Bubbles no more: in-plane trapping and removal of bubbles in microfluidic devices

Gas bubbles present a frequent challenge to the on-chip investigation and culture of biological cells and small organs. The presence of a single bubble can adversely impair biological function and often viability as it increases the wall shear stress in a liquid-perfused microchannel by at least one order of magnitude. We present a microfluidic strategy for in-plane trapping and removal of gas bubbles with volumes of 0.1-500 nL. The presented bubble trap is compatible with single-layer soft lithography and requires a footprint of less than ten square millimetres. Nitrogen bubbles were consistently removed at a rate of 0.14 μL min(-1). Experiments were complemented with analytical and numerical models to comprehensively characterize bubble removal for liquids with different wetting behaviour. Consistent long-term operation of the bubble trap was demonstrated by removing approximately 4000 bubbles during one day. In a case study, we successfully applied the bubble trap to the on-chip investigation of intact small blood vessels. Scalability of the design was demonstrated by realizing eight parallel traps at a total removal rate of 0.9 μL min(-1) (measured for nitrogen).     

Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis

An extremely simple, power-free pumping method for poly(dimethylsiloxane)(PDMS) microfluidic devices is presented. By exploiting the high gas solubility of PDMS, the energy for the pumping is pre-stored in the degassed bulk PDMS, therefore no additional structures other than channels and reservoirs are required. In a Y-shaped microchannel with cross section of 100 microm width x 25 microm height, this method has provided flow rate of 0.5-2 nL s(-1), corresponding to linear velocity of 0.2-0.8 mm s(-1), with good reproducibility. As an application of the power-free pumping, gold nanoparticle-based DNA analysis, which does not rely on the cross-linking mechanism between nanoparticles, has been implemented in a microchannel with three inlets. Target 15mer DNA has been easily and unambiguously discriminated from its single-base substituted mutant. Instead of colorimetric detection in a conventional microtube, an alternative detection technique suitable for microdevices has been discovered-observation of deposition on the PDMS surfaces. The channel layout enabled two simultaneous DNA analyses at the two interfaces between the three laminar streams.     

Gravity-induced convective flow in microfluidic systems: electrochemical characterization and application to enzyme-linked immunosorbent assay tests

A way of using gravity flow to induce a linear convection within a microfluidic system is presented. It is shown and mathematically supported that tilting a 1 cm long covered microchannel is enough to generate flow rates up to 1000 nL.min(-1), which represents a linear velocity of 2.4 mm.s(-1). This paper also presents a method to monitor the microfluidic events occurring in a covered microchannel when a difference of pressure is applied to force a solution to flow in said covered microchannel, thanks to electrodes inserted in the microfluidic device. Gravity-induced flow monitored electrochemically is applied to the performance of a parallel-microchannel enzyme-linked immunosorbent assay (ELISA) of the thyroid-stimulating hormone (TSH) with electrochemical detection. A simple method for generating and monitoring fluid flows is described, which can, for instance, be used for controlling parallel assays in microsystems.     

Microfluidic flow transducer based on the measurement of electrical admittance

A new flow transducer for measuring the flow rate of a conducting fluid in a microchannel is reported. In this paper, the measure of flow of such fluid under laminar flow conditions based on the change of electrical admittance is established with the aid of a pair of electrodes parallel to the line of flow in a glass-PDMS microfluidic device. This flow sensor is simple in design and can be integrated to most of the microfluidic platforms. The effect of flow rate of the electrolyte, the frequency of the applied ac voltage, the voltage applied across the detector electrodes, and the conductivity of the electrolyte are varied to optimize for high sensitivity. The optimized values are then used to demonstrate the measurements of very low flow rates (<1 nL s(-1)). This flow sensor can be extended towards the measurement of chemical and biochemical buffers and reagents.     

Continuous flow in open microfluidics using controlled evaporation

This paper presents a method for programming the flow rate of liquids inside open microfluidic networks (MFNs). A MFN comprises a number of independent flow paths, each of which starts with an open filling port, has a sealed microchannel in which assays can be performed, and an open capillary pump (CP). The MFN is placed over Peltier elements and its flow paths initially fill owing to capillary forces when liquids are added to the filling ports. A cooling Peltier element underneath the filling ports dynamically prevents evaporation in all filling ports using the ambient temperature and relative humidity as inputs. Another Peltier element underneath the CPs heats the pumps thereby inducing evaporation in the CPs and setting the flow rate in the microchannels. This method achieves flow rates in the microchannels ranging from approximately 1.2 nL s(-1) to approximately 30 pL s(-1), and is able to keep 90% of a 0.6 microL solution placed in an open filling port for 60 min. This simple and efficient method should be applicable to numerous assays or chemical reactions that require small and precise flow of liquids and reagents inside microfluidics.     

