Enhanced Photoelectrochemical Detection of Alpha-Fetoprotein Using Dipole Image Effect and Lock-In Amplification

Alpha-fetoprotein (AFP) is a serum biomarker mainly for early stage diagnosis and prognosis of primary liver cancer in clinical analysis. As a label-free analyte-specific biosensor with ultrahigh sensitivity and broad detection range, photoelectrochemical (PEC) sensor is promising for AFP detection. A unique feature of the PEC sensor, the separation of its excitation source and the detection signal, offers a great opportunity in the spatial and temporal domains to enhance its performance. For the spatial domain, AuNPs/TiO2/Au (in short, ATA) sandwiched structure was designed for magnetic resonance generation and light absorption enhancement. The strong light–matter interaction due to the dipole image effect has achieved an over 20 times increase in the sensitivity of the designed sensor. Instead of the typical method that manually switches the light source for photocurrent, lock-in amplification (LIA) was proposed to modulate the light source in the temporal domain. Such modulated signal can be coherently amplified and extracted from a strong noise background, which improves the signal-to-noise ratio (SNR) of the photocurrent signal and leads to a larger measurement range. This designed AFP biosensor exhibited one-order-of-magnitude wider linear detection range from 10 pg mL$^{-{1}}$to$1~\mu \text{g}$mL$^{-{1}}$with a detection limit of 4.5 pg mL$^{-{1}}$.