Modeling and high performance simulation of electrophoretic techniques in microfluidic chips

Electrophoretic separations comprise a group of analytical techniques such as capillary zone electrophoresis, isoelectric focusing, isotachophoresis, and free flow electrophoresis. These techniques have been miniaturized in the last years and now represent one of the most important applications of the lab-on-a-chip technology. A 3D and time-dependent numerical model of electrophoresis on microfluidic devices is presented. The model is based on the set of equations that governs electrical phenomena, fluid dynamics, mass transport, and chemical reactions. The relationship between the buffer characteristics (ionic strength and pH) and surface potential of channel walls is taken into consideration. Numerical calculations were performed by using PETSc-FEM, in a Python environment, employing high performance parallel computing. The method includes a set of last generation preconditioners and solvers, especially addressed to 3D microfluidic problems, which significantly improve the numerical efficiency in comparison with typical commercial software for multiphysics. In this work, after discussing two validation examples, the numerical prototyping of a microfluidic chip for two-dimensional electrophoresis is presented.     

Polytetrafluoroethylene processing characteristics using high-energy X-ray

Polytetrafluoroethylene (PTFE) microstructures’ processing characteristics using X-ray photo dcomposition and desorption are studied in the highest energy region (2 keV to >12 keV). While the exposed surface states are seen melting and boiling from the remaining bubble structure of the irradiated surface, basic photochemistry of PTFE is also same as previous reports and high-aspect ratio structures are successfully formed. We developed new Ni stencil electroformed stencil masks and successfully fabricated first and practical example of PTFE micro fluidic parts. The characteristics of fabricated micro fluidic parts, a PTFE fluid filter for vertical fluid flow operation which works as passive valve, agreed with the calculated results. This suggests that the accuracy of patterning is adequate to apply this technique to fabricate microfluidic parts and other various microparts.     

An Object-Oriented Framework for Multidisciplinary, Multi-Physics, Computational Mechanics

This paper presents the design and development of an object-oriented framework for computational mechanics. The framework has been designed to address some of the major deficiencies in existing computational mechanics software packages. The framework addresses the deficiencies of existing computational mechanics software packages by (a) having a sound design using the state of the art in software engineering, and (b) providing model manipulation features that are common to a large set of computational mechanics problems. The framework provides features that are essential to a large set of computational mechanics problems. The domainspecific features provided by the framework are a geometry sub-system specifically designed for computational mechanics, an interpreted Computational Mechanics Language (CML), a structure for management of analysis projects, a comprehensive data model, model development, model query and analysis management. The domain independent features provided by the framework are a drawing subsystem for data visualization, a database server, a quantity subsystem, a simple GUI and an online help server. It is demonstrated that the framework can be used to develop applications that can: (a) extend or modify important parts of the framework to suit their own needs; (b) use CML for rapid prototyping and extending the functionality of the framework; (c) significantly ease the task of conducting parametric studies; (d) significantly ease the task of modeling evolutionary problems; (e) be easily interfaced with existing analysis programs; and (f) be used to carry out basic computational mechanics research. It is hoped that the framework will substantially ease the task of creating families of software applications that apply existing and upcoming theories of computational mechanics to solve both academic and real world interdisciplinary simulation problems.     

Optimal fuzzy sliding-mode control for bio-microfluidic manipulation

In biometric and biomedical applications, a special transporting mechanism must be designed for the micro total analysis system (μTAS) to move samples and reagents through the microchannels that connect the unit procedure components in the system. An important issue for this miniaturization and integration is the microfluid management technique, i.e., microfluid transportation, metering, and mixing. In view of this, an optimal fuzzy sliding-mode control (OFSMC) based on the 8051 microprocessor is designed and a complete microfluidic manipulated biochip system is implemented in this study, with a pneumatic pumping actuator, two feedback-signal photodiodes and flowmeters for better microfluidic management. This new technique successfully improved the efficiency of biochemical reaction by increasing the effective collision into the probe molecules as the target molecules flow back and forth. The new technique was used in DNA extraction. When the number of Escherichia coli cells was 2×10²–10⁴ in 25 μl of whole blood, the extraction efficiency of immobilized beads with solution flowing back and forth was 600-fold larger than that of free beads.     

Automatic,parallel and fault tolerant mesh generation from CAD

HEXAR, a new software product developed at Cray Research, Inc., automatically generates good quality meshes directly from surface data produced by computeraided design (CAD) packages. The HEXAR automatic mesh generator is based on a proprietary and parallel algorithm that relies on pattern recognition, local mesh refinement and coarsening, and variational mesh smoothing techniques to create all-hexahedral volume meshes. HEXAR generates grids two to three orders of magnitude faster than current manual approaches. Although approximate by design, the resulting meshes have qualities acceptable by many commercial structural and CFD (computational fluid dynamics) software. HEXAR turns mesh generation into an automatic process for most commercial engineering applications.     

