Direct measurement of interactions between stimulation-responsive drug delivery vehicles and artificial mucin layers by colloid probe atomic force microscopy

A novel thermo- and pH-sensitive nanogel particle, which is a core-shell structured particle with a poly(N-isopropylacrylamide) (p(NIPAAm)) hydrogel core and a poly(ethylene glycol) monomethacrylate grafted poly(methacrylic acid) (p(MMA-g-EG)) shell, is of interest as a vehicle for the controlled release of peptide drugs. The interactions between such nanogel particles and artificial mucin layers during both approach and separation were successfully measured by using colloid probe atomic force microscopy (AFM) under various compression forces, scan velocities, and pH values. While the magnitudes of the compression forces and scan velocities did not affect the interactions during the approach process, the adhesive force during the separation process increased with these parameters. The pH values significantly influenced the interactions between the nanogel particles and a mucin layer. A large steric repulsive force and a long-range adhesive force were measured at neutral pH due to the swollen p(MMA-g-EG) shell. On the other hand, at low pH values, the steric repulsive force disappeared and a short-range adhesive force was detected, which resulted from the collapse of the shell layer. The nanogel particles possessed a pH response that was sufficient to protect the incorporated peptide drug under the harsh acidic conditions in the stomach and to effectively adhere to the mucin layer of the small intestine, where the pH is neutral. The relationships among the nanogel particle-mucin layer interactions, pH conditions, scan velocities, and compression forces were systemically investigated and discussed.     

Modeling of flux decline during crossflow ultrafiltration of colloidal suspensions

Mass transfer during crossflow ultrafiltration is mathematically expressed using the two-dimensional convective–diffusion equation. Numerical simulations showed that mass transfer in crossflow filtration quickly reaches a steady-state for constant boundary conditions. Hence, the unsteady nature of the permeate flux decline must be caused by changes in the hydraulic boundary condition at the membrane surface due to cake formation during filtration. A step-wise pseudo steady-state model was developed to predict the flux decline due to concentration polarization during crossflow ultrafiltration. An iterative algorithm was employed to predict the amount of flux decline for each finite time interval until the true steady-state permeate flux is established. For model verification, crossflow filtration of monodisperse polystyrene latex suspensions ranging from 0.064 to 2.16 μm in diameter was studied under constant transmembrane pressure mode. Besides the crossflow filtration tests, dead-end filtration tests were also carried out to independently determine a model parameter, the specific cake resistance. Another model parameter, the effective diffusion coefficient, is defined as the sum of molecular and shear-induced hydrodynamic diffusion coefficients. The step-wise pseudo steady-state model predictions are in good agreement with experimental results of flux decline during crossflow ultrafiltration of colloidal suspensions. Experimental variations in particle size, feed concentration, and crossflow velocity were also effectively modeled.     

On the role of electrostatic forces in the adhesion of polymer particles to solid surfaces

Simultaneous measurements have been made of the adhesive force and double electric charge of particles after their removal from a metal surface. For the systems investigated, the adhesive force and charge on the particles increase with particle diameter according to a power law with an exponent close to 2. Such dependence can be explained on the basis of the electrostatic nature of the adhesive forces. A double electric layer exists at the interface between the particles and the metal surface. A calculation was made of the surface density of charge for the polyvinyl chloride particle-steel system.     

A novel approach for modeling concentration polarization in crossflow membrane filtration based on the equivalence of osmotic pressure model and filtration theory

A theoretical model for prediction of permeate flux during crossflow membrane filtration of rigid hard spherical solute particles is developed. The model utilizes the equivalence of the hydrodynamic and thermodynamic principles governing the equilibrium in a concentration polarization layer. A combination of the two approaches yields an analytical expression for the permeate flux. The model predicts the local variation of permeate flux in a filtration channel, as well as provides a simple expression for the channel-averaged flux. A criterion for the formation of a filter cake is presented and is used to predict the downstream position in the filtration channel where cake layer build-up initiates. The predictions of permeate flux using the model compare remarkably well with a detailed numerical solution of the convective diffusion equation coupled with the osmotic pressure model. Based on the model, a novel graphical technique for prediction of the local permeate flux in a crossflow filtration channel has also been presented.     

