MoS2-mediated gap-mode surface plasmon enhancement: Construction of SPR biosensor for direct detection of LECT2

Serum levels of leukocyte cell-derived chemotaxin-2 (LECT2) have emerged as promising diagnostic biomarker for liver fibrosis. Targeting the LECT2/Tie1 signaling pathway holds potential for innovative treatment approaches to this condition. Despite this, the development of highly sensitive assays for serum LECT2 remains limited. Surface plasmon resonance (SPR), a label-free technique for detecting biomolecular interactions via refractive index (RI) changes, has demonstrated notable sensitivity for biomarker assays, though improving its sensitivity for direct LECT2 detection faces certain challenges. In this study, we present an innovative enhanced SPR biosensor designed to overcome current limitations in LECT2 detection. By incorporating molybdenum disulfide (MoS₂) nanosheets as nano-spacer between the gold film and cyclodextrin functionalized-gold nanoparticles (CD-AuNPs), this gap-mode design significantly enhances the electric field intensity near the gold film surface, which effectively improves the detection sensitivity of the RI changes. Compared to traditional gold-film-only SPR sensors, our sensor achieves a remarkable sensitivity increase from 73.1 to 133.3 deg/RIU, with a commendable quality factor and detection accuracy. By further modifying the specific peptide of the terminal label phenylalanine (TFF) through the host-guest recognition effect of the CD hydrophobic cavity, we achieved a broad linear range and a low limit of detection (LOD = 0.6206 ng/mL) for the detection of the liver fibrosis marker LECT2. Our proposed enhanced SPR sensing platform demonstrates significant potential for clinical applications in LECT2 detection.