| Miniature biomedical assay systems (lab-on-a-chip) are being developed to perform rapid clinical and laboratory chemistry using minimal sample sizes. The operations of these miniature assay devices will involve the transport, manipulation, and preparation of various biological fluids, such as blood or cell suspensions. The essential attributes of microscale fluid mechanics, which differ markedly from those of the macroscale, prompt two important considerations. First, new methodologies must be formulated to characterize the dynamics and behavior of complex biological fluids in various flow geometries at the microscale. Secondly, some conventional approaches to biological sample processing and preparation may need to be supplanted by new strategies that are better suited to the dimensions and the fluid mechanics of microdevices. This dissertation provides a demonstration of each of these areas.; Since blood is likely the most prominent biological fluid that diagnostic systems must consider, developing microfluidic components (channels, pumps, valves) to process blood requires a firm understanding of its non-Newtonian properties at these dimensions and with flow through complicated geometries. To enable this understanding, the first part of this dissertation demonstrated basic methods for characterizing blood flow through three basic flow geometries. Blood flow resistances were determined by measuring pressure drop vs. flow rate relationships. The non-Newtonian properties of blood suspensions in all three geometries were measured using a microscope-based DPIV system, which consisted of illumination with a pulsed laser and image capture by a CCD camera. Successive snapshots of the flow were processed by DPIV software to construct velocity fields, which were compared with Newtonian standards obtained from CFD simulations.; In the second part of the dissertation, a biomimetic method for cell separation based on adhesive rolling and transient tethering has been demonstrated in two designs for microstructured fluidic channels coated with an E-selectin IgG chimera. Using E-selectin-ligand adhesions, efficient capture and several hundred-fold enrichment of HL-60 cells on channel surfaces under continuous sample flow was achieved. Additionally, the difference in flow-driven cell transit speeds through the microstructured fluidic channels (comparing HL-60 vs. U-937 cells in this example) may provide the mechanism for selectively enriching and partially fractionating different types of blood cells. |