Effect of particle shape on crossflow filtration flux

In an effort to further increase the understanding of crossflow filtration, experiments were performed on the influence of particle shape on permeation flux. Five particles of similar density and size distribution but of different shapes were used to test the influence of particle shape, while varying experimental parameters such as crossflow velocity, filtration pressure, solids concentration, membrane morphology and pore size. Particle shape was found to influence the equilibrium flux by the structure of the cake layer formed. Irregularly shaped particles such as branched carbon particles provided higher fluxes due to the high voidage cakes. More regularly shaped particles such as glass spheres resulted in lower fluxes. Platelet aluminium particles had relatively high filtration rates due to the gaps between the plates. The effects of the other experimental parameters typically showed results consistent with previous publications. Using the measured cake mass, a theoretical model based on D'Arcy and Kozeny gave reliable filtration flux compared to the experimental results.     

Microflotation Suppression and Enhancement Caused by Particle/Bubble Electrostatic Interaction

The processes of attachment and detachment of small or medium-sized particles to relatively large bubbles during microflotation are considered in terms of the heterocoagulation theory. Calculations are made for the conditions that the surface potentials are of similar sign and constant, that one of the surface potentials is small, that hydrophobic attraction is absent, and that there are no surface deformations. Under these conditions bubble-particle aggregates may form as a result of an electrostatic attraction which exceeds the repulsive van der Waals force at intermediate distances. Next to electrostatic and van der Waals forces, hydrodynamic and gravitational forces are considered. These forces may overcome the electrostatic repulsion at large distances and promote particle bubble attachment. Strong electrostatic attraction at small distances, arising at a large difference of the surface potentials of the bubble and the particle and of low electrolyte concentrations, can prevent subsequent detachment by hydrodynamic and gravitational forces. With increasing electrolyte concentration the electrostatic barrier increases and the attractive electrostatic force diminishes. As a result, a critical electrolyte concentration for microflotation exists. Above this concentration attachment may still occur but it is followed by detachment. At lower electrolyte concentrations the electrostatic attractive force prevents the detachment. The dependence of the critical electrolyte concentration on the values of the bubble and particle potentials and the Hamaker constant is calculated. The critical concentration does not depend on particle or bubble size if the absolute values of the total detachment force and the total pressing force coincide, which is the case for Stokes and potential flow. For every electrolyte concentration lower than the critical value there are two critical particle sizes that limit the flotation possibility. For small particle sizes attachment is impossible because the pressing force is smaller than the electrostatic barrier. For large particle sizes detachment cannot be prevented because the detachment force exceeds the maximum electrostatic attraction. A microflotation domain of intermediate particle sizes exists in which irreversible heterocoagulation occurs. Copyright 2001 Academic Press.     

Dielectrophoretic levitation in the presence of shear flow: implications for colloidal fouling of filtration membranes

The ability of dielectrophoretic (DEP) forces created using a microelectrode array to levitate particles in a colloidal suspension is studied experimentally and theoretically. The experimental system employs microfabricated electrode arrays on a glass substrate to apply repulsive DEP forces on polystyrene latex particles suspended in an aqueous medium. A numerical model based on the convection-diffusion-migration equation is presented to calculate the concentration distribution of colloidal particles in shear flow under the influence of a repulsive DEP force field. The results obtained from the numerical simulations are compared against trajectory analysis results and experimental data. The results indicate that by incorporating ac electric field-induced DEP forces in a shear flow, particle accumulation and deposition on the flow channel surfaces can be significantly reduced or even completely averted. The mathematical model is then used to indicate how the deposition behavior is modified in the presence of a permeable substrate, representative of tangential flow membrane filtration operations. The results indicate that the repulsive dielectrophoretic (DEP) forces imparted to the particles suspended in the feed can be employed to mitigate membrane fouling in a cross-flow filtration process.     

