A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Bio-Inspired Polymer Microparticles for Targeted Recognition and Response(2014) Arya, Chandamany; Raghavan, Srinivasa R.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Microbeads and microcapsules are container structures that are frequently used in biomedical applications. In this dissertation, we have sought to impart new functionalities to these particles, inspired by phenomena observed with biological cells. We have engineered polymer microparticles that recognize and respond to specific species from the surroundings (e.g. cells, polymer chains, metal ions). Three classes of new microparticles are reported, which are each reminiscent of a different type of biological cell in terms of recognition capabilities and response. In the first part of this dissertation, we create functionalized microbeads from the biopolymer, chitosan, and use these to selectively recognize and capture Circulating Tumor Cells (CTCs) from blood. The microbeads are functionalized with a protein (streptavidin) and packed into an array within a microfluidic device. Blood samples with biotin-labeled CTCs are flowed over the packed bed of chitosan beads. Similar to how macrophages adhere to foreign bacteria (i.e. antibody-antigen interactions), the streptavidin-labeled chitosan beads can selectively recognize and adhere to the biotin-labeled CTCs. We show that such a packed bed of chitosan beads could serve as an inexpensive platform for customized capture of different rare cells (cancer cells, stem cells etc) from blood. In the next study, we develop a class of microbeads that undergo clustering (aggregation) in the presence of specific polymers. The inspiration for this comes from the cells (e.g., platelets) and polymers involved during the formation of blood clots. Our system consists of chitosan microbeads coated with cyclodextrins (sugar molecules with a hydrophobic binding pocket), which are then exposed to a polymer that is decorated with hydrophobic units. The particles bind to the polymer chains via hydrophobic interactions and in turn, the particles are induced to form clusters. Subsequently, the polymer precipitates and forms a matrix around the particle clusters, leading to a structure that is reminiscent of a blood clot (platelets enveloped by a mesh of fibrin chains). Lastly, we develop a class of microparticles that have the ability to selectively destroy other microparticles. The inspiration here is from the body's immune system, where cells like the killer T cells selectively destroy cancer and virus infected cells without harming healthy cells. Towards this end, we synthesize two types of microparticles: chitosan capsules that contain the enzyme glucose oxidase (GOx), and beads of a different biopolymer, alginate that are crosslinked with copper (Cu2+) ions. The chitosan capsules enzymatically convert glucose from the surroundings into gluconate ions. When these capsules approach the alginate/copper beads, the gluconate ions chelate the copper ions, leading to the disintegration of the alginate beads. Other beads that do not contain Cu2+ are not affected in this process.Item Characterization of Electrodeposited Chitosan: an Interfacial Layer for Bio-assembly and Sensing(2009) Buckhout-White, Susan Lynn; Rubloff, Gary W; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Microfluidics and Lab-on-a-Chip devices have revolutionized the field of analytical biology. To fully optimize the potential of the microfluidic environment it is critical to be able to isolate reactions in specific locations within a channel. One solution is found using chitosan, an amine-rich biopolymer with pH responsive solubility. Induction of hydrolysis at patterned electrodes within the fluidic channel provides a means to spatially control the pH, thus enabling biochemical functionalization that is both spatially and temporally programmable. While chitosan electrodeposition has proven to be reliable at producing films, its growth characteristics are not well understood. In situ optical characterization methods of laser reflectivity, fluorescence microscopy and Raman spectroscopy have been employed to understand the growth rate inter diffusion and lateral resolution of the deposition process. These techniques have also been implemented in determining where a molecule bound to an amine site of the polymer is located within the film. Currently, electrodeposited chitosan films are primarily used for tethering of biomolecules in the recreation of metabolic pathways. Beyond just a biomolecular anchor, chitosan provides a way to incorporate inorganic nanoparticles. These composite structures enable site-specific sensors for the identification of small molecules, an important aspect to many Lab-on-a-Chip applications. New methods for creating spatially localized sites for surface enhanced Raman spectroscopy (SERS) has been developed. These methods have been optimized for particle density and SERS enhancement using TEM and Raman spectroscopy. Through optimization, a viable substrate with retained chitosan amine activity capable of integration into microfluidics has been developed.Item An Optical MEMS Sensor for On-chip Catechol Detection(2008-12-08) Dykstra, Peter Hume; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis reports the successful design, fabrication and testing of an optical MEMS sensor for the detection of the toxic phenol, catechol. Catechol's presence in food and drinking water posses a health concern due to its harmful effects on cell respiration. By-products of catechol oxidation have demonstrated increased absorbance changes in a chitosan film in the UV and near UV range. Our reported sensor utilizes patterned SU-8 waveguides and a microfluidic channel to deliver catechol samples to an electrodeposited chitosan film for absorbance measurements at 472 nm. Concentrations as low as 1 mM catechol are detected while control experiments including ascorbic acid display no measurable response. By using optical detection methods, our device does not suffer from many of the problems which plague conventional electrochemical based sensors.