Fabrication and flow test of long-term hydrophilic fluidic chip without using any surface modification treatment

In order to effectively pump liquid in a fluidic chip, the PDMS or SU8 channels were frequently modified by surface treatments to obtain the hydrophilic surface but encountered the problem of the hydrophobic recovery. In this article, long-term highly hydrophilic fluidic chips were demonstrated using rapid fabrication of low-power CO₂ laser ablation and low-temperature glass bonding with an interlayer of liquid crystal polymer (LCP). The intrinsic hydrophilic materials of glass and LCP were beneficial for self-driven flow in the long-term fluidic chip by surface-tension force with no extra fluidic pumps. The higher viscosity fluid could increase the difficulty of self-driven capability. The stability of contact angle and flow test of the chip after 2 months is similar to that at beginning. The high-viscosity human whole blood was successfully driven at an average moving velocity of about 1.89 mm/s for the beginning and at 2.04 mm/s after 2 months. Our fluidic chip simplifies the traditional complex fabrication procedure of glass chips and conquers the problem of traditional hydrophobic recovery.     

Plasma assisted thermal bonding for PMMA microfluidic chips with integrated metal microelectrodes

Fracture of integrated metal microelectrodes likely happens during the thermal bonding process of PMMA [poly (methylmethacrylate)] microfluidic chips. In this paper, the fracture behaviors are studied. The fracture is mainly caused by the plastic deformation of the electrode plate (the PMMA plate with microelectrodes) and the thermal stress of microelectrodes, which is due to the high bonding temperature. To decrease the bonding temperature, a plasma assisted thermal bonding method is evaluated and first used to eliminate the fracture of microelectrodes. In this process, the surface of the cover plate (the PMMA plate with microchannels) is modified using oxygen plasma before the electrode plate is thermally bonded to the cover plate. The parameters of the oxygen plasma treatment are optimized, and the contact angle is decreased from 71.7° to 43.6°. The thermal bonding temperature is optimized, which decreases the temperature from 100 °C to 85 °C. Testing of bonding strength shows an average failure pressure of 1.75 MPa, which is comparable to the bonding strength of 1.46 MPa for chips bonded at 100 °C without plasma modification. In order to demonstrate this bonding method, a PMMA microfluidic chip with integrated copper interdigitated microelectrode arrays for AC electroosmotic pump is fabricated.     

Single-cell-based measurement of supraphysiological thermal injury in human carcinoma cells utilizing a micropatterned hydrogel chip

Hyperthermia affects certain regulatory proteins, kinases or cyclins, resulting in alternations to the cell cycle and even to apoptosis. Damage to the cell plasma membrane is a key factor in the killing of a cell by hyperthermia. Analysis at the single-cell level is necessary for understanding the fundamental mechanisms of hyperthermia-induced cell death and the generation of thermotolerance in surviving cells. Engineering approaches achieving precise control of cellular micropatterning provide the potential for investigating the mechanisms of thermal injury to cells at the single-cell level. The main purpose of this study is to fabricate a hydrogel chip with microwells for cellular patterning and to demonstrate the feasibility of measurement of supraphysiological thermal injury in human carcinoma cells (HeLa cells) at the single-cell level. To accomplish this, measurement of membrane injury by dye leakage post-thermal insult was performed and reported in this work. A hydrogel chip with microwells with different diameters was fabricated. For cell concentrations at 0.5 × 10⁶ cells/mL, the occupancy of cells on the microchip with 40 μm microwells was up to 86.6%, a value far higher than that found on the 30 μm microwells (approximately 78.5%). Most microwells of 30 μm in diameter (about 70%) were occupied by a single cell; hence, the hydrogel chip with 30 μm microwells was suitable for the applications of single-cell-based analysis. The fluorescent images showed that calcein leakage occurred when cell membranes were damaged under supraphysiological temperatures between 43 and 50°C. The normalized intensity of calcein decreased to 32% under a supraphysiological temperature of 43°C for 20 min. The intensity of calcein in cells was less than 20% under a supraphysiological temperature of 50°C. The feasibility of the single-cell-based experiment of thermal injury in the microchip with hydrogel microwells was therefore successfully demonstrated.     

