Ultrasensitive Monolithic Dopamine Microsensors Employing Vertically Aligned Carbon Nanofibers.

Brain-on-Chip devices, which facilitate on-chip cultures of neurons to simulate brain functions, are receiving tremendous attention from both fundamental and clinical research. Consequently, microsensors are being developed to accomplish real-time monitoring of neurotransmitters, which are the benchmarks for neuron network operation. Among these, electrochemical sensors have emerged as promising candidates for detecting a critical neurotransmitter, dopamine. However, current state-of-the-art electrochemical dopamine sensors are suffering from issues like limited sensitivity and cumbersome fabrication. Here, a novel route in monolithically microfabricating vertically aligned carbon nanofiber electrochemical dopamine microsensors is reported with an anti-blistering slow cooling process. Thanks to the microfabrication process, microsensors is created with complete insulation and large surface areas. The champion device shows extremely high sensitivity of 4.52× 104 µAµM-1·cm-2, which is two-orders-of-magnitude higher than current devices, and a highly competitive limit of detection of 0.243 nM. These remarkable figures-of-merit will open new windows for applications such as electrochemical recording from a single neuron.

Electrochemical molecularly bioimprinted siloxane biosensor on the basis of core/shell silver nanoparticles/EGFR exon 21 L858R point mutant gene/siloxane film for ultra-sensing of Gemcitabine as a lung cancer chemotherapy medication.

In search for improvements in bioanalysis electrochemical sensors, for better assessment of anti-cancer drugs, it is necessary for their detection limits to be minimized and the sensitivity and selectivity to be surpassed simultaneously; whereas, resolving any probable interfering with other medical treatments are considered. In this work, a novel approach was adopted for detection and assessment of Gemcitabine (GEM) as an anti-cancer drug based on evaluating its interaction with EGFR exon 21-point mutant gene. An electrochemical nanobiosensor was invented based on a new molecularly bioimprinted siloxane polymer (MBIS) strategy; in which the EGFR exon 21 acts as an identification probe. The roles of multi-walled carbon nanotubes and Ag nanoparticles (NPs) are to perform as a signal amplifier. The MBIS film was prepared by acid-catalysed hydrolysis/condensation of the sample solution, containing Ag NPs, ds-DNA of EGFR exon 21 point mutant gene, GEM as a template molecule, 3-(aminopropyl) trimethoxysilane (APTMS) and tetraethoxysilane. The interaction between the dsDNA and GEM was investigated by employing the modified biosensor and monitoring oxidation signal of guanine and adenine. The produced biosensor was characterized by XRD, FE-SEM, EDS, FT-IR and differential pulse voltammetry. The oxidation signals of adenine and guanine were in linear range when the device was subjected to various concentrations of GEM, from 1.5 to -93 µM, where a low detection limit 12.5 nmol L-1, and 48.8 nmol L-1 were recorded by guanine and adenine respectively. The developed biosensor did perform very well when employed for the actual samples; the stability was also approved which was acceptable for a reasonable time.

Diagnosis of EGFR exon21 L858R point mutation as lung cancer biomarker by electrochemical DNA biosensor based on reduced graphene oxide /functionalized ordered mesoporous carbon/Ni-oxytetracycline metallopolymer nanoparticles modified pencil graphite electrode.

In this present work we made a novel, fast, selective and sensitive electrochemical genobiosensor to detection of EGFR exon 21 point mutation based on two step electropolymerization of Ni(II)-oxytetracycline conducting metallopolymer nanoparticles (Ni-OTC NPs) on the surface of pencil graphite electrode (PGE) which was modified by reduced graphene oxide/carboxyl functionalized ordered mesoporous carbon (rGO/f-OMC) nanocomposite. ssDNA capture probe with amine groups at the5' end which applied as recognition element was immobilized on the rGO/f-OMC/PGE surface via the strong amide bond. Ni-OTC metallopolymer NPs were electropolymerized to rGO/ssDNA-OMC/PGE surface and then hybridization fallows through the peak current change in differential pulse voltammetry (DPV) using Ni-OTC NPs as a redox label. The biosensor was characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), FT-IR spectroscopy, energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry and Nitrogen adsorption-desorption analysis. The Ni-OTC current response verified only the complementary sequence indicating a significant reduction current signal in comparison to single point mismatched and non-complementary and sequences. Under optimal conditions, the prepared biosensor showed long-term stability (21 days) with a wide linear range from 0.1 µM to 3 µM with high sensitivity (0.0188 mA/µM) and low detection limit (120 nM).

Polythiophene supported MnO2 nanoparticles as nano-stabilizer for simultaneously electrostatically immobilization of d-amino acid oxidase and hemoglobin as efficient bio-nanocomposite in fabrication of dopamine bi-enzyme biosensor.

