pH-Dependent Adsorption of Human Serum Albumin Protein on a Polystyrene-Block-Poly(acrylic acid)-Coated PVDF Membrane.

This study reports the investigation of human serum albumin (HSA) adsorption on a poy-styrene-block-poly(acrylic acid) (PS-b-PAA)-coated PVDF membrane, which is a potential smart material for biomedical applications. First, copolymer coating on the membrane surface was successfully performed, due to the hydrophobic interaction of the PS anchoring group with the PVDF membrane. This was confirmed by Fourier transform infrared spectroscopy (FTIR) characterization of the membrane. Then, HSA adsorption onto the coated membrane was assessed and was proved to be strongly dependent on the pH of the protein solution. Indeed, both FTIR mapping and mass balance calculation using UV-visible spectroscopy displayed a greater HSA adsorption on the membrane at pH 5, even though it still took place at higher pH, but to a lower extent. Afterwards, an ionic strength influence study evinced the role of electrostatic interactions between HSA and the PAA layer on HSA adsorption. Dead-end filtration of HSA through the coated membrane confirmed the pH dependence of HSA adsorption on the coated membrane.

In situ structural analysis with a SAXS laboratory beamline on a microfluidic chip.

Recent advances have been made in coupling microfluidic chips with X-ray equipment, enabling structural analysis of samples directly in microfluidic devices. This important step mainly took place at powerful synchrotron facilities because of the need for a beam reduced in size to fit the microfluidic channel dimensions but still intense. In this work, we discuss how improvements of an X-ray laboratory beamline and an optimal design of a microfluidic device allow reliable structural information to be obtained without the need for a synchrotron. We evaluate the potential of these new developments by probing several well known dispersions. These include dense inorganic gold and silica nanoparticles that scatter photons quite intensely, the bovine serum albumin (BSA) macromolecule, with moderate contrast, to highlight possible applications in biology, and latex nanospheres with only weak contrast with the solvent to show the limits of the setup. We established a proof of concept for a versatile setup that will open the way for more complex lab-on-a-chip devices suitable for in situ and operando structural analysis by small angle X-ray scattering analysis without the necessity for a synchrotron source.

Microfluidic Evaporation, Pervaporation, and Osmosis: From Passive Pumping to Solute Concentration.

Evaporation, pervaporation, and forward osmosis are processes leading to a mass transfer of solvent across an interface: gas/liquid for evaporation and solid/liquid (membrane) for pervaporation and osmosis. This Review provides comprehensive insight into the use of these processes at the microfluidic scales for applications ranging from passive pumping to the screening of phase diagrams and micromaterials engineering. Indeed, for a fixed interface relative to the microfluidic chip, these processes passively induce flows driven only by gradients of chemical potential. As a consequence, these passive-transport phenomena lead to an accumulation of solutes that cannot cross the interface and thus concentrate solutions in the microfluidic chip up to high concentration regimes, possibly up to solidification. The purpose of this Review is to provide a unified description of these processes and associated microfluidic applications to highlight the differences and similarities between these three passive-transport phenomena.

Pearl-necklace assembly of human serum albumin with the poly(acrylic acid) polyelectrolyte investigated using small angle X-ray scattering (SAXS).

In this comprehensive study, the interaction of human serum albumin (HSA) with poly(acrylic acid) (PAA) was explored using small angle X-ray scattering (SAXS) combined with chromatography. The results revealed the formation of a complex between HSA macromolecules and PAA chains but solely under some specific conditions of the ionic strength and pH of the medium. In fact, this binding was found to take place only at pH close to 5 and at low ionic strength (0.15 M). Otherwise, for a higher pH and a salt concentration of 0.75 M the HSA-PAA complex tends to dissociate completely showing the reversibility of the complexation. The assessment of the influence of the HSA/PAA molar ratio on the radius of gyration of the complex suggests that 4 HSA molecules could bind to each 100 kDa PAA chain. In addition, the Porod volume evaluation for the same range of the HSA/PAA ratio confirms this assumption. Finally, an all-atom SAXS modelling study using the BUNCH program was conducted to find a compatible model that fits the HSA-PAA complex scattering data. This model allows us to portray the HSA/PAA complex as a pearl-necklace assembly with 4 HSA molecules on the 100 kDa PAA chain.

Development of double porous poly (ε - caprolactone)/chitosan polymer as tissue engineering scaffold.

