Investigation of Microplasma Generation in Dense Medium

This dissertation presents the experimental studies of low energy microplasma discharges in liquid and the model studies of microdischarge-generated microbubbles in liquid. The main focus is to determine the properties of the microbubble and relate them to the initiation and dynamics of the observed microplasma. Microplasma in liquid began to draw researchers’ attention in recent decades because of its low energy input, micron scale size and nanosecond scale duration. The understanding of plasma discharges in gases has been well established; however, the mechanism of plasma initiation in liquid is still unclear. Several theories were proposed to provide different explanations of this mechanism, but none of them have been proven exclusively correct. Results here show that the generation of a microplasma needs higher energy than the generation of a microbubble from the same discharges. This supports the theory that during the microplasma initiation a lower density gaseous site is generated before the microplasma and the microplasma exists inside a microbubble. The typical form of a plasma and bubbles in liquid reported in literature are branch-like structures. Here we report spherical microplasma and microbubble afforded by relatively lower energy input, and it was found that for branched bubbles increasing the ambient pressure was able to reduce the microbubble size and eliminate its branches. The dynamics of the spherical bubbles could be modeled with a customized Rayleigh-Plesset model considering both condensable and incondensable gases in the bubble, the initial neutral temperature and neutral pressure were estimated to be as high as 550 K and 1.2 GPa

Xylem surfactants introduce a new element to the cohesion-tension theory

Vascular plants transport water under negative pressure without constantly creating gas bubbles that would disable their hydraulic systems. Attempts to replicate this feat in artificial systems almost invariably result in bubble formation, except under highly controlled conditions with pure water and only hydrophilic surfaces present. In theory, conditions in the xylem should favor bubble nucleation even more: there are millions of conduits with at least some hydrophobic surfaces, and xylem sap is saturated or sometimes supersaturated with atmospheric gas and may contain surface-active molecules that can lower surface tension. So how do plants transport water under negative pressure? Here, we show that angiosperm xylem contains abundant hydrophobic surfaces as well as insoluble lipid surfactants, including phospholipids, and proteins, a composition similar to pulmonary surfactants. Lipid surfactants were found in xylem sap and as nanoparticles under transmission electron microscopy in pores of intervessel pit membranes and deposited on vessel wall surfaces. Nanoparticles observed in xylem sap via nanoparticle-tracking analysis included surfactant-coated nanobubbles when examined by freeze-fracture electron microscopy. Based on their fracture behavior, this technique is able to distinguish between dense-core particles, liquid-filled, bilayer-coated vesicles/liposomes, and gas-filled bubbles. Xylem surfactants showed strong surface activity that reduces surface tension to low values when concentrated as they are in pit membrane pores. We hypothesize that xylem surfactants support water transport under negative pressure as explained by the cohesion-tension theory by coating hydrophobic surfaces and nanobubbles, thereby keeping the latter below the critical size at which bubbles would expand to form embolisms

Glassy Materials Based Microdevices

Microtechnology has changed our world since the last century, when silicon microelectronics revolutionized sensor, control and communication areas, with applications extending from domotics to automotive, and from security to biomedicine. The present century, however, is also seeing an accelerating pace of innovation in glassy materials; as an example, glass-ceramics, which successfully combine the properties of an amorphous matrix with those of micro- or nano-crystals, offer a very high flexibility of design to chemists, physicists and engineers, who can conceive and implement advanced microdevices. In a very similar way, the synthesis of glassy polymers in a very wide range of chemical structures offers unprecedented potential of applications. The contemporary availability of microfabrication technologies, such as direct laser writing or 3D printing, which add to the most common processes (deposition, lithography and etching), facilitates the development of novel or advanced microdevices based on glassy materials. Biochemical and biomedical sensors, especially with the lab-on-a-chip target, are one of the most evident proofs of the success of this material platform. Other applications have also emerged in environment, food, and chemical industries. The present Special Issue of Micromachines aims at reviewing the current state-of-the-art and presenting perspectives of further development. Contributions related to the technologies, glassy materials, design and fabrication processes, characterization, and, eventually, applications are welcome

