An actuated pump on-chip powered by cultured cardiomyocytes

Cellular functions are frequently exploited as processing components for integrated chemical systems such as biochemical reactors and bioassay systems. Here, we have created a new cell-based microsystem exploiting the intrinsic pulsatile mechanical functions of cardiomyocytes to build a cellular micropump on-chip using cardiomyocyte sheets as prototype bio-microactuators. We first demonstrate cell-based control of fluid motion in a model microchannel without check valves and evaluate the potential performance of the bio-actuation. For this purpose, a poly(dimethylsiloxane) (PDMS) microchip with a microchannel equipped with a diaphragm and a push-bar structure capable of harnessing collective cell fluid mechanical forces was coupled to a cultured pulsating cardiomyocyte sheet, activating cell-based fluid movement in the microchannel by actuating the diaphragm. Cell oscillation frequency and correlated fluid displacement in this system depended on temperature. When culture temperature was increased, collective cell contraction frequency remained cooperative and synchronous but increased, while displacement was slightly reduced. We then demonstrated directional fluid pumping within microchannels using cantilever-type micro-check valves made of polyimide. A directional flow rate of nL min(-1) was produced. This cell micropump system could be further developed as a self-actuated and efficient mechanochemical transducer requiring no external energy sources for various purposes in the future.     

Concepts for a new class of all-polymer micropumps

This paper presents a polymer-based micropump addressing the cost, performance, and system compatibility issues that have limited the integration of on-chip micropumps into microanalysis systems. This pump uses dielectric elastomer actuation to periodically displace fluid, and a pair of elastomeric check valves to rectify the fluid's resulting movement. Its significant features include the use of a transparent substrate, self-priming capability, insensitivity to gas bubbles, and the ability to admit particles. A pump occupying less than 10 mm2 of chip space produced a 77 microl min(-1) flow rate. The pump has a high thermodynamic efficiency and exhibits little performance degradation over 10 hours of operation. In addition to its notable performance, the pump can be fabricated at low cost and directly integrated into microfluidic chips that use planar softlithography-formed structures. The new pump concept, fabrication, and experimental performance are discussed herein.     

A soft-polymer piezoelectric bimorph cantilever-actuated peristaltic micropump

A peristaltic micropump was fabricated and characterized. The micropump was fabricated using soft lithography, and actuated using piezoelectric bimorph cantilevers. The micropump channel was formed by bonding two layers of PDMS, mixed at 5:1 and 30:1 ratios. The channel was fabricated in the 5:1 layer using replica molding (REM), where a very simple and inexpensive template was made by straddling a 75 microm wire over a glass substrate, followed by covering and smoothing over the wire with a piece of aluminium foil. Not only was this template inexpensive and extremely simple to fabricate, it also created a rounded cross-sectional geometry which is favorable for complete valve shutoff. The cantilevers were driven at Vp=+/-90 V with amplified square wave signals generated by a virtual function generator created in LabVIEW. Connections to the micropump were made by placing capillary tubes in the channel, and then sealed between the two layers of PDMS. Machined aluminium clamps were adhered to the tips of the cantilevers with general purpose adhesive. These clamps allowed for aluminium valves, with finely machined tips of dimensions 3 mm by 200 microm, to be held firmly in place. The variables characterized for this micropump were flow rate, maximum attainable backpressure, free cantilever deflection, valve shutoff, and valve leakage. Three actuation patterns with phase differences of 60, 90, and 120 degrees were compared for flow rate and maximum backpressure. It was determined that the 120 degrees signal outperformed the 60 degrees and 90 degrees signals for both maximum flowrate and maximum attainable backpressure. The maximum and minimum flowrates demonstrated by the micropump were 289 nL min(-1) and 53 nL min(-1), respectively. The maximum backpressure attained was 35 300 Pa. It was also demonstrated that the valves fully closed the channels upon actuation, with minimal observed leakage.     

Microfluidic very large scale integration (mVLSI) with integrated micromechanical valves

Microfluidic chips with a high density of control elements are required to improve device performance parameters, such as throughput, sensitivity and dynamic range. In order to realize robust and accessible high-density microfluidic chips, we have fabricated a monolithic PDMS valve architecture with three layers, replacing the commonly used two-layer design. The design is realized through multi-layer soft lithography techniques, making it low cost and easy to fabricate. By carefully determining the process conditions of PDMS, we have demonstrated that 8 × 8 and 6 × 6 μm(2) valve sizes can be operated at around 180 and 280 kPa differential pressure, respectively. We have shown that these valves can be fabricated at densities approaching 1 million valves per cm(2), substantially exceeding the current state of the art of microfluidic large-scale integration (mLSI) (thousands of valves per cm(2)). Because the density increase is greater than two orders of magnitude, we describe this technology as microfluidic very large scale integration (mVLSI), analogous to its electronic counterpart. We have captured and tracked fluorescent beads, and changed the electrical resistance of a fluidic channel by using these miniaturized valves in two different experiments, demonstrating that the valves are leakproof. We have also demonstrated that these valves can be addressed through multiplexing.     

