The effect of injection molding PMMA microfluidic chips thickness uniformity on the thermal bonding ratio of chips

Injection molding PMMA microfluidic chips can significantly improve the efficiency of chips forming. However, due to the coexistence of macro and micro effects in the injection molding process, the thickness uniformity of molding substrates is poor, which will seriously affect the thermal bonding quality of chips. In this paper, the effect of injection molding PMMA microfluidic chips thickness uniformity on the thermal bonding ratio and the quality of micro-channels was studied by experiments and simulations. The results show that when the following three conditions were satisfied during injection molding process, chips bonding ratio reaches to 93.9?% and the distortions of micro-channels caused by thermal bonding were acceptable. Firstly, the cover plates flatness error is smaller than 50–60?μm and substrates flatness error is smaller than 80–90?μm. Secondly, the maximum thickness difference of stack chips (cover plate stack with substrate) is smaller than 70–80?μm. Thirdly, chips thickness of the middle is larger than that of the two ends along their length direction and chips thickness distribute evenly along their width direction. These conclusions can be used for the parameters selection and moulds design during injection molding process of PMMA microfluidic chips.     

Laser polishing and 2PP structuring of inside microfluidic channels in fused silica

This study presents the development of post-processing steps for microfluidics fabricated with selective laser etching (SLE) in fused silica. In a first step, the SLE surface—even inner walls of microfluidic channels—can be smoothed by laser polishing. In addition, two-photon polymerization (2PP) can be used to manufacture polymer microstructures and microcomponents inside the microfluidic channels. The reduction in the surface roughness by laser polishing is a remelting process. While heating the glass surface above softening temperature, laser radiation relocates material thanks to the surface tension. With laser polishing, the RMS roughness of SLE surfaces can be reduced from 12 µm down to 3 nm for spatial wavelength λ < 400 µm. Thanks to the laser polishing, fluidic processes as well as particles in microchannels can be observed with microscopy. A manufactured microfluidic demonstrates that SLE and laser polishing can be combined successfully. By developing two-photon polymerization (2PP) processing in microchannels we aim to enable new applications with sophisticated 3D structures inside the microchannel. With 2PP, lenses with a diameter of 50 µm are processed with a form accuracy rms of 70 nm. In addition, this study demonstrates that 3D structures can be fabricated inside the microchannels manufactured with SLE. Thanks to the combination of SLE, laser polishing and 2PP, research is pioneering new applications for microfluidics made of fused silica.     

The manufacturing of packaged capillary action microfluidic systems by means of CO2 laser processing

In this article we demonstrate a simple yet robust rapid prototyping manufacturing technique for the construction of autonomous microfluidic capillary systems by means of CO₂ laser processing. The final packaging of the microfluidic device is demonstrated using thermal lamination bonding and allows for a turnaround time of approximately 30 min to 3 h from activation of the laser system to device use. The low-cost CO₂ laser system is capable of producing repeatable microfluidic structures with minimum feature sizes superior than 100–150 μm over channel depths of more than 100 μm. This system is utilised to create capillary pump and valve designs within poly (methyl methacrylate) (PMMA) substrates. Such components are part of advanced systems that can self initiate and maintain the flow of various volumes of fluids from an input to a collection reservoir, whilst also controlling the progression of the flow through the various demonstrated valve type structures. The resulting systems could prove a very useful alternative to traditional, non-integrated, fluidic actuation and flow control systems found on-chip, which generally require some form of energy input, have limited portable capabilities and require more complex fabrication procedures.     

A low temperature ultrasonic bonding method for PMMA microfluidic chips

Bonding is a bottleneck for mass-production of polymer microfluidic devices. A novel ultrasonic bonding method for rapid and deformation-free bonding of polymethyl methacrylate (PMMA) microfluidic chips is presented in this paper. Convex structures, usually named energy director in ultrasonic welding, were designed and fabricated around micro-channels and reservoirs on the substrates. Under low amplitude ultrasonic vibration, localized heating was generated only on the interface between energy director and cover plate, with peak temperature lower than T _g (glass transition temperature) of PMMA. With the increasing of temperature, solution of PMMA in isopropanol (IPA) increases and bonding was realized between the contacting surfaces of energy director and cover plate while no solution occurs on the surfaces of other part as their lower temperature. PMMA microfluidic chips with micro-channels of 80 μm × 80 μm were successfully bonded with high strength and low dimension loss using this method.     