Colorimetric immunoassay chip based on gold nanoparticles and gold enhancement

A colorimetric immunoassay chip has been developed based on gold nanoparticles for indicating the antibody–antigen binding activity and gold enhancement for amplifying the specific binding signal. Our investigations showed that the results of immunoassay can be represented by the level of color intensity. They were easily observed by a regular camera or naked eye, which is not needed of sophisticated laboratory equipment. Optimization of experimental conditions was carried out and the colorimetric detection had been compared to the standard chemifluorescent detection. Under the optimized conditions, colorimetric immunoassay chip had been demonstrated to detect different amount of immobilized antigens, i.e., human IgG. The results, i.e., color intensity, were mapped to the concentration of immobilized antigens in a dynamic range of 1–5,000 ng/ml. The proposed detection method does not require any sophisticated optical systems; therefore, it is possible to be miniaturized and integrated into a microfluidic system for developing a portable immunoassay device.     

Achieving high sensing in 0.5 nA for the driving pixel currents in AMOLEDs with settling time of 7 µs by a new external current sensing circuit

A new external current sensing circuit with baseline compensation for the active matrix organic light emitting diode (AMOLED) display is developed herein to achieve the sensing precision of 0.5 nA in pixel with 7 µs of settling time. Current sensing circuit incorporates a new push–pull transient current feedforward whereas the current analog to digital converter (CADC) based digital baseline current compensation incorporates an 11-bit current digital-to-analog converter, a current comparator and a digital control circuit with an 11-bit successive approximation register. The proposed integrated mixed signal IC drives a 6T1C pixel-based AMOLED panel with one horizontal time of 7.7 µs at a scan frequency of 60 Hz. The design readout chip can simultaneously sense and compensate TFT baseline current variation. The readout circuit and the baseline compensation circuit are implemented in the integrated chip with chip area of 125 μm × 46 μm and fabricated via TSMC T18 process. With the standard 3.3 V supply, experimental result shows that the overall power consumption of the chip is 988 µW watt. The minimum LSB current for the CADC is 10 nA and the maximum achievable sampling rate is 500 KS/s. The measured INL and DNL of CADC is 0.84 and 0.98 respectively. Despite of heavy data line parasitic capacitances (2.6 KΩ/20 pF) of the AMOLED display, experimental results show that the proposed circuit can sense 0.5 nA current within 7 µs of settling time. The sensing precision of 0.5 nA within 7 µs are the best among all reported literature to date whereas the current sense range (0.5–500 nA), system sampling rate (142 KS/s), INL (0.84) and DNL (0.98) of the CADC is approximately comparable among all reported.

     

Size-controlled synthesis of gold nanoparticles using a micro-mixing system

A new microfluidic reaction chip capable of mixing, transporting and controlling reactions has been developed for the size-tunable synthesis of gold nanoparticles. This chip allows for an accelerated and efficient approach for the synthesis of gold nanoparticles. The microfluidic reaction chip is made by computer-numerically controlled machining and PDMS casting processes, which integrate a micro-mixer, a normally closed valve and a micro-pump onto a single chip. The micro-mixer is capable of generating a vortex-type flow field, which achieves a mixing efficiency as high as 95% within 1 s. Successful synthesis of dispersed gold nanoparticles has been demonstrated within an 83% shorter period of time (13 min), as compared to traditional methods (around 2 h). By using different volumes of reagents, the dispersed gold nanoparticles are found to have average diameters of 19, 28, 37 and 58 nm. The optical absorption spectra indicate that these synthesized nanoparticles have different surface plasmon resonance peaks, which are 521, 525, 530 and 537 nm, respectively. The development of this microfluidic reaction system holds promise for the synthesis of functional nanoparticles for further biomedical applications.     

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.     

Rapid glucose concentration detection utilizing disposable integrated microfluidic chip

A novel three-dimensional (3D) disposable glucose concentration detection chip is presented. The chip comprises a four-layer polymethyl methacrylate (PMMA) structure and is fabricated using a commercial CO₂ laser and a hot-press bonding technique. In the proposed device, the glucose solution is injected into a double parallel connection micromixer (DPCM) and is mixed with DNS reagent by means of a self-rotation effect. An experimental platform has been created for multiple reaction process by integrating chip and micro-heater. The fluid streams exiting the two circular mixing chambers of the DPCM are then combined and mixed further at a T-type microchannel outlet before passing to a collection chamber. Numerical simulations are performed to analyze the vortex streamline distribution within the DPCM and to estimate the mixing performance. The numerical results show that a mixing efficiency as high as 92.5% can be obtained at low Reynolds numbers (Re = 12). It is found a good linear relation of R ² = 0.9953 from the chip detection method comparing to the traditional method of R ² = 0.9976 at DNS reagent and glucose solution volume ratio of 1:1. In addition, the experimental results show that the accuracy of the glucose concentration measurements obtained using the proposed microfluidic chip is comparable with that of the measurements obtained using a conventional large-scale detection method. Overall, the results presented in this study indicate that the DPCM chip provides a rapid and low-cost means of detecting the concentration of glucose solutions.     

