Ministry of Education (MOE) Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
J Am Chem Soc. 2021 Dec 29;143(51):21648-21656. doi: 10.1021/jacs.1c10081. Epub 2021 Dec 16.
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 × 500 × 500 nm 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.
利用质谱成像（MSI）技术在纳米尺度分辨率下探索单个细胞内的三维（3D）药物分布对于细胞生物学至关重要，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。在此，我们开发了一种微透镜光纤激光解吸后离子化飞行时间质谱仪（MLF-LDPI-TOFMS），用于以 500×500×500nm 体素分辨率对单个细胞内的两种抗癌药物进行 3D 成像。利用微透镜光纤（MLF）获得纳米级解吸，引入 157nm 后离子化激光以提高离子化效率。此外，我们还基于嵌入式均匀圆形聚苯乙烯微球（PMs）开发了一种新的 3D 重建对准方法。我们的研究结果表明，这种 3D 成像技术有可能提供关于特定分子在纳米尺度水平上的 3D 分布的信息。
