Quantitative Molecular Sensing Using DNA Origami
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Mechanical and Aerospace Engineering Honors Theses; 2016
Type I diabetes is considered a worldwide epidemic because its incidence is exponentially increasing. Current treatment of the disease requires blood glucose monitoring and intake of insulin. While there have been many medical advances in devices that monitor glucose and deliver insulin, these treatments can still lead to complications, including but not limited to debilitating hypoglycemia, neuropathy, and death, if not followed properly. To eliminate these complications, there is a need to create a novel approach for continuous and automated glucose monitoring and insulin delivery. This project seeks to address this challenge by creating a DNA nanostructure that can sense changes in the concentration of a target biomolecule. The long-term goal is to use this DNA nanostructure to detect a glucose-protein complex. The nanostructure comprises a DNA hinge with aptamers (short DNA strands with sequences that bind to a specific protein). Initial development and optimization experiments will target the protein thrombin for simplicity and easy availability. We use transmission electron microscopy (TEM) to measure the equilibrium changes in conformation of the hinge upon contact with thrombin. We initially explored two conformations of the hinge: one that opens when it comes into contact with thrombin and another that closes. Preliminary TEM results have shown that the closed structure is more efficient for detection. In the future, we plan to conduct fluorescence experiments to further optimize the protein sensor and measure real-time response. These experiments will lay the foundation for a viable long-term glucose sensor; the sensor can then be paired with a molecular release mechanism to deliver insulin. Ultimately, this type of device could serve as an automated monitoring and delivery system that would make diseases such as diabetes more manageable and eliminate many of the complications that arise from current treatments.
Academic Major: Chemical Engineering
The College of Engineering
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