Thermophoretic manipulation of biocompatible soft materials properties in microfluidic devices

近年来，从单细胞分析到芯片上的器官复制，微流体技术已经被证明在解决生物问题方面非常有用。目前的生物学方法需要体外实验来测试初步假设：通常这些合成环境与他们试图模仿的实际环境几乎没有任何共同之处，因此随后的体内实验成为实际进行必要测试的唯一途径。能够在单个细胞的典型长度尺度上修改生物相容性材料的特性，将开辟一套新的工具，使其能够进行现实的生物测试，从而节省了解疾病发展机制和寻找有效治疗方法的时间。这就是这个提议的动机。目前组织工程领域的挑战很大程度上受限于功能化生物相容性材料的可用性，这些材料可以提供用于指导细胞生长的最佳基质或支架。该提案旨在探索一种创新的方法，在微米尺度上局部操纵软材料的机械、光学和流变特性，从而开发出一类新的功能化材料。该项目将利用微流体环境中的热泳术，通过施加高度局部的温度梯度来诱导聚合物溶液中的浓度梯度。浓度梯度将转化为我可以调整和操纵的性质梯度。这将使我能够制造出具有前所未有的机械性能控制的生物相容性材料，研究细胞的增殖和分化，并揭示癌症侵袭的机制。本提案的主要目标之一是将研究扩展到生物相容性基质，其中机械性能是动态可调的。这将使我能够研究生长组织对外部刺激变化的反应，并模拟伤口愈合的动力学，其中基质的特征在上皮生长时发生变化。此外，我将研究细胞在纤维样和更复杂结构基质上的生长，以诱导控制特定细胞系的增殖、生长甚至分化行为。

In recent years microfluidics has already proven incredibly useful in tackling biological problems, from single cell analyses up to organ reproduced on-a-chip. Current biological approaches require in-vitro experiments to test preliminary hypotheses: often these synthetic environments share little to nothing with the actual environment they are trying to mimic and thus the subsequent in-vivo experiments become the only way to actually perform the necessary tests. Being able to modify the biocompatible material's properties at the length scale typical of a single cell, will open up a new set of tools enabling to perform realistic biological tests that can save time in the process of understanding the mechanisms of the development of a disease and the search for an effective cure. This is what motivates this proposal. Current challenges in the field of tissue engineering are strongly limited by the availability of functionalised biocompatible materials that can provide the optimal substrate or the scaffold to be used to guide the growth of cells. This proposal aims to exploit an innovative way to locally manipulate the mechanical, optical and rheological properties of a soft material at the micron scale, and thus develop a new class of functionalised materials. This project will exploit thermophoresis in a microfluidic environment to induce a concentration gradient in a polymeric solution by imposing a highly localised temperature gradient. The concentration gradient will then translate into a gradient of properties that I will tune and manipulate. This will enable me to generate biocompatible materials with unprecedented control over their mechanical properties where to study the proliferation and differentiation of cells, and shine light on the mechanisms of cancer invasion. One of the main objectives of this proposal is the extension of the study to biocompatible substrate where the mechanical properties are dynamically tunable. This will permit me to investigate the response to a change in external stimuli of a growing tissue and to model the dynamics of wound healing, where the characteristics of the substrate are changing while the epithelium is growing. Additionally, I will investigate the growth of cells on fibre-like and more complex structures substrates, in order to induce control the proliferation, growth and even differentiation of behaviour of specific cell lines.