Search

Detection of rickettsia most commonly done by simple, economical Weil-Felix test which detects IgM antibody. This initial investigation provides limited sound guidance to clinical decisions because of its low specificity and sensitivity. An alternative test, enzyme-linked immunosorbent assay (ELISA) is faster, less complicated, can also be automated. Advancements in molecular method like polymerase chain reaction (PCR) are highly specific, sensitive and rapid assays for detection of rickettsiales in many different samples including blood, tissue etc. This study was carried out to diagnose the rickettsial agent in the north-central (Mymensingh division) area of Bangladesh. In laboratory, we performed ELISA and PCR. The agent was diagnosed up to species level by molecular approach. A total of 150 febrile patients were included. All were clinically suspected cases of rickettsial fever attending inpatient and outpatient department of medicine and pediatrics of Mymensingh Medical College Hospital from Octy 2012 to January 2014. The laboratory tests were performed in Microbiology department of Mymensingh Medical College. Following universal safety precautions blood samples were collected, serum separated and both were stored at -20°C. IgM ELISA and Nested PCR were performed. Several genes by PCR were detected for confirmation of the presence of rickettsial agent in the blood. Among 150 clinically suspected cases 76(50.66%) were positive for ELISA, and 69(46.0%) were positive for PCR. The sensitivity and specificity of ELISA were 92.75% and 85.19% respectively taking PCR as gold standard. The prevalence of rickettsial infection found in this study was very much close to other countries of this Sub continent.

Understanding the growth of mesoporous crystalline materials, such as mesoporous metals, on different substrates can provide valuable insights into the crystal growth dynamics and the redox reactions that influence their electrochemical sensing performance. Herein, it is demonstrated how the amorphous nature of the glass substrate can suppress the typical <111> oriented growth in mesoporous Au (mAu) films. The suppressed <111> growth is manifested as an accumulation of strain, leading to the generation of abundant surface defects, which are beneficial for enhancing the electrochemical activity. The fine structuring attained enables dramatically accelerated diffusion and enhances the electrochemical sensing performance for disease-specific biomolecules. As a proof-of-concept, the as-fabricated glass-grown mAu film demonstrates high sensitivity in electrochemical detection of SARS-CoV-2-specific RNA with a limit of detection (LoD) as low as 1 attomolar (aM)., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test ( n = 20) (Pearson's r = 0.99) and validation ( n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to therapy.

Lattice strain effects on the piezoelectric properties of crystalline ferroelectrics have been extensively studied for decades; however, the strain dependence of the piezoelectric properties at nano-level has yet to be investigated. Herein, a new overview of the super-strain of nanoporous polycrystalline ferroelectrics is reported for the first time using a nanoengineered barium calcium zirconium titanate composition (Ba 0.85 Ca 0.15 )(Ti 0.9 Zr 0.1 )O 3 (BCZT). Atomic-level investigations show that the controlled pore wall thickness contributes to highly strained lattice structures that also retain the crystal size at the optimal value (<30 nm), which is the primary contributor to high piezoelectricity. The strain field derived from geometric phase analysis at the atomic level and aberration-corrected high-resolution scanning transmission electron microscopy (STEM) yields of over 30% clearly show theoretical agreement with high piezoelectric properties. The uniqueness of this work is the simplicity of the synthesis; moreover the piezoresponse d 33 becomes giant, at around 7500 pm V -1 . This response is an order of magnitude greater than that of lead zirconate titanate (PZT), which is known to be the most successful ferroelectric over the past 50 years. This concept utilizing nanoporous BCZT will be highly useful for a promising high-density electrolyte-free dielectric capacitor and generator for energy harvesting in the future., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Immune checkpoint proteins (ICPs) play a major role in a patient's immune response against cancer. Tumour cells usually express those proteins to communicate with immune cells as a process of escaping the anti-cancer immune response. Detecting the major functional immune checkpoint proteins present on cancer cells (such as circulating tumor cells or CTCs) and examining the heterogeneity in their expression at the single-cell level could play a crucial role in both cancer diagnosis and the monitoring of therapy. In this study, we develop a mesoporous gold biosensor to precisely assess ICP heterogeneity in individual cancer cells within a lung cancer model. The platform utilizes a nanostructured mesoporous gold surface to capture CTCs and a Surface Enhanced Raman Scattering (SERS) readout to identify and monitor the expression of key ICP proteins (PD-L1, B7H4, CD276, CD80) in lung cancer cells. The homogeneous and abundant pores in mesoporous 3D gold nanostructures enable increased antibody loading on-chip and an enhanced SERS signal, which are key to our single cell capture, and accurate analysis of ICPs in cancer cells with high sensitivity. Our lung cancer cell line model data showed that our method can detect single cells and analyse the expression of four lung cancer associated ICPs on individual cell surfaces during treatment. To show the potential of our mesoporous gold biosensor in analysing clinical samples, we tested 9 longitudinal Peripheral Blood Mononuclear Cells (PBMC) samples from lung cancer patient before and after therapy. Our mesoporous biosensor successfully captured single CTCs and found that the expression of ICPs in CTCs is highly heterogeneous in both pre-treatment and treated PBMC samples isolated from lung cancer patient blood. We suggest that our findings will help clinicians in selecting the most appropriate therapy for patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Binary metastable semiconductor materials offer exciting possibilities in the field of optoelectronics, such as photovoltaics, tunable photosensors, and detectors. However, understanding their properties and translating them into practical applications can sometimes be challenging, owing to their thermodynamic instability. Herein, we report a temperature-controlled crystallization technique involving electrochemical deposition to produce metastable CuTe 2 thin films that can reliably function under ambient conditions. A series of in situ heating/cooling cycle tests from room temperature to 200 °C followed by spectral, morphological, and compound analyses (such as ultraviolet-visible light spectroscopy, X-ray diffraction (XRD) analysis, and X-ray photoelectron spectroscopy (XPS)) suggest that the seeding electrodes play a key role in the realization of the metastable phase in CuTe 2 films. In particular, CuTe 2 films deposited on Al electrodes exhibit superior crystallinity and long-term stability compared with those grown on a Au substrate. The XRD data of thermally annealed CuTe 2 thin films deposited on Al show a markedly sharp peak, indicating significantly increased crystal-domain sizes. Our method can be used to achieve the metastable phase of CuTe 2 with a bandgap of 1.67 eV and offers outstanding photoresponsivity under different illumination conditions.

