Development of Micro- and Nano-sized Particle Separation Methods based on Electrohydrodynamic Phenomena for Healthcare Applications

Abstract

Separation of micro- and nano-sized particle including cells, proteins, and DNAs is an essential step for dialysis, biochemical analysis, and molecular detection. Especially, microfluidic device has drawn a lot of attention as a smart separating system due to its many advantages, including reduced sample and reagent consumption, rapid analysis, and the potential for parallel, automated operation. This Ph. D. thesis introduces novel separation methods based on electrohydrodynamic phenomena. The developed separation methods are expected to be one of the foundation technologies for future smart healthcare system including point-of-care testing (POCT) and self-diagnosis. Additionally, in terms of development of future smart healthcare system, a novel stretchable strain sensor is introduced in this Ph. D. thesis. At First, we introduce pressure-driven flow-induced miniaturizing free-flow electrophoresis (PDF-induced u-FFE), a novel continuous separation method. In the separation system, the external flow and electric field are applied to particles, such that particle movement is affected by pressure-driven flow, electroosmosis, and electrophoresis. We then analyzed the hydrodynamic drag force and electrophoretic force applied to the particles in the opposite directions. Based on this analysis, micro- and nano-sized particles were separated according to their electrophoretic mobilities with high separation efficiency. Because the separation can be achieved in a simple T-shaped microchannel, without the use of internal electrodes, it offers the advantages of low-cost, simple device fabrication and bubble-free operation, compared with conventional u-FFE methods. Therefore, we expect the proposed separation method to have a wide range of filtering/separation applications in biochemical analysis. Secondly, I propose a novel separation method, which is the first report of using ion concentration polarization (ICP) to separate particles continuously. I analyzed the electrical forces that cause the repulsion of particles in the depletion region formed by ion concentration polarization (ICP). Using the electrical repulsion, micro- and nano-sized particles were separated based on their electrophoretic mobilities. Because the separation of particles was performed using a strong electric field in the depletion region without the use of internal electrodes, it offers the advantages of simple, low-cost device fabrication and bubble-free operation compared with conventional continuous electrophoretic separation methods, such as u-FFE. This separation device is expected to be a useful tool for separating various biochemical samples, including cells, proteins, DNAs and even ions. Thirdly, I introduce a novel continuous cell lysis and separation device using the electrical repulsion in the depletion region formed by ICP. In the depletion region, strong electrophoretic force is applied to charged materials due to the concentrated electric field. We used the strong electrophoretic force for cell lysis and separation of molecule dyes whose size range is order of 1 nm. The results show that cell lysis and separation of nano-sized materials can be achieved in the same device. Furthermore, specific protein in cytoplasm can be separated after cell lysis using the integrated device. Therefore, the developed multifunctional microfluidic chip is expected to be a very useful tool as an integrated system for analyzing biomolecules in cells such as DNAs and proteins which is still a challenging and important issue to biochemists. Fourthly, I introduce a novel nanochannel fabrication method for nanofluidic applications using synchrotron radiation via micro patterned X-ray mask. By using the method, I fabricated extremely long nano-sized channels using synchrotron radiation (width and height: ~200 nm, length: ~2 cm). The X-ray mask used for manufacturing the nano-sized channels can simply be fabricated by depositing metal on microstructures tilted at a specific angle. The proposed method overcomes the limitations of traditional nanofabrication methods, which are complex, expensive, and time-consuming. Using the fabricated nanochannels, the generation of ion concentration polarization, a novel transport phenomenon in nanofluidics, was investigated. Our novel fabrication method should be a useful tool for various nanofluidic applications due to its various advantages, including the simple fabrication process, controllability, and duplicability. Additionally, in the manner of development of future smart healthcare system, I introduce a novel disposable stretchable strain sensor with highly dense nanocrack structure (crack density ~ 10^7 /m) for not only high stretchability but also high sensitivity. I demonstrated the sensing mechanism and sensing performances of the developed sensor and optimized the sensing performances by controlling the crack structure. The results show that the sensor has high stretchability and high sensitivity enough to be adapted to monitoring most of human motions incorporating small deformations to large deformations. Therefore, we expect that the developed sensor can be a very useful tool for sensing various deformations and forces applied on a movable and arbitrarily shaped objects including human skin, which gives a wide range of applications like healthcare and robotics.