Date of Award

Summer 2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Patrick O'Neal

Abstract

Nanotechnology has recently emerged as a powerful modality in many biomedical applications. In particular, several classes of nanoparticles have been employed as cancer therapy and imaging contrast agents. These particles can have architecture of varying complexity, depending on their specific application. These complex architectures are achieved by various chemical techniques usually performed in specific sequences to add complexity and functionality. One such class of nanoparticle, used in tumor treatment and as contrast agents in several optical imaging techniques, is the plasmon resonant metal nanoparticle. The most common metal used for these particles is gold because of its biocompatibility, lack of cellular toxicity, and simple surface chemistry. These particles have specific optical properties in the near infrared spectrum making them ideal for modern cancer therapy and optical imaging. Two examples of these particles are gold nanoshells and gold nanorods, both of which are highly absorptive and scattering at near infrared wavelengths. It is for this reason that they are often employed in photo thermal ablation of tumors using near infrared light. In this type of tumor treatment, the particles are injected intravenously and accumulate in the tumor. After accumulation, a near infrared laser is used to heat the particles and destroy the tumor.

These gold nanoparticles must be modified with biocompatible "stealthing" compounds before they can be injected. This is because of the high efficiency of the body's reticuloendotheial system, which will quickly eliminate materials foreign through cellular phagocytosis. Although techniques for quality control in manufacturing these nanoparticles are used to confirm proper surface modification, their in vivo behavior is very difficult to predict. It is for this reason that real time feedback in nanoparticle therapy is an urgent need and will greatly improve its efficacy.

This dissertation reports the development of a non-invasive optical system capable of reporting the in vivo vascular concentration of these nanoparticles in near real time. The device, termed the pulse photometer, utilizes a technique similar to that used in pulse oximetry. This technique is photoplethysmography, which has many medical applications. One of these is determining the optical characteristics of pulsatile arterial blood, which are affected after the injection of these optically resonant particles. Several prototypes of this are presented in this dissertation. The culmination of this work is the prototype III pulse photometer capable of concurrent nanoparticle monitoring and oximetry. Final testing of this prototype revealed its ability to accurately determine the vascular optical density of gold nanorods compared to ex vivo spectrophotometry, a technique also verified in this dissertation, by statistical Bland-Altman analysis.

Download

Share

COinS