Showing papers by "Gwo-Bin Lee published in 2002"

A new fabrication process for ultra-thick microfluidic microstructures utilizing SU-8 photoresist

Abstract: In this paper we describe a new process for fabricating ultra-thick microfluidic devices utilizing SU-8 50 negative photoresist (PR) by standard UV lithography. Instead of using a conventional spin coater, a simple 'constant-volume-injection' method is used to create a thick SU-8 PR film up to 1.5 mm with a single coating. The SU-8 PR is self-planarized during the modified soft-baking process and forms a highly-uniform surface without any edge bead effect, which commonly occurs while using a spin coater. Photomasks can be in close contact with the PR and a better lithographic image can be generated. Experimental data show that the average thickness is 494.32 ± 17.13 μm for a 500 μm thick film (n = 7) and the uniformity is less than 3.1% over a 10 × 10 cm2 area. In this study, the temperatures for the soft-baking process and post-exposure baking are 120 °C and 60 °C, respectively. These proved to be capable of reducing the processing time and of obtaining a better pattern definition of the SU-8 structures. We also report on an innovative photomask design for fabricating ultra-deep trenches, which prevents the structures from cracking and distorting during developing and hard-baking processes. In this paper, two microfluidic structures have been demonstrated using the developed novel methods, including a micronozzle for thruster applications and a microfluidic device with micropost arrays for bioanalytical applications.

Electrokinetic Injection Techniques in Microfluidic Chips

Abstract: The separation efficiency of a microfluidic chip is influenced to a significant degree by the flow field conditions within the injection microchannel. Therefore, an understanding of the physics of the flow within this channel is beneficial in the design and operation of such a system. The configuration of an injection system is determined by the volume of the sample plug that is to be delivered to the separation process. Accordingly, this paper addresses the design and testing of injection systems with a variety of configurations, including a simple cross, a double-T, and a triple-T configuration. This paper also presents the design of a unique multi-T injection configuration. Each injection system cycles through a predetermined series of steps, in which the electric field magnitude and distribution within the various channels is strictly manipulated, to effectuate a virtual valve. The unique multi-T configuration injection system presented within this paper has the ability to simulate the functions of th...

Micro devices integrated with microchannels and electrospray nozzles using PDMS casting techniques

Abstract: The design, fabrication, and analytical utility of a polydimethylsiloxane (PDMS)-based microfluidic device for electrospray ionization mass spectrometry (ESI-MS) are described. The microdevice is composed of a one-dimensional (1D), or three-dimensional (3D) channel integrated with sample reservoirs, built-in electrodes and silica capillaries as electrospray nozzles. Several innovative fabrication features have been reported in the present study. First, there is no dead-volume region in the connection of the microchannels and capillary nozzles using PDMS casting techniques. Furthermore, there is no bonding process required to form a sealed microchannel, resulting in a simpler fabrication process and providing higher mechanical strength for high-pressure applications. Another advantage of the developed method is the feasibility to fabricate genuine 3D channels integrated with electrospray nozzles such that chip size can be minimized. Electrical contact to apply required high drive voltage for generation of the electrosprays can be also integrated on the microfluidic chip. The micro devices could be mass-produced at low costs and used as a disposable device to generate ESI-MS signals for protein identification from low amounts of protein samples. Compared with commercially available nanospray capillary tips, the microfluidic module gives comparable signal quality for ESI-MS and also offers advantages in convenience and easiness in operation, permitting repeated usages and disposability.

Analysis of the optimal dimension on the electrothermal microactuator

Abstract: A three-dimensional finite element model of an electrothermal microactuator (so-called 'hot–cold-beam actuator') is developed using the ANSYSTM finite element analysis (FEA) simulation program (ANSYS 1992 User's Manual for Revision 5.5.1 (Houston, PA: Swanson Analysis Systems, Inc.)). The actuator is geometrically scaled (except the thickness) to explore the effect of dimension variation on the performance of the actuator. The model is then used to optimize the actuator for robust design. Two types of actuator are also studied here: one with a suspended polysilicon structure and the other with additional gold-layer deposition. The results reveal that a greater deflection can be obtained for gold-plated actuators. An L18 Taguchi matrix is developed to investigate the effects of dimensional variation on the performance of the actuator. It is found that total actuator length contributes the major influence to the performance of the actuator. A maximum deflection is realized as the cold-beam length reaches about 86% of the hot-beam length of the actuator. Experiments are also conducted to verify numerical data. The results are in good agreement with analytical simulations to a certain electrical current regime. Finally, our robust design concludes that a gold-plated actuator with a 250 μm long, 3.5 μm thick, 2 μm wide hot beam and a 215 μm long, 3.5 μm thick, 15 μm wide cold beam can deflect up to 20.2 μm at a driving current of 6.2 mA.

