Dispersion control in microfluidic chips by localized zeta potential variation using the field effect

A new technique to minimize the effects of turn-induced dispersion within U-shaped separation channels by using the field effect within a capacitor to vary the zeta potential along the channel walls in the vicinity of the microchannel is described. The effects of the separation channel geometry, the fluid velocity profile, and the use of the field effect to control the zeta potential on the band distribution in the detection area are extensively discussed. The results for a U-shaped separation channel indicate that varying the zeta potential by controlling the field effect significantly reduces the band dispersion induced by the 90 degrees turns within the channel. Finally, it is shown that the application of the proposed localized zeta potential variation method also results in a correction of the band tilting phenomenon and a reduction in the racetrack effect.     

Band spreading control in electrophoresis microchips by localized zeta-potential variation using field-effect

The paper proposes a new technique, which varies the zeta potential along the channel walls in the vicinity of the microchannel corners in such as a way as to minimize the effects of turn-induced dispersion within U-shaped separation channels. The effects of the separation channel geometry, the fluid velocity profile, and boundary control of the zeta potential on the band distribution in the detection area are all discussed within this paper. The results for the folded square U-shaped separation channel indicate that boundary control of the zeta potential by field-effect significantly reduces the band dispersion induced by the 90[degree] turns. Finally, the results confirm that application of the proposed localized zeta potential variation method results in a correction of the band tilting phenomenon and a reduction in the racetrack effect.     

Microchannel-electrode alignment and separation parameters comparison in microchip capillary electrophoresis by scanning electrochemical microscopy

The end of separation channel in a microchip was electrochemically mapped using the feedback imaging mode of scanning electrochemical microscopy (SECM). This method provides a convenient way for microchannel-electrode alignment in microchip capillary electrophoresis. Influence of electrode-to-channel positions on separation parameters in this capillary electrophoresis-electrochemical detection (CE-ED) was then investigated. For the trapezoid shaped microchannel, detection in the central area resulted in the best apparent separation efficiency and peak shape. In the electrode-to-channel distance ranging from 65 to 15mum, the limiting peak currents of dopamine increased with the decrease of the detection distance due to the limited diffusion and convection of the sample band. Results showed that radial position and axial distance of the detection electrode to microchannel was important for the improvement of separation parameters in CE amperometric detection.     

电泳芯片结构和芯片电泳分离操作参数的模拟、优化和实验验证

选择了L-精氨酸和L-苯丙氨酸为分离样品体系,根据电泳实验提出样品基本参数,通过模拟计算考察了进样管道宽度和进样时间对进样方差的贡献;根据分离度与分离长度拟合曲线确定电泳芯片的有效分离长度;对化学发光柱后衍生管道施加的夹流电压进行了模拟优化,得出氨基酸体系分离分析的电泳芯片设计方案和操作参数为:进样管道宽度为分离管道宽度的1/2,简单进样充样时间应大于5 s,分离管道有效分离长度为30 mm,衍生夹流比1.0~1.6。根据模拟优化结果提出了电泳芯片设计方案,采用整体浇注法制作带有柱后衍生反应器的PDMS电泳芯片,按照模拟计算提出的电压操作参数实现了精氨酸和苯丙氨酸样品体系的准确进样、芯片电泳分离和柱后衍生化学发光检测。电泳过程模拟结果和实验结果相结合,考察了柱后衍生对样品谱带展宽的影响,简单进样过程样品泄露引起的谱峰拖尾现象,并讨论了夹流进样法对减小进样方差和抑制样品泄露的贡献。     

Microchip electrophoresis of N-glycans on serpentine separation channels with asymmetrically tapered turns

