Combination assay of lung cancer associated serum markers using surface-enhanced Raman spectroscopy

The development of an ultrasensitive analysis technique for the combination assay of cancer associated markers is an effective method for the early detection of tumor. Herein, we report a highly sensitive and specific SERS-based sandwich immunoassay for the simultaneous detection of two protein markers associated with lung cancer, including carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE). Two bright SERS tags are prepared by surface modifications of flower-like gold nanoparticles with Raman molecules and target-specific antibodies, and SERS-active magnetic nanoparticles labelled with mixed antibodies are used as immune substrates for capturing the targets and further separating the sandwich structured immune complexes from the mixture. Immunoassays for joint detection of CEA and NSE using both buffer and human serum specimens are performed and the assay results indicate that the proposed SERS-based combination assay of the two markers shows good specificity and ultrahigh sensitivity. The limit of detections of CEA and NSE in human serum specimens are 1.48 pg mL^-1 and 2.04 pg mL^-1, respectively. The proposed SERS immunoassay is expected to be used for multiple-marker assays of any other tumors and to provide a reliable method for the early screening of cancers in clinic.