA is selectively isolated by magnetic separation and adsorbed directly onto an unmodified SPE-Au. The surface-attached mRNA is then measured by differential pulse voltammetry (DPV) in the presence of [Fe(CN)6]4-/3- redox system. This method circumvents the PCR amplification steps as well as simplifies the assay construction by avoiding multiple steps involved in conventional biosensing approaches of using recognition and transduction layers. Our method has demonstrated good sensitivity (LOD = 1.0 pM) and reproducibility (% RSD =

Development of simple and inexpensive method for the analysis of gene-specific DNA methylation is important for the diagnosis and prognosis of patients with cancer. Herein, we report a relatively simple and inexpensive electrochemical method for the sensitive and selective detection of gene-specific DNA methylation in oesophageal cancer. The underlying principle of the method relies on the affinity interaction between DNA bases and unmodified gold electrode. Since the affinity trend of DNA bases towards the gold surface follows as adenine (A) > cytosine (C) > guanine (G)> thymine (T), a relatively larger amount of bisulfite-treated adenine-enriched unmethylated DNA adsorbs on the screen-printed gold electrodes (SPE-Au) in comparison to the guanine-enriched methylated sample. The methylation levels were (i.e., different level of surface attached DNA molecules due to the base dependent differential adsorption pattern) quantified by measuring saturated amount of charge-compensating [Ru(NH3)6]3+ molecules in the surface-attached DNAs by chronocoulometry as redox charge of the [Ru(NH3)6]3+ molecules quantitatively reflects the amount of the adsorbed DNA confined at the electrode surface. The assay could successfully distinguish methylated and unmethylated DNA sequences at single CpG resolution and as low as 10% differences in DNA methylation. In addition, the assay showed fairly good reproducibility (% RSD=

Objective : To find out the clinical presentation of metastatic neck node with unknown primary. Methods : A cross-sectional study done on the admitted patient from four tertiary level hospitals in Dhaka city from January 2010 to September 2010. Results : Most of the cases were squamous cell carcinoma (68.75%). the next common was adenocarcinoma (15.62%) and undifferentiated carcinoma (12.5%). Melanoma was a rare condition (3.13%). The commonest age group was 6th decade (40.63%) which was followed by 5th decade (28%). None of the case was found bellow the age of 30 years. The male to female ratio was 2:1. Commonest metastatic group of lymph node was Level II (50%), followed by Level- III (22%) Level- IV (19%), Level- V (6%) and Level- I (3%). Staging of lymph nodes were N2A (35%), N1 (31%), N2B (16%), N3 (12.5%) and N2C (6.25%) in decreasing order of frequency. About 72% cases are smoker. Conclusion : Metastatic carcinoma with unknown primary tumour commonly present in elderly age group and majority of cases are squmous cell carcinoma . DOI: http://dx.doi.org/10.3329/bjo.v19i2.17631 Bangladesh J Otorhinolaryngol 2013; 19(2): 94-98

Ribonucleic acids (RNAs) are considered as effective and minimally invasive biomarkers for disease diagnosis and prognosis due to their critical role in the regulation of different cellular processes. Over the past several years, the rapid progress in RNA biomarker research has resulted in the development of a large number of high-performance RNA-detection methods. Most of these methods are based on molecular-biology techniques such as quantitative reverse transcription polymerase chain reaction (RT-qPCR), microarrays, and RNA sequencing. In recent years, considerable attention has also been dedicated to developing RNA biosensors, exploiting micro- and nanofabrication technologies, and various readout strategies, including electrochemical and optical transducers. Here, the recent developments of RNA biosensors are concisely reviewed with a special emphasis on electrochemical-detection approaches. The following points are also highlighted: i) all the types of clinically relevant RNAs (mRNAs, miRNAs, lncRNAs) and their diagnostic and prognostic potential in cancer are outlined, ii) major challenges associated with current techniques are identified, followed by a critical analysis of how these challenges have been addressed by different biosensing approaches, and iii) the current requirements that still need to be met for effective screening of RNA biomarkers in both research and clinical settings.