Quantification of particle-bubble interactions using atomic force microscopy: A review

The attachment of particles to bubbles in solution is of fundamental importance to several industrial processes, most notably in the process of froth flotation. During this process hydrophobic particles attach to air bubbles in solution, which allows them to be separated as froth at the surface. The addition of chemicals can help to modulate these interactions to increase the yield of the minerals of interest. Over the past decade the atomic force microscope (AFM) has been adapted for use in studying the forces involved in the attachment of single particles to bubbles in the laboratory. This allows the measurement of actual DLVO (Derjaguin, Landau, Vervey and Overbeek) forces and adhesive contacts to be measured under different conditions. In addition contact angles may be calculated from features of force versus distance curves. It is the purpose of this article to illustrate how the colloid probe technique can be used to make single particle-bubble interactions and to summarise the current literature describing such experiments.     

Evaluation of crossflow filtration models based on shear-induced diffusion and particle adhesion: Complications induced by feed suspension polydispersivity

Specific flux data were obtained during the transient period of flux decline in laminar crossflow filtration. Effects of hydrodynamics on cake parameters such as specific resistance, mass and particle size distribution were studied experimentally. An evaluation of crossflow filtration models suggests that a model based on shear-induced diffusion [1] is a better predictor of specific flux decline than a particle adhesion model [2]. Even for relatively narrowly distributed suspensions, polydispersivity complicates analyses in a manner that is not adequately addressed by these models. Changes in experimental specific cake resistances with module hydrodynamics coupled to the inadequacy of these models for accurately predicting time-dependent specific flux profiles, cake specific resistances, and mass suggests that cake morphology is a key variable that needs to be incorporated in future modeling efforts.     

Critical flux of hard sphere suspensions in crossflow filtration: Hydrodynamic force bias Monte Carlo simulations

A Monte Carlo method is developed for crossflow membrane filtration to determine the critical flux of hard sphere suspensions. Brownian and shear-induced diffusion are incorporated into an effective hydrodynamic force exerted on the hard spheres in a concentrated shear flow. Effects of shear rate and particle size on the critical flux are investigated using hydrodynamic force bias Monte Carlo simulations, providing a baseline of the critical flux.     

Quantitative measurements of the concentration polarisation layer thickness in membrane filtration of oil-water emulsions using NMR micro-imaging

In this paper we report measurements of the thickness of the concentration polarisation layers formed during crossflow membrane filtration of an oil-water emulsion. The formation and development of the oil polarisation layers was visualised non-invasively using NMR chemical shift selective micro-imaging. A series of images was acquired during the transient state of the filtration, (i.e. while the polarisation layer was forming and the flux of filtrate was changing), prior to the establishment of steady state conditions. An estimate of the specific resistance of the concentration polarisation layers was then obtained by determining the average oil layer thicknesses and concentration at a given time from the resulting images and measuring the corresponding (length averaged) flux of filtrate gravimetrically. After the establishment of steady state conditions, the dependence of the steady state filtrate flux on crossflow Reynolds number was found to be consistent with Brownian diffusion being the main mechanism controlling the build-up of the oil polarisation layers, at least under our range of operating conditions.     

Electrostatic double layer force between a sphere and a planar substrate in the presence of previously deposited spherical particles

A finite element model of the electrostatic double layer interaction between an approaching colloidal particle and a small region of a charged planar surface containing four previously deposited particles is presented. The electrostatic interaction force experienced by the approaching particle is obtained by solving the Poisson-Boltzmann equation with appropriate boundary conditions representing this complex geometry. The interaction forces obtained from the detailed three-dimensional finite element simulations suggest that for the many-body scenario addressed here, the electrostatic double layer repulsion experienced by the approaching particle is less than the corresponding sphere-plate interaction due to the presence of the previously deposited particles. The reduction in force is quite significant when the screening length of the electric double layer becomes comparable to the particle radius (kappaa approximately 1). The results also suggest that the commonly used technique of pairwise addition of binary interactions can grossly overestimate the net electrostatic double layer interaction forces in such situations. The simulation methodology presented here can form a basis for investigating the influence of several previously deposited particles on the electrostatic repulsion experienced by a particle during deposition onto a substrate.     

