Current Challenges and Developments in Perovskite-Based Electrochemical Biosensors for Effective Theragnostics of Neurological Disorders.

Early-stage diagnosis of neurological disease and effective therapeutics play a significant role in improving the chances of saving lives through suitable and personalized courses of treatment. Biomolecules are potential indicators of any kind of disorder in a biological system, and they are recognized as a critical quantitative parameter in disease diagnosis and therapeutics, collectively known as theragnostics. The effective diagnosis of neurological disorders solely depends on the detection of the imbalance in the concentration of neurological biomarkers such as nucleic acids, proteins, and small metabolites in bodily fluids such as blood serum, plasma, urine, etc. This process of neurological biomarker detection can lead to an effective prognosis with a prediction of the treatment efficiency and recurrence. While review papers on electrochemical, spectral, and electronic biosensors for the detection of a wide variety of biomarkers related to neurological disorders are available in the literature, the prevailing challenges and developments in perovskite-based biosensors for effective theragnostics of neurological disorders have received scant attention. In this Mini-Review, we discuss the topical advancements in design strategies of perovskite-based electrochemical biosensors with detailed insight into the detection of neurological disease or disorder-specific biomarkers and their trace-level detection in biological fluids with high specificity and sensitivity. The tables in this Review give the performance analysis of recently developed perovskite-based electrochemical biosensors for effective theragnostics of neurological disorders. To conclude, the current challenges in biosensing technology for early diagnosis and therapeutics of neurological disorders are discussed along with a forecast of their anticipated developments.

3D, large-area NiCo2O4 microflowers as a highly stable substrate for rapid and trace level detection of flutamide in biofluids via surface-enhanced Raman scattering (SERS).

A one-pot hydrothermal synthesis of three-dimensional (3D), large-area, bimetallic oxide NiCo2O4 (NCO) microflowers has been developed as a novel substrate for surface-enhanced Raman scattering (SERS) detection of flutamide in biological fluids. The 3D flower-like morphology of the NCO is observed via FESEM micrographs, while the orthorhombic phase formation is confirmed through XRD spectra. Due to the presence of multiple coordination cations of the 3D NCO microflowers (such as Ni2+ and Co2+), the high surface area and surface roughness, the NCO-modified indium tin oxide (NCO/ITO) SERS substrate exhibits a linear detection range from 0.5-500 nM with a low limit of detection (LOD) of 0.1 nM. The SERS substrate provides a high enhancement factor of 1.864 × 106 with an accumulation time of 30 s using a laser source of λ = 532 nm, which can be ascribed to the excellent and rapid interaction between the flutamide molecule and the NCO microflower substrate that leads to photoinduced charge transfer (PICT) resonance. The NCO/ITO substrate exhibits excellent homogeneity and high chemical stability. Besides, the substrate displays an excellent selectivity to flutamide molecules in the existence of other metabolites such as urea, ascorbic acid (AA), glucose, NaCl, KCl, CaCl2, and hydroxyflutamide. The NCO/ITO substrate is successful in the trace-level detection of flutamide in simulated blood serum samples. The strategy outlined here presents a novel strategy for the efficacy of transition metal oxides (TMOs) based electrodes useful for a wide variety of bioanalytical applications.

Silica embedded carbon nanosheets derived from biomass acorn cupule for non-enzymatic, label-free, and wide range detection of α 1-acid glycoprotein in biofluids.

In this work, we demonstrate the first report on a low-cost, non-enzymatic, label-free electrochemical sensing of alpha-1-acid-glycoprotein (α1GP) biomarker in biofluids using silica embedded carbon nanosheets (SEC) derived from acorn cupules biomass. The SEC/GCE sensor exhibits low detection limit (LOD) of 30 ng/mL (LOD = 3 s/m) which is far below the lowest physiological concentration of α1GP and a wide linear detection range from 100 ng/mL to 10 mg/mL which covers entire clinical concentration range reported for various diseases like cancer, sepsis, etc. The sensing mechanism of the sensor relies on the direct electrooxidation of sialic acid from the α1GP structure which hinder the interfacial electron-transfer process of [Fe (CN)6]3-/4- redox probe at the electrode-electrolyte interface. The sensor exhibits excellent selectivity and stability towards detection of α1GP which is ascribed to the presence of embedded silica nanoparticles on the surface of the carbon nanosheets. The successful determination of α1GP in the simulated blood serum sample with good recovery percentage (i.e., from ∼94.03% to ∼103.50%) proves the feasibility of the sensor towards clinical applications. The overall efficacy of the sensor proves it as a promising low-cost, sustainable, and non-enzymatic platform for a wide variety of bioanalytical applications.

Simultaneous sensing of copper, lead, cadmium and mercury traces in human blood serum using orthorhombic phase aluminium ferrite.

We report a facile, one-step solid-state synthesis of aluminium ferrite (AFO) for simultaneous sensing of heavy metal ions (HMIs) namely cadmium (Cd2+), lead (Pb2+), copper (Cu2+) and mercury (Hg2+) in human blood serum. The nanoflake morphology and orthorhombic phase formation of the as-synthesised AFO were revealed through field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) pattern, respectively. The AFO modified glassy carbon electrode (AFO/GCE) exhibits distinct peak potentials for all HMIs with peak separation potential (ΔΕP) of 190 mV, 494 mV and 304 mV for Cd2+-Pb2+, Pb2+-Cu2+ and Cu2+-Hg2+, respectively. Low limits of detection (LOD) of values 1.5 nM, 4 nM, 1.6 nM and 0.5 nM were observed for Hg2+, Cd2+, Pb2+ and Cu2+, respectively which are well below the limits of unsafe concentrations of HMIs reported for human blood. The excellent sensitivity and low LOD can be attributed to the octahedral sites of the AFO perovskite structure with Fe2+/Fe3+ oxidation states which favours the delocalization of charge accumulations at the electrode surface. The sensor is successfully in determination of HMIs in simulated human blood serum using standard addition technique with an excellent recovery percentage. This strategy outlined here can be effectively used for developing various sensing platforms for bioanalytical applications.

