A. James Clark School of Engineering

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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.

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    Motion of an Elastic Capsule in a Trapezoidal Microchannel under Stokes Flow Conditions
    (MDPI, 2020-05-17) Koolivand, Abdollah; Dimitrakopoulos, Panagiotis
    Even though the research interest in the last decades has been mainly focused on the capsule dynamics in cylindrical or rectangular ducts, channels with asymmetric cross-sections may also be desirable especially for capsule migration and sorting. Therefore, in the present study we investigate computationally the motion of an elastic spherical capsule in an isosceles trapezoidal microchannel at low and moderate flow rates under the Stokes regime. The steady-state capsule location is quite close to the location where the single-phase velocity of the surrounding fluid is maximized. Owing to the asymmetry of the trapezoidal channel, the capsule’s steady-state shape is asymmetric while its membrane slowly tank-treads. In addition, our investigation reveals that tall trapezoidal channels with low base ratios produce significant off-center migration for large capsules compared to that for smaller capsules for a given channel length. Thus, we propose a microdevice for the sorting of artificial and physiological capsules based on their size, by utilizing tall trapezoidal microchannels with low base ratios. The proposed sorting microdevice can be readily produced via glass fabrication or as a microfluidic device via micromilling, while the required flow conditions do not cause membrane rupture.
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    Analysis of Flow-Based Microfluidic Gradient Generators for the Study of Bacterial Chemotaxis
    (2015) Wolfram, Christopher James; Rubloff, Gary W; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Chemotaxis is a phenomenon which enables cells to sense concentrations of certain chemical species in their microenvironment and move towards chemically favorable regions. This behavior is best understood in the bacteria Escherichia coli, which exhibits chemotaxis towards a variety of energy sources and signaling molecules. Recent advances in microbiology have engineered the chemotactic properties of bacteria to perform novel functions, but traditional methods of characterizing chemotaxis are not sufficient for such complex applications. The field of microfluidics offers solutions in the form of gradient generators. Many of these gradient generators are flow-based, where a chemical species diffuses across a solution moving through a microchannel. A microfluidic gradient generator was explored as a chemotaxis platform. Sources of error during experimental operation and methods of mitigating this error were demonstrated, and the fundamental theory behind these devices was examined. These devices were determined to be inadequate for the study of bacterial chemotaxis.
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    Lipid-Hydrogel Nanoparticles: Synthesis Methods and Characterization
    (2009) Hong, Jennifer S.; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.
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    Design, Fabrication, and Testing of a Microsystem for Monitoring Bacterial Quorum Sensing
    (2009) Koev, Stephan Todorov; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Most pathogenic bacteria communicate with each other using signaling molecules. Their coordinated behavior, known as quorum sensing (QS), enables them to infect host organisms collectively and form drug-resistant biofilms. The study of bacterial signaling pathways may lead to discovery of new antimicrobials. Lab-on-a-chip technology can significantly accelerate the screening of candidate drugs that inhibit QS. This dissertation develops for the first time miniaturized sensors embedded in microfluidic channels to monitor the activity of an enzymatic pathway that produces signaling molecules. These devices can be used as building blocks of future high-throughput systems for drug discovery. The sensors presented here are gold-coated microcantilevers, and they detect the aminoacid homocysteine, a byproduct of the bacterial signaling pathway. It binds to the gold surface, causing stress and cantilever displacement that is measured optically. Samples are synthesized using bacterial enzymes and tested with the sensors. The minimal detected concentration of homocysteine is 1uM. It is demonstrated that deactivation of the enzymes causes a change in the sensor response; this effect can be used for finding drugs that inhibit the enzyme. The traditional method for measuring cantilever displacement requires an elaborate optical setup, and it can only test one device at a time. Two new methods are developed here to overcome these limitations. The first one uses a transparent cantilever which is also an optical waveguide. Light is coupled from the cantilever to a fixed output waveguide and measured with a photodetector. The cantilever displacement is determined from the change in output power. The change is approximately 0.7% per nanometer displacement. The minimal detectable displacement and surface stress are 6nm and 1.3 mN/m respectively. The second measurement method uses a transparent cantilever that is close to a reflective substrate. When the device is imaged with an optical microscope, an interference pattern forms. The cantilever displacement is calculated from the lateral shift of the interference fringes. This shift is determined from images of the device using custom software. The response of multiple cantilevers is captured by translating the microscope stage. The minimal detectable displacement and surface stress are 1nm and 340 uN/m respectively.
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    Controlled liposome formation and solute encapsulation with continuous-flow microfluidic hydrodynamic focusing
    (2008-12-11) Jahn, Andreas; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Liposomes enable the compartmentalization of compounds making them interesting as drug delivery systems. A drug delivery system (DDS) is a transport vehicle for a drug for in vivo drug administration. Drugs can be encapsulated, bound, or otherwise tethered to the carrier which can vary in size from tens of nanometers to a few micrometers. Liposomal DDSs have shown their capability to deliver drugs in a new fashion, allowing exclusive sales of encapsulated drugs to be extended beyond the initial compound's patent expiration date. However, existing methods to form liposomes and encapsulate drugs are based on bulk mixing techniques with limited process control and the produced liposomes frequently require post-processing steps. In this dissertation, a new method is demonstrated to control liposome formation and compound encapsulation that pushes beyond existing benchmarks in liposome size homogeneity and adjustable encapsulation. The technology utilizes microfluidics for future pharmacy-on-a-chip applications. The microfluidic system allows for precise control of mixing via molecular diffusion with reproducible and controlled physicochemical conditions compared to traditional bulk-phase preparation techniques (i.e. test tubes and beakers). The laminar flow and facile fluidic control in microchannels enables reproducible self-assembly of lipids into liposomes in a sheathed flow-field. Confining a water-soluble compound to be encapsulated to the immediate vicinity where liposome formation is expected to occur reduces sample consumption without affecting liposome loading. The ability to alter the concentration and control the amount of encapsulated compounds within liposomes in a continuous-flow mode is another interesting feature towards tailored liposomal drug delivery. The liposome formation strategy demonstrated in this dissertation offers potential for point-of-care drug encapsulation, eliminating shelf-life limitations inherent to current liposome preparation techniques.