An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood

Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating t...

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Main Authors: Chaithanya Chelakkot, Jiyeon Ryu, Mi Young Kim, Jin-Soo Kim, Dohyeong Kim, Juhyun Hwang, Sung Hoon Park, Seok Bum Ko, Jeong Won Park, Moon Youn Jung, Ryong Nam Kim, Kyoung Song, Yu Jin Kim, Yoon-La Choi, Hun Seok Lee, Young Kee Shin
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Micromachines
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Online Access:https://www.mdpi.com/2072-666X/11/6/560
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author Chaithanya Chelakkot
Jiyeon Ryu
Mi Young Kim
Jin-Soo Kim
Dohyeong Kim
Juhyun Hwang
Sung Hoon Park
Seok Bum Ko
Jeong Won Park
Moon Youn Jung
Ryong Nam Kim
Kyoung Song
Yu Jin Kim
Yoon-La Choi
Hun Seok Lee
Young Kee Shin
author_facet Chaithanya Chelakkot
Jiyeon Ryu
Mi Young Kim
Jin-Soo Kim
Dohyeong Kim
Juhyun Hwang
Sung Hoon Park
Seok Bum Ko
Jeong Won Park
Moon Youn Jung
Ryong Nam Kim
Kyoung Song
Yu Jin Kim
Yoon-La Choi
Hun Seok Lee
Young Kee Shin
author_sort Chaithanya Chelakkot
collection DOAJ
description Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 μL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration.
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spelling doaj.art-bf6f2d2a4e8c4167b093210be92d5ba42023-11-20T02:19:42ZengMDPI AGMicromachines2072-666X2020-05-0111656010.3390/mi11060560An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole BloodChaithanya Chelakkot0Jiyeon Ryu1Mi Young Kim2Jin-Soo Kim3Dohyeong Kim4Juhyun Hwang5Sung Hoon Park6Seok Bum Ko7Jeong Won Park8Moon Youn Jung9Ryong Nam Kim10Kyoung Song11Yu Jin Kim12Yoon-La Choi13Hun Seok Lee14Young Kee Shin15Technical Research Center, Genobio Corp., Seoul 08394, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaDepartment of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, KoreaDepartment of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaIT Convergence Technology Research Laboratory, Electronic and Telecommunications Research Institute, Daejon 34129, KoreaIT Convergence Technology Research Laboratory, Electronic and Telecommunications Research Institute, Daejon 34129, KoreaBio-MAX/N-Bio, Seoul National University, Seoul 08826, KoreaThe Center for Companion Diagnostics, LOGONE Bio Convergence Research Foundation, Seoul 08394, KoreaThe Center for Companion Diagnostics, LOGONE Bio Convergence Research Foundation, Seoul 08394, KoreaLaboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 08394, KoreaTechnical Research Center, Genobio Corp., Seoul 08394, KoreaLaboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, KoreaHere, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 μL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration.https://www.mdpi.com/2072-666X/11/6/560circulating tumor cellsliquid biopsyepithelial cell adhesion molecule (EpCAM)METbiomarker
spellingShingle Chaithanya Chelakkot
Jiyeon Ryu
Mi Young Kim
Jin-Soo Kim
Dohyeong Kim
Juhyun Hwang
Sung Hoon Park
Seok Bum Ko
Jeong Won Park
Moon Youn Jung
Ryong Nam Kim
Kyoung Song
Yu Jin Kim
Yoon-La Choi
Hun Seok Lee
Young Kee Shin
An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
Micromachines
circulating tumor cells
liquid biopsy
epithelial cell adhesion molecule (EpCAM)
MET
biomarker
title An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
title_full An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
title_fullStr An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
title_full_unstemmed An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
title_short An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
title_sort immune magnetophoretic device for the selective and precise enrichment of circulating tumor cells from whole blood
topic circulating tumor cells
liquid biopsy
epithelial cell adhesion molecule (EpCAM)
MET
biomarker
url https://www.mdpi.com/2072-666X/11/6/560
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