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.     

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.     

Modeling and analysis of a 2-DOF bidirectional electro-thermal microactuator

In this paper, a four hot-arm U-shape electro-thermal actuator that can achieve bidirectional motion in two axes is introduced. By selectively applying voltage to different pairs of its four arms, the device can provide actuation in four directions starting from its rest position. It is shown that independent in-plane and out-of-plane motions can be obtained by tailoring the geometrical parameters of the system. The lumped model of the microactuator was developed using electro-thermal and thermo-mechanical analyses and validated using finite element simulations. The device has been fabricated using PolyMUMPs and experimental results are in good agreement with the theoretical predictions. Total in-plane deflections of 4.8 μm (2.4 μm in either direction) and upward out-of-plane deflections of 8.2 μm were achieved at 8 V of input voltage. The large achievable deflections and the higher degree-of-freedom of the proposed device compared to its counterparts, foresee its use in diverse MEMS applications.     

Microflow cytometer incorporating sequential micro-weir structure for three-dimensional focusing

A novel microflow cytometer is proposed in which the sample stream is focused initially in the horizontal (X–Y) plane by two sheath flows and is then focused in the vertical (Y–Z) plane by a sequential micro-weir structure before entering the detection region of the device. The proposed device is fabricated using a modified glass fabrication process, and is then characterized both numerically and experimentally using fluorescent polystyrene beads with diameters of 7 and 15 μm, respectively. The experimental and numerical results confirm the effectiveness of the hydrodynamic sheath flows in centralizing the particles in the horizontal plane prior to entering the sequential micro-weir structure. Furthermore, it is shown numerically that the micro-weir structure confines the particle stream to the center of the vertical plane such that the particles pass through the detection region in a one-by-one fashion can be counted with a high degree of reliability. The experimental results confirm that the proposed 3-D focusing scheme enables the fluorescent beads with different diameters to be reliably sorted and counted.     

Magnetic-fluid core optical fiber

We report the first fabrication of magnetic-fluid core optical fiber (MFCOF). Paraffin-based magnetic fluid is selected as the liquid and filled in a hollow core fiber with the core-diameter of 5 μm and the length of 20 cm. The optical properties of MFCOF were investigated by sending light into them. The wires allow multi-mode operation, and have an optical loss less than 0.6 dB/cm. In contradiction to the traditional liquid core optical fiber, the optical properties of MFCOF can be tunable under the external magnetic field, which may find applications in device physics on combined fields of magnetic fluid and nonlinear fiber optics.     

Novel U-shape gold nanoparticles-modified optical fiber for localized plasmon resonance chemical sensing

A novel fiber-optic localized plasma resonance (FO-LPR) sensor composed of a U-shape optical fiber was proposed and demonstrated in this study. The U-shape optical fiber was fabricated by a femtosecond laser micromachining system. The dimensions of the U-shape zone were 100 μm in depth measured from the surface of the polymer jacket layer, 80 μm in width in the jacket layer, 60 μm in width in the cladding layer. The total length is 5 mm. After laser annealing treatment, the average surface roughness was 205.8 nm as determined by Atom Force Microscope (AFM). The exposed surface of the U-shape fiber was modified with self-assembled gold nanoparticles to produce the FO-LPR sensor. The response of the sensor shows that the signal increases linearly with increasing refractive index. The sensor resolution of the sensor was determined to be 1.06 × 10⁻³ RIU.     

Fabrication of three-dimensional hemispherical structures using photolithography

A photolithography technique using SU-8 and PDMS was developed to fabricate three-dimensional hemispherical structures. This technique utilized a mask-aligner and normal binary coded photomasks to generate hemispherical pits on SU-8, followed by PDMS molding to obtain an array of dome-shaped structures. Using this technique, a microfluidic device was fabricated with a patterning area that consisted of an array of 5 μm wells and dome-shaped structures with 10 μm diameter and 6 μm height. Encoded microbeads, 6 μm in size, were immobilized and patterned in the microfluidic device under flow conditions and a DNA hybridization experiment was performed to demonstrate the incorporation of encoded beads that would enable a high level of multiplexing in bioassays.     

