We focus on studying laser-induced cavitation under widely different physical conditions, from superheated jets to superfluid liquid helium. We use ultra high-speed video imaging to track cavitation bubble dynamics at frame-rates of up to 7 million frames-per-second. Cavitation is induced by focusing a 532 nm pulsed Nd-YAG laser at a spot with a minimum spot size of 150 μm and pulse duration of six ns, which forms high-pressure plasma, leading to a rapidly expanding bubble/void, which subsequently collapses. We mainly study two configurations: (1) laser-induced cavitation in liquid helium inside an optical cryostat and (2) laser-induced cavitation in HCP solid helium. Moreover, we report preliminary results of two promising studies: (3) laser-induced cavitation inside a highly turbulent flow within a square channel and (4) laser-induced break-up inside a cylindrical liquid jet, leading to its atomization. (1) Inside the liquid helium-4, we reach widely different thermodynamic conditions when adjusting the temperature between 1.4 to 5.1 degrees Kelvin. Below the lambda point at T = 2.17 K, the liquid is superfluid, with viscosity appr zero, while above this temperature, regular liquid helium approaches the critical point at ≃ 5.1 K. This greatly changes the cavitation dynamics with different amounts of vapor appearing during cavity growth and collapse, and revealed four regimes of cavitation bubble behavior. We also measure shock velocities and analyze their characteristics. (2) At pressures of roughly 25 atmospheres, superfluid helium (He-II) solidifies. With wavy time-evolving oscillations on its surface when disturbed, the interface between the solid and the superfluid exhibits fascinating behavior with wavy time-evolving oscillations on its surface when disturbed. The interface between liquid and solid can consequently behave similarly to a free surface. Here, we experimentally investigate laser-induced interfacial dynamics at temperatures between 1.2 K and 2 K and at pressures ranging from the melting pressure of approximately 25 atm to a maximum of 39 atm, which covers both the HCP and BCC structure of the solid, using ultra-high-speed imaging at frame rates up to 7 million frames per second. (3) The cavitation inside the turbulent flow; this study aims to investigate the mutual effect of the rapid straining outside the bubble on the coherent vortices within the liquid and the feedback from the modified turbulence on the shape of the vapor cavity, and to include time-resolved particle image velocimetry. (4) The cavitation inside a liquid jet helps break it up into fine spray, which is of interest for injectors in combustion engines.

In the laser-induced cavitation (LIC) technique, a vapor-gas cavity is generated in water, or a soft material by focusing an intense laser pulse into the sample. The high-strain-rate mechanical properties of these samples can be investigated through a real-time size measurement of the expanding cavity bubble. Although this LIC technique has been applied to multiple research fields such as mechanical, biological and medical areas. It is possible to simplify and improve this LIC method by introducing optical-fibers. In this approach, we propose to employ an optical-fiber to deliver the intense laser pulse to an arbitrary position of an optical opaque specimen. At the same time, we also attempt to generate LIC at one end of the optical-fiber. This optical-fiber based LIC is achieved by dip-coating of the laser absorbing film on the fiber end. Thus, the film can absorb the laser pulse and generate LIC within the sample. In this study, the development of the coating material, the introduction of the optical-fiber into the existing LIC system, and the optical-fiber based LIC experiments are performed to characterize high-strain-rate mechanical properties of soft materials. We investigate the coating conditions and verify the consistency of the ablation based on the optimized coating materials. By conducting LIC experiments with gelatin samples, the feasibility of developed LIC method is investigated, LIC events are successfully formed at the fiber end which is inserted into the sample, and the rapid expanding dynamics are imaged with ultrafast stroboscopic microscopy. Using the multiple-exposure images, the expanding speeds and maximum cavity sizes are quantified to provide high-strain-rate characteristics of the soft materials. The inconsistency of the cavitation behavior resulted by the fluctuation of the coating condition and the high power intense laser conducting optical-fiber destruction can be improved by developing new coating method and new protective coating on the fiber end in the future.

