THESIS
2002
xi, 73 leaves : ill. ; 30 cm
Abstract
With the progress of the Human Genome project, there is a tremendous demand for efficient instrument for analyzing DNA-encoded information. The difficulties in handling the vast amount of infomation contained in DNA molecules can be resolved by using microelectronic technologies to convert the biological or chemical responses to an electrical signal and perform analysis in the electrical domain with the well-developed signal processing techniques. In this thesis, our work will focus on the identification of whether a known sequence exists in a DNA sample. The process aims at the application of early disease determination due to the existence of certain gene mutation (e.g. cancer). The process involves the synthesis of the target gene sequence (called probes), applying the sample to be d...[
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With the progress of the Human Genome project, there is a tremendous demand for efficient instrument for analyzing DNA-encoded information. The difficulties in handling the vast amount of infomation contained in DNA molecules can be resolved by using microelectronic technologies to convert the biological or chemical responses to an electrical signal and perform analysis in the electrical domain with the well-developed signal processing techniques. In this thesis, our work will focus on the identification of whether a known sequence exists in a DNA sample. The process aims at the application of early disease determination due to the existence of certain gene mutation (e.g. cancer). The process involves the synthesis of the target gene sequence (called probes), applying the sample to be diagnosis to the probes and determine whether a match is found. In this process, an effective method to detect the DNA matching is becoming very important. Compared with the traditional approach of optical signal based detection system’s, we propose an integrated detection system for biochip applications. The proposed integrated detection system of gene chip takes the advantage of the mature microelectronic fabrication technology, which can be very cheap with the volume production and the accumulated experience on processing, reliability, yield etc.
A CMOS photodiode system form DNA identification has been demonstrated. In order to incorporate the DNA material onto the silicon based material, minor modification to the photodiode fabrication process to incorporate inert metals is necessary. The spectral sensitivity of junction photodiode used for detecting labelled DNA sample in genomic engineering field has been studied. The spectral response of CMOS based photodiode to the optical spectrum related to the emissions of DNA optical label with different UV light excitation sources are presented. It is found that by adjusting the light source spectrum, the spectral response of the photodiode can be used as a natural filter to detect the desired signal. This can significantly simplify the fabrication of integrated biochip for DNA analysis.
A resistance detection system for DNA identification has also been demonstrated. An electrical sensor used for detecting the array-based electrical signal of DNA with nanoparticle probes has been fabricated and experimentally demonstrated. The detection mechanism is based on the attachment of metal nanoparticles (gold or silver) to a DNA molecule and the amount of matched DNA is monitored by the conduction change due to the amount of deposited metal particle. The details of fabrication steps and the procedures of attaching the target probe associated with gold nanoparticles onto the silicon-based fixture are presented in this paper. Experimental results show that a matched and unmatched DNA sample functionalised with gold nanoparticles can be easily distinguished. By using the method of silver enhancement and pre-hybridization, the concentration of 10pM has been achieved. It proves that the sensitivity of the resistance detection system exceeds that of the conventional fluorescence detection system by two orders of magnitude. Compared with the traditional approach of optical signal based detection systems, the proposed approach can significantly simplify the fabrication process of integrated bio-detection system and facilitate the integration of bio-chip application with the mature integrated circuit technology. This resistance-based identification provides a revolutionary approach for DNA identification.
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