Real-Time, Highly Sensitive Detection of Alpha-Fetoprotein in Biological Fluids Using a QCM Sensor Based on a Cu2O@MoS2-Au nanocomposite and Gold Staining

Herein, a highly sensitive, sandwich-type quartz crystal microbalance (QCM) immunosensor is proposed for the quantitative monitoring of alpha-fetoprotein (AFP), a representative tumor marker for hepatocellular carcinoma. A cuprous oxide @ molybdenum disulfide (Cu2O@MoS2) nanohybrid was synthesized and combined with gold nanoparticles. The yield, a Cu2O@MoS2-Au nanocomposite, exhibited coral morphology with an increased surface area for loading more secondary antibodies (Ab(2)), which amplified the mass loading on the QCM electrode's surface. The immunosensor's sensitivity was further enhanced by injecting the gold-staining solution for signal amplification. A self-assembled monolayer of primary antibody (Ab(1)) was also fabricated on the QCM electrode's surface via mercaptoacetic acid immobilization in EDC and NHS. The immunosensor's limit of detection dropped to 35 pg/mL and 90 pg/mL with and without the gold enhancement, respectively. When used to detect AFP in human saliva and serum samples, the immunosensor displayed high selectivity and long-term stability, which indicates its potential for clinically monitoring of biomarkers.

Automated summary

In this study, a highly sensitive sandwich-type quartz crystal microbalance (QCM) immunosensor was developed for the quantitative monitoring of alpha-fetoprotein (AFP), a representative tumor marker for hepatocellular carcinoma. A nanohybrid of cuprous oxide @ molybdenum disulfide (Cu2O@MoS2) combined with gold nanoparticles was synthesized to increase the mass loading on the QCM electrode's surface. The sensor's sensitivity was further enhanced by gold enhancement and a self-assembled monolayer of primary antibody (Ab(1)) was fabricated on the QCM electrode. The immunosensor achieved a detection limit of 35 pg/mL with gold enhancement and 90 pg/mL without gold enhancement.