聚合物表面Parylene C填充工艺及其在力生物学中的应用

Precise modulation and characterization of Young’s modulus on the polymer surface is a significant technical challenge in the mechanobiology study, and the key method to understand the interaction mechanism between cells and mechanical microenvironment. Based on the Parylene MEMS (microelectromechanical system) process, this project will establish the ultra-thin (nominal thickness<10 nm) Parylene C-caulked polymer process, techniques for Young’s modulus modulation on polymer surface and controllable enhancement of Parylene C autofluorescence intensity. Two key scientific problems, the multi-scale diffusion-deposition model of Parylene C and the numerical correlation between the Parylene C autofluorescence intensity and Young’s modulus value, will be solved. Then, the precisely patternable modulation of mechanical property and controllable enhancement of Parylene C autofluorescence intensity will be studied. Finally, a method for mechanical property modulation with a large range (1−1000 kPa), complicated patterns (continuous gradient and discrete patterns) and a high precision (spatial resolution better than 5 μm), and visualized characterization of Young’s modulus will be developed. It is promising to realize a precise modulation of interaction between cells and mechanical microenvironment at the single/sub cellular level. Meanwhile, the achievement from this project will also provide a powerful tool for the study of basic mechanobiological science and physiological mechanism of related major diseases.

聚合物基底表面杨氏模量的精确调控与表征是力生物学研究领域面临的主要技术挑战，是认识细胞−力学微环境相互作用机制的关键方法基础。本项目基于聚对二甲苯微机电系统（Parylene MEMS）工艺，拟解决跨尺度Parylene C“扩散−淀积”机制、Parylene C填充聚合物表面等效杨氏模量的荧光定量读取映射关系等关键科学问题；建立聚合物表面超薄（等效厚度<10 nm）Parylene C填充工艺、聚合物表面力学性能精确调控以及Parylene C自发荧光可控增强等关键技术；实现杨氏模量1−1000 kPa范围可调、连续梯度及离散阵列变化、空间分布精度优于5 μm的聚合物表面力学性能调控以及杨氏模量可视化原位表征方法。有望在单/亚细胞水平实现细胞−力学微环境相互作用的精细调控，为力生物学基础研究及相关疾病机制研究等提供有力工具。

聚合物基底表面杨氏模量的精确调控与表征是力生物学研究领域面临的主要技术挑战，是认识细胞−力学微环境相互作用机制的关键方法基础。应用微纳米技术可以在单/亚细胞（亚微米到数十微米）水平实现细胞−力学微环境作用的精细调控，并受到了广泛关注。本项目基于聚对二甲苯微机电系统（Parylene MEMS）工艺，解决了跨尺度Parylene C“扩散−淀积”机制、Parylene C填充聚合物表面等效杨氏模量的荧光定量读取映射关系等关键科学问题；建立了聚合物表面超薄（等效厚度<10 nm）Parylene C填充工艺、聚合物表面力学性能精确调控以及Parylene C自发荧光可控增强等关键技术；实现了力生物学中常用聚合物聚二甲基硅氧烷（polydimethylsiloxane, PDMS）与单乙烯基封端的聚二甲基硅氧烷（vinyl terminated Polydimethylsiloxane，简称为JPDMS）表面杨氏模量：（1）30~150 kPa、2~250 kPa均匀分布的精确调制；（2）1.5~3 kPa/mm、1~200 kPa/mm的连续梯度可控调制；（3）60~500 μm离散阵列图形化；（4）基于Parylene C自发荧光的局域杨氏模量原位可视化读出。此外，还通过聚丙烯酰胺水凝胶（polyacrylamide hydrogel, PAA）、八甲基环四硅氧烷（octamethyl cyclotetrasiloxane, 简称为Qgel）、胶原蛋白（collagen）三种力生物学常用聚合物以及三维结构化PDMS衬底对本项目所建立的方法进行了测试和验证，实验结果证明本文所建立的方法具有很好的普适性，可以对多种聚合物、多种形貌特征的衬底表面进行杨氏模量的可控精确调制。该项目成果将推动细胞−力学微环境相互作用在单/亚细胞水平的精细调控，为力生物学基础研究及相关疾病机制研究等提供有力工具。