Fabrication of SU-8 photoresist micro–nanofluidic chips by thermal imprinting and thermal bonding

Micro–nanofluidic chips have been widely applied in biological and medical fields. In this paper, a simple and low-cost fabrication method for micro–nano fluidic chips is proposed. The nano-channels are fabricated by thermal nano-imprinting on an SU-8 photoresist layer followed by thermal bonding with a second SU-8 photoresist layer. The micro-channels are produced on the second layer by UV exposure and then thermal bonded by a third layer of SU-8 photoresist. The final micro–nano fluidic chip consists of micro-channels (width of 200.0 ± 0.1 μm and, depth of 8.0 ± 0.1 μm) connected by nano-channels (width of 533 ± 6 nm and, depth of 372 ± 6 nm), which has great potential in molecular filtering and detection.

     

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     

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.     

A single chip, double channel thermal flow meter

The fabrication and experimental characterization of a thermal flow meter, capable of detecting and measuring two independent gas flows with a single chip, is described. The innovative aspect of the sensor is the use of a plastic adapter, thermally sealed to the chip, to convey the gas flow only to the chip areas where the sensors are located. The packaging approach allowed placing two micrometric differential thermal anemometers, present on 4 × 4 mm² silicon chips, into distinct flow channels. The reduced spacing between the sensing structures required positioning of the latter on channel bends, introducing sensitivity reduction and response asymmetries with respect to single channel devices presented earlier. These effects are explained using fluid-dynamic simulations.     

An integrated flow-cell for full sample stream control

In this study, we present a novel three-dimensional hydrodynamic sheath flow chip that allows full control of a sample stream. The chip offers the possibility to steer each of the four side sheath flows individually. The design of the flow-cell exhibits high flexibility in creating different sample stream profiles (width and height) and allows navigation of the sample stream to every desired position inside the microchannel (vertical and horizontal). This can be used to bring the sample stream to a sensing area for analysis, or to an area of actuation (e.g. for cell sorting). In addition, we studied the creation of very small sample stream diameters. In microchannels (typically 25 × 40 μm2), we created sample stream diameters that were five to ten times smaller than the channel dimensions, and the smallest measured sample stream width was 1.5 μm. Typical flow rates are 0.5 μl/min for the sample flow and around 100 μl/min for the cumulated sheath flows. The planar microfabricated chip, consisting of a silicon–glass sandwich with an intermediate SU-8 layer, is much smaller (6 × 9 mm2) than the previously presented sheath flow devices, which makes it also cost-effective. We present the chip design, fluidic simulation results and experiments, where the size, shape and position of the sample stream have been established by laser scanning confocal microscopy and dye intensity analysis.     

Simple and low-cost fabrication of PDMS microfluidic round channels by surface-wetting parameters optimization

Convenient for both biologists and MEMS designers, Polydimethylsiloxane (PDMS) polymer is intensively investigated for its biocompatibility, transparency, high resistance under plasma treatment, flexibility and resistance to high temperature. However, for microfluidic applications, the fabrication of PDMS circular channels is difficult to achieve except by wire moulding. In this article, we present a simple, fast and low-cost fabrication method which can be applied out of clean-room environment. It is based on the deposition of alginic acid sodium salt aqueous solution, enabling the formation of a liquid cylinder on the most hydrophilic part of a hydrophilic/hydrophobic patterned surface. We experimentally studied the interaction between liquid rivulets and surfaces presenting a contrast of wettability and/or a stepwise texture. Subsequent moulding of the half-cylinder of liquid produces round PDMS microfluidic channels. The optimal parameters for hydrophilic/hydrophobic patterns have then been applied to produce the roundest possible channels. The realisation of both straight channels 300–500 μm wide, 1 cm long and 75° tangent chord angle at best, and Y-shaped channels with the same dimensions and 55° TCA is demonstrated.     

