Li Xuzhou, Zhang Wei, Wang William Y, Wu Xiaoqin, Li Yanxiu, Tan Xiaotian, Matera Daniel L, Baker Brendon M, Paulus Yannis M, Fan Xudong, Wang Xueding
Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave., Ann Arbor, MI 48109, USA.
Department of Mechanical Engineering, University of Michigan, 2350 Hayward St., Ann Arbor, MI 48109, USA.
Biomed Opt Express. 2020 Jun 9;11(7):3659-3672. doi: 10.1364/BOE.395369. eCollection 2020 Jul 1.
Emerging cell-based therapies such as stem cell therapy and immunotherapy have attracted broad attention in both biological research and clinical practice. However, a long-standing technical gap of cell-based therapies is the difficulty of directly assessing treatment efficacy via tracking therapeutically administered cells. Therefore, imaging techniques to follow the distribution and migration of cells are greatly needed. Optical coherence tomography (OCT) is a clinically available imaging technology with ultrahigh-resolution and excellent imaging depth. It also shows great potential for cellular imaging. However, due to the homogeneity of current OCT cell labeling contrast agents (such as gold and polymer nanoparticles), only the distribution of entire cell populations can be observed. Precise tracking of the trajectory of individual single cells is not possible with such conventional contrast agents. Microlasers may provide a route to track unique cell identifiers given their small size, high emission intensities, rich emission spectra, and narrow linewidths. Here, we demonstrate that nanowire lasers internalized by cells provide both OCT and fluorescence signal. In addition, cells can be individually identified by the unique lasing emission spectra of the nanowires that they carry. Furthermore, single cell migration trajectories can be monitored both and with OCT and fluorescence microscopy dual-modality imaging system. Our study demonstrates the feasibility of nanowire lasers combined with the dual-modality imaging system for single cell tracking with a high spatial resolution and identity verification, an approach with great utility for stem cell and immunomodulatory therapies.
新兴的基于细胞的疗法,如干细胞疗法和免疫疗法,在生物学研究和临床实践中都引起了广泛关注。然而,基于细胞的疗法长期存在的技术差距在于,难以通过追踪治疗性给药细胞直接评估治疗效果。因此,迫切需要能够追踪细胞分布和迁移的成像技术。光学相干断层扫描(OCT)是一种临床可用的成像技术,具有超高分辨率和出色的成像深度。它在细胞成像方面也显示出巨大潜力。然而,由于目前OCT细胞标记造影剂(如金和聚合物纳米颗粒)的均一性,只能观察到整个细胞群体的分布。使用这种传统造影剂无法精确追踪单个细胞的轨迹。微激光由于其尺寸小、发射强度高、发射光谱丰富和线宽窄,可能提供一种追踪独特细胞标识符的途径。在这里,我们证明细胞内化的纳米线激光可同时提供OCT和荧光信号。此外,细胞可以通过它们所携带的纳米线独特的激光发射光谱进行个体识别。此外,利用OCT和荧光显微镜双模态成像系统,可以监测单细胞的迁移轨迹。我们的研究证明了纳米线激光与双模态成像系统相结合用于高空间分辨率单细胞追踪和身份验证的可行性,这种方法在干细胞和免疫调节疗法中具有很大的实用性。