Showing papers by "Gwo-Bin Lee published in 2003"

Micromachine-based humidity sensors with integrated temperature sensors for signal drift compensation

Abstract: This paper presents a novel technique for the fabrication of a micro humidity sensor with suspending structures. A MEMS device is developed which uses thin-film platinum resistors as temperature sensing elements and a nitride/silicon microstructure suspended at a small distance above the surface of a glass substrate as the movable electrode of a capacitor. A mechanism is proposed for the measurement of the capacitance between the suspended wafer structure and the glass substrate for different values of relative humidity. The fundamental component of the micromachine-based humidity sensor is a nitride/silicon cantilever coated with a vapor-absorbent polymer film (polyimide). A variation in humidity causes moisture-dependent bending of the microcantilever, which changes the measured capacitance between the microcantilever and the substrate. The current experimental data show that the low stiffness of the microcantilever and the large electrode area on the microcantilever tip yield a high degree of sensitivity, i.e. 2.0 nF/% RH. To compensate for the temperature drift of the capacitance signals, the proposed humidity sensor is integrated with a micro resistance-type temperature detector comprised of platinum resistors. The experimental data indicate a low hysteresis value at high relative humidity (>65% RH). The relationship between the measured resistance/capacitance and relative humidity is fully explored and documented. The numerical and experimental samples all indicate a high degree of linearity (R2 = 0.9989), a high stability (±0.76%) and a reasonable response time (1.10 s).

Micro flow cytometers with buried SU-8/SOG optical waveguides

Abstract: This paper reports an innovative micromachine-based flow cytometer integrated with buried optical waveguides on soda-lime glass substrates. A novel optical waveguide using SU-8/spin-on-glass (SOG) double-layer structure is demonstrated, which increases light guiding efficiency due to smoother channel surface and larger difference of refractive index between SU-8 and organic-based SOG. Instead of using complex optical alignment system, detection light source is coupled with the waveguide with direct insertion of an etched optical fiber. A very high coupling efficiency can be achieved using this approach. In this study, the performance of the waveguides and insertion losses are measured. Experimental results show that the optical loss is less than 15 dB for a 40 mm long waveguide. With the integrated optical waveguides, a micro flow cytometer capable of particle counting has been realized. Data show that microparticles can be hydrodynamically focused and counted successfully without fluorescent labeling using the miniaturized flow cytometer with the integrated optical detection system.

Micromachined flow cytometers with embedded etched optic fibers for optical detection

Abstract: This paper presents a device that integrates a micromachined flow cytometer with two embedded etched optic fibers in order to carry out on-line detection of particles and cells. A simple and reliable fabrication process is used to fabricate the cytometer on soda-lime glass substrates. It is shown experimentally that particles/cells can be squeezed hydrodynamically into a narrow stream by two neighboring sheath flows such that they flow individually through a detection region. The resulting scattered light is then detected by etched optic fibers downstream. The proposed approach has the advantage that particles/cells can be counted without the need for fluorescent labeling or delicate optical alignment procedures. The current study confirms the success of the proposed microchip in the counting of polystyrene beads and human blood cells. The results also indicate that the intensity of the scattered light is proportional to the size of the particles/cells, which suggests that the proposed device may offer the potential to distinguish between particles/cells of different sizes.

Electrokinetic focusing injection methods on microfluidic devices.

Abstract: This paper presents an experimental and numerical investigation into electrokinetic focusing injection on microfluidic chips. The valving characteristics on microfluidic devices are controlled through appropriate manipulations of the electric potential strengths during the sample loading and dispensing steps. The present study also addresses the design and testing of various injection systems used to deliver a sample plug. A novel double-cross injection microfluidic chip is fabricated, which employs electrokinetic focusing to deliver sample plugs of variable volume. The proposed design combines several functions of traditional sample plug injection systems on a single microfluidic chip. The injection technique uses an unique sequence of loading steps with different electric potential distributions and magnitudes within the various channels to effectuate a virtual valve.

Micro capillary electrophoresis chips integrated with buried SU-8/SOG optical waveguides for bio-analytical applications

Abstract: This paper reports an innovative micro electrophoresis chip, which is integrated with buried optical waveguides on glass substrates for on-line detection of bio-analytical 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). Etched optic fibers are directly inserted into the waveguide channel for connection of light signal between microfluidic devices and peripheral optical sensors. With these novel approaches, delicate optical systems and tedious alignment procedures are not required for biomedical sample detection, resulting in a more compact or even a portable detection system. Experimental results show the developed micro capillary chip can detect Rhodamine B fluoresceins with a concentration as low as 10 −7 M by using multi-mode optic fibers as the connection of light between buried waveguides and the optical sensor. Two samples have been demonstrated to verify the performance of the chip, including a mixture of Rhodamine B and Cy 3 fluorescent dyes and FITC-labeled polypeptide samples. Both of them can be separated and detected successfully using the proposed device. The proposed device provides a cheap and simple method for on-line detection of biological samples. © 2003 Elsevier B.V. All rights reserved.