Pre-programmable polymer transformers as on-chip microfluidic vacuum generators

This paper develops novel polymer transformers using thermally actuated shape memory polymer (SMP) materials. This paper applies SMPs with thermally induced shape memory effect to the proposed novel polymer transformers as on-chip microfluidic vacuum generators. In this type of SMPs, the morphology of the materials changes when the temperature of materials reaches its glass transition temperature (T _g). The structure of the polymer transformer can be pre-programmed to define its functions, which the structure is reset to the temporary shape, using shape memory effects. When subjected to heat, the polymer transformer returns to its pre-memory morphology. The morphological change can produce a vacuum generation function in microfluidic channels. Vacuum pressure is generated to suck liquids into the microfluidic chip from fluidic inlets and drive liquids in the microchannel due to the morphological change of the polymer transformer. This study adopts a new smart polymer with high shape memory effects to achieve fluid movement using an on-chip vacuum generation source. Experimental measurements show that the polymer transformer, which uses SMP with a T _g of 40°C, can deform 310 μm (recover to the permanent shape from the temporary shape) within 40 s at 65°C. The polymer transformer with an effective cavity volume of 155 μl achieved negative pressures of −0.98 psi. The maximum negative up to −1.8 psi can be achieved with an effective cavity volume of 268 μl. A maximum flow rate of 24 μl/min was produced in the microfluidic chip with a 180 mm long channel using this technique. The response times of the polymer transformers presented here are within 36 s for driving liquids to the end of the detection chamber. The proposed design has the advantages of compact size, ease of fabrication and integration, ease of actuation, and on-demand negative pressure generation. Thus, this design is suitable for disposable biochips that need two liquid samples control. The polymer transformer presented in this study is applicable to numerous disposable microfluidic biochips.     

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.     

An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination

Clinical diagnostics and genomic research often require performing numerous genetic tests. While microfluidic devices provide a low-cost alternative to such demands, integrated microfluidic devices are fabricated using expensive technology not always affordable for single use. However, carryover cross-contamination (CXC) concerns (i.e. either false positive or false negative PCR data) in PCR chips prevent reuse, defying much of the advantages of miniaturized systems developed using expensive MEMS processing. In this work, we present an integrated and reusable PCR–CE glass microfluidic chip capable of multi-chamber PCR and sequential CE, with emphasis on a unique chip reusability approach to avoid CXC. For reliable PCR, the surface of the chamber is re-configured from its virgin hydrophilic (CA < 20°) to hydrophobic (CA > 110°) by silanization. To then extend this silanization method as a chip reusability technique, the silanization coating is ‘stripped and re-silanized’ (SRS) to create a fresh coating prior to each successive PCR run. Experimental confirmation of the effectiveness of SRS method in avoiding the CXC is demonstrated using plasmid DNA and HIV-1 infected DNA samples. We also present passive plug microvalves incorporated in the chip to enable fluid/vapor retention during the PCR and controlled fluid flow from the PCR chamber to the CE section for further analysis.     

Symmetric surficial phaseguides: a passive technology to generate wall-less channels by two-dimensional guiding elements

We present the usage of the symmetrical surficial phaseguides to generate wall-less channels. Wall-less channels are microfluidic channels which contain one or two interfaces with air. The technology is based on the symmetric combination of hydrophilic and hydrophobic surfaces inside the chip both on the top and bottom plate. The hydrophilic surfaces enable liquid propagation because of the capillary effect, while the hydrophobic surfaces are used as phaseguides where the capillary force prevents liquid propagation. The symmetric pattern of phaseguides on top and on bottom of the chip results in a robust guiding of the liquid and thus stable liquid–gas interfaces at the transition from the hydrophilic plate and the hydrophobic phaseguide. In order to apply this technology in various applications, design rules based on analytical derivations are presented and verified by experiments. These rules describe all elements of common channels like corners and intersections as well as design parameters like the channel width and the horizontal misalignment tolerances of the phaseguides. Finally, the technology is applied exemplary to create well-defined hydrogel membranes and to pump liquid through a channel. The main advantages of the technology are the stability of the channel, the large liquid–air interface area, the straight and vertical interface and the easy fabrication method.     

