Principles of microfluidic actuation by modulation of surface stresses

Development and optimization of multifunctional devices for fluidic manipulation of films, drops, and bubbles require detailed understanding of interfacial phenomena and microhydrodynamic flows. Systems are distinguished by a large surface to volume ratio and flow at small Reynolds, capillary, and Bond numbers are strongly influenced by boundary effects and therefore amenable to control by a variety of surface treatments and surface forces. We review the principles underlying common techniques for actuation of droplets and films on homogeneous, chemically patterned, and topologically textured surfaces by modulation of normal or shear stresses

Interfacial Properties Modulate Water Entry Dynamics For Spherical Projectiles

Rigid bodies impacting liquid pools incite splashing and air-entraining cavities that depend on impactor shape, entry speed, surface texture, and free surface conditions. In this body of work, we investigate the influence of interfacial properties on water entry dynamics for free-falling spherical projectiles. Our investigations translate to everyday fluid-structure interactions that are complex and generally conclude beyond the temporal acuity of the naked eye. High-speed videography between 1000 -- 3200 fps is used to digitize the water entry process and measure salient splash features under different initial conditions. We assess splashes arising from the impacts of free-falling hydrophilic spheres with thin, non-woven fabrics resting atop a liquid bath to ascertain alterations to splash crowns, air-cavities, and Worthington jets, when compared to impacts onto an unaltered, quiescent free surface. The inclusion of fabrics promotes air-entrainment for hydrophilic spheres, well below the impact-velocity threshold of 8 m/s otherwise required for cavity formation. Meager amounts of fabric amplifies splash metrics while providing the drag-reducing benefits of flow separation. Punctured fabrics suppress splash crowns normally seen for cavity-producing impacts while intact fabrics generate deeper cavities, higher Worthington jets, and more pronounced splash crowns. We proceed to modulate super-surface splash features, and alter sphere trajectories with impactor surface texture. When fluid flowing around the impactor encounters the hydrophobic surface, flow separation is tripped and air entrained across all entry speeds and impact orientations. We conclude this work by replacing solid impactors with liquid drops impacting passive supersurface particles, an experimental system inspired by the survival of water striders during rainfall. We show the stride\u27\u27s locomotive response, low density, resistance to wetting when briefly submerged, and the ability to regain super-surface rest state, render it impervious to impacting water drops. The compendium of new observations from our work augur well for water entry applications where the coupled dynamics of flow separation and passive trajectory control are desirable

Wetting of Bio-Inspired Complexly-Shaped Fibers and Channels

This Dissertation is centered on studying the wetting of complexly-shaped fibers and channels which is inspired by the Lepidopteran proboscis. From materials science and engineering standpoint, the Lepidopteran proboscis is a multifunctional microfluidic device. The unique materials organization, morphology, structure, and surface properties of the proboscis allows the Lepidopterans to feed on various food sources from highly viscous to very thin liquids while keeping its surface clean. Thus, the study on the proboscis wetting phenomena has drawn great interests of materials scientists and engineers. The shape of the Lepidopteran proboscis has a very special design combining complexly-shaped fibers and channels. However, it remains unknown how this unique shape benefits the multiple functions of the proboscis. In this Dissertation, we investigate the effect of shape on the wetting properties of proboscis by separately studying the wetting of complexly-shaped fibers and channels, and then, applying the gained knowledge to explain various wetting phenomena observed on the Lepidopteran proboscis. In Chapter I, the definition of wetting is introduced and the fundamental studies on wetting of fibers and channels are reviewed. Then the structure and function of Lepidopteran proboscis is introduced, and the motivation for conducting the research in this Dissertation is explained. In Chapter II, several wetting phenomena on the ribbon-like fiber, e.g. the morphological transitions of droplet configurations, stability of coating films, capillary rise of menisci on ribbon-like fiber, and wetting of the ribbon rail are studied experimentally and theoretically. This study sets up the foundation for investigating the wetting phenomena of other complexly-shaped fibers and channels. The developed experimental and theoretical methods are actively used throughout this Dissertation. In Chapter III, the instability of a thin coating film on the internal and external walls of a straight hollow elliptical fiber is studied, and the mechanisms of drop formation from the coating films and the droplet morphology is briefly discussed. Then the study is expanded to the ring made of a curved elliptical tube to cover a broad range of wetting phenomena associated with such complexly-shaped fibers by discussing the effect of ring radius of curvature and the cross-sectional ellipticity. In Chapter IV, a new method for studying the wetting of complexly-shaped channels is developed based on the Princen theory, and examined with the V-shaped channel. Then, the wetting/dewetting of C-shaped channel is systematically studied both experimentally and theoretically. In Chapter V, several wetting phenomena associated with the Lepidopteran proboscises, e.g. the food uptake from a pool of liquid or from a limited volume of liquid, the stability of liquid films deposited on proboscis after dipping it into a nectar source, and self-assembly of proboscis after the insect emerges from the pupa, are discussed based on the study of wetting of complexly-shaped fibers and channels. All the results are summarized in Chapter VI

