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Microfluidic chip for rapid and selective isolation of tumor-derived extracellular vesicles for early diagnosis and metastatic risk evaluation of breast cancer

Authors
 Hogyeong Gwak  ;  Sunyoung Park  ;  Junmoo Kim  ;  Jeong Dong Lee  ;  In-Soo Kim  ;  Seung-Il Kim  ;  Kyung-A Hyun  ;  Hyo-Il Jung 
Citation
 BIOSENSORS & BIOELECTRONICS, Vol.192 : 113495, 2021-11 
Journal Title
BIOSENSORS & BIOELECTRONICS
ISSN
 0956-5663 
Issue Date
2021-11
MeSH
Biosensing Techniques* ; Breast Neoplasms* / diagnosis ; Cell Line, Tumor ; Early Detection of Cancer ; Epithelial-Mesenchymal Transition ; Extracellular Vesicles* ; Female ; Humans ; Microfluidics
Keywords
Early diagnosis ; Epithelial-to-mesenchymal transition ; Extracellular vesicle ; Metastatic risk ; Selective separation
Abstract
The epithelial-to-mesenchymal transition (EMT) index in cancer is a complementary approach for estimating metastatic risk. Considering the demand for evaluating metastatic risk based on liquid biopsies, tumor-derived extracellular vesicles (EVs) can be exploited to generate the EMT index. For the generation of EVs-based EMT index, it is essential to selectively isolate each epithelial cell and mesenchymal cell-derived EVs. This study proposes a novel microfluidic chip for selectively separating two types of EVs in an efficient and timely manner. The microfluidic chip is fully integrated with a micromixer for the creation of efficient collision between EVs and specific antibody-coated microbeads (7 and 15 μm in diameter) and a hydrodynamic particle separator for the stratification of EVs bound microbeads according to the sizes of microbeads. Using this chip, over 90% of EVs expressing the epithelial marker (epithelial cell adhesion molecule, EpCAM) and the mesenchymal marker (CD49f) can be selectively isolated within 6.7 min per 100 μL of sample volume. The clinical relevance of EMT is investigated using plasma samples from 20 breast cancer patients and 10 age-matched controls. The EMT index produced from the microfluidic chip is in a good agreement with the conventional tissue-based EMT index and is significantly high in patients with aggressive breast cancer subtypes, compared with healthy controls. In addition, the patients with high scores on the EMT index (≥5) shows recurrence within 5 years after adjuvant treatment. Predicting EMT-index-based metastatic risk using our microfluidic chip can be beneficial for cancer diagnosis and prognosis.
Full Text
https://www.sciencedirect.com/science/article/pii/S0956566321005327
DOI
10.1016/j.bios.2021.113495
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Il(김승일)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/186747
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