Multi-cell-line micro flow cytometers with buried SU-8/SOG optical waveguides

Abstract: This paper reports a micro flow cytometer integrated with an innovative buried optical waveguide on soda-lime glass substrates. A novel optical waveguide using SU8/SOG (spin-on-glass) double-layer structure was demonstrated. The light guiding efficiency was improved due to smoother channel surface and larger difference of refractive index between SU-8 and organic-based SOG. Instead of using complicated optical alignment system, detection light source was coupled into the waveguide by directly inserting an etched optical fiber. A very high coupling efficiency could be achieved by this approach. In this study, the performance of the waveguides and insertion losses of the chip were measured. Results showed that the optical loss was less than 15 dB for a 40-mm long waveguide. The buried optical waveguide provides a built-in detection source for cell counting. Preliminary results indicated that a multi-cell-line flow cytometer with built-in detection system could be realized.

Variable‐volume‐injection methods using electrokinetic focusing on microfluidic chips

Abstract: This paper adopts a physical model and a numerical simulation approach to study electrokinetic focusing injection on microfluidic chips. The model reflects the principal material transport mechanisms such as electrokinetic migration, ionic concentration, fluid flow, and diffusion. The current study also involves the design and testing of various injection systems used to deliver a sample plug. A novel double-cross injection system has been developed which uses electrokinetic focusing to achieve variable-volume injection of the sample plug. The injection technique uses a unique sequence of loading steps with different electric potential distributions and potential magnitudes within the various channels to effectuate a virtual valve. The proposed design combines several functions of traditional sample plug injection systems on a single microfluidic chip.

Flow-Through Sampling for Electrophoresis-Based Microchips and Their Applications for Protein Analysis

Abstract: This work presents a model behind the operation of a flow-through sampling chip and its application for immunoseparation, as well as its integration with a wash/elution bed for protein purification, concentration, and detection. This device used hydrodynamic pressure to drive the sample flow, and a gating voltage was applied to the electrophoretic channel on the microchip to control the sample loading for the separation and to inhibit sample leakage. The deduced model indicates that the critical gating voltage (VC) that is defined as the minimum gating voltage applied to the microchip for sampling is a function of the pump flow rate, the configuration of the microchannel on the chip, and the electroosmosis of the buffer solution. It was found that the theoretical VC values calculated from the measured electroosmotic mobilities and flow split ratios were comparable to those experimentally obtained from two microchips with different sampling channel sizes. This had an error percentage ranging from 1 to 20%....

Analysis of geometry effects on band spreading of microchip electrophoresis.

Abstract: The geometry and the flow field conditions in the separation microchannel of an electrophoresis chip system may have important impact on the system's separation efficiency. Understanding the geometry effect on the flow field physics in the separation microchannel is beneficial to the design or operation of an electrophoresis system. The turns in a microfabricated separation microchannel generally results in degraded separation quality. To avoid this limitation, channels are constructed with different types of turns to determine the optimum design that minimizes turn-induced band broadening. We have designed and tested various geometric bend ratios to greatly reduce this so-called "racetrack" effect. The effects of the separation channel geometry, fluid velocity profile and bend ratio on the band distribution in the detection area are discussed. Results show that the folded square U-shaped channel is better for miniaturization and simplification. The band tilting was corrected and the racetrack effect reduced in the detection area when the bend ratio is 4:1. The detection time obtained from the present numerical solution matches very well with the experimental data.

MEMS-based temperature control systems for DNA amplification

Abstract: This paper reports an innovative on-chip temperature control system using MEMS technology. Micro temperature sensors and micro heaters are integrated on glass substrates for biomedical applications. The temperature control system consists of thin-film platinum resistors as sensing/heating elements and a layer of polyimide as an isolation layer inside a micromachined chamber. It is demonstrated as a micro PCR (Polymerase Chain Reaction) chip for DNA replication. A high rise and drop rate of temperature field is attained due to low thermal inertia of the micro system. The MEMS-based on-chip temperature control system can be integrated with microfluidic structures (such as micro channels and micro chambers), which are fabricated by easy polymer casting processes. Biomedical applications such as PCR, reactors, and incubators can be realized using the developed method.