Effectiveness of multiple pageable page sizes for commercial applications

This paper investigates the computational characteristics of the software applications that are developed to support typical modern e‐commerce applications. These applications have a significant impact on global commerce, and their influence is expected to continue. We show that the micro‐architectural features of the memory subsystem, assisted by the operating system (such as the use of concurrent pageable page sizes), can significantly improve the performance of these applications. In particular, we show that using 64 kB page size in addition to the default 4 kB page size provides substantial throughput improvements for a typical commercial application (Trade6) without adding any complexity for the application developer or the system administrator. Copyright © 2007 John Wiley & Sons, Ltd.     

Rapid prototyping of PMMA microfluidic chips utilizing a CO<Subscript>2</Subscript> laser

A commercially available CO₂ laser scriber is used to perform the direct-writing ablation of polymethyl-methacrylate (PMMA) substrates for microfluidic applications. The microfluidic designs are created using commercial layout software and are converted into the command signals required to drive the laser scriber in such a way as to reproduce the desired microchannel configuration on the surface of a PMMA substrate. The aspect ratio and surface quality of the ablated microchannels are examined using scanning electron microscopy and atomic force microscopy surface measurement techniques. The results show that a smooth channel wall can be obtained without the need for a post-machining annealing operation by performing the scribing process with the CO₂ laser beam in an unfocused condition. The practicality of the proposed approach is demonstrated by fabricating two microfluidic chips, namely a cytometer, and an integrating microfluidic chip for methanol detection, respectively. The results confirm that the proposed unfocused ablation technique represents a viable solution for the rapid and economic fabrication of a wide variety of PMMA-based microfluidic chips.     

ParFUM: a parallel framework for unstructured meshes for scalable dynamic physics applications

Unstructured meshes are used in many engineering applications with irregular domains, from elastic deformation problems to crack propagation to fluid flow. Because of their complexity and dynamic behavior, the development of scalable parallel software for these applications is challenging. The Charm++ Parallel Framework for Unstructured Meshes allows one to write parallel programs that operate on unstructured meshes with only minimal knowledge of parallel computing, while making it possible to achieve excellent scalability even for complex applications. Charm++’s message-driven model enables computation/communication overlap, while its run-time load balancing capabilities make it possible to react to the changes in computational load that occur in dynamic physics applications. The framework is highly flexible and has been enhanced with numerous capabilities for the manipulation of unstructured meshes, such as parallel mesh adaptivity and collision detection.     

A microfluidic device for array patterning by perpendicular electrokinetic focusing

This paper describes a microfluidic chip in which two perpendicular laminar-flow streams can be operated to sequentially address the surface of a flow-chamber with semi-parallel sample streams. The sample streams can be controlled in position and width by the method of electrokinetic focusing. For this purpose, each of the two streams is sandwiched by two parallel sheath flow streams containing just a buffer solution. The streams are being electroosmotically pumped, allowing a simple chip design and a setup with no moving parts. Positioning of the streams was adjusted in real-time by controlling the applied voltages according to an analytical model. The perpendicular focusing gives rise to overlapping regions, which, by combinatorial (bio) chemistry, might be used for fabrication of spot arrays of immobilized proteins and other biomolecules. Since the patterning procedure is done in a closed, liquid filled flow-structure, array spots will never be exposed to air and are prevented from drying. With this device configuration, it was possible to visualize an array of 49 spots on a surface area of 1 mm². This article describes the principle, fabrication, experimental results, analytical modeling and numerical simulations of the microfluidic chip.     

Status of the TOUGH-FLAC simulator and recent applications related to coupled fluid flow and crustal deformations

This paper presents recent advancement in and applications of TOUGH-FLAC, a simulator for multiphase fluid flow and geomechanics. The TOUGH-FLAC simulator links the TOUGH family multiphase fluid and heat transport codes with the commercial FLAC^3D geomechanical simulator. The most significant new TOUGH-FLAC development in the past few years is a revised architecture, enabling a more rigorous and tight coupling procedure with improved computational efficiency. The applications presented in this paper are related to modeling of crustal deformations caused by deep underground fluid movements and pressure changes as a result of both industrial activities (the In Salah CO₂ Storage Project and the Geysers Geothermal Field) and natural events (the 1960s Matsushiro Earthquake Swarm). Finally, the paper provides some perspectives on the future of TOUGH-FLAC in light of its applicability to practical problems and the need for high-performance computing capabilities for field-scale problems, such as industrial-scale CO₂ storage and enhanced geothermal systems. It is concluded that despite some limitations to fully adapting a commercial code such as FLAC^3D for some specialized research and computational needs, TOUGH-FLAC is likely to remain a pragmatic simulation approach, with an increasing number of users in both academia and industry.     

