Ellipsometry is a powerful tool for the evaluation of the refractive index profile of a film or coating supported on a solid substrate. A well-acknowledged problem, however, is the inverse problem: Given a set of data, under what conditions can a refractive index profile be determined unambiguously? To this end, a series expansion of the Abeles matrix method has been applied to an arbitrary refractive index profile to determine analytic expressions of the ellipsometric ratio rho. Two types of expressions are found: The thin film limit in which the film thickness L is much less than the wavelength of the incident light beam (L << lambda) and the weak contrast limit in which the refractive index of the coating is very near the refractive index of the supporting substrate. In the thin film limit, the first two terms in the series expansion are relatively straight-forward, and they depend on two types of integrals involving the difference between the dielectric profile of the coating and the dielectric constant of the substrate. While higher order terms are possible, they are quite convoluted and do not assist in the inverse problem. In the weak contrast limit, however, the series expansion of rho depends on the moments of the difference between the dielectric profile of the coating and the dielectric constant of the substrate, allowing an analytic expression that applies to coatings that are even much larger than the incident light beam. The expressions associated with both limits are verified through comparison to the numerical evaluation of rho with the Abeles matrix method. The results demonstrate that through judicious selection of the substrate refractive index and incident wavelength, conditions can be created that permit critical insights into the inverse problem for either thin coatings or for coatings that are very near the refractive index of the substrate.

Magnesium and its alloys are promising candidate materials for medical implants because they possess excellent biocompatibility and mechanical properties comparable to bone. Furthermore, secondary surgical operations for removal could be eliminated due to magnesium's biodegradability. However, magnesium's degradation rate in aqueous environments is too high for most applications. It has been reported that hydrophobic textured surfaces can trap a surface gas layer which acts as a protective barrier against corrosion. However, prior studies have not investigated separately the role of the texture and hydrophobic treatments on magnesium corrosion rates. In this study, pillar-shaped microstructure patterns were fabricated on polished high purity magnesium surfaces by ablation with a picosecond laser. Some micropatterned samples were further processed by stearic acid modification (SAM). Micropatterned surfaces with SAM had hydrophobic properties with water droplet contact angles greater than 130°, while the micropatterned surfaces without SAM remained hydrophilic. The corrosion properties of textured and smooth magnesium surfaces in saline solution were investigated using electrochemical impedance spectroscopy (EIS) and optical microscopy. Corrosion rates on both hydrophobic and hydrophilic laser machined surfaces were reduced ∼90% relative to polished surfaces. Surprisingly, corrosion rates were similar for both hydrophobic and hydrophilic surfaces. Indirect evidence of local alkalization near microstructures was found and was hypothesized to stabilize the Mg(OH)2 layer, thereby inhibiting corrosion on hydrophilic surfaces. This is different than the corrosion resistance mechanism for superhydrophobic surfaces which makes use of gas adhesion at the liquid solid interface. These results suggest additional processing to render the magnesium hydrophobic is not necessary since it does not significantly enhance the corrosion resistance beyond what is conferred by micropatterned textures.

Magnesium and magnesium-based alloys have relatively low weight and desirable mechanical properties for many applications in multiple industries including aerospace and automotive. In the past decade, due to its biocompatible nature, the medical field has expressed significant interest in magnesium for biodegradable implant applications. However, utilization of magnesium-based alloys in surgical implant applications is strictly limited by magnesium’s high vulnerability to corrosion causing premature disintegration inside the human body. Hydrophobic (non-wetting) behavior of metal surfaces has been proven to be beneficial for corrosion protection in academic literature. One way of achieving hydrophobic and super-hydrophobic surfaces on metal surfaces without using non-biocompatible coatings is creating uniform microstructures that would alter the wetting characteristics of the surface. This work focuses on creating uniform pillar shaped micro-patterns on smooth pure magnesium surfaces by utilizing a picosecond laser (λ = 355 nm). The study reports the effects of average laser power, partial laser beam overlap and number of laser scans on the height, steepness, roughness of the resultant micro-pillars. Information gathered from this study could be useful in creating more complex or finer micro-structures on magnesium and its alloys to alter their wetting or corrosion characteristics using laser ablation which is a fast, repeatable and an un-convoluted process.