STRENGTHEN OF DPNS FEATURES FOR THERANOSTIC APPLICATIONS AND MECHANICAL-CONTROL OF CHEMOTHERAPEUTIC EFFICACY THROUGH MODULATION OF CELL PROLIFERATION.

Solid tumors are complex biological structures which are composed of cellular and matrix components, everything being perfused by blood vessels. During tumor development, modifications of both biochemical and mechanical parameters are observed and can feedback on one another. Cancer cells constantly interact with their mechanical environment and the whole tissue is mostly confined by its surrounding. Compressive mechanical stress develops in part from cell proliferation and could eventually result in the clamping of blood vessels leading to increased interstitial fluid pressure (hydrostatic pressure). The consequent hypoperfusion poses important obstacles to drug delivery and nanomedicines. In fact, the tortuous tumor microvasculature has blood velocities up to one order of magnitude lower compared to healthy capillary networks. Moreover, the fast angiogenesis during tumor progression leads to high vascular density in solid tumors, large gaps exist between endothelial cells in tumor blood vessels, and tumor tissues show selective extravasation and retention of macromolecular drugs (Enhanced Permeation Retention \u2013 EPR \u2013 effect). These effects have served as a basis for the development of drug delivery systems which are aimed at enhancing tumor tissue targeting and drug therapeutic effectiveness. Over the last 15 years, a plethora of materials and different formulations have been proposed for the realization of nanomedicines. Yet, drug-loading efficiency, sequestration by phagocytic cells, and tumor accumulation of nanoparticle-loaded agents - nanomedicines - are sub-optimal. Starting from these considerations, during my PhD, I studied two complementary approaches: in the first two years my work was focused on implementing the characteristics of Discoidal Polymeric Nanoconstructs designed with controlled geometries and mechanical properties. In the last year, I investigated the role of mechanical stress on chemotherapeutic efficacy. More precisely, this work first reviews the use of deformable discoidal nanoconstructs (DPNs) as a novel delivery strategy for therapeutic and imaging agents. Inspired by blood cell behavior, these nanoconstructs are designed to efficiently navigate the circulatory system, minimize sequestration by phagocytic cells, and recognize the tortuous angiogenic microvasculature of neoplastic masses. In this work, the synthesis, drug loading and release, and physico-chemical characterization of DPNs were enhanced with particular emphasis on the ability to independently control size, shape, surface properties, and mechanical stiffness. Two different loading strategies were tested, namely the straightforward \u201cdirect loading\u201d and the \u201cabsorbance loading\u201d. In the former case, the agent was directly mixed with the polymeric paste to realize DPNs whereas, in the latter case, DPNs were first lyophilized and then rehydrated upon exposure to a concentrated aqueous solution of the agent. Under these two loading conditions, the encapsulation efficiencies and release profiles of three different molecules and their corresponding prodrugs were systematically assessed (1,2-Distearoyl-sn-glycero-3-phosphorylethanolamine lipid chains or 1 kDa PEG chains were directly conjugated with Cy5.5 or methotrexate and Doxorubicin). Moderately hydrophobic compounds with low molecular weight showed encapsulation efficiencies of 80%, with absorption loading (direct loading has efficiencies around 1%). The DOX-DPN showed on triple negative breast cancer cells a toxicity comparable to free DOX. Preliminary in vivo preliminary studies conducted with directly loaded Cy5-DPN demonstrated a fairly solid integration of the imaging compound with the polymer matrix of the particles. The second part of the work dissect what happens to free drugs or to drugs carried by nanovectors once they reach the tumor site. As we mention above, the elevated mechanical stress derived from tumor progression could result in blood vessels clamping with consequent reduction of drug efficacy. It is quite obvious to imagine that if the drug fails to reach the tumor it cannot act on it. Indeed, mechanical stress within the tumor site is present from the early stages of the disease. Our goal was to understand what happens when mechanical stress is not yet so large enough to fully collapse the blood vessels. Are there mechanical alterations that can affect the efficacy of a chemotherapeutic? We studied how mechanical perturbations of the tumor microenvironment could contribute to the mechanical-form of Gemcitabine drug resistance. Specifically, we developed a new in vitro strategy to mimic the mechanical compression stress induced by the stroma during tumor progression. We embedded pancreatic tumor spheroids into agarose polymeric matrix in order to demonstrate the effect of mechanical compressive stress on tumor proliferation. Then, we validated our results with other types of mechanical stresses. Finally, we investigated the therapeutic efficacy of a proliferation-based chemotherapy: Gemcitabine. Collectively, having the physical cues of cancer in mind, it can be important to cross-fertilize the fields of physical oncology and nanomedicine

