Analytica Chimica Acta (v.507, #1)
Editorial board (iii).
Calendar of forthcoming meetings (N1-N2).
Foreword by Ulrich J. Krull (1).
Microchip devices for detecting terrorist weapons by Joseph Wang (3-10).
Escalating threats of terrorist activity have led to urgent demands for innovative devices for on-site detection of chemical and biological agents and explosive materials. Field detection of such hazardous substances requires that a powerful analytical performance be coupled to miniaturized low-powered instrumentation. “Lab-on-a-Chip” devices, where liquids are manipulated in a microchannel network, offer great promise for converting large and sophisticated instruments into powerful field-deployable analyzers. Particularly attractive for on-site security applications is the very small footprint of microchip devices, high degree of integration, high performance, fast response, and versatility. This article reviews a variety of microchip-based protocols and devices for detecting terrorist weapons. Such microfluidic devices offer great promise for transporting the forensic laboratory to the sample source, and providing an early warning prior to terrorist activity, or a rapid post-analysis ‘fingerprints’ of a disaster site. Due to the small footprint of microchip devices, it could be possible to perform multiple assays simultaneously. Such prospects, challenges and applications are discussed.
Keywords: Microchip devices; Explosives; Nerve agents; Biothreat agents;
Integrated microfluidic devices by David Erickson; Dongqing Li (11-26).
“With the fundamentals of microscale flow and species transport well developed, the recent trend in microfluidics has been to work towards the development of integrated devices which incorporate multiple fluidic, electronic and mechanical components or chemical processes onto a single chip sized substrate. Along with this has been a major push towards portability and therefore a decreased reliance on external infrastructure (such as detection sensors, heaters or voltage sources).” In this review we provide an in-depth look at the “state-of-the-art” in integrated microfludic devices for a broad range of application areas from on-chip DNA analysis, immunoassays and cytometry to advances in integrated detection technologies for and miniaturized fuel processing devices. In each area a few representative devices are examined with the intent of introducing the operating procedure, construction materials and manufacturing technique, as well as any unique and interesting features.
Keywords: Integrated microfluidic devices; Lab-on-a-chip; Miniaturized total analysis system; Biochips;
Numerical analysis of the thermal effect on electroosmotic flow and electrokinetic mass transport in microchannels by G.Y Tang; C Yang; C.K Chai; H.Q Gong (27-37).
Joule heating is present in electrokinetically driven flow and mass transport in microfluidic systems. Nowadays, there is a trend of replacing costly glass-based microfluidic systems by the disposable, cheap polymer-based microfluidic systems. Due to poor thermal conductivity of polymer materials, the thermal management of the polymer-based microfluidic systems may become a problem. In this study, numerical analysis is presented for transient temperature development due to Joule heating and its effect on the electroosmotic flow (EOF) and mass species transport in microchannels. The proposed model includes the coupling Poisson–Boltzmann (P–B) equation, the modified Navier–Stokes (N–S) equations, the conjugate energy equation, and the mass species transport equation. The results show that the time development for both the electroosmotic flow field and the Joule heating induced temperature field are less than 1 s. The Joule heating induced temperature field is strongly dependent on channel size, electrolyte concentration, and applied electric field strength. The simulations reveal that the presence of the Joule heating can result in significantly different characteristics of the electroosmotic flow and electrokinetic mass transport in microchannels.
Keywords: Joule heating; Electroosmotic flow; Capillary electrophoresis; Electrokinetic mass transport; Microfluidics thermal management;
Analytical treatment of electrokinetic microfluidics in hydrophobic microchannels by Jun Yang; Daniel Y. Kwok (39-53).
Microfluidics in microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS) devices is complex due to the large surface area to volume ratio. Thus, surface properties play an important role in flow behavior. In this paper, we summarize the effects of electric double layer and surface hydrophobicity of rectangular microchannels on time-dependent electrokinetic flow. Theoretically, we have shown that flow resistance can, in principal, be significantly reduced so that a larger flow rate can be obtained for pressure-driven flow or electric-field-driven flow. This relies on the ability to change surface charges and surface hydrophobicity independently. Our theoretical results provide guidelines for the design and operation of microfluidic flow in rectangular microchannels. Because of liquid slippage, zeta potential determination by traditional method could be overestimated. Taking into account the effect of hydrophobicity, a modified method is proposed to determine the zeta potential and slip coefficient for parallel-plate microchannels with hydrophobic surfaces.
