Cell and Particle Trapping in Microfluidic Systems Using Ultrasonic Standing Waves

Abstract: Analysis methods are currently being miniaturized in order to save time and money while achieving higher sensitivities. The ultimate goal is to create a lab-on-a-chip where all analysis steps and instruments can be automated and integrated into a single chip. In order to perform cellassays and microparticle based bioassays on chip, methods to manipulate particles and cells in microsystems are desired. This thesis describes the development of a non-contact method of manipulating cells and particles in lab-on-a-chip systems based on ultrasonic standing waves. A short review on microfluidics and acoustics is presented, followed by an overview of other techniques for trapping particles and cells in microsystems. Previous work done within the field of acoustic trapping in macro- and microsystems is reviewed before the development and fabrication of the acoustic trapping platform is presented. The trapping platform provides a noncontact way of immobilizing cells and particles in a continuously flowing microsystem. The possiblity to use an array of trapping sites and move particles between different trapping sites is demonstrated. A model bioassays is presented to show the potential of the dynamic arraying concept, where the combination of microfluidics and an array of non-contact trapping sites is used to create a flexible platform for particlebased assays. The platform is also shown to be a gentle way of immobilizing live cells as demonstrated by culturing yeast cells suspended in a standing wave. A viability assay on levitated neural stem cells is also performed to show handling of a more sensitive cell type. The technique is applied to the field of forensics in sample preparation for DNA-analysis in rape cases. The acoustic technique is shown to achieve comparable purities of the separated DNA fraction in a substantially shorter time as compared to the standard methods used today. The results show that the acoustic trapping platform is a flexible and gentle cell handling technique and has the potential to become an important tool for cell and particle handling in microfluidic systems. Finally, an all-glass wet-etched device for acoustic continuous flow separations was demonstrated. Previously reported devices have been manufactured in silicon and the possibility to use glass as base material will lower the chip costs, simplifies the fabrication process and decrease the fabrication time.