Free radical polymerization in multilaminated microreactors: 2D and 3D multiphysics CFD modeling

This paper investigates the modeling of styrene free radical polymerization in two different types of microreactor. A multiphysics model which simultaneously takes into account the hydrodynamics, thermal and mass transfer (convection, diffusion and chemical reaction) is proposed. The set of partial differential equations resulting from the model is solved with the help of the finite elements method either in a 2D or a 3D approach. The different modeled microreactors are on one hand an interdigital multilamination microreactor with a large focusing section, and on the other hand a simple T-junction followed by a straight tube with three different radii. The results are expressed in terms of reactor temperature, polydispersity index, number-average degree of polymerization and monomer conversion for different values of the chemical species diffusion coefficient. It was found that the 2D approach gives the same results as the 3D approach but allows to dramatically reduce the computing time. Despite the heat released by the polymerization reaction, it was found that the thermal transfer in such microfluidic devices is high enough to ensure isothermal conditions. Concerning the polydispersity index, the range of diffusion coefficients over which the polydispersity index can be maintained close to the theoretical value for ideal conditions increases as the tube reactor radius decreases. The interdigital multilamination microreactor was found to act as a tubular reactor of 0.78 mm ID but with a shorter length. This underlines that the use of microfluidic devices can lead to a better control of polymerization reactions.     

Design optimization of an enzymatic assay in an electrokinetically-driven microfluidic device

Microfluidic systems are increasingly popular for rapid and cheap determinations of enzyme assays and other biochemical analysis. In this study reduced order models (ROM) were developed for the optimization of enzymatic assays performed in a microchip. The model enzyme assay used was β-galactosidase (β-Gal) that catalyzes the conversion of Resorufin β-d-galactopyranoside (RBG) to a fluorescent product as previously reported by Hadd et al. (Anal Chem 69(17): 3407–3412, 1997). The assay was implemented in a microfluidic device as a continuous flow system controlled electrokinetically and with a fluorescence detection device. The results from ROM agreed well with both computational fluid dynamic (CFD) simulations and experimental values. While the CFD model allowed for assessment of local transport phenomena, the CPU time was significantly reduced by the ROM approach. The operational parameters of the assay were optimized using the validated ROM to significantly reduce the amount of reagents consumed and the total biochip assay time. After optimization the analysis time would be reduced from 20 to 5.25 min which would also resulted in 50% reduction in reagent consumption.     

Evolution of mixing in a microfluidic reverse-staggered herringbone micromixer

Microfluidic platforms offer a variety of advantages including improved heat transfer, low working volumes, ease of scale-up, and stronger user control on operating parameters. However, flow within microfluidic channels occurs at low Reynolds number (Re), which makes mixing difficult to accomplish. Adding V-shaped ridges to channel walls, a pattern called the staggered herringbone design (SHB), alleviates this problem by introducing transverse flow patterns that enable enhanced mixing. Building on our prior work, we here developed a microfluidic mixer utilizing the SHB geometry and characterized using CFD simulations and complimentary experiments. Specifically, we investigated the performance of this type of mixer for unequal species diffusivities and inlet flows. A channel design with SHB ridges was simulated in COMSOL Multiphysics® software under a variety of operating conditions to evaluate its mixing capabilities. The device was fabricated using soft-lithography techniques to experimentally visualize the mixing process. Mixing within the device was enabled by injecting fluorescent dyes through the device and imaging using a confocal microscope. The device was found to efficiently mix fluids rapidly, based on both simulations and experiments. Varying Re or species diffusion coefficients had a weak effect on the mixing profile, due to the laminar flow regime and insufficient residence time, respectively. Mixing effectiveness increased as the species flow rate ratio increased. Fluid flow patterns visualized in confocal microscope images for selective cases were strikingly similar to CFD results, suggesting that the simulations serve as good predictors of device performance. This SHB mixer design would be a good candidate for further implementation as a microfluidic reactor.     