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 -2  µM -1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Construction of a well-defined mesoporous nanostructure is crucial for applying nonnoble metals in catalysis and biomedicine owing to their highly exposed active sites and accessible surfaces. However, it remains a great challenge to controllably synthesize superparamagnetic CoFe-based mesoporous nanospheres with tunable compositions and exposed large pores, which are sought for immobilization or adsorption of guest molecules for magnetic capture, isolation, preconcentration, and purification. Herein, a facile assembly strategy of a block copolymer was developed to fabricate a mesoporous CoFeB amorphous alloy with abundant metallic Co/Fe atoms, which served as an ideal scaffold for well-dispersed loading of Au nanoparticles (∼3.1 nm) via the galvanic replacement reaction. The prepared Au-CoFeB possessed high saturation magnetization as well as uniform and large open mesopores (∼12.5 nm), which provided ample accessibility to biomolecules, such as nucleic acids, enzymes, proteins, and antibodies. Through this distinctive combination of superparamagnetism (CoFeB) and biofavorability (Au), the resulting Au-CoFeB was employed as a dispersible nanovehicle for the direct capture and isolation of p53 autoantibody from serum samples. Highly sensitive detection of the autoantibody was achieved with a limit of detection of 0.006 U/mL, which was 50 times lower than that of the conventional p53-ELISA kit-based detection system. Our assay is capable of quantifying differential expression patterns for detecting p53 autoantibodies in ovarian cancer patients. This assay provides a rapid, inexpensive, and portable platform with the potential to detect a wide range of clinically relevant protein biomarkers.

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., (© 2022 Wiley-VCH GmbH.)

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., (© 2021 Wiley-VCH GmbH.)

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 2 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 CO 2 adsorption performance. The capacity for CO 2 capturing of gNPCN-150 reached 23.1 mmol/g at 0 °C under 30 bar pressure. This CO 2 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 CO 2 adsorption ability that is ascribed to the presence of the highly organized mesoporosity, inbuilt high content of basic N site for adsorbing more CO 2 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 CO 2 capture., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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.

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., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

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)., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

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.

