Microfabricated bio-mimetic cilia for resonance-enhanced mixing and reaction of biomolecules

A critical challenge for mixing biomolecules in microwell plates is addressed in this dissertation. The mixing and reaction of biomolecules in microwell plates are very important for high-throughput screening in the fields of drug discovery and disease diagnostics. For this reason, a large number of microwells need to be manipulated. However, current approaches have yet to demonstrate efficient mixing performance compatible with microwell plates due to the low inertia and high viscosity of microfluids, i.e., the flows are at very low Reynolds numbers.;To overcome these challenges, a bio-mimetic approach that imitates the high compliance and the beating frequency of biological cilia is investigated in this dissertation. Because the highly compliant cilia can easily collapse due to interaction energy and surface tension, the major challenge in developing a cilia device is the manufacturing of highly compliant cilia. An underwater fabrication method is developed to avoid the cilia collapse by lowering the surface energy of the cilia. Another challenge is to mimic the low beating frequency (10-100 Hz) of biological cilia. The proposed cilia device is excited by a piezo actuator to resonate the cilia in a fluid. Due to the highly compliant nature of the silicone cilia, the resulting actuation frequency is in the beating frequency range of biological cilia. Numerical simulations and experiments are presented to demonstrate microfluidic manipulation by resonance of the cilia.;A cilia mixer compatible with 384-microwell plates is proposed and demonstrated. The mixing performance is characterized and compared with those of both diffusion- and vibration-induced mixers. The experimental and numerical results show that the cilia mixer can significantly reduce the mixing time and the standard deviation because the convective flows generated by the cilia rapidly decrease the variations in the initial mixing conditions.;For biocompatibility test of a cilia assary, the reaction performance of biotin-avidin assay with the cilia mixer is compared to those of the diffusion and the vibration mixer in terms of various concentrations of biotin according to time. The reaction of the cilia mixer reaches equilibrium within 270 seconds, which is 62 times faster than that of the diffusion.