Yu Yue, Zhang Yujia, Chen Yu, Wang Xuekang, Kang Ke, Zhu Nanhang, Wu Yao, Yi Qiangying
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China.
Department of Cardiology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.
ACS Sens. 2023 Apr 28;8(4):1858-1866. doi: 10.1021/acssensors.3c00420. Epub 2023 Apr 17.
Among circulating tumor cell enrichment strategies, immunomagnetic beads (IMBs) have received great attention due to their excellent performance. However, traditional strategies using IMBs normally require an additional mechanical stirring device to fully mix the IMBs and specimens, and this step may cause mechanical cellular damage. In this study, by changing the architecture and motion trajectory control strategy of the IMBs, floating immunomagnetic microspheres (FIMMs) and their matching rotary magnetic manipulation device were proposed to achieve highly efficient CTC capture under a cell-friendly condition. Generally, the FIMMs were prepared through layer-by-layer assembly of the individual functional components, and their stress state governed by either buoyancy or magnetic force was tuned by the rotary magnetic manipulation device. Consequently, recognition of FIMMs and target cells as well as CTC recovery can be simply realized through external magnetic manipulation. Accordingly, satisfactory enrichment efficiencies for CTCs with varied epithelial expression levels were obtained as 92.93 ± 3.23% for MCF-7, 79.93 ± 3.31% for A549, and 92.57 ± 5.22% for HepG2. Besides, an extremely low detection limitation of 5 cells mL can be achieved from complex sample conditions, even the whole blood. In addition, FIMMs successfully enriched 23-56 CTCs from 1.5 mL of blood samples from cancer patients.
在循环肿瘤细胞富集策略中，免疫磁珠（IMBs）因其出色的性能而备受关注。然而，传统的免疫磁珠策略通常需要额外的机械搅拌装置来充分混合免疫磁珠和样本，这一步骤可能会造成细胞机械损伤。在本研究中，通过改变免疫磁珠的结构和运动轨迹控制策略，提出了浮动免疫磁微球（FIMMs）及其配套的旋转磁操纵装置，以在细胞友好的条件下实现高效的循环肿瘤细胞捕获。一般来说，FIMMs是通过单个功能组件的逐层组装制备的，其受浮力或磁力控制的应力状态由旋转磁操纵装置调节。因此，通过外部磁操纵可以简单地实现FIMMs与靶细胞的识别以及循环肿瘤细胞的回收。相应地，对于不同上皮表达水平的循环肿瘤细胞，获得了令人满意的富集效率，MCF-7为92.93±3.23%，A549为79.93±3.31%，HepG2为92.57±5.22%。此外，即使在复杂的样本条件下，甚至是全血中，也能实现低至5个细胞/毫升的极低检测限。此外，FIMMs成功地从1.5毫升癌症患者血样中富集了23 - 56个循环肿瘤细胞。
