Integrated electrochemical velocimetry for microfluidic devices

We present a new electrochemical velocimetry approach with direct electrical output that is capable of complete device-level integration. The steady reduction rate of a reversible redox species at an embedded microband working electrode is monitored amperometrically. Only one working electrode of arbitrary width is required; all three electrodes, including counter and reference electrodes, are integrated on-chip for complete miniaturization of the sensor. Experimental results are complemented by a theoretical framework including a full 3D electrochemical model as well as empirical mass transfer correlations and scaling laws. When the sensor is operated in the convective/diffusive transport controlled mode, the output signal becomes a predictable function of velocity in two distinct regimes: (i) in the low velocity regime, the signal is directly proportional to flow rate, and (ii) in the high velocity regime, the signal scales as the cube root of the mean velocity. The proposed velocimetry technique is applicable to all practicable pressure-driven laminar flows in microchannels with known cross-sectional geometry.     

Disposable microfluidic blood cuvette for measuring hemoglobin concentration

This paper presents a new air-bubble free microfluidic blood cuvette for the measurement of hemoglobin concentration. The microfluidic blood cuvette was filled with blood samples by capillary force, and hemoglobin levels in the blood were determined by measuring absorbance at the wavelength of 530 nm. Two different microfluidic blood cuvettes with dual and single sidewall microchannels were investigated. The microfluidic blood cuvette was fabricated using a polymethyl methacrylate substrate and a dry film photoresist. During the blood-filling process, air was trapped in the dual-sided wall-type cuvettes, while no air trapping occurred in the single sidewall-type cuvettes. The sensitivity of the hemoglobin measurements was more linear in a 105 μm deep microchannel than in a 35 μm deep microchannel.     

Integrated microfluidic preconcentrator and immunobiosensor

We present a microfluidic biosensor that integrates membrane-based preconcentration with fluorescence detection. The concentration membrane was fabricated in polyacrylamide by an in situ photopolymerization technique at the junction of glass microchannels. Liposomes entrapping sulforhodamine B dye molecules were used for signal amplification. The biotin–streptavidin binding system was a model system for evaluating device performance. Biotinylated liposomes were preconcentrated at the membrane by applying an electric field across the membrane. The electric field causes the liposomes to migrate toward the membrane where they are concentrated by a sieving effect. Two orders of magnitude concentration was achieved after applying the electric field for only 2 min. The concentrated bolus was then eluted toward the detection unit, where the biotinylated liposomes were captured by immobilized streptavidin. The integrated system with the preconcentration module shows a 14-fold improvement in signal as opposed to a system that does not include preconcentration.     

Large-area interdigitated array microelectrodes for electrochemical sensing

Advanced photolithography developed for the semiconductor industry has been used to fabricate interdigitated microelectrode arrays that pass steady-state limiting currents of up to 230 nA/μM analyte — 2.5 times more than the most sensitive interdigitated array built to date, and exhibit response times of ∼5 ms. This performance results from the small interelectrode gap and the large active area of the device (4 mm²), a combination enabled by advanced photolithography. We describe the fabrication of these arrays and the characterization of their performance in two environments: an aqueous solution of Ru(NH₃)₆³⁺ and a dinitrotoluene solution in acetonitrile. The scaling of array performance parameters with device dimensions is also presented.     

Compatibility of organic solvents for electrochemical measurements in PDMS-based microfluidic devices

We have investigated the compatibility of some organic solvents commonly used in electrochemistry with microfluidic channels based on poly(dimethylsiloxane) (PDMS) and compared the stability of electrochemical measurements over several hours with how much PDMS swells when immersed in these solvents. Lee et al. (Anal Chem 75: 6544–6554. doi: 10.1021/ac0346712, 2003) have shown that there is a good correlation between swelling of PDMS and the solubility parameter (δ _H) of the various solvents and suggested that δ _H can function as an indication of PDMS compatibility. We show that solvents with a very high swelling ratio can give stable voltammetry over several hours, and thus, we do not find that swelling is a good measure for compatibility with PDMS in electrochemical experiments.     