A simple microfluidic chlorine gas sensor based on gas-liquid chemiluminescence of luminol-chlorine system

In this work, a microfluidic chlorine gas sensor based on gas-liquid interface absorption and chemiluminescence detection was described. The liquid chemiluminescence reagent-alkaline luminol solution can be stably sandwiched between two convex halves of a microchannel by surface tension. When chlorine gas was introduced into the micro device, it was dissolved into the interfacial luminol solution and transferred to ClO(-), and simultaneously luminol was excited and chemiluminescence emitted. The emitted chemiluminescence light was perpendicularly detected by a photomultiplier tube on a certain detection region. The remarkable advantage of the detection system is that both adsorption and detection were carried out at the gas-liquid interface, which avoids the appearance of bubbles. The whole analytical cycle including filling CL reagent, sample injection, CL detection and emptying the device was as short as 30 s. The linear concentration range of chlorine gas detection with direct introduction of sample method is from 0.5 to 478 ppm. The detection limit of this method is 0.2 ppm for standard chlorine gas and the relative standard deviation of five determinations of 3.19 ppm spiked chlorine sample was 5.2%.     

Surface micromachined electrostatically actuated micro peristaltic pump

An electrostatically actuated micro peristaltic pump is reported. The micro pump is entirely surface micromachined using a multilayer parylene technology. Taking advantage of the multilayer technology, the micro pump design enables the pumped fluid to be isolated from the electric field. Electrostatic actuation of the parylene membrane using both DC and AC voltages was demonstrated and applied to fluid pumping based on a 3-phase peristaltic sequence. A maximum flow rate of 1.7 nL min(-1) and an estimated pumping pressure of 1.6 kPa were achieved at 20 Hz phase frequency. A dynamic analysis was also performed with a lumped-parameter model for the peristaltic pump. The analysis results allow a quantitative understanding of the peristaltic pumping operation, and correctly predict the trends exhibited by the experimental data. The small footprint of the micro pump is well suited for large-scale integration of microfluidics. Moreover, because the same platform technology has also been used to fabricate other devices (e.g. valves, electrospray ionization nozzles, filters and flow sensors), the integration of these different devices can potentially lead to versatile and functional micro total analysis systems (microTAS).     

Pressure drop of slug flow in microchannels with increasing void fraction: experiment and modeling

Pressure drop in a gas-liquid slug flow through a long microchannel of rectangular cross-section was investigated. Pressure measurements in a lengthy (～0.8 m) microchannel determined the pressure gradient to be constant in a flow where gas bubbles progressively expanded and the flow velocity increased due to a significant pressure drop. Most of the earlier studies of slug flow in microchannels considered systems where the expansion of the gas bubbles was negligible in the channel. In contrast, we investigated systems where the volume of the gas phase increased significantly due to a large pressure drop (up to 1811 kPa) along the channel. This expansion of the gas phase led to a significant increase in the void fraction, causing considerable flow acceleration. The pressure drop in the microchannel was studied for three gas-liquid systems; water-nitrogen, dodecane-nitrogen, and pentadecane-nitrogen. Inside the microchannel, local pressure was measured using a series of embedded membranes acting as pressure sensors. Our investigation of the pressure drop showed a linear trend over a wide range of void fractions and flow conditions in the two-phase flow. The lengths and the velocities of the liquid slugs and the gas bubbles were also studied along the microchannel by employing a video imaging technique. Furthermore, a model describing the gas-liquid slug flow in a long microchannel was developed to calculate the pressure drop under conditions similar to the experiments. An excellent agreement between the developed model and the experimental data was obtained.     

Capillary pumps for autonomous capillary systems

Autonomous capillary systems (CSs), where liquids are displaced by means of capillarity, are efficient, fast and convenient platforms for many bioanalytical applications. The proper functioning of these microfluidic devices requires displacing accurate volumes of liquids with precise flow rates. In this work, we show how to design capillary pumps for controlling the flow properties of CSs. The capillary pumps comprise microstructures of various shapes with dimensions from 15-250 microm, which are positioned in the capillary pumps to encode a desired capillary pressure. The capillary pumps are designed to have a small flow resistance and are preceded by a constricted microchannel, which acts as a flow resistance. Therefore, both the capillary pump and the flow resistance define the flow rate in the CS, and flow rates from 0.2-3.7 nL s(-1) were achieved. The placement and the shape of the microstructures in the capillary pumps are used to tailor the filling front of liquids in the capillary pumps to obtain a reliable filling behaviour and to minimize the risk of entrapping air. The filling front can, for example, be oriented vertically or tilted to the main axis of the capillary pump. We also show how capillary pumps having different hydrodynamic properties can be connected to program a sequence of slow and fast flow rates in a CS.     

