Combined circuit/device modeling and simulation of integrated microfluidic systems

A combined circuit/device model for the analysis of integrated microfluidic systems is presented. The complete model of an integrated microfluidic device incorporates modeling of fluidic transport, chemical reaction, reagent mixing, and separation. The fluidic flow is generated by an applied electrical field or by a combined electrical field and pressure gradient. In the proposed circuit/device model, the fluidic network has been represented by a circuit model and the functional units of the /spl mu/-TAS (micro Total Analysis System) have been represented by appropriate device models. We demonstrate the integration of the circuit and the device models by using an example, where the output from the fluidic transport module serves as the input for the other modules such as mixing, chemical reaction and separation. The combined circuit/device model can be used for analysis and design of entire microfluidic systems with very little computational expense, while maintaining the desired level of accuracy.     

A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

Generating high-pressure sub-microliter flow rate in packed microchannel by electroosmotic force: potential application in microfluidic systems

We have developed a liquid delivery pump, known as an electroosmotic pump (EOP), based on the electrically induced osmosis principle, which is mainly made of one or several microchannels packed with porous fine dielectric material and connected in parallel. The EOP is tested with methanol, phosphate sodium buffer and their mixture, which can generate pressures from 0.1 to 15 MPa and flow rates of tens of nanoliters per minute to several microliters per minute. Constant and pulsation-free flow from the EOP adapts well to microfluidic systems.     

3D polymeric microfluidic device fabrication via contact liquid photolithographic polymerization (CLiPP)

In this contribution, a new method for the fabrication of complex polymeric microfluidic devices is presented. The technology, contact liquid photolithographic polymerization (CLiPP), overcomes many of the drawbacks associated with other rapid prototyping schemes, such as limited materials choices and time-consuming microassembly protocols. CLiPP shares many traits with other photolithographic methods, but three distinct features: (i) liquid photoresists in contact with the photomask, (ii) readily removed sacrificial materials, and (iii) living radical processes, enable multiple polymeric chemistries and mechanical properties while simultaneously enabling facile fabrication of 3D geometries and surface chemistry control. This contribution details fabrication techniques and methods for the fabrication of high aspect ratio posts covalently bonded to a polymeric substrate, an array of independently stacked bars on top of perpendicular bars, multiple undercut structures fabricated simultaneously, and a complex 3D geometry with intertwined channels.     

Electrokinetic mixing in microfluidic systems

The applications of electrokinetics in the development of microfluidic devices have been widely attractive in the past decade. Electrokinetic devices generally require no external mechanical moving parts and can be made portable by replacing the power supply by small battery. Therefore, electrokinetic-based microfluidic systems can serve as a viable tool in creating a lab-on-a-chip (LOC) or micro-total analysis system (μTAS) for use in biological and chemical assays. Mixing of analytes and reagents is a critical step in realizing lab-on-a-chip. This step is difficult due to the low Reynolds numbers flows in microscale devices. Hence, various schemes to enhance micro-mixing have been proposed in the past years. This review reports recent developments in the micro-mixing schemes based on DC and AC electrokinetics, including electrowetting-on-dielectric (EWOD), dielectrophoresis (DEP), and electroosmosis (EO). These electrokinetic-based mixing approaches are generally categorized as either active or passive in nature. Active mixers either use time-dependent (AC or DC field switching) or time-independent (DC field) external electric fields to achieve mixing, while passive mixers achieve mixing in DC fields simply by virtue of their geometric topology and surface properties, or electrokinetic instability flows. Typically, chaotic mixing can be achieved in some ways and is helpful to mixing under large Péclet number regimes. The overview given in this article provides a potential user or researcher of electrokinetic-based technology to select the most favorable mixing scheme for applications in the field of micro-total analysis systems.     

Ion bridges in microfluidic systems

Recently many microfluidic systems are increasingly equipped with functional units for ionic controls for various applications. In this review article, we define an ion bridge as a structure that controls current or distribution of ions in a microfluidic system, and summarize the ion bridges in the literature in terms of characteristics, fabrication methods, advantages and disadvantages. The ion bridges play two basic roles, namely to ensure electrical contact in a microfluidic network and mechanically separate a liquid phase from another. More interestingly, the charged surfaces of ion bridges, which can be chemically modified, create new characteristics such as permselectivity and concentration polarization. Asymmetric ion transport as well as ionic conductivity through the ion bridges suggests a variety of applications including sample preconcentration, electroosmotic pump, electrospray ionization, electrically driven valve and many others. This review categorizes the ion bridges into several classes and describes the structures, materials, fundamental functions and applications. In Perspectives, new opportunities of microfluidics and nanofluidics provided by the ion bridges are discussed.     

