자기조립 단분자막을 이용한 BioFET형 알부민센서의 제조 및 특성
Fabrication and characterics of bioFET albumin sensor employing new self-assembled monolayer
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There have been many researches about detecting biological molecules, such as protein, RNA, and DNA, which are central to biological processes. Especially, albumin proteins are of great nutritional value and directly involved in the chemical processes essential for life. Generally, there are optical measurement, spectrometers, and electrochemical measurement as the conventional method to analyze biological molecules such as albumin protein. However, all these methods involve time-consuming and multi-stage processes that are expensive and unsuitable for on-line monitoring. To overcome these disadvantages, in this thesis, the new type BioFET(bio field-effect transistor) albumin sensor that is able to diagnose kidney disease easily and rapidly was fabricated and its characteristics were investigated. The FET type biosensors based on MOS(metal-oxide-semiconductor) technology have many advantages that are related to their miniaturization, to their capability of measuring different species on the same silicon chip, and finally to the large-scale production capabilities of the microelectronic industry because they are fabricated by the standard CMOS process. In this thesis, the gold(Au) instead of a conventional dielectric material was used as the gate metal of the proposed BioFET albumin sensor to form the new biological receptor and then the gold gate surface was chemically modified by the new molecular receptor of TBCEA(thiazole benzo crown ether ethylamine)-thioctic acid, so called SAM (self-assembled monolayer) which was designed to be able to combine its functional part with an albumin antibody selectively. The immobilization of the biosensing material is a critical step in the production of sensor because the mechanism for sensing an albumin is the binding interaction between an albumin antibody immobilized on the gate surface and an albumin(antigen) in the test solution. The proposed SAM is appropriately immobilized because the thiols, chemical reactor of SAM, form the covalent bonding on the gold surface strongly. Consequently, the proposed BioFET albumin sensor has the albumin antibodies immobilized on the SAM as a sensing layer. The surface potential difference generated by the binding of antigen-antibody on the gate was taken as the output of a BioFET. The MOSFET as a basic device for making the albumin sensor was designed by the simulation programs that are ATHENA for 2-D process simulation and ATLAS for 2-D device simulation, and then was fabricated by the standard CMOS process. The BioFET albumin sensor was finally fabricated with the immobilization of an albumin antibody on the SAM that was chemically adsorbed on the gold gate surface in the PBS solution with TBCEA-thiotic acid. The SPR and the QCM measurement were performed to confirm the immobilization of the SAM and an albumin antibody. Experimental results obtained from the SPR showed that the resonance angle shifts caused by the formation of the SAM on the gold surface, the albumin antibodies, and the albumins were 0.3, 0.6, and 0.8 degree, respectively, and in case of the QCM measurements the resonance frequency variations were 14, 520, and 490 Hz, respectively. It is means that the proposed new SAM is available to use the receptor. The response of the BioFET albumin sensor was linear between 30 ㎎/L and 100 ㎎/L of albumin concentration and the output voltages for each albumin concentration were 67 ㎷ at 30 ㎎/L, and 148 ㎷ at 100 ㎎/L. It is obviously outstanding results compared with conventional non-FET type biosensors such as paper test. The disadvantages of the FET type semiconductor sensors are the dependence upon light and temperature and the large size reference electrode which hinder the miniaturization of an entire sensor system. To overcome those, the BioFET/QRE(quasi-reference electrode)/REFET(reference-electrode field effect transistor) sensor system employing the differential amplifier method was proposed. The responses of this system with the thin film type platinum(Pt) quasi-reference electrode(QRE) were obtained by the differential amplifier which rejected the noise from both the BioFET and the REFET. The experimental results showed that the noises caused by the light and the temperature disturbance were eliminated by the BioFET/QRE/REFET albumin sensor system. Based on experimental results it will be expected that the proposed BioFET albumin sensor can be applied as a biosensor for diagnosis and treatment of kidney disease, and be commercialized through the further researches.