Mustafa Akbulut

Recent advances in the surface forces apparatus (SFA) technique

The surface forces apparatus (SFA) has been used for many years to measure the physical forces between surfaces, such as van der Waals (including Casimir) and electrostatic forces in vapors and liquids, adhesion and capillary forces, forces due to surface and liquid structure (e.g. solvation and hydration forces), polymer, steric and hydrophobic interactions, bio-specific interactions as well as friction and lubrication forces. Here we describe recent developments in the SFA technique, specifically the SFA 2000, its simplicity of operation and its extension into new areas of measurement of both static and dynamic forces as well as both normal and lateral (shear and friction) forces. The main reason for the greater simplicity of the SFA 2000 is that it operates on one central simple-cantilever spring to generate both coarse and fine motions over a total range of seven orders of magnitude (from millimeters to angstroms). In addition, the SFA 2000 is more spacious and modulated so that new attachments and extra parts can easily be fitted for performing more extended types of experiments (e.g. extended strain friction experiments and higher rate dynamic experiments) as well as traditionally non-SFA type experiments (e.g. scanning probe microscopy and atomic force microscopy) and for studying different types of systems.

Novel method for concentrating and drying polymeric nanoparticles: hydrogen bonding coacervate precipitation.

Nanoparticles have significant potential in therapeutic applications to improve the bioavailability and efficacy of active drug compounds. However, the retention of nanometer sizes during concentrating or drying steps presents a significant problem. We report on a new concentrating and drying process for poly(ethylene glycol) (PEG) stabilized nanoparticles, which relies upon the unique pH sensitive hydrogen bonding interaction between PEG and polyacid species. In the hydrogen bonding coacervate precipitation (HBCP) process, PEG protected nanoparticles rapidly aggregate into an easily filterable precipitate upon the addition various polyacids. When the resulting solid is neutralized, the ionization of the acid groups eliminates the hydrogen bonded structure and the approximately 100 nm particles redisperse back to within 10% of their original size when poly(acrylic acid) and citric acid are used and 45% when poly(aspartic acid) is used. While polyacid concentrations of 1-5 wt % were used to form the precipitates, the incorporation of the acid into the PEG layer is approximately 1:1 (acid residue):(ethylene oxide unit) in the final dried precipitate. The redispersion of dried beta-carotene nanoparticles protected with PEG-b-poly(lactide-co-glycolide) polymers dried by HBCP was compared with the redispersion of particles dried by freeze-drying with sucrose as a cryprotectant, spray freeze-drying, and normal drying. Freeze-drying with 0, 2, and 12 wt % sucrose solutions resulted in size increases of 350%, 50%, and 6%, respectively. Spray freeze-drying resulted in particles with increased sizes of 50%, but no cryoprotectant and only moderate redispersion energy was required. Conventional drying resulted in solids that could not be redispersed back to nanometer size. The new HBCP process offers a promising and efficient way to concentrate or convert nanoparticle dispersions into a stable dry powder form.

Adsorption, Desorption, and Removal of Polymeric Nanomedicine on and from Cellulose Surfaces: Effect of Size

The increased production and commercial use of nanoparticulate drug delivery systems combined with a lack of regulation to govern their disposal may result in their introduction to soils and ultimately into groundwater systems. To better understand how such particles interact with environmentally significant interfaces, we study the adsorption, desorption, and removal behavior of poly(ethylene glycol)-based nanoparticulate drug delivery systems on and from cellulose, which is the most common organic compound on Earth. It is shown that such an adsorption process is only partially reversible, and most of the adsorbate particles do not desorb from the cellulose surface even upon rinsing with a large amount of water. The rate constant of adsorption decreases with increasing particle size. Furthermore, hydrodynamic forces acting parallel to the surfaces are found to be of great importance in the context of particle dynamics near the cellulose surface, and ultimately responsible for the removal of some fraction of particles via rolling or sliding. As the particle size increases, the removal rates of the particles increase for a given hydrodynamical condition.

Preventing adhesion of Escherichia coli O157:H7 and Salmonella Typhimurium LT2 on tomato surfaces via ultrathin polyethylene glycol film.

This work deals with adhesion of Escherichia coli O157:H7 and Salmonella enterica subsp. enterica serovar Typhimurium LT2 (S. Typhimurium LT2) on polyethylene glycol (PEG) coated tomato surfaces. PEG coating was characterized by water contact angle technique, scanning electron microscopy, and secondary ion mass spectrometry. It was shown that PEG films could physisorb on the tomato surfaces after the oxygen plasma treatment, which made some outermost layers of the surfaces hydrophilic. Bacterial adhesion on PEG coated tomato surface was studied by standard plate count, fluorescence microscopy, and scanning electron microscopy techniques. Fully covered PEG film reduced the bacterial attachment 90% or more in comparison to the bare tomato surface. The degree of bacterial attachment decreased exponentially with increasing PEG coverage. When desired, PEG film could be removed by rinsing with water. Overall, this work demonstrates the proof-of-concept that an ultrathin film of polyethylene glycol may be used to effectively inhibit the attachment of pathogenic bacteria on tomato surfaces.