Multiple injection techniques for microfluidic sample handling

Abstract: This paper presents an experimental and numerical investigation into electrokinetic focusing flow injection for bioanalytical applications on 1 x N (i.e., 1 sample inlet port and N outlet ports) and M x N (i.e., M sample inlet ports and N outlet ports) microfluidic chips. A novel device is presented which integrates two important microfluidic phenomena, namely electrokinetic focusing and valveless flow switching within multiported microchannels. The study proposes a voltage control model which achieves electrokinetic focusing in a prefocusing sample injection system and which allows the volume of the sample to be controlled. Using the developed methods, the study shows how the sample may be prefocused electrokinetically into a narrow stream prior to being injected continuously into specified outlet ports. The microfluidic chips presented within this paper possess an exciting potential for use in a variety of techniques, including high-throughput chemical analysis, cell fusion, fraction collection, fast sample mixing, and many other applications within the micrototalanalysis systems field.

Poly(dimethylsiloxane)-based microfluidic device with electrospray ionization-mass spectrometry interface for protein identification.

Abstract: An easy method to fabricate poly(dimethylsiloxane) (PDMS)-based microfluidic chips for protein identification by tandem mass spectrometry is presented. This microchip has typical electrophoretic microchannels, a flow-through sampling inlet, and a sheathless nanoelectrospray ionization (ESI) interface. The surface of the microchannel was modified with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and the generated electroosmotic flow under acidic buffer condition used for the separation was found to be more stable compared to that generated by the microchannel without modification. The feasibility of the device for flow-through sampling, separation, and ESI-MS/MS analysis was demonstrated by the analysis of a standard mixture composed of three tryptic peptides. Results show that four peaks corresponding to three peptide standards and acetylated products of the standard peptide were well resolved and the deduced sequences were consistent with those expected. Furthermore, the compatibility of this device with other miniaturized devices to integrate the whole process was also explored by connecting a miniaturized enzymatic digestion cartridge and a desalting cartridge in series to the sampling inlet of the microchip for the identification of a model protein, beta-casein.

Microfluidic chips for DNA amplification, electrophoresis separation and on-line optical detection

Abstract: This paper reports at innovative microfluidic chip capable of performing DNA amplification (polymerase chain reaction, PCR), electrokinetic sample injection and separation, and on-line optical detection of DNA. All microfluidic modules are integrated on cheap and biocompatible soda-lime glass substrates using a simple and reliable fabrication process. With this approach, DNA samples could be first duplicated using the micro PCR module, then injected and separated in the micro electrophoretic channels driven by electrokinetic forces, and finally detected optically by buried optical waveguides downstream the separation channel. In order to have a better separation efficiency for DNA samples, a novel surface treatment method by coating a thin layer of spin-on-glass (SOG) is developed. Experimental data show that DNA samples can be successfully duplicated using the micro PCR device with less sample and reagent volumes in a shorter period thanks to lower thermal inertia of the micro devices. DNA samples can be injected, separated and detected successfully in the subsequent microfluidic channels. The integrated microfluidic device could be crucial for genetic analysis.

MEMS-based humidity sensors with integrated temperature sensors for signal drift compensation

Abstract: Humidity sensing is essential in such fields as environmental control, process monitoring and biomedical analysis. A microfabricated humidity sensor is developed which uses a nitride/silicon microstructure suspended at a small distance above the surface of a glass substrate as the movable electrode of a capacitor and thin-film platinum resistors as temperature sensing elements. The suspending structure is coated with polyimide - a vapor-absorbent polymer film. Moisture-dependent bending of the micro-cantilever is caused by the variation of humidity. The measured capacitance between the micro suspending structure and the substrate is changed. The humidity sensor is integrated with a platinum resistor as a micro temperature detector for compensation of the capacitance signal drift caused by temperature. A low hysteresis value is indicated at high relative humidity. Because of the large electrode area on the microcantilever tip and the low stiffness of the microcantilever, a high degree of sensitivity is also attained. The relative humidity and calibrated capacitance/resistance is documented and both of the simulated and experimental samples indicate a high stability and a high degree of linearity. The average time constant of the proposed microcantilever-based humidity sensors is 1.10 sec in the relative humidity range of 20 %R.H. to 40 %R.H.

