LUMINESCENCE LIFETIME INSTRUMENTATION DEVELOPMENT FOR MULTI-DYE ANALYSIS

An efficient and accurate luminescence based instrument capable of determining differences in lifetime decay emissions of multiple dyes by using a new multiluminophore lifetime calculation method was developed for eventual use in dual sensing applications. Current methods for monitoring multiple luminescent dyes, such as dual lifetime determination (DLD), do not accurately calculate actual lifetimes. In this work, a mathematical model of the system was produced by using two different computer programs in order to simulate variables and to develop an efficient and accurate method for simultaneously calculating the lifetimes. The calculation method was based on a new correction algorithm recently developed in the research group. Using these models and optical hardware, an instrument was created to be driven by a personal computer equipped with custom LabVIEW software, which also analyzed the recorded data. During testing, the system was able to accurately calculate the lifetimes of two distinct luminophores. It was determined that this system is advantageous over current multi-dye analysis techniques by providing accurate and computationally-efficient calculations with the potential of implementing low-cost materials in the future. This system could eventually be implemented for many dual-sensing applications, where two parameters must be monitored at once. For example, patients suffering from diabetes could use a non-invasive monitor based on this system to detect varying tissue oxygen levels to compensate for enzymatic glucose sensor response

LUMINESCENCE LIFETIME INSTRUMENTATION DEVELOPMENT FOR MULTI-DYE ANALYSIS

An efficient and accurate luminescence based instrument capable of determining differences in lifetime decay emissions of multiple dyes by using a new multiluminophore lifetime calculation method was developed for eventual use in dual sensing applications. Current methods for monitoring multiple luminescent dyes, such as dual lifetime determination (DLD), do not accurately calculate actual lifetimes. In this work, a mathematical model of the system was produced by using two different computer programs in order to simulate variables and to develop an efficient and accurate method for simultaneously calculating the lifetimes. The calculation method was based on a new correction algorithm recently developed in the research group. Using these models and optical hardware, an instrument was created to be driven by a personal computer equipped with custom LabVIEW software, which also analyzed the recorded data. During testing, the system was able to accurately calculate the lifetimes of two distinct luminophores. It was determined that this system is advantageous over current multi-dye analysis techniques by providing accurate and computationally-efficient calculations with the potential of implementing low-cost materials in the future. This system could eventually be implemented for many dual-sensing applications, where two parameters must be monitored at once. For example, patients suffering from diabetes could use a non-invasive monitor based on this system to detect varying tissue oxygen levels to compensate for enzymatic glucose sensor response

Development of a multimodal foveated endomicroscope for the detection of oral cancer

A multimodal endomicroscope was developed for cancer detection that combines hyperspectral and confocal imaging through a single foveated objective and a vibrating optical fiber bundle. Standard clinical examination has a limited ability to identify early stage oral cancer. Optical detection methods are typically restricted by either achievable resolution or a small field-of-view. By combining high resolution and widefield spectral imaging into a single probe, a device was developed that provides spectral and spatial information over a 5 mm field to locate suspicious lesions that can then be inspected in high resolution mode. The device was evaluated on ex vivo biopsies of human oral tumors

Multimodal Foveated Endomicroscope for the Early Detection of Oral and Esophageal Cancer

Digestive tract cancers will be responsible for nearly 30% of all cancer deaths in the United States in 2016. Oral and esophageal cancers alone will result in over 25,000 deaths, with an estimated 65,000 new cases. Most of these deaths can be attributed to the late detection of cancers, when treatment options become more limited. This late detection is often due to the limitations of current standard screening procedures, which often struggle with rapid and reliable recognition of precancerous warning signs. Optical imaging methods have the potential to become powerful, non-invasive early diagnostic tools. However, most systems are often limited by several factors including insufficient optical resolution, limited field of view, or a lack diagnostically relevant data, leading to devices with either low specificity or low sensitivity. This work presents the design and development of several technologies with the goal of creating a multimodal endomicroscope that overcomes the limits of current diagnostic techniques for the early detection of oral and esophageal cancer with high sensitivity and specificity. The first stage in the development of the endomicroscope is the design, fabrication and validation of a miniature foveated objective, which provides both widefield and high resolution imaging in a compact form. The objective accomplishes this task by introducing distortion into the optical system in order to nominally mimic the variable resolution regions in the fovea of the human eye. Two image relay techniques were developed to integrate the objective with (1) a snapshot image spectrometer with the ability to capture spatial and spectral data simultaneously in order to rapidly locate suspicious areas of interest and (2) a custom confocal microscope capable of high resolution imaging to observe morphological changes in the tissue. The performance of the integrated device was evaluated through the imaging of mouse and human cancer samples

Media 1: Confocal foveated endomicroscope for the detection of esophageal carcinoma

Originally published in Biomedical Optics Express on 01 July 2015 (boe-6-7-2311

On the Synthesis and Anticancer Testing of alpha,beta-Unsaturated Ketones as Analogs of Combretastatin-A4

Twenty- one alpha,beta-unsaturated ketone analogs of combretastatin-A4 (CA-4) that were designed for good solubility in aqueous media were synthesized. Compounds defined as Type A were derived from phenylacetone, in which subclass I contained ortho-, meta- or no substituents, sub-class II contained para-substituents, and sub-class III consisted of two substituents. Type B compounds were derived from cyclopropyl 2-fluorobenzyl ketone. The cis-configuration of the target compounds was ascertained through a single crystal X-ray crystallographic analysis of the fluorine-containing compound 8f. Five of the analogs, 8c, 8j and 8l of Type A and 9d and 9i of Type B, were shown to display modest cytotoxic potency (IC50 in the 3.8 - 21 mu M range) against the growth of murine melanoma (B16) and leukemia (L1210) cells in culture. Compounds 8j, 8l and 9i were further tested against MDA-MB-435 human melanoma cells. The cyclopropane-containing compound 9i was the most potent; with an IC50 value of 2.4 mu M. Even though no appreciable effects on interphase microtubules were observed when A-10 cells were treated with 30 mu M 8j or 8l, compound 9i caused extensive microtubule depolymerization at this concentration. These results suggest that compound 9i of Type B has a similar mechanism of action as CA-4 whilst compounds 8j and 8l of Type B are likely to have a different mechanism of action