DNA ligation using a disposable microfluidic device combined with a micromixer and microchannel reactor

A novel PDMS and glass-based microfluidic device consisting of a micromixer and microreactor for DNA ligation is described in this article. The new passive type planar micromixer is 10.33 mm long and composed of a straight channel integrated with nozzles and pillars, and the microreactor is composed of a serpentine channel. Mixing was enhanced by convective diffusion facilitated by the nozzles and pillars. The performance of the micromixer was analytically simulated and experimentally evaluated. The micromixer showed a good mixing efficiency of 87.7% at a 500 μL/min flow rate (Re = 66.5). DNA ligation was successfully performed using the new microfluidic device, and ligation time was shortened from 4 h to 5 min. When used for on-chip ligation, this new micromixer offers advantages of disposability and portability.     

Theoretical performance of a coiled coil piezoelectric bimorph

The electromechanical coupling behaviour of a novel, highly coiled piezoelectric strip structure is developed in full, in order to expound its performance and efficiency. The strip is doubly coiled for compactness and, compared to a standard straight actuator of the same cross-section, it is shown that the actuator here offers better generative forces and energy conversion, and substantial actuated displacements, however, at the expense of a much lower stiffness. The device is therefore proposed for high-displacement, quasi-static applications.     

Challenges in particulate polymerization reactor modeling and optimization: A population balance perspective

In the present article, recent developments on modeling and optimization of particulate polymerization processes are reviewed. A unified population balance approach is described to follow the time evolution of molecular and morphological polymer properties in batch and continuous polymerization reactors. The numerical methods as well as the computational issues related with the solution of the dynamic population balance equation are critically assessed. The orthogonal collocation on finite elements (OCFE) method and the fixed-pivot technique (FPT) are then applied to a free-radical batch polymerization reactor to calculate the dynamic evolution of the molecular weight distribution (MWD). Moreover, theoretical and experimental results are shown on the dynamic evolution of particle size distribution (PSD) in a suspension polymerization reactor. Recent advances in on-line monitoring of “polymer quality” are briefly discussed in the context of available hardware and software sensors. The problem of real-time optimization of polymerization processes under parametric uncertainty is also examined. Finally, new issues related with the modeling, numerical solution and control of multidimensional population balance equations are conferred.     

Microfluidic reactor array device for massively parallel in situ synthesis of oligonucleotides

We have designed and fabricated a microfluidic reactor array device for massively parallel in situ synthesis of oligonucleotides (oDNA). The device is made of glass anodically bonded to silicon consisting of three level features: microreactors, microchannels and through inlet/outlet holes. Main challenges in the design of this device include preventing diffusion of photogenerated reagents upon activation and achieving uniform reagent flow through thousands of parallel reactors. The device embodies a simple and effective dynamic isolation mechanism which prevents the intermixing of active reagents between discrete microreactors. Depending on the design parameters, it is possible to achieve uniform flow and synthesis reaction in all of the reactors by proper design of the microreactors and the microchannels. We demonstrated the use of this device on a solution-based, light-directed parallel in situ oDNA synthesis. We were able to synthesize long oDNA, up to 120 mers at stepwise yield of 98%. The quality of our microfluidic oDNA microarray including sensitivity, signal noise, specificity, spot variation and accuracy was characterized. Our microfluidic reactor array devices show a great potential for genomics and proteomics researches.     

On-chip encapsulation via chaotic mixing

A microfluidic device for production of uniform size capsules with a prescribed membrane thickness is described. It is versatile, novel and suitable for various polymerization reactions. Parameters such as polymerization time and reagent concentrations can be precisely tuned to control the membrane properties. The device features a part which allows to overcome the diffusion barrier by initiating interfacial polymerization via chaotic mixing. It also allows the termination of the reaction and the collection of the resulting capsules. We observe different typical dynamical phenomena occurring in capsules during their flow along the microchannel, namely wrinkling of the membrane, parachute and bullet shapes and bursting of the capsules due to strong hydrodynamical flow. In addition to production, the monitoring of capsule dynamics in flow gave a possibility to estimate the elastic surface modulus \(E_{{\rm S}}\) and the membrane thickness t. We found that \(E_{{\rm S}}\) can be as low as 6 × 10^?3 N m^?1 and that the thickness can be below 100 nm. This microfluidic device is therefore capable of producing uniform size capsule solutions with suitable membrane properties for the controlled release of drugs, and as a model system of red blood cells for microhydrodynamics experiments.     

