The isolation and characterization of circulating tumor cells (CTCs) has great potential for non-invasive biopsy. In this study, a surface-enhanced Raman spectroscopy (SERS) method was developed using magnetic nanoparticles and a solid SERS-active substrate integrated with an external field-assisted microfluidic device to efficiently isolate CTCs from blood samples. A new SERS substrate was used, developed by physically modifying the surface with a femtosecond laser, sputtering the active SERS layer and chemically modifying the surface with anti-EpCAM antibodies. Magnetic nanoparticles (Fe2O3) were coated with SERS active metal and then modified with para-mercaptobenzoic acid (p-MBA), which acts simultaneously as a Raman reporter and a linker with anti-EpCAM antibodies. The sensitive immune recognition of tumor cells is aided by the introduction of a controlled external magnetic field into the microfluidic chip. The integration of the SERS-active platform and p-MBA labeled immuno-Ag@Fe2O3 nanostructures with the microfluidic device ensures lower demand for samples and analytes, precise operation, increases the reproducibility of spectral responses and enables miniaturization and portability of the presented approach. We used four target tumor cell lines with relatively large (human prostate metastatic adenocarcinoma cells (LNCaP)), medium (adenocarcinomic human alveolar basal epithelial cells (A549)), weak (human prostate tumor line (PC3)) and no expression of EpCAM (tumor cells) cervical cancer (HeLa)) to estimate the detection limits on the basis of constructed calibration curves blood samples from lung cancer patients were used to validate the developed method.[1]

1. M. Czaplicka, K. Niciński, A. Nowicka, T. Szymborski i A. Kamińska, Cancers, 2020, 12 (3315), 1-21.