Simulations of DNA stretching by flow field in microchannels with complex geometry

Recently, we have reported the experimental results of DNA stretching by flow field in three microchannels (C. H. Lee and C. C. Hsieh, Biomicrofluidics 7(1), 014109 (2013)) designed specifically for the purpose of preconditioning DNA conformation for easier stretching. The experimental results do not only demonstrate the superiority of the new devices but also provides detailed observation of DNA behavior in complex flow field that was not available before. In this study, we use Brownian dynamics-finite element method (BD-FEM) to simulate DNA behavior in these microchannels, and compare the results against the experiments. Although the hydrodynamic interaction (HI) between DNA segments and between DNA and the device boundaries was not included in the simulations, the simulation results are in fairly good agreement with the experimental data from either the aspect of the single molecule behavior or from the aspect of ensemble averaged properties. The discrepancy between the simulation and the experimental results can be explained by the neglect of HI effect in the simulations. Considering the huge savings on the computational cost from neglecting HI, we conclude that BD-FEM can be used as an efficient and economic designing tool for developing new microfluidic device for DNA manipulation.     

Evaluation of the Kirkwood approximation for the diffusivity of channel-confined DNA chains in the de Gennes regime

We use Brownian dynamics with hydrodynamic interactions to calculate both the Kirkwood (short-time) diffusivity and the long-time diffusivity of DNA chains from free solution down to channel confinement in the de Gennes regime. The Kirkwood diffusivity in confinement is always higher than the diffusivity obtained from the mean-squared displacement of the center-of-mass, as is the case in free solution. Moreover, the divergence of the local diffusion tensor, which is non-zero in confinement, makes a negligible contribution to the latter diffusivity in confinement. The maximum error in the Kirkwood approximation in our simulations is about 2% for experimentally relevant simulation times. The error decreases with increasing confinement, consistent with arguments from blob theory and the molecular-weight dependence of the error in free solution. In light of the typical experimental errors in measuring the properties of channel-confined DNA, our results suggest that the Kirkwood approximation is sufficiently accurate to model experimental data.     

Patterning nanowire and micro-∕nanoparticle array on micropillar-structured surface: Experiment and modeling

DNA molecules in a solution can be immobilized and stretched into a highly ordered array on a solid surface containing micropillars by molecular combing technique. However, the mechanism of this process is not well understood. In this study, we demonstrated the generation of DNA nanostrand array with linear, zigzag, and fork-zigzag patterns and the microfluidic processes are modeled based on a deforming body-fitted grid approach. The simulation results provide insights for explaining the stretching, immobilizing, and patterning of DNA molecules observed in the experiments.     

On-chip assay of the effect of topographical microenvironment on cell growth and cell-cell interactions during wound healing

Wound healing is an essential physiological process for tissue homeostasis, involving multiple types of cells, extracellular matrices, and growth factor/chemokine interactions. Many in vitro studies have investigated the interactions between cues mentioned above; however, most of them only focused on a single factor. In the present study, we design a wound healing device to recapitulate in vivo complex microenvironments and heterogeneous cell situations to investigate how three types of physiologically related cells interact with their microenvironments around and with each other during a wound healing process. Briefly, a microfluidic device with a micropillar substrate, where diameter and interspacing can be tuned to mimic the topographical features of the 3D extracellular matrix, was designed to perform positional cell loading on the micropillar substrate, co-culture of three types of physiologically related cells, keratinocytes, dermal fibroblasts, and human umbilical vein endothelial cells, as well as an investigation of their interactions during wound healing. The result showed that cell attachment, morphology, cytoskeleton distribution, and nucleus shape were strongly affected by the micropillars, and these cells showed collaborative response to heal the wound. Taken together, these findings highlight the dynamic relationship between cells and their microenvironments. Also, this reproducible device may facilitate the in vitro investigation of numerous physiological and pathological processes such as cancer metastasis, angiogenesis, and tissue engineering.     

Electrowetting on dielectric device with crescent electrodes for reliable and low-voltage droplet manipulation

Digital microfluidics based on electrowetting on dielectric is an emerging popular technology that manipulates single droplets at the microliter or even the nanoliter level. It has the unique advantages of rapid response, low reagent consumption, and high integration and is mainly applied in the field of biochemical analysis. However, currently, this technology still has a few problems, such as high control voltage, low droplet velocity, and continuity in flow, limiting its application. In this paper, through theoretical analysis and numerical simulation, it is deduced that a drive electrode with a crescent configuration can reduce the driving voltage. The experimental results not only validate this deduction but also indicate that crescent electrode can improve the droplet motion continuity and the success in split rate.     

