Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform

Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. A novel acoustofluidic platform is developed by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed‐loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS‐induced heating triggers local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher cellular drug uptake in the FUS focal region. This differential drug uptake induces locally confined DNA damage and glioblastoma cell death in the 3D environment. The capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response are demonstrated in a 3D in vitro tumor mode. This has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue.     

Pumping,spraying, and mixing of fluids by electric fields

The mechanism of electrostatic spraying of insulating fluids, such as air or organic solvents, into relatively conductive fluids, such as water, is investigated in this work. Experiments with air sprayed into water through an electrified capillary showed that the pressure inside the capillary increases, reaches a maximum, and then decreases as the applied voltage is increased. The initial pressure increase is due to the electric stress on the fluid interface, while the decrease is due to the Coulombic electrohydrodynamic flow generated near the end of the capillary. It is shown that electric fields can cause simultaneous pumping, spraying, and mixing of fluids. This phenomenon is demonstrated for air and kerosene in water.     

Effect of a poly(dimethylsiloxane) modified polyolefin additive on the processing and surface properties of LLDPE

A polydimethylsiloxane (PDMS) modified polyolefin (obtained by reacting an ethylene‐ethyl acrylate‐maleic anhydride (EEAMA) copolymer with an amine terminated PDMS in the melt phase) was used as a processing aid to facilitate the extrusion of linear low density polyethylene (LLDPE). In blends of LLDPE and PDMS modified polyolefin (PMPO), apparent viscosity and shear stress at the die wall are reduced in comparison to pure LLDPE, and extrusion instabilities are delayed as evidenced by the fact that extrudate surface roughness only occurs at higher shear rates when the additive is present. A higher PDMS content in the PMPO leads to a more pronounced delay of extrusion instabilities. Single‐screw extrusion of LLDPE compounds with a PMPO results in nearly doubled throughput per unit input energy. The reduction of viscosity and improvements in extrudate quality are attributed to the decreasing surface free energy of the PMPO with an increasing PDMS content, as determined by contact angle measurements. Chemical composition analysis of the extrudate surface and cross‐section reveals silicon enrichment at the surface. The friction coefficients of pure PMPO and PMPO/LLDPE blends are measured and found to decrease as a result of the presence of PDMS. POLYM. ENG. SCI., 47:1309–1316, 2007. © 2007 Society of Plastics Engineers     

Global behavior of the diffusion coefficient for the Van Der Waals binary mixture

We describe the general dependence of the diffusion coefficient associated with the Van der Waals binary mixture on the temperature, number densities, and relative strengths of molecular interaction parameters. The task is facilitated by the fact that for Kac-type intermolecular potentials, in the long-range limit, the diffusion coefficient becomes simply related to the product of a partial compressibility and the curvature of the equilibrium free energy in the space of number densities. Therefore the different kinds of behavior found can be classified according to the scheme of Scott and Van Konynenburg for the global phase diagram of the same model mixture.Paper presented at the Tenth Symposium on Thermophysical Properties, June 20–23, 1988, Gaithersburg, Maryland, U.S.A.     

Monte Carlo circuits for the abelian permutation group intersection problem

Summary We show that the problem of computing a basis for an abelian transitive permutation group is in N C ^k and also we show that the problem of computing a basis for an abelian permutation group and the problem of computing the intersection of two abelian groups acting on n points, can be solved in depth (log n)^k on a Monte Carlo Boolean circuit of polynomial size. Moreover the latter two problems are shown to be in N C ^k in the restricted case of bounded number of generators.     

