Fluidic interconnections for microfluidic systems: A new integrated fluidic interconnection allowing plug‘n’play functionality

A crucial challenge in packaging of microsystems is microfluidic interconnections. These have to seal the ports of the system, and have to provide the appropriate interface to other devices or the external environment.

Integrated fluidic interconnections appear to be a good solution for interconnecting polymer microsystems in terms of cost, space and performance. Following this path we propose a new reversible, integrated fluidic interconnection composed of custom-made cylindrical rings integrated in a polymer house next to the fluidic network. This allows plug‘n’play functionality between external metal ferrules and the system.

Theoretical calculations are made to dimension and model the integrated fluidic interconnection.

Leakage tests are performed on the interconnections, in order to experimentally confirm the model, and detect its limits.     

Monolithic fabrication of electro-fluidic polymer microchips

Integration of electronic wiring with microfluidic chips is an important process as it allows electrical interactions with the fluidic media, for example required for resistive and capacitive sensing. It is also necessary in order to implement various actuation and control mechanisms such as pumping, electrophoresis and temperature control. Typically electrical wire traces are added to microfabricated fluidic chips using metal deposition processes that are carried out after the fluidic chip has been fabricated. The process for adding the wiring is complicated and is limited to select metals that can be deposited by evaporation or sputtering. We present a single step method for integrating electrical wires into polymer microfluidic chips that are fabricated by a hot embossing process. This process can flexibly embed any kind of commercially available metal wire with a microfluidic chip and the wiring may be integrated to come into surface contact with the fluid or may be embedded in close proximity to (but insulated from)the fluid paths for example for local heating purposes. This method significantly reduces total processing time and is thus a valuable method for wire integration into polymer chips. We demonstrate two applications—a microelectrolysis chip and a heater chip that were fabricated using this methodology. The design, fabrication process and the initial test results are presented.     

Characterization of a multi-chip microelectrofluidic bench for modular fluidic and electric interconnections

We present the design, fabrication, and characterization of a multi-chip microelectrofluidic bench, achieving both fluidic and electric interconnections with simple and low pressure-loss interconnections. The microelectrofluidic bench provides easy alignment of fluidic interconnection using microfabricated annular fluidic connectors; also provides simple electric interconnection using isotropic conductive adhesives at room temperature. Thus, the present microelectrofluidic bench provides a modular concept for fluidic and electric interconnection. In experimental study, we characterize pressure losses, electric resistances loss, and pressure stability of the interconnection. The average pressure drop per each fluidic contact is measured 0.12 ± 0.19 kPa at the DI water flow rate from 10 to 100 μl min⁻¹. The electric resistance per each electric contact is measured as 0.64 ± 0.29 Ω. The fluidic interconnection endures maximum pressure of 115 ± 11 kPa. The present microelectrofluidic bench, therefore, offers a simple and low pressure-loss electrofluidic modular interconnection for electrofluidic multi-chip microsystems.     

Optimized design and fabrication of a microfluidic platform to study single cells and multicellular aggregates in 3D

A microfluidic platform for cell motility analysis in a three-dimensional environment is presented. The microfluidic device is designed to study migration of both single cells and cell spheroids, in particular under spatially and temporally controlled chemical stimuli. A layout based on a central microchannel confined by micropillars and two lateral reservoirs was selected as the most effective. The microfluidics have an internal height of 350 μm to accommodate cell spheroids of a considerable size. The chip is fabricated using well-established micromachining techniques, by obtaining the polydimethylsiloxane replica from a Si/SU-8 master. The chip is then bonded on a 170-μm-thick microscope glass slide to allow high spatial resolution live microscopy. In order to allow the cost-effective and highly repeatable production of chips with high aspect ratio (5:1) micropillars, specific design and fabrication processes were optimized. This design permits spatial confinement of the gel where cells are grown, the creation of a stable gel–liquid interface and the formation of a diffusive gradient of a chemoattractant (>48 h). The chip accomplishes both the tasks of a microfluidic bioreactor system and a cell analysis platform avoiding critical handling of the sample. The experimental fluidic tests confirm the easy handling of the chip and in particular the effectiveness of the micropillars to separate the Matrigel? from the culture media. Experimental tests of (i) the stability of the gradient, (ii) the biocompatibility and (iii) the suitability for microscopy are presented.     

