Light-actuated high pressure-resisting microvalve for on-chip flow control based on thermo-responsive nanostructured polymer

A simple light-actuated microvalve using a quartz halogen illuminator with tungsten filament was introduced to manipulate flow path effectively in micro-total analysis systems, which reduces system complexity and the need for on-chip integration. The microvalve device in cyclic olefin copolymer (COC) microchip functions very well based on the thermo-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), whose pressure-tolerance can be tuned by changing the mechanical strength of polymer monolith inside the microchannel with the choice of suitable amount of monomer and crosslinker. The response time and pressure resistance of the valve can be optimized by the tetrahydrofuran composition in the polymerization mixture as well. Very importantly, the microvalve can withstand the leakage pressure up to around 1350 psi, and its opening and closing response time is only 4.0 and 6.2 s respectively. Microchips with such valves will be very useful in drug delivery, chemical analysis and proteomic analysis.     

Microfluidic sequential injection analysis system based on polydimethylsiloxane (PDMS) chip with integrated pneumatic-actuated valves

A sequential injection analysis (SIA) system based on polydimethylsiloxane (PDMS) chip with integrated pneumatic-actuated valves was developed. A novel SIA operation mode using multiphase laminar flow effect and pneumatic microvalve control was proposed. The sample and reagent solutions were synchronously loaded and injected in the chip-based sample injection module instead of multi-step sequential injection by a multiposition valve and a reciprocating pump as in conventional SIA system. The sample and reagent injection volumes were reduced to ca. 1.1 nL. The present system has the advantages of simple structure, fast and convenient operation, low sample and reagent consumption, and high degree of integration and automation. The system operation conditions were optimized using fluorescein as model sample. Its feasibility in biological analysis was preliminarily demonstrated in enzyme inhibition assay.     

Band broadening effects in capillary column recycle gas chromatography with valves

Sources leading to band broadening and peak distortion have been studied in a capillary column recycle system, based on a commercial microvalve. The ferrule system was a major contributor to band broadening. It was found that the quality of connections is very critical but the internal volume of the valve is not important. The pressure pulses resulting from each switching operation produced some band broadening with substances that had just been transferred through the valve but no adverse effects were noticed when they had travelled some distance into the column. Flow into valve cavities and through tees also produced a drop in efficiency. It is not clear whether this is solely due to problems in column connection or if changes in flow pattern also contribute. The activity of the valve toward polar substances was also assessed. No attempt was made to deactivate valve surfaces. The components of the Grob test mixture were almost unaffected but highly polar and acidic compounds such as nitrophenol showed severe losses. No evidence for catalysis was found.     

How the capillary burst microvalve works

The capillary burst microvalve offers an attractive means to regulate microliquid flow owing to its simple structure and operation process. However, there existed no rigorous theoretical work to elucidate how the valve works and consequently to predict the valve-bursting condition. Therefore, here we report the theoretical investigation of how the capillary burst valve can stop the advancing liquid meniscus and when it bursts. We confirm our theory with experiments using a centrifugal microfluidic valve system fabricated by soft lithography.     

Electrically controlled microvalves to integrate microchip polymerase chain reaction and capillary electrophoresis

Microvalves are key in realizing portable miniaturized diagnostic platforms. We present a scalable microvalve that integrates well with standard lab on a chip (LOC) implementations, yet which requires essentially no external infrastructure for its operation. This electrically controlled, phase-change microvalve is used to integrate genetic amplification and analysis via capillary electrophoresis--the basis of many diagnostics. The microvalve is actuated using a polymer (polyethylene glycol, PEG) that exhibits a large volumetric change between its solid and liquid phases. Both the phase change of the PEG and the genetic amplification via polymerase chain reaction (PCR) are thermally controlled using thin film resistive elements that are patterned using standard microfabrication methods. By contrast with many other valve technologies, these microvalves and their control interface scale down in size readily. The novelty here lies in the use of fully integrated microvalves that require only electrical connections to realize a portable and inexpensive genetic analysis platform.     

