Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Colloidal drug probe : Method development and validation for adhesion force measurement using Atomic Force Microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between a model drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from dry powder inhaler (DPI) formulations. Model silica probes of approximately 4 lm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres pre-attached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/ hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Measuring the adhesion force on natural fibre surface using scanning probe microscopy

This work has focused on measuring the adhesion forces on both untreated and atmospheric helium plasma treated single jute fibre surfaces using scanning probe microscopy (SPM). The measurements were conducted on three differently aged surfaces for one week, three weeks and six weeks using a standard silicon nitride tip in force-volume (f-v) mode. Up to 256 adhesion data points were collected from various locations on the surface of the studied fibres using in-house developed software and the resulting data were statistically analysed by the histogram method. Results obtained from this analysis method were found to be very consistent with a small statistical variation. The work of adhesion, Wa, was calculated from measured adhesion force using the Johnson–Kendall–Roberts (JKR) and Derjaguin–Muller–Toporov (DMT) models. Increases in both adhesion force and work of adhesion were observed on jute fibre with certain levels of atmospheric plasma treatment and ageing time.

Influence of Particle Size, Applied Compression, and Substratum Material on Particle-Surface Adhesion Force Using the Centrifuge Technique

The centrifuge technique was used to investigate the influence of particle size, applied compression, and substrate material (stainless steel, glass, Teflon, and poly(vinyl chloride)) on particle-surface adhesion force. For this purpose, phosphatic rock (rho(p) = 3090 kg/m(3)) and manioc starch particles (rho(p) = 1480 kg/m(3)) were used as test particles. A microcentrifuge that reached a maximum rotation speed of 14 000 rpm and which contained specially designed centrifuge tubes was used in the adhesion force measurements. The curves showed that the adhesion force profile followed a normal log distribution. The adhesion force increased linearly with particle size and with the increase of each increment of compression force. The manioc starch particles presented greater adhesion forces than the phosphatic rock particles for all particle sizes studied. The glass substrate showed a higher adherence than the other materials, probably due to its smoother topographic surface roughness in relation to the other substrata.

Quantitative characterization of adhesion and stiffness of corneal lens of Drosophila melanogaster using atomic force microscopy

Atomic force Microscopy (AFM) has become a versatile tool in biology due to its advantage of high-resolution imaging of biological samples close to their native condition. Apart from imaging, AFM can also measure the local mechanical properties of the surfaces. In this study, we explore the possibility of using AFM to quantify the rough eye phenotype of Drosophila melanogaster through mechanical properties. We have measured adhesion force, stiffness and elastic modulus of the corneal lens using AFM. Various parameters affecting these measurements like cantilever stiffness and tip geometry are systematically studied and the measurement procedures are standardized. Results show that the mean adhesion force of the ommatidial surface varies from 36 nN to 16 nN based on the location. The mean stiffness is 483 +/- 5 N/m, and the elastic modulus is 3.4 +/- 0.05 GPa (95% confidence level) at the center of ommatidia. These properties are found to be different in corneal lens of eye expressing human mutant tau gene (mutant). The adhesion force, stiffness and elastic modulus are decreased in the mutant. We conclude that the measurement of surface and mechanical properties of D. melanogaster using AFM can be used for quantitative evaluation of `rough eye' surface. (C) 2015 Elsevier Ltd. All rights reserved.

Mapping of adhesion forces on soil minerals in air and water by atomic force spectroscopy (AFS)

The adhesion force between an atomic force microscope (AFM) tip and sample surfaces, mica and quartz substrates, was measured in air and water. The force curves show that the adhesion has a strong dependence on both the surface roughness and the environmental conditions surrounding the sample. The variability of the adhesion force was examined in a series of measurements taken at the same point, as well as at different places on the sample surface. The adhesion maps obtained from the distribution of the measured forces indicated regions contaminated by either organic compounds or adsorbed water. Using simple mathematical expressions we could quantitatively predict the adhesion force behavior in both air and water. The experimental results are in good agreement with theoretical calculations, where the adhesion forces in air and water were mostly associated with capillary and van der Waals forces, respectively. A small long-range repulsive force is also observed in water due to the overlapping electrical double-layers formed on both the tip and sample surfaces.

Adhesion and dispersion of salmeterol xinofoate from lactose interactive mixtures for inhalation - can surface roughness of carriers determine performance

The objective was to understand the influence of the surface roughness of lactose carriers on the adhesion and dispersion of salmeterol xinafoate (SX) from interactive mixtures. The surface roughness of lactose carriers was determined by confocal microscopy. Particle images and adhesion forces between SX and lactose particles were determined by Atomic Force Microscopy. The dispersion of SX (2.5%) from interactive mixtures with lactose was determined using a twin-stage impinger (TSI) with a Rotahaler® at an airflow rate of 60L/min. SX was analysed using a validated HPLC assay. The RMS Rq of lactose carriers ranged from 0.93-2.84μm, the Fine Particle Fraction (FPF) of SX ranged between 4 and 24 percent and average adhesion force between a SX and lactose particles ranged between 49 and 134 nN. No direct correlation was observed between the RMS Rq of lactose carriers and either the FPF of SX for the interactive mixtures or the adhesion force of a SX on the lactose particles; however, the presence of fine lactose associated with the carrier surface increased the FPF of SX. Dispersion through direct SX detachment from the carrier surface was not consistent with the poor correlations described and was more likely to occur through complex particulate interactions involving fine lactose.

