Development of High Throughput Multi-functional Opto-electric Biochip System
Date Issued
2005
Date
2005
Author(s)
Jhuang, Cong-You
DOI
zh-TW
Abstract
In this dissertation, a high throughput multi-functional opto-electric biochip system was built. The system named OBMorph, which is an acronym of Opto-bioMorphin, was designed to analyze the biomolecular interaction on a protein biochip. This instrument based on ellipsometry theory can be utilized in high-tech industries, which may include semiconductor manufacturing, inspec-tion equipment, CD/DVD disks, and other thin-film related operations. In addi-tion, application to biomedical area can include film thickness, physical parame-ters, concentration, mass, density, kinetic constants, binding specificity, and so on. By using the wave-plate to modulate phase retardane, the bio-tech detection ac-curacy can be significantly improved. The testing data obtained clearly indicate that OBMorph system is able to undertake accurate measurement for biomedical applications.
OBMorph adopted a paraboloidal mirror to vary the incident angle, the wave-plates to modulate phase retardation, a reference optical path to stabilize the optical source, and a flow-injection system to drive bio-sample into the bio-chip. In order to having high precision in the ellipsometry subsystem of OB-Morph, it adopt a 0.4μm accuracy servomotor to control the stage that carried the right angle mirror and to control the variation of the incident angle. By using this method, a ±0.001°angular control accuracy between 20°to 80°can be achieved. The interrogation angle could be retrieved accurately which leads to much higher sensitivity and stability by identifying Brewster’s angle of the stan-dard tester. This biosensor developed in this thesis is phase modulated ellipsome-try, which utilized a wave-plate to modulate phase retardance. By using this wave plate modulation method, the phase retardance dectected becomes more stable when compared to that of the piezoelectric actuator driven method. In our system, a reference optical path would be carried out, and the light souce in-stability would be reduced with the feedback of the reference beam. With above mentioned arrangements, OBMorph could serve a research and a high throughput measurement tool in biomedical measurement.
In the procedures of detecting the bio reactions, the transfer function of sys-tem must be applied to calibrate and analysis the ellipsometry parameters of the samples and this will improve the accuracy. The commercial reflected mirror, the bare silicon wafer, and the wafer coated with 300 nm chromium film were taken as the standard testers. As the experimental results, the error is about 3% of the measured gold thickness which is calculated by the system function ac-cording the bare silicon wafer. After that, the biomolecular interactions called enzyme-link immunosorbent assay, ELISA have been measured. OBMorph shows good ability to distinguish every step of the reactions. Since the experi-mental results and the simulation data agree well with each other, it is proven that ellipsometer possesses both great resolution and high throughput within OB-Morph. Furthermore, this system is equipped with high-efficiency flow injec-tion system that can measure not only the immobilized monolayer of IgG and bio-linker but also the thickness of bio layers. In summary, both the simulation and the experimental results obtained proved that OBMorph has many advan-tages in the bio-molecular measurement arena.
Subjects
橢偏術
表面電漿共振
ellipsometry
surface plasmon resonance
Type
thesis