Design and fabrication of SU-8 micro optic fiber holder with cantilever-type elastic microclips

The optic alignment module containing out-of-plane 3D micro lenses, and micro optic fiber holders have been fabricated using tilted UV lithography technique in water with SU-8 photoresist (Ling and Lian in Proc SPIE 4979:402–409, 2007). Each holder is a circumscribed quadrilateral formed by a V-groove and pairs of fixed microclips, which will hold the fiber in position through the elastic deformation when the fiber is inserted. Since these microclips were fixed cantilever beams and its effective beam length, the distance between the fixed end of the beam and beam–fiber contact point, is very short (~62.5 μm), the stress on the beam is high even under a small (few microns) deformation. The inserted optical fiber was either too loose to lose its alignment accuracy, or too tight causing the clips to break because of dimensional tolerance. It becomes very difficult, if not impossible, to use them in practical applications. Therefore, the key issue of fabricating optical alignment module is to have a suitable stiffness of microclips with an appropriate deformation during the fiber insertion, which can provide enough force to hold the fiber for accurate alignment and avoid introducing neither significant viscous deformation nor the damage to the clips. In this paper, a novel technique to fabricate SU-8 cantilever beam as elastic clamping device in optical fiber holder is proposed. Simulation based on SU-8 material properties indicates that for a 250-μm-long, 50-μm-thick SU-8 beam the clamping force per unit beam width will range from 10 to 100 Newton/m as the deflection increased from 1.4 to 14 μm. This predicted performance is comparable to or even better than that of existing silicon nitride microclips in optical fiber holding application [Bostock et al. in J Micromech Microeng 8(4):343–360, 1998]. By using a two-mask process, we have fabricated free-end cantilever beams as fiber holding clips. In order to have longer beams over V-groove, the slots in the V-groove were introduced, which allow the beams extended deeper into the sloped V-groove walls. The micro alignment module with 250-μm-length cantilever beams as microclips for housing 125-μm-diameter optical fibers has been successfully fabricated using a 300-μm-thick SU-8 photoresist layer by a two-mask UV lithography processes. This approuch offers significant advantages over other techniques with respect to costs of material, simple in equipment, and easy in manufacture. These optical fiber holders with elastic microclips combined with pre-aligned out-of-plane 3D micro lenses make it possible that to build an integrated micro optic system with precise alignment accuracy on a wafer-scale.     

Microfocusing using the thermal actuation of microbubbles

This paper describes the microfocusing in a microchannel using the thermal actuation of a pair of microbubbles. A microbubble was produced from de-ionized (DI) water with an integrated microheater, and the volume was controlled by applying voltage. The microfocusing was demonstrated with a polydimethylsiloxane (PDMS) device consisting of two layers. The top layer included a microchannel that was 300 μm wide and 50 μm high. It was flanked by a pair of reservoirs. The bottom layer provided a microheater underneath the reservoir. Upon heating, DI water boiled immediately over the microheater and formed a microbubble that came out of the reservoir in a perpendicular direction toward the fluid. The fluid was focused from 300 to 22 μm, as the distance between the apexes of the arch-shaped microbubbles was shortened due to expansion, which was maintained at a flow velocity up to approximately 17.8 mm s⁻¹. The temperature of the water in the reservoir was estimated to reach the boiling point within 62 or 160 ms, depending on the substrate.     

Fabrication of metallic micromolds by laser and electro-discharge micromachining

A method of creating metallic micromolds with features that have high-aspect ratios is described in this paper. The proposed manufacturing process utilizes laser micromachining to cut the negative two-dimensional profiles of the desired microfeatures and fluidic network patterns on a 100 μm thick brass sheet. The positive relief of the cut pattern is then created by using electro-discharge micromachining (micro-EDM) die-sinking the metallic mask onto a brass substrate. The final substrate with the desired relief pattern becomes the molding tool used for either elastomer casting or thermoplastic hot embossing. To validate the proposed fabrication methodology and evaluate the quality of surface finishes, a brass mold master of a T-channel micromixer (50 μm width, 25 μm height) is developed and multiple replicated devices are cast on this mold using poly-di-methyl-siloxane (PDMS). The surface finish of both the original micromold master and final molded channels on PDMS are measured using an optical profiler and found to have a roughness of approximately 400 nm Ra. The ability of the proposed fabrication technique to create high-aspect ratio features is illustrated by manufacturing a Y-channel micromixer with an aspect ratio of 4. Experimental results are discussed and suggestions for improvement are presented.     