On-chip PCR amplification of genomic and viral templates in unprocessed whole blood

Performing medical diagnosis in microfluidic devices could scale down laboratory functions and reduce the cost for accessible healthcare. The ultimate goal of such devices is to receive a sample of blood, perform genetic amplification (polymerase chain reaction—PCR) and subsequently analyse the amplified products. DNA amplification is generally performed with DNA purified from blood, thus requiring on-chip implementation of DNA extraction steps with consequent increases in the complexity and cost of chip fabrication. Here, we demonstrate the use of unprocessed whole blood as a source of template for genomic or viral targets (human platelet antigen 1 (HPA1), fibroblast growth factor receptor 2 (FGFR2) and BK virus (BKV)) amplified by PCR on a three-layer microfluidic chip that uses a flexible membrane for pumping and valving. The method depends upon the use of a modified DNA polymerase (Phusion™). The volume of the whole blood used in microchip PCR chamber is 30 nl containing less than 1 ng of genomic DNA. For BKV on-chip whole blood PCR, about 3000 copies of BKV DNA were present in the chamber. The DNA detection method, laser-induced fluorescence, used in this article so far is not quantitative but rather qualitative providing a yes/no answer. The ability to perform clinical testing using whole blood, thereby eliminating the need for DNA extraction or sample preparation prior to PCR, will facilitate the development of microfluidic devices for inexpensive and faster clinical diagnostics.     

Microchannel emulsification for mass production of uniform fine droplets: integration of microchannel arrays on a chip

We present a novel microchannel emulsification (MCE) system for mass-producing uniform fine droplets. A 60 × 60-mm MCE chip made of single-crystal silicon has 14 microchannel (MC) arrays and 1.2 × 10⁴ MCs, and each MC array consists of many parallel MCs and a terrace. A holder with two inlet through-holes and one outlet through-hole was also developed for simply infusing each liquid and collecting emulsion products. The MCE chip was sealed well by physically attaching it to a flat glass plate in the holder during emulsification. Uniform fine droplets of soybean oil with an average diameter of 10 μm were reliably generated from all the MC arrays. The size of the resultant fine droplets was almost independent of the dispersed-phase flow rate below a critical value. The continuous-phase flow rate was unimportant for both the droplet generation and the droplet size. The MCE chip enabled mass-producing uniform fine droplets at 1.5 ml h⁻¹ and 1.9 × 10⁹ h⁻¹, which could be further increased using a dispersed phase of low viscosity.     

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.     

On-chip CO<Subscript>2</Subscript> incubation for pocket-sized microfluidic cell culture

We have developed an on-chip CO₂ incubation system based on mass/heat transfer from aqueous solutions of bicarbonate source to cell culture media through a permeable poly(dimethylsiloxane) (PDMS) wall. Heating a carbonate-buffered bicarbonate solution successfully regulated CO₂ generation without any feedback control. Because a microfluidic cell culture chip with the incubation system does not require an external chamber or gas supply, the entire microfluidic cell culture setup becomes pocket sized. Using 5 ml of 0.8 M sodium bicarbonate with 65 mM sodium carbonate as the water jacket, the chip maintained the temperature, osmolality, and pH of 750 μl cell culture medium within physiological levels when the chip was placed on a 37°C surface. The osmolality shift and pCO₂ of the media reservoir stabilized within <5 mmol/kg and 5.0 ± 1.0% over at least 9 days. The incubation capabilities were demonstrated through microfluidic culture of COS-7 epithelial cells under an inverted microscope for 17 days.     

Through-silicon via technologies for interconnects in RF MEMS

In this paper, we describe the application of through-silicon via (TSV) interconnects in Radio Frequency Micro-electro-mechanical systems (RF MEMS). Using TSV technologies as grounding connections, a Ku band miniature bandpass filter is designed and fabricated. Measured results show an insertion loss of 1.9 dB and a bandwidth of 20%. The chip size is 9.6 × 4 × 0.4 mm³. Using TSV as interconnections for 3 dimensional millimeter-wave integrated circuits, a silicon micromachined vertical transition with three layers is presented. TSV, alignment, bonding and wafer thinning technologies are used to fabricate the sample. This transition has an insertion loss of less than 6.7 dB from 26 to 34 GHz and its amplitude variation is less than 2 dB. The total size of the chip is 6.3 × 3.2 mm².     