Keywords: Electrokinetics; Microfluidics; Surface effects;
Cationic polymer coatings for design of electroosmotic flow and control of DNA adsorption by Xuezhu Liu; David Erickson; Dongqing Li; Ulrich J Krull (55-62).
A difficulty with the design and operation of an electrokinetically operated DNA hybridization microfluidic chip is the opposite direction of the electroosmotic flow and electrophoretic mobility of the oligonucleotides. This makes it difficult to simultaneously deliver targets and an appropriate hybridization buffer simultaneously to the probe sites. In this work we investigate the possibility of coating the inner walls of the microfluidic system with hexadimentrine bromide (polybrene, PB) and other cationic polymers in order to reverse the direction of electroosmotic flow so that it acts in the same direction as the electrophoretic transport of the oligonucleotides. The results indicated that the electroosmotic flow (EOF) in channels that were coated with the polymer could be reversed in 1× TBE buffer or 1× SSC buffer. Under these conditions, the DNA and EOF move in the same direction, and the flow can be used to deliver DNA to an area for selective hybridization within the channel. The effects of coating the surface of a nucleic acid microarray with polybrene were also studied to assess non-selective adsorption and stability. The polybrene coating significantly reduced the extent of non-selective adsorption of oligonucleotides in comparison to adsorption onto a glass surface, and the coating did not alter the extent of hybridization. The results suggest that use of the coating makes it possible to achieve semi-quantitative manipulation of nucleic acid oligomers for delivery to an integrated microarray or biosensor.
Keywords: Microfluidics; DNA microarray; Electroosmotic flow; Hybridization;
Simple quantitative optical method for monitoring the extent of mixing applied to a novel microfluidic mixer by Matthew S. Munson; Paul Yager (63-71).
A novel scheme that allows the quantification of the extent of diffusive mixing between two fluids is introduced. The method, which relies upon an increase in the fluorescence intensity of fluorescein at basic pH, allows quantification of the extent of interdiffusion without requiring a full three dimensional mapping of the concentration of the dye. This allows for the characterization of mixers that could otherwise only be characterized by confocal microscopy, such as microfluidic mixing devices. The detection scheme is used to characterize a novel and highly efficient microfluidic mixer that is based on the principle of creating small fluid striations, and has been fabricated with polymeric laminate films. In this and many other mixers, the fluidic interfaces are oriented orthogonal to the optical axis, so that spatial variations in the intensity that change with the extent of mixing cannot be imaged. A 1.8 and 3.0-fold enhancement in the rate of mixing over that in a straight channel was seen after the first and second mixing units, respectively. This mixing detection scheme allows easy and inexpensive comparison of different types of mixers over a wide range of conditions.
Keywords: Mixing; Microfluidics; Polymeric laminates; Detection; Lab-on-chip;
Effects of viscosity on droplet formation and mixing in microfluidic channels by Joshua D. Tice; Adam D. Lyon; Rustem F. Ismagilov (73-77).
This paper characterizes the conditions required to form nanoliter-sized droplets (plugs) of viscous aqueous reagents in flows of immiscible carrier fluid within microfluidic channels. For both non-viscous (viscosity of 2.0 mPa s) and viscous (viscosity of 18 mPa s) aqueous solutions, plugs formed reliably in a flow of water-immiscible carrier fluid for Capillary number less than 0.01, although plugs were able to form at higher Capillary numbers at lower ratios of the aqueous phase flow rate to the flow rate of the carrier fluid (in all the experiments performed, the Reynolds number was less than 1). The paper also shows that combining viscous and non-viscous reagents can enhance mixing in droplets moving through straight microchannels by providing a nearly ideal initial distribution of reagents within each droplet. The study should facilitate the use of this droplet-based microfluidic platform for investigation of protein crystallization, kinetics, and assays.
Keywords: Viscosity; Microfluidic; Mixing; Multiphase; Droplet; Plug;
High-resolution liquid chromatographic separations in 400 nm deep micro-machined silicon channels and fluorescence charge-coupled device camera detection under stopped-flow conditions by D. Clicq; S. Vankrunkelsven; W. Ranson; C. De Tandt; G.V. Baron; G. Desmet (79-86).