Automation for continuous analysis on microchip electrophoresis using flow-through sampling.

Abstract: Automation of electrophoretic microchips for sequential analysis of different samples is demonstrated. This system used an autosampler, which was on-line connected to the microchip and the whole process including sample loading and injection, analysis and data acquisition as well as washing were all automated. Rhodamin B at different concentrations was first loaded into a hydrodynamic flow stream by an autosampler, delivered to the microchip, and then sequentially injected into the electrophoretic microchannel for analysis and detection. Automation was achieved by running two independent programs, one for sample loading by an autosampler and the other one for electrophoretic injection by voltage switching, on the same computer. Using this sampling chip, each loaded volume (0.2-1 microL) can be injected for dozens of electrophoretic analyses (1-10 nL for each injection). The variances caused by the external connections, which did not affect the electrophoretic analysis but would cause band broadening of the loaded sample in the hydrodynamic flow stream, were theoretically deduced. Results indicate that the dead volume (approximately 300 nL) due to the connection fitting on the chip could lead to dilution of the loaded sample by a factor of one when 0.2 microL of sample was loaded. Such a design allows sequential analysis of a series of samples while the running buffer is continuously pumped into the connection capillary as well as microchannels for washing between two loaded samples to minimize cross contamination without human intervention. Using this sampling chip, the required sample amount and handling time can be greatly reduced compared to the manual method.

A new fabrication process for a flexible skin with temperature sensor array

Abstract: In the present study, a new technique for fabrication of a flexible skin with 64 sensors inside a 7×7 mm2 area is reported. Each sensor has a dimension of 110 μm×110 μm. A simplified fabrication process using platinum resistors as sensing materials and polyimide layers as flexible substrates is developed. Systematic investigation of the performance of the sensors has been conducted, including sensors on rigid and flexible substrates for comparison. Sensors on rigid substrates have a sensitivity of 74.6 mV/°C with a cut‐off frequency of 90 kHz using a constant‐current circuit. Sensors on the flexible skin have been experimentally proven to have the same sensitivity as those on the rigid substrate. Moreover, the frequency response has been improved due to lower inertia for sensors on the flexible skin. The flexible skin with a temperature sensor array could be easily attached on a highly curved surface to detect temperature distribution inside a small area. The development of the temperature sensor...

Micro Flow Cytometers with Buried SU-8/SOG Optical Waveguides for On-line Cell Counting

Abstract: This paper reports an innovative miniaturized flow cytometer with on-line optical detection function. Microfluidic structures are integrated with buried optical waveguides on soda-lime glass substrates for on-line cell counting. A novel optical waveguide structure consists of SU-8/SOG (spin-on-glass) double-layer is demonstrated and used as an integrated optical detection device. Detection light can be guided through sample fluids and collected by the buried optical waveguides. Fluorescence labeling is not required for cell counting using the developed device. Experimental results show that diluted whole blood samples can be hydrodynamically focused and counted successfully.

Microfluidic Device with Integrated Protein Digestion, Peptide Separation and Nanospray Interface on Poly (Dimethylsiloxane) PDMS Substrate

Abstract: Here we present an easy method to fabricate the poly (dimethylsiloxane) (PDMS)-based microfluidic chips with integrated functions for protein identification by tandem mass spectrometry using replica-molding techniques. This microchip has typical electrophoretic microchannels, a pulled nano-electrospray ionization (ESI) capillary tip at the outlet and a cartridge packed with the trypsin-immobilized beads attached to sample reservoir of the device. Moreover, a novel frit made-up by photopolymer technique was fabricated near the front of the separation channel, where the C18 beads were packed for de-salting. Using β-casein as a test protein, the MS spectra acquired from different migration times indicate that the digested fragments were separated. Moreover, some signature peptides of beta-casein were clearly identified by matching their detected molecular weights as well as sequences with those obtained from the database.

Micro Electrophoresis Chips with On-chip Optical Waveguides Utilizing Novel Buried SU-8/SOG Double Layers

Abstract: This paper reports an innovative micro electrophoresis chip, which is integrated with buried optical waveguides on glass substrates for on-line detection of biomedical samples. A novel buried optical waveguide structure using SU-8/SOG (spin-on-glass) double layers is demonstrated, which can increase light guiding efficiency due to large difference of refractive index between SU-8 (n = 1.8, after hard-baking) and organic-based SOG (n = 1.36). With this novel approach, delicate optical system and even microscopy are not required for biomedical sample detection, resulting in a more compact or even a portable detection system.