A microfluidic-based hydrodynamic trap: design and implementation

We report an integrated microfluidic device for fine-scale manipulation and confinement of micro- and nanoscale particles in free-solution. Using this device, single particles are trapped in a stagnation point flow at the junction of two intersecting microchannels. The hydrodynamic trap is based on active flow control at a fluid stagnation point using an integrated on-chip valve in a monolithic PDMS-based microfluidic device. In this work, we characterize device design parameters enabling precise control of stagnation point position for efficient trap performance. The microfluidic-based hydrodynamic trap facilitates particle trapping using the sole action of fluid flow and provides a viable alternative to existing confinement and manipulation techniques based on electric, optical, magnetic or acoustic force fields. Overall, the hydrodynamic trap enables non-contact confinement of fluorescent and non-fluorescent particles for extended times and provides a new platform for fundamental studies in biology, biotechnology and materials science.     

Reproducibility in capillary supercritical fluid chromatography: Comparison of injection techniques

An analysis of the precision obtained using commercially available microvalve injectors is reported for three modes of injection: conventional split; timed-split; and direct. Results from this study show that good precision (< 3% RSD for external standard and < 1% RSD for internal standard methods) can be obtained with capillary supercritical fluid chromatography (SFC). However, particular attention must be paid to the type of valve used, the orientation of the column relative to the valve, the mode of interfacing or connecting the column to the valve, and the type of pressure or density programming used for the analysis as all of these factors will affect the reproducibility.     

Hydrodynamic injection with pneumatic valving for microchip electrophoresis with total analyte utilization

A novel hydrodynamic injector that is directly controlled by a pneumatic valve has been developed for reproducible microchip CE separations. The PDMS devices used for the evaluation comprise a separation channel, a side channel for sample introduction, and a pneumatic valve aligned at the intersection of the channels. A low pressure (≤ 3?psi) applied to the sample reservoir is sufficient to drive sample into the separation channel. The rapidly actuated pneumatic valve enables injection of discrete sample plugs as small as ~ 100?pL for CE separation. The injection volume can be easily controlled by adjusting the intersection geometry, the solution back pressure, and the valve actuation time. Sample injection could be reliably operated at different frequencies (< 0.1?Hz to > 2?Hz) with good reproducibility (peak height relative standard deviation ≤ 3.6%) and no sampling biases associated with the conventional electrokinetic injections. The separation channel was dynamically coated with a cationic polymer, and FITC-labeled amino acids were employed to evaluate the CE separation. Highly efficient (≥ 7.0 × 103 theoretical plates for the ~2.4-cm-long channel) and reproducible CE separations were obtained. The demonstrated method has numerous advantages compared with the conventional techniques, including repeatable and unbiased injections, little sample waste, high duty cycle, controllable injected sample volume, and fewer electrodes with no need for voltage switching. The prospects of implementing this injection method for coupling multidimensional separations for multiplexing CE separations and for sample-limited bioanalyses are discussed.     

Reduction of matrix interferences and improvement of detection power in flame AAS by a high-performance flow/hydraulic high-pressure nebulization system for sample introduction (HPF/HHPN)

Summary For analysis of highly concentrated salt solutions, the samples are injected into a high-performance carrier stream and transported to a special high-pressure nebulization nozzle (max. pressure: 400 bar/40 MPa). An aerosol of very small droplets is formed only by the high fluid pressure without using nebulization gas. The nozzle replaces the pneumatic nebulizer (high-performance flow/hydraulic high-pressure nebulization system: HPF/HHPN). In comparison with pneumatic nebulization, matrix interferences are significantly reduced and sensitivity is improved by factors of 2 to 8 (depending on the element and matrix to be analyzed). For the determination of 10 elements in the matrices Al (30 g/l), Fe (150 g/l) and Cu (330 g/l), the element-specific improvement of the detection power by a factor of 4.1 to 9.7 for Al, 1.3 to 4.9 for Fe and 1.3 to 10 for Cu is achieved.     

