Microfluidics for High-Pressure Inertial Focusing : Focusing, Separation and Concentration of Micro and Sub-micron Particles

Abstract: The birth of microsystems set the ground for technologies never imagined before, for it is not only the small size what characterizes the miniaturized systems, but unique phenomena arise in the micro scale. This thesis relates to one such unique phenomenon, inertial focusing, a phenomenon that occurs in microfluidic systems if very special conditions are met and that allows for fine manipulation of particles in fluid samples. This ability is key in a bigger picture: the analysis of complex fluids, where rare particles of interest may be present in very few numbers amongst a myriad of others, making the task difficult – if not impossible. A system exploiting inertial focusing allows, for instance, to focus, separate, isolate and concentrate such rare particles of interest, and even to transfer them to another fluid, thereby enabling/facilitating their detection and analysis. Examples of rare particles of interest in complex fluids are circulating tumor cells in blood, that give away the presence of cancer, extracellular vesicles also in blood, that contain biomarkers with physiological and pathological information about the patient, or bacteria in natural water, where the species present and their numbers are to be monitored for safety reasons and/or biological studies. This thesis covers the state of art physical principles behind the phenomenon and extends the understanding both in theory and applications. Specifically, the technology is extended to allow for manipulation of sub-micron particles, a range of interest as it comprises bacteria, viruses and organelles of eukaryotic cells. This was possible by an analysis of the balance of forces in play and by the integration of inertial focusing in high-pressure systems (up to 200 bar). In a second block, a very special line of inertial focusing is introduced and developed; inertial focusing in High Aspect Ratio Curved (HARC) microfluidics. These systems, engineered to rearrange the force field responsible for the particle manipulation, not only achieve excellent performances for focusing and concentration of particles, but also extreme resolution in their separation (mathematically unlimited; demonstrated experimentally for differences in size down to 80 nm). Perhaps more important than the performance, the systems are stable, intuitive and simpler to design, attributes that we hope will make the technology and its outstanding benefits more accessible to the community. With its remarkable performance, it would not come as a surprise if, in the near future, inertial focusing makes a strong impact on how analyses are performed nowadays and opens up for possibilities beyond the current state of the art.