Contrast-Enhanced Ultrasound for the Assessment of Response to Therapy

Accurate assessment of cancer response to therapy is important for effective treatment outcome and limiting unnecessary therapeutics. The clinical gold standard for evaluating response to therapy consists of tracking changes in volume, which works well for cytotoxic treatments such and radio or chemo therapies, which directly induce cancer cell death. However, tumor volume is ineffective for tracking response to treatments such as antiangiogenic therapies, which target the formation of new blood vessels, and often lags behind the real effect of the drugs. Studies have shown that techniques such as dynamic contrast-enhanced magnetic resonance imaging, computed tomography, and positron emission tomography perform better at predicting and assessing response to therapy than changes in volume. However, these imaging modalities are expensive, cumbersome, expose patients to ionizing radiation, and use contrast agents that can often be harmful to patients. Contrast-enhanced ultrasound (CEUS) is an imaging modality that is inexpensive, real-time, and uses microbubble contrast agents that are safe and can be used to obtain quantitative measurements of blood perfusion and levels of endothelial biomarker expression. Moreover, CEUS has been shown to assess response to therapy more accurately than tumor volume in rodent tumor models. The first hypothesis of this dissertation is that that CEUS can evaluate and track response to therapies more accurately than changes in tumor volume. The results show that CEUS can assess response to therapies that are disruptive to tumor vessel formation earlier than tumor volume. Specifically, the techniques discussed here include perfusion imaging, ultrasound molecular imaging of angiogenesis biomarkers, and acoustic angiography, which can provide metrics about microvessel morphology and density. The second hypothesis is that CEUS can be performed using phase-change contrast agents (PCCAs). PCCAs have better circulation times than conventional microbubbles and can be small enough to escape the vasculature for extravascular diagnostic imaging, and thus, may provide multiple advantages for the assessment of response to therapy. The development of techniques to perform perfusion and molecular imaging using PCCAs is described. The results show that PCCAs can be used for intravascular molecular imaging, but major modifications to the formulation are required to obtain meaningful measurements of perfusion.Doctor of Philosoph

Synthesis and characterization of acoustic-sensitive perfluorinated microvesicles and nanocapsules for theranostic application