Functional Block Copolymers as Platforms for Patterned Immobilization

Block copolymers are renowned for their microphase separation in bulk, in solution and in the form of thin films. The present dissertation takes an original approach at the utilization of thin films of block copolymers as new candidates for chemical nanopatterning. Functional / reactive libraries of two block copolymer systems, namely, PS-b-PI and PMMA-b-PS were developed. Detailed investigations on para-fluoro thiol reaction including its applicability in water were also carried out

Design and fabrication of biocompatible scaffolds for the regeneration of tissues

Regenerative medicine and tissue engineering attempt to repair or improve the biological functions of tissues that have been damaged or have ceased to perform their role through three main components: a biocompatible scaffold, cellular component and bioactive molecules. Nanotechnology provide a toolbox of innovative scaffold fabrication procedures in regenerative medicine. In fact, nanotechnology, using manufacturing techniques such as conventional and unconventional lithography, allows fabricating supports with different geometries and sizes as well as displaying physical chemical properties tunable over different length scales. Soft lithography techniques allow to functionalize the support by specific molecules that promote adhesion and control the growth of cells. Understanding cell response to scaffold, and viceversa, is a key issue; here we show our investigation of the essential features required for improving the cell-surface interaction over different scale lengths. The main goal of this thesis has been to devise a nanotechnology-based strategy for the fabrication of scaffolds for tissue regeneration. We made four types of scaffolds, which are able to accurately control cell adhesion and proliferation. For each scaffold, we chose properly designed materials, fabrication and characterization techniques