We report on a study exploring the possibilities of silicon etched, flat-rectangular nano-channels for the acceleration of liquid chromatography separations. Using the shear-forces originating from a moving channel part to propagate the mobile phase flow, a mixture of two neutral coumarin dyes could be separated in less than 50 ms and with a resolution of over N=106 plates/m. The obtained experimental van Deemter-plot show a good agreement with the theoretical expectations and has a minimal plate height around H=1.0 μm (k=1.5) and H=0.6 μm (k=0.5). The different steps in the fabrication of the nano-channels, and the advantages of a novel detection scheme, based on fluorescent charge-coupled device-array imaging under stopped-flow conditions, are discussed as well.
Keywords: Miniaturization; LC; van Deemter-plot; Shear-driven flow; Separation time;
Peak tailing in electrophoresis due to alteration of the wall charge by adsorbed analytes a by Karim Shariff; Sandip Ghosal (87-93).
When analytes containing cationic components, such as proteins, are separated in fused silica capillaries or micro-chips, they adsorb strongly to the negatively charged channel walls. Broadened and highly asymmetric peaks in the detector signal is symptomatic of the presence of such wall interactions. Band broadening is caused by the introduction of shear into the electroosmotic flow which leads to Taylor dispersion. The shearing flow in turn is caused by axial variations in zeta-potential due to adsorbed analytes. In this paper, numerical solutions of the coupled electro-hydrodynamic equations for fluid flow and the advection-diffusion equation for analyte concentration are presented in the limit of thin Debye layers. The simulations reproduce many of the qualitative effects of wall adsorption familiar from observation. Further, the simulation results are compared, and found to agree very well (to within a percent for characteristic values of the parameters) with a recently developed asymptotic theory.
Keywords: Capillary zone electrophoresis; Dispersion; Wall interactions;
Design and development of microfabricated capillary electrophoresis devices with electrochemical detection by R.S. Keynton; T.J. Roussel; M.M. Crain; D.J. Jackson; D.B. Franco; J.F. Naber; K.M. Walsh; R.P. Baldwin (95-105).
Our efforts have been focused on developing a self-contained and transportable microfabricated electrophoresis (CE) system with integrated electrochemical detection (ED). The current prototype includes all necessary electrodes “on-chip” and utilizes miniaturized CE and ED supporting electronics custom designed for this purpose. State-of-the-art design/modeling tools and novel microfabrication procedures were used to create recessed platinum electrodes with complex geometries and the CE/ED device from two patterned ultra-flat glass substrates. The electrodes in the bottom substrate were formed by a self-aligned etch and deposition technique followed by a photolithographic lift-off process. The microchannels (20 μm deep×65 μm wide (average)) were chemically etched into the top substrate followed by thermal bonding to complete the microchip device. CE/ED experiments were performed using 0.02 M phosphate buffer (pH 6), an analyte/buffer solution (2.2 mM dopamine, 2.3 mM catechol) and varying separation voltages (0–500 V) with a custom electronics unit interfaced to a laptop computer for data acquisition. Detection limits (S/N=3) were found to be at the micromolar level and a linear detection response was observed up to millimolar concentrations for dopamine and catechol. The microchip CE/ED system injected 50 pl volumes of sample, which corresponded to mass detection limits on the order of 200 amol. For the first time, an integrated “on-chip” multi-electrode array CE/ED device was successfully designed, fabricated and tested. The majority of the electrodes (six out of eight) in the array were capable of detecting dopamine with the amplitude of the signal (i.e., peak heights) decreasing as the electrode distance from the channel exit increased.
Keywords: Capillary electrophoresis; Electrochemical detection; ‘On-chip’ integrated electrodes;
Separation of fluorescent derivatives of hydroxyl-containing small molecules on a microfluidic chip by David A Wicks; Paul C.H Li (107-114).
Capillary electrophoresis (CE) on a microchip has been employed in this work because of the need to separate and detect fluorescent derivatives on some licorice-derived compounds, namely glycyrrhizin (GL), isoliquiritigenin (IQ). These compounds, which contain only phenolic or aliphatic hydroxyl (secondary) groups, are hard to derivatize in aqueous solutions. Although there are some fluorescent reagents that will react with hydroxyl groups, these reactions are usually achieved in aprotic solvents, but not in aqueous solutions. The only fluorescent reagent that works in aqueous solvents is 5-([4,6-dichlorotriazin-2-yl]amino)fluorescein (DTAF), but it has mostly been employed to label macromolecules. For the first time, we have successfully fluorescently label two hydroxyl-containing small molecules, GL and IQ in aqueous solutions. The reaction products were separated by CE and detected fluorescently on a microfluidic chip within 100 s. For comparison, the separation was also carried out on a commercial CE system using UV absorbance detection.