Effect of electrostatic, hydrodynamic, and Brownian forces on particle trajectories and sieving in normal flow filtration

Particle deposition and fouling are critical factors governing the performance of microfiltration and ultrafiltration systems. Particle trajectories were evaluated by numerical integration of the Langevin equation, accounting for the combined effects of electrostatic repulsion, enhanced hydrodynamic drag, and Brownian diffusion. In the absence of Brownian forces, particles are unable to enter the membrane pores unless the drag associated with the filtration velocity can overcome the electrostatic repulsion. Brownian forces significantly alter this behavior, allowing some particles to enter the pore even at low filtration velocities. The average particle transmission, evaluated from the probability of having a particle enter the pore, increases with increasing filtration velocity due to the greater hydrodynamic drag force on the particle. These results provide important insights into particle behavior in membrane systems.     

Crossflow microfiltration of mono-dispersed deformable particle suspension

Crossflow microfiltration of mono-dispersed deformable particles of Saccharomyces cerevisiae and Ca-alginate, and rigid PMMA particles was conducted to compare the structure of the flux-limiting layer. The effects of particle deformation due to the frictional drag and mass of the cake, and the area contact among particles on the reduction of porosity were examined to determine how these variations lead to an increase in filtration resistance. The dynamic analysis proposed by Lu and Hwang (AIChE J. 41 (1995) 1443–1455) was modified to examine cake formation during crossflow filtration of deformable particles by taking the transient effect of cake compression and the effect of the area contact between particles into consideration. In situ measurement of filter cake thickness using the infrared reflection method was applied to verify the theoretical results. Both experimental and simulated results showed that the cake formed by deformable particles exhibits a rapid increase in flow resistance or a decrease in local porosity and a high resistant limiting layer is formed next to the filter medium during filtration due to the deformation of particles.     

Resolving the coupled effects of hydrodynamics and DLVO forces on colloid attachment in porous media

Transport of colloidal particles in porous media is governed by the rate at which the colloids strike and stick to collector surfaces. Classic filtration theory has considered the influence of system hydrodynamics on determining the rate at which colloids strike collector surfaces, but has neglected the influence of hydrodynamic forces in the calculation of the collision efficiency. Computational simulations based on the sphere-in-cell model were conducted that considered the influence of hydrodynamic and Derjaguin-Landau-Verwey-Overbeek (DLVO) forces on colloid attachment to collectors of various shape and size. Our analysis indicated that hydrodynamic and DLVO forces and collector shape and size significantly influenced the colloid collision efficiency. Colloid attachment was only possible on regions of the collector where the torque from hydrodynamic shear acting on colloids adjacent to collector surfaces was less than the adhesive (DLVO) torque that resists detachment. The fraction of the collector surface area on which attachment was possible increased with solution ionic strength, collector size, and decreasing flow velocity. Simulations demonstrated that quantitative evaluation of colloid transport through porous media will require nontraditional approaches that account for hydrodynamic and DLVO forces as well as collector shape and size.     

Adhesion between Silica Particle and Mica Surfaces in Water and Electrolyte Solutions

An atomic force microscope (AFM) is used to study the adhesion between a silica sphere and a mica plate in pure water and solutions of monovalent cations (LiCl, NaCl, KCl, and CsCl). It is found that the adhesive force depends not only on the electrolyte concentration but also on the hydration enthalpy of cations and the contact time of the particle on the surface. Possible mechanisms by which the observed phenomena can be explained consistently are discussed extensively. It is suggested that the adhesive force is closely related to the structure of the layer of cations and water molecules adsorbed on the surfaces: the strong adhesive force is obtained when highly hydrated cations (Li(+), Na(+)) are adsorbed to form a thick but weakly adsorbed layer, while the weak adhesive force is observed when poorly hydrated cations (Cs(+), K(+)) are adsorbed to form a thin but strongly adsorbed layer. Copyright 2000 Academic Press.     