Orientador : Dr. Rilton Alves de FreitasCoorientador : Dr. Nicolas TsapisCoorientador : Dr. Roberto PontaroloTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas. Defesa: Curitiba, 15/02/2017Inclui referências : f. 39-45;64-67;92-94;147-153Área de concentração: Insumos, medicamentos e correlatosResumo: Compostos fluorados são intensamente utilizados como agentes de contraste ultrassônicos (ACU) por facilitar o diagnóstico de diversas doenças via geração de imagens em temporeal. Todos os ACU disponíveis comercialmente são microbolhas constituídas por um núcleo gasoso fluorado que é estabilizado por finas camadas de fosfolipídios, proteínas ou surfactantes. Infelizmente, a aplicação teranóstica (i.e. habilidade terapêutica e diagnóstica) de tais compostos é severamente limitada devido a (i) baixa estabilidade do componente fluorado, (ii) tamanho inerente à escala micrométrica, (iii) ausência de compartimentos efetivos para acumulação de fármacos. A fim de superar estas limitações, nós propomos duas estratégias distintas para aumentar a persistência do núcleo fluorado e, simultaneamente, prover interfaces funcionais para encapsulação de fármacos. A primeira abordagem envolve a intercalação de quitosana com fosfolipídios (DSPC) a fim de aumentar a estabilidade de microvesículas contendo o gás fluorado decafluorobutano (C4F10). A afinidade entre DSPC e quitosana foi inicialmente verificado através de técnicas sensíveis de superfície e microscopia de fluorescência. Análises de ressonância magnética nuclear de 19F (19F-RMN) e imagens ultrassônicas in vitro mostraram sinais intensos do componente gasoso após 48h, o dobro comparado com amostras sem quitosana. Desta forma, o revestimento com quitosana foi capaz de prolongar a estabilidade de microvesículas e consiste em uma plataforma adequada pra acumulação de fármacos. A camada interfacial formada por DSPA-quitosana pode, portanto, incrementar o potencial teranóstico de microvesículas. Entretanto, o uso de gás fluorado impôs uma importante restrição à estabilização de vesículas na escala nanométrica. Assim, a segunda estratégia estudada neste trabalho foi focada no desenvolvimento de agentes com habilidade teranóstica na nanoescala. Para tal, buscou-se encapsular um líquido fluorado, o perfluorohexano (PFH; C6F14), dentro um rígida cápsula polimérica de polilactídio (PLA). A fim de melhorar a interação entre polímeros biodegradáveis para com perfluorocarbonos, nós sintetizamos polímeros de PLA contendo grupamentos terminais fluorados com cinco diferentes comprimentos (desde C3F7 até C13F27) via polimerização por abertura de anel do D,L-lactídio. Resultados de relaxação 19F spin-spin mostraram a presença de interações entre os componentes fluorados e, subsequentemente, todos os polímeros foram formulados em nanocápsulas (NC) esféricas com um diâmetro de 150 nm como verificado por microscopia eletrônica de transmissão. Ensaios de 19F-RMN mostraram que as NC preparadas com polímeros fluorados dobraram a eficiência de encapsulação de PFH comparado com derivativos não fluorados. Estas NC aumentaram a ecogenicidade em 10 vezes para modalidades de imagens ultrassonoras fundamental e harmônica. Além disso, a vaporização acústica do PFH foi realizada por ultrassom focalizado, através da observação de cápsulas fragmentadas ou despedaçadas em diversas amostras. Os efeitos provenientes dos grupamentos fluorados foram explorados via avaliação da morfologia de microcápsulas (MC) produzidas com os polímeros. Finalmente, tanto as NC como as MC apresentam um interessante potencial teranóstico, sendo capazes de efetuar diagnóstico assistido por ultrassom e são potencialmente hábeis em liberar fármacos quando irradiados por altas pressões acústicas.Abstract: Fluorinated materials are intensively used as ultrasound contrast agents (UCA) to facilitate the diagnosis of many diseases by real-time imaging. All the commercially available UCAs are microbubbles constituted by a perfluorinated gaseous-core stabilized by a monolayer of phospholipids, proteins or surfactants. Unfortunately, the theranostic application (i.e. therapeutic and diagnostic ability) of such materials are severely limited by the (i) poor stability of the fluorinated component, (ii) inherent micrometer size range and (iii) lack of effective compartments for drug accumulation. To overcome these limitations, we proposed two different strategies to improve the persistence of the fluorinated core and simultaneously provide functional interfaces for drug encapsulation. The first approach involves intercalating chitosan with phospholipids (DSPC) to increase the stability of microvesicles containing the fluorinated gas decafluorobutane (C4F10). The affinity of DSPC and chitosan was disclosed by surface sensitive techniques and fluorescence microscopy. 19F nuclear magnetic resonance (19F-NMR) and in vitro ultrasound of chitosancoated microvesicles exhibited intense signals of the gaseous-component after 48 h, twice as long compared to plain samples. Altogether, chitosan increased the stability of microvesicles and is a suitable platform for drug accumulation. As a result, the chitosanphospholipid shell may enhance the theranostic potential of related microvesicles. However, the use of a fluorinated gas-core imposed an important restriction to stabilize submicrometric vesicles. Therefore, the second strategy was focused in developing a theranostic agent at the nanoscale by entrapping a liquid fluorinated core of perfluorohexane (PFH; C6F14) into a rigid polymeric shell of polylactide (PLA). To enhance the interaction of biodegradable polymers with perfluorocarbons, we synthesized PLA polymers containing five distinct lengths of fluorinated end-groups (from C3F7 until C13F27) by ring-opening polymerization of D,L-lactide. A greater extent of fluorous interactions was indicated by 19F spin-spin relaxation time and, subsequently, all the block copolymers were formulated into spherical nanocapsules (NC) with average diameter of 150 nm as verified by transmission electron microscopy. 19F-NMR showed that NC produced with fluorinated polymers increased two-fold the encapsulation efficiency of PFH compared with non-fluorinated derivatives. As a result, the NC echogenicity increased 10-fold for both fundamental and harmonic ultrasound imaging modalities. In addition, acoustic drop vaporization of PFH was successfully attained by focused ultrasound as observed by fragmented or disrupted morphologies in many samples. Effects of the fluorinated end-groups were further explored by a morphological evaluation of microcapsules (MC) produced with the polymers. Finally, both NC and MC present an interesting theranostic potential, being able to perform ultrasound-assisted diagnosis and potentially release drug contents when irradiated by high acoustic pressures.Résumé: Les composés fluorés sont très utilisés dans les agents de contraste ultrasonore (ACU) pour faciliter le diagnostic de nombreuses maladies par imagerie en temps réel. Tous les ACU commerciaux sont des microbulles de gaz perfluoré stabilisé par une monocouche de phospholipides, protéines ou tensioactifs. Cependant, l'application théranostique (de la contraction de thérapeutique et de diagnostic) de ces matériaux est sévèrement limitée par (i) la faible stabilité du composé fluoré, (ii) leur taille micrométrique et (iii) le manque de compartiments efficaces pour l'encapsulation d'un principe actif. Nous avons proposé deux stratégies différentes pour améliorer la stabilité du coeur fluoré et fournir simultanément des interfaces fonctionnelles pour l'encapsulation d'un principe actif. La première approche a consisté à intercaler le chitosane avec des phospholipides (DSPC) pour augmenter la stabilité de microvésicules contenant du gaz fluoré décafluorobutane (C4F10). L'affinité du DSPC et du chitosane a été révélée par des techniques de caractérisation de surface et par microscopie à fluorescence. Les microvésicules contenant du chitosane ont présenté des signaux intenses de la composante gazeuse en résonance magnétique nucléaire du fluor (RMN 19F) et en échographie in vitro après 48 h, deux fois plus longtemps que les échantillons sans chitosane. Le chitosane permet ainsi d'augmenter la stabilité des microvésicules et constitue une plateforme appropriée pour l'encapsulation de médicaments. La coque de chitosane-phospholipide pourrait donc améliorer le potentiel théranostique de ces microvésicules. Cependant, l'utilisation d'un coeur gazeux a rendu la stabilisation de vésicules submicrométriques difficile. Par conséquent, la deuxième stratégie s'est focalisée sur le développement d'un agent théranostique à l'échelle nanométrique en piégeant un coeur fluoré liquide de perfluorohexane (PFH; C6F14) dans une enveloppe polymère rigide de polylactide (PLA). Pour améliorer l'interaction des polymères biodégradables avec les perfluorocarbones, nous avons synthétisé des polymères PLA contenant cinq longueurs différentes de groupes terminaux fluorés (de C3F7 à C13F27) par polymérisation par ouverture de cycle du D,L-lactide. Les mesures de temps de relaxation spin-spin 19F ont démontré la présence d'interactions fluorophiles intenses entre les chaînons fluorés et le PFH. Les polymères ont ensuite été formulés en nanocapsules (NCs) sphériques de 150 nm de diamètre, comme vérifié par microscopie électronique en transmission. La RMN 19F a montré que l'efficacité d'encapsulation du PFH dans les capsules est doublée grâce à l'utilisation des polymères fluorés comparé aux dérivés non fluorés. Par conséquent, la réponse acoustique des NCs a été multipliée par dix avec les deux modes d'imagerie fondamentale et harmonique. En outre, l'utilisation d'ultrasons focalisés a permis la vaporisation acoustique de gouttelettes de PFH, confirmée par l'observation de morphologies fragmentées ou perturbées dans de nombreux échantillons. Les effets des groupes terminaux fluorés ont été davantage explorés par une évaluation morphologique des microcapsules (MCs) produites avec les polymères. Finalement, les NCs et MCs présentent un potentiel théranostique intéressant, puisqu'elles permettent d'effectuer un diagnostic assisté par ultrasons et de libérer potentiellement un principe actif lorsqu'elles sont soumises à des pressions acoustiques élevées