Photopolymerized check valve and its integration into a pneumatic pumping system for biocompatible sample delivery

In this paper, we present a simple check valve whose operation mimics that of venous valves. Our check valve has a mono-leaflet and is constructed via an in situ fabrication method inside the PDMS platform. For the smooth operation of the valve's leaflet, the elasticity and the shape of the leaflet and the lubrication between the leaflet and the channel surface are important. We used 4-hydroxybutyl acrylate (4-HBA) as an elastic and photopolymerizable leaflet material. We mixed the triton X-100 with the 4-HBA pre-polymer solution for the adequate lubrication of the leaflet. We constructed the micro-pumping system by combining two venous-like check valves with an oscillating polymeric diaphragm driven by pneumatic force, and measured the flow rate according to the change of pumping frequency. We also investigated the pump's feasibility as a delivery system of biocompatible materials by using mouse embryo fibroblast cells.     

On-chip pumping for pressure mobilization of the focused zones following microchip isoelectric focusing

Isoelectric focusing (IEF), traditionally accomplished in slab or tube gels, has also been performed extensively in capillary and, more recently, in microchip formats. IEF separations performed in microchips typically use electroosmotic flow (EOF) or chemical treatment to mobilize the focused zones past the detection point. This report describes the development and optimization of a microchip IEF method in a hybrid PDMS-glass device capable of controlling the mobilization of the focused zones past the detector using on-chip diaphragm pumping. The microchip design consisted of a glass fluid layer (separation channels), a PDMS layer and a glass valve layer (pressure connections and valve seats). Pressure mobilization was achieved on-chip using a diaphragm pump consisting of a series of reversible elastomeric valves, where a central diaphragm valve determined the volume of solution displaced while the gate valves on either side imparted directionality. The pumping rate could be adjusted to control the mobilization flow rate by varying the actuation times and pressure applied to the PDMS to actuate the valves. In order to compare the separation obtained using the chip with that obtained in a capillary, a serpentine channel design was used to match the separation length of the capillary, thereby evaluating the effect of diaphragm pumping itself on the overall separation quality. The optimized mIEF method was applied to the separation of labeled amino acids.     

AC electroosmotic pump with bubble-free palladium electrodes and rectifying polymer membrane valves

We present the design, test and theoretical analysis of a novel micropump. The purpose is to make a pump with large flow rate (approximately 10 microL min-1) and high pressure capacity (approximately 1 bar) powered by a low voltage DeltaV<30 V. The pump is operated in AC mode with an electroosmotic actuator in connection with a full wave rectifying valve system. Individual valves are based on a flexible membrane with a slit. Bubble-free palladium electrodes are implemented in order to increase the range of applications and reduce maintenance.     

A water-activated pump for portable microfluidic applications

An on-chip micropump for portable microfluidic applications was investigated using mathematical modeling and experimental testing. This micropump is activated by the addition of water, via a dropper, to ionic polymer particles that swell due to osmotic effects when wetted. The resulting particle volume increase deflects a membrane, forcing a separate fluid from an adjacent reservoir. The micropump components, along with the microfluidic components, are fabricated using the contact liquid photolithographic polymerization (CLiPP) method. The maximum flow rate achieved with this pump is 17 microL per minute per mg of dry polymer particles of 355-425 microm in diameter. The pump flow rate may be controlled by adjusting the particle size and amount, the membrane properties, and the channel dimensions. The experimental results demonstrate good agreement with an analytical model describing the particle swelling and its coupling with resistive forces from the bending membrane, viscous flow in the microchannel, and interfacial effects. Key features of this micropump are that it can be placed directly on a microdevice, and that it requires only a small amount of water and no external power supply to function. Therefore, this pumping system is useful for applications in which a highly portable device is required.     

Development of an on-line low gas pressure cell for laser ablation-ICP-mass spectrometry.