A pneumatic micromixer facilitating fluid mixing at a wide range flow rate for the preparation of quantum dots

A novel fluid micromixer based on pneumatic perturbation and passive structures was developed. This micromixer facilitates integration and is applicable to fluid mixing over a wide range of flow rates. The microfluidic mixing device consists of an S-shaped structure with two mixing chambers and two barriers, and two pneumatic chambers designed over the S-shaped channel. The performance of the micromixer for fluids with wide variation of flow rates was significantly improved owing to the integration of the pneumatic mixing components with the passive mixing structures. The mixing mechanism of the passive mixing structures was explored by numerical simulation, and the influencing factors on the mixing efficiency were investigated. The results showed that when using a gas pressure of 0.26 MPa and a 100 m-thick polydimethylsiloxane (PDMS) pneumatic diaphragm, the mixing of fluids with flow rates ranging from 1 to 650 L/min was achieved with a pumping frequency of 50 Hz. Fast synthesis of CdS quantum dots was realized using this device. Smaller particles were obtained, and the size distribution was greatly improved compared with those obtained using conventional methods.     

In-line monitoring of droplets deformation and recovering and polymer degradation during extrusion

An extruder can be operated as a torque rheometer by setting an external control of the processing variables and adding an in-line optical detector and an on-off mechanical valve at the extruder die exit. Various operational modes can be used including constant, ramp and sinusoidal changes of the die-head pressure. With the valve closed, a fixed amount of polymer is added and the extruder put into operation, controlling the screw rotation speed via software, having a proportional/integral/derivative controller. Polymer degradation can be followed recording changes in barrel pressure and torque. After processing, the valve is opened and the molten polymer discharged under a controlled die-head pressure, manipulating again the screw rotation speed. The polymer mixture morphology can be scanned during the discharge of the melt flow by the in-line turbidimeter, showing the deformation/recovery of the second phase droplets.     

Development and multiplexed control of latching pneumatic valves using microfluidic logical structures

Novel latching microfluidic valve structures are developed, characterized, and controlled independently using an on-chip pneumatic demultiplexer. These structures are based on pneumatic monolithic membrane valves and depend upon their normally-closed nature. Latching valves consisting of both three- and four-valve circuits are demonstrated. Vacuum or pressure pulses as short as 120 ms are adequate to hold these latching valves open or closed for several minutes. In addition, an on-chip demultiplexer is demonstrated that requires only n pneumatic inputs to control 2(n-1) independent latching valves. These structures can reduce the size, power consumption, and cost of microfluidic analysis devices by decreasing the number of off-chip controllers. Since these valve assemblies can form the standard logic gates familiar in electronic circuit design, they should be useful in developing complex pneumatic circuits.     

Layer-to-layer parallel fluidic transportation system by addressable fluidic gate arrays

This paper presents addressable fluidic gate arrays for a layer-to-layer parallel fluidic transportation system. The proposed addressable fluidic gate consists of double valves driven by pneumatic pressure. One of the double valves is controlled by the row channel and the other is controlled by the column channel for row/column addressing. Our study applies addressable fluidic gate arrays to layer-to-layer transportation beyond a typical in-plane fluidic network system. The layer-to-layer transportation makes it possible to collect targeted samples from a testing well plate. 3 x 3 fluidic gate arrays based on the proposed concept are developed and tested. A single PDMS valve (phi400 microm) can be closed by 75.0 kPa. The demonstrated fluidic system is based on all PDMS structures by taking account of its disposable use. This paper also reports a dome-shaped chamber for robust sealing and a switching valve with a bistable diaphragm for memory function.     

An active bubble trap and debubbler for microfluidic systems

We present a novel, fully integrated microfluidic bubble trap and debubbler. The 2-layer structure, based on a PDMS valve design, utilizes a featured membrane to stop bubble progression through the device. A pneumatic chamber directly above the trap is evacuated, and the bubble is pulled out through the gas-permeable PDMS membrane. Normal device operation, including continuous flow at atmospheric pressure, is maintained during the entire trapping and debubbling process. We present a range of trap sizes, from 2 to 10 mm diameter, and can trap and remove bubbles up to 25 muL in under 3 h.     

