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A Fluid Multivalent Magnetic Interface for High-Performance Isolation and Proteomic Profiling of Tumor-Derived Extracellular Vesicles
Authors:Qi Niu  Dr. Yun Shu  Yuanqiang Chen  Dr. Zhi Huang  Zhixian Yao  Dr. Xiaofeng Chen  Fanghe Lin  Jianzhou Feng  Chen Huang  Dr. Hua Wang  Dr. Hongming Ding  Prof. Chaoyong Yang  Dr. Lingling Wu
Affiliation:1. The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Centre of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China

These authors contributed equally to this work.;2. School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China

These authors contributed equally to this work.;3. Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, China

These authors contributed equally to this work.;4. Institute of Molecular Medicine, Department of Gastrointestinal Surgery, Clinical Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

These authors contributed equally to this work.;5. Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, China;6. The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Centre of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China;7. School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China;8. Institute of Molecular Medicine, Department of Gastrointestinal Surgery, Clinical Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Abstract:Isolation and analysis of tumor-derived extracellular vesicles (T-EVs) are important for clinical cancer management. Here, we develop a fluid multivalent magnetic interface (FluidmagFace) in a microfluidic chip for high-performance isolation, release, and protein profiling of T-EVs. The FluidmagFace increases affinity by 105-fold with fluidity-enhanced multivalent binding to improve isolation efficiency by 13.9 % compared with a non-fluid interface. Its anti-adsorption property and microfluidic hydrodynamic shear minimize contamination, increasing detection sensitivity by two orders of magnitude. Moreover, its reversibility and expandability allow high-throughput recovery of T-EVs for mass spectrometric protein analysis. With the chip, T-EVs were detected in all tested cancer samples with identification of differentially expressed proteins compared with healthy controls. The FluidmagFace opens a new avenue to isolation and release of targets for cancer diagnosis and biomarker discovery.
Keywords:Extracellular Vesicles  Fluid Interface  Interfacial Reaction  Liquid Biopsy  Microfluidics
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