A. James Clark School of Engineering
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Item THREE-DIMENSIONAL BIOPATTERNING TECHNOLOGY AND APPLICATION FOR ENZYME-BASED BIOELECTRONICS(2018) Chu, Sangwook; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Integration of biomaterials with 3-D micro/nano devices and systems offers exciting opportunities for developing miniature bioelectronics with enhanced performances and advanced modes of operation. However, the limited wetting property of such small scale 3-D structures (Cassie-Baxter wetting) presents a potential challenge in these developments considering most biological materials require storage in buffered aqueous solutions due to their inherently narrow stability window. In this thesis research, an electrowetting-assisted 3-D biomanufacturing technology has been developed enabling highly selective and programmable biomolecular assembly on 3-D device components. The successful integration of microscale 3-D device structures created via conventional microfabrication techniques with a nanoscale molecular assembly of Tobacco mosaic virus (TMV), enabled hierarchical and modular material assembly approaches for creating highly functional and scalable enzyme-integrated microsystems components. The potential limitation in 3-D bio-device integration associated with the surface wettability has been investigated by adapting Si-based micropillar arrays (μPAs) as model 3-D device structures, and a cysteine-modified TMV (TMV1cys), as the biomolecular assembler which can functionalize onto electrode surfaces via a self-assembly. The comparative studies using μPAs of varying pillar densities have provided clear experimental evidence that the surface coverage of TMV1cys self-assembly on the μPA is strongly correlated with structural density, indicating the structural hydrophobicity as a key limiting factor for 3-D bio-device integration. The 3-D electro-bioprinting (3D-EBP) technology developed in this work leverages the hydrophobic surface wettability by adapting a capacitive wettability-control technique, known as electrowetting. The biological sample liquid was selectively introduced into the microcavities using a custom-integrated bioprinting system, allowing for patterning of the TMV1cys self-assembly on the μPA substrates without the limitations of the structural density. The functional integrity of the TMV1cys post 3D-EBP allowed conjugations of additional biological molecules within the 3-D substrates. Particularly in this work, immobilization of glucose oxidase (GOx) has been achieved via a hierarchical on-chip immobilization method incorporating 3D-EBP. Combined with the enhanced and scalable enzymatic reaction density on-chip and the electrochemical conversion strategies, the innovative 3D biomanufacturing technology opens up new possibilities for next-generation enzyme-based bioelectronics.Item A Microfluidic Programmable Array for Label-free Detection of Biomolecules(2011) Dykstra, Peter Hume; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)One of the most promising ways to improve clinical diagnostic tools is to use microfluidic Lab-on-a-chip devices. Such devices can provide a dense array of fluidic components and sensors at the micro-scale which drastically reduce the necessary sample volumes and testing time. This dissertation develops a unique electrochemical sensor array in a microfluidic device for high-throughput, label-free detection of both DNA hybridization and protein adsorption experiments. The device consists of a patterned 3 x 3 grid of electrodes which can be individually addressed and microfluidic channels molded using the elastomer PDMS. The channels are bonded over the patterned electrodes on a silicon or glass substrate. The electrodes are designed to provide a row-column addressing format to reduce the number of contact pads required and to drastically reduce the complexity involved in scaling the device to include larger arrays. The device includes straight channels of 100 micron height which can be manually rotated to provide either horizontal or vertical fluid flow over the patterned sensors. To enhance the design of the arrayed device, a series of microvalves were integrated with the platform. This integrated system requires rounded microfluidic channels of 32 micron height and a second layer of channels which act as pneumatic valves to pinch off selected areas of the microfluidic channel. With the valves, the fluid flow direction can be controlled autonomously without moving the bonded PDMS layer. Changes to the mechanism of detection and diffusion properties of the system were examined after the integration of the microvalve network. Protein adhesion studies of three different proteins to three functionalized surfaces were performed. The electrochemical characterization data could be used to help identify adhesion properties for surface coatings used in biomedical devices or for passivating sensor surfaces. DNA hybridization experiments were performed and confirmed both arrayed and sensitive detection. Hybridization experiments performed in the valved device demonstrated an altered diffusion regime which directly affected the detection mechanism. On average, successful hybridization yielded a signal increase 8x higher than two separate control experiments. The detection limit of the sensor was calculated to be 8 nM.