An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood
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
Affiliations
Chaithanya Chelakkot
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Jiyeon Ryu
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Mi Young Kim
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Korea
Jin-Soo Kim
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Korea
Dohyeong Kim
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Juhyun Hwang
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Sung Hoon Park
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Seok Bum Ko
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Jeong Won Park
IT Convergence Technology Research Laboratory, Electronic and Telecommunications Research Institute, Daejon 34129, Korea
Moon Youn Jung
IT Convergence Technology Research Laboratory, Electronic and Telecommunications Research Institute, Daejon 34129, Korea
Ryong Nam Kim
Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Korea
Kyoung Song
The Center for Companion Diagnostics, LOGONE Bio Convergence Research Foundation, Seoul 08394, Korea
Yu Jin Kim
The Center for Companion Diagnostics, LOGONE Bio Convergence Research Foundation, Seoul 08394, Korea
Yoon-La Choi
Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 08394, Korea
Hun Seok Lee
Technical Research Center, Genobio Corp., Seoul 08394, Korea
Young Kee Shin
Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea
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.
