Diagnosis of Neglected Tropical Zoonotic Disease, Leptospirosis in a Clinical Sample Using a Photothermal Immunosensor.

Photothermal biosensing based on nanomaterials has gained increasing attention because of its universality and simplicity. Diagnostics of neglected tropical diseases (NTDs) in low-resource settings are challenging in terms of speed, accuracy, and cost-effectiveness. By exploiting the photothermal property of carbon nanotubes (CNTs), simple thermometric measurements can be used to generate quantitative biochemical readouts. Herein, a photothermal immunosensor for leptospirosis detection based on a CNT-labeled monoclonal antibody is established through the sensitive monitoring of the target biomarker LipL32 with a simple thermometer. Under optimum conditions, a linear range up to 106 pg/mL with a limit of detection (LOD) of 300 fg/mL was obtained. Overall, the proposed immunoassay exhibited good precision, selectivity, and acceptable stability. Clinical patient sample analysis with the photothermal sensor proved the differential diagnosis of leptospirosis along with other febrile illnesses. On the other hand, we have also characterized the photothermal sensor platform with surface morphological and spectral techniques to confirm the robust and successful fabrication of the immunosensor. The fabricated photothermal sensor could be used as a potential diagnostic tool for the early detection of NTDs in patients from resource-limited settings, as it does not require sample pretreatment, sophisticated equipment, or skilled labor. Moreover, the developed photothermal assay follows ASSURED criteria, very crucial for diagnosis in resource-limited settings.

Comparison of partitioned survival modeling with state transition modeling approaches with or without consideration of brain metastasis: a case study of Osimertinib versus pemetrexed-platinum.

BACKGROUND: The partitioned survival model (PSM) and the state transition model (STM) are widely used in cost-effectiveness analyses of anticancer drugs. Using different modeling approaches with or without consideration of brain metastasis, we compared the quality-adjusted life-year (QALY) estimates of Osimertinib and pemetrexed-platinum in advanced non-small cell lung cancer with epidermal growth factor receptor mutations. METHODS: We constructed three economic models using parametric curves fitted to patient-level data from the National Health Insurance Review and Assessment claims database from 2009 to 2020. PSM and 3-health state transition model (3-STM) consist of three health states: progression-free, post-progression, and death. The 5-health state transition model (5-STM) has two additional health states (brain metastasis with continuing initial therapy, and with subsequent therapy). Time-dependent transition probabilities were calculated in the state transition models. The incremental life-year (LY) and QALY between the Osimertinib and pemetrexed-platinum cohorts for each modeling approach were estimated over seven years. RESULTS: The PSM and 3-STM produced similar incremental LY (0.889 and 0.899, respectively) and QALY (0.827 and 0.840, respectively). However, 5-STM, which considered brain metastasis as separate health states, yielded a slightly higher incremental LY (0.910) but lower incremental QALY (0.695) than PSM and 3-STM. CONCLUSIONS: Our findings indicate that incorporating additional health states such as brain metastases into economic models can have a considerable impact on incremental QALY estimates. To ensure appropriate health technology assessment decisions, comparison and justification of different modeling approaches are recommended in the economic evaluation of anticancer drugs.

Capillary and Electrodynamic Forces-Driven Separation Detection of Metal Ions Using a Disposable Microfluidic Sensor with a Composite Electrode.

