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The detection of trace amounts of explosive materials is critical to the security at mass transit centers (e.g., airports and railway stations). In a typical screening process, a trap is used to probe a surface of interest to collect and transfer particulate residue to a detector for analysis. The collection of residues from the surface being probed is widely viewed as the limiting step in this process. A multi-institutional study was performed to establish a methodology for the evaluation of sampling media collection efficiencies. Dry deposited residues of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), C-4 (an RDX-based explosive), and pentaerythritol tetranitrate (PETN) were harvested from acrylonitrile butadiene styrene (ABS) plastic, ballistic nylon (NYL), and uncoated aluminum surfaces using muslin, Texwipe cotton, and stainless-steel mesh traps. Transfer and collection efficiencies of the sample media were calculated based on liquid chromatography-mass spectrometry analysis. Dry transfer efficiencies (DTE%) to all tested surfaces were greater than 75%, with transfer to ABS plastic being the lowest. Collection efficiency (CE%) varied significantly across the traps and the surfaces, yet some conclusions can be drawn; nylon had the lowest CE% for all cases (â¼10%), and the stainless steel mesh had the lowest CE% for the evaluated traps (â¼20%). Though the testing parameters have been standardized among the participants to establish a framework for an independent comparison of contact sampling media and surfaces, substantial variations in the DTE% and the CE% were observed, suggesting that other variables can affect contact sampling.
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Substâncias Explosivas , Tetranitrato de Pentaeritritol , Humanos , Espectrometria de Massas , Têxteis , TriazinasRESUMO
The solubility advantage of amorphous solid dispersions (ASDs) is contingent upon supersaturation being generated and maintained. If crystals are present within an ASD, these crystals directly result in lost solubility advantage, and may also seed crystal growth leading to desupersaturation. The goal of this study was to evaluate the impact of residual crystals on ASD supersaturation profiles. Indomethacin-copovidone (PVPVA) ASDs with different levels of residual crystallinity were manufactured by hot melt extrusion (HME). PVPVA at 5 and 50 µg/mL was found to be a highly effective nucleation and crystal growth inhibitor of indomethacin at high supersaturation. Evidence of polymer adsorption onto indomethacin crystals was observed by atomic force microscopy and scanning electron microscopy. HME ASDs containing 0-25% residual crystallinity demonstrated lost solubility advantage, along with minimal desupersaturation during non-sink dissolution testing. While bulk seeds did not properly represent the impact of residual crystals, extensive polymer adsorption onto residual seed crystals resulted in poisoned crystal growth, limiting the potential dissolution performance consequences. Several risk factors related to the presence of residual crystallinity were identified: polymeric crystal growth inhibition effectiveness, seed properties, and supersaturation conditions.
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Cristalização , Polímeros/química , Adsorção , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , SolubilidadeRESUMO
The London-van der Waals (L-vdW) force between a particle and a surface strongly depends on the topography and the chemical properties of the interacting surfaces. Although a great deal of work has been done to understand the effect of topographical heterogeneity on the L-vdW adhesion, the role of chemical heterogeneity has been discussed only rarely. This study makes an attempt to quantify the magnitude and range of the L-vdW force acting on a spherical particle in the vicinity of a chemically patterned surface. Specifically, an ideal system of a smooth spherical particle approaching a surface composed of parallel stripes of chemically distinct materials with different Hamaker constants is considered. The L-vdW forces for such systems are determined by solving the London dispersion potential for the entire volumes of the adhering bodies from first principles, using Hamaker's microscopic approach. The computational results elucidate that a chemical interface can apply a tangential L-vdW force, in addition to the normal L-vdW force, on nearby particles. This can cause lateral motion of particles neighboring a chemically inhomogeneous surface. The magnitude of the tangential L-vdW force is found to be maximum when the particle is centered at the interface and shows a gradual drop as it moves away from this location. The magnitude and range of the tangential L-vdW force can be large for large colloidal particles in close contact with a chemically patterned surface whose materials have distinct Hamaker constants. This study suggests that the tangential L-vdW force field generated by a chemical interface can be utilized as a tool to manipulate the path of an approaching particle to facilitate selective adhesion.
