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Biomacromolecule interactions and sensor engineering with single-walled carbon nanotubes

Posted on:2015-10-12Degree:Ph.DType:Thesis
University:College of Medicine - Mayo ClinicCandidate:Gong, XunFull Text:PDF
GTID:2471390017995567Subject:Biomedical engineering
Abstract/Summary:
The many unique properties of single-walled carbon nanotubes (SWCNT) have led interest in their research for a range of potential applications. It is well known that DNA molecules readily wrap around SWCNTs to create water soluble, and biocompatible hybrids (DNA-SWCNT). In concert with many recent studies into DNA molecules and custom materials design, the door is open for SWCNT engineering for biomedical applications. In recent years, SWCNT conjugates have been explored for a variety of applications from scaffolds, to drug delivery, to sensors and beyond. However, despite the amount of early enthusiasm and research, there currently is a limited number of SWCNT-based technologies in the commercial and medical realm. Major factors that contribute to this phenomenon include the heterogeneity of the material and subsequently the complexity of their properties especially in the biological context. The focus of this thesis is to begin addressing the latter for DNA-SWCNT on several fronts of the iterative process of biomaterials design including: material properties, sensor engineering, and cellular interactions.;Despite the amount of research on applications of DNA-SWCNT, there is much contention on their exact surface organization. Through multiple complementary techniques and the development of novel analytical methods, a model of DNA-SWCNT surface structure was proposed. Next, DNA-SWCNT endocytosis was imaged. Pharmacological and genetic methods were used to study both the kinetics and mechanism of DNA-SWCNT cellular uptake. Once inside the cell, we took advantage of DNA-SWCNT properties and spatial locations of endosomes to create a sensor system that detects intracellular analyte concentrations with both spatial and temporal resolution. As current study of intracellular signaling often involve the study of time and population averaged cellular changes, this new tool to study single cell responses with spatial resolution can significantly improve our basic understanding of cellular machinery. Additionally, as pathophysiologic phenomena often begins with disturbance of intracellular equilibrium, the ability for intracellular analyte detection can potentially be engineered for disease early detection.;Finally, we studied DNA-SWCNT structural changes in biologically relevant aqueous solutions and discovered new and interesting properties of nanomaterial associations with proteins and with each other. While these findings complicate future in vivo research, the unique preferences of DNA-SWCNTs for protein types opens the door for engineering of selective nanomaterial-protein interactions for purification and sensor applications.;As we delve into the field of nanomedicine, it is important to concurrently develop new methods to facilitating new understandings. This thesis is an examplar of such work where novel techniques were used to elucidate new understandings. Though every material is unique, they often share similar properties. Thus, the concepts learned and tools gained from the study of single-walled carbon nanotubes can also serve as starting points for future investigations of other materials. A culmination of several works, this thesis serves to bridge fundamental knowledge gaps and advance the field of nanomaterials.
Keywords/Search Tags:Single-walled carbon, DNA-SWCNT, Sensor, Engineering, Interactions
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