We design actuated cilia that can maneuver microscopic particles normal to a microfluidic channel wall and transport microscopic particles parallel to the channel wall. For identifying the design specifications, we employ a hybrid LBM/LSM computational model, to simulate hydrodynamic interactions between oscillating elastic cilia and microscopic particles in a microfluidic channel. The oscillating synthetic cilia are elastic filaments tethered to the channel wall and actuated by sinusoidal force acting at their free ends. The cilia are arranged in a square pattern. The microscopic particle is a neutrally buoyant solid sphere, which is sufficiently small compared to the cilium length and inter-cilium distances, so that the particle can move freely inside the ciliated layer. We study the effect of actuation frequency on the particle motion inside the ciliated layer. We show that depending on the frequency, particles can be either driven away from the ciliated channel wall or drawn towards the wall. We also examine how to use inclined cilia to transport particles along the ciliated layer. We show that the particle transport along the ciliated layer can be regulated by the frequency of cilium oscillation. The results uncover a new route for regulating particle position and transport in microfluidic devices.

The lymphatic system has three primary roles: transporting lipids, transporting immune cells, and maintaining fluid balance. Each one of these roles are influenced by the presence of flow. Inflammation increases lymph flow, lipid uptake is enhanced by flow, cancer cell migration increases in the presence of flow, and lymphatic permeability and lymphatic contractility respond to changes in flow. Flow is very important to lymphatic function, and yet, there are no in vitro models that incorporate both luminal (flow along cell lumen) and transmural (flow through cell lumina) flow for lymphatics. To address this need, a microfluidic device has been developed that can incorporate both of these types of flow. This is achieved by driving flow through a channel which creates a pressure gradient that drives fluid through a porous membrane into an adjacent channel. Following several design iterations, the device can be easily fabricated, imaged, and cells can grow and survive in it. Permeability experiments have been performed in static and flow, 0.175 mL/min (0.5 dyne/cm²), cases. The effective permeability of dextran in the static and flow cases was calculated to be 0.0083 μm/s and 2.05 μm/s respectively. While the effective permeability of bodipy in the static and flow cases was calculated to be 0.0053 μm/s and 2.57 μm/s respectively. The static values are similar to values obtained in a transwell study by Dixon et al. As mentioned, lipid uptake is increased in the presence of flow and these numbers suggest the same. In addition to permeability studies, experiments were performed with cancer cells suspended in a collagen gel. Two image processing techniques were used to quantify cancer cell migration. The first technique was used to calculate the number of cells present at the beginning of the experiment and the number of cells that were ever present during the experiment in that particular z slice. The static case yielded a cell flux of 15 additional cells. While the two flow cases, within interstitial flow range, had a flux of 24 and 40 cells. This suggests that flow increases migration in cancer cells and is in agreement with the literature. The second technique was used to show that the cells in the static and flow cases are similarly motile, but the flow case is more directed in the z direction towards the membrane. The future work for this device is quite extensive, but a strong foundation centered around basic capabilities like inducing flow, seeding cells, and imaging has been formed.

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 77-78). Also available on the World Wide Web.

Controlled drug delivery devices provide numerous advantages such as reduced side effects, higher therapeutic efficiency and improved patient compliance. Biodegradable polymer has become the most important material for controlled drug delivery device because of the excellent biocompatibility and tunable physicochemical properties. Biodegradable polymeric drug delivery devices are usually processed into various types of micro-particles due to the ease of fabrication and administration. However, controlling the drug release kinetics of these microparticles is still a challenge. One important reason is that drug release kinetics is significantly influenced by the microstructure of drug delivery devices, which is difficult to control. 　Microfluidic method is a group of technologies involved in the manipulation of fluids using channels in the scale of micrometers. Microfluidic method is particularly useful in controlling the structure of micro-droplets and generating homogeneous droplets. Therefore, microfluidics suggests great potential in controlling microstructures of drug delivery devices and drug release kinetics. 　In this study, biodegradable polymer based controlled drug delivery devices were fabricated using microfluidic method. Various types of microstructures were developed such as microspheres, core-shell microspheres, hollow microspheres and hydrogel microspheres. The results showed that microstructures were well controlled by fluid flow rates and geometries of capillary microfluidic devices. Both hydrophobic and hydrophilic drugs could be delivered by choosing drug delivery devices with suitable microstructures. 　Drug release kinetics of biodegradable polymeric microspheres has been studies a lot, yet complete understanding is still to be achieved. The diameter is an important factor which contributes to the drug release kinetics. However, the influence of diameter has not been systemically studied because monodisperse microspheres are difficult to obtain. Using microfluidic method, monodisperse PLGA microspheres with different diameters were fabricated to study the influence of diameter on drug release kinetics. It was found that diameter only influence the duration of the first phase (lag phase) in drug release process and smaller microspheres exhibited shorter lag phase. The relatively faster expansion of smaller microspheres was found to be responsible for the size effect by monitoring physicochemical changes during drug release. 　Rifampicin, a broad-spectrum antibiotic, was encapsulated by PLGA microspheres and PLGA-alginate core-shell microspheres. The long-term antimicrobial effects of drug loaded microspheres were investigated by drug release test and antimicrobial test against Staphylococcus aureus. The results showed that drug delivery devices could provide antimicrobial effect for more than one month. These drug delivery devices show potential in applications of controlled drug delivery and long-term antimicrobial therapy. 　In conclusion, drug delivery devices with different microstructures were fabricated using microfluidic method. The diameter of PLGA microspheres only influence the first phase of drug release profile (lag phase) and smaller microspheres exhibited shorter lag phase. The size effect is due to the relatively faster expansion rate of smaller microspheres. Rifampicin loaded PLGA microspheres and PLGA-alginate core-shell microspheres could provide sustained release of rifampicin for more than one month. The released rifampicin was able to inhibit the growth of Staphylococcus aureus. The controlled drug delivery devices presented showed great potential in long-term antimicrobial applications. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--Mechanical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Yoda, Minami; Committee Member: Aidun, Cyrus; Committee Member: Breedveld, Victor; Committee Member: Fedorov, Andrei; Committee Member: Zhu, Cheng. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph. D.)--University of Canterbury, 2009. / Typescript (photocopy). "January, 2009." Includes bibliographical references (p. 213-227). Also available via the World Wide Web.

Thesis (M.S.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2007. / Includes bibliographical references.

Thesis (Ph. D.)--Oregon State University, 2006. / Printout. Includes bibliographical references. Also available on the World Wide Web.

This thesis aims to address the challenges of the development of cost-effective and rapid assays for the accurate counting of CD4+ T cells and quantification of HIV-1 viral load for resource-constrained settings. The lack of such assays has severely affected people living in disease prevalent areas. CD4+ T cells count information plays a vital role in the effective management of HIV-1 disease. Here, we present a flow-free magnetic actuation platform that uses antibody-coated magnetic beads to efficiently capture CD4+ T cells from a 30 μL drop of whole blood. On-chip cell lysate electrical impedance spectroscopy has been utilized to quantify the isolated CD4 cells. The developed assay has a limit of detection of 25 cells per μL and provides accurate CD4 counts in the range of 25–800 cells per μL. The whole immunoassay along with the enumeration process is very rapid and provides CD4 quantification results within 5 min time frame. The assay does not require off-chip sample preparation steps and minimizes human involvement to a greater extent. The developed impedance-based immunoassay has the potential to significantly improve the CD4 enumeration process especially for POC settings. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

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