DNA translocation through short nanofluidic channels under asymmetric pulsed electric field

Investigation of single molecule DNA dynamics in confined environments has led to important applications in DNA analysis, separation, and sequencing. Here, we studied the electrophoretic transport of DNA molecules through nanochannels shorter than the DNA contour length and calculated the associated translocation time curves. We found that the longer T4 DNA molecules required a longer time to traverse a fixed length nanochannel than shorter λ DNA molecules and that the translocation time decreased with increasing electric field which agreed with theoretical predictions. We applied this knowledge to design an asymmetric electric pulse and demonstrate the different responses of λ and T4 DNA to the pulses. We used Brownian dynamics simulations to corroborate our experimental results on DNA translocation behaviour. This work contributes to the fundamental understanding of polymer transport through nanochannels and may help in designing better separation techniques in the future.     

考虑管间液滴形成和下落过程的吸收器模拟及分析

针对以溴化锂水溶液为工质的水平管吸收器，考虑管底部液滴形成和管间下落过程，建立了描述管间滴状形成和下落吸收过程传热传质耦合数学模型。根据数值计算结果，分析了溶液温度、浓度和吸收速率沿管排不同位置和水平管管间的变化，分析了管间距对吸收器整体传热传质性能的影响。结果表明，滴状吸收过程约占总吸收量的30%。与实验数据的对比说明提出的数学模型是合理的。     

Onset of channeling during DNA electrophoresis in a sparse ordered post array

The “channeling hypothesis” of DNA electrophoresis in sparse, ordered arrays of posts predicts that the DNA will move through the array relatively unhindered if (i) the spacing between the posts is larger than the DNA coil and (ii) the electric field lines are straight. We tested this hypothesis by studying the electrophoretic separation of a small plasmid DNA (pUC19, 2686 base pairs) and a large, linear DNA (λ-DNA, 48 500 base pairs) in a hexagonal array of 1 μm diameter posts with a pitch of 7 μm. At low electric field strengths, these DNAs are separated due to the long-lived, rope-over-pulley collisions of λ-DNA with the posts. The resolution is lost as the electric field increases due to the onset of channeling by the λ-DNA. Using a diffusive model, we show that channeling arises at low electric fields due to the finite size of the array. This channeling is not intrinsic to the system and is attenuated by increasing the size of the array. Higher electric fields lead to intrinsic channeling, which is attributed to the disparate time scales for a rope-over-pulley collision and transverse diffusion between collisions. The onset of channeling is a gradual process, in agreement with extant Brownian dynamics simulation data. Even at weak electric fields, the electrophoretic mobility of λ-DNA in the array is considerably higher than would be expected if the DNA frequently collided with the posts.     

An electrohydrodynamic flow in ac electrowetting

In ac electrowetting, hydrodynamic flows occur within a droplet. Two distinct flow patterns were observed, depending on the frequency of the applied electrical signal. The flow at low-frequency range was explained in terms of shape oscillation and a steady streaming process in conjunction with contact line oscillation. The origin of the flow at high-frequency range has not yet been explained. We suggest that the high-frequency flow originated mainly from the electrothermal effect, in which electrical charge is generated due to the gradient of electrical conductivity and permittivity, which is induced by the Joule heating of fluid medium. To support our argument, we analyzed the flow field numerically while considering the electrical body force generated by the electrothermal effect. We visualized the flow pattern and measured the flow velocity inside the droplet. The numerical results show qualitative agreement with experimental results with respect to electric field and frequency dependence of flow velocity. The effects of induced-charge electro-osmosis, natural convection, and the Marangoni flow are discussed.     

Block-and-break generation of microdroplets with fixed volume

We introduce a novel type of droplet generator that produces droplets of a volume set by the geometry of the droplet generator and not by the flow rates of the liquids. The generator consists of a classic T-junction with a bypass channel. This bypass directs the continuous fluid around the forming droplets, so that they can fill the space between the inlet of the dispersed phase and the exit of the bypass without breaking. Once filled, the dispersed phase blocks the exit of the bypass and is squeezed by the continuous fluid and broken off from the junction. We demonstrate the fixed-volume droplet generator for (i) the formation of monodisperse droplets from a source of varying flow rates, (ii) the formation of monodisperse droplets containing a gradation of solute concentration, and (iii) the parallel production of monodisperse droplets.     

Study for optical manipulation of a surfactant-covered droplet using lattice Boltzmann method

In this study, we simulated deformation and surfactant distribution on the interface of a surfactant-covered droplet using optical tweezers as an external source. Two optical forces attracted a single droplet from the center to both sides. This resulted in an elliptical shape deformation. The droplet deformation was characterized as the change of the magnitudes of surface tension and optical force. In this process, a non-linear relationship among deformation, surface tension, and optical forces was observed. The change in the local surfactant concentration resulting from the application of optical forces was also analyzed and compared with the concentration of surfactants subjected to an extensional flow. Under the optical force influence, the surfactant molecules were concentrated at the droplet equator, which is totally opposite to the surfactants behavior under extensional flow, where the molecules were concentrated at the poles. Lastly, the quasi-equilibrium surfactant distribution was obtained by combining the effects of the optical forces with the extensional flow. All simulations were executed by the lattice Boltzmann method which is a powerful tool for solving micro-scale problems.     

