Tunable microfluidic using low-cost 3D printed resistance regulator

Abstract

Inertial microfluidics is an emerging technology for cell and microparticle separation by utilizing size-dependent inertial forces and Dean migration effects to manipulate particles focusing behaviour within the microchannels. As channel dimensions are key design parameters for sorting particles of defined sizes, different channel geometries and outlet designs have to be fabricated for specific cell applications. The goal of this project is to develop a “tunable microfluidics device” concept by connecting a resistance regulator to a main inertial particle sorting device. By controlling the hydrodynamic resistance of the channel outlet using an additional resistance chip, this can alter particle focusing positions in the main channel to “fine-tune” the separation performance without the need to fabricate new devices. Extracellular vesicles (EVs) are cell-derived nanoscale bioparticles which are widely used for cell-cell communications. As a proof-of-concept for microfluidic EVs purification, we developed a low-cost resistance regulator to control the separation efficiencies of nanoparticles (50 nm and 500 nm) in an arcuated microchannel (ExoArc). We first performed channel resistance modelling based on electrical circuit analogy to characterize the volume eluents of the arcuated channel when connected to a 2nd microchannel of different lengths (resistance chip). This was validated experimentally based on volume output measurements, and we further confirmed that this can affect the separation performance of the nanoparticles using nanoparticle tracking analysis (NTA). Finally, we fabricated a low-cost multiport valve using 3D printing which serves as the resistance regulator that can be automated by Arduino microcontroller. A casing was also 3D printed to house all the microfluidics chips and electronic components to form a closed and integrated prototype. Taken together, the developed platform can be adapted for any cell sorting applications by changing the main inertial focusing device and varying the outlet resistances via the resistance regulator to control the separation performance.