Microfluidic Wheatstone bridge for rapid sample analysis

We developed a microfluidic analogue of the classic Wheatstone bridge circuit for automated, real-time sampling of solutions in a flow-through device format. We demonstrate precise control of flow rate and flow direction in the "bridge" microchannel using an on-chip membrane valve, which functions as an integrated "variable resistor". We implement an automated feedback control mechanism in order to dynamically adjust valve opening, thereby manipulating the pressure drop across the bridge and precisely controlling fluid flow in the bridge channel. At a critical valve opening, the flow in the bridge channel can be completely stopped by balancing the flow resistances in the Wheatstone bridge device, which facilitates rapid, on-demand fluid sampling in the bridge channel. In this article, we present the underlying mechanism for device operation and report key design parameters that determine device performance. Overall, the microfluidic Wheatstone bridge represents a new and versatile method for on-chip flow control and sample manipulation.     

Microfluidic routing of aqueous and organic flows at high pressures: fabrication and characterization of integrated polymer microvalve elements

This paper presents the first systematic engineering study of the impact of chemical formulation and surface functionalization on the performace of free-standing microfluidic polymer elements used for high-pressure fluid control in glass microsystems. System design, chemical wet-etch processes, and laser-induced polymerization techniques are described, and parametric studies illustrate the effects of polymer formulation, glass surface modification, and geometric constraints on system performance parameters. In particular, this study shows that highly crosslinked and fluorinated polymers can overcome deficiencies in previously-reported microvalve architectures, particularly limited solvent compatibility. Substrate surface modification is shown effective in reducing the friction of the polymer-glass interface and thereby facilitating valve actuation. A microchip one-way valve constructed using this architecture shows a 2 x 10(8) ratio of forward and backward flow rates at 7 MPa. This valve architecture is integrated on chip with minimal dead volumes (70 pl), and should be applicable to systems (including chromatography and chemical synthesis devices) requiring high pressures and solvents of varying polarity.     

Microfluidic based single cell microinjection

We report a microfluidic based approach for single cell microinjection in which fluid streams direct a cell onto a fixed microneedle in contrast to moving a microneedle towards an immobilized cell, as done in conventional methods. The approach simplifies microinjection and offers the potential for flow through automated microinjection of cells.     

Design and dynamic characterization of "single-stroke" peristaltic PDMS micropumps

In this paper, we present a monolithic PDMS micropump that generates peristaltic flow using a single control channel that actuates a group of different-sized microvalves. An elastomeric microvalve design with a raised seat, which improves bonding reliability, is incorporated into the micropump. Pump performance is evaluated based on several design parameters--size, number, and connection of successive microvalves along with control channel pressure at various operating frequencies. Flow rates ranging 0-5.87 μL min(-1) were observed. The micropump design demonstrated here represents a substantial reduction in the number of/real estate taken up by the control lines that are required to run a peristaltic pump, hence it should become a widespread tool for parallel fluid processing in high-throughput microfluidics.     

Converting steady laminar flow to oscillatory flow through a hydroelasticity approach at microscales

We report a hydroelasticity-based microfluidic oscillator that converts otherwise steady laminar flow to oscillatory flow. It incorporates an elastic diaphragm to enhance nonlinearity of the flow. Negative differential flow resistance is observed. High-frequency oscillatory flow is produced passively through interactions among hydrodynamic, elastic and inertial forces, without resorting to external actuators and control equipment. Driven by fluid flow and pressure, this device can operate in either steady laminar flow or oscillatory flow states, or work as a valve. Its applications for flow control and operation, and mixing enhancement are demonstrated.     

用于间质液检测的微针阵列研究进展

间质液是疾病诊断生物标志物的重要来源。微针阵列作为一种微创技术进入皮下间质液可以避免接触血管和神经,使用时疼痛感较小,易被患者接受,在多种领域都有广泛的应用。使用微针阵列检测间质液可以为临床诊断提供更多信息,研发制备简单、稳定性强和功能多样的微针阵列逐渐成为研究热点。本文介绍了间质液中生物标志物检测对人体健康监测的重要意义,总结了用于间质液检测的微针阵列的分类以及微针阵列制备所使用材料,着重介绍了微针阵列在间质液中采样与检测应用,讨论了微针阵列在间质液检测中的发展前景以及面临的挑战。