Magnetic “Squashing” of Circulating Tumor Cells on Plasmonic Substrates for Ultrasensitive NIR Fluorescence Detection

Detection of circulating tumor cells (CTCs) in patient's blood is an important approach to cancer diagnosis and prognosis, but has been challenging due to the rarity of cells. Here, a magnetic‐enhanced capturing of CTCs onto a plasmonic gold (pGOLD) chip, through a microfluidic immunomagnetic method, is demonstrated. Owing to the squashed/flattened morphology of cancer cells by magnetic forces and the resulting close proximity of near‐infrared (NIR) labels on cells to the pGOLD surface, an ultrahigh NIR fluorescence enhancement of ≈50–120‐fold is observed, drastically enhancing the ability of CTC detection, imaging, and analysis. Fluorescence enhanced, multiplexed protein biomarkers detection of CTCs is conducted for cancer cell spiked samples as well as CTCs in cancer patient's blood. Low CTC concentrations are detected down to ≈1 cell mL −1 with capture efficiency up to ≈90%. Mechanical manipulation of cells by magnetic and other forces on plasmonic substrates represents a promising approach to ultrasensitive bio‐analytical applications.