Manufacture of microfluidic glass chips by deep plasma etching, femtosecond laser ablation, and anodic bonding

Two dry subtractive techniques for the fabrication of microchannels in borosilicate glass were investigated, plasma etching and laser ablation. Inductively coupled plasma reactive ion etching was carried out in a fluorine plasma (C₄F₈/O₂) using an electroplated Ni mask. Depth up to 100 μm with a profile angle of 83°–88° and a smooth bottom of the etched structure (Ra below 3 nm) were achieved at an etch rate of 0.9 μm/min. An ultrashort pulse Ti:sapphire laser operating at the wavelength of 800 nm and 5 kHz repetition rate was used for micromachining. Channels of 100 μm width and 140 μm height with a profile angle of 80–85° were obtained in 3 min using an average power of 160 mW and a pulse duration of 120 fs. A novel process for glass–glass anodic bonding using a conductive interlayer of Si/Al/Si has been developed to seal microfluidic components with good optical transparency using a relatively low temperature (350°C).     

Interfacing microfluidics to LDI-MS by automatic robotic spotting

We developed a method of interfacing microfluidics with mass spectrometry (MS) using a robotic spotting system to automate the contact spotting process. We demonstrate that direct and automated spotting of analyte from multichannel microfluidic chips to a custom microstructured MALDI target plate was a simple, robust, and high-throughput method for interfacing parallel microchannels using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Using thermoplastic cyclic olefin copolymer (COC) polymer microfluidic chips containing eight parallel 100 μm × 46 μm microchannels connected to a single input port, spotting volume repeatability and MALDI-MS signal uniformity are evaluated for a panel of sample peptides. The COC microfluidic chips were fabricated by hot embossing and solvent bonding techniques followed by chip dicing to create open ends for MS interfacing. Using the automatic robotic spotting approach, microfluidic chip-based reversed-phase liquid chromatography (RPLC) separations were interfaced with electrochemically etched nanofilament silicon (nSi) target substrate, demonstrating the potential of this approach toward chip-based microfluidic separation coupled with matrix-free laser desorption/ionization mass spectrometry.     

Disposable microfluidic blood cuvette for measuring hemoglobin concentration

This paper presents a new air-bubble free microfluidic blood cuvette for the measurement of hemoglobin concentration. The microfluidic blood cuvette was filled with blood samples by capillary force, and hemoglobin levels in the blood were determined by measuring absorbance at the wavelength of 530 nm. Two different microfluidic blood cuvettes with dual and single sidewall microchannels were investigated. The microfluidic blood cuvette was fabricated using a polymethyl methacrylate substrate and a dry film photoresist. During the blood-filling process, air was trapped in the dual-sided wall-type cuvettes, while no air trapping occurred in the single sidewall-type cuvettes. The sensitivity of the hemoglobin measurements was more linear in a 105 μm deep microchannel than in a 35 μm deep microchannel.     

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.

     

Modeling of capacitively coupled contactless conductivity detection on microfluidic chips

A novel equivalent circuit model of capacitively coupled contactless conductivity detection (C4D) on microfluidic chips is presented. The impedance of the solution in microchannels facing the two electrodes for C4D was first introduced in the model of C4D on microfluidic chips. The electrodes and the solution facing electrodes were divided into individual segments in the model, and the effect of the length of divided segments on the model was studied. A back-calculating method was put forward to calculate the stray capacitance between the electrodes, and the variation between the calculated value and the simulated value was only 6 %. To evaluate the accuracy of the model, a hybrid poly (methyl methacrylate) (PMMA)/polydimethylsiloxane (PDMS) microchip was fabricated and a simple model was built. Compared with the outputs of the simple model, the data predicted by the novel model show a much closer fit to experimental results, and the variations were within 8 % over a wide concentration range of 1–500 μm for potassium chloride.     

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.     

A facile strategy to integrate robust porous aluminum foil into microfluidic chip for sorting particles

High efficiency integration of functional microdevices into microchips is crucial for broad microfluidic applications. Here, a device-insertion and pressure sealing method was proposed to integrate robust porous aluminum foil into a microchannel for microchip functionalization which demonstrate the advantage of high efficient foil microfabrication and facile integration into the microfluidic chip. The porous aluminum foil with large area (10 × 10 mm²) was realized by one-step femtosecond laser perforating technique within few minutes and its pores size could be precisely controlled from 3 μm to millimeter scale by adjusting the laser pulse energy and pulse number. To verify the versatility and flexibility of this method, two kinds of different microchips were designed and fabricated. The vertical-sieve 3D microfluidic chip can separate silicon dioxide (SiO₂) microspheres of two different sizes (20 and 5 μm), whereas the complex stacking multilayered structures (sandwich-like) microfluidic chip can be used to sort three different kinds of SiO₂ particles (20, 10 and 5 μm) with ultrahigh separation efficiency of more than 92%. Furthermore, these robust filters can be reused via cleaning by backflow (mild clogging) or disassembling (heavy clogging).     