Integrated microelectrode hot electron electrochemiluminescent sensor for microfluidic applications

Electrochemiluminescence using insulator-covered electrodes to tunnel emit hot electrons into solution is a sensitive and selective method of quantitative chemical analysis. Immunoassays can be performed by binding antibodies to the working electrode surface, and labeling the secondary antibody or analyte with luminophores. In this paper we present a miniaturized hot electron-induced electrochemiluminescence device with sub-nanomolar detection limits, where both the working electrode and counter electrode are integrated into a single chip. Microfluidics are fabricated in polydimethylsiloxane elastomer, or fluid confinement by patterned hydrophobic areas are integrated into the same device. Devices are processed on both silicon and glass substrates, using either oxidized silicon, or aluminum thin films covered by atomic layer deposited alumina, as the working electrodes. Different electrode geometries are compared in terms of detection efficiency and luminescence uniformity.     

Potentiometric characterisation of a dual-stream electrochemical microfluidic device

A microfluidic device is presented with off-chip electrodes residing in a reservoir and connected via micro-capillaries to the Y-shaped microfluidic channel. The device is tested by potentiometric measurements involving dual-stream laminar flow of two aqueous solutions carrying different electrolytes at various concentrations. Open circuit potentials are measured for a series of solutions of alkali metal chlorides and tetraalkylammonium chlorides as well as for dilute hydrochloric acid. The open circuit potential for the microfluidic chip was calculated by taking into account the diffusion potential at finite ionic strength as well as the potential difference introduced by the reference electrode system. The liquid junction potential developed at the boundary of the co-flowing aqueous solutions may be manipulated to have greater or lesser relative contributions to the measured open circuit potential based on use of electrolyte salts having cation and anion pairs of similar or dissimilar mobilities in solution. A reasonable agreement between theoretical and experimental values of the open circuit potential is observed for these situations. The results show that simple microfluidic structures possess a rich environment for exploration and application of the solution chemistry of ions.     

基于MSP430单片机的电化学传感检测系统设计

介绍了一种基于单片机的小型电化学传感检测系统,详述了检测系统的整体设计框架和各模块设计.检测系统内部设计有绝对值电路和峰值电流检测电路,大大提高了检测系统的性能.通过对葡萄糖传感器和乳酸传感器进行实验,结果表明:检测系统性能可靠,操作简单,与传统电化学工作站有很好的线性相关性.     

Construction and characterisation of a modular microfluidic system: coupling magnetic capture and electrochemical detection

This work presents the fabrication and characterisation of a versatile lab-on-a-chip system that combines magnetic capture and electrochemical detection. The system comprises a silicon chip featuring a series of microband electrodes, a PDMS gasket that incorporates the microfluidic channels, and a polycarbonate base where permanent magnets are hosted; these parts are designed to fit so that wire bonding and encapsulation are avoided. This system can perform bioassays over the surface of magnetic beads and uses only 50 μL of bead suspension per assay. Following detection, captured beads are released simply by sliding a thin iron plate between the magnets and the chip. Particles are captured upstream from the detector and we demonstrate how to take further advantage of the system fluidics to determine enzyme activities or concentrations, as flow velocity can be adjusted to the rate of the reactions under study. We used magnetic particles containing β-galactosidase and monitored the enzyme activity amperometrically by the oxidation of 4-aminophenol, enzymatically produced from 4-aminophenyl-β-d-galactopyranoside. The system is able to detect the presence of enzyme down to approximately 50 ng mL⁻¹.     

Rice-like CuO nanostructures for sensitive electrochemical sensing of hydrazine

In this work, a low temperature aqueous chemical growth methodology was used for the fabrication of CuO nanostructures. The as-synthesised nanostructures were then elaborately characterised by number of analytical techniques such as scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). The obtained nanostructures were observed to possess interlaced rice-shaped structural features with the length and width of individual rice determined to be in the range of 200–300 nm and 50–100 nm respectively. The unique nanostructures when utilised as electrode material exhibited excellent electro-catalytic potential towards oxidation of hydrazine in alkaline media. The excellent conductive of CuO added by the high surface area of obtained nanorice-like structures enabled development of highly sensitive (3087 µA mM⁻¹ cm⁻²), selective and stable electrochemical sensor for hydrazine. In addition, the successfully application of the developed sensor in spiked tap, bottled and industrial water samples for the detection of hydrazine suggested its feasibility for practical environmental application.