Polymer blend made from poly(ε - caprolactone)/chitosan (PCL/CHT) offers interesting opportunities for biological applications. The paper presents a new way to fabricate PCL/CHT double-porosity (macrovoids with interconnected microporosity) membrane materials from a chemical optimization of the solvent and non-solvent phases and from a modified phase inversion technique. By varying the PCL/CHT proportion, it is shown that it is possible to improve the chemical and physical properties of the CHT carbohydrate polymer. The PCL/CHT membranes are fully characterized in term of physico-chemical properties (ATR-FTIR, XRD and DSC) to understand the miscibility of the two-polymer blend. Morphological characterization by SEM shows that by increasing CHT wt% in the blend, the size of the macrovoids was increasing. Rapid enzymatic degradation of PCL from all the blend was found by using lipase (from P. cepacia). The mechanisms at the origin of the morphological structuration of the material is also discussed. To test the ability to operate these materials as small diameter vascular scaffolds, cell culture with human umbilical vein endothelial cells (HUVECs) were carried out on the membrane and the results analyzed with laser scanning confocal microscopy (LSCM). Data suggest that the blend membrane with higher concentration of CHT polymer wt% have suitable properties that promote high number of cells on the surface by maintaining cellular cytoskeleton integrity within 3 days. The blend membrane with a double porous morphology could be potentially applicable in future for small diameter vascular graft application. The surface macrovoids (20-90 µm) could be useful for three-dimensional cellular adhesion and proliferation and interconnected microporous spongy network (7-20 µm) is expected to transfer essential nutrients, oxygen, growth factor between the macrovoids and the supernatant.

Double porous poly (Ɛ-caprolactone)/chitosan membrane scaffolds as niches for human mesenchymal stem cells.

In this paper, we developed membrane scaffolds to mimic the biochemical and biophysical properties of human mesenchymal stem cell (hMSC) niches to help direct self-renewal and proliferation providing to cells all necessary chemical, mechanical and topographical cues. The strategy was to create three-dimensional membrane scaffolds with double porosity, able to promote the mass transfer of nutrients and to entrap cells. We developed poly (Ɛ-caprolactone) (PCL)/chitosan (CHT) blend membranes consisting of double porous morphology: (i) surface macrovoids (big pores) which could be easily accessible for hMSCs invasion and proliferation; (ii) interconnected microporous network to transfer essential nutrients, oxygen, growth factors between the macrovoids and throughout the scaffolds. We varied the mean macrovoid size, effective surface area and surface morphology by varying the PCL/CHT blend composition (100/0, 90/10, 80/20, 70/30). Membranes exhibited macrovoids connected with each other through a microporous network; macrovoids size increased by increasing the CHT wt%. Cells adhered on the surfaces of PCL/CHT 100/0 and PCL/CHT 90/10 membranes, that are characterized by a high effective surface area and small macrovoids while PCL/CHT 80/20 and PCL/CHT 70/30 membranes with large macrovoids and low effective surface area entrapped cells inside macrovoids. The scaffolds were able to create a permissive environment for hMSC adhesion and invasion promoting viability and metabolism, which are important for the maintenance of cell integrity. We found a relationship between hMSCs proliferation and oxygen uptake rate with surface mean macrovoid size and effective surface area. The macrovoids enabled the cell invasion into the membrane and the microporosity ensured an adequate diffusive mass transfer of nutrients and metabolites, which are essential for the long-term maintenance of cell viability and functions.

Interfacially driven transport theory: a way to unify Marangoni and osmotic flows.

We show that the solvent behaviour in both diffusio-osmosis and Marangoni flow can be derived from a simple model of colloid-interface interactions. We demonstrate that the direction of the flow is regulated by a single value of the attractive parameter covering the purely repulsive and attractive-repulsive interaction cases. The proposed universality between diffusio-osmosis and Marangoni flow is extended further to include diffusio-phoresis. In particular, an object immersed to a colloidal solution moves towards the low concentration of the colloidal particles in the case of colloid-interface repulsion and towards the high concentration of the colloidal particles in the case of colloid-interface attraction. The approach combines the methods of fluid dynamics, molecular physics and transport phenomena and provides a tractable explanation of how the colloid-interface interactions affect the momentum balance and the transport phenomena (interfacially driven transport).

