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| Advances in Microfluidic Sorting of Extracellular Vesicles |
| Cao Changming1,2,3, Li Zhen4,5, Tian Yanhong2,3, An Rong1,2,3*, Ren Tianling4,5* |
1(School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China)
2(Key Laboratory of Micro-systems and Micro-structures Manufacturing of Ministry of Education, Harbin Institute of Technology, Harbin 150080, China)
3(National Key Laboratory of Precision Welding & Joining of Materials and Structures, Harbin Institute of Technology, Harbin 150001, China)
4(School of Integrated Circuits, Tsinghua University, Beijing 100084, China)
5(Beijing National Research Center for Information Science and Technology (BNRist), Tsinghua University, Beijing 100084, China) |
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Abstract Extracellular vesicles (EVs) are one type of membrane-enclosed particles released by cells into the extracellular environment. EVs are ubiquitously present in various body fluids including blood and urine. They serve as biomarkers for numerous diseases, owing to their content of diverse biomolecules like proteins and nucleic acids. The extraction and analysis of EVs are crucial for the rapid diagnosis and treatment of diseases. Traditional techniques employed for sorting EVs, such as differential ultracentrifugation, need a substantial amount of sample material and involve costly instrumentation. Conversely, microfluidic sorting techniques offer several benefits, including miniaturization, high recovery rates and integration, thus making them more suitable for the application in medical institutions and clinics. This review categorized microfluidic sorting methods into label-free passive, label-free active, fixed-substrate immunoaffinity and free-bead immunoaffinity sorting, introduced the research progress of these methods in the field of EVs isolation. The characteristics including purity, recovery, flux and difficulty in chip fabrication of each method are summarized and compared in the review. In addition, the review envisaged the future development directions for microfluidic sorting of EVs, which included sorting indexes improvement, sorting costs reduction and separation cut-off size decrement. For label-free sorting, acoustophoresis is more promising due to the advantages in achieving high purity and throughput, as well as the capability to sort nano-sized EVs. Acoustophoresis also enables monolithic integration of acoustic sensing modules for EV concentration. For immunoaffinity sorting, the technology using free beads has advantages of high capture efficiency and chip reusability, which is suitable for continuous and batch sorting scenarios.
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Received: 15 March 2024
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Corresponding Authors:
*E-mail: anr@hit.edu.cn; rentl@tsinghua.edu.cn
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