Circulating tumor cells (CTCs) are single cancer cells or cancer cell clusters that are present in the circulatory system. Assessing CTC levels in patients can aid in the early detection of cancer metastasis and is essential for the purposes of accurate cancer prognosis. However, current in vitro blood tests are limited by the insufficient blood samples and low concentration levels of CTCs, which presents a major challenge for practical biosensing devices. In this work, we propose the first

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... ace plasmon resonance (SPR) fiber probe to work intravenously, which offers a real-time detection of CTCs in bloodstreams. By exposing the protein-functionalized fiber probe to circulating blood, a continuous capture of CTCs ensures a constant increase in enrichment and hence greatly enhances enumeration accuracy. The performance of our plasmonic fiber probe was demonstrated to specifically detect Michigan Cancer Foundation-7 (MCF-7) breast cancer cells in flowing whole mouse blood. Further, a detection limit of ~1.4 cells per microliter was achieved by using an epithelial cell adhesion molecule (EpCAM) antibody-based receptor layer and a 15 min enrichment period. This pilot study validates real-time CTC detection directly in the bloodstream by using plasmonic fiber probes, which exhibit promising clinical potential for in vivo diagnostic tests involving low concentration biomarkers in circulating blood.