3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays.

Tumor-on-chips have become an effective resource in cancer research. However, their widespread use remains limited due to issues related to their practicality in fabrication and use. To address some of these limitations, we introduce a 3D-printed chip, which is large enough to host ~1 cm3 of tissue and fosters well-mixed conditions in the liquid niche, while still enabling the formation of the concentration profiles that occur in real tissues due to diffusive transport. We compared the mass transport performance in its rhomboidal culture chamber when empty, when filled with GelMA/alginate hydrogel microbeads, or when occupied with a monolithic piece of hydrogel with a central channel, allowing communication between the inlet and outlet. We show that our chip filled with hydrogel microspheres in the culture chamber promotes adequate mixing and enhanced distribution of culture media. In proof-of-concept pharmacological assays, we biofabricated hydrogel microspheres containing embedded Caco2 cells, which developed into microtumors. Microtumors cultured in the device developed throughout the 10-day culture showing >75% of viability. Microtumors subjected to 5-fluorouracil treatment displayed <20% cell survival and lower VEGF-A and E-cadherin expression than untreated controls. Overall, our tumor-on-chip device proved suitable for studying cancer biology and performing drug response assays.

Steric and Slippage Effects on Mass Transport by Using an Oscillatory Electroosmotic Flow of Power-Law Fluids.

In this paper, the combined effect of the fluid rheology, finite-sized ions, and slippage toward augmenting a non-reacting solute's mass transport due to an oscillatory electroosmotic flow (OEOF) is determined. Bikerman's model is used to include the finite-sized ions (steric effects) in the original Poisson-Boltzmann (PB) equation. The volume fraction of ions quantifies the steric effects in the modified Poisson-Boltzmann (MPB) equation to predict the electrical potential and the ion concentration close to the charged microchannel walls. The hydrodynamics is affected by slippage, in which the slip length was used as an index for wall hydrophobicity. A conventional finite difference scheme was used to solve the momentum and species transport equations in the lubrication limit together with the MPB equation. The results suggest that the combined slippage and steric effects promote the best conditions to enhance the mass transport of species in about 90% compared with no steric effect with proper choices of the Debye length, Navier length, steric factor, Womersley number, and the tidal displacement.

Electrochemical degradation of the antibiotic ciprofloxacin in a flow reactor using distinct BDD anodes: Reaction kinetics, identification and toxicity of the degradation products.

The performances of distinct BDD anodes (boron doping of 100, 500 and 2500 ppm, with sp3/sp2 carbon ratios of 215, 325, and 284, respectively) in the electrochemical degradation of ciprofloxacin - CIP (0.5 L of 50 mg L-1 in 0.10 M Na2SO4, at 25 °C) were comparatively assessed using a recirculating flow system with a filter-press reactor. Performance was assessed by monitoring the CIP and total organic carbon (TOC) concentrations, oxidation intermediates, and antimicrobial activity against Escherichia coli as a function of electrolysis time. CIP removal was strongly affected by the solution pH (kept fixed), flow conditions, and current density; similar trends were obtained independently of the BDD anode used, but the BDD100 anode yielded the best results. Enhanced mass transport was achieved at a low flow rate by promoting the solution turbulence within the reactor. The fastest complete CIP removal (within 20 min) was attained at j = 30 mA cm-2, pH = 10.0, and qV = 2.5 L min-1 + bypass turbulence promotion. TOC removal was practically accomplished only after 10 h of electrolysis, with quite similar performances by the distinct BDD anodes. Five initial oxidation intermediates were identified (263 ≤ m/z ≤ 348), whereas only two terminal oxidation intermediates were detected (oxamic and formic acids). The antimicrobial activity of the electrolyzed CIP solution was almost completely removed within 10 h of electrolysis. The characteristics of the BDD anodes only had a marked effect on the CIP removal rate (best performance by the least-doped anode), contrasting with other data in the literature.