Thermally responsive coatings of poly(N-isopropylacrylamide), or poly(NIPAAm), have a volume phase transition temperature (VPTT) near 32 °C. Below this temperature, the coating imbibes water and swells. Above this temperature, the coating rejects water and collapses. Herein, a spinning disk method is used to determine the hydrodynamic shear stress necessary to remove 10 μm polystyrene (PS) microspheres capped with either carboxylic acid (COOH) functionality or immunoglobulin (IgG) proteins from the coatings as a function of coating thickness and temperature. In the case of the PS-COOH, the hydrodynamic shear stress necessary to remove the microspheres was consistently larger below the VPTT than above the VPTT of the poly(NIPAAm) coating. In the case of PS-IgG, the trend was reversed, in which the hydrodynamic shear stress necessary to remove the microspheres was consistently smaller below the VPTT than above the VPTT. Simple scaling relationships were developed to explain the findings within the Johnson-Kendall-Roberts (JKR) model of contact mechanics, which illustrates the delicate interplay between the pull-off force and contact radius (as determined by the coating shear modulus) in governing particle removal from soft surfaces with hydrodynamic forces.

This project focuses on studying the optimal design of a drug delivery system based on niosomes (non-ionic surfactants vesicles) embedded in a hydrogel network (chitosan) to ensure full control of the release time and dosage of cancer treatment drugs for localized delivery. Here we present data on the molecular interactions facilitating specific binding at tumor cell surfaces to aid in the treatment of ovarian, brain and lung cancers to name a few. We have done three types of characterizations to determine the basic design parameters for a personalized cancer treatment. First, we determined how fundamental surface interactions can be optimized to target and attack tumor integrity and boundaries. We used confocal microscopy and Xenogen imaging to determine how data from cells and in-vivo models compare. Second, we determined the parameters of chemotherapeutic agents that can act individually or in a cocktail configuration in both in-vitro and in-vivo studies. We used light scattering and transmission electron microscopy to determine the topography for guidance on the design of the drug delivery process. Third, we found that specific targeting can be accomplished by optimizing the binding between drug molecules and mucin 1 (MUC1) found on the surface of epithelial-derived tumors. We used attenuated total internal reflection Fourier transform infrared (ATR-FTIR) spectroscopy to elucidate the interactions that enhance the selectivity of our drug delivery system with respect to model cancer systems. In addition, we used chlorotoxin, a carrier-type polypeptide known to bind to a broad number of tumors. By identifying and optimizing these two methodologies, we have found that tumor and normal cells can be selectively targeted. The significant advantage of applying a localized treatment is the avoidance of systemic exposure to chemotherapy drugs thereby limiting their side effects. Citation Format: Marzenna Wiranowska, Ryan Toomey, Rana Falahat, Norma Alcantar. Design for a flexible localized drug delivery system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3615.

A natural surfactant was studied to simulate the dispersion process of crude oil in water. The interfacial phenomena of this natural dispersant was compared with a commercially available chemical dispersant, COREXIT EC9500A. This functional surfactant was extracted from the mucilage of the Opuntia ficus-indica cactus species. The evaluation to determine the efficacy to disperse crude oil of the cactus-based mucilage extract (nongelling extract, NE) was based on characterizing surface and interfacial tension, dispersion efficiency, mixing effects, salinity effects, stability, and droplets size distributions. We found that surface tension values follow a linear relationship with respect to the natural logarithm of the concentrations of NE. The application of NE in the water phase led to decreasing oil/water interfacial tensions. Surface tension tests were also used to quantify the effect of oil-in-water (O/W) emulsion ratios once either natural or commercialized dispersants were added. A key finding of our work is that the surface tension between typical 6% and 3% v/v O/W emulsions was significantly reduced with the addition of discrete amounts of NE. This result indicated that the dynamic balance between O/W and water-in-oil (W/O) emulsions was thermodynamically more stable toward O/W emulsion states with NE. We also found that O/W emulsions with higher dispersion effectiveness were formed for both 10 and 35 practical salinity units, as the dispersant to oil ratios increased, with a significant correlation to the mixing energy. We observed that the O/W emulsions with natural dispersants had a significantly smaller weighted average diameter compared to those with COREXIT EC9500A. Such a phenomenon can be explained by understanding intermolecular interactions due to the structure and type of dispersant. In conclusion, cactus-based mucilage extracts could be used as environmentally benign dispersants and, therefore, reduce negative social perceptions of the application of dispersants to clean up spilled oil.

