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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. [ABSTRACT FROM AUTHOR]

Assessing tumour necrosis factor-α (TNF-α) 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-α protein. Monoclonal anti-TNF-α antibodies (anti-TNF-α 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-α protein in both phosphate buffer saline (PBS) and artificial saliva (AS). The change in the threshold voltage of the gate (∆VT) 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-α, 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-α detection in AS by electrical measurement. [ABSTRACT FROM AUTHOR]

According to the European statistics, approximately 26 million patients worldwide suffer from heart failure (HF), and this number seems to be steadily increasing. Inflammation plays a central role in the development of HF, and the pro-inflammatory cytokine Tumor necrosis factor-α (TNF-α) represents inflammation gold-standard biomarker. Early detection plays a crucial role for the prognosis and treatment of HF. An Ion Sensitive Field Effect Transistor (ISFET) based on silicon nitride transducer and biofunctionalized with anti-TNF-α antibody for label-free detection of salivary TNF-α is proposed. Electrochemical impedance spectroscopy (EIS) was used for TNF-α detection. Our ImmunoFET offered a detection limit of 1 pg mL−1, with an analytical reproducibility expressed by a coefficient of variance (CV) resulted < 10% for the analysis of saliva samples, and an analyte recovery of 94 ± 6%. In addition, it demonstrated high selectivity when compared to other HF biomarkers such as Inteleukin-10, N-terminal pro B-type natriuretic peptide, and Cortisol. Finally, ImmunoFET accuracy in determining the unknown concentration of TNF-α was successfully tested in saliva samples by performing standard addition method. The proposed ImmunoFET showed great promise as a complementary tool for biomedical application for HF monitoring by a non-invasive, rapid and accurate assessment of TNF-α. [Display omitted] • Antibody-functionalization of ion-sensitive field effect transistor (ISFET) for tumor necrosis factor-α detection in saliva. • Electrochemical impedance spectroscopy for tumor necrosis factor-α quantification. • Heart failure monitoring by saliva analysis. [ABSTRACT FROM AUTHOR]

Cortisol, a steroid hormone mostly known as "the stress hormone," plays many essential functions in humans due its involvement in several metabolic pathways. It is well-known that cortisol dysregulation is implied in evolution and progression of several chronic pathologies, including cardiac diseases such as heart failure (HF). However, although several sensors have been proposed to date for the determination of cortisol, none of them has been designed for its determination in saliva in order to monitor HF progression. In this work, a silicon nitride based Immuno field-effect transistor (ImmunoFET) has been proposed to quantify salivary cortisol for HF monitoring. Sensitive biological element was represented by anti-cortisol antibody bound onto the ISFET gate via 11-triethoxysilyl undecanal (TESUD) by vapor-phase method. Potentiometric and electrochemical impedance spectroscopy (EIS) measurements were carried out for preliminary investigations on device responsiveness. Subsequently, a more sensitive detection was obtained using electrochemical EIS. The proposed device has proven to have a linear response (R2 always >0.99), to be sensitive (with a limit of detection, LoD, of 0.005 ± 0.002 ng/mL), selective in case of other HF biomarkers (e.g. N-terminal pro B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-α), and interleukin 10 (IL-10)), and accurate in cortisol quantification in saliva sample by performing the standard addition method. • Development of ion-sensitive field effect transistor (ISFET) based on silicon nitride for salivary cortisol detection. • Rapid antibody immobilisation onto the ISFET sensing gate via 11-triethoxysilyl undecanal (TESUD) by vapor-phase method. • Cortisol quantification for heart failure monitoring by saliva analysis. [ABSTRACT FROM AUTHOR]