I-Yu Huang

Development of a Novel Flexural Plate Wave Biosensor for Immunoglobulin-E Detection by Using SAM and MEMS Technologies

This paper presents the design, fabrication and characterization of a novel flexural plate wave (FPW) microsensor for immunoglobulin-E (IgE) detecting applications. The propagation membrane is constructed with SiO2/Si3N4/ZnO multilayers and be released from the silicon substrate as a floating thin-plate by using bulk micromachining technology. The ultrasonic flexural plate waves are launched and received by a pair of Cr/Au interdigital transducers (IDTs) on the surface of the ZnO piezoelectric thin film. In this study, we demonstrated a high C-axis orientation ZnO piezoelectric thin film deposition, an IgE self-assembly monolayer (SAM) immobilization and a FPW allergy microsensor with 21 MHz center frequency and 233 cm3/g mass sensitivity. This is the first report demonstrating human IgE detection by an FPW-based microsensor.

Development and Characterization of FPW Based Allergy Biosensor

This paper presents a novel flexural plate wave (FPW) allergy microsensor with integrated cystamine-based self-assembly monolayers (SAMs) for the detection of immunoglobulin-E (IgE) concentration in human serum. The propagation membrane of the FPW biosensor is constructed with Si/SiO2/Si3N4/ZnO multi thin-films and released from the 512 mum-thick 4-inch silicon substrate as a floating thin-plate by using bulk micromachining technology. To improve the yield and performance, a 3 mum-thick silicon diaphragm of the FPW device is designed in this research. The ultrasonic flexural plate waves are launched and received by a pair of Cr/Au interdigital transducers (IDTs) on the surface of the ZnO piezoelectric thin film. In this study, a 3 nm-height cystamine-glutaldehyde SAMs is developed for the immobilization of IgE antibody. The implemented FPW-based allergy biosensor with relatively high mass sensitivity (17200 cm2/g) and perfect sensing linearity (99.99%) of human IgE antigen is demonstrated in this paper.

A CEA Concentration Measurement System Using FPW Biosensors and Frequency-shift Readout IC

In this paper, a CEA (carcinoembryonic antigen) concentration measurement system using flexural plate wave (FPW) biosensors and a frequency-shift readout IC is presented. The proposed frequency-shift readout method employs a programmable frequency generator and a peak detecting scheme to estimate the resonant frequency. The programmable frequency generator provides a frequency scanning range from 0.9 MHz to 25 MHz according to the characteristics of the FPW biosensors. Particularly, the proposed frequency-shift readout circuit filters and amplifies the FPW biosensors signals such that the requirements for the following voltage peak detector can be relaxed. Therefore, the sensitivity and performance of the CEA sensing system are also enhanced. The sensitivity of the peak detector is 5 mV at the highest signal rate, 50 MHz. The proposed frequency-shift readout circuit is implemented using a typical 0.18 μm CMOS technology. The power consumption of the proposed CEA concentration measurement system is 7.69 mW justified by HSPICE simulations.

Effects of a glutaraldehyde cross-linking layer on a quartz crystal microbalance–based α-fetoprotein biosensor with cystamine self-assembly monolayer

To identify the extreme low concentration of alpha-fetoprotein (AFP) antigen in human serum for early detection of hepatocellular carcinoma, we aim to develop a high-sensitivity and low-cost AFP biosensor using quartz crystal microbalance (QCM) and cystamine self-assembly monolayer (SAM) technologies. In this study, the surface topographies of concentrations (0.1 and 1.0 mg/mL) of AFP antibody with and without 1.25% glutaraldehyde cross-linking layer will be analyzed by an atomic force microscope system to investigate the effects of the glutaraldehyde layer on the sensing characteristics of the QCM-based AFP biosensor. According to our experimental results, the mass sensitivity was improved almost doubly (from 0.07 to 0.146 Hz mL mg−1) as the glutaraldehyde layer was added between the 20-mM cystamine SAM and the low-concentration (0.1 mg/mL) AFP antibody. Either with or without the glutaraldehyde layer, higher mass sensitivity (0.163 to 0.335 Hz mL mg−1) was obtained as the AFP antibody concentration increased to 1.0 mg/mL. However, a large AFP antibody requirement will increase fabrication cost and limit disposable application. We also demonstrated that high sensing linearities (95.67 to 99.6%) of the QCM-AFP biosensors can be achieved without being obviously affected by the glutaraldehyde layer and AFP antibody concentration.

The effect of glutaraldehyde cross-linking layer on QCM based alpha-fetoprotein biosensor

To identify the extreme low concentration of alpha-fetoprotein (AFP) antigen in human serum for early detection of hepatocellular carcinoma (HCC), this paper aims to develop a high-sensitivity and low-cost AFP biosensor using quartz crystal microbalance (QCM) and cystamine self-assembly monolayer (SAM) technologies. QCM-based biosensors usually require smaller sampling, lower testing cost and fewer responding time than the conventional analysis system. The QCM-based AFP biosensor coated with a 20 mM cystamine SAM and a 1.0 mg/mL AFP antibody layer shows a high mass-sensitivity (0.35 Hz mL mg−1) and sensing linearity (98.6%). However, its mass-sensitivity will be reduced to 0.092 Hz mL mg−1 as the concentration of AFP antibody is decreased to 0.1 mg/mL. In this study, a 1.25 % glutaraldehyde cross-linking layer was added between the cystamine SAM and the AFP antibody to improve the mass-sensitivity (0.128 Hz mL mg−1) as the AFP antibody concentration is low (0.1 mg/mL). The surface topographies of cystamine and glutaraldehyde will be analyzed by an atomic force microscope (AFM) system to investigate the effects of the glutaraldehyde layer on the QCM based AFP biosensor.