Silicon-on-insulator microfluidic device with monolithic sensor integration for /spl mu/TAS applications

A novel concept for the integration of liquid phase charge sensors into microfluidic devices based on silicon-on-insulator (SOI) technology is reported. Utilizing standard silicon processing we fabricated basic microfluidic cross geometries comprising of 5-10-mm-long and 55-/spl mu/m-wide channels of 3 /spl mu/m depth by wet sacrificial etching of the buried oxide of an SOI substrate. To demonstrate the feasibility of fluid manipulation along the channel we performed electroosmotic pumping of a dye-labeled buffer solution. At selected positions along the channel we patterned the 205-nm thin top silicon layer into freely suspended, 10-/spl mu/m wide bars bridging the channel. We demonstrate how these monolithically integrated bars work as thin-film resistors that sensitively probe changes of the surface potential via the field effect. In this way, a combination of electrokinetic manipulation and separation of charged analytes together with an on-chip electronic detection can provide a new basis for the label-free analysis of, for example, biomolecular species as envisaged in the concept of micrototal analysis systems (/spl mu/TAS) or Lab-on-Chip (LOC).     

Development of microfluidic device for electrical/physical characterization of single cell

A novel device with microchannels for flowing cells and twin microcantilever arrays for measuring the electrical impedance of a single cell is proposed. The fabrication process is demonstrated and the twin microcantilever arrays have been successfully fabricated. In our research, we measured the electrical impedance for normal and abnormal red blood cell over the frequency range from 1 Hz to 10 MHz. From the electrical impedance experiment of normal and abnormal red blood cell, it was examined that the electrical impedance between normal and abnormal red blood cells was significantly different in magnitude and phase shift. In this paper, we show that the normal cell can be taken apart from the abnormal cell by electrical impedance measurement. Therefore, it is expected that the applicability of this technology can be used in cellular studies such as cell sorting, counting or membrane biophysical characterization.     

一种电驱动双活塞式气体流量标准装置的研制

为了解决活塞式气体流量标准装置的最大检定流量受活塞缸容积限制的问题,开发了一种双活塞式气体流量标准装置。该装置利用2个活塞交替运行连续产生标准流量。简述了该双活塞式气体流量标准装置的检定原理,根据临界流流量计的检定规程和流量特性研究了装置的检定模型,介绍了装置软硬件设计,对装置进行重复性实验,结果表明:重复性优于0.05%,可以用于临界流流量计的检定。     

Thermal conductivity measurement of liquids in a microfluidic device

A new microfluidic-based approach to measuring liquid thermal conductivity is developed to address the requirement in many practical applications for measurements using small (microlitre) sample size and integration into a compact device. The approach also gives the possibility of high-throughput testing. A resistance heater and temperature sensor are incorporated into a glass microfluidic chip to allow transmission and detection of a planar thermal wave crossing a thin layer of the sample. The device is designed so that heat transfer is locally one-dimensional during a short initial time period. This allows the detected temperature transient to be separated into two distinct components: a short-time, purely one-dimensional part from which sample thermal conductivity can be determined and a remaining long-time part containing the effects of three-dimensionality and of the finite size of surrounding thermal reservoirs. Identification of the one-dimensional component yields a steady temperature difference from which sample thermal conductivity can be determined. Calibration is required to give correct representation of changing heater resistance, system layer thicknesses and solid material thermal conductivities with temperature. In this preliminary study, methanol/water mixtures are measured at atmospheric pressure over the temperature range 30–50°C. The results show that the device has produced a measurement accuracy of within 2.5% over the range of thermal conductivity and temperature of the tests. A relation between measurement uncertainty and the geometric and thermal properties of the system is derived and this is used to identify ways that error could be further reduced.     