Cavitation detection and characterization for small scale nozzles and fuel injectors

Cavitation occurs when the liquid pressure drops below a critical threshold causing rapid bubble growth and violent collapse. The presence of cavitation inside fuel injector nozzles has been linked not only to damage associated with cavity collapse near the walls but has been found to enhanced fuel spray atomization. Proper fuel atomization increases engine performance while reducing fuel emissions. The majority of laboratory experimental studies found in the literature are highly reliant on optical access to the working fuel, requiring transparent material, specific geometry, and relatively slow flows to enable even minimally time-resolved optical images with ex-pensive high-speed cameras. While such studies are appropriate for gaining intuition into the types and spatial locations of cavitation phenomena possible in nozzle flows at high Re, there is a need for techniques which can not only be reliably employed at idealized laboratory conditions, but also can be deployed to study real steel fuel injectors while also yielding quantitative information. The objective of this work is to develop alternative non-intrusive acoustic and vibration methods to experimentally study cavitation phenomena in fuel injectors. First, a study was conducted utilizing a combination of optical and acoustic techniques to determine onset and activity of cavitation in small scaled nozzles. Experiments are conducted with acrylic nozzles of various geometry. Unfocused single element transducers are used for acoustic sensing, while digital imaging is used for optical study. Cavitation onset thresholds and development are studied as functions of flow rate and nozzle geometry. Substantial agreement between optical and acoustic methods was observed for both onset and development regimes of cavitation in nozzles. A second study was conducted utilizing laser Doppler vibrometry to measure the vibration response of a commercial fuel injector. An attempt was made to use injector flexural oscillations to determine the void fraction for different fuel injector conditions. Experiments were performed at the Oak Ridge National Laboratory on a commercial grade field injector using cyclopentane fuel with varying injection pressure and fuel temperature as control parameters. Frequency shift and mode shape are measured and correlated with cavitation-inducing control parameters. Analysis suggests that observed frequency shifts may allow inference of dynamic void fraction during cavitation in nozzles.2020-07-02T00:00:00

