Mitigation of Channel Clogging in a Microfluidic Device for Capturing Circulating Tumor Cells
Tomoki Konishi*, Yuki Jingu*, Tatsuya Yoshizawa*, Masaru Irita*, Toshihiro Suzuki**, and Masanori Hayase*,
*Department of Mechanical Engineering, Faculty Science and Technology, Tokyo University of Science
2641 Yamazaki, Noda, Chiba 277-0034, Japan
**General Medical Education and Research Center, Teikyo University, Tokyo, Japan
Deterministic lateral displacement (DLD) based microfluidic devices have been developed for capturing circulating tumor cells (CTCs) from the peripheral blood. There was frequent and problematic channel clogging around the micro-post array formed on a microchannel of the device. In this study, various agents were dispersed into the blood specimen to avoid clogging. At first, platelet aggregation was considered to be the cause of the clogging, but even plasmin, which was assumed to decompose platelet aggregations, did not show obvious inhibition of the clogging. Then, enzymes used for cell detachment from tissue were examined and decomposition of the clogging residue was observed. Finally, dispersion of deoxyribonuclease into a blood specimen was found to be effective for the inhibition of clogging. The existence of DNA in the clogging residue was also confirmed by propidium iodide (PI) staining, suggesting DNA adhering to the micro-post.
-  L. Chaffer and R. A. Weinberg, “A Perspective on Cancer Cell Metastasis,” Science, Vol.331, pp. 1559-1564, 2011.
-  W. J. Allard et al., “Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases,” Clinical Cancer Research, Vol.10, pp. 6897-6904, 2004.
-  S. Ariyasu et al., “Selective capture and collection of live target cells using a photoreactive silicon wafer device modified with antibodies via a photocleavable linker,” Langmuir, Vol.28, No.36, pp. 13118-13126, 2012.
-  S. Nagrath et al., “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature, Vol.450, pp. 1235-1239, 2007.
-  C. Jin et al., “Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments,” Lab Chip., Vol.14, No.1, pp. 32-44, 2014.
-  R. F. Alexander and A. I. Spriggs, “The differential diagnosis of tumour cells in circulating blood,” J. Clinical Pathology, Vol.13, No.5, pp. 414-424, 1960.
-  H. Okano et al., “Enrichment of circulating tumor cells in tumor-bearing mouse blood by a deterministic lateral displacement microfluidic device,” Biomedical Microdevices, Vol.17, No.3, 59, 2015.
-  N. M. Karabacak et al., “Microfluidic, marker-free isolation of circulating tumor cells from blood samples,” Nature Protocols, Vol.9, pp. 694-710, 2014.
-  A. Yusa et al., “Development of a new rapid isolation device for circulating tumor cells (CTCs) using 3d palladium filter and its application for genetic analysis,” PLOS ONE, Vol.9, e88821, 2014.
-  Z. Liu et al., “Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure,” Biomicrofluidics, Vol.7, 011801, 2013.
-  K. Loutherback et al., “Deterministic separation of cancer cells from blood at 10 mL/min,” AIP Advances, Vol.2, 042107, 2012.
-  M. Hosokawa et al., “Size-selective microcavity array for rapid and efficient detection of circulating tumor cells,” Anal. Cehm., Vol.82, pp. 6629-6635, 2010.
-  B. Shashni et al., “Simple and convenient method for the isolation, culture, and recollection of cancer cells from blood by using glass-bead filters,” ACS Biomater. Sci. Eng., Vol.5, pp. 438-451, 2018.
-  B. Shashni et al., “Size-based differentiation of cancer and normal cells by a particle size analyzer assisted by a cell-recognition PC software,” Biol. Pharm. Bull., Vol.41, pp. 487-503, 2018.
-  T. S. H. Tran et al., “Open channel deterministic lateral displacement for particle and cell sorting,” Lab on a Chip, Vol.17, pp. 3592-3600, 2017.
-  L. Huang et al., “Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture,” Biomicrofluidics, Vol.11, 011501, 2017.
-  L. R. Huang et al., “Continuous particle separation through deterministic lateral displacement,” Science, Vol.304, pp. 987-990, 2004.
-  D. W. Inglis et al., “Critical particle size for fractionation by deterministic lateral displacement,” Lab Chip., Vol.6, No.5, pp. 655-658, 2006.
-  N. Tottori et al., “Separation of viable and nonviable mammalian cells using a deterministic lateral displacement microfluidic device,” Biomicrofluidics, Vol.10, 014125, 2016.
-  J. D’Silva et al., “Inhibition of clot formation in deterministic lateral displacement array for processing large volumes of blood for rare cell capture,” Lab on a Chip, Vol.15, pp. 2240-2247, 2015.
-  K. H. K. Wong et al., “Anti-thrombotic strategies for microfluidic blood processing,” Lab on a Chip, Vol.18, pp. 2146-2155, 2018.
-  R. Kosaka et al., “Improvement of hemocompatibility in centrifugal blood pump with hydrodynamic bearings and semi-open impeller: in vitro evaluation,” Artificial Organs, Vol.33, pp. 798-804, 2009.
-  H. Hoshi, T. Shinshi, and S. Takatani, “Third-generation blood pumps with mechanical noncontact magnetic bearings,” Artificial Organs, Vol.30, pp. 324-338, 2006.
-  T. Tsukada and T. Ogawa, “On the mecanism of platelet retention by glass bead column. The platelet adhesiveness on glass head columns (Hellem II) was stdied by scanning electron-microscopy,” Jpn. J. Clin. Hematol., Vol.14, pp. 777-784, 1973 (in Japanese).
-  E. Fuentes et al., “Inhibition of platelet activation and thrombus formation by adenosine and inosine: studies on their relative contribution and molecular modeling,” PLOS ONE, Vol.9, e112741, 2014.
-  J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, and W. Strover (Eds.), “Current Protocols in Immunology,” John Wiley & Sons, Inc., 1996.
-  T. Y. Chao and T. M. Chu, “Effect of indomethacin on tumor-infiltrating lymphocytes of a spontaneously developed murine mammary adenocarcinoma,” Cancer Immunol Immnother, Vol.30, pp. 158-164, 1989.
This article is published under a Creative Commons Attribution-NoDerivatives 4.0 International License.