Date of Award
Master of Science (MS)
Separation, isolation, and enrichment of targeted nano- and microparticles are critical to a variety of biomedical applications from clinical research (development of therapeutics and diagnostics) to fundamental investigations that require concentration of specific cells from culture, separation of target species from heterogenous mixtures, or controlled perturbation of cells and microorganisms to determine their response to stimuli. Numerous techniques are available for bench-scale and medical settings; however, these traditional approaches are often labor intensive, time-consuming, costly, and/or require modification of the target. Efficiency and specificity are also lacking. Recently, techniques that exploit the similar scales of microfluidic technologies and the intrinsic properties of cells have allowed for increased automation, reduced reagent waste, and decreased cost, as well as improved performance. So-called lab-on-a-chip (LOC) approaches enable rapid fabrication and optimization of small-scale, low-volume microchannels capable of high performance enrichment and separation owing to precise control of the forces driving the manipulation. Depending on the physics underlying a particular method, devices are classified as optical, hydrodynamic, dielectrophoretic, magnetic, or acoustic.
Acoustics, and specifically ultrasound, permits noncontact cell separation and retention, which reduces the potential for undesirable surface interactions and physical stress on sensitive biological samples. Typically, separation is achieved by pinning a standing wave perpendicular (conventional lateral acoustophoresis) or parallel (longitudinal acoustic trapping) to the direction of flow. In this thesis, we report a novel longitudinal standing bulk acoustic wave (LSBAW) microfluidic channel that incorporates pairs of pillar arrays oriented perpendicular to the inflow direction. The pillar arrays act as ‘pseudo walls’ that locally amplify the pressure in the enrichment zone, which can be tuned to overcome the drag force for particles of size greater than a critical diameter. Thus, these particles are preferentially retained within the nodes of the local pressure field. In our study, model predictions were used to guide experimental trapping of particles in microchannels with two pillar configurations.
We created six different microfluidic channels with varying inlet/outlet geometries, widths, and pillar shapes. Model results showed pressure field amplification caused by the ‘pseudo walls’ bounding the enrichment zone of each design. We also demonstrated trapping of polystyrene beads (5 μm and 20 μm) and 10 μm fluorescent hollow glass spheres during actuation at various predicted half-wave resonances of these devices. Certain channel architectures achieved acoustic field amplification suitable for particle trapping at flow rates up to ~20 μL/min. In addition, the simulated pressure fields (eigenmodes) were consistent with experimentally observed mode shapes, which validated our modeling approach. Computational and experimental results suggest that LSBAW pillar geometries and flow parameters can be tuned to achieve enhanced enrichment of targeted particles in a predefined region.
J. Mark Meacham
Amit Pathak David Peters