The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors and physical forces in the tumor microenvironment. Due to the lack of a comprehensive investigation of tumor tissue viscoelasticity, the relationship between such physical properties and cancer malignancy remains poorly understood. Here, the viscoelastic properties of breast cancer spheroids, 3D (in vitro) tumor models, are studied in relation to their metastatic potentials by imposing controlled, dynamic compression within a microfluidic constriction, and subsequently monitoring the relaxation of the imposed deformation. By adopting a modified Maxwell model to extract viscoelastic properties from the compression data, the benign (MCF-10A) spheroids are found to have higher bulk elastic modulus and viscosity compared to malignant spheroids (MCF-7 and MDA-MB-231). The relaxation is characterized by two timescales, captured by a double exponential fitting function, which reveals a similar fast rebound for MCF-7 and MCF-10A. Both the malignant spheroids exhibit similar long-term relaxation and display residual deformation. However, they differ significantly in morphology, particularly in intercellular movements. These differences between malignant spheroids are demonstrated to be linked to their cytoskeletal organization, by microscopic imaging of F-actin within the spheroids, together with cell-cell adhesion strength.

@en

We introduce Microgel-based Etalon Membranes (MEMs), based on the combination of stimuli-responsive microgels with an etalon, which is an optical device consisting of two reflecting plates and is used to filter specific wavelengths of light. The microgels are sandwiched between two reflective layers and, in response to a stimulus (e.g., temperature, pH, or biomarker concentration), swell or de-swell, thereby changing the distance between the two reflective layers and generating multiple peaks in the reflectance spectra. This property gives a MEM the unique capability of simultaneous separation and tunable responses to environmental changes and/or biomarker concentrations. We propose a design based on gold layers on a silicon nitride wafer membrane. Our comprehensive characterization, employing permeability experiments, in situ optical reflectance spectroscopy, in-liquid atomic force microscopy (AFM) analysis, and captive bubble contact angle measurements, elucidates the dynamic response of MEM to pH, temperature, and glucose stimuli and the corresponding effect of microgel swelling/de-swelling on the membrane properties, e.g., permeability. The AFM results confirm the dynamic changes of the microgel layer’s thickness on the membrane surface in response to the stimuli. Although the microgel’s swelling/de-swelling influences the effective pore radius, the decrease in the membrane’s permeance is limited to less than 10%. In the swollen state of the microgels, the etalon membranes show a prominent hydrophilic behavior, while they become less hydrophilic in the microgels’ de-swollen state. This work introduces MEM and provides novel insights into their behavior. The fundamental understanding that we reveal opens the way to applications ranging from point-of-care testing to continuous environmental monitoring.

@en

Background: Electrohydrodynamic (EHD) drying relies on the generation of a corona wind that is created with a high electric potential between an emitter and a ground electrode. The impinging corona wind enhances convective heat and mass transport close to the sample, which is positioned on the ground electrode. Although EHD drying is reported to have large potential for milder and energy efficient drying, most studies have only evaluated its potential at the lab scale and for specific applications. Scope and approach: This review focusses on discussing the underlying physical phenomena that may be expected to influence the performance of EHD drying processes. Specifically, we discuss how corona wind changes due to discharge behaviour as it is influenced by moisture release during drying, how the microstructural properties of the product could influence electromigration in the drying material and how EHD drying could be efficiently and safely scaled up for biobased & food products. We conclude with an outlook to the research that still is required to concretize the potential of EHD drying in practice. Key findings and conclusions: In EHD drying, electrical discharge induces airflow which enhances external convective drying. Studies coupling physical phenomena are still lacking, although some possible couplings are mentioned in chapter 2. Internal mass transfer is enhanced due to presence of an electrical potential over the product, which can cause several electrically-driven transport phenomena as discussed in chapter 3. Several drying setups have been explored in industry, of which the characteristics are summarized in chapter 4.

