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Continuous centrifugal microfluidics (CCM) isolates heterogeneous circulating tumor cells via full automation

 Hyeong Jung Woo  ;  Seung-Hoon Kim  ;  Hyo Jung Kang  ;  Soo-Hwan Lee  ;  Seung Joon Lee  ;  Jong Man Kim  ;  Ogan Gurel  ;  Soo Yeol Kim  ;  Hye Ran Roh  ;  Jungmin Lee  ;  Yeonsoo Park  ;  Hyun Young Shin  ;  Yong-Il Shin  ;  Sun Min Lee  ;  So Yeon Oh  ;  Young Zoon Kim  ;  Jung-Il Chae  ;  Seoyoung Lee  ;  Min Hee Hong  ;  Byoung Chul Cho  ;  Eun Sook Lee  ;  Klaus Pantel  ;  Hye Ryun Kim  ;  Minseok S Kim 
 THERANOSTICS, Vol.12(8) : 3676-3689, 2022-05 
Journal Title
Issue Date
Automation ; Cell Line, Tumor ; Cell Separation / methods ; Epithelial Cell Adhesion Molecule / genetics ; ErbB Receptors / genetics ; Humans ; Microfluidics / methods ; Neoplastic Cells, Circulating* / metabolism
cancer heterogeneity ; circulating tumor cells ; continuous centrifugal microfluidics ; full automation ; unbiased isolation
Understanding cancer heterogeneity is essential to finding diverse genetic mutations in metastatic cancers. Thus, it is critical to isolate all types of CTCs to identify accurate cancer information from patients. Moreover, full automation robustly capturing the full spectrum of CTCs is an urgent need for CTC diagnosis to be routine clinical practice. Methods: Here we report the full capture of heterogeneous CTC populations using fully automated, negative depletion-based continuous centrifugal microfluidics (CCM). Results: The CCM system demonstrated high performance (recovery rates exceeding 90% and WBC depletion rate of 99.9%) across a wide range of phenotypes (EpCAM(+), EpCAM(-), small-, large-sized, and cluster) and cancers (lung, breast, and bladder). Applied in 30 lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR) mutations, the system isolated diverse phenotypes of CTCs in marker expression and size, implying the importance of unbiased isolation. Genetic analyses of intra-patient samples comparing cell-free DNA with CCM-isolated CTCs yielded perfect concordance, and CTC enumeration using our technique was correlated with clinical progression as well as response to EGFR inhibitors. Conclusion: Our system also introduces technical advances which assure rapid, reliable, and reproducible results, thus enabling a more comprehensive application of robust CTC analysis in clinical practice.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Lee, Seoyoung(이서영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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