Autoantibodies produced by the patients' own immune systems in response to foreign substances are emerging as an attractive biomarker for early detection of cancer. These serum immunobiomarkers are produced in large quantities despite the presence of very less amount of the corresponding antigens, and thus presenting themselves as a novel class of stable and minimally invasive disease biomarkers especially for cancer diagnosis. Although a plethora of research, including conventional molecular biology-based as well as cutting-edge optical and electrochemical strategies (biosensor), have been conducted to detect autoantibodies, most of these strategies are yet to be readily applicable in the off-laboratory settings at clinics. Herein, we detail the biogenesis, diagnostic, prognostic and therapeutic potential of autoantibodies as cancer biomarkers. With the particular emphasis on cutting-edge advances in electrochemistry, optical (surface plasmon resonance) and microfluidics techniques, this review entrusts the unmet needs and challenges of autoantibody detection approaches and provides a future perspective of the presented strategies. We believe this review can potentially guide the researchers towards the development of robust, reliable and sensitive detection strategies for tumor-associated autoantibodies and translation of these biomarkers to real clinical settings for diagnosis and prognosis of cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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-NPFe 2 O 3 NC). In this method, the Au-NPFe 2 O 3 NC 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-NPFe 2 O 3 NC-bound exosomes were transferred to the tissue-specific, antibody-modified, screen-printed electrode. As a proof of principle, we used a specific placental marker, placenta alkaline phosphatase (PLAP), to detect exosomes secreted from placental cells. The peroxidase-like activity of Au-NPFe 2 O 3 NC was then used to accomplish an enzyme-linked immunosorbent assay (ELISA)-based sensing protocol for naked-eye observation along with UV-visible and electrochemical detection of PLAP-specific exosomes present in placental cell-conditioned media. We demonstrated excellent agreement in analytical performance for the detection of placental cell-derived exosomes (i.e., linear dynamic range, 10 3 -10 7 exosomes/mL; limit of detection, 10 3 exosomes/mL; relative standard deviation (%RSD) of <5.5% for n = 3) using with and without commercial "total exosome isolation kit"-based preisolation step. We envisage that this highly sensitive, rapid, and inexpensive assay could be useful in quantifying specific populations of exosomes for various clinical applications, focusing on pregnancy complications.

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 = <5%, for n = 3). This strategy avoids the use of natural enzyme horseradish peroxidase (HRP), traditional PCR based amplification and bisulfite treatment steps that are generally used in many conventional DNA methylation assays. We envisage that our assay could be a low-cost platform with great potential for genome-wide DNA methylation analysis in point-of-care applications.

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-NPFe 2 O 3 NC). The target miRNA was directly adsorbed onto the gold surfaces of Au-NPFe 2 O 3 NC via gold-RNA affinity interaction. The electrocatalytic activity of Au-NPFe 2 O 3 NC was then used for the reduction of ruthenium hexaammine(III) chloride (RuHex, [Ru(NH 3 ) 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 = 1.0pM) and reproducibility (% RSD = <5%, for n = 3) for detecting FAM134B mRNA in two cancer cell lines and a small cohort of clinical samples (number of samples = 26) collected from patients with oesophageal cancer. The analytical performance of our method is validated with a standard qRT-PCR analysis. We believe that our PCR-free approach holds a great promise for the analysis of tumor-specific mRNA in clinical samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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-NPFe 2 O 3 NC) for the development of a molecular sensor with enhanced electrocatalytic and colorimetric (naked eye) detection of autoantibodies. The results showed that Au-NPFe 2 O 3 NC exhibits enhanced peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB) in the presence of H 2 O 2 at room temperature (25 °C) and follows the typical Michaelis-Menten kinetics. The autoantibody sensor based on this intrinsic property of Au-NPFe 2 O 3 NC resulted in excellent detection sensitivity [limit of detection (LOD) = 0.08 U/mL] and reproducibility [percent relative standard deviation (% RSD) = <5% for n = 3] for analyzing p53-specific autoantibodies using electrochemical and colorimetric (naked eye) readouts. The clinical applicability of the sensor has been tested in detecting p53-specific autoantibody in plasma obtained from patients with epithelial ovarian cancer high-grade serous subtype (EOCHGS, number of samples = 2) and controls (benign, number of samples = 2). As Au-NPFe 2 O 3 NC possess high peroxidase-like activity for the oxidation of TMB in the presence of H 2 O 2 [TMB is a common chromogenic substrate for HRP in enzyme-linked immunosorbent assays (ELISAs)], we envisage that our assay could find a wide range of application in developing ELISA-based sensing approaches in the fields of medicine (i.e., detection of other biomarkers the same as p53 autoantibody), biotechnology, and environmental sciences.