We designed and fabricated microfluidic devices with serpentine separation channels and asymmetrically tapered turns, thus allowing high efficiency separations and minimizing band broadening associated with the “racetrack” effect. We evaluated the performance of these devices by measuring the variation in separation efficiency with separation length, electric field strength, taper ratio of the turns, and number of turns. N‐Glycans derived from ribonuclease B and labeled with 8‐aminopyrene‐1,3,6‐trisulfonic acid were electrophoretically separated on serpentine channels with separation lengths of 11, 18, 22, and 36 cm at electric field strengths from 750 to 1750 V/cm. Separations on the 36‐cm channel produced plate numbers up to 940 000 with an analysis time under 3.1 min, whereas separations on the 22‐cm channel had a shorter analysis time (less than 1.25 min), still with respectable efficiencies (up to 600 000 plates). Turn‐induced dispersion was minimized with taper ratios 2 and 3, whereas having two or four 180° turns along with the separation length did not impact the overall efficiency. The developed device was used to analyze native and desialylated N‐glycans derived from the blood serum of an ovarian cancer patient and a disease‐free individual. Separation efficiencies similar to that achieved with the model glycans from ribonuclease B were attained for these biological samples.     

Electroosmotic flow mixing in zigzag microchannels

In this study we performed numerical and experimental investigations into the mixing of EOFs in zigzag microchannels with two different corner geometries, namely sharp corners and flat corners. In the zigzag microchannel with sharp corners, the flow travels more rapidly near the inner wall of the corner than near the outer wall as a result of the higher electric potential drop. The resulting velocity gradient induces a racetrack effect, which enhances diffusion within the fluid and hence improves the mixing performance. The simulation results reveal that the mixing index is approximately 88.83%. However, the sharp-corner geometry causes residual liquid or bubbles to become trapped in the channel at the point where the flow is almost stationary, when the channel is in the process of cleaning. Accordingly, a zigzag microchannel with flat-corner geometry is developed. The flat-corner geometry forms a convergent-divergent type nozzle which not only enhances the mixing performance in the channel, but also prevents the accumulation of residual liquid or bubbles. Scaling analysis reveals that this corner geometry leads to an effective increase in the mixing length. The experimental results reveal that the mixing index is increased to 94.30% in the flat-corner zigzag channel. Hence, the results demonstrate that the mixing index of the flat-corner zigzag channel is better than that of the conventional sharp-corner microchannel. Finally, the results of Taguchi analysis indicate that the attainable mixing index is determined primarily by the number of corners in the microchannel and by the flow passing height at each corner.     

Injection and flow control system for microchannels

In spite of considerable efforts, flow control in micro-channels remains a challenge owing to the very small ratio of channel/supply-system volumes, as well as the induction of spurious flows by extremely small pressure or geometry changes. We present here an inexpensive and robust system for flow control in a microchannel system, based on a dynamic control of reservoir pressures at the end of each channel. This system allows flow equilibration with a time constant smaller than one second, and is also able to maintain stable flux from stopped flow to many microl min(-1) range over several hours. It is robust to changes in ambient pressure and temperature. This system further includes a feature for sub-microliter sample injection during the experiment. We quantify flow control in elastomer and thermoplastic channels, and demonstrate the impact on one application of the system, namely the reproducible, automated separation of large DNA by electrophoresis in a self-organized magnetic bead matrix in a microchannel.     

Fast separation of oligonucleotide and triplet repeat DNA on a microfabricated capillary electrophoresis device and capillary electrophoresis

A laser-induced fluorescence detection system coupled with a highly sensitive silicon-intensified target (SIT) camera is successfully applied to the imaging of a band for DNA fragment labeling by fluorescence dye in a microchannel, and to the visualizing of the separation process on a microfabricated chip. We demonstrated that an only 6 mm separation channel is sufficient for the separation of triplet repeat DNA fragment and DNA molecular marker within only 12 s. The separation using the microfabricated capillary electrophoresis device is confirmed to be at least 18 times faster than the same separation carried out by conventional capillary electrophoresis with 24.5 cm effective length. The use of a short capillary with 8.5 cm effective length is also efficient for fast separation of DNA; however, the microchip technology is even faster than capillary electrophoresis using a short capillary.     

