Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device

Daisuke Onoshima; Tetsunari Hase; Naoto Kihara; Daiki Kuboyama; Hiromasa Tanaka; Naoya Ozawa; Hiroshi Yukawa; Mitsuo Sato; Kenji Ishikawa; Yoshinori Hasegawa; Makoto Ishii; Masaru Hori; Yoshinobu Baba

doi:10.1021/acsmeasuresciau.2c00057

Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device

ACS Meas Sci Au. 2022 Dec 8;3(2):113-119. doi: 10.1021/acsmeasuresciau.2c00057. eCollection 2023 Apr 19.

Authors

Daisuke Onoshima¹, Tetsunari Hase², Naoto Kihara³, Daiki Kuboyama⁴, Hiromasa Tanaka⁵, Naoya Ozawa², Hiroshi Yukawa^{1

4

6}, Mitsuo Sato⁵, Kenji Ishikawa⁶, Yoshinori Hasegawa^{2

7}, Makoto Ishii², Masaru Hori⁶, Yoshinobu Baba^{1

4

8}

Affiliations

¹ Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
² Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
³ AGC Inc., Marunouchi 1-5-1, Chiyoda-ku, Tokyo 100-8405, Japan.
⁴ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
⁵ Division of Host Defense Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Daikominami 1-1-20, Higashi-ku, Nagoya 461-8673, Japan.
⁶ Center for Low-Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
⁷ National Hospital Organization, Nagoya Medical Center, 4-1-1, Sannomaru, Naka-ku, Nagoya 460-0001, Japan.
⁸ Institute of Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan.

Abstract

Considering the challenges in isolating circulating tumor cells (CTCs) pertaining to cellular stress and purity, we report the application of a blood microfiltration device as an optimal approach for noninvasive liquid biopsy to target CTCs. We experimentally analyzed the filtration behavior of the microfilter using pressure sensing to separate tumor cells from leukocytes in whole blood. This approach achieved an average recovery of >96% of the spiked tumor cells and depletion of >99% of total leukocytes. Furthermore, we carried out genomic profiling of the CTCs using the blood microfiltration device. The method was also applied in a clinical setting; DNA amplification was performed using a small number of microfiltered CTCs and epidermal growth factor receptor mutations were successfully detected to characterize the efficacy of molecularly targeted drugs against lung cancer. Overall, the proposed method can provide a tool for evaluating efficient filtration pressure to concentrate CTCs from whole blood.