Microfluidic integrated circuits for signal processing using analogous relationship between pneumatic microvalve and MOSFET

In this paper, a new concept and potential demonstration of functional microfluidic integrated circuits using MEMS technology are presented. The fluidic integrated circuits were constructed utilizing analogous relationship between MOSFET and pneumatic microvalve with a diaphragm structure. The signal transmitted through the circuit is the fluidic signal, that is, the pressure or the flow-rate of the fluid. The pneumatic microvalve in this study is expressed by small-signal equivalent model similar to that of a MOSFET. Small signal behavior of microfluidic integrated circuits can be expected using the model, if the parameters in the model are extracted properly from fabricated microvalves. As an example of a fluidic circuit, pressure inverting amplifiers including integrated two microvalves were fabricated and evaluated. As a result, they showed sharp pressure transfer curves similar to MOS inverter circuits. A maximum pressure gain of 32.0 dB was obtained, and it can be used for pressure amplification in analog applications. In addition, they can be used as pressure inverter logic circuits for digital applications. Although the theory and design environment of the new microvalve circuit technology have not been established yet, multifunctional fluidic analog and digital circuits can be realized for special application fields different from electronic integrated circuits.     

High aspect ratio tapered hollow metallic microneedle arrays with microfluidic interconnector

We present a novel microfabrication method for a tapered hollow metallic microneedle array and its complete microfluidic packaging for drug delivery and body fluid sampling applications. Backside exposure of SU-8 through a UV transparent substrate was investigated as a means of fabricating a dense array of tall (up to 400 μm) uniformly tapered SU-8 pillar structures with angles in the range of 3.1–5° on top of the SU-8 mesa. Conformal electroplating of metals on top of the array of the tapered SU-8 pillars, lapping of the tip of the metallic microneedles with planarizing polymer, and removal of the SU-8 sacrificial layers resulted in an array of tapered hollow metallic microneedles with a fluidic reservoir on the backside. A microfluidic interconnector assembly was designed and fabricated using SU-8 and conventionally machined PMMA in a way that it has a male interconnector, which directly fits into the fluidic reservoir of the microneedle array at one end and the other male interconnector, which provides fluidic interconnection to external devices at the other end. The fluid flow rate was measured and it showed 0.69 μL/s. per microneedle when the pressure of 6.89 KPa (1 psi) was applied.     

Pneumatically bidirectional microfluidic regulation using Venturi pumps by deep RIE and bonding technology

 A novel design for bidirectional fluidic motion has been demonstrated which is widely used in the biochip or microfluidic component. Two miniaturized Venturi pumps as well as pneumatic servo system are designed to easily control the bidirectional fluidic motion by simple fabrication. The pumping velocity is 0.86 μl/min at a 2.75 slpm (standard liter per minute) air flow read from mass flow controller (MFC) for totally 4.3 μl blue ink in a 300 μm wide by 300 μm deep channel. The higher airflow, the faster fluidic pumping speed. Numerical simulation is performed to correlate the experimental data of fluidic speed and air flow in microchannel. The test chip with two Venturi pumps and channel was batchedly fabricated by silicon deep reactive ion etching (RIE) and glass anodic bonding. The ICP LIGA process is also investigated after deep RIE followed the electroforming and hot embossing. Received: 10 August 2001/Accepted: 24 September 2001     

Computational and performance analysis of a continuous magnetophoretic bioseparation chip with alternating magnetic fields

This paper presents the modeling and optimization of a magnetophoretic bioseparation chip for isolating cells, such as circulating tumor cells from the peripheral blood. The chip consists of a continuous-flow microfluidic platform that contains locally engineered magnetic field gradients. The high-gradient magnetic field produced by the magnets is spatially non-uniform and gives rise to an attractive force on magnetic particles flowing through a fluidic channel. Simulations of the particle–fluid transport and the magnetic force are performed to predict the trajectories and capture lengths of the particles within the fluidic channel. The computational model takes into account key forces, such as the magnetic and fluidic forces and their effect on design parameters for an effective separation. The results show that the microfluidic device has the capability of separating various cells from their native environment. An experimental study is also conducted to verify and validate the simulation results. Finally, to improve the performance of the separation device, a parametric study is performed to investigate the effects of the magnetic bead size, cell size, number of beads per cell, and flow rate on the cell separation performance.     