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Amorphous solid dispersions are widely used to enhance the oral bioavailability of poorly water-soluble drugs. Polymeric additives are commonly used to delay crystallization of the drug from the supersaturated solutions formed upon ASD dissolution by influencing the nucleation and growth of crystals. However, there is limited evidence regarding the mechanisms by which polymers stabilize supersaturated drug solutions. The current study used experiments and computational modeling to explore polymer-drug interactions in aqueous solutions. Nucleation induction times for supersaturated solutions of nine drugs in the presence of five newly synthesized cellulose-based polymers were evaluated. The polymers had carboxylic acids substituents with additional variations in the side-chain structure: (1) one with a single side chain and a carboxylic acid termination, (2) three with a branched side chain terminated with a carboxylic and an alcohol group (varying the cellulose linkage and the length of the hydrocarbon side chain), and (3) one with a branched side chain with two carboxylic acid end groups. The polymers with a short side chain and one carboxylic acid were effective, whereas the polymers with the two carboxylic acids or a long hydrocarbon chain were less effective. Atomic force microscopy experiments, evaluating polymer adsorption onto amorphous drug films, indicated that the effective polymers were uniformly spread across the surface. These results were supported by molecular dynamics simulations of a polymer chain in the presence of a drug aggregate in an aqueous environment, whereby the effective materials had a higher probability of establishing close contacts and more negative estimated free energies of interaction. The insights provided by this study provide approaches to design highly effective polymers to improve oral drug delivery.
Assuntos
Celulose/química , Sistemas de Liberação de Medicamentos , Ésteres/química , Éteres/química , Disponibilidade Biológica , Ácidos Carboxílicos/química , Celulose/síntese química , Cristalização , Ésteres/síntese química , Éteres/síntese química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Polímeros/química , Solubilidade , Água/químicaRESUMO
HYPOTHESIS: Surface effects arising from roughness and deformation can negatively affect the results of AFM contact experiments. Using the non-contact portion of an AFM deflection curve is therefore desirable for estimating the Hamaker constant, A, of a solid material. A previously validated non-contact quasi-dynamic method for estimating A is revisited, in which the cantilever tip is now always represented by an "effective sphere". In addition to simplifying this previous method, accurate estimates of A can still be obtained even though precise knowledge of the nanoscale geometric features of the cantilever tip are no longer required. EXPERIMENTS: The tip's "effective" radius of curvature, Reff, is determined from a "calibration" step, in which the tip's deflection at first contact with the surface is measured for a substrate with a known Hamaker constant. After Reff is known for a given tip, estimates of A for other surfaces of interest are then determined. FINDINGS: An experimental study was conducted to validate the new method and the obtained results are in good agreement with predictions from the Lifshitz approximation, when available. Since Reff accounts for all geometric uncertainties of the tip through a single fitted parameter, no visual fitting of the tip shape was required.
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In order to minimize the effects of surface roughness and deformation, a new method for estimating the Hamaker constant, A, of solids using the approach-to-contact regime of an atomic force microscope (AFM) is presented. First, a previous "jump-into-contact" quasi-static method for determining A from AFM measurements is analyzed and then extended to include various AFM tip-surface force models of interest. Then, to test the efficacy of the "jump-into-contact" method, a dynamic model of the AFM tip motion is developed. For finite AFM cantilever-surface approach speeds, a true "jump" point, or limit of stability, is found not to appear, and the quasi-static model fails to represent the dynamic tip behavior at close tip-surface separations. Hence, a new "quasi-dynamic" method for estimating A is proposed that uses the dynamically well-defined deflection at which the tip and surface first come into contact, dc, instead of the dynamically ill-defined "jump" point. With the new method, an apparent Hamaker constant, Aapp, is calculated from dc and a corresponding quasi-static-based equation. Since Aapp depends on the cantilever's approach speed, vc, and the AFM's sampling resolution, δ, a double extrapolation procedure is used to determine Aapp in the quasi-static (vc â 0) and continuous sampling (δ â 0) limits, thereby recovering the "true" value of A. The accuracy of the new method is validated using simulated AFM data. To enable the experimental implementation of this method, a new dimensionless parameter τ is introduced to guide cantilever selection and the AFM operating conditions. The value of τ quantifies how close a given cantilever is to its quasi-static limit for a chosen cantilever-surface approach speed. For sufficiently small values of τ (i.e., a cantilever that effectively behaves "quasi-statically"), simulated data indicate that Aapp will be within â¼3% or less of the inputted value of the Hamaker constant. This implies that Hamaker constants can be reliably estimated using a single measurement taken with an appropriately chosen cantilever and a slow, yet practical, approach speed (with no extrapolation required). This result is confirmed by the very good agreement found between the experimental AFM results obtained using this new method and previously reported predictions of A for amorphous silica, polystyrene, and α-Al2O3 substrates obtained using the Lifshitz method.
