Microfabrication technologies for soft and bio materials and their applications

在过去的50年里，已经开发了几种用于硬材料（例如硅和玻璃）的微制造技术，这些技术使得能够合成复杂的微机电系统（MEMS）。微制造的下一个重大挑战是使用软聚合物、凝胶和生物材料组装和构建复杂的仿生结构，用于诊断、药物发现、植入体内或构建可以像人工器官一样发挥功能的组织结构。生物MEMS（BioMEMS）中使用的微加工技术仍处于起步阶段，因为MEMS中使用的许多技术不能直接适用。 我的研究计划侧重于制造技术的发展，可以处理生物相关的材料，并用它来构建bioMEMS设备。我们结合了各种添加剂和传统的制造方法，使用生物和软材料构建复杂的3D微结构。我们已经开发出能够以管、杆、片和其他形状的形式制造细胞的致密3D结构的方法。与此同时，我们还创造了新的制造方法来构建大面积聚合物膜装置，这些装置可以用作人工肺来进行气体交换。 基于我们最近的成功，该研究计划的目的是调查生物制造过程背后的基础科学，这些过程支撑生物材料形成组织样结构。特别是，我们将专注于在体外重建体内组织的微结构，通过在适当的时间提供正确的生物化学和生物物理线索，使细胞生物材料能够自组织并产生具有功能组织特征的复杂生物组织。另一个焦点是制造3D、大面积、紧凑但可折叠的膜结构对于生物MEMS设备（例如人工肺和肾脏）是重要的。我们将探索新的增材制造方法来制造这种目前很难实现的膜结构。利用这些技术，我们将制造生物MEMS器件，并将其应用于人工器官和生物3D神经网络。我们将开发具有仿生血管网络的3D硅胶人工肺，能够交换足够的氧气，以拯救呼吸窘迫的成年人。我们还将使用生物制造方法来制造基于组织的生物混合肺，其结合了联合收割机气体交换和泵送。最后，我们还将重建脑组织的分层结构，并整合外部电极来创建生物人工神经网络。 该研究计划将为微/生物制造，微流体和生物MEMS的学生提供丰富的培训机会。通过创新的想法和成功实施的跟踪记录，该计划旨在对全球bioMEMS研究产生决定性影响。

Over the past 50 years, several microfabrication technologies have been developed for hard materials such as Silicon and glass that have enabled synthesis of complex microelectromechanical systems (MEMS). The next grand challenge in microfabrication is to assemble and build complex biomimetic structures using soft polymers, gels and biological materials for use in applications such as diagnostics, drug discovery, implantation into the body or to build tissue like structures that can function like artificial organs. The microfabrication technologies used in biological MEMS (BioMEMS) are still in their infancy as many of the techniques used in MEMS cannot be directly adapted. My research program focuses on development of fabrication technologies that can handle biologically relevant materials and use it to build bioMEMS devices. We have combined various additive and conventional fabrication methods to build complex 3D microstructures using biological and soft materials. We have developed methods capable of fabricating dense 3D constructs of cells in the form of tubes, rods, sheets and other shapes. In parallel, we have also created new fabrication methods to construct large area polymeric membrane devices that can function as artificial lungs to perform gas exchange. Building on our recent successes, the aim of this research program is to investigate the fundamental science behind the biofabrication processes that underpin the formation of tissue like architecture from biomaterials. In particular, we will focus on recreating the microarchitecture of the in-vivo tissue, in-vitro by providing the right biochemical and biophysical cues at appropriate times to allow the cellular biomaterial to self organize and produce complex biological organization with functional tissue characteristics. Another focus is the fabrication of 3D, large area, compact yet ultrathin membrane architectures are important for bioMEMS devices such as artificial lungs and kidneys. We will explore new additive manufacturing approaches for fabricate such membrane architectures that are very difficult to realize currently. Using these technologies, we will fabricate bioMEMS devices with applications as artificial organs and biological 3D neural networks. We will develop 3D silicone artificial lungs with biomimetic vascular network that would be able to exchange sufficient oxygen to rescue adults in respiratory distress. We will also use biofabrication methods to fabricate tissue based biohybrid lungs that combine gas exchange and pumping. Finally, we will also recreate the layered architecture of the brain tissue and integrate external electrodes to create bioartificial neural network. This research program will provide a rich training opportunity for students in micro/biofabrication, microfluidics and bioMEMS. Through the innovative ideas and track record of successful implementation, the program aims to make a definitive impact on the bioMEMS research worldwide.