A novel, highly selective and sensitive voltammetric bi-enzyme biosensor for sensing dopamine (DA), in presence of H2O2 which resulted as d-alanine enzymatic oxidation, was fabricated on the basis of simultaneously electrostatically immobilization of d-amino acid oxidase (DAAO) and hemoglobin (Hb) on MnO2 nanoparticles (MnO2 NPs) enriched poly thiophene (PTh). Cyclic voltammetry (CV), technique was applied for electropolymerization of thiophene on glassy carbon electrode (GCE) surface and MnO2 NPs dispersed on PTh network by soaking PTh/GCE in potassium permanganate (KMnO4) solution. Excellent catalytic properties and large surface area of MnO2 NPs/PTh composite caused it was used as an enzymes immobilization host in this developed bi-enzyme biosensor. The developed biosensor was characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and CV. The performance of the modified bi-enzyme biosensor was investigated in terms of its response time, detection limit, sensitivity, stability and selectivity in a lab environment. The composite of DAAO-Hb/MnO2 NPs/PTh to construct a bi-enzyme biosensor in this study showed a linear response with DA in the concentration range of 0.04-9.0µM with R-squared value of 0.994 (for S/N=3) and its sensitivity and detection limite were about 12.801µA/µM and 41nM respectively. Also this bi-enzyme biosensors exhibited high selectivity, rapid response (5s) and long-term stability (42days). At the end, the proposed biosensor was applied successfully in human serum as real sample.

Enzymatic biosensor based on entrapment of d-amino acid oxidase on gold nanofilm/MWCNTs nanocomposite modified glassy carbon electrode by sol-gel network: Analytical applications for d-alanine in human serum.

Sensing and determination of d-alanine is studied by using an enzymatic biosensor which was constructed on the basis of d-amino acid oxidase (DAAO) immobilization by sol-gel film onto glassy carbon electrode surface modified with nanocomposite of gold nanofilm (Au-NF) and multiwalled carbon nanotubes (MWCNTs). The Au-NF/MWCNT nanocomposite was prepared by applying the potentiostatic technique for electrodeposition of Au-NF on the MWCNT immobilized on glassy carbon electrode surface. The modified electrode is investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), linear sweep voltammetry (LSV) and cyclic voltammetry(CV) techniques. The linear sweep voltammetry was used for determination of d-alanine and the results showed an excellent linear relationship between biosensor response and d-alanine concentration ranging from 0.25µM to 4.5µM with correction coefficient of 0.999 (n=20). Detection limit for the fabricated sensor was calculated about 20nM (for S/N=3) and sensitivity was about 56.1µAµM-1cm-2. The developed biosensor exhibited rapid and accurate response to d-alanine, a good stability (4 weeks) and an average recovery of 98.9% in human serum samples.

First report on hemoglobin electrostatic immobilization on WO3 nanoparticles: application in the simultaneous determination of levodopa, uric acid, and folic acid.

This work describes the first report about the simultaneous determination of levodopa (L-DOPA) with folic acid (FA) and uric acid (UA) based on electrocatalytic oxidation of L-DOPA with peroxidase properties of hemoglobin (Hb) in the presence of H2O2 as Hb activator. Bovine Hb was electrostatically immobilized on WO3 nanoparticles (WO3NPs) in pH between Hb and WO3NP isoelectric points, and subsequently, a carbon paste electrode (CPE) was modified with the obtained WO3NPs-Hb and multiwalled carbon nanotubes (MWCNTs). The resulting biosensor supplied a sensitive and suitably stable biosensor for the simultaneous determination of L-DOPA, UA, and FA. The obtained linear range and detection limit for L-DOPA, UA, and FA were completely acceptable, and the biosensor response time for these molecules was relatively short so that it reaches about 95 % of its maximum response in less than 10 s. The applicability of the current biosensor was confirmed with the determination of L-DOPA in the presence of fixed amounts of FA and UA in some real samples by the standard addition method.

Glassy carbon electrode modified with horse radish peroxidase/organic nucleophilic-functionalized carbon nanotube composite for enhanced electrocatalytic oxidation and efficient voltammetric sensing of levodopa.

A novel and selective enzymatic biosensor was designed and constructed for voltammetric determination of levodopa (L-Dopa) in aqueous media (phosphate buffer solution, pH=7). Biosensor development was on the basis of to physically immobilizing of horse radish peroxidase (HRP) as electrochemical catalyst by sol-gel on glassy carbon electrode modified with organic nucleophilic carbon nanotube composite which in this composite p-phenylenediamine (pPDA) as organic nucleophile chemically bonded with functionalized MWCNT (MWCNT-COOH). The results of this study suggest that prepared bioorganic nucleophilic carbon nanotube composite (HRP/MWCNT-pPDA) shows fast electron transfer rate for electro oxidation of L-Dopa because of its high electrochemical catalytic activity toward the oxidation of L-Dopa, more--NH2 reactive sites and large effective surface area. Also in this work we measured L-Dopa in the presence of folic acid and uric acid as interferences. The proposed biosensor was characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), FT-IR spectroscopy and cyclic voltammetry (CV). The differential pulse voltammetry (DPV) was used for determination of L-Dopa from 0.1 µM to 1.9 µM with a low detection limit of 40 nM (for S/N=3) and sensitivity was about 35.5 µA/µM. Also this biosensor has several advantages such as rapid response, high stability and reproducibility.