Keywords: 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF); Glycyrrhizin (GL); Isoliquiritigenin (IQ); Licorice-derived compounds; Microfluidic chip; Fluorescent detection; Capillary zone electrophoresis (CZE); UV absorbance detection;
Miniature biochip system for detection of Escherichia coli O157:H7 based on antibody-immobilized capillary reactors and enzyme-linked immunosorbent assay by Joon Myong Song; Tuan Vo-Dinh (115-121).
In this work, we report Escherichia coli O157:H7 detection using antibody-immobilized capillary reactors, enzyme-linked immunosorbent assay (ELISA), and a biochip system. ELISA selective immunological method to detect pathogenic bacteria. ELISA is also directly adaptable to a miniature biochip system that utilizes conventional sample platforms such as polymer membranes and glass. The antibody-immobilized capillary reactor is a very attractive sample platform for ELISA because of its low cost, compactness, reuse, and ease of regeneration. Moreover, an array of capillary reactors can provide high-throughput ELISA. In this report, we describe the use of an array of antibody-immobilized capillary reactors for multiplex detection of E. coli O157:H7 in our miniature biochip system. Side-entry laser beam irradiation to an array of capillary reactors contributes significantly to miniaturized optical configuration for this biochip system. The detection limits of E. coli O157:H7 using the ELISA and Cy5 label-based immunoassays were determined to be 3 and 230 cells, respectively. This system shows capability to simultaneously monitor multifunctional immunoassay and high sensitive detection of E. coli O157:H7.
Keywords: Biochip; Enzyme-linked immunosorbent assay; Escherichia coli O157:H7; Antibody-immobilized capillary;
Biosensing in microfluidic channels using fluorescence polarization by Vamsi K. Yadavalli; Michael V. Pishko (123-128).
Microfabricated microfluidic devices provide useful platforms for sensing and conducting immunoassays for high throughput screening and drug discovery. In this paper, fluorescence polarization (FP) has been used as a technique for probing binding events within 500 μm and smaller microfluidic channels fabricated in polydimethylsiloxane. The binding of concanavalin A to a lectin-dextran and a glycoprotein-acetylcholinesterase has been used to demonstrate the homogeneous, ratioing format of fluorescence polarization for the quick and accurate determination of extremely low concentrations. Concentrations of concanavalin A in the 0.2–1.0 nmole range were detected within 500 μm channels. Polarization has also been used to sense for a polyaromatic hydrocarbon (PAH) within a microfluidic channel using binding to a TRITC-labeled antibody. Specifically, concentrations of pyrene in a 10–40 nmole range were sensed in 500 μm microfluidic channels. We have also demonstrated a simple pH sensor based on the change in anisotropy of a pH sensitive fluorophore-SNAFL. The ease of fabrication and measurement using such polarization-based devices make them extremely suitable for micro-sized sensors, assays and total analysis systems.
Keywords: Microfluidic channels; Fluorescence; Polarization;
Composite poly(dimethylsiloxane)/glass microfluidic system with an immobilized enzymatic particle-bed reactor and sequential sample injection for chemiluminescence determinations by Zhang-Run Xu; Zhao-Lun Fang (129-135).
A three-layer poly(dimethylsiloxane) (PDMS)/glass microfluidic system for performing on-chip solid-phase enzymatic reaction and chemiluminescence (CL) reaction was used for the determination of glucose as a model analyte. A novel method for the immobilization of controlled-pore-glass based reactive particles on PDMS microreactor beds was developed, producing an on-chip solid-phase reactor that featured large reactive surface and low flow impedance. Efficient mixing of reagent/sample/carrier streams was achieved by incorporating chaotic mixer structures in the microfluidic channels. A conventional sequential injection (SI) system was adapted for direct coupling with the microfluidic system, and combined with hydrostatic delivery of reagents to achieve efficient and reproducible sample introduction at 10 μl levels. A detection limit of 10 μM glucose (3σ), and a precision of 3.1% RSD (n=7, 0.2 mM glucose) were obtained using the SI-microfluidic-CL system integrated with a glucose oxidase (GOD) reactor. Carryover was <5% at a throughput of 20 samples/h.
Keywords: Microfluidic chips; Sequential injection; Solid-phase reactors; Chemiluminescence; Immobilized enzymes; Glucose;
Miniaturized measurement system for ammonia in air by B.H. Timmer; K.M. van Delft; R.P. Otjes; W. Olthuis; A. van den Berg (137-143).