@en

Brittle fracturing of materials is common in natural and industrial processes over a variety of length scales. Knowledge of individual particle dynamics is vital to obtain deeper insight into the atomistic processes governing crack propagation in such materials, yet it is challenging to obtain these details in experiments. We propose an experimental approach where isotropic dilational strain is applied to a densely packed monolayer of attractive colloidal microspheres, resulting in fracture. Using brightfield microscopy and particle tracking, we examine the microstructural evolution of the monolayer during fracturing. Furthermore, we propose and test a parameter termed Weakness that estimates the likelihood for particles to be on a crack line, based on a quantified representation of the microstructure in combination with a machine learning algorithm. Regions that are more prone to fracture exhibit an increased Weakness value, however the exact location of a crack depends on the nucleation site, which cannot be predicted a priori. An analysis of the microstructural features that most contribute to increased Weakness values suggests that local density is more important than orientational order. Our methodology and results provide a basis for further research on microscopic processes during the fracturing process.@en

Hypothesis: High-frequency interfacial rheology of complex interfaces remains challenging yet it is central to the performance of multiphase soft matter products. We propose to use ultrasound-driven bubble dynamics to probe the high-frequency rheology of a colloid monolayer used as model system with controlled interactions and simultaneous monitoring of the microstructure. We hypothesize that by comparing the response of colloid-coated bubbles with that of a bare bubble under identical experimental conditions, it is possible to detect the non-linear response of the monolayer and use it to extract interfacial rheological properties at 10⁴s⁻¹. Experiments: Using high-speed video-microscopy, the dynamics of colloid-coated bubbles were probed to study the micromechanical response of the monolayer to high-frequency deformation. Protocols analogous to stress-sweep and frequency-sweep were developed to examine the stress–strain relationships. A simple model, motivated by the observed non-linear responses, was developed to estimate the interfacial viscoelastic parameters. Findings: The estimated elastic moduli of colloid monolayers at 10⁴s⁻¹ are about an order of magnitude larger than those measured at 1 s⁻¹. The monolayers exhibit non-linear viscoelasticity for strain amplitudes as small as 1%, and strain-softening behaviour. These findings highlight the applicability of acoustic bubbles as high-frequency interfacial probes.

@en

The dissolution of bubbles confined in porous media is relevant to applications such as carbon sequestration and soil remediation. Recent numerical work indicates that a rich variety of collective dissolution behaviors can be obtained depending on the initial solute concentration, the size distribution of bubbles and the structure of the porous network. However, there is only sparse experimental evidence that supports these findings. Here, we present an experimental study that uses optical microscopy to track the dissolution of CO₂ bubbles in a two-dimensional porous network etched on a microfluidic chip filled with CO₂–saturated water. We consider two distinct level of initial liquid supersaturation for situations involving a single isolated bubble and small bubble clusters, and observe dissolution, growth or a combination of these processes. A pore-network model is used to complement the experimental observations with information on local concentration development. The model captures qualitatively the evolution of the bubble size in each case tested experimentally and enables shedding light on the interplay between the inter- and intra-pore diffusive fluxes in driving the dissolution process.

@en

Within the tumor microenvironment (TME), cancer cells use mechanotransduction pathways to convert biophysical forces to biochemical signals. However, the underlying mechanisms and functional significance of these pathways remain largely unclear. The upregulation of mechanosensitive pathways from biophysical forces such as interstitial flow (IF), leads to the activation of various cytokines, including transforming growth factor-β (TGF-β). TGF-β promotes in part via a Smad-dependent signaling pathway the epithelial–mesenchymal transition (EMT) in cancer cells. The latter process is linked to increased cancer cell motility and invasion. Current research models have limited ability to investigate the combined effects of biophysical forces (such as IF) and cytokines (TGF-β) in a 3D microenvironment. We used a 3D-matrix based microfluidic platform to demonstrate the potentiating effect of IF on exogenous TGF-β induced upregulation of the Smad-signaling activity and the expression of mesenchymal marker vimentin in A549 lung cancer spheroids. To monitor this, we used stably integrated fluorescent based reporters into the A549 cancer cell genome. Our results demonstrate that IF enhances exogenous TGF-β induced Smad-signaling activity in lung cancer spheroids embedded in a matrix microenvironment. In addition, we observed an increased cell motility for A549 spheroids when exposed to IF and TGF-β. Our 3D-microfluidic model integrated with real-time imaging provides a powerful tool for investigating cancer cell signaling and motility associated with invasion characteristics in a physiologically relevant TME.@en