Adsorption and removal dynamics of polymeric micellar nanocarriers loaded with a therapeutic agent on silica surfaces

Obtaining a better understanding of the adsorption behavior of polymeric nanomedicines is important to properly assess their distribution and fate and to develop successful strategies for minimizing their distribution in the environment. In this study, the adsorption and removal dynamics of a model polymeric nanomedicine of systematically varied sizes – levofloxacin loaded poly(ethyleneglycol-b-e-caprolactone) – on and from silica surfaces are investigated using a quartz crystal microbalance with dissipation (QCM-D). For all the sizes of the nanomedicine investigated (90 nm, 110 nm, 149 nm, 174 nm, 207 nm, and 305 nm), the adsorbate mass on the silica followed a roughly exponential trend with respect to time during the exposure stage, suggesting first-order adsorption kinetics. The adsorption rate constant decreased with the increasing particle size. Furthermore, we have developed a modified Leveque equation to describe the mass transport and adsorption behavior of the nanoparticulate dispersion inside the QCM-D chamber. The derivation involved the application of a bipolar coordinate system to the continuity, Navier–Stokes, and convective–diffusion equations. The adsorption rate constants calculated using the derived equation were found to match the experimental results well. The derived equation is important not only in the field of environmental science but also in many other fields as QCM-D is heavily used to characterize the dynamic adsorption behavior of various types of materials including polymers, proteins, and nanoparticles.

Uptake and translocation of polymeric nanoparticulate drug delivery systems into ryegrass

This study focuses on the transport behavior of model polymeric nanoparticulate drug delivery systems (PNDDSs) across ryegrass roots to determine whether uncontrolled and accidental releases of PNDDSs may enter into the food chain. It was shown that uptake of PNDDS ranging from 46 nm to 271 nm into ryegrass roots could take place. Upon exposing ryegrass to an aqueous PNDDS dispersion for 312 h, 91 ± 6%, 64 ± 3%, and 26 ± 8% of PNDDSs were localized in and on the ryegrass for 46 nm, 159 nm, and 271 nm PNDDS, respectively. The overall transport of PNDDSs from the solution to the ryegrass could be modeled well as a first-order adsorption process, which was followed by a first-order uptake process. The adsorption of PNDDSs onto the roots was found to be much faster than the uptake of PNDDSs into the roots.

Transport of Polymeric Nanoparticulate Drug Delivery Systems in the Proximity of Silica and Sand

The contamination of the environment with traditional therapeutics due to metabolic excretion, improper disposal, and industrial waste has been well-recognized. However, knowledge of the environmental distribution and fate of emerging classes of nanomedicine is scarce. This work investigates the effect of surface chemistry of polymeric nanoparticulate drug delivery systems (PNDDS) on their adsorption dynamics and transport in the vicinity of environmentally relevant surfaces for a concentration comparable with hospital and pharmaceutical manufacturing effluents. To this end, five different types of paclitaxel-based nanomedicine having different polymer stabilizers were employed. Their transport behavior was characterized via quartz crystal microbalance, sand column, spectrofluorometry, and dynamic light scattering techniques. PNDDS having positive zeta-potential displayed strong adsorption onto silica surfaces and no mobility in porous media of quartz sand, even in the presence of humic acid. The mobility of negatively charged PNDDS strongly depended on the amount and type of salt present in the aqueous media: Without any salt, such PNDDS demonstrated no adsorption on silica surfaces and high levels of mobility in sand columns. The presence of CaCl2 and CaSO4, even at low ionic strengths (i.e. 10 mM), induced PNDDS adsorption on silica surfaces and strongly limited the mobility of such PNDSS in sand columns.