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Cohesive Hamaker constants of solid materials are measured via optical and dielectric properties (i.e., Lifshitz theory), inverse gas chromatography (IGC), and contact angle measurements. To date, however, a comparison across these measurement techniques for common energetic materials has not been reported. This has been due to the inability of the community to produce samples of energetic materials that are readily compatible with contact angle measurements. Here we overcome this limitation by using physical vapor deposition to produce thin films of five common energetic materials, and the contact angle measurement approach is applied to estimate the cohesive Hamaker constants and surface energy components of the materials. The cohesive Hamaker constants range from 85zJ to 135zJ across the different films. When these Hamaker constants are compared to prior work using Lifshitz theory and nonpolar probe IGC, the relative magnitudes can be ordered as follows: contact angle>Lifshitz>IGC. Furthermore, the dispersive surface energy components estimated here are in good agreement with those estimated by IGC. Due to these results, researchers and technologists will now have access to a comprehensive database of adhesion constants which describe the behavior of these energetic materials over a range of settings.
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Realistic descriptions of interfacial contact between rough, deformable surfaces under load are difficult to obtain; however, this contact is of great import in a wide range of applications. Here, we detail, through experiment and computational simulation, the interfacial contact between four common traps and five commonly investigated surfaces encountered in explosives detection applications associated with airport security. The Young's modulus and hardness of four traps and seven substrates were measured using nanoindentation. These properties determine how deformation occurs when traps are applied for contact sampling of explosives. The nanoindentation data were analyzed using the Oliver-Pharr method, and an indenter area function was created using silicon and gold as the reference materials. The Young's moduli of the traps ranged from 0.2 to 8 GPa, while those of the surfaces ranged from 0.5 to 4 GPa. The hardness values of the traps ranged from 0.005 to 0.22 GPa, while those of the surfaces ranged from 0.02 to 0.2 GPa. For each of 20 scenarios (4 traps, 5 surfaces), six contact simulations were performed. In these contact simulations, the Greenwood-Willliamson microcontact model was used to represent the behavior of the asperities on the traps, while the Timoshenko Beam model was used to describe the macroscopic behavior of the bulk trap materials spanning the space between asperities. This combination of feature- and trap-scale modeling provides a more realistic description of the interfacial contact than either model applied individually. The calculated distributions of separation distances between the traps and surfaces when the traps were contacted with the surfaces under a normal load were compared to estimate the relative effectiveness of the traps at interrogating the topography of the surfaces. This method is proposed as a tool to guide the development of trap materials for surface sampling and surface cleaning applications.
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The bioavailability of orally administered drugs that exhibit poor aqueous solubility can be enhanced with the use of supersaturating dosage forms. Stabilization of these forms by preventing or inhibiting crystallization in solution is an important area of study. Polymers can be used to stabilize supersaturated systems; however, the properties that impact their effectiveness as crystal growth rate inhibitors are not yet fully understood. In this study, the impact of various polymers on the crystal growth rate of felodipine and the conformation of these polymers adsorbed to crystalline felodipine was investigated in order to gain a mechanistic understanding of crystal growth inhibition. It was determined that polymer hydrophobicity impacted polymer adsorption as well as adsorbed polymer conformation. Polymer conformation impacts its surface coverage, which was shown to directly correlate to the polymer's effectiveness as a growth rate inhibitor. By modeling this correlation, it is possible to predict polymer effectiveness given the surface coverage of the polymer.