Emulsions stabilized by nanoparticles, known as Pickering emulsions, exhibit remarkable stability, which enables applications ranging from encapsulation, to advanced materials, to chemical conversion. The layer of nanoparticles at the interface of Pickering droplets is a semi-permeable barrier between the two liquid phases, which can affect the rate of release of encapsulates, and the interfacial transfer of reactants and products in biphasic chemical conversion. A gap in our fundamental understanding of diffusion in multiphase systems with particle-laden interfaces currently limits the optimal development of these applications. To address this gap, we developed an experimental approach for in situ, real-time quantification of concentration fields in Pickering droplets in a Hele-Shaw geometry and investigated the effect of the layer of nanoparticles on diffusion of solute across a liquid–liquid interface. The experiments did not reveal a significant hindrance on the diffusion of solute across an interface densely covered by nanoparticles. We interpret this result using an unsteady diffusion model to predict the spatio-temporal evolution of the concentration of solute with a particle-laden interface. We find that the concentration field is only affected in the immediate vicinity of the layer of particles, where the area available for diffusion is affected by the particles. This defines a characteristic time scale for the problem, which is the time for diffusion across the layer of particles. The far-field concentration profile evolves towards that of a bare interface. This localized effect of the particle hindrance is not measurable in our experiments, which take place over a much longer time scale. Our model also predicts that the hindrance by particles can be more pronounced depending on the particle size and physicochemical properties of the liquids and can ultimately affect performance in applications.@en

Understanding the evolution of solute concentration gradients underpins the prediction of porous media processes limited by mass transfer. Here, we present the development of a mathematical model that describes the dissolution of spherical bubbles in two-dimensional regular pore networks. The model is solved numerically for lattices with up to 169 bubbles by evaluating the role of pore network connectivity, vacant lattice sites and the initial bubble size distribution. In dense lattices, diffusive shielding prolongs the average dissolution time of the lattice, and the strength of the phenomenon depends on the network connectivity. The extension of the final dissolution time relative to the unbounded (bulk) case follows the power-law function, B^k/ ℓ, where the constant ℓ is the inter-bubble spacing, B is the number of bubbles, and the exponent k depends on the network connectivity. The solute concentration field is both the consequence and a factor affecting bubble dissolution or growth. The geometry of the pore network perturbs the inward propagation of the dissolution front and can generate vacant sites within the bubble lattice. This effect is enhanced by increasing the lattice size and decreasing the network connectivity, yielding strongly nonuniform solute concentration fields. Sparse bubble lattices experience decreased collective effects, but they feature a more complex evolution, because the solute concentration field is nonuniform from the outset.

@en

Colloidal gels possess a memory of previous shear events, both steady and oscillatory. This memory, embedded in the microstructure, affects the mechanical response of the gel, and therefore enables precise tuning of the material properties under careful preparation. Here we demonstrate how the dynamics of a deformable inclusion, namely a bubble, can be used to locally tune the microstructure of a colloidal gel. We examine two different phenomena of bubble dynamics that apply a local strain to the surrounding material: dissolution due to gas diffusion, with a characteristic strain rate of ∼10-3 s-1; and volumetric oscillations driven by ultrasound, with a characteristic frequency of ∼104 s-1. We characterise experimentally the microstructure of a model colloidal gel around bubbles in a Hele-Shaw geometry using confocal microscopy and particle tracking. In bubble dissolution experiments, we observe the formation of a pocket of solvent next to the bubble surface, but marginal changes to the microstructure. In experiments with ultrasound-induced bubble oscillations, we observe a striking rearrangement of the gel particles into a microstructure with increased local ordering. High-speed bright-field microscopy reveals the occurrence of both high-frequency bubble oscillations and steady microstreaming flow; both are expected to contribute to the emergence of the local order in the microstructure. These observations open the way to local tuning of colloidal gels based on deformable inclusions controlled by external pressure fields.

