Effective Transport Template for Particle Separation in Microfluidic Bumper Arrays

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Microfluidic bumper arrays are increasingly being used for the size-based sorting of particle suspensions. The separation mechanism is based on the interaction between a spatially periodic array of obstacles and the suspended particles as they are driven through the obstacle lattice either by volume forces or by the Stokesian drag of the surrounding fluid. By this mechanism, a focused stream of suspended particles of different sizes entering the lattice splits into different currents, each entraining assigned ranges of particle dimensions, and each characterized by a specific angle with respect to the main device axis. In this work, we build up on recent results stemming from macrotransport process theory to derive a closed-form solution for the steady-state distribution of advecting-diffusing particles in the presence of anisotropic dispersion, which typically characterizes large-scale behavior of particle motion through the periodic lattice. Attention is focused on separation resolution, that ultimately controls the feasibility of the separation in specific applications

Dispersion phenomena in microchannels: Transition from Taylor-Aris to convection-dominated regime

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.This article addresses the qualitative and quantitative properties of solute transport and dispersion in microchannel of finite-length. As the Peclet number increases a transition from the Taylor-Aris to a new regime referred as convection dominated dispersion occurs, which is controlled by the velocity profile near the stagnation points at the solid walls. The properties characterizing dispersion dominated regime can be used for analytical purposes as a chromatographic-based velocimetry and for determining the eventual occurrence of slip at the solid walls of microchannels

5-Fluorouracil degradation rate as a predictive biomarker of toxicity in breast cancer patients treated with capecitabine

Capecitabine is an oral prodrug of 5-fluorouracil with a relevant role in the treatment of breast cancer. Severe and unexpected toxicities related to capecitabine are not rare, and the identification of biomarkers is challenging. We evaluate the relationship between dihydropyrimidine dehydrogenase, thymidylate synthase enhancer region and methylenetetrahydrofolate reductase polymorphisms, 5-fluorouracil degradation rate and the onset of G3–4 toxicities in breast cancer patients. Genetic polymorphisms and the 5-fluorouracil degradation rate of breast cancer patients treated with capecitabine were retrospectively studied. Genetic markers and the 5-fluorouracil degradation rate were correlated with the reported toxicities. Thirty-seven patients with a median age of 58 years old treated with capecitabine for stages II–IV breast cancer were included in this study. Overall, 34 (91.9%) patients suffered from at least an episode of any grade toxicity while nine patients had G3–4 toxicity. Homozygous methylenetetrahydrofolate reductase 677TT was found to be significantly related to haematological toxicity (OR = 6.5 [95% IC 1.1–37.5], P = 0.04). Three patients had a degradation rate less than 0.86 ng/mL/106 cells/min and three patients greater than 2.1 ng/mL/106 cells/min. At a univariate logistic regression analysis, an altered value of 5-fluorouracil degradation rate (values < 0.86 or >2.10 ng/mL/106 cells/min) increased the risk of G3–4 adverse events (OR = 10.40 [95% IC: 1.48–7.99], P = 0.02). A multivariate logistic regression analysis, adjusted for age, comorbidity and CAPE-regimen, confirmed the role of 5-fluorouracil degradation rate as a predictor of G3–4 toxicity occurrence (OR = 10.9 [95% IC 1.2–96.2], P = 0.03). The pre-treatment evaluation of 5-fluorouracil degradation rate allows to identify breast cancer patients at high risk for severe 5-FU toxicity

Combining electrostatic, hindrance and diffusive effects for predicting particle transport and separation efficiency in deterministic lateral displacement microfluidic devices

Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection-diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique

Fractionation of a three-particle mixture by Brownian sieving hydrodynamic chromatography

Particles ranging in size from a few nanometers (exosomes or viruses) to a few micrometers (bacteria or red blood cells) can be sorted using a size-based separation process. One of the simplest techniques is provided by hydrodynamic chromatography (HDC) which typically requires long channels to achieve adequate resolution. A new separation mechanism based on a Brownian sieving effect coupled with HDC has recently been proposed to overcome these limitations. An efficiency improvement of up to 2000 % has been predicted for a two-size mixture. The aim of this work is to study and optimize a modified geometry useful for obtaining the simultaneous separation of a three-size diluted suspension. The results suggest a significant performance improvement, up to 3000 %, over the standard HDC

Toward minimal complexity models of membrane reactors for hydrogen production

Membrane reactors are inherently two-dimensional systems that require complex models for an accurate description of the different transport phenomena involved. However, when their performance is limited by mass transport within the reactor rather than by the selective product permeation across the membrane, the 2D model may be significantly simplified. Here we extend results previously found for methane steam reforming membrane reactors to show that such simplified two-dimensional model admits either a straightforward analytical solution for the cross-section averaged concentration profile, or can be reduced to a 1D model with an enhanced Sherwood number, depending on the stoichiometry of the reaction considered. Interestingly, the stoichiometry does not affect the expression of the enhanced Sherwood number, indicating that a versatile tool has been developed for the determination of membrane reactor performance at an extremely low computational cost and good degree of accuracy

Standard of care and promising new agents for the treatment of mesenchymal triple-negative breast cancer