Tunable Microstructured Membranes in Organs-on-Chips to Monitor Transendothelial Hydraulic Resistance.

Tissue engineering is an interdisciplinary field, wherein scientists from different backgrounds collaborate to address the challenge of replacing damaged tissues and organs through the in vitro fabrication of functional and transplantable biological structures. Because the development and optimization of tissue engineering strategies rely on the complex interaction of cells, materials, and the physical-chemical tissue microenvironment, there is a need for experimental models that allow controlled studies of these aspects. Organs-on-chips (OOCs) have recently emerged as in vitro models that capture the complexity of human tissues in a controlled manner, while including functional readouts related to human organ physiology. OOCs consist of multiple microfluidic cell culture compartments, which are interfaced by porous membranes or hydrogels in which human cells can be cultured, thereby providing a controlled culture environment that resembles the microenvironment of a certain organ, including mechanical, biochemical, and geometrical aspects. Because OOCs provide both a well-controlled microenvironment and functional readouts, they provide a unique opportunity to incorporate, evaluate, and optimize materials for tissue engineering. In this study, we introduce a polymeric blend membrane with a three-dimensional double-porous morphology prepared from a poly(ɛ-caprolactone)-chitosan blends (PCL-CHT) by a modified liquid-induced phase inversion technique. The membranes have different physicochemical, microstructural, and morphological properties depending on different PCL-CHT ratios. Big surface pores (macrovoids) provide a suitable microenvironment for the incorporation of cells or growth factors, whereas an interconnected small porous (macroporous) network allows transfer of essential nutrients, diffusion of oxygen, and removal of waste. Human umbilical vein endothelial cells were seeded on the blend membranes embedded inside an OOC device. The cellular hydraulic resistance was evaluated by perfusing culture medium at a realistic transendothelial pressure of 20 cmH2O or 2 kPa at 37°C after 1 and 3 days postseeding. By introducing and increasing CHT weight percentage, the resistance of the cellular barrier after 3 days was significantly improved. The high tuneability over the membrane physicochemical and architectural characteristics might potentially allow studies of cell-matrix interaction, cell transportation, and barrier function for optimization of vascular scaffolds using OOCs. Impact Statement Organs-on-chips (OOCs) offer interesting potential for progress in the treatment of diseases and injury in the growing field of tissue engineering and regenerative medicine. The article presents a new way to develop polymer membrane with a tunable microstructured morphology and to implement this biomaterial inside an OOC device. The reader should find measurements of the transendothelial hydraulic resistance in real time during endothelial cells culture: a simple and controlled way of mimicking human physiological condition for vascular tissue regeneration. This combination of novel biomaterial inside an OOC will explore innovative ideas in tissue engineering field.

Pore cross-talk in colloidal filtration.

Blockage of pores by particles is found in many processes, including filtration and oil extraction. We present filtration experiments through a linear array of ten channels with one dimension which is sub-micron, through which a dilute dispersion of Brownian polystyrene spheres flows under the action of a fixed pressure drop. The growth rate of a clog formed by particles at a pore entrance systematically increases with the number of already saturated (entirely clogged) pores, indicating that there is an interaction or "cross-talk" between the pores. This observation is interpreted based on a phenomenological model, stating that a diffusive redistribution of particles occurs along the membrane, from clogged to free pores. This one-dimensional model could be extended to two-dimensional membranes.

Drying colloidal systems: Laboratory models for a wide range of applications.

The drying of complex fluids provides a powerful insight into phenomena that take place on time and length scales not normally accessible. An important feature of complex fluids, colloidal dispersions and polymer solutions is their high sensitivity to weak external actions. Thus, the drying of complex fluids involves a large number of physical and chemical processes. The scope of this review is the capacity to tune such systems to reproduce and explore specific properties in a physics laboratory. A wide variety of systems are presented, ranging from functional coatings, food science, cosmetology, medical diagnostics and forensics to geophysics and art.

Interfacially driven transport in narrow channels.