@en

Oil foams stabilized by crystallizing agents exhibit outstanding stability and show promise for applications in consumer products. The stability and mechanics imparted by the interfacial layer of crystals underpin product shelf life, as well as optimal processing conditions and performance in applications. Shelf life is affected by the stability against bubble dissolution over a long time scale, which leads to slow compression of the interfacial layer. In processing flow conditions, the imposed deformation is characterized by much shorter time scales. In practical situations, the crystal layer is therefore subjected to deformation on extremely different time scales. Despite its importance, our understanding of the behavior of such interfacial layers at different time scales remains limited. To address this gap, here we investigate the dynamics of single, crystal-coated bubbles isolated from an oleofoam, at two extreme time scales: the diffusion-limited time scale characteristic of bubble dissolution, ∼104 s, and a fast time scale characteristic of processing flow conditions, ∼10-3 s. In our experiments, slow deformation is obtained by bubble dissolution, and fast deformation in controlled conditions with real-time imaging is obtained using ultrasound-induced bubble oscillations. The experiments reveal that the fate of the interfacial layer is dramatically affected by the dynamics of deformation: after complete bubble dissolution, a continuous solid layer remains; after fast, oscillatory deformation of the layer, small crystals are expelled from the layer. This observation shows promise toward developing stimuli-responsive systems, with sensitivity to deformation rate, in addition to the already known thermoresponsiveness and photoresponsiveness of oleofoams.

@en

Bubbles in complex fluids are often desirable, and sometimes simply inevitable, in the processing of formulated products. Bubbles can rise by buoyancy, grow or dissolve by mass transfer, and readily respond to changes in pressure, thereby applying a deformation to the surrounding complex fluid. The deformation field around a stationary, spherical bubble undergoing a change in radius is simple and localized, thus making it suitable for rheological measurements. This article reviews emerging approaches to extract information on the rheology of complex fluids by analysing bubble dynamics. The focus is on three phenomena: changes in radius by mass transfer, harmonic oscillations driven by an acoustic wave, and bubble collapse. These phenomena cover a broad range of deformation frequencies, from 10⁻⁴–10⁶ Hz, thus paving the way to broadband microrheology using bubbles as active probes. The outstanding challenges that need to be overcome to achieve a robust technique are also discussed.

@en

Contactless manipulation of microparticles using acoustic waves holds promise for applications ranging from cell sorting to threedimensional (3D) printing and tissue engineering. However, the unique potential of acoustic trapping to be applied in biomedical settings remains largely untapped. In particular, the main advantage of acoustic trapping over optical trapping, namely the ability of sound to propagate through thick and opaque media, has not yet been exploited in full. Here we demonstrate experimentally the use of the recently developed technique of single-beam acoustical tweezers to trap microbubbles, an important class of biomedically relevant microparticles. We show that the region of vanishing pressure of a propagating vortex beam can confine a microbubble by forcing low-amplitude, nonspherical, shape oscillations, enabling its full 3D positioning. Our interpretation is validated by the absolute calibration of the acoustic trapping force and the direct spatial mapping of isolated bubble echos, for which both find excellent agreement with our theoretical model. Furthermore, we prove the stability of the trap through centimeter-thick layers of bio-mimicking, elastic materials. Finally, we demonstrate the simultaneous trapping of nanoparticle-loaded microbubbles and activation with an independent acoustic field to trigger the release of the nanoparticles. Overall, using exclusively acoustic powering to position and actuate microbubbles paves the way toward controlled delivery of drug payloads in confined, hard-to-reach locations, with potential in vivo applications.

@en

Yield-stress fluids naturally trap small bubbles when their buoyancy applies an insufficient stress to induce local yielding of the material. Under acoustic excitation, trapped bubbles can be driven into volumetric oscillations and apply an additional local strain and stress that can trigger yielding and assist their release. In this paper we explore different regimes of microbubble oscillation and translation driven by an ultrasound field in a model yield-stress fluid, a Carbopol microgel. We first analyse the linear bubble oscillation dynamics to measure the local, high-frequency viscosity of the material. We then use acoustic pressure gradients to induce bubble translation and examine the elastic part of the response of the material below yielding. We find that, at moderate pressure amplitude, the additional stresses applied by volumetric oscillations and acoustic radiation forces do not lead to any detectable irreversible bubble motion. At high pressure amplitude, we observe non-spherical shape oscillations that result in erratic bubble motion. The critical pressures we observe differ from the predictions of a recent model of shape oscillations in soft solids. Based on our findings, we discuss possible reasons for the lack of bubble release in Carbopol and suggest other systems in which ultrasound-assisted bubble rise may be observed. This journal is

@en