Chitosan microfiber fabrication using a microfluidic chip and its application to cell cultures

In this study, a poly-methyl-methacrylate (PMMA) microfluidic chip with a 45° cross-junction microchannel is fabricated using a CO₂ laser machine to generate chitosan microfibers. Chitosan solution and sodium tripolyphosphate (STPP) solution were injected into the cross-junction microchannel of the microfluidic chip. The laminar flow of the chitosan solution was generated by hydrodynamic focusing. The diameter of laminar flow, which ranged from 30 to 50 μm, was controlled by changing the ratio between chitosan solution and STPP solution flow rates in the PMMA microfluidic chip. The laminar flow of the chitosan solution was converted into chitosan microfibers with STPP solution via the cross-linking reaction; the diameter of chitosan microfibers was in the range of 50–200 μm. The chitosan microfibers were then coated with collagen for cell cultivation. The results show that the chitosan microfibers provide good growth conditions for cells. They could be used as a scaffold for cell cultures in tissue engineering applications. This novel method has advantages of ease of fabrication, simple and low-cost process.     

A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices

Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm²) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.     

Computer-based algorithms for multiple criteria and multiple constraint level integer linear programming

This paper investigates algorithm development and implementation for multicriteria and multiconstraint level (MC²) integer linear programming problems. MC² linear programming is an extension of linear programming (LP) and multiple criteria (MC) linear programming and a promising computer-aided decision technique in many applications. Here, we present two of the most recent techniques, the MC² branch-and-partition algorithm and the MC² branch-and-bound algorithm, to solve MC² integer linear programs. We describe the design and implementation of a C++ software library for these approaches, and then conduct a comparison study in terms of computational efficiency and complexity through a series of empirical tests.     

Design and simulation of a thermo transfer type MEMS based micro flow sensor for arterial blood flow measurement

Thermo transfer type MEMS (Micro Electro Mechanical System) based micro flow sensing device have promising potential to solve the limitation of implantable arterial blood flow rate monitoring. The present paper emphasizes on modeling and simulation of MEMS based micro flow sensing device, which will be capable of implantable arterial blood flow rate measurement. It describes the basic design and model architecture of thermal type micro flow sensor. A pair of thin film micro heaters is designed through MEMS micro machining process and simulated using CoventorWare; a finite element based numerical code. A rectangular cross section micro channel has been modeled where in micro heater and thermal sensors are embedded using the same CoventorWare tools. Some promising and interesting results of thermal dissipation depending upon very small amount of flow rate through the micro channel are investigated. It is observed that measuring the variation of temperature difference between downstream and upstream, the variation of fluid flow rate in the micro channel can be measured. The numerical simulation results also shows that the temperature distribution profile of the heated surface depends upon microfluidic flow rate i.e. convective heat transfer is directly proportional to the microfluidic flow rate on the surface of the insulating membrane. The simplified analytical model of the thermo transfer type flow sensor is presented and verified by simulation results, which are very promising for application in arterial blood flow rate measuring in implantable micro devices for continuous monitoring of cardiac output.     

化学工程中的计算流体力学

本文评述了计算流体力学在化学化工研究和开发中的重要地位,介绍了各种模拟方法研究的现状、存在的困难和一些发展中的前沿领域。与传统应用领域相比,化学工程领域主要面对的是复杂多相流体系统及流动、传递和反应相耦合的过程,基于单尺度统计平均的传统连续介质方法已很难满足对产品结构和过程工艺精确设计的要求,而多尺度方法与粒子方法的结合是一条有效的途径。它通过对复杂系统满足的稳定性条件的分析以及对复杂界面和间断性的合理描述实现跨尺度关联的模拟,从而量化介观结构与行为、建立准确的宏观模型。这种结合无论是对湍流、汽液或气固多相流等传统的难题,还是对微流动、生物流、聚合物流动、颗粒流及散料力学等前沿领域,都带来了新的可能性,也将为化学化工领域的研发工作提供更有力的手段。     

Development and characterisation of integrated microfluidics on waveguide-based photonic platforms fabricated from hybrid materials