Silicon–glass instrumented solid-phase extraction–zone electrophoresis microchip with thin amorphous silicon film electrodes: performance in immunoaffinity analysis

Silicon–glass microchips were designed and fabricated for on-chip solid phase extraction (SPE) and zone electrophoresis studies. The solvent channels for extraction and the separation channels for analyses were fabricated sequentially on the silicon device. Electrical contacts were integrated in a fused silica glass lid. Amorphous silicon thin film electrodes were fabricated for high voltage and conductivity detection. A chip installation rack with electrical and fluidic contacts was constructed to facilitate the experiments. Simulation was used to elucidate both the liquid flow and the electric field distribution. The operational performance of the microchips was demonstrated by using a fluorescein isothiocyanate (FITC)-labelled testosterone derivative as the model analyte and fluorescein as both the negative control and the calibration compounds. In SPE an immunosorbent, based on recombinant anti-testosterone Fab-fragments, was immobilized to activated Sepharose gel. Simultaneous monitoring of the movement of FITC-testosterone from SPE cavity through the channel to the detection point was performed with a laser-induced fluorescence detector. The observed limit of detection for FITC-testosterone was 2 μM.     

SAW nanopump for handling droplets in view of biological applications

This paper reports on the fabrication and development of a surface acoustic waves (SAW) platform dedicated to digital micro fluidics for biological applications. SAW at about 20 MHz are generated by InterDigital Transducers (IDT) laid on a LiNbO₃ piezoelectric substrate. An electrical characterization of the IDT is reported and first results related to droplet handling with the SAW platform are given. We show that accurate droplet displacement is the result of both a radio frequency (RF) pulsed excitation and a chemical pre-treatment of the platform surface. For biological applications the droplet carrying the biomaterial is squeezed between the platform and a cover to increase the surface exchange between the droplet and hydrophilic functionalized areas. Out of such areas the free displacement is significantly improved by a surface hydrophobic pre-treatment. Moreover, the fabrication of additional hydrophilic micro tracks is shown to be a solution for crossing these areas without droplet splitting. This result is a key point to validate the structure of the novel micro fluidic platform proposed in this paper.     

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.     

Influence of tool fabrication process on characteristics of hot embossed polymer microfluidic chips for electrospray

Fabrication techniques for mass manufacture of disposable polymer microfluidic chips are important for electrospray application used in mass spectrometry. Hot embossing offers advantages over traditional MEMS fabrication techniques and is the focus of this research. The aim of the paper is to evaluate hot embossed open channel polymer chips using two different hot embossing tools. One tool was fabricated in nickel using the electroforming process, and the other in high carbon bright steel by laser machining technique using a pulsed Nd:YAG laser that is normally used for conventional applications. Process parameters are determined and measurement of dimensions and surface roughness of tools and chips are presented. Depending on the fabrication method, each tool exhibits its own characteristic profile feature and surface roughness. Polystyrene and polycarbonate substrates embossed with the electroformed tool exhibited lowest surface roughness of 48 nm compared to 450 nm for the laser machined tool. The embossed microfluidic chips were tested for fluid flow and electrospray and showed good performance.     

Experimental and computational study of gas bubble removal in a microfluidic system using nanofibrous membranes

This paper presents a simple and efficient method for removing gas bubbles from a microfluidic system. This bubble removal system uses a T-junction configuration to generate gas bubbles within a water-filled microchannel. The generated bubbles are then transported to a bubble removal region and vented through a hydrophobic nanofibrous membrane. Four different hydrophobic Polytetrafluorethylene membranes with different pore sizes ranging from 0.45 to 3 μm are tested to study the effect of membrane structure on the system performance. The fluidic channel width is 500 μm and channel height ranges from 100 to 300 μm. Additionally, a 3D computational fluid dynamics model is developed to simulate the bubble generation and its removal from a microfluidic system. Computational results are found to be in a good agreement with the experimental data. The effects of various geometrical and flow parameters on bubble removal capability of the system are studied. Furthermore, gas–liquid two-phase flow behaviors for both the complete and partial bubble removal cases are thoroughly investigated. The results indicate that the gas bubble removal rate increases with increasing the pore size and channel height but decreases with increasing the liquid flow rate.