Assuntos
Polímeros/química , Adsorção , Felodipino , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Tamanho da Partícula , Soluções , Propriedades de SuperfícieRESUMO
Poor aqueous solubility is a major hindrance to oral delivery of many emerging drugs. Supersaturated drug solutions can improve passive absorption across the gastrointestinal tract membrane as long as crystallization can be inhibited, enhancing the delivery of such poorly soluble therapeutics. Polymers can inhibit crystallization and prolong supersaturation; therefore, it is desirable to understand the attributes which render a polymer effective. In this study, the conformation of a polymer adsorbed to a crystal surface and its impact on crystal growth inhibition were investigated. The crystal growth rate of a poorly soluble pharmaceutical compound, felodipine, was measured in the presence of hydroxypropyl methylcellulose acetate succinate (HPMCAS) at two different pH conditions: pH 3 and pH 6.8. HPMCAS was found to be a less effective growth rate inhibitor at pH 3, below its pKa. It was expected that the ionization state of HPMCAS would most likely influence its conformation at the solid-liquid interface. Further investigation with atomic force microscopy (AFM) revealed significant differences in the conformation of HPMCAS adsorbed to felodipine at the two pH conditions. At pH 3, HPMCAS formed coiled globules on the surface, whereas at pH 6.8, HPMCAS adsorbed more uniformly. Thus, it appeared that the reduced effectiveness of HPMCAS at pH 3 was directly related to its conformation. The globule formation leaves many felodipine growth sites open and available for growth units to attach, rendering the polymer less effective as a growth rate inhibitor.
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Felodipino/química , Polímeros/química , Água/química , Cristalização , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Microscopia de Força Atômica , Conformação Molecular , SolubilidadeRESUMO
The goal of this work was to evaluate the ability of photothermal-induced resonance (PTIR) to measure the local infrared absorption spectra of crystalline organic drug nanoparticles embedded within solid matrices. Herein, the first reports of the chemical characterization of sub-100 nm organic crystals are described; infrared spectra of 90 nm griseofulvin particles were obtained, confirming the chemical resolution of PTIR beyond the diffraction limit. Additionally, particle size distributions via dynamic light scattering and PTIR image analysis were found to be similar, suggesting that the PTIR measurements are not significantly affected by inhomogeneous infrared absorptivity of this system. Thus as medical applications increasingly emphasize localized drug delivery via micro/nanoengineered structures, PTIR can be used to unambiguously chemically characterize drug formulations at these length scales.
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Griseofulvina/análise , Microscopia de Força Atômica/métodos , Nanopartículas/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Griseofulvina/química , Nanopartículas/química , Espectrofotometria Infravermelho/métodosRESUMO
Atomic force microscopy (AFM) was used to investigate the effect of relative humidity (RH) on the adhesion forces between silicon nitride AFM probes, hydrophilic stainless steel, and hydrophobic Perspex® (polymethylmethacrylate, PMMA). In addition, AFM-based phase contrast imaging was used to quantify the amount and location of adsorbed water present on these substrates at RH levels ranging from 15% to 65% at 22°C. Both the adhesion forces and the quantities of adsorbed moisture were seen to vary with RH, and the nature of this variation depended on the hydrophobicity of the substrate. For the Perspex®, both the adhesion force and the amount of adsorbed moisture were essentially independent of RH. For the stainless steel substrate, adsorbed moisture increased continuously with increasing RH, while the adhesion force rose from a minimum at 15% RH to a broad maximum between 25% and 35% RH. From 35% to 55% RH, the adhesion force dropped continuously to an intermediate level before rising again as 65% RH was approached. The changes in adhesion force with increasing relative humidity in the case of the stainless steel substrate were attributed to a balance of effects associated with adsorbed, sub-continuum water on the cantilever and steel. Hydrogen bonding interactions between these adsorbed water molecules were thought to increase the adhesion force. However, when significant quantities of molecular water adsorbed, these molecules were expect to decrease adhesion by screening the van der Waals interactions between the steel and the cantilever tip, and by increasing the separation distance between these solid surfaces when they were 'in contact'. Finally, the slight increase in adhesion between 55% and 65% RH was attributed to true capillary forces exerted by continuum water on the two solid surfaces.
