A split-type photoelectrochemical biosensor using GSH-loaded liposomes in situ stimulation of ATA photoelectrode for the sensitive detection of AFP.

A non-enzymatic signal-amplified photoelectrochemical (PEC) was developed for the highly sensitive detection of alpha-fetoprotein (AFP) by employing glutathione-loaded liposomes (GSH@Lip) and AuNPs/TiO2/Au (ATA) photoelectrodes. The ATA composite integrated well-designed optical trapping structure and to excite multiple light absorption via modes such as localized surface plasmon resonance (LSPR) and magnetic resonance mode. Furthermore, the signal was amplified using the high-loaded capacity of liposomes and the highly efficient GSH molecules to enhance the photocurrent of the ATA photoelectrodes. Specifically, AFP-specific recognition followed by centrifugation enriched with a large number of glutathione-encapsulated liposomes, whereas GSH can serve as an electron donor to scavenge the hole and inhibit the charge recombination. The incorporation of GSH-loaded liposomes into photoelectrochemical (PEC) immunoassays provides an enzyme-free alternative, eliminating the need for natural enzymes (e.g., HRP or ALP) while offering superior stability and simplified operation compared to conventional enzyme-based methods. The developed split-type PEC biosensor demonstrated outstanding analytical performance for AFP within the concentration range of 10-3 to 103 ng mL-1, achieving a low limit of detection (LOD) of 0.86 pg mL-1, this covers the clinically relevant concentration range of AFP in patients with HCC (20-400 ng mL-1). Noteworthy, for its stability, broad detection range, and rapid response, this biosensor presents an effective approach for cancer marker detection.