     

Critical pressure for capillary valves in a Lab-on-a-Disk: CFD and flow visualization

Capillary valves are used as pressure barriers to control flow sequencing in microfluidic devices. Influence of valves height on liquid flow pattern and critical pressure are studied through flow visualization and CFD predictions (Gambit® 2.2.30 and FLUENT® 6.2.16). Both hydrophilic and hydrophobic walls are studied. Results show that the surface tension plays a major role in the liquid progress through the microchannel/valve and also in the valve filling process. Critical pressure varies linearly with the valve hydraulic diameter in the range 0.91 < D_h < 3.5 [mm] according to: P = 14.14 · D_h + 47.42 [Pa].     

Blood flow driven by surface tension in a microchannel

This study aims to identify distinct blood flow characteristics in a microchannel at different sloping angles. The channel is determined by a bottom hydrophilic stripe on a glass substrate and a fully covered hydrophobic glass substrate. The channel has a height of 3 μm, and a width of 100 μm. It is observed that increasing the sloping angle from −90° (downward flow) to 90° (upward flow) increases the blood flow rate monotonically. These peculiar behaviors on the micro scale are explained by a dynamic model that establishes the balance among the inertial, surface tension, gravitational, and frictional forces. The frictional force is further related to the effective hematocrit. The model is used to calculate the frictional force, and thus the corresponding hematocrit, which is smaller when the blood flows upward, reducing the frictional force.     

新型快速准分子激光微加工方法制备毛细管电泳芯片的研究

选用聚合材料聚甲基丙烯酸甲酯(PMMA)代替玻璃,石英等作为毛细管电泳芯片的基片材料.在19 kV,5 Hz及5mm/min的加工参数下,采用新型快速准分子激光微加工方法完成了毛细管电泳芯片的制备.实验结果表明该方法加工过程简单,耗时短,自动化程度高,有效提高了芯片成品率和加工质量.芯片与相同尺寸的盖片在105℃、160 N、恒温20 min条件下通过热压键合在一起,得到密闭性好的整体芯片.最后在芯片上应用激光诱导荧光检测法对Cy5染料完成了分离检测,获得了重复性很好的检测信息.     

Simulation and experiment research on vaporizing liquid micro-thruster

In the present work, a micro-thruster chip with dimension of 19.5 mm × 9.5 mm was fabricated with MEMS technologies for the experiment study of vaporizing liquid micro-thruster. In addition, a full 3D computational model was constructed to simulate the aft section of a vaporizing liquid micro-thruster for investigating flow characteristics. The results show that there were four distinct flow patterns observed in this study including snake flow, vapor-droplet flow, vapor-droplet-jet flow, and vapor flow. To prevent the failure of micro-thruster chip from generating of snake flow, the heating treatment of an empty micro-thruster chip at 300 °C for 2 h was the key factor. The generation of vapor flow preliminarily proved that the concept of vaporizing liquid micro-thruster chip was feasible. Furthermore, the numerical model in this study successfully provided the thrust estimation. The channel cross-section of 1 mm × 100 μm designed in this study was fit for developing a micro-thruster of O(mN) (ranging from 1 to 6 mN approximately). The numerical simulation could match better with the experiment results for the vapor flow cases if the flow oscillation was taken into consideration, and the heating channel of micro-thruster was lengthened to completely vaporize the liquid water.     

基于单片机的新型热量表

本文用超声波在流动液体中顺流与逆流的时间差来测量流速,测量芯片采用TDC-GPS,控制器采用MSP430。此热量表可避免传统热量表的阻塞问题,实现了与无线抄表系统相结合,可在无人监管情况下实现对用户供热信息的监控。