电渗泵在微柱液相上的应用

 设计评价了一种能够取代机械泵的电渗泵 (EOP) ,该泵可以产生 2 0MPa～ 6 0MPa的输出压力和几十nL/min～ 3μL/min的输出流量 ;用乙腈 水作为流动相 ,在 14cm× 32 0 μmi d (C18,5 μm )微柱上分离了萘、蒽、菲3种物质的混合试样 ,证明EOP在微柱液相领域有广阔的应用前景。     

Compact disk (CD)-shaped device for single cell isolation and PCR of a specific gene in the isolated cell

For immediate discrimination among isolated cells we propose a novel device and technique for isolation of cells and sequential detection of specific gene(s) within them by polymerase chain reaction (PCR). In this study, we isolated Salmonella enterica cells and detected the Salmonella-specific invA gene from isolated cells by PCR on a compact disk (CD)-shaped device. This device enabled liquid flow by centrifugal force without a micro pump, and was fabricated from silicon wafer and glass to avoid evaporation of a small amount of reagent. One device has 24 microchannels, and 313 microchambers integrated on each microchannel. One microliter of PCR mixture containing cells was separated into microchambers on the device at 5000 rpm for 30 s. Each microchamber contained approximately 1.5 nL PCR mixture. A Poisson distribution of S. enterica cells was observed for different densities of cell suspension. At 200 cells μL^?1 of S. enterica or less, isolated single cells could be determined on the device by amplification of DNA of the invA gene; at 400 cells μL^?1, chambers containing no, one, two, or three cells could be determined on the device. Selective detection of S. enterica was achieved by PCR from a mixture of S. enterica and Esherichia coli on the CD-shaped device.     

Microfluidic chemostat and turbidostat with flow rate, oxygen, and temperature control for dynamic continuous culture

This work reports on an instrument capable of supporting automated microscale continuous culture experiments. The instrument consists of a plastic-PDMS device capable of continuous flow without volume drift or evaporation. We apply direct computer controlled machining and chemical bonding fabrication for production of fluidic devices with a 1 mL working volume, high oxygen transfer rate (k(L)a≈0.025 s(-1)), fast mixing (2 s), accurate flow control (±18 nL), and closed loop control over temperature, cell density, dissolved oxygen, and pH. Integrated peristaltic pumps and valves provide control over input concentrations and allow the system to perform different types of cell culture on a single device, such as batch, chemostat, and turbidostat continuous cultures. Continuous cultures are demonstrated without contamination for 3 weeks in a single device and both steady state and dynamically controlled conditions are possible.     

A passive pumping method for microfluidic devices

The surface energy present in a small drop of liquid is used to pump the liquid through a microchannel. The flow rate is determined by the volume of the drop present on the pumping port of the microchannel. A flow rate of 1.25 microL s(-1) is demonstrated using 0.5 microL drops of water. Two other fluid manipulations are demonstrated using the passive pumping method: pumping liquid to a higher gravitational potential energy and creating a plug within a microchannel.     

A simple nanoelectrospray arrangement with controllable flowrate for mass analysis of submicroliter protein samples

A simple arrangement for nanoelectrospray ionization using a conventional syringe pump connected to a pulled unmodified capillary has been evaluated. This arrangement avoids several disadvantages associated with metal-coated nanoelectrospray emitters. The relatively large orifice (approximately 9 microns) at the pulled capillary tip reduces sample clogging and the use of the pump minimizes spray disruption due to gas bubbles. Subattomole detection limit was achieved with nanomolar protein sample solutions at 5-10 nL/min flowrates using an LCQ mass spectrometer. Submicroliter samples can be loaded from the tip orifice and stored inside the capillary to virtually eliminate any dead volume, and then be electrosprayed for extended periods at well-controlled flowrates.     

Fuel cell-powered microfluidic platform for lab-on-a-chip applications

The achievement of a higher degree of integration of components--especially micropumps and power sources--is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (μDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO(2) from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4-18 μL min(-1) while having an available power between 1-4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO(2) pumping action to flow the required analytes through a particular microfluidic design.     