Simulation of advanced microfluidic systems with dissipative particle dynamics

Computational Fluid Dynamics (CFD) is widely and successfully used in standard design processes for microfluidic μTAS devices. But for an increasing number of advanced applications involving the dynamics of small groups of beads, blood cells or biopolymers in microcapillaries or sorting devices, novel simulation techniques are called for. Representing moving rigid or flexible extended dispersed objects poses serious difficulties for traditional CFD schemes. Meshless, particle-based simulation approaches, such as Dissipative Particle Dynamics (DPD) are suited for addressing these complicated flow problems with sufficient numerical efficiency. Objects can conveniently be represented as compound objects embedded seamlessly within an explicit model for the solvent. However, the application of DPD and related methods to realistic problems, in particular the design of microfluidics systems, is not well developed in general. With this work, we demonstrate how the method appears when used in practice, in the process of designing and simulating a specific microfluidic device, a microfluidic chamber representing a prototypical bead-based immunoassay developed in our laboratory (Glatzel et al. 2006a, b; Riegger et al. 2006). Thomas Steiner: born Glatzel.     

Color to gray conversions in the context of stereo matching algorithms

This study tackles the image color to gray conversion problem. The aim was to understand the conversion qualities that can improve the accuracy of results when the grayscale conversion is applied as a pre-processing step in the context of vision algorithms, and in particular dense stereo matching. We evaluated many different state of the art color to grayscale conversion algorithms. We also propose an ad-hoc adaptation of the most theoretically promising algorithm, which we call Multi-Image Decolorize (MID). This algorithm comes from an in-depth analysis of the existing conversion solutions and consists of a multi-image extension of the algorithm by Grundland and Dodgson (The decolorize algorithm for contrast enhancing, color to grayscale conversion, Tech. Rep. UCAM-CL-TR-649, University of Cambridge, 2005) which is based on predominant component analysis. In addition, two variants of this algorithm have been proposed and analyzed: one with standard unsharp masking and another with a chromatic weighted unsharp masking technique (Nowak and Baraniuk in IEEE Trans Image Process 7(7):1068–1074, 1998) which enhances the local contrast as shown in the approach by Smith et al. (Comput Graph Forum 27(2), 2008). We tested the relative performances of this conversion with respect to many other solutions, using the StereoMatcher test suite (Scharstein and Szeliski in Int J Comput Vis 47(1–3):7–42, 2002) with a variety of different datasets and different dense stereo matching algorithms. The results show that the overall performance of the proposed MID conversion are good and the reported tests provided useful information and insights on how to design color to gray conversion to improve matching performance. We also show some interesting secondary results such as the role of standard unsharp masking vs. chromatic unsharp masking in improving correspondence matching.     

CFD simulation of gas–liquid flow behaviour in an air-lift reactor: determination of the optimum distance of the draft tube

CFD simulation in an air-lift reactor containing a draft tube was employed. Three different layouts between the draft tube and the wall were used to determine the optimum distance between them. Appropriate distance of the draft tube and the wall was determined for the designing purposes, and the best distance was calculated. The simulation results were compared with the experimental results of the Menzel et al. Also it was also proven that the optimum distance results in the best possible effective mixing, higher rotary movements of the liquid and gas, and consequently improves the reactor performance.     

Continuous-flow ATP amplification system on a chip

In this study, we constructed a novel microfluidic device for continuous-flow ATP amplification, using the SU-8:PDMS method. Sepharose beads immobilized with adenylate kinase and pyruvate kinase was packed into a microfluidic chamber to form lamination layer. Dry film type SU-8 was suitable to form a very thick mold for beads column reactor and its dam structure. A good correlation between amplified luminescence and initial ATP concentration was observed in this system. The gradient of amplification when performing six cycles of continuous-flow ATP amplification was 1.72^N.     

