Nanoscale Three-Dimensional Imaging of Drug Distributions in Single Cells via Laser Desorption Post-Ionization Mass Spectrometry
Nanoscale Three-Dimensional Imaging of Drug Distributions in Single Cells via Laser Desorption Post-Ionization Mass Spectrometry
复制标题
通过激光解吸后电离质谱对单细胞中药物分布进行纳米级三维成像
DOI：
10.1021/jacs.1c10081
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发表时间：
2021-12-16
影响因子：
15
通讯作者：
Hang, Wei
中科院分区：
文献类型：
--
作者：
Li, Xiaoping;Hang, Le;Hang, Wei
利用质谱仪成像(MSI)技术探索单个细胞内纳米级分辨率的三维药物分布在细胞生物学中是至关重要的，但由于横向分辨率、检测灵敏度和重建问题的限制，这仍然是一个巨大的挑战。为此，研制了一台微透镜光纤激光解吸后电离飞行时间质谱仪(MLF-LDPI-TOFMS)，用于在500×500×500 nm(3)体素分辨率下对两种抗癌药物在单细胞内进行三维成像。利用微透镜光纤(MLF)实现了纳米尺度的解吸，并引入了157 nm的后电离激光来提高电离产率。在此基础上，提出了一种基于均匀圆形聚苯乙烯微球(PM)的三维重建对准方法。我们的发现表明，这种3D成像技术有可能提供关于纳米级特定分子的3D分布的信息。
Exploring the three-dimensional (3D) drug distribution within a single cell at nanoscale resolution with mass spectrometry imaging (MSI) techniques is crucial in cellular biology, yet it remains a great challenge due to limited lateral resolution, detection sensitivities, and reconstruction problems. Herein, a microlensed fiber laser desorption post-ionization time-of-flight mass spectrometer (MLF-LDPI-TOFMS) was developed for the 3D imaging of two anticancer drugs within single cells at a 500 x 500 x 500 nm(3) voxel resolution. Nanoscale desorption was obtained with a microlensed fiber (MLF), and a 157 nm post-ionization laser was introduced to enhance the ionization yield. Furthermore, a new type of alignment method for 3D reconstruction was developed on the basis of our embedded uniform circular polystyrene microspheres (PMs). Our findings demonstrate that this 3D imaging technique has the potential to provide information about the 3D distributions of specific molecules at the nanoscale level.