When colloids flow in a narrow channel, the transport efficiency is controlled by the non-equilibrium interplay between colloid-wall interactions and hydrodynamics. In this paper, a general, unifying description of colloidal dispersion flow in a confined system is proposed. A momentum and mass balance founded framework implementing the colloid-interface interactions is introduced. The framework allows us to depict how interfacial forces drive the particles and the liquid flows. The interfacially driven flow (osmotic or Marangoni flows for repulsive or attractive colloid-wall interactions respectively) can be directly simulated in 2D domains. The ability of the model to describe the physics of transport in a narrow channel is discussed in detail. The hydrodynamic nature of osmosis and the associated counter-pressure are mechanically related to the colloid-interface interactions. The simulation shows an unexpected transition from axial plug to pillar accumulation for colloidal accumulation at a channel bottleneck. This transition has important consequences in transport efficiencies. Existing limiting cases, such as diffusio-osmosis, are recovered from the simulations, showing that the framework is physically well-founded. The model generalizes the existing approaches and proves the hydrodynamic character of osmosis, which cannot be fully described by purely thermodynamic considerations.

Membranes: A Variety of Energy Landscapes for Many Transfer Opportunities.

A membrane can be represented by an energy landscape that solutes or colloids must cross. A model accounting for the momentum and the mass balances in the membrane energy landscape establishes a new way of writing for the Darcy law. The counter-pressure in the Darcy law is no longer written as the result of an osmotic pressure difference but rather as a function of colloid-membrane interactions. The ability of the model to describe the physics of the filtration is discussed in detail. This model is solved in a simplified energy landscape to derive analytical relationships that describe the selectivity and the counter-pressure from ab initio operating conditions. The model shows that the stiffness of the energy landscape has an impact on the process efficiency: a gradual increase in interactions (such as with hourglass pore shape) can reduce the separation energetic cost. It allows the introduction of a new paradigm to increase membrane efficiency: the accumulation that is inherent to the separation must be distributed across the membrane. Asymmetric interactions thus lead to direction-dependent transfer properties and the membrane exhibits diode behavior. These new transfer opportunities are discussed.

Bacteria Delay the Jamming of Particles at Microchannel Bottlenecks.

Clogging of channels by complex systems such as mixtures of colloidal and biological particles is commonly encountered in different applications. In this work, we analyze and compare the clogging mechanisms and dynamics by pure and mixture suspensions of polystyrene latex particles and Escherichia coli by coupling fluorescent microscopic observation and dynamic permeability measurements in microfluidic filters. Pure particles filtration leads to arches and deposit formation in the upstream side of the microfilter while pure bacteria form streamers in the downstream zone. When mixing particle and bacteria, an unexpected phenomenon occurs: the clogging dynamics is significantly delayed. This phenomenon is related to apparent "slippery" interactions between the particles and the bacteria. These interactions limit the arches formation at the channels entrances and favour the formation of dendritic structures on the pillars between the channels. When these dendrites are eroded by the flow, fragments of the deposit are dragged towards the channels entrances. However, these bacteria/particles clusters being lubricated by the slippery interactions are deformed and stretched by the shear thus facilitating their passage through the microchannels.

Colloidal Jamming Dynamics in Microchannel Bottlenecks.

The purpose of this work is to examine the interplay between hydrodynamic conditions and physicochemical interactions from filtration experiments of microparticles. Experiments are performed in microfluidic filters with real-time visualization at pore scale. Both flow rate and pressure are measured with time to analyze the dynamics of pore clogging and permeability. Flux stepping experiments are performed at different physicochemical conditions to determine the different clogging conditions. The results allow distinguishing different clogging behaviors according to filtration conditions which are discussed by considering particle-particle and particle-wall colloidal interactions whose main characteristics are an important repulsive barrier at 0.01 mM, a significant secondary minimum at 10 mM, and low repulsive barrier at 100 mM. Clogging delay at moderate ionic strength and deposit fragility and associated sweeping out of aggregates of particles at high ionic strength are discussed from the deposit structure, specific resistance, and deposit relaxation analyses. It has also been observed that an opening angle at microchannel entrance causes rapid clogging, this effect being more pronounced when the repulsion is partially screened. Three different scenarios are discussed by analogy to crowd swarming: panic scenario (0.01 mM) where repulsion between particles induce pushing effects leading to the creation of robust arches at pore entrances; herding instinct scenario (10 mM) where the attraction (in secondary minima) between particles enhances the transport in pores and delays clogging; and sacrifice scenario (100 mM) where the capture efficiency is high but the aggregate formed at the wall is fragile.

Collective dynamics of flowing colloids during pore clogging.

