Zhu Zhixian, Wu Dan, Li Shuang, Han Yu, Xiang Nan, Wang Cailian, Ni Zhonghua
School of Mechanical Engineering, And Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing, 211189, China.
Nanjing Medical University, Nanjing, 210011, Jiangsu, China; Department of Oncology, Jiangyin People's Hospital, Jiangyin, 214400, China.
Anal Chim Acta. 2021 Jan 25;1143:306-314. doi: 10.1016/j.aca.2020.11.001. Epub 2020 Nov 6.
A polymer-film inertial microfluidic jigsaw (PIMJ) sorter with trapezoidal spiral channels using the jigsaw puzzle method was proposed to realize precise and high-throughput rare cell separation. The PIMJ sorter was fabricated by assembling laser-patterned polymer-film layers of different thicknesses. After illustrating the conceptual design and fabrication process, the effects of the cross-sectional dimension, particle size, and operational flow rate on particle focusing were systematically explored under a broad flow rate range. Then, the separation performances of the PIMJ sorter were characterized using the binary particle mixture and the blood samples spiked with four types of tumor cells. The results indicated that the complete separation of the binary particles with a minimum size difference of 2 μm was successfully realized at a high throughput up to 3000 μL/min. A high recovery ratio of 90.57%-94.14% and a high purity of 48.67%-79.05% were achieved for the separation of rare tumor cells from white blood cells (WBCs). Finally, the PIMJ sorter was successfully employed for separating rare circulating tumor cells (CTCs) from the metastatic breast and lung cancer patients with a capture ratio of 7-226 CTCs per 5 mL sample. The results proved the high sensitivity and high reliability of the PIMJ sorter. The PIMJ sorter is expected to be a potential device for precise CTC separation towards the clinical applications.
提出了一种采用拼图法的具有梯形螺旋通道的聚合物薄膜惯性微流控拼图（PIMJ）分选器，以实现精确且高通量的稀有细胞分离。PIMJ分选器通过组装不同厚度的激光图案化聚合物薄膜层制成。在阐述了概念设计和制造过程之后，在较宽的流速范围内系统地研究了横截面尺寸、颗粒大小和操作流速对颗粒聚焦的影响。然后，使用二元颗粒混合物和掺入四种肿瘤细胞的血样对PIMJ分选器的分离性能进行了表征。结果表明，在高达3000 μL/min的高通量下成功实现了最小尺寸差为2μm的二元颗粒的完全分离。从白细胞（WBC）中分离稀有肿瘤细胞时，回收率高达90.57%-94.14%，纯度高达48.67%-79.05%。最后，PIMJ分选器成功用于从转移性乳腺癌和肺癌患者中分离稀有循环肿瘤细胞（CTC），每5 mL样品的捕获率为7-226个CTC。结果证明了PIMJ分选器的高灵敏度和高可靠性。PIMJ分选器有望成为用于临床应用中精确CTC分离的潜在设备。