A novel micropump droplet generator for aerosol drug delivery: Design simulations

One challenge of generating a liquid aerosol is finding an efficient way to break up bulk amounts of the compound into micron-sized droplets. Traditional methods of aerosol generation focus on the principle of creating the liquid droplets by blowing air at high speed over or through a liquid. In this study, a novel micropump droplet generator (MDG) is proposed based on a microfluidics device to produce monodisperse droplets on demand (DoD). The micropump design was employed to both pump the fluid into the air and to encourage droplet breakup and aerosol formation. Computational simulation modeling of the new MDG was developed and validated with comparisons to experimental data for current generators. The device was found to produce an aerosol similar to a vibrating orifice DoD device. Most importantly, the input power required by the newly proposed device (MDG) was several orders of magnitude below existing DoD generators for a similar droplet output. Based on the simulation results obtained in comparison with current DoD generators, the MDG device performed effectively at higher frequencies, smaller nozzle diameters, and regardless of the liquid viscosity of the solution.     

电子商务模拟实验系统的研究与开发

电子商务教学具有非常强的实践性,要求学生在了解电子商务相关理论知识的同时,也应该具备熟练运用网络进行电子商务活动的实践技能.因此,电子商务专业必须具备适合实践教学的网络环境和模拟实训系统.电子商务模拟实验系统在设计与实现过程中,采用了B/S模式开发,能够综合体现信息流、资金流、物流运作特点.本系统具有网上银行、CA认证、B2C交易中心、B2B交易中心、C2C交易中心、学生实验测评系统、系统后台管理等功能,重点突出了实战性、开放性的原则.     

Molecular diffusion analysis of dynamic blood flow and plasma separation driven by self-powered microfluidic devices

Integration of microfluidic devices with pressure-driven, self-powered fluid flow propulsion methods has provided a very effective solution for on-chip, droplet blood testing applications. However, precise understanding of the physical process governing fluid dynamics in polydimethylsiloxane (PDMS)-based microfluidic devices remains unclear. Here, we propose a pressure-driven diffusion model using Fick''s law and the ideal gas law, the results of which agree well with the experimental fluid dynamics observed in our vacuum pocket-assisted, self-powered microfluidic devices. Notably, this model enables us to precisely tune the flow rate by adjusting two geometrical parameters of the vacuum pocket. By linking the self-powered fluid flow propulsion method to the sedimentation, we also show that direct plasma separation from a drop of whole blood can be achieved using only a simple construction without the need for external power sources, connectors, or a complex operational procedure. Finally, the potential of the vacuum pocket, along with a removable vacuum battery to be integrated with non-PDMS microfluidic devices to drive and control the fluid flow, is demonstrated.     

Modeling the coalescence of sessile droplets

This paper proposes a simple scenario to describe the coalescence of sessile droplets. This scenario predicts a power-law growth of the bridge between the droplets. The exponent of this power law depends on the driving mechanism for the spreading of each droplet. To validate this simple idea, the coalescence is simulated numerically and a basic experiment is performed. The fluid dynamics problem is formulated in the lubrication approximation framework and the governing equations are solved in the commercial finite element software COMSOL. Although a direct comparison of the numerical results with experiment is difficult because of the sensitivity of the coalescence to the initial and operating conditions, the key features of the event are qualitatively captured by the simulation and the characteristic time scale of the dynamics recovered. The experiment consists of inducing coalescence by pumping a droplet through a substrate which grows and ultimately coalesces with another droplet resting on the substrate. The coalescence was recorded using high-speed imaging and also confirmed the power-law growth of the neck.     

A numerical study on the dynamics of droplet formation in a microfluidic double T-junction

In this study, droplet formations in microfluidic double T-junctions (MFDTD) are investigated based on a two-dimensional numerical model with volume of fluid method. Parametric ranges for generating alternating droplet formation (ADF) are identified. A physical background responsible for the ADF is suggested by analyzing the dynamical stability of flow system. Since the phase discrepancy between dispersed flows is mainly caused by non-symmetrical breaking of merging droplet, merging regime becomes the alternating regime at appropriate conditions. In addition, the effects of channel geometries on droplet formation are studied in terms of relative channel width. The predicted results show that the ADF region is shifted toward lower capillary numbers when channel width ratio is less than unity. The alternating droplet size increases with the increase of channel width ratio. When this ratio reaches unity, alternating droplets can be formed at very high water fraction (wf = 0.8). The droplet formation in MFDTD depends significantly on the viscosity ratio, and the droplet size in ADF decreases with the increase of the viscosity ratio. The understanding of underlying physics of the ADF phenomenon is useful for many applications, including nanoparticle synthesis with different concentrations, hydrogel bead generation, and cell transplantation in biomedical therapy.     