A disposable microfluidic channel sensor printed on a plastic platform was developed to analyze heavy metal ions (HMIs) as a model target species. Precise separation and detection of multiple targets were established by symmetrically applying a small AC potential on the carbon channel walls to induce an electrodynamic force. The separation device was constructed by covering it with a plastic lid to achieve capillary action in the channel. The sample flow rate was regulated by the hydrophilicity of the lid plastic and electrodynamic convection by the AC field, which was characterized by the contact angle measurement and the additional electrodynamic force. The flow variables and their relevance to the capillary phenomena were demonstrated, and the analytical parameters were optimized. The working electrode was modified with poly(diamino terthiophene) anchored with nanosized graphene oxide (pDATT/GO) to enhance the detection performance. The experimental variables for separating and detecting the target species were optimized according to the AC frequency and amplitude, sample flow rate, electrolytes, pH, temperature, and applied potential for detection. The linear dynamic ranges were between 0.1 and 200.0 ppb, with detection limits of 0.04 ± 0.023, 0.29 ± 0.05, 0.07 ± 0.011, and 0.14 ± 0.06 ppb for Cu2+ Cd2+, Hg2+, and Pb2+, respectively. Finally, the reliability of the proposed method was evaluated through analysis of HMIs in real water samples. The results were matched to those obtained through parallel analysis using ICP-MS at a 95% confidence level.

Fast Aptamer Generation Method Based on the Electrodynamic Microfluidic Channel and Evaluation of Aptamer Sensor Performance.

We demonstrate for the first time a fast aptamer generation method based on the screen-printed electrodynamic microfluidic channel device, where a specific aptamer selectively binds to a target protein on channel walls, following recovery and separation. A malaria protein as a model target, Plasmodium vivax lactate dehydrogenase (PvLDH) was covalently bonded to the conductive polymer layer formed on the carbon channel walls to react with the DNA library in a fluid. Then, the AC electric field was symmetrically applied on the channel walls for inducing the specific binding of the target protein to DNA library molecules. In this case, the partitioning efficiency between PvLDH and DNA library in the channel was attained to be 1.67 × 107 with the background of 5.56 × 10-6, which was confirmed using the quantitative polymerase chain reaction (qPCR). The selectively captured DNAs were isolated from the protein and separated in situ to give five aptamers with different sequences by one round cycle. The dissociation constants (Kd) of the selected aptamers were determined employing both electrochemical impedance spectroscopy (EIS) and the fluorescence method. The sensing performance of each aptamer was evaluated for the PvLDH detection after individual immobilization on the screen-printed array electrodes. The most sensitive aptamer revealed a detection limit of 7.8 ± 0.4 fM. The sensor reliability was evaluated by comparing it with other malaria sensors.

Hydrogen Evolution and Oxygen Reduction Reactions in Acidic Media Catalyzed by Pd4 S Decorated N/S Doped Carbon Derived from Pd Coordination Polymer.

The template-free synthesis and the characterization of an active electrocatalyst are performed for both the hydrogen evolution and oxygen reduction reactions in acidic media. In this work, the unique chelation mode of benzene-1,4-dithiocarboxamide (BDCA) is first used to synthesize a novel palladium-BDCA coordination polymer (PdBDCA) as a precursor of palladium sulfide nanoparticles-decorated nitrogen and sulfur doped carbon (Pd4 S-SNC). The newly synthesized PdBDCA and Pd4 S-SNC nanoparticles are characterized using chemical, electrochemical, and surface analysis methods. Notably, the nanoparticles obtained at 700 °C exhibit the remarkable catalytic property for the hydrogen evolution reaction in 0.5 m H2 SO4 , showing the overpotential of 32 mV (vs reversible hydrogen electrode (RHE)) and Tafel slope of 52 mV dec-1 , which are comparable to that of Pt/C. The catalyst also shows a high oxygen reduction activity, offering the half-wave and onset potentials of 0.92 and 0.77 V (vs RHE) in 0.5 m H2 SO4 , with improved methanol tolerance and long-term stability compared with Pt/C. The present study gives a way for the design of excellent electrocatalyst for the energy conversion devices in the corrosive acidic environment.

A novel DNA binding protein-based platform for electrochemical detection of miRNA.

We present a novel amplification-free sandwich type platform assay for electrochemical detection of miRNA. The assay is based on T4 DNA polymerase mediated synthesis of the p53 binding DNA sequence at the 3' end of target miRNA. The resulting miRNA-DNA chimera is detected via an electrochemical sandwich hybridization assay where HRP-labelled p53 binds to its recognition sequence and an amperometric signal is generated by hydroquinone-mediated enzymatic reduction of H2O2. The limit of detection of our assay was estimated to be 22 fM with a linear dynamic range of 100 fM-1 nM. This new platform method of detecting miRNA shows superior performance to conventional electrochemical miRNA biosensors and has the potential for amplification-free analysis of miRNA with high specificity and sensitivity.