Digital microfluidic design and optimization of classic and new fluidic functions for lab on a chip systems

This paper deals with microfluidic studies for lab-on-a-chip development. The first goal was to develop microsystems immediately usable by biologists for complex protocol integrations. All fluid operations are performed on nano-liter droplet independently handled solely by electrowetting on dielectric (EWOD) actuation. A bottom-up architecture was used for chip design due to the development and validation of elementary fluidic designs, which are then assembled. This approach speeds up development and industrialization while minimizing the effort in designing and simplifying chip-fluidic programming. Dispensing reproducibility for 64 nl droplets obtained a CV below 3% and mixing time was only a few seconds. Ease of the integration was demonstrated by performing on chip serial dilutions of 2.8-folds, four times. The second part of this paper concerns the development of new innovative fluidic functions in order to extend EWOD-actuated digital fluidics’ capabilities. Experiments of particle dispensing by EWOD droplet handling are reported. Finally, work is shown concerning the coupling of EWOD actuation and magnetic fields for magnetic bead manipulation.     

A method of water pretreatment to improve the thermal bonding rate of PMMA microfluidic chip

A new method of water pretreatment for thermal bonding polymethylmethacrylate microfluidic chip was proposed in this paper. The bonding rate (effective bonding area) of microfluidic chip under different pretreatment time was studied and the mechanism of this method was discussed. The main thermal bonding parameters were as follows: bonding pressure 1.4 ~ 1.9 Mpa, temperature 91 ~ 93°C, time 360 s. The experimental result shows that this method can increase the effective bonding area, improve the bonding quality of the microfluidic chip compared to the conventional thermal bonding method. The optimal water pretreatment time is 1 h with the bonding rate increased by 34% compared with the conventional thermal bonding method. The pollution to the micro-channels is avoided and the performance of the microfluidic system will be reserved with this water pretreatment method. This method is available for the biochemical analysis of the chip, and holds the benefits of easy-operation, high-efficiency and low-cost properties.     

A Microfabricated Nebulizer for Liquid Vaporization in Chemical Analysis

A miniaturized nebulizer chip for vaporization of liquid samples for mass spectrometry has been designed, fabricated, and characterized for fluidic and thermal performance. Silicon/glass chip has a liquid sample channel placed centrally between symmetric nebulizer gas channels. The liquid sample is nebulized and vaporised by an integrated platinum heater. The vaporized sample exits through an etched nozzle, and is ionized by an external corona needle. The ions are analysed by a mass spectrometer. The chip has been fabricated in both anisotropically wet etched and DRIE versions in silicon, with an anodically bonded Pyrex glass cover plate. Three different fluidic inlet designs are presented, with both through-wafer and edge insert versions. The shape of the erupting gas jet has been visualized by infrared thermography by using a low-diffusivity imaging screen and high heat capacity helium as a test gas. Dimensions of the jet's thermal footprint on the screen show that the jet is very narrow and confined, and this is confirmed in mass spectrometry results. This confined jet supplies the sample to the ionization region near corona tip, enabling efficient use of very small sample amounts and submicroliter flows.1591     

3D-printed membrane microvalves and microdecoder

A microfluidic system for multichannel switching and multiphase flow control has potential uses in pneumatic soft robotics and biological sampling systems. At present, the membrane microvalves used in microfluidic systems are mostly constructed using a multilayer bonding process so that the device cannot withstand high pressures. In this paper, we demonstrate a design method and the properties of a bondless membrane microvalve fabricated using a commercial 3D printer. We used a multijet (MJP) 3D printer to print a 100-μm-thick and 6-mm-diameter membrane from a relatively hard material (1700 MPa). The membrane’s high toughness ensures that it does not need negative pressure to reopen. The measured operation frequency was less than 2.5 Hz under a pneumatic pressure of 14.5 kPa. We also 3D-printed an integrated Quake-style microfluidic decoder network by combining 8 valves in series to demonstrate the integrability of the microvalve. The decoder chip was demonstrated to control the ON/OFF state of the four coded fluidic channels, with the droplets being generated from selected channels according to the valve action. Therefore, such 3D-printed microvalves are highly integrable, have a high manufacturing efficiency, and can be applied in pneumatic controllers, sample switchers and integrated print heads.

