Center for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China.
Department of Electronic Science and Technology, University of Science and Technology of China, Hefei, Anhui 230027, China.
ACS Biomater Sci Eng. 2020 May 11;6(5):3187-3196. doi: 10.1021/acsbiomaterials.9b01986. Epub 2020 May 1.
Tracing magnetically labeled cells with magnetic resonance imaging (MRI) is an emerging and promising approach to uncover behaviors of cells in cell therapy. Today, existing methods for the magnetic labeling of cells are cumbersome and time-consuming, which has greatly limited the progress of such studies on cell therapy. Thus, in this study, using the flow cytometric loading technology, we develop a sonoporation-based microfluidic chip (i.e., a microfluidic chip integrated with ultrasound; MCU), to achieve the safe, instant, convenient, and continuous magnetic labeling of cells. For the MCU we designed, a suitable group of operating conditions for safely and efficiently loading superparamagnetic iron oxide (SPIO) nanoparticles into DC2.4 cells was identified experimentally. Under the identified operating conditions, the DC2.4 cells could be labeled in approximately 2 min with high viability (94%) and a high labeling quantity of SPIO nanoparticles (19 pg of iron per cell). In addition, the proliferative functions of the cells were also well maintained after labeling. Furthermore, the imaging ability of the DC2.4 cells labeled using the MCU was verified by injecting the labeled cells into the leg muscle of the C57BL/6 mice. The results show that the excellent imaging outcome can be continuously achieved for 7 days at a density of 10 cells/mL. This work can provide insight for the design of magnetic cell labeling devices and promote the MRI-based study of cell therapies.
利用磁共振成像 (MRI) 追踪标记的磁性细胞是揭示细胞在细胞治疗中的行为的一种新兴且有前途的方法。如今,细胞的磁性标记的现有方法繁琐且耗时,这极大地限制了细胞治疗方面的此类研究的进展。因此,在这项研究中,我们使用流式细胞加载技术,开发了一种基于声孔作用的微流控芯片(即集成超声的微流控芯片;MCU),以实现细胞的安全、即时、方便和连续的磁性标记。对于我们设计的 MCU,通过实验确定了将超顺磁性氧化铁 (SPIO) 纳米颗粒安全且有效地加载到 DC2.4 细胞中的合适操作条件组。在确定的操作条件下,大约 2 分钟即可用高活力(94%)和高 SPIO 纳米颗粒标记量(每细胞 19 皮克铁)对 DC2.4 细胞进行标记。此外,标记后细胞的增殖功能也得到了很好的维持。此外,通过将标记的细胞注入 C57BL/6 小鼠的腿部肌肉,验证了使用 MCU 标记的 DC2.4 细胞的成像能力。结果表明,在 10 细胞/mL 的密度下,可连续 7 天获得优异的成像效果。这项工作可为磁性细胞标记设备的设计提供思路,并促进基于 MRI 的细胞治疗研究。