     

A novel microfluidic high-throughput resistive pulse sensing device for cells analysis

Microfluidic impedance-based devices offer a simple method for counting and sizing particles and cells in fields of biomedical research and clinical diagnosis. In this work, we present design, fabrication and operational characteristics of a novel high throughput original MEMS-based Coulter counter. This microfluidic device possesses two sub channels including two pairs of coplanar Au/Cr electrodes in each channels which allows double detection of the particles simultaneously and increases the throughput. The present design provides minimizing the cross talk and obviating the need for hydrodynamic focusing of the sample particles by adjusting Y shape insulation obstacle in direction of flow. Moreover, reducing coincidence events and removing electrode polarization effect were purposed by applying optimum sizes for electrodes considering the ease of fabrication and low costs. The reliability of the novel device was evaluated for polystyrene particles and cancer cells in conductive solutions. Results, which were recorded as relative resistance pulses across four sensing zones, illustrate the capability of the double-channel proposed device in detecting, counting and sizing 10 and 20 µm polystyrene particles. The superiority of present design was proved by relative counting error of below 3 and 11% for the 10 µm and 20 µm particles, respectively and a throughput of hundreds particles per second. Aiming at demonstrating the functionality of the proposed device in the biomedical area, counting of SP2/0 cells was performed. The measured counting outputs for cells in the size range of 5.63–17.6 µm were validated with results of hemocytometer cell counter, with relative error less than 7%.

     

Positioning system for particles in microfluidic structures

Fast continuous flow detection of biomolecules in lab-on-a-chip structures is a challenging task. Combining these molecules with small magnetic particles, the interaction between their stray field and, e.g., magneto-resistive sensors can be used to indirectly prove the biomolecules. To position the particles on top of a sensor array at the bottom of the flow channel, we propose a microfluidic structure of changing channel height combining hydrodynamic and gravitational effects. We present numerical calculations predicting an increase in the capture rate by more than 100% in comparison to a straight channel. We experimentally realize an optical analysis of the specific binding of biotin-functionalized Chemagen beads on a streptavidin-coated surface. To prove the binding is not due to the surface effects, a second uncoated bead species is employed.     

Synergistic effects of micro/nano modifications on electrodes for microfluidic electrochemical ELISA

Microfluidic electrochemical sensing has been considered to be highly efficient. However, we showed, by using numerical simulations in this study, that a planar electrode formed on the bottom of a microchannel is exposed to only a small fraction of analytes in amperometric detection. We also showed that three-dimensional (3D) micropillar electrodes significantly improve the detection current. The practical performance was evaluated using 3D micropillar electrodes fabricated by photolithography. The output current increased as the diameters of the micropillars decreased, as predicted by the simulations. It is noteworthy that the current enhancements obtained with the 3D electrodes were larger than those expected from an increase in the surface area. Further increase in current was achieved by electrical deposition of nanoporous gold-black onto the surface of the 3D electrode: when a 3D electrode with micropillars 30 μm in diameter was used, the output current was approximately 20 times that obtained with a 2D electrode without modification. The applicability of the micropillar electrodes was demonstrated in electrochemical enzyme-linked immunosorbent assay (ELISA) of bone metabolic marker proteins. Although an increase in the surface area of the electrode leads to more noise in general, there is no significant difference in the signal-to-noise ratio between the modified 3D electrode and the 2D electrode without modification in the ELISA experiments. This nanoporous micropillar electrode could potentially be a useful component for the development of on-site diagnosis systems.     

A simple polymer based electrochemical transistor for micromolar glucose sensing

A simple and inexpensive glucose sensor with micromolar sensitivity is demonstrated. The sensor utilizes a poly(3,4-ethyelenedioxythiphene) poly(styrene sulfonate) (PEDOT:PSS) based electrochemical transistor in which all the electrodes and the channel were made with the same polymer. The sensor was fabricated in a one step fabrication process using inexpensive and rapid xurography technique and is able to detect glucose concentrations from approximately 1 μM to 10 mM and showed adequate change for glucose levels in the range of human saliva (8-210 μM) without utilizing any external electron mediators.     

