Abstracts Biological Sciences

Development of techniques for rapid isolation and separation of particles in digital microfluidics

by Nejad Hojatollah Rezaei

Digital microfluidics (DMF) has emerged as a powerful platform for both research and development in life science studies. The platform functions based on handling small volumes of samples and reagents in the form of discrete droplets using the well-established electrowetting on dielectric (EWOD) method. Based on EWOD, different techniques (operators) have been developed to accurately manipulate, dispense, split and merge droplets of different volumes. Despite the advances made in the DMF technology especially in the use of EWOD in scaling down laboratory procedures, there is lack of understanding and hence development of techniques for particle/cell manipulation and isolation on DMF (as compared to the alternative platform called continuous microfluidics). This has hindered the capability of DMF in full-scale miniaturization of laboratory procedures requiring particle/cell isolation at any of their steps. This research focuses on addressing this problem and developing reliable techniques to manipulate, concentrate and isolate different types of particles/cells. The techniques presented here are particularly developed to limit the use of external devices and also cover a wide range of particles and cells with different physical properties (including size, density, material and electromagnetic properties). They include magnetic collection, hydrodynamic focusing, dielectrophoresis positioning of the particles. The magnetic collection method, a rather simple but effective and widely used in biochemistry, is implemented on DMF for capturing target analytes. The hydrodynamic focusing method, functioning based on the density and size of the particles, were developed and integrated into DMF (for the first time) using especial electrode geometry facilitating the rotation of the droplet. The dielectrophoresis–based particle manipulation is optimized to achieve high resolution and controllability in particle patterning on DMF. The applicability of each of these techniques are demonstrated for different biological and physical applications including on-chip DNA purification (using the magnetic collection technique), ultra-low DNA concentration (using the hydrodynamic focusing technique for achieving desired concentrations of particles), and cell and particle patterning and cell culturing on a DMF platform (using the dielectrophoresis positioning technique). The diversity and flexibility of these techniques will enable the use of DMF devices for especially point-of-care applications.