PRECLINICAL DEVELOPMENT OF SINGLE WALLED CARBON NANOTUBE-BASED OPTICAL BIOSENSORS

Authors

Eric M. Hofferber, University of Nebraska - LincolnFollow

First Advisor

Nicole Iverson

Date of this Version

Spring 4-22-2021

Citation

Hofferber, E. Preclinical Development of Single Walled Carbon Nanotube-Based Optical Biosensors. 2021

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Biological Engineering, Under the Supervision of Professor Nicole M. Iverson. Lincoln, Nebraska: April, 2021

Copyright © 2021 Eric M. Hofferber

Abstract

High resolution, long-term monitoring of key biological analytes would improve patient outcomes by providing earlier detection of disease states and improved efficacy of treatment. One class of biosensors that have gained much attention in recent years are optical biosensors. Optical probes are attractive biosensors due to their noninvasive nature of detection, as certain light can pass through tissue, water, and blood. Single walled carbon nanotubes (SWNT) are a specific type of optical biosensor that fluoresce in the near infrared range of the electromagnetic spectrum and offer unparalleled spatial and temporal resolution. SWNT have been applied as biosensors in vitro, ex vivo, and in vivo for a growing library of key biological analytes. However, biocompatibility concerns, complex detection schemes, and platform incorporation have hindered translation of this promising class of biosensor to the clinical setting. Herein, novel characterization methods to determine SWNT fate, a simple detection scheme demonstrating the first successful detection of SWNT sensors in a large animal model, and novel platforms for localization of real time SWNT sensors are described. As a hydrophobic nanoparticle made of pure carbon, biocompatibility concerns persist when SWNT are used for biological applications. Following application in vivo, novel methods were developed to extract and quantify SWNT sensors accounting for the majority of the initial implant, and subsequent Raman spectroscopy measurements on excised tissue resulted in no detectable SWNT aggregation. Nanotechnology laboratories are not well suited for large animal housing or handling, and detection schemes for SWNT are typically complex and immobile. To this end, a simple detection scheme of a noncoherent light source and a near-infrared spectrometer was applied to show successful detection of a SWNT fluorescence signal in a large animal for the first time. Finally, SWNT incorporation into platforms for localization have led to delayed or attenuated responses to the target analyte in the past. SWNT-hydrogel platforms were developed to investigate the underlying mechanisms for the delayed response, and platforms were developed that offered SWNT localization with negligible effect on sensitivity.

Advisor: Nicole M. Iverson