Off line simulation system of machining processes

The primary objective for modeling of machining processes is to develop a predictive capability of machining performance in order to facilitate effective planning of machining operations. This capability leads to faster implementation, higher performance, quality at a lower cost. This comes about due to improved selection of machining parameters, optimal fixture design and the avoidance of tool failure. The simulation system presented simultaneously considers the effect of cutter geometry, the cutter's initial position errors, workpiece geometry, machine tool dynamics, and workpiece/fixture system dynamics on the machining process.The integration of all of the above in one model provides an off-line tool to simulate and optimize the machining parameters and the fixture configuration cutting both lead and production time. The modular nature of the simulation system presented allows for the study of many different machining processes. The cutting forces in this system are modeled using a mechanistic approach. NURBS curves and surfaces are utilized for the geometric modeling and simulation of the machining process. While a finite element method is used to model and analyze the workpiece/fixture dynamics. Two case studies are presented to demonstrate the practical application of the presented simulation. The first case presents the optimization of the fixture configuration of a generic automotive component. While the second case presents the results of simulations performed on a novel mill/grind machining process. This process is a combination of face milling and grinding in one operation. Some simulated results are presented along with experimental validation.     

Behavior of a train of droplets in a fluidic network with hydrodynamic traps

The behavior of a droplet train in a microfluidic network with hydrodynamic traps in which the hydrodynamic resistive properties of the network are varied is investigated. The flow resistance of the network and the individual droplets guide the movement of droplets in the network. In general, the flow behavior transitions from the droplets being immobilized in the hydrodynamic traps at low flow rates to breaking up and squeezing of the droplets at higher flow rates. A state diagram characterizing these dynamics is presented. A simple hydrodynamic circuit model that treats droplets as fluidic resistors is discussed, which predicts the experimentally observed flow rates for droplet trapping in the network. This study should enable the rational design of microfuidic devices for passive storage of nanoliter-scale drops.     

元胞自动机在景观格局优化中的应用

在景观格局优化方法的发展过程中,以景观模拟演化为核心的景观格局优化模式已显示出优越性,这种模式在大量景观变化模拟预测结果形成的状态空间中搜索景观格局的优化方案,优化的客观性和自动化程度较高。但由于目前在景观尺度上的格局和过程相互作用规律尚缺乏定量的描述,限制了这种优化模式的发展。而基于元胞自动机的空间直观模型,由于元胞自动机固有的特点,在解决一系列技术难点的前提下,有望解决这一模式在目前发展中受到的限制。本文介绍了元胞自动机的原理和在景观生态学中的已有应用,认为元胞自动机获得广泛应用的原因在于,它有且仅有以下3个最本质的特征：状态的表达在空间上的离散性;状态变化的表达在时间上的离散性;状态转变的空间相关性。在此基础上,阐释了元胞自动机应用于景观格局演化的一般优势和相对优势,以及它在景观格局优化应用中存在的困难。针对这些困难,提出了部分的解决方案。最后对于以基于广义元胞自动机的空间直观模型为核心的景观格局优化模式,提出了一个可能的体系结构和流程图。     

Finite-time formation control of nonaffine nonlinear systems under directed communication interactions

This paper studies the problem of finite-time formation tracking control for networked nonaffine nonlinear systems with unmeasured dynamics and unknown uncertainties/disturbances under directed topology. A unified distributed control framework is proposed by integrating adaptive backstepping control, dynamic gain control and dynamic surface control based on finite-time theory and consensus theory. Auxiliary dynamics are designed to construct control gains with non-Lipschitz dynamics so as to guarantee finite-time convergence of formation errors. Adaptive control is used to compensate for uncertain control efforts of the transformed systems derived from original nonaffine systems. It is shown that formation tracking is achieved during a finite-time period via the proposed controller, where fractional power terms are only associated with auxiliary dynamics instead of interacted information among the networked nonlinear systems in comparison with most existing finite-time cooperative controllers. Moreover, the continuity of the proposed controller is guaranteed by setting the exponents of fractional powers to an appropriate interval. It is also shown that the improved dynamic surface control method could guarantee finite-time convergence of formation errors, which could not be accomplished by conventional dynamic surface control. Finally, simulation results show the effectiveness of the proposed control scheme.