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.     

SU-8 as resist material for deep X-ray lithography

 A new negative tone resist for deep X-ray lithography is presented. This resist is a nine parts to one mixture of the EPON SU-8 resin with 2,2-bis-(3,5-dichloro-4-hydroxyphenyl)propane (Tetrachlorobisphenol A, TCBA), the latter acting as the photoinitiator. The resist was irradiated at the synchrotron source of DCI at LURE. It was dried for 7 to 20 days beforehand over silica gel while under a light vacuum (20 mbar). Best results for a 150 μm high resist were obtained with a X-ray bottom dose of 3 kJ cm⁻³ and a post exposure bake at 33 °C. Differential Scanning Calorimetry measurements (DSC) determined the glass transition temperature of the resist. The glass transition for the undried, loose resist was 34.7 °C, and it was 28.7 °C when the resist was pressed on a silicon substrate. For a sample of the dried resist, the glass transition was 33.4 °C for the loose resist and 29.8 °C when it was pressed on a Silicon substrate. CD measurements were made on top surface of a set of 100 μm long columns structures, which were produced in 150 μm of this resist. These structures have a constant 100 μm pitch, and the structures themselves varied in width from 20 to 17 μm. For these structures, the CD was calculated to be 0.15 ± 0.03 μm. Received: 8 February 2000/Accepted: 3 March 2000     

Ultrafast measurement of transient electroosmotic flow in microfluidics

We present a non-intrusive molecular dye based method, i.e., laser-induced fluorescence photobleaching anemometer (LIFPA), to significantly increase temporal resolution (TR) for velocity measurement of fast transient electrokinetic flows. To our knowledge, the TR has been for the first time achieved to 5–10 μs, about 100 times better than that published from state-of-the-art micro particle image velocimetry (μPIV), which is currently the most widely used velocimetry in the microfluidics community. The new method provides us with new opportunities to study experimentally the fundamental phenomena of unsteady electrokinetics (EK) and to validate relevant theoretical models. One application of the new method is demonstrated by measuring the rise time of DC electroosmotic flows (EOFs) in a microcapillary of 10 μm in diameter.     

Dual confocal laser-induced fluorescence/moveable contactless conductivity detector for capillary electrophoresis microchip

A new dual simultaneous detector was developed for capillary electrophoresis microchip. Confocal laser-induced fluorescence (LIF) and moveable contactless conductivity detection (MCCD) were combined together for the first time. The two detection systems shared a common detection cell and could respond simultaneously. They were mutually independent and advantageous in analyses of mixtures containing organic and inorganic ions. The confocal LIF had high sensitivity and the MCCD could move along the separation channel and detect in different positions of the channel. The detection conditions of the dual detector were optimized. Rhodamine B was used to evaluate the performance of the dual detector. The limit of detection of the confocal LIF was <5 nM, and that of the MCCD was 0.1 μM. The dual detector had highly sensitivity and could offer response easily, rapidly and simultaneously.     

