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Electrochemical detection and analysis of tumor-derived extracellular vesicles to evaluate malignancy of pancreatic cystic neoplasm using integrated microfluidic device

 N G Gurudatt  ;  Hogyeong Gwak  ;  Kyung-A Hyun  ;  Se-Eun Jeong  ;  Kyungyeon Lee  ;  Sunyoung Park  ;  Moon Jae Chung  ;  Seong-Eun Kim  ;  Jung Hyun Jo  ;  Hyo-Il Jung  
 BIOSENSORS & BIOELECTRONICS, Vol.226 : 115124, 2023-04 
Journal Title
Issue Date
Biosensing Techniques* ; Extracellular Vesicles* ; Humans ; Lab-On-A-Chip Devices ; Neoplasms, Cystic, Mucinous, and Serous* / metabolism ; Pancreatic Neoplasms*
Diagnostics ; EMT index ; Extracellular vesicles ; Malignant progression ; Precancer
Tumor-derived extracellular vesicles (tdEVs) are one of the most promising biomarkers for liquid biopsy-based cancer diagnostics, owing to the expression of specific membrane proteins of their cellular origin. The investigation of epithelial-to-mesenchymal transition (EMT) in cancer using tdEVs is an alternative way of evaluating the risk of malignancy transformation. An ultra-sensitive selection and detection methodology is an essential step in developing a tdEVs-based cancer diagnostic device. In this study, we developed an indium-tin-oxide (ITO) sensor integrated microfluidic device consisting of two main parts: 1) a multi-orifice flow-fractionation (MOFF) channel for extraction of pure EVs by removing blood cellular debris, and 2) an ITO sensor coupled with a geometrically activated surface interaction (GASI) channel for enrichment and quantification of tdEV. The microfluidic channel and the ITO sensors are assembled with a 3D printed magnetic housing to prevent sample leakage and to easily attach/detach the sensors to/from the microfluidic channel. The tdEVs were successfully captured on the specific antibody modified ITO surfaces in the integrated microfluidic channel. The integrated sensors showed an excellent linear response between 103 and 109 tdEVs/mL. Simultaneous evaluation of the epithelial and mesenchymal markers on the tdEV surfaces successfully revealed the EMT index of the corresponding pancreatic cancer cells. Our ITO sensor integrated microfluidic device showed excellent detection in the clinically relevant tdEVs-concentration range for patients with pancreatic cystic neoplasms. Hence, this system is expected to open a new avenue for liquid biopsy-based cancer prognostics and diagnostics.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Chung, Moon Jae(정문재) ORCID logo https://orcid.org/0000-0002-5920-8549
Jo, Jung Hyun(조중현) ORCID logo https://orcid.org/0000-0002-2641-8873
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