Cell motion and recovery in a two-stream microfluidic device

The motion of cells in a two-stream microfluidic device designed to extract cryoprotective agents from cell suspensions was tested under a range of conditions. Jurkat cells (lymphoblasts) in a 10% dimethylsulfoxide solution were driven in parallel with phosphate-buffered saline solution wash streams through single rectangular channel sections and multiple sections in series. The influence of cell-stream flow rate and cell volume fraction (CVF) on cell viability and recovery were examined. The channel depth was 500 μm, and average cell stream velocity within the channels was varied from 3.6 to 8.5 mm/s corresponding with cell stream Reynolds numbers of 2.6–6.0. Cell viability measured at device outlets was high for all cases examined indicating no significant cell damage within the device. Downstream of a single stage, cell recoveries measured 90–100% for average cell stream velocities ≥6 mm/s and for CVFs up to 20%. Cell recovery downstream of multistage devices also measured 90–100% after a critical device population time. This time was found to be five times the average cell residence time within the device. The measured recovery values were significantly larger than those typically obtained using conventional cell washing methods.     

Analysis of sperm concentration and motility in a microfluidic device

A home-use device that allows rapid and quantitative sperm quality analysis is desirable but not yet fully realized. To aid this effort, this article presents a microfluidic device capable of quantifying sperm quality in terms of two critical fertility-related parameters—motile sperm concentration and motility. The microdevice produces flow field for sperms to swim against, and sperms that overcame the flow within a specified time are propelled along in a separate channel and counted via resistive pulse technique. Data are compared to two control methods clinically utilized for sperm quality exam—hemocytometer and the sperm quality analyzer. Results reveal the numbers of pulses generated by passage of sperms correlates strongly with the two control methods: pulse number from 0 to 335 corresponds to progressively motile sperm concentrations from 0 to 19 × 10⁶/ml (hemocytometer) and Sperm Motility Index from 0 to 204 (sperm quality analyzer). The microdevice should be applicable to facilitate self-assessment of sperm quality at home.     

Highly efficient dual-channel cytometric-detection of micron-sized particles in microfluidic device

To demonstrate the ability to efficiently count and identify suspended micron-sized particles by simultaneously detecting their fluorescence emission and light scattering in microfabricated channel, a compact configuration that used a polydimethylsiloxane (PDMS) microfabricated channel as interrogation component, hydrodynamic focusing for particle control, and a simple free-space optical setup for signal detection, was accordingly developed. Subsequently, a quantitative count of 1.013 μm diameter fluorescently labeled beads in suspension was implemented in a microfluidic device employing both fluorescence emission and light scattering at average particle throughput ranging from 83 to 416 particles/s. As a result, the detection efficiencies above 88% for both signals and correlation percentages above 97% between them were routinely achieved. In addition, it was shown that effective differentiation of 1.013 μm fluorescently labeled beads from various unlabeled beads in mixed populations of high mixing ratios had been successfully realized in this microfluidic-device-based instrumentation. Finally, the demonstrated system was used to detect fluorescein isothiocyanate (FITC) labeled nonpathogenic bacteria of Escherichia coli (E. coli) DH5α. The results showed the detection efficiencies above 89.7% for fluorescence emission and 94.5% for light scattering signals, and a correlation of 94.9% between the two signals at an average throughput of 350 cells/s have been obtained. As a comparison, the detection accuracies of the dual-channel cytometric detection of the FITC-labeled E. coli DH5α cells in the microfluidic device are approximately 84.3% and 88.8% for fluorescence emission and light scattering respectively when compared against a manual cell count using a haemocytometer as a standard.     

In-situ measurement of magnetic nanoparticle quantity in a microfluidic device

Microsystem Technologies - In this article we demonstrate a method for the accurate in situ determination of the quantity of the entrapped magnetic nanoparticles in the reaction chamber of a...     

Experimental study of microbubble coalescence in a T-junction microfluidic device

This study presents the microbubble coalescence process in a confined microchannel. Triple T-junction microfluidic devices with different main channel size were designed to generate monodispersed microbubble pairs with air/n-butyl alcohol–glycerol solution as the working system. The head-on collision of microbubble pair was realized in the microfluidic devices. Three collision results including absolute coalescence, probabilistic coalescence, and non-coalescence were distinguished. The effects of liquid viscosities and two-phase superficial velocities on the coalescence behavior were determined. The results showed that microbubble coalescence process in the confined space was slightly faster than in the free space. Increasing liquid viscosity apparently prevents coalescence. In the probabilistic coalescence region, higher two-phase superficial velocity could reduce the percentage of coalescence events. Two characteristic parameters representing the bubble contact time and film drainage time have been introduced to analyze the microbubble coalescence behaviors and a linear correlation could clearly distinguish the coalescence and non-coalescence region.     