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.     

Improving utilization of reconfigurable resources using two-dimensional compaction

Partial reconfiguration allows parts of the reconfigurable chip area to be configured without affecting the rest of the chip. This allows placement of tasks at run time on the reconfigurable chip. Area management is a very important issue which highly affect the utilization of the chip and hence the performance. This paper focuses on a major aspect of moving running tasks to free space for new incoming tasks (compaction). We study the effect of compacting running tasks to free more contiguous space on the system performance. First, we introduce a straightforward compaction strategy called Blind compaction. We use its performance as a reference to measure the performance of other compaction algorithms. Then we propose a two-dimensional compaction algorithm called one-corner compaction. This algorithm runs with respect to one chip corner. We further extend this algorithm to the four corners of the chip and introduce the four-corners compaction algorithm. Finally, we compare the performance of these algorithms with some existing compaction strategies: Brebner, G. and Diessel, O. (Proceedings of the 11th international workshop on field programmable gate arrays (FPL), pp. 182–191, 2001); Diesel, O. and ElGindy, H. (Proceedings of the 5th Australasian conference on parallel and real-time systems (PART), pp. 191–200, 1998); Diesel, O., et al. (IEE proceedings on computers and digital techniques, vol. 147, pp. 181–188, 2000). The simulation results show improvement in average task allocation time when using the four-corners compaction algorithm by 15% and in chip utilization by 16% over the Blind compaction. These results outperform the existing strategies.

An immunoassay using an electro-microchip, nanogold probe and silver enhancement

This paper presents a novel immunoassay using an electro-microchip to detect the immuno-reaction signal, gold nanoparticles (ANPs) as a label of antigen or antibody and as a catalyst for silver precipitation, and the silver enhancement reaction to magnify the detection signal. This study is based on the direct immunoassay (two-layer format) and the sandwich immunoassay (three-layer format). The ANPs are introduced to the electro-microchip by the specific binding of the antibodies–ANPs conjugates and then coupled with silver enhancement to produce black spots of silver metal. The silver precipitation constructs a “bridge” between two electrodes of the electro-microchip allowing the electrons to pass, and the variation of the impedance can be easily measured with a commercial LCR meter. Different gap sizes (20, 50, 100, and 200 μm) of the electrodes of electro-microchips were designed for the sensitivity study. The experimental data show that a chip with a 200 μm gap has the highest sensitivity. There is a significant difference in impedance between the experiment and the negative control after 10 min reaction time. The proposed method requires less time and fewer steps than the conventional enzyme-linked immunosorbent assay. In addition, it shows a high detection sensitivity [10 μg/mL of 1st antibody (IgG) immobilized on slides and 10 ng/mL of antigen (protein A)], and there is a clear distinction between the signal intensity and the logarithm of the sample concentration. This new immunoassay has potential applications in proteomics research and clinical diagnosis.     

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.     

Fluorescence detection in a micro flow cytometer without on-chip fibers

This paper describes a novel concept of integrated on-chip fiber free laser-induced fluorescence detection system. The poly-dimethylsiloxane (PDMS) chip was fabricated using soft lithography and was bonded with a glass substrate of 150 μm thickness that reduced the distance of channel-to-sidewall to less than 180 μm. The cells and particles detection was conducted by an external single fiber close to the glass substrate that transmitted laser light for simultaneous excitation and receipt of the emission light signals. The performance of the proposed device was demonstrated using fluorescence beads, stained white blood cells, and yeast cells. The experimental results showed the simplicity and flexibility of the proposed device configuration which can provide convenient on-chip integration interface for fast, high throughput, and low-cost laser-induced fluorescence detection micro flow cytometer.     

In-situ fabrication of polymer microsieves for ��TAS by slanted angle holography

We present a simple, versatile method for the in-situ fabrication of membranes inside a microfluidic channel during a chip manufacturing process using only two extra slanted angle holographic exposure steps. This method combines the strengths of both inclined UV exposure and holographic lithography to produce micrometer-sized three-dimensional sieving structures. Using a common chip material, the photoresist material SU-8, together with this method, a leak-free membrane-channel connection is obtained. The resulting membranes are monodisperse, with a very well-defined pore geometry (i.e., microsieves with a pore diameter between 500 nm and 10 μm) that is easily controllable with the holographic set-up. The selectivity of in-situ fabricated microsieves with a pore diameter of 2 μm will be demonstrated using polystyrene beads of 1 and 3 μm.