This dissertation develops a computational method for simulating laser-induced cavitation and investigates the mechanism behind the formation of non-spherical bubbles induced by long-pulsed lasers. The proposed computational method accounts for the laser emission and absorption, phase transition, and the dynamics and thermodynamics of a two-phase fluid flow. In this new method, the model combines the Navier-Stokes (NS) equations for a compressible inviscid two-phase fluid flow, a new laser radiation equation, and a novel local thermodynamic model of phase transition. The Navier-Stokes equations are solved using the FInite Volume method with Exact two-phase Riemann solvers (FIVER). Following this method, numerical fluxes across phase boundaries are computed by constructing and solving one-dimensional bi-material Riemann problems. The new laser radiation equation is derived by customizing the radiative transfer equation (RTE) using the special properties of laser, including monochromaticity, directionality, high intensity, and a measurable focusing or diverging angle. An embedded boundary finite volume method is developed to solve the laser radiation equation on the same mesh created for the NS equations. The fluid mesh usually does not resolve the boundary and propagation directions of the laser beam, leading to the challenges of imposing the boundary conditions on the laser domain. To overcome this challenge, ghost nodes outside the laser domain are populated by mirroring and interpolation techniques. The existence and uniqueness of the solution are proved for the two-dimensional case, leveraging the special geometry of the laser domain. The method is up to second-order accuracy, which is also proved, and verified using numerical tests. A method of latent heat reservoir is developed to predict the onset of vaporization, which accounts for the accumulation and release of latent heat. In this work, the localized level set method is employed to track the bubble surface. Furthermore, the continuation of phase transition is possible in laser-induced cavitation problems, especially for long-pulsed lasers. A method of local correction and reinitialization is developed to account for continuous phase transitions. Several numerical tests are presented to verify the convergence of these methods. This multiphase laser-fluid coupled computational model is employed to simulate the formation and expansion of bubbles with different shapes induced by different long-pulsed lasers. The simulation results show that the computational method can capture the key phenomena in the laser-induced cavitation problems, including non-spherical bubble expansion, shock waves, and the ``Moses effect''. Additionally, the observed complex non-spherical shapes of vapor bubbles generated by long-pulsed laser reflect some characteristics (e.g., direction, width) of the laser beam. The dissertation also investigates the relation between bubble shapes and laser parameters and explores the transition between two commonly observed shapes -- namely, a rounded pear-like shape and an elongated conical shape -- using the proposed computational model. Two laboratory experiments are simulated, in which Holmium:YAG and Thulium fiber lasers are used respectively to generate bubbles of different shapes. In both cases, the predicted bubble nucleation and morphology agree reasonably well with the experimental observation. The full-field results of laser radiance, temperature, velocity, and pressure are analyzed to explain bubble dynamics and energy transmission. It is found that due to the lasting energy input, the vapor bubble's dynamics is driven not only by advection, but also by the continued vaporization at its surface. Vaporization lasts less than 1 microsecond in the case of the pear-shaped bubble, compared to over 50 microseconds for the elongated bubble. It is thus hypothesized that the bubble's morphology is determined by a competition between the speed of bubble growth due to advection and continuous vaporization. When the speed of advection is higher than that of vaporization, the bubble tends to grow spherically. Otherwise, it elongates along the laser beam direction. To test this hypothesis, the two speeds are defined analytically using a model problem and then estimated for the experiments using simulation results. The results support the hypothesis and also suggest that when the laser's power is fixed, a higher laser absorption coefficient and a narrower beam facilitate bubble elongation. / Doctor of Philosophy / Laser-induced cavitation is a process where laser beams create bubbles in a liquid. This phenomenon is widely applied in research and microfluidic applications for precise control of bubble dynamics. It also naturally occurs in various laser-based processes involving liquid environments. Understanding laser-induced cavitation is important for enhancing the effectiveness and safety of related technologies. However, experimental studies encounter limitations, highlighting the development of numerical methods to advance the understanding of laser-induced cavitation. The laser-induced cavitation can be roughly described as localized boiling through thermal radiation. The detailed physics involves the absorption of laser light by a liquid, the formation of vapor bubbles due to localized heating, and the dynamics of both the bubbles and the surrounding liquid. The first part of the dissertation introduces a new computational method for modeling these phenomena. The dynamics of the two-phase flow are modeled by the Navier-Stokes equations, which are solved using the FInite Volume method with Exact two-phase Riemann solvers (FIVER). The absorption of the laser light is modeled by a new laser radiation equation, which is derived from laser energy conservation and special properties of the laser. An embedded boundary finite volume method is developed to solve this equation on the same mesh created for the NS equations. Additionally, a method of latent heat reservoir is developed to predict the onset of vaporization. In this work, the level set method is employed to track the bubble surface, and a method of local correction and reinitialization is developed to account for possible continuous phase transitions. After developing this new method, several test cases are simulated. The simulation results show that the method can capture the key phenomena in the laser-induced cavitation problems, including the absorption of laser light, non-spherical bubble expansion, and shock waves. When the laser pulse is comparable to or longer than the acoustic time scale (long-pulsed laser), vapor bubbles generated often have complex non-spherical shapes. The bubble shapes reflect some characteristics (e.g., direction, width) of the laser beam. The second part of the dissertation investigates the relation between bubble shapes and laser parameters. Two laboratory experiments are simulated, in which two different lasers are used to generate bubbles of different shapes, namely, a rounded pear-like shape and an elongated conical shape. In both cases, the simulated bubbles exhibit shapes and sizes that reasonably match the experimental results. The simulation results of temperature, pressure, and velocity fields are analyzed to explain bubble dynamics and energy transmission. The analysis shows that the expansion of bubbles induced by long-pulsed lasers is determined not only by advection but also by the continued vaporization at its surface. Vaporization lasts less than $1$ microsecond in the case of the pear-shaped bubble, compared to over $50$ microseconds for the elongated bubble. It is thus hypothesized that the bubble expansion is determined by a competition between the speed of bubble growth due to advection and continuous vaporization. When the speed of advection is higher than that of vaporization, the bubble tends to grow spherically. Otherwise, it elongates along the laser beam direction. To test this hypothesis, the two speeds are defined analytically using a model problem and then estimated for the experiments using simulation results. The results support the hypothesis and also suggest that when the laser's power is fixed, a higher laser absorption coefficient and a narrower beam facilitate bubble elongation.