Pectin polysaccharides have significant potential as all-natural, non-toxic "green" coatings that exhibit thermally-cued swelling behavior. Herein, ultra-thin coatings of highly-esterified pectin polysaccharides were cross-linked with calcium chloride (CaCl2) and their swelling in water was investigated with ellipsometry. At low temperatures, the coatings swell to 2-3 times their dry layer thickness. As the temperature is increased, the coatings show a pronounced decrease in swollen thickness, reminiscent of the hydrophilic-hydrophobic transition observed in lower critical solution temperature (LCST) polymers. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy establishes that this transition is driven by dehydration of the esterified galacturonic acid residues along the pectin backbone. By adjusting both the CaCl2 concentration used to crosslink the pectin coatings as well as pH of swelling medium, the pectin coatings could be judiciously tuned for a desired swelling response as a function of temperature. Due to their non-toxic and responsive nature, it was further demonstrated that such coatings could be used in applications to control cell adhesion.

In vitro fabrication of tissues is sought for developing platforms to screen candidate drugs and study tissue morphogenesis, and ultimately to regenerate damaged organs. In this study, a modified microcontact printing technique with patterned shape-shifting poly(N-isopropylacrylamide) hydrogels was used to print organized 3T3 fibroblast tissue precursors to target surfaces coated with either fibronectin, collagen type I or poly-l-lysine. The patterned hydrogels directed cell-organization on the stamp, and a subsequent shape-shift of the hydrogel triggered instantaneous release of the tissue precursor from the stamp. It was observed that post printing, the tissue precursors underwent rapid repolarization with the emergence of focal adhesion complexes on a time-scale much faster compared to cells seeded by standard sedimentation. Moreover, a minimum stamp pressure was necessary for transfer, however, at stamp pressures above approximately 1psi, cell viability was strongly compromised. To demonstrate the ability to print other cell types using this transfer printing technique, skeletal myoblast tissue precursors were also printed. These results suggest that tissue modules can be organized and transferred with intact pre-patterned morphologies from shape-changing hydrogel structures using a microcontact printing technique. This approach may enable the bottom-up construction of high cell density, scaffold-free tissues with programmed configuration down to the individual cell level.

“Bottom-up” assembly of fully functional cell-based materials has enormous potential for replicating endogenous tissues. Currently, most tissue-engineering strategies are based on incorporating dissociated cells into an artificial three-dimensional matrix of supportive structural elements that direct cellular migration, proliferation, and organization. The matrix provides “top-down” guidance cues that impose assembly directions on the cells; however, the matrix also competes for space and limits fully functional, cell-dense tissues. This article focuses on bottom-up fabrication of functional tissue by cell sheet engineering. Cell sheet engineering is based on the sequential stacking and adhesion of confluent and organized cell monolayers from two-dimensional cell culture without the need for artifical scaffolds or structural intermediates. The resulting functional cellular monolayers (either individually or as stacked sheets) can then be directly implanted into living systems. Clinical successes are highlighted as well as attempts to overcome the vascularization limit often observed in engineered tissues.

