Modulated ultrasound-enabled particle and cell separation in surface acoustic wave microfluidic devices

Abstract

In recent years considerable amount of research focussed on development of the socalled lab-on-a-chip (LoC) devices that feature complex laboratory sample preparation functions (such as sample washing, sorting, detection or drug delivery) on the microscale. These devices offer lower manufacturing costs, reagent use and the required sample size can be as small as a few microlitres. In this thesis, particle and cell separation is investigated utilising the primary acoustic radiation force in a surface acoustic wave device. After providing review of similar techniques, various phase and frequency modulation methods are proposed for achieving target separation based on size, density or compressibility difference. A special form of primary acoustic radiation force is presented for surface wave devices and is used to obtain particle trajectories in modulated fields for fast analytical comparison of the proposed methods. Experiments for size-based particle separation reveal 95% efficiency and >85% purity for particle size ratio as small as 1.45. Physical property-based separation of iron-oxide and polystyrene microparticles shows even higher figures of merit: >95% efficiency and >90% purity illustrating the versatility of the method. Biological cell separation is performed on human red blood cells and white blood cells, displaying 94% efficiency and >84% purity. Bandpass sorting of particles and cells is also proposed and validated by experiments. Various numerical models are developed for flow and acoustic field simulation, including investigation of secondary acoustic radiation force, and finally a Monte-Carlo study is carried out to verify the superiority of modulated acoustic sorting methods compared to static acoustic field separation techniques.