Nanozyme-based electrochemical biosensors for disease biomarker detection.

In recent years, a new group of nanomaterials named nanozymes that exhibit enzyme-mimicking catalytic activity has emerged as a promising alternative to natural enzymes. Nanozymes can address some of the intrinsic limitations of natural enzymes such as high cost, low stability, difficulty in storage, and specific working conditions (i.e., narrow substrate, temperature and pH ranges). Thus, synthesis and applications of hybrid and stimuli-responsive advanced nanozymes could revolutionize the current practice in life sciences and biosensor applications. On the other hand, electrochemical biosensors have long been used as an efficient way for quantitative detection of analytes (biomarkers) of interest. As such, the use of nanozymes in electrochemical biosensors is particularly important to achieve low cost and stable biosensors for prognostics, diagnostics, and therapeutic monitoring of diseases. Herein, we summarize the recent advances in the synthesis and classification of common nanozymes and their application in electrochemical biosensor development. After briefly overviewing the applications of nanozymes in non-electrochemical-based biomolecular sensing systems, we thoroughly discuss the state-of-the-art advances in nanozyme-based electrochemical biosensors, including genosensors, immunosensors, cytosensors and aptasensors. The applications of nanozymes in microfluidic-based assays are also discussed separately. We also highlight the challenges of nanozyme-based electrochemical biosensors and provide some possible strategies to address these limitations. Finally, future perspectives on the development of nanozyme-based electrochemical biosensors for disease biomarker detection are presented. We envisage that standardization of nanozymes and their fabrication process may bring a paradigm shift in biomolecular sensing by fabricating highly specific, multi-enzyme mimicking nanozymes for highly sensitive, selective, and low-biofouling electrochemical biosensors.

MicroRNAs in ovarian cancer and recent advances in the development of microRNA-based biosensors.

Ovarian cancer is the most aggressive of all gynaecological malignancies and is the leading cause of cancer-associated mortality worldwide. Over the recent years, there has been a sharp increase in this mortality rate, mostly due to late diagnosis, which can be attributed to the lack of an early and specific biomarker. Under this scenario, recent interest has shifted towards ovarian cancer associated miRNAs which play strong regulatory roles in various cellular processes. miRNAs have emerged as promising non/minimally invasive cancer biomarkers for improved diagnostic, prognostic and streamlined therapeutic applications. A large number of miRNA assays have been reported that are based on nucleic acid detection-based techniques such as RT-qPCR, microarrays and RNA sequencing methods. Despite demonstrating commendable analytical performances, these laboratory-based techniques are expensive and hence not ideally suited for routine use in resource-limited settings. In recent years, considerable attention has been dedicated to the development of relatively simple, rapid and inexpensive miRNA biosensor strategies. Among these, electrochemical sensors have shown a great promise towards point-of-care diagnostics, due to their inherent advantages such as simplicity, sensitivity, amenability to high levels of multiplexing as well as low cost. In this paper, we provide an overview of the potential role of miRNAs in ovarian cancer, as well as recent advances in the development of nanotechnology-based, optical, and electrochemical biosensing-strategies for miRNA detection.

Chiral Pd6L8 Nanocube Pairs: Recognition of Chiral Amino Acids via Electrochemistry.