The pathologic definition of triple negative breast cancer (TNBC) relies on the absence of expression of estrogen, progesterone and HER2 receptors. However, this BC subgroup is distinguished by a wide biological, molecular and clinical heterogeneity. Among the intrinsic TNBC subtypes, the mesenchymal type is defined by the expression of genes involved in the epithelial to mesenchymal transition, stromal interaction and cell motility. Moreover, it shows a high expression of genes involved in proliferation and an immune-suppressive microenvironment. Several molecular alterations along different pathways activated during carcinogenesis and tumor progression have been outlined and could be involved in immune evasion mechanisms. Furthermore, reverting epithelial to mes-enchymal transition process could lead to the overcoming of immune-resistance. This paper reviews the current knowledge regarding the mesenchymal TNBC subtype and its response to conventional therapeutic strategies, as well as to some promising molecular target agents and immunotherapy. The final goal is a tailored combination of cytotoxic drugs, target agents and immunotherapy in order to restore immunocompetence in mesenchymal breast cancer patients

A discussion of possible approaches to the integration of thermochemical storage systems in concentrating solar power plants

One of the most interesting perspectives for the development of concentrated solar power (CSP) is the storage of solar energy on a seasonal basis, intending to exploit the summer solar radiation in excess and use it in the winter months, thus stabilizing the yearly production and increasing the capacity factor of the plant. By using materials subject to reversible chemical reactions, and thus storing the thermal energy in the form of chemical energy, thermochemical storage systems can potentially serve to this purpose. The present work focuses on the identification of possible integration solutions between CSP plants and thermochemical systems for long-term energy storage, particularly for high-temperature systems such as central receiver plants. The analysis is restricted to storage systems potentially compatible with temperatures ranging from 700 to 1000 ◦C and using gases as heat transfer fluids. On the basis of the solar plant specifications, suitable reactive systems are identified and the process interfaces for the integration of solar plant/storage system/power block are discussed. The main operating conditions of the storage unit are defined for each considered case through process simulation

Estimate of the height of molten metal reactors for methane cracking

Methane Cracking represents one of the most promising routes to CO2-free hydrogen production.The methane decomposition reaction is typically carried out in fixed or fluidized catalytic beds, where the metal catalyst is supported on porous ceramic particles. By proper choice of the metal catalyst, the catalytic reaction environment allows to obtain sizeable reaction rates at operating temperatures as low as 700°C. Besides, in solid catalytic beds, the catalyst is swiftly deactivated due to the massive (i.e. stoichiometric) deposition of the solid carbon product. One way to bypass carbon deposition is to use a molten metal bath (which may or may not contain catalytic metal components) as a reaction environment, where methane bubbles are introduced at the bottom of the bath and are progressively converted as they rise through the liquid metal. The key point of this process is that, owing to a large density difference between the solid carbon phase and the molten metal, the solid product of the reaction floats on top of the liquid metal and can be thus mechanically skimmed. In this article, we develop an analytical approach to the estimate of the bath height, which constitutes one of the most critical design parameters of the process. Specifically, based on the observation that in practical applications the reacting bubble is in the kinetics-controlled regime, we obtain the conversion vs time solution for a bubble of given initial size. On the assumption of ideal gaseous mixture behaviour, the knowledge of the conversion curves allows to estimate the bubble diameter as a function of time during the rise of the bubble through the molten metal. This piece of information is then post-processed to obtain the bubble motion as a function of time. The elimination of the time parameter between the two solutions allows to construct a conversion-height map for different diameters of the bubbles

Calcium Looping for Thermochemical Storage: Assessment of Intrinsic Reaction Rate and Estimate of Kinetic/Transport Parameters for Synthetic CaO/Mayenite Particles from TGA Data

Mayenite-supported CaO represents an affordable and safetycompliant candidate material for thermochemical storage processes. We here analyze the thermogravimetric analysis (TGA) performance of synthetic CaO/mayenite micrometric powder under carbonatation/calcination looping and develop a model to interpret and analyze the experimental results. In the experimental campaign, calcination is run at 900 degrees C, while the carbonatation temperature is varied between 600 and 800 degrees C. For the carbonatation reaction, a generalized shrinking core model assuming a thermodynamically consistent first-order kinetic and a conversion-dependent diffusivity of CO2 inside the porous CaCO3 layer is validated through TGA carbonatation tests conducted with CO2/N-2 mixtures at different compositions. Interestingly, the kinetic constant of this reaction is found to be relatively insensitive to the temperature in the interval considered. In contrast, diffusion-limited regimes are never found for the calcination reaction so that this phase of the cycle can be predicted based on a single kinetic constant of the heterogeneous reaction. This constant is found to follow the typical Arrhenius-type dependence on temperature. Sizably different kinetic and transport parameters are obtained in the first carbonation performed on virgin CaO/mayenite particles with respect to those associated with subsequent cycles. When different parameters are afforded for the first and following cycles, the shrinking core model proposed closely predicts the TGA data over five CaO/CaCO3 cycles. The results found constitute an essential preliminary piece of information for designing equipment geometry and operating conditions of industrial-scale reactors. In this respect, knowledge of the parameters defining the intrinsic reaction rates and diffusive transport is essential in defining the optimal conversion of the material associated with minimal looping time