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<p>Autoinjectors are pen-like devices that typically deliver drug products of 2 mL or less. They shield the needle before and after use, reducing patient anxiety from needle phobia and mitigating the risk of needlestick injuries and accidental contamination. Additionally, automatic delivery ensures more consistent needle penetration depth and injection force than manual injection methods. </p> <p><br></p> <p>To optimize autoinjector design, this thesis presents experimentally validated computational models that describe the processes of needle insertion, drug delivery, and transport of subcutaneously administered therapeutic proteins in the body. A multi-objective optimization framework is also proposed to guide the design of autoinjectors.</p> <p><br></p> <p>This thesis focuses on spring-driven autoinjectors, the most common type of autoinjector. It begins with an overview of the interactions between the spring-driven autoinjector, tissue, and therapeutic proteins. Moving on to Chapter 2, a computational model is presented to accurately predict the kinematics of the syringe barrel and plunger during the needle insertion process.</p> <p><br></p> <p>In Chapter 3, we present a quasi-steady model for the drug delivery process, which considers the rheology of therapeutic proteins. The Carreau model is adopted to describe protein viscosity, and explicit relationships between flow rate and pressure drop in the needle are derived. Furthermore, the applicable regime for the power-law model for protein viscosity is identified.</p> <p><br></p> <p>Chapter 4 quantifies the impact of sloshing and cavitation on therapeutic proteins in the syringe. Additionally, a workflow is presented to integrate available simulation tools to predict the performance of spring-driven autoinjectors. The influence of each design parameter of spring-driven autoinjectors on their performance is also discussed. </p> <p><br></p> <p>The spring-driven autoinjector delivers therapeutic proteins through subcutaneous administration. To gain insights into the transport process of therapeutic proteins, Chapter 5 presents a physiologically-based pharmacokinetic model that has been validated against experimental data for humans and rats. The lymph flow rate significantly affects the bioavailability of therapeutic proteins. This finding highlights the importance of studying the transport of therapeutic proteins in the lymphatic system in future research.</p> <p><br></p> <p>Chapter 6 provides a multi-objective design optimization framework for the spring-driven autoinjector. The computational model is replaced with an accurate deep neural network surrogate to improve the computational efficiency.  Using this surrogate model, we conduct a sensitivity analysis to identify essential design parameters. After that, we perform multi-objective optimization to find promising design candidates.</p> <p><br></p> <p>Chapter 7 presents a model for bubble dynamics in a protein solution. An explicit expression for the bubble dissolution rate is derived, enabling extraction of the interfacial properties of the protein-coated interface from the measured bubble radii. Moreover, analytical solutions for the response of a protein-coated bubble to an imposed acoustic pressure are derived. This work provides insight into protein-coated bubbles, which are used as vehicles to deliver drugs, as active miniature tracers to probe the rheology of soft and biological materials, or as contrast agents to enhance the ultrasound backscatter in ultrasonic imaging.</p> <p><br></p> <p>At last, in Chapter 8, we introduce a model for laser-induced cavitation that considers several key factors, such as liquid compressibility, heat transfer, and non-equilibrium evaporation and condensation. Our model's predictions for the time-course of bubble radii have been validated with experimental data. Moreover, our model reveals that the reduction of the bubble's oscillation amplitude is primarily due to a decrease in the number of vapor molecules inside the bubble, highlighting the crucial role of phase change in laser-induced cavitation bubbles.</p> <p><br></p> <p>The developed computational models and framework provide crucial insights into the development of spring-driven autoinjectors and cavitation bubbles. These studies can also enhance the efficacy and safety of the delivery of therapeutic proteins, ultimately improving patient outcomes.</p>

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