Development of microchannels of tunable stiffness for the study of migration of T-cells

Abstract

Cell migration plays a crucial role in various physiological and pathological processes, including immune response and cancer metastasis. The complex interplay of the cancer cells with the microenvironment and the immune cell recruitment has emerged as a critical aspect in the progression of colorectal cancer. Cytotoxic T lymphocytes infiltrate the tumour microenvironment to exert anti-tumour immunity. To get to the tumour stroma, cells have to extravasate the vascular endothelial barrier in a process called transendothelial migration. We herein develop a microfluidic device capable of investigating the migration of T cells within an environment that closely mimics In vivo tissue characteristics. We have developed different protocols to fabricate microchannels of two different materials, polydimethylsiloxane, and polyacrylamide. Photolithography and novel microfabrication techniques have been employed to acquire confined microchannels. The microchannels successfully recreated key aspects of In vivo environment, enabling precise control of size and confinement. We have studied and confirmed the advantages of using hydrogels in microfluidics and their tuneable mechanical properties have been proved. Finally, the PDMS microfluidic chip has been tested with Jurkat cells and we have confirmed the suitability of the device for studying T cell migration profiles.