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.     

High-aspect-ratio through-hole array microfabricated in a PMMA plate for monodisperse emulsion production

Microchannel (MC) emulsification is a promising technique for producing monodisperse emulsions consisting of highly uniform droplets. The authors developed a high-aspect-ratio microstructure (HARMST) made of poly(methyl methacrylate) (PMMA) as a new MC emulsification device. A PMMA straight-through MC array plate consisting of 31,250 through-holes with a 7.3 × 22.9-μm oblong section and a 200-μm depth was fabricated by a process of synchrotron radiation (SR) lithography and etching. Oblong MCs fabricated in a PMMA straight-through MC array were highly uniform with a coefficient of variation of less than 2%. The fabricated PMMA straight-through MC array plate was used to produce water-in-oil (W/O) emulsions. Monodisperse W/O emulsions with average droplet diameters of approximately 25 μm and a minimum coefficient of variation of 3.2% were produced via a hydrophobic PMMA straight-through MC array. The PMMA straight-through MC array plate also produced monodisperse W/O emulsions at droplet production rates of up to 1.7 × 10⁴/s. The PMMA straight-through MC array plates developed in this work are expected to expand the application field of emulsification using straight-through MC array plates, which have previously been made of single-crystal silicon.     

PMMA microfluidic chip fabrication using laser ablation and low temperature bonding with OCA film and LOCA

A new PMMA microfluidic chip fabrication method by combining laser ablation technology with low-temperature bonding using optically clear adhesive (OCA) film and liquid optically clear adhesive (LOCA) was presented in this paper. The deformation and clogging issues of the microfluidic channel were well solved. The effective bonding area ratio of microfluidic chips could be greatly improved by adjusting bonding temperature and bonding time. The crevices around the microchannels were effectively eliminated by coating treatment of LOCA. The bonding strength and waterproof of PMMA microfluidic chips coating with/without LOCA were also evaluated in this paper.

     

Characterization of a new system for space-resolved simultaneous in situ measurements of hydrocarbons and dissolved oxygen in microchannels

A space-resolved in situ measurement technique based on laser Raman spectroscopy with high detection sensitivity is described. This method allows the simultaneous detection of the concentrations of dissolved molecular oxygen and of hydrocarbons as well as oxidation products in organic liquids in a microchannel during reaction. It can be used as a new tool for detailed kinetic studies of liquid-phase reaction. Raman spectra are produced using an argon ion laser at 488 nm with a continuous optical power of 100 mW. This radiation is coupled into a microscope and a microchannel. The arising Raman stray light is detected with a spectrometer and a sensitive CCD camera. Special optics were used to collect as much light as possible on the CCD detector. This results in high signals and low noise levels. In order to demonstrate the usefulness of the system, cyclohexane oxidation by oxygen was investigated. In a feasibility study for the products of the cyclohexane oxidation, a limit of detection of 0.05 % m/m for cyclohexanol and 0.01 % m/m for cyclohexanone was achieved. Molecular oxygen dissolved in cyclohexane could be detected at the relevant concentration ranges for carrying out the oxidation of cyclohexane with a limit of detection of 0.01 % m/m. An optically transparent microchannel reactor was built, which can be used up to temperatures of 503 K and pressures of 8 MPa. With this reactor and the in situ measurement technique, space-resolved studies with a measuring volume of 5 μm × 5 μm × 38 μm can now be realized. The spectral selectivity and sensitivity of the measurement technique applied to cyclohexane oxidation, and the characteristics of the spatially resolved measurement technique are discussed.     

Submicron polymer structures with X-ray lithography and hot embossing

This article describes the process chain for replication of submicron structures with varying aspect ratios (AR) up to 6 in polymethylmethacrylate (PMMA) by hot embossing to show the capability of the entire LIGA process to fabricate structures with these dimensions. Therefore a 4.7 μm thick layer of MicroChem 950k PMMA A11 resist was spin-coated on a 2.3 μm Ti/TiO _x membrane. It was patterned with X-ray lithography at the electron storage ring ANKA (2.5 GeV and λ _c ≈ 0.4 nm) at a dose of 4 kJ/cm³ using a Si₃N₄ membrane mask with 2 μm thick gold-absorbers. The samples were developed in GG/BDG and resulted in AR of 6–14. Subsequent nickel plating at 52°C resulted in a 200 μm thick nickel tool of 100 mm diameter, which was used to replicate slit-nozzles and columns in PMMA. Closely packed submicron cavities with AR 6 in the nickel shim were filled to 60% during hot embossing.     

