Nanoscience and Microsystems ETDs

Publication Date

Fall 10-14-2019

Abstract

Diagnostic assays are designed to detect a unique analyte profile in a disease of interest. Nucleic acids contain an information-dense sequence, and thus are ideal candidates for unique analytes. The gold-standard of nucleic-acid-based detection is PCR which has high sensitivity, but involves time, expertise, and cost. DNA molecular logic technology holds much promise as an alternative molecular detection method due to the potential to save cost and expertise, while also achieving a high sensitivity. However, nucleic acid detection in biomedical applications carries with it the difficulty of choice of appropriate sequence and potential biological sample background.

This work describes the development and testing of a DNA molecular logic implementation of a viral assay for dengue virus. This work initiated with an attempt at an implementation of a solution-based viral assay. The challenges arising from the solution-based implementation, suggested the need for additional tools and designs, and have given rise to the computational aims. Included in this work is the development of computational tools for aiding the design of DNA molecular logic bioassays, and the use of these tools in bioassay design. The tools developed are a continuous kinetic model of the DNA-based assay elements, a discrete stochastic model to characterize limit of detection, and an algorithm to search databases for assay target sequences. The result of this work are tools that may be used in the context of DNA-based bioassay design. Future directions suggest work on developments to the bioassay. These include an acoustophoretic microparticle-based assay for signal enrichment and a microarray-based host gene expression profile.

Keywords

DNA nanotechnology, dengue virus, diagnostic detection, DNA molecular logic, DNA bioassay, chemical kinetic modelling, stochastic kinetic modelling, target sequence search

Sponsors

National Science Foundation Grants 1525553, 1518861, 1318833 and NIH NIAID 5 R21 AI115105-02

Document Type

Dissertation

Language

English

Degree Name

Nanoscience and Microsystems

Level of Degree

Doctoral

Department Name

Nanoscience and Microsystems

First Committee Member (Chair)

Steven W. Graves

Second Committee Member

Darko Stefanovic

Third Committee Member

Matthew R. Lakin

Fourth Committee Member

Jason Gans

Fifth Committee Member

Ronen Polsky

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