面向细胞精准手术的飞秒激光水凝胶单细胞阵列加工方法

Cell precision surgery related research on living single cell plays a critical role on modern precision medicine and cell engineering. However, the lack of efficient and flexible biocompatible micro-structure fabrication approach makes it impossible to achieve single cell isolation high throughput, mildly with no injure and keep the cell to be active as well. Therefore, in the proposal, a novel femtosecond-laser-based fabrication of hydrogel composite single cell array for cell precision surgery application is proposed. The underlying mechanisms of the interaction between femtosecond laser and hydrogel film are investigated and simulated, to achieve much more precision control over parameters for UV curing of hydrogel and optimization of micro-cavity morphology. Then, micro-cavity array on hydrogel film surface will be fabricated on the femtosecond laser fabrication experiment system, and single cell isolate and culture experiments will be carried out to optimize the parameters of hydrogel and femtosecond laser. The single cell isolation and culture experiment results are going to provide reliable theoretical basis and a novel approach for high-throughput single cell surgery study. This piece of research is going to improve the development of femtosecond laser fabrication on soft material, as well as the further development on the interdisciplinary fields including micro/nano fabrication, biomedical and precision medical.

在活体单细胞水平上，开展细胞精准手术研究对现代精准医疗和细胞工程具有非常重要的意义。然而由于缺乏高效率、高灵活性的生物兼容微结构加工方法，单细胞精准手术中很难实现高通量、温和、无损的单细胞分离及高活性单细胞培养，极大地制约了相关学科领域的发展。本项目提出一种面向活体单细胞精准手术的飞秒激光水凝胶单细胞阵列加工新方法；通过飞秒激光与柔性水凝胶薄膜相互作用机理研究与建模分析，实现更为精确的紫外固化水凝胶参数控制及飞秒激光加工水凝胶微坑面型优化控制；构建飞秒激光加工系统，实现高通量水凝胶微坑加工；在此基础上，开展基于水凝胶微坑阵列的单细胞无损分离与培养实验研究，为面向高通量单细胞精准手术的研究提供可靠的理论依据与新的实现方法。该研究不但对提高我国柔性材料微纳加工水平具有重要意义，还将进一步提升我国在微纳制造、生物工程、精准医疗等多学科交叉前沿领域的原始创新能力。

针对现代精准医疗和细胞分子生物学领域细胞精准手术对单细胞阵列的需求，本项目提出一种可用于一体化单细胞分离与培养的飞秒激光水凝胶图形化加工方法。修正飞秒激光与水凝胶相互作用机理模型并进行热流体动力学仿真分析；优化水紫外光固化参数制备生物性能良好的水凝胶薄膜；构建飞秒激光加工系统并进行高通量水凝胶微坑阵列面型优化控制；最终实现了基于水凝胶微坑阵列的单细胞分离与培养实验研究，为面向高通量单细胞精准手术的研究提供可靠的理论依据与新的实现方法。