An on-line low gas pressure cell device has been developed for elemental analysis using laser ablation-ICP-mass spectrometry (LA-ICPMS). Ambient gas in the sample cell was evacuated by a constant-flow diaphragm pump, and the pressure of the sample cell was controlled by changing the flow rate of He-inlet gas. The degree of sample re-deposition around the ablation pit could be reduced when the pressure of the ambient gas was lower than 50 kPa. Produced sample aerosol was drawn and taken from the outlet of the diaphragm pump, and directly introduced into the ICP ion source. The flow rate of He gas controls not only the gas pressure in the sample cell, but also the transport efficiency of the sample particles from the cell to the ICP, and the gas flow rate must be optimized to maximize the signal intensity of the analytes. The flow rates of the He carrier and Ar makeup gas were tuned to maximize the signal intensity of the analytes, and in the case of (238)U from the NIST SRM610 glass material, the signal intensity could be maximized with gas flow rates of 0.4 L/min for He and 1.2 L/min for Ar. The resulting gas pressure in the cell was 30 - 35 kPa. Using the low gas pressure cell device, the stability in the signal intensities and the resulting precision in isotopic ratio measurements were evaluated. The signal intensity profile of (63)Cu obtained by laser ablation from a metallic sample (NIST SRM976) demonstrated that typical spikes in the transient signal, which can become a large source of analytical error, were no longer found. The resulting precision in the (65)Cu/(63)Cu ratio measurements was 2 - 3% (n = 10, 2SD), which was half of the level obtained by laser ablation under atmospheric pressure (6 - 10%). The newly developed low-pressure cell device provides easier optimization of the operational conditions, together with smaller degrees of sample re-deposition and better stability in the signal intensity, even from a metallic sample.     

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.     

Electrically actuated, pressure-driven microfluidic pumps

In order to make the lab-on-a-chip concept a reality, it is desirable to have an integrated component capable of pumping fluids through microchannels. We have developed novel, electrically actuated micropumps and have integrated them with microfluidic systems. These devices utilize the build-up of electrolysis gases to achieve pressure-driven pumping, only require small voltages (approximately 10 V), and have approximate dimensions of 5 cm x 3 cm x 2 cm. Furthermore, these micropumps are composed of relatively inexpensive materials, and the reversible sealability of their poly(dimethylsiloxane) body to different microfluidic arrays enables repeated uses of the same pump. Under an applied potential of 10 V, three different micropumps had average flow rates of 8-13 microL min(-1) for water being pumped through five different 2 cm-long, 5500 microm(2) cross-sectional-area channels in poly(methyl methacrylate), in approximate agreement with predicted pump rates. We have also evaluated pump operation at the lower applied potential of 8 V and observed an average flow rate of 6.1 microL min(-1) for a pump-channel system. The current micropump design is capable of sustaining pumping pressures in the range of 300 kPa. The various advantages of these micropumps make them well suited for use in lab-on-a-chip analysis techniques.     

PDMS-based microfluidics for proteomic analysis

A microfluidic poly(dimethylsiloxane) (PDMS) microdevice was realized, combining on-line protein electrophoretic separation, selection, and digestion of a protein of interest for identification by mass spectrometry. The system includes eight integrated valves and one micropump dedicated to control the flow operations. Myoglobin was successfully isolated from bovine serum albumin (BSA), then selected using integrated valves and digested in a rotary micromixer. Proteolytic peptides were recovered from the micromixer for protein identification. Total analysis from sample injection to protein identification is performed under 30 minutes, with samples of tens of nanolitres. The paper shows that PDMS technology can be successfully used for integrating complex preparation protocols of proteic samples prior to MS analysis.     

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.     

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.     

On-chip pressure injection for integration of infrared-mediated DNA amplification with electrophoretic separation

Poly(dimethylsiloxane) (PDMS) membrane valves were utilized for diaphragm pumping on a PDMS-glass hybrid microdevice in order to couple infrared-mediated DNA amplification with electrophoretic separation of the products in a single device. Specific amplification products created during non-contact, infrared (IR) mediated polymerase chain reaction (PCR) were injected via chip-based diaphragm pumping into an electrophoretic separation channel. Channel dimensions were designed for injection plug shaping via preferential flow paths, which aided in minimizing the plug widths. Unbiased injection of sample could be achieved in as little as 190 ms, decreasing the time required with electrokinetic injection by two orders of magnitude. Additionally, sample stacking was promoted using laminar or biased-laminar loading to co-inject either water or low ionic strength DNA marker solution along with the PCR-amplified sample. Complete baseline resolution (Res = 2.11) of the 80- and 102-bp fragments of pUC-18 DNA marker solution was achieved, with partially resolved 257- and 267-bp fragments (Res = 0.56), in a separation channel having an effective length of only 3.0 cm. This resolution was deemed adequate for many PCR amplicon separations, with the added advantage of short separation time-typically complete in <120 s. Decreasing the amount of glass surrounding the PCR chamber reduced the DNA amplification time, yielding a further enhancement in analysis speed, with heating and cooling rates as high as 13.4 and -6.4 degrees C s(-1), respectively. With the time requirements greatly reduced for each step, it was possible to seamlessly couple IR-mediated amplification, sample injection, and separation/detection of a 278-bp fragment from the invA gene of <1000 starting copies of Salmonella typhimurium DNA in approximately 12 min on a single device, representing the fastest PCR-ME integration achieved to date.     