Abstract Chlorotoxin is a scorpion-derived peptide that preferentially binds to tumor cells of neuroectodermal origin, like glioma, but not to normal non-transformed cells. We have previously reported the development of a targeted nanodelivery system using chlorotoxin. Chlorotoxin has been studied as an imaging and targeting agent for drug and radioisotope delivery, but the mechanism of interaction of chlorotoxin with cancer cells has not been well understood and it needs to be further evaluated in order to optimize its use as a targeting compound for cancer cells. In this study, we used U87 human glioma cell line to evaluate the binding kinetics of chlorotoxin by Attenuated Total Reflection Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. As a sensitive and label free technique, ATR-FTIR is a powerful diagnostic tool for the comparison of cancer cells with normal cells. First, we characterized the signature spectra of chlorotoxin and U87 cells by assigning and evaluating the infrared absorption bands and their second derivatives. Next, we studied the spectral differences between U87 cells incubated with and without chlorotoxin for incremental time periods ranging from 15 minutes to 24 hours. We also examined the metabolic changes in U87 cells induced with chlorotoxin at different incubation time points by measuring the ratios of integrated areas corresponding to different chemical conformations of proteins, lipids, carbohydrates, and nucleic acids. Our results revealed spectral changes in U87 cells at different stages of incubation with chlorotoxin. The most notable change occurred after 30 minutes of incubation, where the band assigned to CH3 bending of lipid membranes shifted from 1456 cm-1 to 1450 cm-1. Consequently, a new shoulder appeared at wavenumber of 1466 cm-1 assigned to CH2 bending of lipid membranes for U87 cells treated with chlorotoxin. These changes indicate a direct interaction due to the presence of a molecular binding site between chlorotoxin and the lipids of the cell membrane. Another significant alternation occurred after 1 hour of incubation of U87 cells with chlorotoxin in the spectral region assigned for nucleic acids. This interaction included a large upshift of the band at 1036 cm-1 to 1051 cm-1 assigned to C-O stretching vibrations of ribose ring in RNA due to the hydrogen bonding with chlorotoxin. These findings suggest at least two different interactions of chlorotoxin with U87 human glioma cells that can be further explored for improving chlorotoxin containing drug delivery systems. We are currently using the ATR-FTIR method to conduct control experiments by measuring possible interactions of chlorotoxin with normal human astrocytes. Citation Format: Rana Falahat, Marzenna Wiranowska, Ryan Toomey, Norma Alcantar. Interactions of glioma cells with chlorotoxin: an ATR-FTIR spectroscopy study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3909.

The micromanipulation of biological samples is important for microbiology, pharmaceutical science, and related bioengineering fields. In this work, we report the fabrication and characterization of surface-attached microbeam arrays of 20 μm width and 25 μm height made of poly(N-isopropylacrylamide), a thermoresponsive polymer, with embedded spherical or octopod Fe3O4 nanoparticles. Below 32 °C, the microbeams imbibe water and buckle with an amplitude of approximately 20 μm. Turning on an AC-magnetic field induces the microbeam array to expel water due to the heating effect of the nanoparticles (magnetic hyperthermia), leading to a reversible transition from a buckled to nonbuckled state. It is observed that the octopod nanoparticles have a heating rate 30% greater (specific absorption rate, SAR) than that of the spherical nanoparticles, which shortens the time scale of the transition from the buckled and nonbuckled state. The return of the microbeams to the buckled state is accomplished by turning off the AC magnetic field, the rate of which is dictated by dissipation of heat and is independent of the type of nanoparticle. It is further demonstrated that this transition can be used to propel 50 μm spherical objects along a surface. While the motion is random, this study shows the promise of harnessing shape-shifting patterns in microfluidics for object manipulation.

Responsive surfaces: a review of the dependence of protein adsorption on the reversible volume phase transition in stimuli-responsive polymers. Specifically addressed are a widely studied subset: thermoresponsive polymers. Findings are also generalizable to other materials which undergo a similarly reversible volume phase transition. As of 2015, over 100 000 articles have been published on stimuli-responsive polymers and many more on protein-biomaterial interactions. Significantly, fewer than 100 of these have focused specifically on protein interactions with stimuli-responsive polymers. These report a clear trend of increased protein adsorption in the collapsed state compared to the swollen state. This control over protein interactions makes stimuli-responsive polymers highly useful in biomedical applications such as wound repair scaffolds, on-demand drug delivery, and antifouling surfaces. Outstanding questions are whether the protein adsorption is reversible with the volume phase transition and whether there is a time-dependence. A clear understanding of protein interactions with stimuli-responsive polymers will advance theoretical models, experimental results, and biomedical applications.