Adhesion-Induced Instability in Asperities

Adhesive forces between two approaching asperities will deform the asperities, and under certain conditions this will result in a sudden runaway deformations leading to a jump-to-contact instability. We present finite element-based numerical studies on adhesion-induced deformation and instability in asperities. We consider the adhesive force acting on an asperity, when it is brought near a rigid half-space, due to van der Waals interaction between the asperity and the half-space. The adhesive force is considered to be distributed over the volume of the asperity (body force), thus resulting in more realistic simulations for the length scales considered. Iteration scheme based on a ``residual stress update'' algorithm is used to capture the effect of deformation on the adhesion force, and thereby the equilibrium configuration and the corresponding force. The numerical results are compared with the previous approximate analytical solutions for adhesion force, deformation of the asperity and adhesion-induced mechanical instability (jump-to-contact). It is observed that the instability can occur at separations much higher,and could possibly explain the higher value of instability separation observed in experiments. The stresses in asperities, particularly in case of small ones, are found to be high enough to cause yielding before jump -to-contact. The effect of roughness is considered by modeling a spherical protrusion on the hemispherical asperity.This small-scale roughness at the tip of the asperities is found to control the deformation behavior at small separations, and hence are important in determining the friction and wear due to the jump-to-contact instability.

Energy loss due to adhesion in longitudinal impact of elastic cylinders

Adhesive interaction between impacting bodies can cause energy loss, even in an otherwise elastic impact. Adhesion force induces tensile stress in the bodies, which modifies the stress wave profile and influences the restitution behavior. We investigate this effect by developing a finite element framework, which incorporates a Lennard-Jones-type potential for modeling the adhesive interaction between volume elements. With this framework, the classical problems in contact mechanics can be revisited without the restrictive surface-force approximation. In this paper, we study the longitudinal impact of an elastic cylinder on a rigid half-space with adhesion. In the absence of adhesion, this problem reduces to the impact between two identical cylinders in which there is no energy loss. Adhesion causes a fraction of energy in the stress waves to remain in the cylinder as residual stress waves. This apparent loss in kinetic energy is shown to be a unique function of maximum tensile strain energy. We have developed a 1-D model in terms of interaction force parameters, velocity and material properties to estimate the tensile stain energy. We show that this model can be used to predict practically important phenomena like capture wherein the impacting bodies stick together. (C) 2013 Elsevier Masson SAS. All rights reserved.

Interaction between single molecules of Mac-1 and ICAM-1 in living cells: An atomic force microscopy study

The interaction between integrin macrophage differentiation antigen associated with complement three receptor function (Mac-1) and intercellular adhesion molecule-1 (ICAM-1), which is controlled tightly by the ligand-binding activity of Mac-1, is central to the regulation of neutrophil adhesion in host defense. Several "inside-out" signals and extracellular metal ions or antibodies have been found to activate Mac-1, resulting in an increased adhesiveness of Mac-1 to its ligands. However, the molecular basis for Mac-1 activation is not well understood yet. In this work, we have carried out a single-molecule study of Mac-1/ICAM-1 interaction force in living cells by atomic force microscopy (AFM). Our results showed that the binding probability and adhesion force of Mac-1 with ICAM-1 increased upon Mac-1 activation. Moreover, by comparing the dynamic force spectra of different Mac-1 mutants, we expected that Mac-1 activation is governed by the downward movement of its alpha 7 helix. (c) 2007 Elsevier Inc. All rights reserved.

Electrostatic force microscope for probing surface charges in aqueous solutions.

A scanning force microscope was converted to an electrostatic force microscope by charging the usually neutral cantilever with phospholipids. The electrostatic force microscope was used to study surface electrostatic charges of samples in aqueous solutions. Lysozymes, DEAE-Sephadex beads, 3-propyltriethoxysilane-treated glass and mica were imaged in water or phosphate buffer with electrostatic force microscopy. The adhesion force measured when a charged probe and oppositely charged specimen interacted was up to 500 times greater than when a bare probe was used. This dramatic increase in measured adhesion force can be attributed to the energy required to break the salt bridges formed between the charged probe and the specimen. The use of phospholipids to functionalize the cantilever tip allows the incorporation of other biomolecules and ligands that can be used as biologically specific tips (e.g., receptors, drugs) for the study of intermolecular interactions.

Growth of liquid bridge in AFM

Capillary forces are dominant in adhesive forces measured with an atomic force microscope (AFM) in ambient air, which are thought to be dependent on water film thickness, relative humidity and the free energy of the water film. In this paper, besides these factors, we study the nature of the 'pull-off' force on a variety of atmospheres as a function of the contact time. It is found that capillary forces strongly depend on the contact time. In lower relative humidity atmosphere, the adhesion force is almost independent of the contact time. However, in higher relative humidity, the adhesion force increases with the contact time. Based on the experiment and a model that we present in this paper, the growth of the liquid bridge can be seen as undergoing two processes: one is water vapour condensation; the other is the motion of the thin liquid film that is absorbed on the substrate. The experiment and the growth model presented in this paper have direct relevance to the working mechanism of AFM in ambient air.