Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong 999077, China.
Light, Nanomaterials & Nanotechnologies (L2n), CNRS-EMR 7004, University of Technology of Troyes, 10000 Troyes, France.
Biosensors (Basel). 2022 Nov 3;12(11):968. doi: 10.3390/bios12110968.
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 surface 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 minute 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.
循环肿瘤细胞 (CTCs) 是存在于循环系统中的单个癌细胞或癌细胞簇。评估患者的 CTC 水平有助于早期发现癌症转移，对于准确的癌症预后至关重要。然而，目前的体外血液检测受到血液样本不足和 CTC 浓度低的限制，这对实用的生物传感设备提出了重大挑战。在这项工作中，我们提出了第一个用于静脉内的表面等离子体共振 (SPR) 光纤探头，可实时检测血液中的 CTC。通过将蛋白功能化的光纤探头暴露于循环血液中，可以连续捕获 CTC，从而确保富集的持续增加，从而大大提高了计数的准确性。我们的等离子体光纤探头的性能被证明可以特异性地检测到流动的全鼠血液中的密歇根癌症基金会-7 (MCF-7) 乳腺癌细胞。进一步地，通过使用上皮细胞黏附分子 (EpCAM) 抗体作为受体层和 15 分钟的富集时间，实现了约 1.4 个细胞/微升的检测限。这项初步研究通过使用等离子体光纤探头直接在血液中实时检测 CTC，这为涉及循环血液中低浓度生物标志物的体内诊断测试提供了有前景的临床潜力。