One-step rapid fabrication of paper-based microfluidic devices using fluorocarbon plasma polymerization

In this work, we demonstrated an all-dry, top-down, and one-step rapid process to fabricate paper-based microfluidic devices using fluorocarbon plasma polymerization. This process is able to create fluorocarbon-coated hydrophobic patterns on filter paper substrates while maintaining the trench and detection regions intact and free of contamination after the fabrication process, as confirmed by attenuated total reflectance–Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We have shown that the processing time is one critical factor that influences the device performance. For the device fabricated with a sufficiently long processing time (180 s), the sample fluid flow can be well confined in the patterned trenches. By testing the device with an 800 μm channel width, a sample solution amount as small as 4.5 μL is sufficient to perform the test. NO₂ ^? assay is also performed and shows that such a device is capable for biochemical analysis.     

Modeling and control of an LDPE autoclave reactor

A two-compartment four-cell model is developed for the adiabetic slim type autoclave reactor for free radical polymerization of low density polyethylene (LDPE). It is possible to determine not only the reactor performance represented by the monomer conversion and the reaction temperature but also the properties of the polymer product characterized by the average molecular weight and the polydispersity. It turns out that the reactor performance predicted is in good agreement with the plant data and the properties of the polymer product are estimated within reasonable ranges of actual values. The steady state multiplicity is found to exist and is examined by constructing the bifurcation diagram. The effects of various operation parameters on the reactor performance and the polymer properties are investigated systematically to show that the temperature distribution plays the central role for the properties of the polymer products. Therefore, it is essential to establish a good control strategy for the temperature in each compartment. The adaptive pole-placement control algorithm is applied to the temperature control of the adiabatic slim type autoclave reactor. The recursive least square method is used for the model identification. To accomplish a satisfactory control, the estimator and controller are initialized during the period of start-up. It is shown that the reactor system can be adaptively controlled by the pole-placement control algorithm, especially when the reactor temperature distribution is changed.     

Development of microfluidic devices incorporating non-spherical hydrogel microparticles for protein-based bioassay

This paper describes the fabrication of a microfluidic device for use in protein-based bioassays that effectively incorporates poly(ethylene glycol) (PEG) hydrogel microparticles within a defined region. The microfluidic device is composed of a polymerization chamber and reaction chamber that are serially connected through the microchannel. Various shapes and sizes of hydrogel microparticles were fabricated in the polymerization chamber by photopatterning and moved to the reaction chamber by pressure-driven flow. All of the hydrogel microparticles were retained within the reaction chamber due to an in-chamber integrated microfilter with smaller mesh size than hydrogel microparticles. Hydrogel microparticles were able to encapsulate enzymes without losing their activity, and different concentrations of glucose were detected by sequential bienzymatic reaction of hydrogel-entrapped glucose oxidase (GOX) and peroxidase (POD) inside the microfluidic device using fluorescence method. Importantly, there was a linear correspondence between fluorescence intensity and the glucose concentration over the physiologically important range of 1.00–10.00 mM. D. Choi and E. Jang contributed equally to this work.     

A study of molecular diffusion across a water/oil interface in a Y–Y shaped microfluidic device

The diffusion behaviour of Co(II) ion in an aqueous homogeneous system and that of 8-hydroxyquinoline (8HQ) in a heterogeneous liquid–liquid system was measured in a Y–Y shaped microfluidic device. We propose a modified version of a previously published equation for a static system to describe the diffusion behaviour of chemical species in this microfluidic device. Specific adaptations of the original equation to the micro environment are illustrated and discussed. The model proposed successfully fitted the diffusion of Co(II) in a homogeneous system (aqueous solutions) and 8HQ across a water/oil interface. We envisage the application of the proposed equation for the discrimination of the diffusion contribution in solvent extraction kinetic studies.     

A high-shear, low Reynolds number microfluidic rheometer

We present a microfluidic rheometer that uses in situ pressure sensors to measure the viscosity of liquids at low Reynolds number. Viscosity is measured in a long, straight channel using a PDMS-based microfluidic device that consists of a channel layer and a sensing membrane integrated with an array of piezoresistive pressure sensors via plasma surface treatment. The micro-pressure sensor is fabricated using conductive particles/PDMS composites. The sensing membrane maps pressure differences at various locations within the channel in order to measure the fluid shear stress in situ at a prescribed shear rate to estimate the fluid viscosity. We find that the device is capable to measure the viscosity of both Newtonian and non-Newtonian fluids for shear rates up to 10⁴ s^?1 while keeping the Reynolds number well below 1.     