Fabrication and performance of a microfluidic traveling-wave electrophoresis system

A microfluidic traveling-wave electrophoresis (TWE) system is reported that uses a locally defined traveling electric field wave within a microfluidic channel to achieve band transport and separation. Low voltages, over a range of -0.5 to +0.5 V, are used to avoid electrolysis and other detrimental redox reactions while the short distance between electrodes, ～25 μm, provides high electric fields of ～200 V cm(-1). It is expected that the low voltage requirements will simplify the future development of smaller portable devices. The TWE device uses four interdigitated electrode arrays: one interdigitated electrode array pair is on the top of the microchannel and the other interdigitated electrode array pair is on the microchannel bottom. The top and bottom substrates are joined by a PDMS spacer that has a nominal height of 15 μm. A pinched injection scheme is used to define a narrow sample band within an injection cross either electrokinetically or hydrodynamically. Separation of two dyes, fluorescein and FLCA, with baseline resolution is achieved in less than 3 min and separation of two proteins, insulin and casein is demonstrated. Investigation of band broadening with fluorescein reveals that sample band widths equivalent to the diffusion limit can be achieved within the microfluidic channel, yielding highly efficient separations. This low level of band broadening can be achieved with capillary electrophoresis, but is not routinely observed in microchannel electrophoresis. Sample enrichment can be achieved very easily with TWE using a device with converging electric field waves controlled by two sets of independently controlled interdigitated electrodes arrays positioned serially along the microchannel. Sample enrichment of 40-fold is achieved without heterogeneous buffer/solvent systems, sorptive, or permselective materials. While there is much room for improvement in device fabrication, and many capabilities are yet to be demonstrated, it is anticipated that the capabilities and performance demonstrated herein will enable new lab-on-a-chip processes and systems.     

Reversed-phase liquid chromatography on a microchip with sample injector and monolithic silica column

In micro total analysis systems, liquid chromatography (LC) works under pressure-driven flow is the essential analysis component. There were not, however, much works on microchip LC. Here we developed a microchip for reversed-phase LC using porous monolithic silica. The chip consisted of a double T-shaped injector and a approximately 40-cm serpentine separation channel. The octadecyl-modified monolithic silica was prepared in the specified part of the channel on the microchip using sol-gel process. Furthermore, the effect of geometry of turn sections on band dispersion at turns was examined under pressure-driven flow. High separation efficiencies of 15,000-18,000 plates/m for catechins were obtained using the LC chip.     

Study on the influence of cross-sectional area and zeta potential on separation for hybrid-chip-based capillary electrophoresis using 3-D simulations

Hybrid chips combing microchips with capillaries have displayed particular advantages in achieving UV-vis and mass spectroscopic detection. In this work, systematic 3-D numerical simulations have been carried out to explore the influence of junction interface cross-sectional area and ζ-potential distribution on sample band broadening in hybrid-chip electrophoresis separation. In this case, the ratio of cross-sectional area of chip to capillary channel (S(ratio) ) is used as the parameter of the variation in junction interface cross-sectional area. Theoretical simulations demonstrated that the decrease of the S(ratio) would increase the separation efficiency in the hybrid-chip-based CE with uniform ζ-potential distribution. ζ-potential distribution along the axial direction of the channel also affects mass transport in hybrid-chip-based CE. Therefore, the effect of ζ-potential distribution has been considered in the 3-D simulation. Theoretical simulation results reveal that ζ-potential distribution rather than the interface cross-sectional area variation (S(ratio) ) controls the sample band broadening and manipulates sample separation efficiency in the hybrid-chip-based CE with non-uniform ζ-potential distribution. Both the theoretical simulations and experimental results show that optimal hybrid-chip CE separation efficiency can be achieved at S(ratio) =1.     

平面二维毛细管电泳初探

在石英单晶表面制成短形截面的毛细管柱上进行了电泳实验。由于矩形柱比国形住有更大散热侧面积且石英单晶的导热性能远远优于熔融石英,所以可施加较高的场强,不仅提高了住效,而且缩短了分离时间。两个相交的通道之间形成自然连接,可实现二维分离,并消除了死体积。     

Elastic-inertial separation of microparticle in a gradually contracted microchannel