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).     

Glass/SU‐8 microchip for electrokinetic applications

In this communication, we describe the fabrication and electric characterization of a hybrid glass/SU‐8 microchannels for high‐performance electrokinetic applications. The bonding process employed SU‐8 film as intermediate layer with reduced baking times; all the procedure took less than 50 min (only about 10 min disregarding the cleaning and dehydration steps). Additionally, further steps to improve the adhesion of the substrate to the SU‐8 were not needed. The developed configuration aggregates the advantages of both substrates, including (i) simple fabrication techniques; (ii) high compatibility for integration of microelectromechanical, optical, and electrochemical components (SU‐8); (iii) high and stable electroosmotic mobility (μ_EO); and (iv) satisfactory heat dissipation capacity (glass). Electroosmotic mobilities were measured as a function of the pH using the current monitoring method, whereas the heat dissipation capacity was investigated through Ohm's law plots for both glass and glass/SU‐8 microchips. The measured μ_EO values were similar for both microdevices, with mobilities of the order of 4.0–4.5 × 10^?4 cm² V^?1 cm^?1 at 4–12 pH range using phosphate buffer (10 and 20 mmol/L). The heat dissipation assays were carried out in microchannels filled with 20 mmol/L phosphate buffer. A considerable Joule heating was observed only at electric field strengths greater than 580 V cm^?1 in hybrid glass/SU‐8 microdevices, representing a substantial increase of 48% when compared to all SU‐8 microdevices.     

Chemically resistant microfluidic valves from Viton® membranes bonded to COC and PMMA

We present a reliable technique for irreversibly bonding chemically inert Viton? membranes to PMMA and COC substrates to produce microfluidic devices with integrated elastomeric structures. Viton? is widely used in commercially available valves and has several advantages when compared to other elastomeric membranes currently utilised in microfluidic valves (e.g. PDMS), such as high solvent resistance, low porosity and high temperature tolerance. The bond strength was sufficient to withstand a fluid pressure of 400 kPa (PMMA/Viton?) and 310 kPa (COC/Viton?) before leakage or burst failure, which is sufficient for most microfluidic applications. We demonstrate and characterise on-chip pneumatic Viton? microvalves on PMMA and COC substrates. We also provide a detailed method for bonding fluorinated Viton? elastomer, a highly chemically compatible material, to PMMA and COC polymers. This allows the production of microfluidic devices able to handle a wide range of chemically harsh fluids and broadens the scope of the microfluidic platform concept.     

An integrated AC electrokinetic pump in a microfluidic loop for fast and tunable flow control

We have built a dedicated lab on a chip to study the performance of an integrated electrokinetic micropump, driven by a low voltage AC signal. This micropump consists of an array of interdigitated electrodes and is here integrated in a microfluidic loop. We demonstrate that this device can pump continuously and reproducibly electrolyte solutions of low to moderate ionic strength. The pumping speed reaches up to 500 [micro sign]m s(-1) in 20 [micro sign]m deep and 100 [micro sign]m wide channels with a driving signal in the 1-10 kHz range and an amplitude of only a few volts. In addition, we have observed an interesting reversal of the pumping direction at higher frequencies (50-100 kHz). Our device permits a systematic and automated exploration of the influence of the ionic strength thanks to an integrated micromixer.     

Expandable microspheres for the handling of liquids

Two novel concepts for controlled handling of liquids in microfluidic systems are presented: a one-shot micropump and a normally open one-shot valve based on thermo-expanding Expancel microspheres. Expancel microspheres are small spherical plastic particles that, when heated, increase their volume considerably. We show that liquid volumes in the nanoliter range can be actuated against a counter pressure of at least 100 kPa and fluid flow can be inhibited in a microchannel against pressures of at least 100 kPa.