Interest in using optical methods in the development of noninvasive clinicaldiagnostic and therapeutic techniques for brain diseases has widely increased due to theirsimplicity, safety, and affordability. The main limitations of light-based techniques usedfor brain theranostics are the strong light scattering in the scalp and skull, which causedecrease of spatial resolution, low contrast, and small penetration depth. To address thischallenge, our group has previously introduced a transparent nanocrystallineyttria-stabilized-zirconia (nc-YSZ) cranial implant material which implant possesses themechanical strength and biocompatibility that are prerequisites for a clinically-viablepermanent cranial implant for patients.

This implant possesses the mechanical strength and biocompatibility that areprerequisites for a clinically-viable permanent cranial implant for patients. A potentialbenefit of this optical window is an improvement of light-based therapeutic techniquesthat rely on sufficient light penetration to a target embedded in tissue such asphotobiomodulation, photodynamic therapy, and optogenetics. Another application of thisoptical window is noninvasive visualization of brain blood vessels, hematomas, and smallpathologic structures (including cancerous growth) with high resolution. This isimportant for diagnosis and treatment of many diseases such as tumors of the brain,vascular pathologies, and so forth. In this dissertation, I investigated (1) characteristicsand durability of transparent nc-YSZ implants; (2) feasibility of chronic brain imagingthrough the implant; (3) multimodal imaging across the implant to generate anarteriovenous vascular map; (4) through-scalp VIS-NIR light delivery and microvascularimaging.

Cavitation is a micron-scale process in which short-lived vapor bubbles form and collapse, giving way to intense, localized effects in the surrounding liquid. The phenomenon of cavitation was first noted to cause undesired damage on nautical equipment via erosion from strong emitted shockwaves as well as microjets that form when cavitation collapses near solid boundaries. More recently, cavitation studies have sought to exploit this process as a multitool for applications such as photothermal therapy, microfluidic pumping, and surface cleaning among other uses. However, several cavitation mechanisms continue to contribute to mechanical failure via surface erosion, thermal damage and collateral impacts expanding beyond the intended targeted regions. While fluid and optical properties may influence the formation threshold of cavitation, the physical surroundings such as interfaces and boundaries largely determine the collapse dynamics which is the primary effect utilized for said applications. An overwhelming number of investigated applications use a single cavitation event near a static structure to initiate jet formation, but this limits the available control to the stand-off distance defined by the ratio between the bubble distance to the wall and the maximum bubble radius. Two studies are presented which demonstrate how laser-induced cavitation impact can be controlled effectively or avoided entirely. First, a detailed study investigates how varying the temporal and spatial separation of two interacting cavitation bubbles can affect the resulting jet speed. The double bubble system is found to generate fast jets capable of perforating soft materials with a minimized surface damage compared to a single bubble impact. A novel experimental proof of concept is reported to use this system for needless injection without the need for clean room fabrication of micronozzles as is required by previous works. A second experimental study reports the use of simple casted gas entrapping microstructures to influence the migration of cavitation collapse. The air pockets act as compressible interfaces and expand during the primary cavitation event and repel the bubble away from the surface. This process can be employed as a method to mitigate cavitation erosion or enhance agitation in low Reynolds number flows in an on-demand and localized manner. The final section briefly explores characterization of thermocavitation, a second form of cavitation formation via energy deposition by continuous wave irradiation.

Windows to the Brain (WttB) platform can improve patient care by enabling the delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically-recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for facilitating diagnosis and treatment of a wide variety of brain pathologies and neurological disorders including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases.

We have developed a novel transparent nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant (“window”) that can be used for laser and optogenetic therapy. Since light can be easily transmitted through it without undergoing excessive attenuation—the main obstacle for optical therapy and diagnostics of deep targets—this material was selected as an excellent candidate. To evaluate the potential of nc-YSZ cranial implants for optical therapy and imaging of the brain, we (1) demonstrated increased photon density in the brain of mice qualitatively and quantitatively with WttB in comparison to native skull using optical coherence tomography; (2) developed drug delivery techniques including micro-needling and application of pneumatic pressure to improve the drug perfusion of optical clearing agents to ex-vivo porcine skin; (3) confirmed the in vivo biocompatibility of nc-YSZ using a dorsal window chamber model; (4) evaluated the bactericidal effect of lasers by imaging of bioluminescent E. coli under WttB.

Demand for increased heat fluxes in high-power thermal management applications drives research into improved cooling techniques. Liquid and two-phase cooling methods provide cost-effective and potent means of heat extraction. Sprays of atomized liquid, in particular, deliver very high heat flux due to large cooling surface area, rapid evaporation, and continuous delivery of fresh cold liquid to the target. Sprays are difficult to model and study due to the inherent complexity of highly dynamic two-phase flows and the wide range of factors which influence the cooling effects. A detailed study of the impact of liquid droplets, alone and in sequential trains, onto a variety of impact surfaces is presented, with examination of the fluid properties, impact characteristics, and environmental conditions that govern the dynamics of the liquid after im-pact and the overall cooling effect. The interaction of successive droplets in a train is found to dramatically influence heat transfer, depending on the frequency of impacts.

As a spray is used to cool a target surface, a liquid film will often develop. A thermal bound-ary layer develops within the liquid film, reducing the effective cooling rate by isolating hot liq-uid near the surface. Agitation will minimize the thermal boundary layer, restoring the heat flux. Optical cavitation presents a unique method of non-intrusively breaking down the thermal boundary layer. By inducing cavitation within the layer, near the surface, the growth and collapse of the bubble will draw cool liquid from outside the boundary layer and deposit it near the surface. To achieve this effect, the optical and fluid conditions that contribute to cavitation are explored, in particular looking at the growth and collapse dynamics and the sequences of bub-bles resulting from irradiation by a continuous wave laser. Novel experimental observations of asymmetric collapse phenomena are reported, and among the first measurements of cavitation frequency for continuous wave laser irradiation are reported.