A multifunctional nanoparticulate theranostic system with simultaneous chemotherapeutic, photothermal therapeutic, and MRI contrast capabilities

Multifunctional nanomedicines with imaging and multimodal therapies have become a new trend in the current development of cancer therapy. Herein, we report the use of a Flash NanoPrecipitation approach for fabricating a multifunctional nanoparticulate theranostic system (MNTS) simultaneously encapsulating paclitaxel, gold nanoparticles, and iron oxide nanoparticles in poly(ethylene oxide)-block-poly(e-caprolactone) (PEO-b-PCL). The combination of these building blocks in a single system translates into an advance nanomedicine with concurrent chemotherapeutic, photothermal therapeutic, and MRI contrast properties. Using dynamic light scattering, the hydrodynamic diameter of MNTS was found to range from 50 nm to 500 nm with the mean size of 190 ± 14 nm. The co-localization of paclitaxel, gold nanoparticles, and iron oxide nanoparticles were confirmed via scanning- and cryo-transmission electron microscopy. At a paclitaxel concentration of 100 pM, the cell viability after a 72 h treatment of MNTS was 35 ± 3% and 31 ± 1% for MCF-7 and MDA-MB-231 cell lines, respectively while that of bare paclitaxel was 77 ± 2% and 91 ± 3%, respectively. Irradiation of MNTS with a 200 mW laser (532 nm) for 5 min during the treatment stage resulted in a further 20% and 226% decrease in the viability of MCF-7 and MDA-MB-231, respectively. MRI relaxivity measurements revealed that the T2 relaxation times of MNTS was 47 ± 5 ms and significantly different from that of most human anatomical parts susceptible to cancer.

Metal-Organic-Inorganic Nanocomposite Thermal Interface Materials with Ultralow Thermal Resistances

As electronic devices get smaller and more powerful, energy density of energy storage devices increases continuously, and moving components of machinery operate at higher speeds, the need for better thermal management strategies is becoming increasingly important. The removal of heat dissipated during the operation of electronic, electrochemical, and mechanical devices is facilitated by high-performance thermal interface materials (TIMs) which are utilized to couple devices to heat sinks. Herein, we report a new class of TIMs involving the chemical integration of boron nitride nanosheets (BNNS), soft organic linkers, and a copper matrix-which are prepared by the chemisorption-coupled electrodeposition approach. These hybrid nanocomposites demonstrate bulk thermal conductivities ranging from 211 to 277 W/(m K), which are very high considering their relatively low elastic modulus values on the order of 21.2-28.5 GPa. The synergistic combination of these properties led to the ultralow total thermal resistivity values in the range of 0.38-0.56 mm2 K/W for a typical bond-line thickness of 30-50 μm, advancing the current state-of-art transformatively. Moreover, its coefficient of thermal expansion (CTE) is 11 ppm/K, forming a mediation zone with a low thermally induced axial stress due to its close proximity to the CTE of most coupling surfaces needing thermal management.

Metallic nanocomposites as next-generation thermal interface materials

Thermal interface materials (TIMs) are an integral and important part of thermal management in electronic devices. The electronic devices are becoming more compact and powerful. This increase in power processed or passing through the devices leads to higher heat fluxes and makes it a challenge to maintain temperatures at the optimal level during operation. Herein, we report a free standing nanocomposite TIM in which boron nitride nanosheets (BNNS) are uniformly dispersed in copper matrices via an organic linker, thiosemicarbazide. Integration of these metal-organic-inorganic nanocomposites was made possible by a novel electrodeposition technique where the functionalized BNNS (f-BNNS) experience the Brownian motion and reach the cathode through diffusion, while the nucleation and growth of the copper on the cathode occurs via the electrochemical reduction. Once the f-BNNS bearing carbonothioyl/thiol groups on the terminal edges come into the contact with copper crystals, the chemisorption reaction takes place. We performed thermal, mechanical, and structural characterization of these nanocomposites using scanning electron microcopy (SEM), diffusive laser flash (DLF) analysis, phase-sensitive transient thermoreflectence (PSTTR), and nanoindentation. The nanocomposites exhibited a thermal conductivity ranging from 211 W/mK to 277 W/mK at a filler mass loading of 0–12 wt.%. The nanocomposites also have about 4 times lower hardness as compared to copper, with values ranging from 0.27 GPa to 0.41 GPa. The structural characterization studies showed that most of the BNNS are localized at grain boundaries — which enable efficient thermal transport while making the material soft. PSTTR measurements revealed that the synergistic combinations of these properties yielded contact resistances on the order of 0.10 to 0.13 mm2K/W, and the total thermal resistance of 0.38 to 0.56 mm2K/W at bondline thicknesses of 30–50 pm. The coefficient of thermal expansion (CTE) of the nanocomposite is 11 ppm/K, which lies between the CTEs of aluminum (22 ppm/K) and silicon (3 ppm/K), which are common heat sink and heat source materials, respectively. The nanocomposite can also be deposited directly on to heat sink which will simplify the packaging processes by removing one possible element to assemble. These unique properties and ease of assembly makes the nanocomposite a promising next-generation TIM.