A micro surface tension pump (MISPU) in a glass microchip

A non-membrane micro surface tension pump (MISPU) was fabricated on a glass microchip by one-step glass etching. It needs no material other than glass and is driven by digital gas pressure. The MISPU can be seen working like a piston pump inside the glass microchip under a microscope. The design of the valves (MISVA) and pistons (MISTON) was based on the surface tension theory of the micro surface tension alveolus (MISTA). The digital gas pressure controls the moving gas-liquid interface to open or close the input and output MISVAs to refill or drive the MISTON for pumping a liquid. Without any moving parts, a MISPU is a kind of long-lasting micro pump for micro chips that does not lose its water pumping efficiency over a 20-day period. The volumetric pump output varied from 0 to 10 nl s(-1) when the pump cycle time decreased from 5 min to 15 s. The pump head pressure was 1 kPa.     

Lab on a chip packing of submicron particles for high performance EOF pumping

The packing of submicrometer sized silica beads inside a microchannel was enabled by a novel method which avoids the complication and limitations of generating a frit using conventional approaches and the restriction of flow using a submicrometer sized weir. A micrometer sized weir and two short columns of 5 μm and 800 nm silica beads packed in succession behind the weir together functioned as a high pressure frit to allow the construction of a primary packed bed of 390 nm silica beads. This packed bed microchannel was tested as an EOF pump, wherein it exhibited superior performance with regards to pressure tolerance, i.e., sustaining good flow rate under extremely high back pressure, and maximal pressure generation. Under a modest applied electric field strength of 150 V/cm, the flow rate against a back pressure of 1200 psi (～8.3 MPa) was 40 nL/min, and the maximal pressure reached 1470 psi (～10 MPa). This work has demonstrated that it is possible to create a high performance packed bed microchannel EOF pump using nanometer sized silica beads, as long as proper care is taken during the packing process to minimize the undesirable mixing of two different sized particles at the boundaries between particle segments and to maximize the packing density throughout the entire packed bed.     

Automated microfluidic platform for studies of carbon dioxide dissolution and solubility in physical solvents

We present an automated microfluidic (MF) approach for the systematic and rapid investigation of carbon dioxide (CO(2)) mass transfer and solubility in physical solvents. Uniformly sized bubbles of CO(2) with lengths exceeding the width of the microchannel (plugs) were isothermally generated in a co-flowing physical solvent within a gas-impermeable, silicon-based MF platform that is compatible with a wide range of solvents, temperatures and pressures. We dynamically determined the volume reduction of the plugs from images that were accommodated within a single field of view, six different downstream locations of the microchannel at any given flow condition. Evaluating plug sizes in real time allowed our automated strategy to suitably select inlet pressures and solvent flow rates such that otherwise dynamically self-selecting parameters (e.g., the plug size, the solvent segment size, and the plug velocity) could be either kept constant or systematically altered. Specifically, if a constant slug length was imposed, the volumetric dissolution rate of CO(2) could be deduced from the measured rate of plug shrinkage. The solubility of CO(2) in the physical solvent was obtained from a comparison between the terminal and the initial plug sizes. Solubility data were acquired every 5 min and were within 2-5% accuracy as compared to literature data. A parameter space consisting of the plug length, solvent slug length and plug velocity at the microchannel inlet was established for different CO(2)-solvent pairs with high and low gas solubilities. In a case study, we selected the gas-liquid pair CO(2)-dimethyl carbonate (DMC) and volumetric mass transfer coefficients 4-30 s(-1) (translating into mass transfer times between 0.25 s and 0.03 s), and Henry's constants, within the range of 6-12 MPa.     

An electronic Venturi-based pressure microregulator

Microfluidic systems often use pressure-driven flow to induce fluidic motion, but control of pumps and valves can necessitate numerous external connections or an extensive external control infrastructure. Here, we describe an electronically controlled pressure microregulator that can output pressures both greater and less than atmospheric pressure over a range of 2 kPa from a single pressurized air input of 110 kPa. Multiple independently controlled microregulators integrated in one device can potentially share the same air input. The microregulator operates by using embedded resistive heaters to vary the temperature of a gas flowing through a converging-diverging Venturi nozzle between 25 degrees C and 85 degrees C with a resolution of 33 Pa degrees C(-1). We established the switching speed of the microregulator by accurately moving 1 microL droplets of water in a microchannel via pneumatic propulsion. Droplet deceleration from approximately 1 cm s(-1) to zero velocity required less than 0.8 s. The component is readily integrable into most device designs containing fluidic channels and electronics without introducing additional fabrication complexity.