A FLOW-THROUGH ACOUSTIC WAVEGUIDE FOR TWO-PHASE BUBBLY FLOW VOID FRACTION MEASUREMENT

In the Spallation Neutron Source (SNS) facility at Oak Ridge National Laboratory (ORNL), the deposition of a high-energy proton beam into the liquid mercury target forms bubbles whose asymmetric collapse cause Cavitation Damage Erosion (CDE) to the container walls, thereby reducing its usable lifetime. One proposed solution for mitigation of this damage is to inject a population of microbubbles into the mercury, yielding a compliant and attenuative medium that will reduce the resulting cavitation damage. This potential solution presents the task of creating a diagnostic tool to monitor bubble population in the mercury flow in order to correlate void fraction and damage. Details of an acoustic waveguide for the eventual measurement of two-phase mercury-helium flow void fraction are discussed. The assembly’s waveguide is a vertically oriented stainless steel cylinder with 5.08cm ID, 1.27cm wall thickness and 40cm length. For water experiments, a 2.54cm thick stainless steel plate at the bottom supports the fluid, provides an acoustically rigid boundary condition, and is the mounting point for a hydrophone. A port near the bottom is the inlet for the fluid of interest. A spillover reservoir welded to the upper portion of the main tube allows for a flow-through design, yielding a pressure release top boundary condition for the waveguide. A cover on the reservoir supports an electrodynamic shaker that is driven by linear frequency sweeps to excite the tube. The hydrophone captures the frequency response of the waveguide. The sound speed of the flowing medium is calculated, assuming a linear dependence of axial mode number on modal frequency (plane wave). Assuming that the medium has an effective-mixture sound speed, and that it contains bubbles which are much smaller than the resonance radii at the highest frequency of interest (Wood’s limit), the void fraction of the flow is calculated. Results for water and bubbly water of varying void fraction are presented, and serve to demonstrate the accuracy and precision of the apparatus.Supported by the ORNL Spallation Neutron Source, which is managed by UT- Battelle, LLC, under contract DE-AC05-00OR22725 for the U.S. Department of Energy

Numerical and experimental analysis on microbubble generation and multiphase mixing in novel microfluidic devices

In this study, a novel K-junction microfluidic junction and a conventional cross-junction were investigated numerically and experimentally for microbubble generation and multiple fluids mixing. In the K-junction, liquid solutions were injected into the junction via three liquid inlet channels, along with inert nitrogen gas supplied via the gas inlet channel, to periodically generate microbubbles in a controlled manner at the outlet channel. Numerical simulations based on Finite Volume method and Volume of Fluid (VOF) technique and experiments of both the K-junction and the cross-junction were conducted. The effect of parameters such as contact angle, surface tension, viscosity, gas pressure and gas-liquid flow ratios on the microbubble size distribution was investigated. The process of microbubble generation, obtained through high speed camera imaging and the numerical simulation, has shown good agreement in both junctions as well as the influence of viscosity and gas-liquid flow ratios for the K-junction and cross-junction. It was indicated that parameters like solution viscosities, gas-to-liquid flow ratios, gas inlet pressure, and their combination have a significant influence on the microbubble diameter, which was found to be in the range of 70-240 µm when using micro capillaries of 100 µm inner diameter. The multiple fluids mixing study was investigated by using two or three different polymer solutions for the cross-junction and the K-junction respectively in simulations and experiments. It can be seen that the mixing process obtained from simulations agrees well with experimental results and chaotic mixing was found in the mixing area of the K-junction, with higher mixing efficiency than the cross junction. Fluorescent images of microbubbles generated by using polymer solutions with dyes inside have shown the devices’ potential of encapsulating fluorescent dyes and polymers on the shell of bubbles and could be adopted as a method to encapsulate active pharmaceutical ingredients for potential applications in drug delivery