Correction for 'Gold-loaded nanoporous iron oxide nanocubes: a novel dispersible capture agent for tumor-associated autoantibody analysis in serum' by Sharda Yadav et al., Nanoscale, 2017, 9, 8805-8814.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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(NH 3 ) 6 ] 3+ molecules in the surface-attached DNAs by chronocoulometry as redox charge of the [Ru(NH 3 ) 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= <5%) with better sensitivity and specificity by analysing various levels of methylation in two cell lines and eight fresh tissues samples from patients with oesophageal squamous cell carcinoma. Finally, the method was validated with methylation specific-high resolution melting curve analysis and Sanger sequencing methods., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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@NPFe 2 O 3 NC)-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@NPFe 2 O 3 NC with p53 antigens, our method utilises a two-step strategy that involves (i) magnetic capture and isolation of autoantibodies using p53/Au@NPFe 2 O 3 NC 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 = <5%, for n = 3) for detecting p53 autoantibodies in serum and has also been successfully applied to analyse a small cohort of clinical samples obtained from colorectal cancer. We believe that the highly inexpensive, rapid, sensitive, and specific nature of our assay could potentially aid in the development of an early diagnostic tool for cancer and related diseases.

The aim of this study was to determine the frequency of structural variations in nose & paranasal sinuses in computed tomography in Bangladeshi people. This retrospective study was done at the Sir Salimullah Medical College Mitford Hospital and Apollo Hospitals, Dhaka, Bangladesh. Fifty (50) CT scan of Nose and Para nasal sinuses were collected from the patients presented with different sinonasal pathologies in OPD, IPD of both hospitals from July 2013 to June 2014. The scans were reviewed for the presence of different structural variations of nose and paranasal sinuses. The age range of the patients was 25 to 65 years. The most common anatomical variation in this study was hypertrophied inferior turbinate (82%) followed by ethmoidal bulla (70%), deviated nasal septum (64%), agar nasi cell (40%), concha bullosa (38%). In most of the patients we found more than one variation. There is wide range of anatomical variations in nose and paranasal sinuses which might be regarded as the aetiological factors of different sinonasal pathologies. To maximize patients' benefit and to avoid unexpected situations during surgeries as well as dreadful complications, individualized pre-planning through tomographic study should be considered.

Metastatic dissemination into lymph nodes of neck occurs frequently in head neck cancers which down grade the patient's curability and survival. Neck dissection is a curable option for its management. To evaluate the complications following different types of neck dissection. This cross sectional study was conducted among patients undergone different types of neck dissection due to cervical nodal metastasis and attended follow up during July 2010 to June 2011 in Department of ENTs and Head-Neck surgery Dhaka Medical College Hospital, Dhaka, Bangladesh. Among 30 selected patient, 23 were male (76.67%) and 7 were female (23.33%), age ranged from 31-72 years (Mean=59.1±5.44). In different modalities of neck dissection 11 were modified neck dissection (36.67%) and 10(33.33%) were radical neck dissection. Common indication was carcinoma of unknown origin (66.67%). Involved neck nodes were commonly level II-IV (69.99%). Nodal stage was N2(50%) and N3 (40%).Common immediate complications were bleeding 03(10%), facial oedema 02 (6.67%) and thoracic duct injury 02(6.67%). Intermediate complications were seroma 05(16.67%), wound infection 04(13.33%) and chylous fistula 02(6.67%), Late Complications were hypertrophic scar 07(23.33%) and shoulder syndrome 06(20%). Proper indications, skilled surgery along with early recognize and treatment in both early and late manifestations of neck dissection preventing its grave sequence.

Histoplasma capsulatum is an endemic granulomatous fungus disease. Involving the larynx of an immunocompetent patient with this is a rare manifestation. A sixty years old farmer who was previously diagnosed and treated as pulmonary tuberculosis was presented as a progressive change of voice and intermittent attack of unproductive cough with no history of stridor and fever for last 7 months. Clinical and imaging investigations were suggestive of laryngeal tuberculosis or laryngeal neoplasm. Laryngoscopy revealed edema, erythema and leukoplakia of the right vocal cord. Histopathological report showed intracellular hyphae of Histoplasma capsulatum, features were consistent with histoplasmosis. Patient were treated accordingly and improved. Laryngeal histoplasmosis present as a mimicker of squamous cell carcinoma or tuberculosis, may lead to the misdiagnosis and mistreatment of tuberculosis or laryngeal cancer. A high index of suspicion and a thorough histologic workup is needed to establish the diagnosis correctly.