Development of an ImmunoFET for Analysis of Tumour Necrosis Factor- (alfa) in Artificial Saliva: Application for Heart Failure Monitoring

Assessing tumour necrosis factor-(alfa) (TNF-(alfa)) levels in the human body has become an essential tool to recognize heart failure (HF). In this work, label-free, rapid, easy to use ImmunoFET based on an ion-sensitive field effect transistor (ISFET) was developed for the detection of TNF-(alfa) protein. Monoclonal anti-TNF-(alfa) antibodies (anti-TNF-(alfa) mAb) were immobilized on an ISFET gate made of silicon nitride (Si3N4) after salinization with 11-(triethoxysilyl) undecanal (TESUD). The obtained ISFET functionalized with the mAbs (ImmunoFET) was used to detect TNF-(alfa) protein in both phosphate buffer saline (PBS) and artificial saliva (AS). The change in the threshold voltage of the gate (DVT) showed approximately linear dependency on the concentration of the antigens in the range 5-20 pg/mL for both matrixes. The cross-selectivity study showed that the developed ImmunoFET demonstrated to be selective towards TNF-(alfa), when compared to other HF biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-10 (IL-10), and cortisol, even if further experiments have to be carried out for decreasing possible unspecific absorption phenomena. To the best of our knowledge, this is the first ImmunoFET that has been developed based on Si3N4 for TNF-(alfa) detection in AS by electrical measurement

Development of biosensors for non-invasive measurements of heart failure biomarkers in saliva

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A silicon nitride ISFET-based immunosensor for Tumor Necrosis Factor-alpha detection in saliva. A promising tool for heart failure monitoring

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Electrochemical Impedance Spectroscopy Microsensor Based on Molecularly Imprinted Chitosan Film Grafted on a 4-Aminophenylacetic Acid (CMA) Modified Gold Electrode, for the Sensitive Detection of Glyphosate

International audienceA novel electrochemical impedance spectroscopy (EIS) microsensor was implemented for the dosage of traces of glyphosate, in real and synthetic water samples. Molecularly imprinted chitosan was covalently immobilized on the surface of the microelectrode previously modified with 4-aminophenylacetic acid (CMA). The characterization of the resulting microelectrodes was carried out by using cyclic voltammetry measurement (CV), scanning electron microscopy (SEM), and electrochemical impedance spectrometry (EIS). EIS responses of the CS-MIPs/CMA/Au microsensor toward GLY was well-proportional to the concentration in the range from 0.31 × 10 −9 to 50 × 10 −6 mg/mL indicating a good correlation. The detection limit of GLY was 1 fg/mL (S/N = 3). Moreover, this microsensor showed good reproducibility and repeatability, high selectivity, and can be used for the detection of GLY in river water

Experimental Study and Mathematical Modeling of a Glyphosate Impedimetric Microsensor Based on Molecularly Imprinted Chitosan Film

International audienceA novel impedimetric microsensor based on a double-layered imprinted polymer film has been constructed for the sensitive detection of the herbicide, glyphosate (GLY), in water. It is based on electropolymerized polypyrrole films, doped with cobaltabis(dicarbollide) ions ([3,3′-Co(1,2-C2B9H11)2]), as a solid contact layer between the gold microelectrode surface and the molecularly imprinted chitosan film (CS-MIPs/PPy/Au). Electrochemical Impedance Spectroscopy (EIS) was used for the characterization of the CS-molecular imprinted polymers (MIPs)/PPy/Au in the presence of GLY concentrations between 0.31 pg/mL and 50 ng/mL. Experimental responses of CS-MIPs/PPy/Au are modeled for the first time using an exact mathematical model based on physical theories. From the developed model, it was possible to define the optimal range of the parameters that will impact the quality of impedance spectra and then the analytical performance of the obtained microsensor. The obtained microsensor shows a low detection limit of 1 fg/mL (S/N = 3), a good selectivity, a good reproducibility, and it is regenerabl

On the impedance spectroscopy of field-effect biosensors

Impedance spectroscopy is an electrochemical technique widely used for the electrical characterization of the behavior of biomaterials in all kinds of biosensors. Field-effect devices, and in particular ion-sensitive field-effect transistors (ISFETs), have been extensively studied as transducers for biosensing. They however have not been much analyzed with impedance spectroscopy, because they typically generate non-Faradaic capacitance measurements, since there is no charge transfer through the insulating gate in contact with the liquid solution. We have recently experimentally shown that Faradaic-like impedance spectroscopy spectra can be obtained with ISFET devices, allowing high-sensitivity measurements for different pH and biomarker concentrations. In this paper, we report that both Faradaic-like and non-Faradaic impedance behavior can be well understood by a DC and small-signal AC model of the ISFET working in different conditions. Faradaic-like impedance measurements are described by the operation of the ISFET in subthreshold conditions. A Nyquist plot semicircle is obtained, corresponding to the transimpedance 1/gm of the ISFET in parallel to the gate capacitances. We show that this behavior is independent of the presence of membrane material on the gate surface. In these conditions, the change in the semicircle diameter for different pH or biomarker concentrations can be understood by the change of 1/gm corresponding to a threshold voltage shift of the transistor. This description is illustrated with our recent results for pH measurements and the detection of tumor necrosis factor-α with functionalized devices in standard solutions in the concentration range of 1–20 pg/ml. The use of the impedance spectroscopy technique takes advantage of the exponential behavior of the gm(VGS) curves in the subthreshold (weak inversion) operation of the ISFET. This results in a large signal amplification, where a small change in the threshold voltage results in a large change in the impedance spectrum, thus achieving an increased precision in the measurement of the device response to changes in the analyte concentration.Peer reviewe

Development of a Chitosan/Nickel Phthalocyanine Composite based Conductometric Micro‐sensor for Methanol Detection

International audienceThin-film composite of chitosan/nickel phthalocyanine (NiPc) was electrochemically deposited on the fingers of interdigitated gold electrodes, applying chronoamperometric polymerization technique. The presence of crystallized NiPc in the chitosan was confirmed by EDX and FTIR analysis. Acetone, ethanol, and methanol gas-sensing properties of the films prepared at optimum conditions were studied at atmospheric temperature, through differential measurements at an optimized frequency of 10 kHz, using a lock-in amplifier. The conductometric sensor presents the highest sensitivity of 60.2 μS.cm−1(v/v) for methanol and 700 ppm as the limit of detection. For validation, the methanol content of a commercial rubbing alcohol was determined

Novel immunoFET based on impedance spectroscopy for cortisol detection: application for heart failure

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Electrochemical Immunosensor for NT-proBNP Detection in Artificial Human Saliva: Heart Failure Biomedical Application

Monitoring of circulating N-terminal proBNP (NT-proBNP) biomarkers is crucial for the diagnosis of people suffering from heart failure (HF). In this work, we describe a novel ultra-sensitive NT-proBNP immunosensor for NT-proBNP detection in artificial human saliva. The surface of the developed immunosensor based on gold working microelectrodes (WEs) was biofunctionalized through carboxyl diazonium to immobilize anti-NT-proBNP antibodies. The chemical surface modification of WEs was carried out by cyclic voltammetery CV whilst the quantification of NT-proBNP biomarkers was made by electrochemical impedance spectroscopy (EIS). The immunosensor has demonstrated a linear detection response within the range 1–20 pg/mL for NTproBNP detection in artificial human saliva with a good selectivity in the presence of other interferences

Theoretical study and analytical performance of a lysozyme impedimetric microsensor based on a molecularly imprinted chitosan film

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