Ru Zhang, Chandrababu Rejeeth, Wei Yan, Kun Qian, R. Zhang, C. Rejeeth and K. Qian
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China
Serum biomarkers in the form of proteins (e.g. CD44) have been demonstrated with high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high sample complexity and low molecular abundance in serum, detection and profiling of biomarkers rely on efficient extraction by materials and device. In this work, we demonstrated a novel approach using hyaluronic acid (HA) modified materials/device for extraction, detection, and profiling of serum biomarkers via ligand-protein interactions. We constructed Fe3O4@SiO2@HA particles with different sizes through layer-by-layer assembling and for the first time applied HA functionalized particles for facile extraction and sequence identification of CD44 in serum by mass spectrometry (MS). Further, we performed profiling of HA binding serum proteome providing a new preliminary benchmark for construction of future database and investigated the selected surface chemistries of particles for capture of proteins in serum. Our work not only built a platform technology for CD44 extraction/detection and HA binding proteome identification, but also guided the design of ligand affinity based approaches for antibody-free analysis of serum biomarkers towards diagnostic applications.