Pulsed laser processing is a technique to induce optical and structural changes in materials, such as oxide line and ring structures, when metallic samples are irradiated with high intensity lasers in oxygen and mixed atmospheres. The oxides, which can have very different electrical and optical properties, are gaining momentum in novel technical applications such as electrochromic devices, electrodes in microbatteries, gas sensors, and catalysts, among others. When a femtosecond laser irradiates a transition metal thin film, the thin film reacts with the gaseous species, producing different chemical and structural phases, depending on the localized atmosphere and laser irradiance characteristics, e.g. the fluence, polarization, and duration of exposure. Here we present a processing study of femtosecond (fs) laser processing on molybdenum (Mo) thin films. The laser used is an Ytterbium-doped oscillator in the near infrared (1028 nm), ultrafast (230 fs pulse width), and with a high repetition rate (54 MHz). Irradiations are done under ambient air as well as pure oxygen gas conditions to document how the oxidations occur under varying environments. Our results indicate that the high heating rates and electric-fields associated with laser processing allow the production of different phases and that a detailed fine-tuning of different variables can manipulate the oxidation of the samples. Raman spectroscopy, scanning electron microscopy, and atomic force microscopy are used in characterizing the oxidation of the different phases for the different irradiation parameters chosen. Our results indicate a high correlation between the increasing of the alpha-MoO3 formation area with the increasing of gas concentration and pressure.

Spray atomization and droplet dynamics are research topics that have existed for many decades. Their prevalence in manufacturing, energy generation and other practical applications is undeniable, though researchers have often overlooked the importance of understanding the physics of atomization or droplet impact characteristics in the ongoing effort to improve efficiency. In this talk, I will address the atomization of thermodynamically unstable "flashing" sprays and the splashing mechanisms of single droplets impinging on flat, smooth surfaces. The related heat transfer phenomena for cooling applications are also addressed. These topics are motivated by efforts to improve the thermal protection provided by cryogenic spray cooling in laser dermatological procedures, increasing the throughput of the spray production of nano and micro-scale particulates used as dyes and catalysts, and in modeling of the release and dispersion of flammable or hazardous chemicals through large-scale collisions with storage containers.

Through the use of high-speed video imaging, phase Doppler interferometric measurements and numerical modeling of the two-phase flow taking place within spray nozzles, a detailed picture of the processes involved in flash atomization are attained. Results reveal that flashing fluid jets under low superheats undergo many dynamic processes leading to eventual droplet formation, including the nucleation of vapor bubbles within the nozzle interior and their subsequent expansion and explosion. At high superheats, a stable "flare flashing" regime is attained resulting in very fine atomization. These insights may lead to improved nozzle designs to better control the atomization process.

High-speed imaging of droplet impacts also reveals new insights into the mechanisms of splashing. The surrounding ambient air pressure, fluid viscosity, and fluid-surface affinity are found to profoundly influence the initiation and characteristics of splashing. A new analytical model explaining the mechanisms of crown splashing is developed along with correlations predicting the threshold of splashing.

The cooling behavior of an impacting single droplet and train of droplets on a heated substrate (T = 60oC) for various pool conditions is explored. The effects of several variables such as impact velocity, droplet diameter, pool depth, and impact frequency on the cooling dynamics are explored. Fast response resistance temperature detectors (RTD) embedded at the surface of the aluminum substrate allows for temperature measurement below the droplet impact. A high speed video camera recorded the dynamics of cavity formation within the pool upon the impact of falling droplets. Droplet diameter and impact velocity were also measured using the high speed video. The instantaneous heat flux and net heat extraction at the surface were obtained using a finite-time step integration of Duhamel’s theorem.

Heat transfer appears to be maximized within an intermediate pool depth for the single droplet impacts. At this intermediate pool depth, the impact crater almost reached the pool bottom, suggesting that cold droplet fluid made contact with the substrate, maximizing the cooling effect. Outside this intermediate pool depth, the heat flux appears to decrease. At the lower pool depth, cold droplet fluid is pushed away from the measurement point once the cavity reaches the substrate. Above the optimal pool depth, the droplet does not enter the crater formed by the previous droplet, preventing it from reaching the substrate. For a train of droplets, there seems to be several regions where the heat flux is further reduced due to collision of droplet with emerging jet. It was also found that dry surface provides better heat flux with the heat flux decreasing with formation of thin film. In regards to multiple RTDs, the farther the RTD is from the point of impact, the lower the cooling effects.

A variety of medical conditions (e.g., traumatic brain injury, cerebral edema, stroke, brain tumors) necessitate surgical craniectomy to access the brain, followed by the placement of a cranial implant to replace the excised cranial bone. Cranial implants provide mechanical protection to the brain, and are made from a variety of materials ranging from polymers to metals and ceramics. Despite this variety of implant options, all current cranial implants for patient use lack optical transparency which could allow for brain imaging or therapy without additional open-skull procedures. The “Window to the Brain” is a novel transparent cranial implant made from a tough, biocompatible ceramic called nanocrystalline-Yttria Stabilized Zirconia. Preliminary studies have shown that this material allows for acute brain imaging in vivo, but its suitability for chronic use has not been established. In this dissertation, I investigated (1) the stability of the optical access provided by the window for chronic brain imaging in vivo; (2) functional and structural imaging techniques across the window; (3) laser bacterial antifouling strategies for use with the window; (4) characterization of the window’s optical properties which impact imaging. This work provides answers to some of the key remaining questions regarding the feasibility of a transparent cranial implant for chronic structural and functional brain imaging based on nc-YSZ.