Ultra-selective, trace level detection of As3+ ions in blood samples using PANI coated BiVO4 modified SPCE via differential pulse anode stripping voltammetry.

We report a novel, facile hydrothermal synthesis of bismuth vanadate (BiVO4) nanoflakes coated with polyaniline (PANI) via electrodeposition on screen-printed carbon electrode (SPCE) for trace level detection of arsenic in biological samples. The crystallinity and monoclinic scheelite structure of as-synthesised BiVO4 nanoflakes was analysed using X-Ray diffraction (XRD) and the surface morphology and chemical analysis of the flake-like BiVO4 and PANI coated BiVO4 modified SPCE (PANI@BiVO4/SPCE) were studied using Field emission scanning electron microscopy (FESEM), Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). The presence of VO4 tetrahedra and VO43- group along with oxy-functional groups were confirmed using Raman and FTIR analysis, respectively. Under optimized conditions, the sensor could detect As3+ ions via differential pulse anodic stripping voltammetry (DPASV) technique with remarkable low limit of detection (LOD) of 0.0072 ppb (which is far below the MCL testified values) and exhibited a sensitivity of 6.06 µA ppb-1 cm-2 for a linear range of 0.01 to 300 ppb. This improved sensing aptitude can be ascribed to the synergetic effect of PANI and BiVO4 by providing high electrical conductivity and high electrocatalytic active sites via VO43- tetrahedra, respectively. The sensor showed an outstanding selectivity in detection of As3+ ions in trace levels in simulated blood serum samples with excellent recovery percentages thus making it an ideal platform to develop numerous electrochemical sensing platforms for bioanalytical applications.

Facile synthesis of large area pebble-like ß-NaFeO2 perovskite for simultaneous sensing of dopamine, uric acid, xanthine and hypoxanthine in human blood.

Here, we report a facile one-step solid-state reaction assisted synthesis of ß-NaFeO2 perovskite for simultaneous sensing of Dopamine (DA), Uric Acid (UA), Xanthine (Xn) and Hypoxanthine (Hxn) in human blood. The orthorhombic phase formation in ß-NaFeO2 with the presence of octahedral sites is confirmed through x-ray diffraction (XRD) and Raman spectroscopy while high surface area pebble-like morphology is observed through scanning electron microscopy (SEM). The sensor exhibits distinct oxidation potentials for DA, UA, Xn and Hxn with a peak separation (ΔEp) between DA-UA, UA-Xn and Xn-Hxn as 134 mV, 388 mV and 360 mV, respectively. The sensor exhibits an excellent selectivity, sensitivity and low limits of detection (LOD) of 2.12 nM, 158 nM, 129 nM and 95 nM for DA, UA, Xn and Hxn, respectively which are well below the lower limits of their presence in physiological ranges in human body fluids. The sensor shows an excellent selectivity and it was successfully employed in simultaneous sensing of DA, UA, Xn and Hxn in simulated blood serum samples with excellent recovery percentages. This is the first report on low-cost ß-NaFeO2 modified GCE for simultaneous electrochemical sensing of biomolecules which can be applied for numerous bioanalytical applications.

One-step solvothermal synthesis of nanoflake-nanorod WS2 hybrid for non-enzymatic detection of uric acid and quercetin in blood serum.

Herein, we report a novel, one-step solvothermal assisted thermal decomposition synthesis of nanoflake-nanorod tungsten disulphide (WS2) nanomaterial and its application for non-enzymatic electrochemical sensing of uric acid (UA) and quercetin. The as-synthesised WS2 was characterized using X-ray diffraction (XRD), Raman spectrometer, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). SEM analysis revealed the growth of 2D-1D nanoflake-nanorod hybrid nanostructure of 2H phase WS2 with greater defects and metal edges. Under optimized conditions, the WS2 modified glassy carbon electrode (WS2/GCE) facilitated the effective sensing of UA and quercetin which was measured using differential pulse voltammetry (DPV) technique. The sensor exhibited a low limit of detection (LoD) of 1.2 µM, the sensitivity of 312 nA/µM.cm2 for the dynamic range from 5 µM to 1 mM towards UA while an even lower of 2.4 nM and sensitivity of 258 nA/nM cm2 in the dynamic range of 10 nM-50 µM for quercetin. The enhanced sensing ability of the sensor attributed towards the synergetic effect of 2D-1D hybrid structure of WS2, wherein the 2D nanoflakes enhance the electrocatalytic property of WS2 with shorter diffusion length and 1D nanorods offer large surface area which provides greater number of active sites for sensing. Further, the sensor showed a remarkable selectivity towards UA and quercetin in the presence of ascorbic acid (AA), dopamine (DA), sodium (Na+), chloride (Cl-), calcium (Ca2+) and glucose. The sensor was further employed in successful detection of UA and quercetin in the simulated blood serum sample with excellent recovery percentages. The proposed synthesis route can be used to develop WS2 based electrochemical sensing platforms useful for various bioanalytical applications.