Onoshima Daisuke, Hase Tetsunari, Kihara Naoto, Kuboyama Daiki, Tanaka Hiromasa, Ozawa Naoya, Yukawa Hiroshi, Sato Mitsuo, Ishikawa Kenji, Hasegawa Yoshinori, Ishii Makoto, Hori Masaru, Baba Yoshinobu
Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
ACS Meas Sci Au. 2022 Dec 8;3(2):113-119. doi: 10.1021/acsmeasuresciau.2c00057. eCollection 2023 Apr 19.
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.
考虑到在分离循环肿瘤细胞（CTC）时面临的与细胞应激和纯度相关的挑战，我们报告了一种血液微滤装置的应用，它是用于靶向CTC的非侵入性液体活检的最佳方法。我们通过压力传感对微滤器的过滤行为进行了实验分析，以从全血中分离肿瘤细胞和白细胞。该方法实现了加样肿瘤细胞平均回收率>96%，总白细胞清除率>99%。此外，我们使用血液微滤装置对CTC进行了基因组分析。该方法也应用于临床；使用少量微滤后的CTC进行DNA扩增，并成功检测到表皮生长因子受体突变，以表征分子靶向药物对肺癌的疗效。总体而言，所提出的方法可为评估从全血中浓缩CTC的有效过滤压力提供一种工具。
