Plasmonic metal nanoparticles as efficient mass tags for ion signal amplification and ultrasensitive detection of protein markers

Highlights: • Efficient utilization of LSPR property of noble metal nanoparticle for generating abundant mass reporter ions. • Plasmonic metal nanoparticle as ion reservoir for MS signal amplification. • Specific and sensitive detection of high-mass protein in complex biological sample. -- Abstract: The development of sensitive and specific analytical methods is critical for the discovery of molecular biomarkers, which assists disease diagnosis and understanding biological processes. Herein, a highly sensitive method is developed using antibody-conjugated plasmonic metal nanoparticles for the detection of targeted biomarkers down to low attomole level via coupling of immunoassay techniques with laser ionization mass spectrometry (LI-MS). The conjugated antibodies target specific antigens, while the metal nanoparticles act as mass tags and ion reservoirs for the signal amplification. With the characteristic localized surface plasmon resonance (LSPR) properties, gold (AuNPs) and silver nanoparticles (AgNPs) undergo explosive ionization upon laser irradiation to generate abundant characteristic mass reporter ions for strong MS signal amplification. With the antibody-conjugated NPs, detection of trace proteins in various biological samples with complex matrix environment, including urine, cell lysates, and animal tissues was demonstrated.