     

Automating fluid delivery in a capillary microfluidic device using low-voltage electrowetting valves

A multilayer capillary polymeric microfluidic device integrated with three normally closed electrowetting valves for timed fluidic delivery was developed. The microfluidic channel consisted two flexible layers of poly (ethylene terephthalate) bonded by a pressure-sensitive adhesive spacer tape. Channels were patterned in the spacer tape using laser ablation. Each valve contained two inkjet-printed silver electrodes in series. Capillary flow within the microchannel was stopped at the second electrode which was modified with a hydrophobic monolayer (valve closed). When a potential was applied across the electrodes, the hydrophobic monolayer became hydrophilic and allowed flow to continue (valve opened). The relationship between the actuation voltage, the actuation time, and the distance between two electrodes was performed using a microfluidic chip containing a single microchannel design. The results showed that a low voltage (4.5 V) was able to open the valve within 1 s when the distance between two electrodes was 1 mm. Increased voltages were needed to open the valves when the distance between two electrodes was increased. Additionally, the actuation time required to open the valve increased when voltage was decreased. A multichannel device was fabricated to demonstrate timed fluid delivery between three solutions. Our electrowetting valve system was fabricated using low-cost materials and techniques, can be actuated by a battery, and can be integrated into portable microfluidic devices suitable for point-of-care analysis in resource-limited settings.     

Fabrication techniques to realize CMOS-compatible microfluidicmicrochannels

With microfluidic systems becoming more prominent, fabrication techniques for microfluidic systems are increasingly more important. An interesting alternative to existing fabrication techniques is to embed fluidic systems within an integrated circuit by micromachining materials in the integrated circuit itself. This paper describes novel methods for fabricating one component in the complementary metal-oxide-semiconductor (CMOS) microfluidic system, the microchannel. These techniques allow direct integration of sensors, actuators, or other electronics with the microchannel. This method expands the functional applications for microfluidic systems beyond their current abilities. By utilizing the methods described within this paper, a complete “smart” microfluidic system could be batch fabricated on a single integrated circuit (IC) chip     

Design and fabrication of a novel microfluidic nanoprobe

The design and fabrication of a novel microfluidic nanoprobe system are presented. The nanoprobe consists of cantilevered ultrasharp volcano-like tips, with microfluidic capabilities consisting of microchannels connected to an on-chip reservoir. The chip possesses additional connection capabilities to a remote reservoir. The fabrication uses standard surface micromachining techniques and materials. Bulk micromachining is employed for chip release. The microchannels are fabricated in silicon nitride by a new methodology, based on edge underetching of a sacrificial layer, bird's beak oxidation for mechanically closing the edges, and deposition of a sealing layer. The design and integration of various elements of the system and their fabrication are discussed. The system is conceived mainly to work as a "nanofountain pen", i.e., a continuously writing upgrade of the dip-pen nanolithography approach. Moreover, the new chip shows a much larger applicability area in fields such as electrochemical nanoprobes, nanoprobe-based etching, build-up tools for nanofabrication, or a probe for materials interactive analysis. Preliminary tests for writing and imaging with the new device were performed. These tests illustrate the capabilities of the new device and demonstrate possible directions for improvement.     

Pressure-resistant and reversible on-tube-sealing for microfluidics

We present the design, manufacturing, and characterization of a novel miniaturized on-tube-seal configuration for microfluidic devices. The seal is based on a previously developed world-to-chip spring-based interface by Kortmann et al. (Lab Chip 9:1455–1460, 2009a), which enables rapid and reliable microfluidic connections. In this study, the dead volumes, the contact pressure, the discontinuous fluidic-profile transmission, and the space requirements were significantly optimized by a new on-tube-seal configuration. Maintaining the advantages of the previously described interface, the new on-tube-seal configuration has a dead volume of only 18 nl, withstands pressures higher than 2,800 kPa with only 3.8 N applied contact force, and allows continuous capillary to chip fluidic profile transmission. The on-tube-seal configuration consists of a miniaturized o-ring (0.5 × 0.3 mm) integrated into a 1/16″ tubing that reduces space requirements to a minimal sealing grid of 1.59 mm and is easily adaptable to any planar channel opening of micro fluidic devices. In summary, we present a novel combination of gasket and tubing, which we termed on-tube-seal that allows simple, rapid, and reliable world-to-chip sealing.     