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Umidade , Propriedades de Superfície , Microscopia de Força Atômica , Microscopia Eletrônica de VarreduraRESUMO
It is of increasing importance to understand how explosive particles adhere to surfaces in order to understand how to remove them for detection in airport or other security settings. In this study, adhesion forces between royal demolition explosive (cyclotrimethylenetrinitramine) (RDX), pentaerythritol tetranitrate (PETN), and trinitrotoluene (TNT) in their crystalline forms and aluminum coupons with three finishes, acrylic melamine (clear coating), polyester acrylic melamine (white coating) automotive finishes, and a green military-grade finish, were measured and modeled. The force measurements were performed using the atomic force microscopy (AFM)-based colloidal probe microscopy (CPM) method. Explosive particles were mounted on AFM cantilevers and repeatedly brought in and out of contact with the surfaces of interest while the required force needed to pull out of contact was recorded. An existing Matlab-based simulator was used to describe the observed adhesion force distributions, with excellent agreement. In these simulations, the measured topographies of the interacting surfaces were considered, although the geometries were approximated. The simulations were performed using a van der Waals force-based adhesion model and a composite effective Hamaker constant. It was determined that certain combinations of roughness on the interacting surfaces led to preferred particle-substrate orientations that produced extreme adhesion forces.
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A successful approach to calculating van der Waals (vdW) forces between irregular bodies is to divide the bodies into small cylindrical volume elements and integrate the vdW interactions between opposing elements. In this context it has been common to use Hamaker's expression for parallel plates to approximate the vdW interactions between the opposing elements. This present study shows that Hamaker's vdW expression for parallel plates does not accurately describe the vdW interactions for co-axial cylinders having a ratio of cylinder radius to separation distance (R/D) of 10 or less. This restricts the systems that can be simulated using this technique and explicitly excludes consideration of topographical or compositional variations at the nanoscale for surfaces that are in contact or within a few nm of contact. To address this limitation, approximate analytical expressions for nonretarded vdW forces between finite cylinders in different orientations are derived and are shown to produce a high level of agreement with forces calculated using full numerical solutions of the corresponding Hamaker's equations. The expressions developed here allow accurate calculation of vdW forces in systems where particles are in contact or within a few nm of contact with surfaces and the particles and/or surfaces have heterogeneous nanoscale morphology or composition. These calculations can be performed at comparatively low computational cost compared to the full numerical solution of Hamaker's equations.
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Orientational anisotropy of collagen molecules is integral to the mechanical strength of collagen-rich tissues. We have previously reported a novel methodology to synthesize highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties approaching those of native tendon. Decorin, a small leucine-rich proteoglycan (SLRP), binds to fibrillar collagen and has been suggested to enhance the mechanical properties of tendon. Based on the structure of natural decorin, we have previously designed and synthesized a peptidoglycan (DS-SILY) that mimics decorin both structurally and functionally. In this study, we investigated the effect of the incorporation of DS-SILY on the mechanical properties and structural organization of ELAC threads. The results indicated that the addition of DS-SILY at a molar ratio of 30:1 (collagen:DS-SILY) significantly enhanced the ultimate stress and ultimate strain of the ELAC threads. Furthermore, differential scanning calorimetry revealed that the addition of DS-SILY at a molar ratio of 30:1 resulted in a more thermally stable collagen structure. However, addition of DS-SILY at a higher concentration (10:1 collagen:DS-SILY) yielded weaker threads with mechanical properties comparable to collagen control threads. Transmission electron microscopy revealed that the addition of DS-SILY at a higher concentration (10:1) resulted in pronounced aggregation of collagen fibrils. More importantly, these aggregates were not aligned along the long axis of the ELAC, thereby compromising the overall tensile properties of the material. We conclude that incorporation of an optimal amount of DS-SILY is a promising approach to synthesize mechanically competent collagen-based biomaterials for tendon tissue engineering applications.
