A Trachea-Inspired Bifurcated Microfilter Capturing Viable Circulating Tumor Cells via Altered Biophysical Properties as Measured by Atomic Force Microscopy

Authors

  • Minseok S. Kim,

    Corresponding author
    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
    • POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea.
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  • Jinhoon Kim,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Wonho Lee,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Sang-Joon Cho,

    1. Research and Development Center, Park Systems, Korea
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  • Jin-Mi Oh,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • June-Young Lee,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Sanghyun Baek,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Yeon Jeong Kim,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Tae Seok Sim,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Hun Joo Lee,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
    2. Interdisciplinary Program of Integrated, Biotechnology, Sogang University, Korea
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  • Goo-Eun Jung,

    1. Research and Development Center, Park Systems, Korea
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  • Seung-Il Kim,

    1. Department of Surgery, Yonsei University College of Medicine, Korea
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  • Jong-Myeon Park,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
    2. Department of Chemistry and Center for Bioactive, Molecular Hybrids, Yonsei University, Korea
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  • Jin Ho Oh,

    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
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  • Ogan Gurel,

    1. MOT Research Center, CTO Office, Samsung Advanced Institute of Technology, Korea and Samsung Advanced Institute of Health Sciences & Technology, SungKyunKwan University, Korea
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  • Soo Suk Lee,

    Corresponding author
    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
    • POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea.
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  • Jeong-Gun Lee

    Corresponding author
    1. POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea
    • POCT In Vitro Diagnostics Group, R&D Solution Group, Samsung Advanced Institute of Technology (SAIT), San 14, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do, Korea.
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Abstract

Circulating tumor cells (CTCs), though exceedingly rare in the blood, are nonetheless becoming increasingly important in cancer diagnostics. Despite this keen interest and the growing number of potential clinical applications, there has been limited success in developing a CTC isolation platform that simultaneously optimizes recovery rates, purity, and cell compatibility. Herein, a novel tracheal carina-inspired bifurcated (TRAB) microfilter system is reported, which uses an optimal filter gap size satisfying both 100% theoretical recovery rate and purity, as determined by biomechanical analysis and fluid–structure interaction (FSI) simulations. Biomechanical properties are also used to clearly discriminate between cancer cells and leukocytes, whereby cancer cells are selectively bound to melamine microbeads, which increase the size and stiffness of these cells. Nanoindentation experiments are conducted to measure the stiffness of leukocytes as compared to the microbead-conjugated cancer cells, with these parameters then being used in FSI analyses to optimize the filter gap size. The simulation results show that given a flow rate of 100 μL min−1, an 8 μm filter gap optimizes the recovery rate and purity. MCF-7 breast cancer cells with solid microbeads are spiked into 3 mL of whole blood and, by using this flow rate along with the optimized microfilter dimensions, the cell mixture passes through the TRAB filter, which achieves a recovery rate of 93% and purity of 59%. Regarding cell compatibility, it is verified that the isolation procedure does not adversely affect cell viability, thus also confirming that the re-collected cancer cells can be cultured for up to 8 days. This work demonstrates a CTC isolation technology platform that optimizes high recovery rates and cell purity while also providing a framework for functional cell studies, potentially enabling even more sensitive and specific cancer diagnostics.

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