Separation of microparticle in viscoelastic fluid is highly required in the field of biology and clinical medicine. For instance, the separation of the target cell from blood is an important prerequisite step for the drug screening and design. The microfluidic device is an efficient way to achieve the separation of the microparticle in the viscoelastic fluid. However, the existing microfluidic methods often have some limitations, including the requirement of the long channel length, the labeling process, and the low throughput. In this work, based on the elastic-inertial effect in the viscoelastic fluid, a new separation method is proposed where a gradually contracted microchannel is designed to efficiently adjust the forces exerted on the particle, eventually achieving the high-efficiency separation of different sized particles in a short channel length and at a high throughput. In addition, the separation of WBCs and RBCs is also validated in the present device. The effect of the flow rate, the fluid property, and the channel geometry on the particle separation is systematically investigated by the experiment. With the advantage of small footprint, simple structure, high throughput, and high efficiency, the present microfluidic device could be utilized in the biological and clinical fields, such as the cell analysis and disease diagnosis.     

Novel coupling mechanism-based imaging approach to scanning electrochemical microscopy for probing the electric field distribution at the microchannel end

A novel coupling mechanism-based imaging approach to scanning electrochemical microscopy (SECM) was used to image the distribution of electric field at the end channel of a poly(dimethylsiloxane) (PDMS) capillary electrophoresis (CE) microchip in the absence of redox species. The coupling imaging mechanism was systematically investigated and qualitatively illustrated. It was proved that the distribution of solution potentials within the scanning plane caused a different reduction rate of water at the tip electrode, which led to the variation in tip current. Within the scanning plane, the solution potentials measured in the central area of the microchannel were usually higher than those measured outside. The SECM images showed a strong dependence on tip potential, tip-to-channel distance, and separation potential. According to the Tafel equation, SECM images were converted to parameters that directly showed the distribution of solution potential. Change in the solution potential along the central axial line of the microchannel was also continuously sensed by allowing the tip to approach the microchannel in the presence of high voltage. Using dopamine as a model compound, the effect of solution potential on electrochemical detection was estimated by detecting separation parameters.     

Optimal configuration of capillary electrophoresis microchip with expansion chamber in separation channel

This study develops a novel capillary electrophoresis (CE) microfluidic device featuring a conventional cross-form injection system and an expansion chamber located at the inlet of the separation channel. The combined injection system/expansion chamber arrangement is designed to deliver a high-quality sample band into the separation channel such that the detection performance of the device is enhanced. Numerical simulations are performed to investigate the electrokinetic transport processes in the microfluidic device and to establish the optimal configuration of the expansion chamber. The results indicate that an expansion chamber with an expansion ratio of 2.5 and an expansion length of 500 microm delivers a sample plug with the correct shape and orientation. With this particular configuration, the peak intensities of the sample are sharp and clearly distinguishable in the detection region of the separation channel. Therefore, this configuration is well suited for capillary electrophoresis applications which require a highly sensitive resolution of the sample plug. The novel CE microfluidic device developed in this study has an exciting potential for use in high-performance, high-throughput chemical analysis applications and in many other applications throughout the field of micro-total-analysis-systems.     

A low-leakage sample plug injection scheme for crossform microfluidic capillary electrophoresis devices incorporating a restricted cross-channel intersection

This study develops a crossform CE microfluidic device in which a single-circular barrier or a double-circular barrier is introduced at the cross-channel intersection. Utilizing a conventional crossform injection scheme, it is shown that these barriers reduce sample leakage and deliver a compact sample band into the separation channel, thereby ensuring an enhanced detection performance. A series of numerical and experimental investigations are performed to investigate the effects of the barrier type and the barrier ratio on the flow streamlines within the microchannel and to clarify their respective effects on the sample leakage ratio and sample plug variance during the injection process. The results indicate that a single-circular barrier injector with a barrier ratio greater than 20% and a double-circular barrier injector with a barrier ratio greater than 40% minimize the sample leakage ratio and produce a compact sample plug. As a result, both injectors have an excellent potential for use in high-quality, high-throughput chemical analysis procedures and in many other applications throughout the micro-total analysis systems field.     

