Collaborative Research: Laser-Assisted Orifice-Free Fabrication of Viscous Alginate Microspheres

这项合作研究的目的是验证这样一种假设，即可以使用一种不基于使用孔口的新工艺，从高度粘滞的流体系统中可控制地制造出尺寸一致的微球。基于孔板的技术限制了从粘性流体快速生产不同尺寸微球的灵活性。利用金属箔作为动态释放层的激光辅助无孔制造技术将特别适用于粘度在100 mpa或更高的流体。主要的研究活动包括：1)利用时间分辨成像研究和数学模型所获得的过程动力学知识，演示和优化所提出的激光辅助正向传输技术；以及2)阐明激光辅助制备微球的流体动力学。海藻酸钠将被用作包裹活细胞的模型流体。特别是，将大鼠内皮细胞悬浮液作为代表性活性成分添加到海藻酸钠溶液中进行包埋。我们将对所制备的微球进行物理和生物学性能的实验评价，本研究的成功将扩展金属箔辅助激光前向传输制备粘性微球的知识。粘性微球尺寸的精确控制具有重要的制造意义，因为在组织工程和药物输送等大多数微球应用中，其尺寸分布可以决定其应用的成败。更广泛的影响还将包括一批训练有素的学生，准备在科学、技术、工程和数学学科中从事职业生涯。通过这项研究获得的新知识，生物医学制造和生物材料加工课程将进一步发展，使学生接触到制造技术的最新进步。

The objective of this collaborative study is to test the hypothesis that encapsulated microspheres with a uniform size can be controllably fabricated from a highly viscous fluid system using a novel process not based on the use of an orifice. Orifice-based techniques limit the flexibility in rapidly producing different size microspheres from viscous fluids. The laser-assisted orifice-free fabrication technique, utilizing a metallic foil as the dynamic release layer, will be especially suitable for fluids with a viscosity on the order of 100 mPa's or higher. Key research activities include 1) demonstrating and optimizing the proposed laser-assisted forward transfer technique using the process dynamics knowledge gained from a time-resolved imaging study and mathematical modeling; and 2) elucidating the fluid dynamics of the laser-assisted fabrication of encapsulated microspheres. Sodium alginate will be used as a model fluid to encapsulate living cells. In particular, rat endothelial cell suspension will be added to the sodium alginate solutions as a representative active ingredient to be encapsulated. The fabricated microspheres will be experimentally evaluated in terms of physical and biological properties.Success in this research will expand the knowledge for viscous microsphere fabrication using metallic-foil assisted laser forward transfer. The precise control of viscous encapsulated microsphere size is of great manufacturing importance since the size distribution can determine the success in most microsphere applications such as tissue engineering and drug delivery. Broader impacts also will include a pipeline of well-trained students ready to undertake careers in Science, Technology, Engineering, and Mathematics disciplines. With the new knowledge gained from this study, Biomedical Manufacturing and Processing of Biomaterials courses will be further developed to expose students to state-of-the-art advances in manufacturing technologies.