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. 2022 Dec 16;13(12):2235.
doi: 10.3390/mi13122235.

A Novel Cortisol Immunosensor Based on a Hafnium Oxide/Silicon Structure for Heart Failure Diagnosis

Hamdi Ben Halima  1 , Nadia Zine  1 , Joan Bausells  2 , Nicole Jaffrezic-Renault  1 , Abdelhamid Errachid  1
Affiliations

A Novel Cortisol Immunosensor Based on a Hafnium Oxide/Silicon Structure for Heart Failure Diagnosis

Hamdi Ben Halima et al. Micromachines (Basel). .

Abstract

Assessing cortisol levels in human bodies has become essential to diagnose heart failure (HF). In this work, we propose a salivary cortisol detection strategy as part of an easily integrable lab-on-a-chip for detection of HF biomarkers. Our developed capacitive immunosensor based on hafnium oxide (HfO2)/silicon structure showed good linearity between increasing cortisol concentration and the charge-transfer resistance/capacitance. Moreover, the developed biosensor was demonstrated to be highly selective toward cortisol compared to other HF biomarkers such as tumor necrosis factor (TNF-α) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The precision of our developed biosensor was evaluated, and the difference between the determined cortisol concentration in saliva and its expected one is <18%.

Keywords: capacitance; cortisol; electrochemical impedance spectroscopy; hafnium oxide; heart failure.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Semi-developed cortisol formula.
Figure 2
Figure 2
Characterization of the sample surface roughness with atomic force microscopy (AFM) in tapping mode using post-deposition annealing process (PDA) at different temperatures of 400 °C (a), 500 °C (b), and 600 °C (c).
Figure 3
Figure 3
Functionalization procedure of the HfO2 surface.
Figure 4
Figure 4
MNPs-COOH biofunctionalization with anti-cortisol antibody.
Figure 5
Figure 5
Experimental setup.
Figure 6
Figure 6
Contact angle on (A) bare HfO2 before surface activation; (B) bare HfO2 after surface activation by UV/ozone; (C) following TESUD formation.
Figure 7
Figure 7
(A) Example of Nyquist plots for the Randles equivalent circuit model obtained by analyzing cortisol standard solutions in PBS (2, 10, 15, and 50 ng mL−1). EIS frequency ranged from 5 Hz to 100 kHz, and a sinus amplitude of 25 mV with polarization potential of −1.5 V; (B) sensitivity curves obtained by analyzing standard solution containing cortisol or other HF biomarkers (e.g., TNF-α and NT-proBNP) in the concentration range 2–50 ng mL−1 using the HfO2 substrate functionalized with anti-cortisol antibody.
Figure 8
Figure 8
SEM image of functionalized TESUD substrates with Ab-Ag-Ab-MNP (magnetic nanoparticles) biorecognition: left side: SEM image; right side: scheme.
Figure 9
Figure 9
(A) Capacitance–voltage plots for cortisol detection using the capacitance biosensor; (B) the calibration curves of the cortisol detection (black curve) and the two interferences: TNF-α (red curve) and NT-proBNP (blue curve).
Figure 10
Figure 10
(A) Capacitance–voltage plots for TNF-α detection; (B) for NT-proBNP detection using the capacitive immunosensor.
See this image and copyright information in PMC

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