Manipulating forces between surfaces: applications in colloid science and biophysics

It is the forces between the microscopic constituents of materials which to a large extent determine the macroscopic properties. For example, it is the differences in bonding between the carbon atoms which determines the different physical properties of carbon and graphite. The same is true in colloidal systems. In colloidal systems, there are three common types of long-range interactions between particles: van der Waals forces, electrical double layer forces and steric forces. In this paper, examples as to how these forces can be modified and even manipulated will be given. To convincingly demonstrate these effects, it is necessary to measure these interaction forces. We have achieved this by using the principles of atomic force microscopy (AFM). The principle is simple, a small particle, 5-30 microm, is attached onto a small weak cantilever spring. The interaction between this particle and another particle or a surface is measured by monitoring the deflection of the spring as the two particles are moved together. In this paper, I shall give examples of direct measurements of van der Waals, electrical double layer and steric forces and show how they can be modified and how these modifications affect the properties of bulk suspensions. Similar principles are involved in the interactions of biological materials. However, nature is much cleverer than man such that many of the macromolecules on cell surfaces are able to specifically recognise only one other molecule. An example of this recognition-type interaction, namely, cholera toxin interacting with the glycolipid Gm1, will also be presented. Finally, the adhesion of cells to surfaces of different surface chemistries has been determined; this is of significance in many fields ranging from fouling of filtration membranes on the one hand to the biocompatibility of surgical implants on the other.     

Modeling of concentration polarization and depolarization with high-frequency backpulsing

Rapid backpulsing to reduce membrane fouling during crossflow microfiltration and ultrafiltration is studied by solving the convection-diffusion equation for concentration polarization and depolarization during cyclic operation with transmembrane pressure reversal. For a fixed duration of reverse filtration, there is a critical duration of forward filtration which must not be exceeded if the formation of a cake or gel layer on the membrane surface is to be avoided. The theory also predicts an optimum duration of forward filtration which maximizes the net flux, since backpulsing at too high of frequency does not allow for adequate permeate collection during forward filtration relative to that lost during reverse filtration, whereas backpulsing at too low of frequency results in significant flux decline due to cake or gel buildup during each period of forward filtration. In general, short backpulse durations, low feed concentrations, high shear rates, and high forward transmembrane pressures give the highest net fluxes, whereas the magnitude of the reverse transmembrane pressure has a relatively small effect.Rapid backpulsing experiments with yeast suspended in deionized water performed with a flat-sheet crossflow microfiltration module and cellulose acetate membranes with 0.07 μm average pore diameter. The optimum forward filtration times were found to be 1.5, 3, and 5 s, respectively, for backpulse durations of 0.1, 0.2, and 0.3 s. Both theory and experiment gave net fluxes with backpulsing of about 85% of the clean membrane flux (0.022 cm/s = 790 l/m² h), whereas the long-term flux in the absence of backpulsing is an order-of-magnitude lower (0.0026 cm/s = 94 l/m² h).     

In-situ investigations on the SILAR-growth of ZnS films as studied by tapping mode atomic force microscopy

Tapping mode atomic force microscopy (TM-AFM) has been successfully used for in-situ imaging of the deposition of ZnS films with the successive ionic layer adsorption and reaction (SILAR) method. The films were deposited in-situ using the commercial TM-AFM liquid cell as a flow-through reactor. The potential of TM-AFM has been used to study the growth of ZnS on different substrates up to 50 SILAR cycles. Reactants and rinsing water were alternately exchanged in the cell by a computer controlled valve system. In comparison to earlier work performed with the conventional AFM operated in contact mode, imaging artefacts introduced by lateral shear forces can be largely eliminated with TM-AFM. On glass the roughness is observed to decrease initially until typical island formation takes place at a larger number of deposition cycles. On mica island formation can be observed right from the beginning of the process and the roughness increases with increasing number of deposition cycles.     

Solid particle in the boundary layer of a rising bubble

The hydrodynamic interaction of a solid particle and the boundary layer around a rising bubble is analyzed in the before-contact state (BCS) of a flotation act. The lagging of the particle behind the basic outer flow is accounted for. The forces acting on the particle are qualitatively examined. A new term is introduced in the force balance — the migration force. An expression for the collision efficiency is proposed that concerns a particle already entrained in the bubbles boundary layer.