Thermophoretic manipulation of biocompatible soft materials properties in microfluidic devices

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.

The planned research will produce scientific results of high fundamental and applied significance. The field of biocompatible nano-functionalised materials represent a hot current research topic and the possibilities that this project will bring to the field will exponentially increase the capabilities compared to current approaches, increasing the chances to give answers to studies devoted to improve health. To push the boundary of science, microfluidic can be used to develop the next generation of biocompatible environment, where complex properties such as stiffness of the substrate, rheology, capability to deliver nutrient in a controlled manner, all work together to guide the growth of cells into complex life-like tissue. The proposed research focuses on a challenging and rewarding topic in the field of functionalised biomaterials and substantially contribute to its overall advancement. Scientific results from the research will be made public as papers in leading international journals, since currently studies on functionalized advanced materials are well received in high-impact journals of general interest.
Additionally, this project will also impact the field by establishing a novel characterization technique based on thermophoresis. This, together with the introduction of microfluidic fabrication of thermally induced concentration gradient material, will become a model micro-fabrication technique.
The availability of new biocompatible material with controlled mechanical and optical properties will then permit to perform in vitro experiments devoted to the study of mechano-sensing and differentiation of different kind of cells, including cancer and animal stem cells.
By providing a set of innovative tools to generate biocompatible materials on which to grow tissue and cell cultures, it will be possible to better understand, for example, the mechanisms of cancer invasion and wound healing. The results obtained by this project will thus have a clear impact on the society. Moreover, there will be an immediate impact also on other research conducted in medical facilities that will take advantage of such a platform. As a consequence, the increased capability to understand how to fight certain diseases will open the possibility to develop new cures, with an immediate impact not only on the society but also on the economy of the country.