The self-assembly of PdX2 (X- = ClO4- and PF6-) with C3-symmetric l- and d-L [L = (2S,2'S,2″S)- and (2R,2'R,2″R)-[benzenetricarbonyltris(azanediyl)]tris(3-phenylpropane-2,1-diyl)triisonicotinate] produces the chiral nanocube pair [Pd6(l-L)8](X)12 and [Pd6(d-L)8](X)12 (X- = ClO4- and PF6-, respectively) with an inner cavity of 12.3 × 12.3 × 12.3 Å3. These chiral nanocubes are effective for the enantiorecognition of various chiral amino acids via the square-wave-voltammetry technique. In the present study, the site of enantiorecognition was confirmed by density functional theory calculated interactions between each nanocube and the chiral amino acids, and the calculated interactions were coincident with the shifts of the electrochemical oxidation potentials.

Electrodynamic Force Derived in-Channel Separation and Detection of Au Nanoparticles Using an Electrochemical AC Microfluidic Channel.

In this study, we have established the separation of Au nanoparticles (AuNPs) using a symmetrical AC electric field applied-electrochemical microfluidic device composed of carbon channel and detection electrodes. The lateral movement of AuNPs in the channel under the AC field was analyzed by simulation using the mathematically derived equations, which were formulated from Newtonian fluid mechanics. It shows that the nanoparticles are precisely separated according to their respective mass or size difference in a short time. The experimental parameters affecting the separation and detection of AuNPs were optimized in terms of applied frequency, amplitude, flow rate, buffer concentration, pH dependency, and temperature. The final separation was performed at 1.0 V amplitude with 8.0 MHz frequency at 0.4 µL/min flow rate for the separation, and the potential of 1.0 V was applied for the amperometric detection of AuNPs in a 0.1 M PBS. Before and after the separation, AuNPs (diameter range: 3-60 nm) were confirmed by UV-visible spectroscopy and transmission electron microscopy. In this case, the separation resolution was 3 nm with an enhanced separation efficiency of up to 597,503 plates/m for the AuNPs. In addition, the amperometric current response of the detection electrode under the AC field application was also enhanced by the sensitivity 5-fold compared with the absence of the AC field.

Detection of Nitric Oxide from Living Cells Using Polymeric Zinc Organic Framework-Derived Zinc Oxide Composite with Conducting Polymer.

Sensitive and selective detection of nitric oxide (NO) in the human body is crucial since it has the vital roles in the physiological and pathological processes. This study reports a new type of electrochemical NO biosensor based on zinc-dithiooxamide framework derived porous ZnO nanoparticles and polyterthiophene-rGO composite. By taking advantage of the synergetic effect between ZnO and poly(TTBA-rGO) (TTBA = 3'-(p-benzoic acid)-2,2':5',2″-terthiophene, rGO = reduced graphene oxide) nanocomposite layer, the poly(TTBA-rGO)/ZnO sensor probe displays excellent electrocatalytic activity and explores to detect NO released from normal and cancer cell lines. The ZnO is immobilized on a composite layer of poly(TTBA-rGO). The highly porous ZnO offers a high electrolyte accessible surface area and high ion-electron transport rates that efficiently catalyze the NO reduction reaction. Amperometry with the modified electrode displays highly sensitive response and wide dynamic range of 0.019-76 × 10-6 m with the detection limit of 7.7 ± 0.43 × 10-9 m. The sensor probe is demonstrated to detect NO released from living cells by drug stimulation. The proposed sensor provides a powerful platform for the low detection limit that is feasible for real-time analysis of NO in a biological system.

Analysis of Phthalate Esters in Mammalian Cell Culture Using a Microfluidic Channel Coupled with an Electrochemical Sensor.

An analytical tool to monitor trace phthalate was developed using a microfluidic channel device coupled with a novel electrochemical biosensor. At first, the electrochemical sensor was constructed with biomimetic layers to reveal a large hydrogen over potential by controlling the surface charge and hydrophobicity through assembling with a lipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and a cationic molecule (toluidine blue O) bonded to a conductive polymer. The modified electrode possessing a highly negative polarization potential (approximately -1.8 V vs Ag/AgCl) can uptake sparingly soluble phthalate ester (PEs) compounds in aqueous media. Each sensor probe material was characterized employing SEM, AFM, XPS, QCM, TEM, UV-visible, and impedance spectroscopy. The microfluidic channel is used first to concentrate and separate trace amounts of phthalates, and then the sensor probe is installed at the end of channel. Experimental variables affecting the PEs analysis were assessed and optimized in terms of biomimetic layer composition and analytical conditions. The linear dynamic range and detection limits of the PEs were 0.15 nM-10.0 µM and ∼12.5 pM with relative standard deviations <5%. The proposed method was applied to evaluate the effect of endocrine disruptors on mammalian kidney cells, where the cell samples show in-taking percentages between 1.8 and 7.0% to the total PEs according to the incubation time.

