Nucleolin protein-mediated specific detection of circulating cancer cells by U-bent optical fiber sensor

Abstract

Circulating Tumor Cells (CTCs) have emerged as an eligible biomarker for liquid biopsy. These cells are released in peripheral circulation at a very early stage from the tumor mass via metastatic or non-metastatic cascade. These cells provide a non-invasive method for cancer detection and monitoring. In this work, Gold Nanoparticle (GNP) decorated U-bent optical fiber was used as a sensor platform. For specific detection of cancer cells, an antibody for nucleolin protein which over-expresses on their surface was employed as a receptor. This Localized Surface Plasmon Resonance (LSPR) based biosensor poses salient features like high sensitivity, ease of fabrication, low cost, and handling. For sensor fabrication, optical fiber was decladded, bent in a U-shape, and cleaned. After GNPs, U-bent fiber was coated with cysteamine. The concentration and incubation time of cysteamine was optimized as they played a critical role in the sensitivity and specificity of the sensor. Next, the amine group of cysteamines was treated with glutaraldehyde to which the antibody was attached. Ethanolamine was used as a blocking agent and its incubation time was also optimized. The sensor was introduced to 104 MCF-7 cells and 105 WBCs in PBS buffer and the binding absorbance for 2 hours was monitored. The obtained absorbance for MCF-7 cells and WBCs was around 0.05±0.011 and 0.002±0.0015 O.D. respectively, which indicated a very high specificity of the sensor for cancer cells. The obtained results are promising and pave the way to develop a highly specific and affordable point-of-care device for cancer detection and monitoring.