This article reports on a detailed investigation of sol–gel processed hybrid organic–inorganic materials for use in lab-on-a-chip (LoC) applications. A particular focus on this research was the implementation of integrated microfluidic circuitry in waveguide-based photonic sensing platforms. This objective is not possible using other fabrication technologies that are typically used for microfluidic platforms. Significant results on the surface characterisation of hybrid sol–gel processed materials have been obtained which highlight the ability to tune the hydrophilicity of the materials by careful adjustment of material constituents and processing conditions. A proof-of-principle microfluidic platform was designed and a fabrication process was established which addressed requirements for refractive index tuning (essential for waveguiding), bonding of a transparent cover layer to the device, optimized sol–gel deposition process, and a photolithography process to form the microchannels. Characterisation of fluid flow in the resulting microchannels revealed volumetric flow rates between 0.012 and 0.018 μl/min which is characteristic of capillary-driven fluid flow. As proof of the integration of optical and microfluidic functionality, a microchannel was fabricated crossing an optical waveguide which demonstrated that the presence of optical waveguides does not significantly disrupt capillary-driven fluid flow. These results represent the first comprehensive evaluation of photocurable hybrid sol–gel materials for use in waveguide-based photonic platforms for lab-on-a-chip applications.     

A microvalve for hybrid microfluidic systems

A hybrid valve for lab on chip applications is presented. The valve is assembled by bonding poly (methyl methacrylate), PMMA, and silicon-based elastomers. The process used to promote the hybrid bonding includes the deposition of an organosilane (TMSPM) on the thermoplastic polymer, PMMA to interface PMMA and elastomers. For this study, a membrane in ELASTOSIL^? is bonded in correspondence of the end of two microfluidic channels of a fabricated PMMA microfluidic chip. Prior the bonding, a plasma etching process has been used to remove the TMSPM in a confined circular area. This process made possible to bond selectively the edge of a membrane leaving free to move its central part. Actuating the membrane with an external positive pressure or vacuum is possible, respectively, to obstruct or to connect the microfluidic channels. The microvalve may be simply integrated in microfluidic devices and permits the control of microvolumes of fluid in processes such as transport, separation, and mixing. The deposition of the TMSPM, the bonding of the valve and its actuation has been characterized and tested. The flow rate control of liquids through the valve has been characterized. The results have been discussed and commented. The valve can stand up to 14 psi without showing leakages.     

Applications and perspectives on microfluidic technologies in ships and marine engineering: a review

More than 71% of the earth’s surface area is occupied by ocean, and the shipping has become one of the most common forms of transportation. There are many applications for rapid on-site detection in ships and marine engineering in general. However, owing to the limited space and environmental conditions, large-scale laboratory equipment cannot be utilized on ships and offline examination methods cannot meet the needs for rapid detection and analysis of problems. Microfluidic technologies provide an excellent platform where various biological and chemical reactions can be completed on very small microfluidic chips. The combination of microfluidic technologies and ship and marine engineering will have important theoretical significance and practical value. These applications mainly include ballast water analysis, lubricating oil analysis, monitoring oil spill, ship exhaust gas detection and ship sewage detection. Therefore, in this paper, we have summarized the current applications of microfluidic technologies in ships and marine engineering and suggested prospects for the potential research directions in the future.     

A low molecular weight cut-off polymer–silicate membrane for microfluidic applications

In this article, we report a novel approach to fabricating a low molecular weight cut-off membrane that could readily be employed for several microfluidic applications. The reported structure was created by selectively retaining a precursor solution [5% (w/v) maleic anhydride, 21% (v/v) (37:1) acrylamide/bisacrylamide, and 0.2% (w/v) VA-086 photoinitiator] in a chosen location of a microfluidic network via capillary forces and then photo-polymerizing the mixture. The pores in the resulting membrane were subsequently filled with 3-aminopropyltriethoxysilane, heated, and then treated with sodium silicate solution and heated again, giving a structure having reduced porosity. The composite membrane thus created has been shown to have a molecular weight cut-off that is at least an order of magnitude smaller than other photo-polymerized microfluidic membranes reported in the literature. Moreover, this polymer–silicate structure was observed to be capable of blocking electroosmotic flow, thereby generating a pressure gradient around its interface with an open microchannel upon application of an electric field across the microchannel-membrane junction. In this study, a fraction of the resulting hydrodynamic flow was successfully guided to an electric field free analysis channel to implement a pressure-driven assay. With our current design pressure-driven velocities, up to 1.8 mm/s was generated in the electric field free analysis channel for an applied voltage of 2 kV in the pumping section. Finally, the functionality of this integrated microfluidic device was demonstrated by implementing a reverse phase chromatographic separation using the pressure-driven flow generated on-chip.