Abstract: A proof of concept of a reflection-based nanohole array sensor system is presented for discriminating between migration-competent cancer cells that maintain the integrity of the actin cortex and those cells lacking the actin cortex and thus unable to migrate. The system performance is analyzed by studying the spectral features of the reflected light by live single cells in contact with the nanohole array. We demonstrate that the presence of the actin cortex, needed for cell migration, in three different colorectal cancer cell lines (HT29, CaCo2, SW480) significantly affect the optical response (through the refractive index quantification), enabling high sensitivity and specificity in cell discrimination. These findings suggest that reflection-mode plasmonic biosensors offer a practical and efficient platform for label-free cellular analysis, with potential applications for discriminating tumour tissues in the operating room.

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