Inhalation is an increasingly important route for non-invasive drug delivery for both systemic and local applications. Control of particle droplet size and throughput plays a critical role in the efficient and effective delivery of often expensive medications to the lung. Drugs designed to treat pulmonary diseases or for systemic absorption through the alveolar capillary bed require optimum particle sizes (2 to 6 µm) for effective delivery. Current advanced commercial devices such as Omron and ParieFlow produce droplets or aerosols by a vibrating mesh. All these devices suffer from broad particle size (poly-disperse) distributions and lack of size control capability, and also are plagued by clogging of the mesh orifices used.

The new drug delivery device presented in this dissertation has demonstrated capability for control of particle size within the optimum size range at low drive power and desirable throughput and freedom from clogging. The new device employs a novel silicon-based ultrasonic nozzle with multiple Fourier horns in resonance designed to operate based on the phenomena of Faraday waves at the frequency range of 1 to 2.5 MHz. The superior performance and batch fabrication economy of the centimeter-size nozzles have demonstrated the potential towards commercialization of the new delivery device.

The nozzle consists of a drive section and a resonator section. The resonator section is made of multiple Fourier horns in cascade. The nozzle is designed to vibrate at the resonance frequency of the multiple Fourier horns. A lead zirconate titanate (PZT) piezoelectric transducer is bonded on the drive section to excite mechanical vibrations (displacement) along the nozzle axis. The PZT transducers are fed by a driving circuit. The resultant vibration amplitude on the nozzle end face (tip of the distal horn) is greatly magnified. As the liquid fed from a plastic tubing to the nozzle’s tip, a liquid layer is maintained on the surface of the nozzle tip to form standing capillary waves and production of monodisperse droplets when the tip vibration amplitude exceeds a threshold value.

The major objective of this dissertation research is to devise and develop methods to accomplish a high level of performance and robustness for a standalone nebulization module. Significant advances have been made towards the objective.

The so-called magnonic crystals (MCs), the new metamaterial struc- tures made of periodic variations in geometric parameters and/or properties of magnetic materials, are being actively studied worldwide. In contrast to the well-established photonic crystals (PCs), MCs possess the capability of controlling the generation and transmission of information-carrying magnetostatic waves (MSWs) at microwave fre- quencies by a bias magnetic field. A new theoretical approach based on Walker's equation which is capable of efficiently analyzing mag- netostatic volume waves (MSVWs) propagation characteristics in one-dimensional (1-D) and two-dimensional (2-D) MCs was developed through this dissertation research. The validity of this theoretical approach was subsequently verified by extensive experimental results with excellent agreements.

MC-based tunable microwave devices were also envisaged and realized. Specifically, the performance characteristics of wideband tunable microwave filters and phase shifters, and waveguides, are detailed in this dissertation. In device fabrication, both the 1-D MC consisting of pe- riodic channels and the 2-D MC consisting of periodic holes in square lattices were prepared by wet etching technique. The magnetically-tuned bandgaps created in the 1-D and 2-D MCs were shown to func- tion as tunable band stop filters (BSFs). Furthermore, the large phase shifts associated with the left and right flat passbands of the bandgap facilitated construction of tunable wideband microwave phase shifters. Compared to all existing magnetically-tuned phase shifters, the MC-based phase shifters are significantly smaller in dimension and possess much larger phase tuning rate and phase shifts. Finally, confinement of magnetostatic forward volume waves (MSFVWs) was demonstrated both theoretically and experimentally.

Electric potential distribution in nanoscale electroosmosis has been investigated using the nonequilibrium molecular dynamics ( NEMD), whose results are compared with the continuum based Poisson-Boltzmann (PB) theory. If the bin size of the MD simulation is no smaller than a molecular diameter and the focusing region is limited to the diffusion layer, the ionic density profiles on the bins of the MD results agree well with the predictions based on the PB theory for low and moderate bulk ionic concentrations. The PB equation breaks down at high bulk ionic concentrations, which is also consistent with the macroscopic description.

A method for comparing related nozzle designs possessing widths proportional to their frequencies over a broad frequency range is presented and utilized on asymmetric multiple Fourier nozzle designs. The underlying causes of the frequency dependent performance of the nozzle designs are explored and compared. Based on this knowledge, a better understanding of the operation of the nozzles is obtained. From this understanding, nozzle designs intended to operate at higher frequencies can be built in a more effective manner.

Medicinal particles or aerosols of the size range from 1 to 5 µm at high output rates are required for efficient and effective inhaled drug delivery to rapidly administer a large dose of medicine to the lung. Current commercial devices all suffer from broad aerosol size distributions, with a geometrical standard deviation (GSD) range of 1.5 to >4.0, making it difficult to deliver sufficient drug to targeted sites precisely and rapidly. The silicon-based megahertz multiple-Fourier horn ultrasonic nozzles (MFHUNs) presented in this dissertation have been shown capable of producing such micrometer-sized particles (aerosols) at high output rate and low electrical drive power. The precise control of aerosol size and much narrower size distribution achieved by the new device will greatly improve targeting of treatment within the respiratory tract and improve delivery efficiency, resulting in better efficacy, fewer side effects, shorter treatment times, and lower medication costs compared with the existing nebulizers. The basic ultrasonic nozzle consists of a drive section and a resonator section with a lead zirconate titanate (PZT) transducer bonded on the drive section to excite large mechanical vibrations on the end face of the distal horn to initiate instability of megahertz (MHz) Faraday waves on the free liquid surface. In operation, a medicinal liquid layer with a certain thickness is formed on the end face of the nozzle tip via a silica tube. The dramatic resonance effect among the multiple Fourier horns and high growth rate of the MHz Faraday waves excited on the medicinal liquid layer together facilitate ejection of monodisperse aerosols of desirable size range (2-5 µm) at low electrical power(<1.0W). The interaction between the medicinal liquid layer and the MFHUN was studied for optimization of nozzle designs. The effect of variations of the medicinal liquid layer on the performance of MFHUN was minimized by increasing the half-power bandwidth of the MFHUN. The temporal instability of Faraday waves has been observed and studied on both a planar liquid layer and a spherical water drop. The critical excitation displacement of the nozzle end face for temporal instability of MHz Faraday waves on the liquid layer was verified via measuring the threshold drive voltage. The theoretical prediction of the aerosol diameter was verified by the size analyses of aerosols produced at the drive frequencies of 1.0, 1.5 2.0 and 2.5 MHz. A number of common pulmonary drugs have been nebulized with desirable aerosol sizes and output rates using the pocket-size units consisting of a single nozzle or twin nozzles. A versatile ultrasonic nebulizer that utilizes a twin-nozzle of multiple Fourier horns at 1-2 MHz drive frequencies has also been realized to demonstrate the capability of doubling the aerosol output rate of the same drug solution as well as simultaneous aerosolization of two different drug solutions.