Precise intracellular delivery is essential for many biomedical applications, such as genome-editing and intracellular mechanism investigation. This article presents the development of an automated intracellular delivery approach using a robot-aided microscope system with 3-D reconstruction information. A series of optical section images is sampled by objective lens movement and restored on the computer. After several processes, including deconvolution, segmentation, and 3-D reconstruction of sampled images, the optimal delivery position can be acquired via geometry analysis based on the proposed volume-based model. Guided by this 3-D information, a robust controller that can compensate for external disturbances is utilized to manipulate micropipettes to deliver exogenous materials into single cells. Reconstruction accuracy experiments are performed on the cell nucleus, and the results are compared with a confocal fluorescent microscope. Intracellular nucleus delivery experiments are further conducted by using the proposed robotic microscope system. Compared with the widely adopted methods without 3-D information, the proposed approach demonstrates substantial improvement.

中文翻译：

---

使用具有三维图像重建信息的机器人细胞显微镜系统进行精确的自动细胞内递送

精确的细胞内递送对于许多生物医学应用至关重要，例如基因组编辑和细胞内机制研究。本文介绍了使用具有3D重建信息的机器人辅助显微镜系统自动进行细胞内递送的方法。通过物镜移动对一系列光学截面图像进行采样，然后在计算机上恢复。经过包括反卷积，分割和采样图像的3-D重建在内的多个过程之后，可以基于所提出的基于体积的模型通过几何分析来获取最佳传递位置。在此3-D信息的指导下，可以补偿外部干扰的强大控制器被用来操纵微量移液器，以将外源物质输送到单个细胞中。在细胞核上进行重建精度实验，并将结果与​​共聚焦荧光显微镜进行比较。使用提出的机器人显微镜系统进一步进行细胞内核传递实验。与没有3-D信息的广泛采用的方法相比，所提出的方法显示出实质性的改进。