System-oriented dispersion models of general-shaped electrophoresis microchannels

This paper presents a system-oriented model for analyzing the dispersion of electrophoretic transport of charged analyte molecules in a general-shaped microchannel, which is represented as a system of serially connected elemental channels of simple geometry. Parameterized analytical models that hold for analyte bands of virtually arbitrary initial shape are derived to describe analyte dispersion, including both the skew and broadening of the band, in elemental channels. These models are then integrated to describe dispersion in the general-shaped channel using appropriate parameters to represent interfaces of adjacent elements. This lumped-parameter system model offers orders-of-magnitude improvement in computational efficiency over full numerical simulations, and is verified by results from experiments and numerical simulations. The model is used to perform a systematic parametric study of serpentine channels consisting of a pair of complementary turn microchannels, and the results indicate that dispersion in a particular turn can contribute to either an increase or decrease of the overall band broadening. The efficiency and accuracy of the system model is further demonstrated by its application to general-shaped channels that occur in practice, including a serpentine channel with multiple complementary turns and a multi-turn spiral-shaped channel. The results indicate that our model is an accurate and efficient simulation tool useful for designing optimal electrophoretic separation microchips.     

Separation of mixtures of particles in a multipart microdevice employing insulator-based dielectrophoresis

Dielectrophoresis is the electrokinetic movement of particles due to polarization effects in the presence of non-uniform electric fields. In insulator-based dielectrophoresis (iDEP) regions of low and high electric field intensity, i.e. non-uniformity of electric field, are produced when the cross-sectional area of a microchannel is decreased by the presence of electrical insulating structures between two electrodes. This technique is increasingly being studied for the manipulation of a wide variety of particles, and novel designs are continuously developed. Despite significant advances in the area, complex mixture separation and sample fractionation continue to be the most important challenges. In this work, a microchannel design is presented for carrying out direct current (DC)-iDEP for the separation of a mixture of particles. The device comprises a main channel, two side channels and two sections of cylindrical posts with different diameters, which will generate different non-uniformities in the electric field on the main channel, designed for the discrimination and separation of particles of two different sizes. By applying an electric potential of 1000 V, a mixture of 1 and 4 μm polystyrene microspheres were dielectrophoretically separated and concentrated at the same time and then redirected to different outlets. The results obtained here demonstrate that, by carefully designing the device geometry and selecting operating conditions, effective sorting of particle mixtures can be achieved in this type of multi-section DC-iDEP devices.     

On-chip solid phase extraction coupled with electrophoresis using modified magnetic microspheres as stationary phase

A poly(dimethylsiloxane)(PDMS)/glass hybrid microchip for on-line solid phase extraction (SPE) and electrophoresis separation has been developed and evaluated. The SPE microchannel was crossed to the electrophoresis microchannel. All the microfluidic channels were etched on the glass substrate. The magnetic microspheres were coated with hydroxyl-terminated poly-dimethylsiloxane (PDMS-OH) serving as extraction phase, which could be conveniently immobilized into the sample pretreatment channel by magnetic field. The PDMS-OH microspheres were mobilized into and out of the pretreatment channel by injection flow. The 0.1 μmol/L solution of fluorescence isothiocyanate (FITC)-labeled phenylalanine (Phe) was electrically injected into the SPE channel and extracted onto the PDMS-OH microspheres bed. The enriched FITC-labeled Phe was electrically eluted by 9 mmol/L sodium acetate containing 10% acetonitrile and electrically driven into the electrophoresis channel and then separated. The preconcentration factor could reach 87.5 after sufficient extraction. A linear preconcentration curve was obtained with the initial FITC-labeled Phe concentration ranging from 6 nmol/L to 300 nmol/L (R ²=0.9922) with 200 s loading time. The detection limit (S/N=3) for the FITC-labeled Phe was 3 nmol/L.     

Peak broadening in microchip electrophoresis: a discussion of the theoretical background

A review on peak (band, zone) broadening in electromigration separation methods is presented, mainly covering articles published between the begining of 2000 and middle of 2002. Most attention is drawn to work dealing with microchip electrophoresis performed in micrototal analysis systems (microTAS) or the lab-on-a-chip, but many of the results are significant for capillary zone electrophoresis in general. The paper reviews the theoretical background of the peak dispersion due to the geometry of the separation channel, the transversal nonhomogeneity of the electroosmootic flow, and electromigration dispersion (sample overload) connected with the occurrence of the system zones (system peaks, system eigenpeaks).