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

Anal Chim Acta. 2021 May 29:1161:338468. doi: 10.1016/j.aca.2021.338468. Epub 2021 Apr 2.

Abstract

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.

Keywords: Biosensor; Electrochemical impedance spectroscopy; Heart failure; ImmunoFET; Saliva analysis; Tumor necrosis factor-α.

MeSH terms

  • Biosensing Techniques*
  • Heart Failure* / diagnosis
  • Humans
  • Immunoassay
  • Reproducibility of Results
  • Saliva
  • Silicon Compounds
  • Tumor Necrosis Factor-alpha

Substances

  • Silicon Compounds
  • Tumor Necrosis Factor-alpha
  • silicon nitride