The development of a miniaturized ammonia sensor made using microsystem technology is described. Gas is sampled in a sampler comprising two opposite channels separated by a gas permeable, water repellent polypropylene membrane. Subsequently, the acid sample solution is pumped into a selector where an alkaline solution is added to ionize all sampled ambient acid gasses, resulting in an enhanced selectivity. In the selector, the ammonia can diffuse through a second membrane into a purified water stream where an electrolyte conductivity sensor quantifies the resulting ammonium concentration. The realized system is shown to be selective enough not to be influenced by normal ambient carbon dioxide concentrations. Experiments with a gas flow of 3 ml/min, containing ammonia concentrations ranging from 9.8 to 0.3 ppm in a nitrogen carrier flow, into a 15 μl/min sample solution flow and finally into a 5 μl/min purified water stream have been carried out and show that the system is sensitive to ammonia concentration below 1 ppm.
Keywords: Gaseous ammonia sensor; Microfluidics;
Droplet-based microfluidic lab-on-a-chip for glucose detection by Vijay Srinivasan; Vamsee K Pamula; Richard B Fair (145-150).
A microfluidic lab-on-a-chip (LoC) platform for in vitro measurement of glucose for clinical diagnostic applications is presented in this paper. The LoC uses a discrete droplet format in contrast to conventional continuous flow microfluidic systems. The droplets act as solution-phase reaction chambers and are manipulated using the electrowetting effect. Glucose is measured using a colorimetric enzyme-kinetic method based on Trinder’s reaction. The color change is detected using an absorbance measurement system consisting of a light emitting diode and a photodiode. The linear range of the assay is 9–100 mg/dl using a sample dilution factor of 2 and 15–300 mg/dl using a sample dilution factor of 3. The results obtained on the electrowetting system compare favorably with conventional measurements done on a spectrophotometer, indicating that there is no change in enzyme activity under electrowetting conditions.
Keywords: Electrowetting; Droplet; Glucose; Lab-on-a-chip; Microfluidics;
Dielectrophoretic fluidic cell fractionation system by Youlan Li; Karan V.I.S. Kaler (151-161).
This paper presents the development and experimental verification of a DEP fluidic system capable of fractionation of intact biological cells in suspension into purer subpopulations. This was accomplished by employing a specially shaped nonuniform electric field, synthesized by microfabricated planar microelectrode arrays, housed on an insulating glass substrate. To improve the efficiency of cell sorting, the microelectrodes are individually biased by a variable frequency alternating current (ac) voltage source, which allows us to exploit both positive and negative dielectrophoresis (DEP) to affect cell separation. Furthermore, through suitable establishment of a cell stream supported by sheath flow, such fractionation is achieved in a continuous fashion. The proposed DEP fluidic fractionation may be configured to operate in three (3) different modes. In this work, however, a detailed account is only presented for one mode of operation. The simulation of the electric field and force profiles, together with the experimental results obtained on model cells (plant protoplasts), confirm our theoretical predictions and furthermore demonstrate improvements in both separation efficiency and throughput over a wide range of frequencies (10 Hz to 5 kHz).
Keywords: Dielectrophoresis; Isomotive; Microelectrode array; Fluidic; Separation; Continuous fractionation;
Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection by Lung-Ming Fu; Ruey-Jen Yang; Che-Hsin Lin; Yu-Jen Pan; Gwo-Bin Lee (163-169).
This paper presents an innovative micro flow cytometer which is capable of counting and sorting cells or particles. This compact device employs electrokinetic forces rather than the more conventional hydrodynamic forces technique for flow focusing and sample switching, and incorporates buried optical fibers for the on-line detection of cells or particles. This design approach results in a compact microfluidic system and an easier integration process. The proposed cytometer integrates several critical modules, namely electrokinetic-focusing devices, built-in control electrodes, buried optical fibers for on-line detection, and electrokinetic flow switches for bio-particle collection. A linear relationship exists between the focused stream width (d) and the focusing ratio (F/φ), which is estimated to be D≈134.5−53.8F/φ. The relationship between the particle velocity (U) and the applied voltage (V) is also investigated. Numerical and experimental data confirm the effectiveness of the device when applied to the counting and sorting of 10 μm diameter particles and red blood cells.
Keywords: Flow cytometer; Electrokinetically driven; Cell counting; Cell sorting; Electrokinetic-focusing; Optical waveguides;