Analysis of mixing during melt-melt blending in twin screw extruders using reactive polymer tracers

Mixing during melt-melt blending of segregated polypropylene melt streams in a co-rotating twin screw extruder was experimentally investigated. The mixing limited reaction between two polymer reactive tracers, which are terminally functionalized polyolefin oligomers, was used to determine the mixing performance of a kneading block section. The selected functional groups were succinic anhydride and a primary amine, and Fourier-Transform Infrared Spectrometry (FT-IR) was used to determine the anhydride conversion. In the absence of interfacial tension, the reaction conversion was directly related to the amount of interfacial area generated. Experiments were completed to study the effects of operating conditions, kneading block design, and polymer material properties. The screw speed effect was observed to be non-linear because of competing contributions from shear rate, residence time, channel fill, and viscous heating. The mixing performance of kneading blocks backed by a reverse conveying element was observed to follow the trend of: forward > reverse > neutral. For each kneading block design, the mixing performance decreased with an increase in polymer viscosity.     

On the estimation of characteristic indoor air quality parameters using analytical and numerical methods

Indoor exposure to air contaminants penetrating from the outdoor environment depends on a number of key processes and parameters such as the ventilation rate, the geometric characteristics of the indoor environment, the outdoor concentration and the indoor removal mechanisms. In this study two alternative methods are used, an analytical and a numerical one, in order to study the time lag and the reduction of the variances of the indoor concentrations, and to estimate the deposition rate of the air contaminants in the indoor environment employing both indoor and outdoor measurements of air contaminants. The analytical method is based on a solution of the mass balance equation involving an outdoor concentration pulse which varies sinusoidally with the time, while the numerical method involves the application of the MIAQ indoor air quality model assuming a triangular pulse. The ratio of the fluctuation of the indoor concentrations to the outdoor ones and the time lag were estimated for different values of the deposition velocity, the ventilation rate and the duration of the outdoor pulse. Results have showed that the time lag between the indoor and outdoor concentrations is inversely proportional to the deposition and ventilation rates, while is proportional to the duration of the outdoor pulse. The decrease of the ventilation and the deposition rate results in a rapid decrement of the variance ratio of indoor to outdoor concentrations and to an increment of the variance ratio, respectively. The methods presented here can be applied for gaseous species as well as for particulate matter. The nomograms and theoretical relationships that resulted from the simulation results and the analytical methods respectively were used in order to study indoor air phenomena. In particular they were used for the estimation of SO2 deposition rate. Implications of the studied parameters to exposure studies were estimated by calculating the ratio of the indoor exposure to the exposure outdoors. Limitations of the methods were explored by testing various scenarios which are usually met in the indoor environment. Strong indoor emissions, intense chemistry and varying ventilation rates (opening and closing of the windows) were found to radically influence the time lag and fluctuation ratios.     

Inactivation of Endogenous Rice Flour β-Glucanase by Microwave Radiation and Impact on Physico-chemical Properties of the Treated Flour

The apparent reduction of β-glucan (BG) molecular weight in rice-based gluten-free (GF) breads fortified with cereal BG concentrates reveals the presence of β-glucanase activity in rice flour. Inactivation of endogenous β-glucanase in rice flour thus seems to be a necessary step when developing GF breads enriched with BG of high molecular weight. The aim of this work was to study the thermal inactivation of endogenous β-glucanase in rice flour by means of microwave (MW) processing; rice flours preconditioned at four different moisture levels (13, 16, 19, 25 %) were treated by MW radiation at 900 W and five MW treatment times (ranging from 40 s to 8 min, applied stepwise at 20-s intervals). The effects of microwaves on starch crystallinity, pasting, and thermal properties of MW-treated rice flours were also explored. The β-glucanase activity in rice flours was assessed by the rate of decrease in specific viscosity of a dilute solution of a purified β-glucan preparation, upon addition of flour extracts. MW proved to be a useful alternative for thermal inactivation of endogenous β-glucanase in rice flours when applied to moistened samples. The inactivation process followed a first-order kinetic response and the apparent rate constant of thermal inactivation increased exponentially with the moisture content of the flour, M, according to the equation 0.0146·exp (0.212·M) (R ²?=?0.97). The MW time required for complete β-glucanase inactivation was only 4 min when the initial flour moisture increased to 25 %. Following MW treatment, the starch crystallinity was unaffected (p?>?0.05) and the side effects of the treatment on flour pasting and thermal properties were rather negligible.