Fabrication of a guide block for measuring a device with fine pitch area-arrayed solder bumps

This paper describes the design and fabrication of a guide block and micro probes, which were used for a vertical probe card to test a chip with area-arrayed solder bumps. The size of the fabricated guide block was 10 mm × 6 mm. The guide block consisted of 172 holes to insert micro probes, 2 guide holes for exact alignment, and 4 holes for bolting between the guide block and the housing of a PCB. Pitch and size of the inserting holes were 80 μm, and 90 μm × 30 μm, respectively. A silicon on insulator wafer was used as the substrate of the guide block to reduce micro probes insertion error. The micro probes were made of nickel–cobalt (Ni–Co) alloy using an electroplating method. The length and thickness of the micro probes were 910 and 20 μm, respectively. A vertical probe card assembled with the fabricated guide block and micro probes showed good x–y alignment and planarity errors within ±4 and ±3 μm, respectively. In addition, average leakage current and contact resistance were approximately 0.35 nA and 0.378 ohm, respectively. The proposed guide block and micro probes can be applied to a vertical probe card to test a chip with area-arrayed solder bumps.     

Fabrication of large-volume microfluidic chamber embedded in glass using three-dimensional femtosecond laser micromachining

We report on fabrication of large-volume, square-shaped microfluidic chamber embedded in glass by scanning a tightly focused femtosecond laser beam inside a porous glass immersed in water. After the hollow structure is created in the porous glass substrate, the fabricated glass sample is post-annealed at 1,050°C during which it can be sintered into a compact glass. By the use of this technique, a 1 mm × 1 mm × 100 μm microchamber connected to four microfluidic channels is created inside the transparent glass substrate, showing that our technique allows for fabrication of not only thin channel structures with arbitrary lengths and configurations, but also hollow structures with infinitely large sizes.     

Micromachining of passive planar micromixer on poly (methyl methacrylate) substrate with excimer laser ablation

Excimer laser ablation technique was introduced into this work to fabricate a passive planar micromixer on the PMMA substrate. T-junction shaped and width-changed S-shaped microchannels were both designed in this micromixer to enhance mixing effect. The mixing experiment of distilled water and Rhodamine B with injection flow rate of 500 and 1,500 μm/s validates the mixing effectivity of this micromixer, and indicates the feasibility of excimer laser ablation in the microfabrication of μ-TAS device.     

Design, fabrication and testing of a high performance silicon piezoresistive Z-axis accelerometer with proof mass-edge-aligned-flexures

This paper presents design, fabrication and testing of a quad beam silicon piezoresistive Z-axis accelerometer with very low cross-axis sensitivity. The accelerometer device proposed in the present work consists of a thick proof mass supported by four thin beams (also called as flexures) that are connected to an outer supporting rim. Cross-axis sensitivity in piezoresistive accelerometers is an important issue particularly for high performance applications. In the present study, low cross-axis sensitivity is achieved by improving the device stability by placing the four flexures in line with the proof mass edges. Various modules of a finite element method based software called CoventorWare^™ was used for design optimization. Based on the simulation results, a flexure thickness of 30 μm and a diffused resistor doping concentration of 5 × 10¹⁸ atoms/cm³ were fixed to achieve a high prime-axis sensitivity of 122 μV/Vg, low cross-axis sensitivity of 27 ppm and a relatively higher bandwidth of 2.89 kHz. The designed accelerometer was realized by a complementary metal oxide semiconductor compatible bulk micromachining process using a dual doped tetra methyl ammonium hydroxide etching solution. The fabricated accelerometer devices were tested up to 13 g static acceleration using a rate table. Test results of fabricated devices with 30 μm flexure thickness show an average prime axis sensitivity of 111 μV/Vg with very low cross-axis sensitivities of 0.652 and 0.688 μV/Vg along X-axis and Y-axis, respectively.     

Fabrication of a metal protector for a fiber sensor using through-mask electrochemical micromachining with pulse DC power

The purpose of this study is to fabricate a stainless steel protector for a weak fiber sensor after first stripping the polymer outer-layer off the fiber. In addition to protecting the fiber sensor, the stainless steel protector is required to connect the detection target and the sensor which requires drilling holes in the protector. We accomplished this by electrochemical micromachining the stainless steel protector using pulse DC, using 1 kV/m, 6.62% weight concentration of NaCl electrolyte solution, 500 rpm anode rotating rate, a 5 MHz pulse frequency, a 50% duty factor, and 6 min of machining time with a ring cathode gave the best results, producing an average hole-radius of 231.36 μm.