A silicon nitride ISFET based immunosensor for tumor necrosis factor-alpha detection in saliva. A promising tool for heart failure monitoring

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-alpha (TNF-alpha) represents inflammation gold-standard biomarker. Early detection plays a crucial role for the prognosis and treat-ment of HF. An Ion Sensitive Field Effect Transistor (ISFET) based on silicon nitride transducer and bio-functionalized with anti-TNF-alpha antibody for label-free detection of salivary TNF-alpha is proposed. Electrochemical impedance spectroscopy (EIS) was used for TNF-alpha 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-alpha 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-alpha. (C) 2021 Published by Elsevier B.V.