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

1
Technical Research Center, Genobio Corp., Seoul 08394, Korea
2
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 07061, Korea
3
IT Convergence Technology Research Laboratory, Electronic and Telecommunications Research Institute, Daejon 34129, Korea
4
Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Korea
5
The Center for Companion Diagnostics, LOGONE Bio Convergence Research Foundation, Seoul 08394, Korea
6
Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 08394, Korea
7
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
8
Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea
9
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea
10
The Center for Anti-Cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Micromachines 2020, 11(6), 560; https://doi.org/10.3390/mi11060560
Received: 30 April 2020 / Revised: 22 May 2020 / Accepted: 26 May 2020 / Published: 30 May 2020
(This article belongs to the Section B:Biology and Biomedicine)
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. View Full-Text
Keywords: circulating tumor cells; liquid biopsy; epithelial cell adhesion molecule (EpCAM); MET; biomarker circulating tumor cells; liquid biopsy; epithelial cell adhesion molecule (EpCAM); MET; biomarker
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Chelakkot, C.; Ryu, J.; Kim, M.Y.; Kim, J.-S.; Kim, D.; Hwang, J.; Park, S.H.; Ko, S.B.; Park, J.W.; Jung, M.Y.; Kim, R.N.; Song, K.; Kim, Y.J.; Choi, Y.-L.; Lee, H.S.; Shin, Y.K. An Immune–Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood. Micromachines 2020, 11, 560.

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