Synthesis of magnetic Fe3O4–Au hybrids for sensitive SERS detection of cancer cells at low abundance

Abstract

This work reports a facile synthesis of magnetic hybrids (Fe₃O₄–Au hybrids) with high SERS activity for detecting a low abundance of cancer cells. We labeled Raman reporter molecule 4-aminothiophenol (4-ATP) and the antibody of CEA (anti-CEA) on Fe₃O₄–Au hybrid nanoparticles (anti-CEA/4-ATP/Fe₃O₄–Au) as SERS tags and anti-CEA-labeled Au NPs (anti-CEA/Au) as SERS-active substrates to improve detection sensitivity. In the presence of CEA positive-expressed cancer cells (such as non-small lung cancer cells, A549), sandwich structures were formed as both SERS tags and SERS-active substrates could be bound to CEA at cell surfaces, leading to the formation of SERS hot spots at the junction of SERS tags and SERS-active substrates. As a result, an enhanced SERS signal of 4-ATP arose, which could be used to detect CEA on cell surfaces. This assay can specifically detect CEA-expressed A549 cells at a very low abundance (∼10 cells mL⁻¹) and can be used for evaluating CEA expression levels of different cancer cells line. This assay has the advantages of high sensitivity (because the SERS technique itself enables the detection of very low concentration analytes, even single molecules), high specificity (because of the enhanced SERS signal arising in sandwich configuration, which is formed in specific antigen–antibody interaction events), and high efficiency (because the magnetic SERS tags can concentrate the captured cells and separate them from the complex detection system without repetitive washing steps). These features make our developed assay a rapid and facile method to sensitively detect a low abundance of cancer cells.