A fluidic interconnection system for polymer-based microfluidic devices

A microfabricated fluidic interconnection system for polymer-based microfluidic nebulizer chips is presented and discussed. The new interconnection mechanism can be used to make fluidic connection between external capillary and the polymer microfluidic chip. The connector mechanism was fabricated using a combination of mechanical milling and laser micromachining. Preliminary leakage tests were performed to demonstrate that the interconnection system is leak-free and pressure tests were performed to evaluate the burst pressure (maximum working pressure). The interconnection system has several advantages over commercially available Nanoport™ interconnection system. The new fluidic interconnection system implemented onto a microfluidic nebulizer chip was successfully tested for desorption electrospray ionization mass spectrometry applications. The performance of the chip using the new connector mechanism was excellent demonstrating the usability of the new connector mechanism.     

Illumination and scattered light detection using a light source consisting of sub-micrometer defect arrays formed on a extremely flat light waveguide core

We have previously argued that an optical sensor combined total analysis system (TAS) is one of the indispensable functional components needed to realize a “ubiquitous human healthcare” system. To achieve this goal, we have proposed a fundamental structure for illuminating a minute cell or particle running along a microfluidic channel using a flat waveguide construction. It is desirable that the TAS light source should be arranged as close to the specimen flow as possible in order to acquire the necessary optical properties; hence, artificial defects formed on the surface of a flat light waveguide are considered to be a promising candidate for realizing the arbitrary-shaped light source for a highly functional optical TAS structure. Based on this idea, we fabricated a structure, constructing a flat and square light source consisting of rectangular solids, sub-micrometer in size, with a 1-μm thick and a 12-μm wide light waveguide core. We successfully trial-manufactured an optical TAS chip with a fluidic channel containing a 14 × 10-μm cross section, and an extremely flat light waveguide core. We repeatedly confirmed that the defect array could function as an approximately square light source when a 650-nm wavelength laser power was carefully introduced. Furthermore, we developed a hybrid numerical calculation method base on the finite-difference, time-domain method together with the beam propagation method. Utilizing this hybrid method, we evaluated the optical response when a particle runs across the light source while changing the aperture length of a shading mask to obtain signals with both higher intensity and shorter full width at half maximum. The numerical results were compared with experimental results obtained using an image acquisition system, and demonstrated good qualitative accord.     

Monolithic integration of Pb(Zr,Ti)O3 thin film based resonators using a complete dry microfabrication process

Monolithic fabrication of lead zirconate titanate [Pb(Zr,Ti)O₃ or PZT] based thin film resonant devices such as microcantilevers, Lamb wave and bulk acoustic wave resonators are demonstrated. High-performance PZT thin films with a thickness of 2.6 μm are prepared on a silicon on insulator wafer by a sputtering deposition process. A highly selective reactive ion etching process is employed for micro-patterning of PZT, platinum electrodes, and SiO₂ insulation layer. Self-actuation of the PZT microcantilevers is demonstrated and the frequency response is characterized using a laser Doppler vibrometer. The frequency response of the Lamb wave resonator is evaluated by measuring its transmission characteristic using a network analyzer. For a Lamb wave resonator with a length of 240 μm and an interdigital period of 80 μm, the 1st order and 2nd resonance frequencies are 15.3 and 41.8 MHz, respectively.     

Rapid prototyping of PMMA microfluidic chips utilizing a CO<Subscript>2</Subscript> laser

A commercially available CO₂ laser scriber is used to perform the direct-writing ablation of polymethyl-methacrylate (PMMA) substrates for microfluidic applications. The microfluidic designs are created using commercial layout software and are converted into the command signals required to drive the laser scriber in such a way as to reproduce the desired microchannel configuration on the surface of a PMMA substrate. The aspect ratio and surface quality of the ablated microchannels are examined using scanning electron microscopy and atomic force microscopy surface measurement techniques. The results show that a smooth channel wall can be obtained without the need for a post-machining annealing operation by performing the scribing process with the CO₂ laser beam in an unfocused condition. The practicality of the proposed approach is demonstrated by fabricating two microfluidic chips, namely a cytometer, and an integrating microfluidic chip for methanol detection, respectively. The results confirm that the proposed unfocused ablation technique represents a viable solution for the rapid and economic fabrication of a wide variety of PMMA-based microfluidic chips.