Continuous centrifugal microfluidics (CCM) isolates heterogeneous circulating tumor cells via full automation
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Continuous centrifugal microfluidics (CCM) isolates heterogeneous circulating tumor cells via full automation. / Woo, Hyeong Jung; Kim, Seung-Hoon; Kang, Hyo Jung; Lee, Soo-Hwan; Lee, Seung Joon; Kim, Jong Man; Gurel, Ogan; Kim, Soo Yeol; Roh, Hye Ran; Lee, Jungmin; Park, Yeonsoo; Shin, Hyun Young; Shin, Yong-Il; Lee, Sun Min; Oh, So Yeon; Kim, Young Zoon; Chae, Jung-Il; Lee, Seoyoung; Hong, Min Hee; Cho, Byoung Chul; Lee, Eun Sook; Pantel, Klaus; Kim, Hye Ryun; Kim, Minseok S.
in: THERANOSTICS, Jahrgang 12, Nr. 8, 2022, S. 3676-3689.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Continuous centrifugal microfluidics (CCM) isolates heterogeneous circulating tumor cells via full automation
AU - Woo, Hyeong Jung
AU - Kim, Seung-Hoon
AU - Kang, Hyo Jung
AU - Lee, Soo-Hwan
AU - Lee, Seung Joon
AU - Kim, Jong Man
AU - Gurel, Ogan
AU - Kim, Soo Yeol
AU - Roh, Hye Ran
AU - Lee, Jungmin
AU - Park, Yeonsoo
AU - Shin, Hyun Young
AU - Shin, Yong-Il
AU - Lee, Sun Min
AU - Oh, So Yeon
AU - Kim, Young Zoon
AU - Chae, Jung-Il
AU - Lee, Seoyoung
AU - Hong, Min Hee
AU - Cho, Byoung Chul
AU - Lee, Eun Sook
AU - Pantel, Klaus
AU - Kim, Hye Ryun
AU - Kim, Minseok S
N1 - © The author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Automation
KW - Cell Line, Tumor
KW - Cell Separation/methods
KW - Epithelial Cell Adhesion Molecule/genetics
KW - ErbB Receptors/genetics
KW - Humans
KW - Microfluidics/methods
KW - Neoplastic Cells, Circulating/metabolism
U2 - 10.7150/thno.72511
DO - 10.7150/thno.72511
M3 - SCORING: Journal article
C2 - 35664056
VL - 12
SP - 3676
EP - 3689
JO - THERANOSTICS
JF - THERANOSTICS
SN - 1838-7640
IS - 8
ER -