Development of an FPW Biosensor with Low Insertion Loss and High Fabrication Yield for Detection of Carcinoembryonic Antigen

In the last two decades, various flexural plate-wave (FPW)-based biosensors with low phase velocity, low operation frequency, high sensitivity, and short response time, have been developed. However, conventional FPW transducers have low fabrication yield because controlling the thickness of silicon/isolation/metal/piezoelectric multilayer floating thin-plate is difficult. Additionally, conventional FPW devices usually have high insertion loss because of wave energy dissipation to the silicon substrate or outside area of the output interdigital transducers (IDTs). These two disadvantages hinder the application of FPW devices. To reduce the high insertion loss of FPW devices, we designed two focus-type IDTs (fan-shaped and circular, respectively) that can effectively confine the launched wave energy, and adopted a focus-type silicon-grooved reflective grating structure (RGS) that can reduce the wave propagation loss. To accurately control the thickness of the silicon thin-plate and substantially improve the fabrication yield of FPW transducers, a 60 °C/27 °C two-step anisotropic wet etching process was developed. Compared with conventional FPW devices (with parallel-type IDTs and without RGS), the proposed FPW devices have lower insertion loss (36.04 dB) and higher fabrication yield (63.88%). Furthermore, by using cystamine-based self-assembled monolayer (SAM) nanotechnology, we used the improved FPW device to develop a novel FPW-based carcinoembryonic antigen (CEA) biosensor for detection of colorectal cancer, and this FPW-CEA biosensor has a low detection limit (5 ng/mL), short response time (<10 min), high sensitivity (60.16–70.06 cm2/g), and high sensing linearity (R-square = 0.859–0.980).

Development of suspended planar two port micro transformer for RF wireless application

In order to improve the quality-factor and magnetic coupling factor of micro transformer at high operating frequency, this paper presents two-port micro transformer utilizing micro-electro-mechanical systems (MEMS) technology are featured with very small chip size (0.7 mm×0.7 mm×0.5 mm) and constructed of a 0.32 μm-thick TaN/Ta/Cu bottom electrode, 10 μm-height supporting copper via, and a 6 μm-thick suspended spiral copper conducting layer with 10 μm air gap. Measurement results show the implemented two-port micro transformer demonstrates very high magnetic coupling factor (0.78) and quality-factor (17.2) at 5.2 GHz operating frequency.

Development of microthermoelectric generators using integrated suspending bridge-type polysilicon thin-film thermopiles

Abstract. We describe the development of novel suspension bridge-type microthermoelectric generators (μ-TEGs) having 64,000 to 147,000 serial-connected thermocouples in a 1-centimeter-square chip area using surface micromachining techniques. Each microthermocouple is constructed by a pair of n/p bridge-type polysilicon thin-film thermolegs and a pair of cold- and hot-side Cr/Au metal planes. Under a controlled fixed temperature difference between the cold/hot sides, the open-circuit voltage and the output power of the proposed μ-TEGs are simulated by commercial software (ANSYS). The influences of thermocouple thermo-leg dimensions and number of thermocouples on the thermoelectric characteristics of presented μ-TEGs are investigated. The implemented suspension bridge-type thermopile has a 2.5-μm-height air-gap separation from substrate and its fabrication yield is higher than 75% in the laboratory environment. The measured maximum temperature difference between the cold/hot sides of the proposed μ-TEGs is about 1.29°C, a maximum open-circuit voltage of 4.64  V/cm2 and output power of 0.65  μW/cm2 can be obtained.

Improvement of insertion loss and quality factor of flexural plate-wave-based alpha-fetoprotein biosensor using groove-type reflective grating structures

Abstract. Conventional flexural plate-wave (FPW) transducers have limited applications in biomedical sensing due to their disadvantages such as high insertion loss and low quality factor. To overcome these shortcomings, we propose a FPW transducer on a low phase velocity insulator membrane (5-μm-thick SiO2) with a novel groove-type reflective grating structure design. Additionally, a cystamine self-assembly monolayer and a glutaraldehyde cross-linking layer are implemented on the backside of the FPW device to immobilize alpha-fetoprotein (AFP) antibody. A FPW-based AFP biosensor with low detection limit (5  ng/mL) can be achieved and used to measure the extreme low concentration of AFP antigen in human serum for early detection of hepatocellular carcinoma. The proposed FPW-based AFP biosensor also demonstrates a very high quality factor (206), low insertion loss (−40.854  dB), low operating frequency (6.388 MHz), and high sensing linearity (90.7%).

A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique

A protein concentration measurement system with two-port flexural plate-wave (FPW) biosensors using a frequency-shift readout technique is presented in this paper. The proposed frequency-shift readout method employs a peak detecting scheme to measure the amount of resonant frequency shift. The proposed system is composed of a linear frequency generator, a pair of peak detectors, two registers, and a subtractor. The frequency sweep range of the linear frequency generator is limited to 2 MHz to 10 MHz according to the characteristics of the FPW biosensors. The proposed frequency-shift readout circuit is carried out on silicon using a standard 0.18 μm CMOS technology. The sensitivity of the peak detectors is measured to be 10 mV. The power consumption of the proposed protein concentration measurement system is 48 mW given a 0.1 MHz system clock.