Single-step replicable microfluidic check valve for rectifying and sensing low Reynolds number flow

This paper presents a new microfluidic check valve well suited for low Reynolds number flow rate sensing, micropump flow rectification, and flow control in lab-on-a-chip devices. The valve uses coupling between fluid movement in a channel and an elastomeric column (flap) suspended in the fluid path to generate a strong anisotropic flow resistance. Soft lithography-based molding techniques were used to fabricate the valve, allowing for a low-cost, single-step fabrication process. Three valves—having heights of 25, 50, and 75 μm, respectively—were fabricated and experimentally evaluated; the best of them demonstrated a maximum fluidic diodicity of 4.6 at a Reynolds number of 12.6 and a significant diodicity of 1.6 at the low Reynolds number of 0.7. The valve’s notable low Reynolds number response was realized by adopting a design methodology that balances the stiffness of the elastomer flap and adhesion forces between the flap and its seat. A pair of elastomer check valves integrated with a miniature membrane actuator demonstrated a flow rectification efficiency of 29.8%. The valve’s other notable features include a wide bandwidth response, the ability to admit particles without becoming jammed, and flow rate sensing capability based on optical flap displacement measurements.     

A fluidic interconnection system for polymer-based microfluidic devices

A microfabricated fluidic interconnection system for polymer-based microfluidic nebulizer chips is presented and discussed. The new interconnection mechanism can be used to make fluidic connection between external capillary and the polymer microfluidic chip. The connector mechanism was fabricated using a combination of mechanical milling and laser micromachining. Preliminary leakage tests were performed to demonstrate that the interconnection system is leak-free and pressure tests were performed to evaluate the burst pressure (maximum working pressure). The interconnection system has several advantages over commercially available Nanoport™ interconnection system. The new fluidic interconnection system implemented onto a microfluidic nebulizer chip was successfully tested for desorption electrospray ionization mass spectrometry applications. The performance of the chip using the new connector mechanism was excellent demonstrating the usability of the new connector mechanism.     

Integrated soft sensing of coke-oven temperature

This paper describes an integrated soft-sensing method of estimating the coke-oven temperature (COT). First, the characteristics of the coking process (change in direction of gas flow, coke-pushing series) are analyzed. Two variables are introduced to more precisely describe the COT: COTM is the COT on the machine side and COTC is the COT on the coke side. Next, that analysis is used to select the regenerating chambers where thermocouples should be installed; and the temperatures at the tops of the regenerating chambers on the machine side (TTRMs) and on the coke side (TTRCs) are used as auxiliary variables in soft sensing. Then, two types of linear-regression (LR) models are built, one in 12 variables and one in one variable; and supervised distributed neural networks (SDNNs) are also built to estimate COTM and COTC. The LR model in 12 variables and the SDNN models are integrated to accurately describe the nonlinear relationship between COTM (COTC) and the TTRMs (TTRCs) under normal conditions. Supervised clustering is used to divide the sample space into several subspaces, and a neural network is built for each one. The LR model in one variable [the average TTRM (TTRC)] is employed to estimate COTM (COTC) for abnormal conditions. An expert coordinator balances the outputs of these models. A model adaptive unit periodically updates the parameters of the soft-sensing model to reflect changes in the operating conditions and environment. Finally, the model was implemented in an optimization and control system for the COT. The results of actual runs demonstrate the effectiveness of the model.     

Nanocrystalline graphite-like pyrolytic carbon film electrode for electrochemical sensing of hydrazine

Pyrolytic carbon film (PCF) electrode fabricated by a non-catalytic chemical vapor deposition (CVD) process was used as an electrochemical sensor for the detection of hydrazine. The electrode response was found to be electrocatalytic producing a reduction in the overpotential compared to other unmodified carbon-based electrodes such as glassy carbon (GC), basal-plane pyrolytic graphite (BPPG), and edge-plane pyrolytic graphite (EPPG) electrodes. The overall number of electrons involved in the electro-oxidation of hydrazine, the number of electrons involved in the rate-determining step, and diffusion coefficient of hydrazine at PCF electrode were estimated using cyclic voltammetry and chronoamperometry. The performance of PCF electrode was comparable to and in some cases even better than many chemically modified electrodes in terms of detection limit, linear dynamic range, and sensitivity. Moreover, the sensor exhibited fast response time (within 2 s), high response stability, and reproducibility. All the results indicated this sensor is suitable for hydrazine analysis.