Experimental study of diffusion-based extraction from a cell suspension

A recently proposed application of microfluidics is the post-thaw processing of biological cells. Numerical simulations suggest that diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood cells is viable and more efficient than centrifugation, the conventional method of DMSO removal. In order to validate the theoretical model used in these simulations, a prototype was built and the flow of two parallel streams, a suspension of Jurkat cells containing DMSO and a wash stream that contained neither cells nor DMSO, was characterized experimentally. DMSO transport in a rectangular channel (depth 500 μm, width 25 mm and overall length 125 mm) was studied as a function of three dimensionless parameters: depth ratio of the streams, cell volume fraction in the cell solution, and the Peclet number (Pe) based on channel depth, average flow rate and the diffusion coefficient for DMSO in water. In our studies, values of Pe ranged from O(10³) to O(10⁴). Laminar flow was ensured by keeping the Reynolds number between O(1) and O(10). Experimental results based on visual and quantitative data demonstrate conclusively that a microfluidic device can effectively remove DMSO from liquid and cell laden streams without compromising cell recovery. Also, flow conditions in the microfluidic device appear to have no adverse effect on cell viability at the outlet. Further, the results demonstrate that we can predict the amount of DMSO removed from a given device with the theoretical model mentioned previously.     

Control of the quality of polymer products in continuous reactors: comparison of performance of state estimators with and without updating of parameters

In the paper the control of the product quality in polymerization reactors is analysed in the presence of persistent perturbations (unmodeled disturbances, modeling errors), as met in industrial reactors. The free radical polymerization of methyl-methacrylate in a continuous stirred tank reactor is studied. It is shown that state estimators (Extended Kalman Filters) with constant parameters cannot give offset free performance. Criteria for the selection of a set of parameters to be updated as additional states in the filter and to evaluate their effectiveness in opposing the action of realistic perturbations are given by an analysis of the linearized model of the system. Performance of different types of estimators, including one and two-time scale filters, with and without updating of parameters, is analysed by simulation on the full order process and the predictions made by previous analysis are confirmed. In the most common case of presence of perturbations affecting the energy balance and the concentration of initiator in the reactor, offset free control of the molecular weight of the product can be achieved by means of a filter which is based only on measurements of temperature and conversion and makes an update of two parameters. In the case that also the kinetic model of the polymerization reaction is affected by errors, a two-time scale filter, which makes use also of Molecular Weight values and updates three parameters, becomes necessary to obtain offset free performance.     

Enhanced bioreaction efficiency of a microfluidic mixer toward high-throughput and low-cost bioassays

Microscale bioreactors are an important tool in performing bioassays. The speed and efficiency of these devices is often limited by the rate of reagent mixing. In spite of the various micromixing approaches, the coupled mixing/reaction process has yet to be clearly understood. This article presents experimental and computational studies on the enhancement of bioreaction rates using a novel cilia reactor. In the experiments, a biotin-avidin assay and a DNA hybridization assay were conducted to show the benefit of a cilia bioreactor compared with a simple diffusion reactor. A cilia reactor showed a shorter reaction time for approaching equilibrium. A numerical computation examined the bioreaction rate of the cilia reactor compared with the diffusion for (1) a biotin-avidin assay, (2) an immunoassay, and (3) a DNA hybridization assay. The reaction rate was characterized for each assay using the Damk?hler number (Da). When Da was greater than 10², the ratio of reaction time for the diffusion to cilia reactors linearly increased with Da, which could also save reagent usage by lowering the concentration of reagent probes. However, when the system had a Da smaller than 10², the reaction time of a cilia reactor could not be shortened because the assay was dominated by reaction rather than fluid mixing. The results offer a general approach for enhancing bioreaction rates by employing microfluidic mixers for a bioassay.