A novel micro flow cytometer with 3-dimensional focusing utilizing dielectrophoretic and hydrodynamic forces

Abstract: This paper reports a micro flow cytometer with an innovative 3-dimensional focusing function that can concentrate particles/cells at the center of sample stream, resulting in a high-precision cell counting. Focusing of the sample flow is a critical issue for micro flow cytometers while counting the particles/cells using a buried optical waveguide. Appreciable errors could occur if the particles are randomly distributed vertically even though they have been focused horizontally. In this paper, a 3-D focusing micromachined flow cytometer is demonstrated using the combination of dielectrophoretic (DEP) and hydrodynamic forces. Three major modules have been integrated on glass substrates to form the microfluidic device, including a hydrodynamically driven flow cytometer, microelectrode arrays for dielectrophoretic forces and etched optical fibers for on-line cell detection. With this approach, cells with different sizes could be counted without fluorescence labeling and delicate optical alignment procedures are not required. Experimental data show that high-precision particle/cell counting could be achieved.

Platform technology for manipulation of cells, proteins and DNA

Abstract: MEMS has been an enabling technology for biomedical applications recently. Not only does it provide an instrument to obtain information on molecular level, but it also allows us to manipulate bio-molecules efficiently. Micro devices and systems for manipulation of biological objects such as cells, proteins and DNA have been demonstrated. In this study, we report a technique using dielectrophoretic forces to manipulate micro particles. First, the concept of several manipulation techniques is reviewed. Then we focus on novel manipulation modes. With the help of these biochips, we are able to perform manipulation of micro particles/cells.

Novel surface modification methods and surface property analysis for separation of dna bio-molecules using capillary electrophoresis

Abstract: This paper presents systematic investigation on the surface properties of electroosmotic flows (EOF) inside microchannels for quartz, glass and PDMS based materials. Two novel methods to modify the surface properties of glass-based microchannels for capillary electrophoresis (CE) are developed. Instead of using complicated and time-consuming chemical silanization procedures for surface modification of the CE channels, two simple and reliable methods utilizing organic-based spin-on-glass (SOG) and water-soluble acrylic resin are reported, providing a fast and batch process for surface modification of glass-based CE channels. The proposed methods are evaluated using separation of @X-l 74 DNA makers. Experimental data sholv that separation efficiency is greatly improved. In addition, long-term stability of the SOG coating is also verified in this study.

M/spl times/N micro flow switches using electrokinetic forces

Abstract: This paper presents experimental and numerical investigation on electrokinetic-focusing 1/spl times/N (1 sample inlet-port and N outlet-ports) and M/spl times/N (M sample inlet-ports and N outlet-ports) flow switches for bio-analytical applications. The microfluidic device integrates two important microfluidic phenomena, including electrokinetic-focusing and valveless flow switching inside multi-ported microchannels. A voltage control model is proposed, which achieves electrokinetic focusing/switching in a pre-focusing flow switch system. Using the developed methods, the sample can be electrokinetically pre-focused to a narrow stream and can be continuously injected into desired outlet ports. The microfluidic chip presented here is promising for high-throughput chemical analysis, cell fusion, fraction collection, fast sample mixing and many other applications in the field of micro-total-analysis systems.

Design and fabrication issues on micromachined oxygen sensors for miniaturized energy consumption measurement systems

Abstract: The size and cost of indirect calorimeters hinder their application in hospitals. This study employs micro-electromechanical systems MEMS techniques to develop oxygen sensors as one part of a miniaturized energy consumption measurement system for premature babies. Typically, the system is designed to operate at high oxygen concentrations. Accordingly, the current study deals with the development of oxygen sensors capable of sensing higher concentrations of oxygen at a low operation temperature of 150°C. The proposed gas sensors consist of a polysilicon resistor and a sensing metal-oxide film placed on a thermally isolated silicon-nitride membrane or bridge. The sensing film is a tin oxide sheet, which has been doped with a low concentration of 2wt% Li. This study involves the development of three different types of oxygen sensors, which are distinguished from each other by the structure of their microheaters. The first type is a microheater on a silicon nitride membrane, the second type employs a membrane located on a thin silicon layer, and the third type uses a bridge membrane with a thin underlying layer of silicon. At an operating temperature of 150°C, the power consumptions of these three sensors are found to be 24 mW, 223 mW and 1240 mW, respectively. The resulting experimental data indicate that the proposed oxygen sensors are capable of detecting oxygen with concentrations ranging from 21% to 50%, and that they exhibit a linear output behavior. These characteristics render the oxygen sensors suitable for use in most clinical applications within a hospital environment.