Passive microfluidic gas valves using capillary pressure

In this study, we developed micro gas valves which can control the gas pressure inside microfluidic systems in a simple and passive way. We designed a microfluidic chip having a liquid reservoir, a gas chamber and a microchannel connecting them to demonstrate both a micro relief valve and a micro regulator on a chip. We fabricated and tested the microfluidic chip to check the feasibility of the proposed micro valves. Test results show that when the gas pressure is greater than the relief pressure the micro relief valve discharges the gas decreasing the system pressure down to the atmospheric pressure. Also, the micro regulator kept the system pressure constant regardless of the degree of the over-pressure at pressure source. The proposed valves would be good candidates for cheap and reliable gas pressure controller in various microfluidic systems using gases.     

On-Line Testing of Lab-on-Chip Using Reconfigurable Digital-Microfluidic Compactors

Dependability is an important system attribute for microfluidic lab-on-chip devices. On-line testing offers a promising method for detecting defects, fluidic abnormalities, and bioassay malfunctions during chip operation. However, previous techniques for reading test outcomes and analyzing pulse sequences are cumbersome, sensitive to the calibration of capacitive sensors, and error-prone. We present a built-in self-test (BIST) method for on-line testing of digital microfluidic lab-on-chip. This method utilizes microfluidic compactors based on droplet-based AND gates, which are implemented using digital microfluidics. An optimization method is proposed to schedule logic AND operations in the compactor to minimize the end time for the compaction procedure. Dynamic reconfiguration of these compactors ensures low area overhead and it allows BIST to be interleaved with bioassays in functional mode. We evaluate the on-line testing method using a multiplexed in vitro diagnostics bioassay.     

Non-destructive on-chip imaging flow cell-sorting system for on-chip cellomics

We have developed a non-destructive imaging flow cell-sorting system using an ultra-high-speed camera (shutter speed of 1/10,000 s) with a real-time image analysis unit and a poly(methyl methacrylate) (PMMA)-based disposable microfluidic chip for single-cell-based on-chip cellomics. It has a 3-D micropipetting device that supports fully automated sorting and collection of samples. The entire fluidic system is implemented in a disposable plastic chip, enabling biological samples to be lined up in a laminar flow using hydrodynamic focusing. Its optical system enables direct observation-based cell identification using specific image indexes and phase-contrast/fluorescence microscopy, real-time image processing. It has a non-destructive, wider dynamic range, sorting procedure using mild electrostatic force in a laminar flow; agarose gel electrodes are used to prevent electrode loss and electrolysis bubble formation. The microreservoir used for recultivating collected target cells is contamination-free. An integrated ultra-high-speed droplet polymerase chain reaction measurement module is used for DNA/mRNA analysis of the collected target cells. This system was used to separate cardiomyocyte cells from a mixture of various cells. All the operations were automated using the 3-D micropipetting device. The results demonstrate that this imaging flow cell-sorting system is practically applicable for biological research and clinical diagnosis.     

A highly reliable integrated PDMS interconnector with a long cast flange for microfluidic systems

This paper presents a highly reliable macro to micro domain interconnection technology for microfluidic applications using Polydimethylsiloxane (PDMS) casting techniques. Characteristic to the interconnectors are long flanges fabricated in the PDMS film; therefore the contact area between PDMS and tubes is considerably increased compared to other interconnection technologies. Thus, both glass capillaries and Polytetrafluoroethylene (PTFE) tubes can be held in position very reliably and rigidly. To test the reliability of the interconnectors, PTFE tubes were successfully connected to microfluidic chips without the aid of any liquid adhesives. Both leakage and pull-out tests demonstrated the functionality and reliability of the PDMS interconnectors; no leakage was detected under a working pressure up to 400?kPa. A pull-out test yielded a pull-out force of 22.45?N. Furthermore, once a casting mould is fabricated, it can be re-used as a template repeatedly achieving a low cost technology and making it suitable for batch production.