國立臺灣大學應用力學研究所李世光2006-07-262018-06-292006-07-262018-06-292005-07-31http://ntur.lib.ntu.edu.tw//handle/246246/21753由於醫藥科技的發達，大部分早期造成人類高死亡率的疾病已有許多藥物控制。然而 現今許多新的疾病出現或者是已知疾病的變種，使得人類面臨新的威脅。面對捲土重來的 已知疾病，開發快速檢測方式與有效藥物篩選，是所有生物製藥技術的共同目標所在，期 望對於人類疾病進行有效的控制與治療，當今蓬勃發展之生物晶片即是一極具潛力的檢測 方式。以結核病為例，此一疾病發病率逐漸攀升，貧困地區尤其受到嚴重威脅，每年死亡 人數甚至超過愛滋病、瘧疾、腹瀉及熱帶病死亡人數之和。目前肺結核之診斷除了一般胸 部X光檢查，主要是靠痰液之檢查。然而痰液檢查之敏感性不高且相當耗時，要蒐集多次 痰液檢查且需經一個多月才能獲得完整之報告，因此經常延誤治療的時機。在卡介苗接種 的成效一再被質疑之下，開發新的檢測方法以因應結核菌之大量篩檢，和快速且有效治療 肺結核的藥物之篩選 是一重要的課題。 生醫晶片的相關檢測技術中，有以下發展的趨勢，即(1)為非接觸式(non-contact)，檢測 不會影響被測體;(2)具高靈敏度(high sensitivity)、大頻寬(wide bandwidth)及小量測體積 (small probe volume)等。同時在全球生醫晶片之試樣與檢體均快速縮小的狀況下，只有光電 檢測技術才是最為適用量測方式，目前使用最廣、精確度較高、使用廣泛光電檢測技術有 橢偏術(Ellipsometry)、表面電漿共振術(surface plasmon resonance, SPR)、以及最近一年來才 被應用在商業儀器上的波導干涉儀(Waveguide Interferometry)。 配合總計畫所提出「光生化型晶片系統於藥物篩選與疾病檢測之研發」之計劃，本子 計畫負責「特用型光生化型晶片儀」之研究開發。一方面利用本研究團隊所發展已具雛形 之創新多功能光電生醫晶片儀(Opto-BioMorphin，OBMorph)改良，進行表面電漿共振相位 偵測技術之開發，並進行高速量測橢偏儀之光機設計，橢偏儀功能的量測速率增加十倍， 大大提升其應用之優勢。本子計劃於本年度執行期間亦有另一重要突破：廣泛蒐集相關檢 測資訊，提出與目前最新晶片檢測技術同步之波導干涉技術。本技術不僅是採用波導干涉 之量測技術，更整合旋轉分析板雙偏極光干涉技術，讓本系統具有即時檢測的潛力。 除了檢測平台之開發外，本計畫與總計劃及其他子計劃共同開發之肺結核疾病篩選系 統，對於其鎖定之結核病抗原抗和抗體蛋白質，進行生化結合反應之量測，並獲得初步結 果，印證本TBMorph系統配合計劃開發之結核病篩選目標物，確實具有篩選結核病之能力， 且具結核病藥物篩選之潛力。而新開發之旋轉分析板雙偏極光干涉技術也已進行生物分子 反應量測，證明本計畫開發的技術可應用於生物檢測之上。此外，本研究計畫進一步利用 TBMorph的表面電漿共振相位偵測技術來觀察因血糖濃度不同所造成的折射率變化，證實 TBMorph於一般醫學檢測應用之可行性。Human beings have been threatened by tuberculosis for a long time. However, as the mortality rising gradually, especially those from depressed area, this problem is getting more seriously as time goes by. Death count that can be attributed to tuberculosis every year is more than the summation of those for AIDS, malaria, diarrhea and tropical diseases. In addition to x-ray photograph and test of skin tubercle bacillus, sputum test is currently the major way to diagnose tuberculosis. This method includes smear dyeing of mycobacteria and germiculture. However, sputum test suffers from low sensitivity and long detection time. Besides, repeatedly test, it usually takes more than a month to get a complete report. The opportune moment is often wasted. While more the more people suspect the effect of BCG vaccine, it is necessary to develop new methods to handle large number of tubercle bacillus detection. The vigorously progressing biochip is a promising technique. The trends of biochip-related technique are as follows. (1) Use non-contact technique to avoid influence the sample. (2) To achieve high sensitivity, wide bandwidth and small probe volume. At the same time as the worldwide trend to reduce of the sample for biochip, opto-electric technique is the most suitable detection method. Out of all these opto-electronic techniques, surface plasmon resonance, ellispsometry, and waveguide interferometry developed within the last year are some of the most promising techniques for wide spread use. This sub-project is in charge of development of the TBMorph (Tuberculosis Morph) in coordination with the main project to pursue the research on the “Opto-BioMorphin” that used in the epidemic detection and the drug development. On one hand, the phase detection surface plasmon resonance has been brought up and been integrated into TBMorph. The measuring speed of Ellipsometer function has been improved and the speed has increased 10 times. This became a new advantage for TBMorph’s applications. On the other hand, there is a very important breakthrough of this year execution. The rotating analyzer-based dual polarized waveguide interferometer has been successfully accomplished. This newly developed technique not only adopts Waveguide Interferometry but also integrates the dual polarized phase shifting metrology. The system thus has the potential to have the real-time measurement ability. Besides the development of the detecting platforms, the preliminary results of biochemical binding reaction between TB and antibody were also carried out by TBMorph in this sub-project. It proved that TBMorph has the ability to select the better antibody that has strong specificity to pulmonary tuberculosis. The newly developed technique, “the rotating analyzer-based dual polarized waveguide interferometer”, also has been proved its ability in bio-reactions measurement. The reaction between human IgG and anti-IgG has been successfully measured. Moreover, TBMorph can also detect the variation in reflection index due to the change in the concentration of glucose by utilizing phase detection SPR function. The experimental results of glucose detection are a strong support that TBMorph can be widely used in biological examination.application/pdf856785 bytesapplication/pdfzh-TW國立臺灣大學應用力學研究所光生化檢測儀生醫晶片橢偏儀表面電漿共振儀波導干涉儀Opto-BioMorphinOBMorphbiochipellipsometerSurface Plasmon ResonanceWaveguide Interferometry[SDGs]SDG3[SDGs]SDG11reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/21753/1/932323B002012.pdf