Dopamine D4 receptors linked to protein kinase G are required for changes in dopamine release followed by locomotor activity after repeated cocaine administration.

We previously found that the dopamine D2-type receptors (D2 and D3 receptors), coupled to protein kinase G (PKG), upregulate locomotor activity after repeated cocaine administration. In this study, D4 receptors, another type of D2 receptor also coupled to PKG, were examined to determine their requirement in the regulation of locomotor activity after repeated cocaine administration. The results demonstrated that repeated injections of cocaine (20 mg/kg), given once a day for seven consecutive days, significantly increased extracellular dopamine concentrations. Intra-caudate infusion of the D4 receptor agonist, PD168077 (10 nmol), and the PKG inhibitor, KT5823 (2 nmol), significantly decreased the repeated cocaine-induced increase in dopamine levels and locomotor activity. However, intra-caudate infusion of KT5823, but not PD168077, decreased ∆FosB immunoreactivity elevated by repeated cocaine administration. These findings suggest that D4 receptors linked to PKG could be a key modulator for dopamine release required for changes in locomotor activity caused by repeated cocaine exposure.

Dual-signal output biosensor for the detection of program death-ligand 1 and therapy progress monitoring of cancer.

A disposable dual-output biosensor to detect program death-ligand 1 (PD-L1) was developed for immunotherapy progress monitoring and early cancer detection in a single experimental setup. The aptamer probe was assembled on rGO composited with carboxylated terthiophene polymer (rGO-pTBA) to specifically capture PD-L1 protein labeled with a new redox mediator, ortho-amino phenol para sulphonic acid, for amperometric detection. Each sensing layer was characterized through electrochemical and surface analysis experiments, then confirmed the sensing performance. The calibration plots for the standard PD-L1 protein detection revealed two dynamic ranges of 0.5-100.0 pM and 100.0-500.0 pM, where the detection limit was 0.20 ± 0.001 pM (RSD ≤5.2%) by amperometry. The sensor reliability was evaluated by detecting A549 lung cancer cell-secreted PD-L1 and clinically relevant serum levels of soluble PD-L1 (sPD-L1) using both detection methods. In addition, therapeutic trials were studied through the quantification of sPD-L1 levels for a small cohort of lung cancer patients. A significantly higher level of sPD-L1 was observed for patients (221.6-240.4 pM) compared to healthy individuals (16.2-19.6 pM). After immunotherapy, the patients' PD-L1 level decreased to the range of 126.7-141.2 pM. The results indicated that therapy monitoring was successfully done using both the proposed methods. Additionally, based on a comparative study on immune checkpoint-related proteins, PD-L1 is a more effective biomarker than granzyme B and interferon-gamma.

Disposable amperometric glycated hemoglobin sensor for the finger prick blood test.