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Colágeno/química , Decorina/química , Eletroquímica/métodos , Mimetismo Molecular , Varredura Diferencial de Calorimetria , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Oxirredução , Reologia , Resistência à TraçãoRESUMO
Dextran and polyethylene glycol (PEG) are often covalently bound to the surface of polydimethylsiloxane (PDMS) for the purpose of modifying its hydrophilicity and biocompatibility. In this work, the effects of the dextran and PEG on the morphology, wetting, and surface charge of the resulting surfaces were quantified and correlated with changes in the amount of fibrinogen and albumin adsorbed from aqueous solution. PDMS films were functionalized in a microwave oxygen plasma to create surface hydroxyl groups that were subsequently aminated by incubation in a (3-aminopropyl)trimethoxysilane (APTES) solution. Oxidized dextran and PEG-aldehyde were linked to the surface amines via reductive amination. This process resulted in low surface coverage of immobilized PEG in the end-on conformation and a more uniform and dense distribution of side-on immobilized dextran. The immobilized dextran reduced the contact angle of the PDMS film from 109° to 80° and neutralized the zeta potential over the pH range from 3 to 11. An atomic force microscope was used to measure the interaction force between the modified PDMS and a model hydrophobic surface (polystyrene latex) and a model hydrophilic surface (silica) in aqueous solution to show that van der Waals and hydrophobic attractive forces are the dominant forces for protein adsorption in this system. The PEG- and dextran-modified PDMS were exposed to BSA and fibrinogen to test their resistance to protein adsorption. The coatings were ineffective at reducing the adsorption of either molecule, and the dextran-modification of the PDMS caused more BSA to adsorb than in the case of the unmodified PDMS.
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Dextranos/química , Fibrinogênio/química , Polietilenoglicóis/química , Soroalbumina Bovina/química , Adsorção , Animais , Bovinos , Membranas Artificiais , Micro-Ondas , Oxirredução , Poliestirenos/química , Dióxido de Silício/química , Soluções , Propriedades de Superfície , Água/química , MolhabilidadeRESUMO
The interactions between nanoparticles and rough surfaces are of great scientific and engineering importance and have numerous applications in surface science and biotechnology. Surface geometry and roughness play crucial roles in observed particle adhesion forces. We previously developed a model and simulation approach to describe adhesion between microscale bodies. This work provides detailed descriptions of the modeling framework, with associated experimental validation, applied to nanoscale systems. The physical systems of interest include nanoscale silicon nitride adhering to different surfaces in both dry and aqueous environments. To perform the modeling work, precise descriptions of the geometry of the particle and the roughness of the particle and substrate were generated. By superimposing the roughness and geometry models for the particle and the substrate, it was possible to precisely describe the spatial configurations of the adhering surfaces. The interacting surfaces were then discretized, and the adhesion force between the two surfaces was calculated by using Hamaker's additive approach, based on van der Waals interactions. In the experimental work, an atomic force microscope (AFM) was used to measure the adhesion force (pull-off force) between nanoscale silicon nitride cantilever tips and a range of substrates in different environments. The measured and predicted force distributions were compared, and good agreement was observed between theory and experiment.
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Two mycocardial infarction biomarkers, myoglobin (MG) and cardiac troponin I (cTnI), were quantified at biological levels and in undiluted serum without sample pretreatment using surface plasmon resonance (SPR) sensors. To achieve detection of biomarkers in undiluted serum (72 mg/mL total protein concentration), minimization of the nonspecific signal from the serum protein was achieved by immobilizing the antibody for the biomarkers on an N-hydroxysuccinimide activated 16-mercaptohexadecanoic acid self-assembled monolayer. This monolayer reduces the nonspecific signal from serum proteins in such a manner that short exposure of the sensor to serum prior to analysis prevents any further nonspecific adsorption during analysis. Thus, sensing of MG and cTnI was achieved on the basis of the difference between signals from the active sensor and a reference sensor that captured background interference. This resulted in direct measurement of these biomarkers in undiluted serum. Detection limits for both markers were below 1 ng/mL, which is below the threshold needed to detect myocardial infarction. Detecting biomarkers in the low ng/mL range without signal amplification in such a complex matrix as serum corresponds to a selectivity of 108. The root-mean-square-error (RMSE) of calibration was below 2 ng/mL.