Ultra-wideband electronics, design methods, algorithms, and systems for dielectric spectroscopy of isolated B16 tumor cells in liquid medium

Quantifying and characterizing isolated tumor cells (ITCs) is of interest in surgical pathology and cytology for its potential to provide data for cancer staging, classification, and treatment. Although the independent prognostic significance of circulating ITCs has not been proven, their presence is gaining clinical relevance as an indicator. However, researchers have not established an optimal method for detecting ITCs. Consequently, this Ph.D. dissertation is concerned with the development and evaluation of dielectric spectroscopy as a low-cost method for cell characterization and quantification. In support of this goal, ultra-wideband (UWB), microwave pulse generator circuits, coaxial transmission line fixtures, permittivity extraction algorithms, and dielectric spectroscopy measurement systems were developed for evaluating the capacity to quantify B16-F10 tumor cells in suspension. First, this research addressed challenges in developing tunable UWB circuits for pulse generation. In time-domain dielectric spectroscopy, a tunable UWB pulse generator facilitates exploration of microscopic dielectric mechanisms, which contribute to dispersion characteristics. Conventional approaches to tunable pulse generator design have resulted in complex circuit topologies and unsymmetrical waveform morphologies. In this research, a new design approach for low-complexity, tunable, sub-nanosecond and UWB pulse generator was developed. This approach was applied to the development of a novel generator that produces symmetrical waveforms (patent pending 60/597,746). Next, this research addressed problems with transmission-reflection (T/R) measurement of cell suspensions. In T/R measurement, coaxial transmission line fixtures have historically required an elaborate sample holder for containing liquids, resulting in high cost and complexity. Furthermore, the algorithms used to extract T/R dielectric properties have suffered from myriad problems including local minima and half-wavelength resonance. In this dissertation, a simple coaxial transmission line fixture for holding liquids by dispensing with the air-core assumption inherent in previous designs was developed (patent pending 60/916,042). In addition, a genetic algorithm was applied towards extracting dielectric properties from measurement data to circumvent problems of local minima and half wavelength resonance. Finally, in this research the capacity for using dielectric properties to quantify isolated B16-F10 tumor cells in McCoy\u27s liquid medium was investigated. In so doing, the utility of the Maxwell-Wagner mixture formula for cell quantification was demonstrated by measuring distinct dielectric properties for differing volumes of cell suspensions using frequency- and time-domain dielectric spectroscopy