PARAMETRIC ANALYSIS OF DRUG DISTRIBUTION DURING INFUSIONS INTO THE BRAIN USING AN AXISYMMETRIC MODEL WITH BACKFLOW / ANÁLISIS PARAMÉTRICO DE LA DISTRIBUCIÓN DE DROGA DURANTE INFUSIONES EN EL CEREBRO CON UN MODELO AXISIMÉTRICO CON REFLUJO / A ANÁLISE PARAMÉTRICA DE DISTRIBUIÇÃO DE DROGAS NO CÉREBRO DURANTE INFUSÕES COM UM MODELO AXISYMMETRIC COM REFLUXO

Convection-enhanced delivery as a means to deliver therapeutic drugs directly to the brain has shown limited clinical efficacy, primarily attributed to the phenomena of backflow, in which the infused fluid flows preferentially along the shaft catheter rather than forward into the tissue. We have previously developed a finite element model of backflow that includes both material and geometric nonlinearities and the free boundary conditions associated with the displacement of the tissue away from the external surface of the catheter. However, that study was limited to predictions of the tissue deformation and resulting convective fluid velocity in the interstitial space. In this study, we use results from that model to solve for the distribution of the infused therapeutic agent. We demonstrate that a significant percentage of the infused drug is not transported into the region of tissue located forward from the catheter tip, but instead is transported into the region along the lateral sides of the catheter. For lower flow rates, this study suggests that the use of a catheter with a larger radius may be preferable since it will provide the higher amount of drug to be transported to the tissue in front of the catheter. In contrast, for higher flow rates consistent with clinical infusions, the radius of the infusion catheter had minimal effect on the distribution of the infused drug, with most being transported into the tissue around the shaft of the catheter.

Convection-enhanced delivery es una técnica que permite transportar drogas directamente en el cerebro para el tratamiento de enfermedades del sistema nervioso central. Este método ha mostrado una eficacia limitada debido principalmente al fenómeno de reflujo (backflow), según el cual, el fluido inyectado fluye preferiblemente a lo largo del catéter y no hacia el tejido delante de la punta. Previamente desarrollamos un modelo de elementos finitos para representar el reflujo, el cual incluye las no linealidades geométricas y del material y las condiciones de borde libre asociadas con el desplazamiento del tejido en la superficie externa del catéter. Sin embargo, ese modelo solo predice la deformación del tejido y el campo de velocidades en el espacio intersticial. En este estudio, hemos utilizado los resultados provenientes del mencionado modelo bifásico para resolver la ecuación de transporte de masa y predecir la distribución de droga suministrada. Se pudo demostrar que un porcentaje significativo de droga no penetra en el tejido ubicado delante de la punta del catéter, sino que es transportado hacia el tejido ubicado alrededor del catéter. Para bajo caudales, este estudio sugiere que el uso de un catéter con un radio mayor permitiría transportar una mayor cantidad de droga hacia el tejido al frente de la punta. Por otro lado, para los mayores caudales usados en la práctica clínica, el radio del catéter tiene un efecto marginal en la distribución del fármaco, y la mayor cantidad de droga se transporta hacia el tejido ubicado alrededor del catéter.

Convection-enhanced delivery é uma técnica para o transporte de drogas directamente no cérebro para tratar doenças do sistema nervoso central. Este método tem demonstrado eficácia limitada devido, principalmente, ao fenómeno de refluxo (refluxo), através do qual, de preferência, o fluido injectado flui através do cateter para o tecido e não à frente da ponta. Anteriormente desenvolvido um modelo de elementos finitos para representar a refluxo, que inclui geométricas e não-linearidades do material e as condições associadas com a extremidade livre de deslocamento da trama na superfície exterior do cateter. No entanto, este modelo apenas prevê deformação do tecido e campo de velocidades no espaço intersticial. Neste estudo, foram utilizados os resultados do modelo de duas fases acima referidas, para resolver a equação de transporte e prever a distribuição de massa de medicamentos fornecidos. Demonstrou-se que uma percentagem significativa da droga não penetra no tecido localizado em frente da ponta do cateter, que é transportado para o tecido que rodeia o cateter. Para as taxas de fluxo baixas, este estudo sugere que o uso de um cateter com um raio maior do que transportar uma maior quantidade de droga para o tecido em frente da ponta. Além disso, para taxas de fluxo mais elevadas utilizadas na prática clínica, o raio do cateter tem um efeito marginal sobre a distribuição da droga, e tanto fármaco é transportado para o tecido que rodeia o cateter.