Highly Sensitive Diagnostic Assay for the Detection of Protein Biomarkers Using Microresonators and Multifunctional Nanoparticles

Abstract

We developed a novel gravimetric immunoassay for sensitive detection of multiple protein biomarkers using silicon microcantilever arrays and multifunctional hybrid nanoparticles. Magnetic-photocatalytic hybrid nanoparticles with a highly crystalline TiO2 shell were synthesized using a solvothermal reaction without a calcination process. After functionalizing the hybrid nanoparticles and silicon cantilevers with antibodies, the nanoparticles were used to magnetically separate target biomarkers from human serum. Frequency changes of the microcantilevers due to the binding of the nanoparticles were measured using a dip-and-dry method. Frequency changes were further amplified using a photocatalytic silver reduction reaction. Several biomarkers, including interleukin-6, interferon-gamma, and alpha-fetoprotein, were selectively detected using arrays of eight silicon microcantilevers. The detection limit of this assay was similar to 0.1 pg/mL, which is superior to the clinical threshold of the biomarkers.