Atomic force microscopy studies of protein interactions with lipid membranes

The behaviour of biological components in cellular membranes is vital to the function of cells however many vital phenomena associated with membrane functions are not yet fully understood. Supported lipid bilayers provide a model of real cellular membranes. This thesis examines how increasing the complexity of model lipid bilayers through changes in lipid composition, membrane protein content and cytoskeletal interactions can be used to extract significant biological information with biophysical techniques and analysis. The atomic force microscope (AFM) is a powerful tool in the study of biological systems allowing both three dimensional sub-nanometer resolution and mechanical interrogation under physiological conditions. The recent arrival of high-speed atomic force microscopy has transformed the information and processes which can be obtained, enabling direct imaging of biomolecular processes in real time. The work in this thesis shows that the AFM cannot only be used to investigate membranes but also deposit them in situ at lateral scales comparable to their height. Studies of confining lipid and protein diffusion in these quasi-one dimensional systems shows confinement reduces mobility of lipid with important implications on the behaviour of pores and defects cellular membranes. Studies of lipid phase behaviour of compositions thought be simplified models of the cell membrane lipid content show evidence that the small “raft” domains detected in real cells are not stable equilibrium phase separated domains, but non-equilibrium compositional fluctuations. Actin polymerisation induced at positively charged bilayers in non-polymerising conditions provides new insight into polymerisation processes whilst also describing a simple novel method to create “synthetic” robust actin-membrane scaffolds with controllable coverage. This polymerisation process was then applied to coating of lipid microbubbles for combined ultrasound imaging and drug delivery applications. The addition of the actin coating increased bubbles lifetimes, stability, elasticity and stiffness whilst allowing the attachment of model drug carriers

Droplet behavior on superhydrophobic surfaces: Interfaces, interactions, and transport

The primary objective of the present work is to study droplet dynamics on smooth hydrophobic and textured superhydrophobic surfaces, and to understand the dependence of interfacial interaction mechanisms on surface morphology. ^ A detailed understanding of the dynamics of droplet response to an applied electric field is essential for implementation of electrowetting techniques in various devices. In the first part of the thesis, a systematic study of the transient response in terms of contact angle and contact radius of a sessile droplet on a smooth hydrophobic surface under electrical actuation is presented. A scaling analysis predicts the response time of a droplet during step actuation. It is shown that during time-varying electrical actuation of a droplet, in addition to the primary frequency response at the electrical forcing frequency, the droplet oscillation exhibits sub-harmonic oscillation at half the forcing frequency. ^ The remaining part of the thesis focuses on the design, fabrication and characterization of superhydrophobic surfaces, and droplet behavior on such surfaces. A simple yet highly effective concept of fabricating hierarchical structured surfaces using a single-step deep reactive ion etch process is proposed. The surfaces show enhanced anti-wetting characteristics, and lower contact angle hysteresis compared to single-roughness surfaces. A novel hybrid surface morphology incorporating communicating and non-communicating air gaps is proposed to enhance capillary pressure. The pressure balance during droplet impingement indicates that the effective water hammer is dependent on the surface morphology, and is significantly lower compared to that on smooth surfaces. ^ The last part of the thesis includes evaporative phase change on flat and textured surfaces. An understanding of the evaporation characteristics of the droplet, and accompanying convection flow field on hydrophobic and superhydrophobic surfaces is important to several applications. In this dissertation, droplet evaporation characteristics on unheated and heated hydrophobic and superhydrophobic surfaces with negligible contact angle hysteresis are investigated systematically. A vapor-diffusion-only model is shown to overpredict the rate of evaporation on superhydrophobic surfaces, and the disparity increases with substrate heating. The evaporation characteristics are explained in terms of the evaporative cooling, and vapor buoyancy induced convection. ^ Improved understanding of the convective flow mechanism inside an evaporating droplet can assist in non-intrusive particle manipulation inside a micro-droplet. The recirculating convective flow field inside a water droplet evaporating on hydrophobic and superhydrophobic surfaces is attributed to the thermal buoyancy induced convection. The flow pattern inside the droplet enables understanding of the dependence of flow behavior on the nature of the substrate. High recirculating flow velocity in droplets evaporating on superhydrophobic surfaces is proposed to enable `on-the-spot\u27 mixing in droplets for microfluidics application