Rapid and label-free detection of BNP and NT-proBNP in human serum using Ti-doped MoTex film-based extended-gate FET biosensors for heart failure diagnosis

Abstract

This study presents the first successful RF sputtering of Ti-doped MoTe_x films onto flexible polyimide (PI) substrates, serving as active sensing layers in extended-gate field-effect transistors (EGFETs). These nanostructured sensors are designed for clinical applications, including accurate pH monitoring and selective detection of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the serum of heart failure patients. The structural, compositional, and morphological characteristics of the films were investigated using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). EGFET devices fabricated under varying Ti plasma powers (0, 10, 20, and 30 W) demonstrated a strong correlation between structural modifications and sensing performance. The film produced at 20 W exhibited the best results, with a pH sensitivity of 59.02 mV/pH, ultra-low hysteresis (∼ 0.3 mV), and minimal drift (0.25 mV/h). After 180 days, the sensor maintained a near-Nernstian response of ∼ 58.9 mV/pH, confirming excellent long-term stability. It also withstood 500 bending cycles without performance degradation, highlighting its mechanical robustness. For biosensing applications, the Ti-doped MoTe_x film was modified with APTES and functionalized with BNP or NT-proBNP antibodies through 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking. The resulting biosensor exhibited high sensitivity for BNP and NT-proBNP over a wide dynamic range (10⁻²–10⁵ pg/mL). Measurements from patient serum samples closely aligned with enzyme-linked immunosorbent assay (ELISA) results, demonstrating its clinical reliability.