The analysis of glycated hemoglobin (HbA1C) content in blood samples is crucial for the diagnosis of diabetes, and it still demands to practically use plenty of a blood sample and a complicated procedure. Hence, we report the development of a disposable amperometric HbA1C sensor for the finger prick blood test through a simple treatment of a drop of blood. To fabricate the sensor probe, the conducting polymer, poly(terthiophene benzoic acid) (pTTBA), was electrochemically grown onto the gold nanoparticles (AuNPs) coated-screen printing electrode, followed by the covalent attachment of aminophenyl boronic acid (APBA) to pTTBA as a host to capture HbA1C in the sample. The catalytic reduction response of hydrogen peroxide by HbA1C itself captured on the sensor probe was monitored as an analytical signal. The experimental parameters for the HbA1C analysis were optimized in terms of concentration of H2O2, pH, temperature, applying potential, and interferences. Under the optimized conditions, the linear dynamic range of HbA1C by amperometry was determined to be from 0.1 to 1.5% and the detection limit was to be 0.052 ± 0.02%. The reliability of the proposed HbA1C sensor was evaluated through the comparison of the results among the conventional method, the impedance method, and the proposed amperometry using a drop of a human peripheral blood sample.

Ultrasensitive and selective electrochemical diagnosis of breast cancer based on a hydrazine-Au nanoparticle-aptamer bioconjugate.

Human epidermal growth factor receptor 2 (HER2) and HER2-overexpressing breast cancer cells were detected using an electrochemical immunosensor combined with hydrazine and aptamer-conjugated gold nanoparticles (AuNPs). The sensor probe was fabricated by covalently immobilizing anti-HER2 onto a nanocomposite layer that was composed of self-assembled 2,5-bis(2-thienyl)-1H-pyrrole-1-(p-benzoic acid) (DPB) on AuNPs. The hydrazine-AuNP-aptamer bioconjugate, where the hydrazine reductant was directly attached onto AuNPs to avoid the nonspecific deposition of silver on the sensor surface, was designed and used to reduce silver ion for signal amplification selectively. The silver-stained target cells were visualized easily by the bare eye and an optical microscope, and the cells were quantitatively analyzed using stripping voltammetry. The parameters affecting the analytical response were optimized. The proposed sensor was capable of differentiating between HER2-positive breast cancer cells and HER2-negative cells. This method exhibited an excellent diagnosis method for the ultrasensitive detection of SK-BR-3 breast cancer cells in human serum samples with a detection limit of 26 cells/mL.

Electron-transfer mediator for a NAD-glucose dehydrogenase-based glucose sensor.

A new electron-transfer mediator, 5-[2,5-di (thiophen-2-yl)-1H-pyrrol-1-yl]-1,10-phenanthroline iron(III) chloride (FePhenTPy) oriented to the nicotinamide adenine dinucleotide-dependent-glucose dehydrogenase (NAD-GDH) system was synthesized through a Paal-Knorr condensation reaction. The structure of the mediator was confirmed by Fourier-transform infrared spectroscopy, proton and carbon nucler magnetic resonance spectroscopy, and mass spectroscopy, and its electron-transfer characteristic for a glucose sensor was investigated using voltammetry and impedance spectroscopy. A disposable amperometric glucose sensor with NAD-GDH was constructed with FePhenTPy as an electron-transfer mediator on a screen printed carbon electrode (SPCE) and its performance was evaluated, where the addition of reduces graphene oxide (RGO) to the mediator showed the enhanced sensor performance. The experimental parameters to affect the analytical performance and the stability of the proposed glucose sensor were optimized, and the sensor exhibited a dynamic range between 30 mg/dL and 600 mg/dL with the detection limit of 12.02 ± 0.6 mg/dL. In the real sample experiments, the interference effects by acetaminophen, ascorbic acid, dopamine, uric acid, caffeine, and other monosaccharides (fructose, lactose, mannose, and xylose) were completely avoided through coating the sensor surface with the Nafion film containing lead(IV) acetate. The reliability of proposed glucose sensor was evaluated by the determination of glucose in artificial blood and human whole blood samples.

Protein kinase G regulates dopamine release, ΔFosB expression, and locomotor activity after repeated cocaine administration: involvement of dopamine D2 receptors.

