Acoustic Bubbles in Microfluidics for Biological and Biomedical Applications

With the development of microfluidics in recent years, micro/nano-scale bubbles have been considered an emerging tool and become a field of growing interest for addressing many challenges in various Lab on a Chip (LOC) applications. Researchers found that when acoustic fields interact with bubbles in microfluidics, it will cause various interesting physical phenomena, which offers promising abilities in the manipulation of cells, fluids and particles and provides effective ways for biological and biomedical applications. The overall research objective of this dissertation is to study the acoustic bubbles in microfluidics for biological and biomedical applications. In this dissertation, we present research findings on trapping and controlling the acoustic bubble in microfluidics for various biological and biomedical applications, such as fluid transportation, ultrasound thrombolysis, cancer cell trapping, patterning, and culture. Using the numerical and experimental method, we study acoustic microstreaming for fluid flow control and acoustic radiation force for particle manipulation. With the soft lithography and 3D microfabrication techniques, we design and fabricate several acoustic bubble-based microfluidic devices for the thrombolysis study and circulating tumor cells (CTCs) manipulation. Specifically, we developed a method via creating cavity structures inside a recirculated microchannel to trap air-liquid interfaces for generating bi-directional acoustic microstreaming flow for pumping blood mimicking fluids and biological samples, demonstrating potential real-world applications in bi-directional fluid flow control. In addition, we developed an acoustic bubble-based microfluidic platform for quantitative study of the performance of bubble-assisted ultrasound thrombolysis with different acoustic parameters. We also created an “all in one” platform that is used for trapping, rotating and culturing circulating tumor cells in blood flow by controlling the acoustic bubble in microfluidics. Besides simplifying conventional complex CTC processing procedures, this ABSTRACT platform also shows great potential for downstream analysis of tumor cells, such as monitoring the progression of metastasis and personalized drug testing. Finally, we used a micropillar array in a microfluidic device to trap bubbles with the predesigned geometry and then pattern the cells with the acoustic actuation, providing an effective approach to co-culture cells for future tissue engineering applications. The work presented in this dissertation provides an inexpensive, rapid, biocompatible and simple approach for multifunctional sample processing related to human health. With more advanced theoretical and experimental development, we believe that acoustic bubble-based microfluidics will play more important roles in biomedical and biological applications and solve challenging problems in many scientific and engineering fields.