Continuous cell cross over and lysis in a microfluidic device

Complex sample preparation processes are major stumbling blocks for the development of lab-on-a-chip (LOC). We herein advance a microfluidic device for chemical cell lysis using a cell cross over (CCO) technology for the purpose of minimizing the sample preparation steps. The proposed device allows cells to continuously cross over from a cell carrier to a cell lysis solution in a CCO region and to be automatically lysed. For the successful CCO and cell lysis, microflow patterns and cell movements in the CCO region are investigated by experimental as well as numerical studies. EL-4 mammalian cells are used for the demonstration of the performance of the proposed device. The DNA sample obtained from the developed device is quantitatively and qualitatively compared with the one obtained from a conventional chemical cell lysis method by using a UV–Vis spectrophotometer and gel electrophoresis. The quantitative analysis shows that the recovered DNA is 86% compared to the one obtained from the conventional chemical cell lysis.     

Self-priming of liquids in capillary autonomous microfluidic systems

We present a numerical approach to the capillary rise dynamics in microfluidic channels of complex 3D geometries. In order to optimize the delivery of specific biological fluids to target regions in microfluidic capillary autonomous systems (CAS), we analyze self-priming of liquid water into a microfluidic device consisting of a microfluidic channel that feeds a rectangular microfluidic cavity trough an appropriately designed micro-chamber. The target performance criteria in our optimization are (1) fast and complete wetting of the cavity bottom while (2) minimizing the probability of trapping air bubble in the device. The numerical model is based on the lattice Boltzmann method (LBM) and a three-dimensional single-component multiple-phase (SCMP) scheme. By using a parallel implementation of this algorithm, we investigate the physical processes related to the invasion of the liquid–gas interfaces in rectangular cavities at different liquid–solid contact angle and shapes of the transition micro-chamber. The numerical results has successfully captured important qualitative and some key quantitative effects of the liquid–solid contact angle, the roughness of the cavity edges, the depth of the holes and shape of the micro-chambers. Moreover, we present and validate experimentally simple geometrical optimizations of the microfluidic device that ensure the complete filling the microfluidic cavity with liquid. Critical parameters related to the overall priming time of the device are presented as well.     

Electroosmotic pumps and their applications in microfluidic systems

Electroosmotic pumping is receiving increasing attention in recent years owing to the rapid development in micro total analytical systems. Compared with other micropumps, electroosmotic pumps (EOPs) offer a number of advantages such as creation of constant pulse-free flows and elimination of moving parts. The flow rates and pumping pressures of EOPs matches well with micro analysis systems. The common materials and fabrication technologies make it readily integrateable with lab-on-a-chip devices. This paper reviews the recent progress on EOP fabrications and applications in order to promote the awareness of EOPs to researchers interested in using micro- and nano-fluidic devices. The pros and cons of EOPs are also discussed, which helps these researchers in designing and constructing their micro platforms.     

Mathematical analysis of oxygen transfer through polydimethylsiloxane membrane between double layers of cell culture channel and gas chamber in microfluidic oxygenator

For successful cell culture in microfluidic devices, precise control of the microenvironment, including gas transfer between the cells and the surrounding medium, is exceptionally important. The work is motivated by a polydimethylsiloxane (PDMS) microfluidic oxygenator chip for mammalian cell culture suggesting that the speed of the oxygen transfer may vary depending on the thickness of a PDMS membrane or the height of a fluid channel. In this paper, a model is presented to describe the oxygen transfer dynamics in the PDMS microfluidic oxygenator chip for mammalian cell culture. Theoretical studies were carried out to evaluate the oxygen profile within the multilayer device, consisting of a gas reservoir, a PDMS membrane, a fluid channel containing growth media, and a cell culture layer. The corresponding semi-analytical solution was derived to evaluate dissolved oxygen concentration within the heterogeneous materials, and was found to be in good agreement with the numerical solution. In addition, a separate analytical solution was obtained to investigate the oxygen pressure drop (OPD) along the cell layer due to oxygen uptake of cells, with experimental validation of the OPD model carried out using human umbilical vein endothelial cells cultured in a PDMS microfluidic oxygenator. Within the theoretical framework, the effects of several microfluidic oxygenator design parameters were studied, including cell type and critical device dimensions.