Based on direct numerical simulations of the coupled motion of particles and fluid, this study analyzes the collective hydrodynamic and colloidal effects of flowing microparticles during the formation of different 3D clogging patterns at a pore entrance. Simulations of flowing suspensions through a pore with various simulation conditions show that particle concentration and surface interactions play a major role in the occurrence of the bridging phenomenon (simultaneous adhesion of many particles). In the absence of DLVO repulsive forces, plugging is characterized by the temporal reduction of the bulk permeability when increasing the volume fraction of the flowing suspension up to 20%. Under these conditions, different structures of particle aggregates (from cluster to cake plug) are formed at the pore entrance yielding different evolution rates of hydrodynamic resistance to the flow. Taking into account DLVO repulsive forces in simulations for a particle concentration equal to 10%, we observe the transition from dendritic structures (for low repulsion) to dense aggregates (for high repulsion). At high DLVO repulsive forces, the scenario of pore clogging is controlled by the collective behavior of many interacting particles. It leads to the formation of a jamming phase (Wigner glass phase) with transient clusters of interacting particles at the pore entrance. The network of jammed particles collapses when the force chains among the particles are overcome by the flow stress. The build-up and the collapse of the jammed phase at the pore entrance induce temporal permeability fluctuations. According to the relative magnitude of particle-particle and particle-wall interactions, when the jammed phase is disorganized by the flow, the residual force in the network can accelerate particles and lead to particle adhesion at the wall inducing a pore blockage and a rapid reduction of the bulk permeability.

A general approach for predicting the filtration of soft and permeable colloids: the milk example.

Membrane filtration operations (ultra-, microfiltration) are now extensively used for concentrating or separating an ever-growing variety of colloidal dispersions. However, the phenomena that determine the efficiency of these operations are not yet fully understood. This is especially the case when dealing with colloids that are soft, deformable, and permeable. In this paper, we propose a methodology for building a model that is able to predict the performance (flux, concentration profiles) of the filtration of such objects in relation with the operating conditions. This is done by focusing on the case of milk filtration, all experiments being performed with dispersions of milk casein micelles, which are sort of ″natural″ colloidal microgels. Using this example, we develop the general idea that a filtration model can always be built for a given colloidal dispersion as long as this dispersion has been characterized in terms of osmotic pressure Π and hydraulic permeability k. For soft and permeable colloids, the major issue is that the permeability k cannot be assessed in a trivial way like in the case for hard-sphere colloids. To get around this difficulty, we follow two distinct approaches to actually measure k: a direct approach, involving osmotic stress experiments, and a reverse-calculation approach, that consists of estimating k through well-controlled filtration experiments. The resulting filtration model is then validated against experimental measurements obtained from combined milk filtration/SAXS experiments. We also give precise examples of how the model can be used, as well as a brief discussion on the possible universality of the approach presented here.

Formation of bacterial streamers during filtration in microfluidic systems.

Bacterial behavior during filtration is complex and is influenced by numerous factors. The aim of this paper is to report on experiments designed to make progress in the understanding of bacterial transfer in filters and membranes. Polydimethylsiloxane (PDMS) microsystems were built to allow direct dynamic observation of bacterial transfer across different microchannel geometries mimicking filtration processes. When filtering Escherichia coli suspensions in such devices, the bacteria accumulated in the downstream zone of the filter forming long streamers undulating in the flow. Confocal microscopy and 3D reconstruction of streamers showed how the streamers are connected to the filter and how they form in the stream. Streamer development was found to be influenced by the flow configuration and the presence of connections or tortuosity between channels. Experiments showed that streamer formation was greatest in a filtration system composed of staggered arrays of squares 10 µm apart.

Filtration method characterizing the reversibility of colloidal fouling layers at a membrane surface: analysis through critical flux and osmotic pressure.

A filtration procedure was developed to measure the reversibility of fouling during cross-flow filtration based on the square wave of applied pressure. The principle of this method, the apparatus required, and the associated mathematical relationships are detailed. This method allows for differentiating the reversible accumulation of matter on, and the irreversible fouling of, a membrane surface. Distinguishing these two forms of attachment to a membrane surface provides a means by which the critical flux may be determined. To validate this method, experiments were performed with a latex suspension at different degrees of destabilization (obtained by the addition of salt to the suspension) and at different cross-flow velocities. The dependence of the critical flux on these conditions is discussed and analysed through the osmotic pressure of the colloidal dispersion.