Protein kinase G (PKG) activation has been implicated in the regulation of synaptic plasticity in the brain. This study was conducted to determine the involvement of PKG-associated dopamine D2 (D2) receptors in the regulation of dopamine release, ΔFosB expression and locomotor activity in response to repeated cocaine exposure. Repeated systemic injections of cocaine (20 mg/kg), once a day for seven consecutive days, increased cyclic guanosine monophosphate (cGMP) and extracellular dopamine concentrations in the dorsal striatum. Inhibition of neuronal nitric oxide synthase (nNOS), cGMP or PKG and stimulation of D2 receptors decreased the repeated cocaine-induced increase in dopamine concentrations. Similar results were obtained by the combining nNOS, cGMP or PKG inhibition with stimulation of D2 receptors. Parallel to these data, PKG inhibition, D2 receptor stimulation, and combining PKG inhibition with stimulation of D2 receptors decreased the repeated cocaine-induced increases in ΔFosB expression and locomotor activity. These findings suggest that control of D2 receptors by PKG activation after repeated cocaine is responsible for upregulating dopamine release and sustained long-term changes in gene expression in the dopamine terminals and gamma-aminobutyric acid neurons of the dorsal striatum, respectively. This upregulation may contribute to behavioral changes in response to repeated exposure to cocaine.

Synthesis and evaluation of the cytotoxic activities of some isatin derivatives.

A series of isatin derivatives, 1-butyl-5/7-chloro/fluoro-3-((4-methoxybenzyl)imino)indolin-2-ones (3a-d), 6-butyl-chloro/fluoro-6H-indolo[2,3-b]quinoxalines (4a-h), and 5/7-chloro/fluoro-3-((4-methoxybenzyl)imino)indolin-2-ones (5a-h) were synthesized and characterized by using Fourier transform (FT)-IR, (1)H- and (13)C-NMR spectroscopy, mass spectrometric and elemental analysis. The substances were further subjected to in vitro cytotoxicity evaluation against HeLa, SK-BR-3, and MCF-7 cells. The results showed that quinoxalines 4d, 4e, and 4g; and indolin-2-one 5f display significant in vitro cytotoxic activities against HeLa cells and further the compound 4d has resulted in highest cytotoxicity in the entire series studied. In addition, 5f was shown to display substantial activity against all the three cell lines used in the current study.

Ni/Ni(OH)2-rGO nanocomposites sensor for the detection of long forgotten mycotoxin, xanthomegnin.

Xanthomegnin, a known fungal toxin, secondary metabolite, and pigment diffuses from the dermatophytes has gained attention as local virulence factor because of the mutagenicity, toxicity, cytocidal, and immunosuppressive properties. Not only as a dermatophyte in skin related disorders, the production of xanthomegnin is implicated as a powerful diagnostic marker in patients suffering from ocular mycoses. Incidentally also attributed to death in livestock's majorly by exposing themselves to food-borne fungi like Aspergillus and Penicillium. The production of xanthomegnin in dermetophytic species Trichophyton rubrum, found commonly in infected skin and nails. In this study nickel/nickel hydroxide nanoparticles decorated reduced graphene oxide (Ni/Ni(OH)2-rGO) modified glassy carbon electrode has been successfully used for non-enzymatic detection of xanthomegnin. The Ni/Ni(OH)2-rGO composites were synthesized through a simple microwave assisted technique with less harmful reducing agent. The UV-visible spectroscopy (UV-vis), X-ray photoelectron spectroscopy (XPS), Scanning electron microscopy - energy dispersive X-ray spectroscopy (SEM-EDS), and electrochemical investigations demonstrated the robust formation of the sensor. The sensor exhibited improved electrochemical properties with enhanced electrochemical active area and excellent electrochemical behavior towards xanthomegnin detection with a limit of detection of 0.12 µM. The selectivity, stability, and analytical recovery studies proved the potential use of the sensor for the detection of xanthomegnin in real samples. Further, the sensor successfully detected xanthomegnin produced by the Trichophyton rubrum, the most common superficial fungus, accounting for at least 60% of all superficial fungal infections in humans. Validation studies showed satisfiable and quantifiable amount of xanthomegnin in comparison with common bench mark UV-Vis studies meant for fungal mycotoxin detection.