Capacitive Lock-In Biosensor for Label-Free Detection of NT-proBNP

Heart failure remains a leading cause of morbidity and mortality worldwide, demanding rapid and reliable biomarker-based diagnostics for effective disease management. In this work, we introduce and experimentally validate a capacitive lock-in-based biosensor for the label-free detection of N-terminal pro-B-type natriuretic peptide (NT-proBNP), an established biomarker for heart failure. Operating frequencies of 80 Hz and 400 Hz are selected for large (0.267 mm2) and small (0.026 mm2) electrodes, respectively. These frequencies correspond to a phase angle of ∼15° in the transition region, providing the optimal balance between capacitive sensitivity, signal attenuation and noise suppression. Electrode miniaturization yields a five-fold sensitivity enhancement, achieving −4.39 and +3.33 mV/decade concentration (R2 = 0.95) in 1× PBST for the X and Y channels, respectively, over a dynamic range of 3.2–2000 ng/mL. Reproducibility is demonstrated across three sensors, while specificity is confirmed through a reference sensor functionalized with anti-cardiac troponin I. These findings establish capacitive lock-in detection as a robust and sensitive approach for cardiac biomarker quantification, with strong potential for point-of-care and wearable applications.