何國川臺灣大學：化學工程學研究所葉威明Yeh, Wei-MingWei-MingYeh2007-11-262018-06-282007-11-262018-06-282005http://ntur.lib.ntu.edu.tw//handle/246246/52057本研究中主要分成三大部份， 首先我們以methacrylic acid （MAA）為單體、trimethylolpropane trimethacrylate（TRIM）為交聯 劑，在目標分子（template）—嗎啡（morphine, MO）的存在下，利 用沈澱聚合（precipitation polymerization）的方法製作出嗎啡分子模 版（molecularly imprinted polymer, MIP），比較傳統塊狀聚合（bulk polymerization）與沈澱聚合所製備分子模版的粒徑分布、表面形態與 表面積等特性分析，並以styrene與MAA單體掺混的方式聚合分子模 版，比較不同官能基單體掺混對嗎啡的吸附效果，分析單體官能基與 模版選擇性的影響，並在不同嗎啡濃度下測量分子模版吸附量，以 Scatchard plot估算沈澱聚合分子模版的脫附常數（KD）為0.45 mM與 吸附嗎啡的最大量（Bmax）可達186 µmole/g。 第二部分，將3,4-Ethylenedioxythiophene (EDOT)作為單體，以 電聚方式包覆沈澱聚合後之分子模版於導電玻璃ITO 上作為修飾電 極（MIP/PEDOT），以定電位方法感測嗎啡，線性感測範圍為0.1~2.0 mM，MIP/PEDOT 修飾電極的靈敏度為41.63 µA/cm2 *mM，感測下限 為0.3 mM（S/N=3），模版效率為1.11。另一方面以EDOT 做為模版 單體，分別合成嗎啡（MIP-PEDOTMO）與膽固醇（MIP-PEDOTChol） 分子模版修飾電極，以PEDOT 薄膜催化嗎啡的能力，定電位的方式 感測嗎啡，線性感測範圍為0.1~1 mM，MIP-PEDOTMO 修飾電極的靈 敏度為91.86 µA/cm2 *mM，感測下限為0.2 mM（S/N=3），模版效率為1.32。膽固醇感測方面，因為膽固醇為非電活性物質，所以無法直 接以電流的訊號判斷濃度，故於溶液中加入赤血鹽為電流指示劑，利 用MIP-PEDOTChol 修飾電極上膽固醇的特殊孔洞，對吸附膽固醇後造 成PEDOT 高分子鏈的收縮，使得指示劑分子於修飾膜中通透量增 加，間接測量指示劑電流與濃度的關係來感測溶液中的膽固醇， MIP-PEDOTChol 修飾電極吸附膽固醇後電流變化的線性範圍為0~20 µM，靈敏度為11.768 nA/cm2 *µM，模版效率為1.81。另一方面，也 利用膽固醇容易吸附在MIP-PEDOTChol 修飾電極上的特殊孔洞，使修 飾薄膜電容發生改變，感測線性範圍為0~10 µM，MIP-PEDOTChol 修 飾電極靈敏度分別為5.92 µF/cm2 *µM，模版效率為2.21。 最後，將MIP-PEDOTMO 製備於商用IDA 上，以銀膠與FeCl3 溶 液製作成Ag/AgCl 的參考電極，電位變動在感測200 秒內不超過0.4 mV（vs. Ag/AgCl/sat’d KCl），線性感測範圍為0.01~0.10 mM，靈敏 度為0.0894 A/cm2 *mM，模版效率為4.71，感測下限可達0.02 mM （S/N=3）。並利用微機電製程方式，自製三極式微電極感測嗎啡，線 性感測範圍為0.01~0.2 mM，MIP-PEDOTMO 修飾薄膜於自製微電極 的靈敏度為171.47 µA/cm2 *mM，模版效率為1.19，感測下限為0.2 µM （S/N= 3）。In this work, molecular imprinted polymers (MIPs) of morphine (MO) were prepared through precipitation polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) in the presence of MO templates. The distributions of particle size, morphologies, and surface areas were compared with bulk polymerization. Furthermore, the copolymers of styrene and MAA with different functional groups were synthesized and the adsorption of MO was measured. From the Scatchard plot, the dissociation constant and the maximum amount of adsorption were calculated 0.45 mM and 186 µmole/g, respectively. Poly(3,4-ethylenedioxythiophene) (PEDOT) was utilized to immobilize the MIP particles onto the indium tin oxide (ITO) glass as a MIP/PEDOT-modified electrode. The sensitivity of MIP/PEDOT with amperometric detection of MO was 41.63 µA/cm2*mM, ranging from 0.1 to 2 mM. The detection limit and imprinting efficiency were 0.3 mM (S/N=3) and 1.11, respectively. On the other hand, the PEDOT was also used to prepare the MIP modified electrodes of MO (MIP-PEDOTMO) and cholesterol (MIP-PEDOTChol) directly. The PEDOT film was capable of electro-catalyze oxidize of MO and detected MO in MIP-PEDOTMO modified electrode with the amperometric method. The sensitivity of MIP-PEDOTMO was 91.86 µA/cm2*mM, ranging from 0.1 to 1 mM MO. The detection limit was 0.2 mM (S/N=3) and the imprinting efficiency was 1.32. As for the detection of cholesterol (Chol), Chol was electro-inactive and the oxidation current of Chol can’t be obtained directly. Therefore, K3Fe(CN)6 was served as an indicator for the current response in the solution. As Chol was adsorbed on the MIP-PEDOTChol IV modified electrode, the MIP polymer chain shrank and increased the porosity of MIP. Such an increase in porosity was expected to result in an increase in the diffusive permeability of the MIP and an enhancement of Faradic current of the K3Fe(CN)6. The sensitivity of MIP-PEDOT with indirect amperometric method was 11.768 nA/cm2*µM from 0 to 20 µM. The imprinting efficiency was 1.81. The capacitive detection of Chol has been developed using the MIP-PEDOTChol modified electrode. A capacitance decreased could be obtained as Chol adsorbed on the sites of MIP film. The sensitivity of capacitance shift was 5.92 µF/cm2*µM from 0 to 10 µM and the imprinting efficiency was 2.21. Finally, the MIP-PEDOT was prepared on the commercial interdigital array (IDA). The Ag/AgCl reference electrode (RE) was prepared with silver glue and FeCl3 solution. The variation of RE potential was less than 0.4 mV (vs. Ag/AgCl’sat KCl) in 200s. The sensitivity was 0.0894 A/cm2*mM from 0.01 to 0.10 mM and the imprinting efficiency was 4.71. The detection limit was 0.02 mM (S/N=3). With micro-fabrication process, we were able to fabricate the MIP-PEDOT electrode in a three-electrode system for sensing MO. The sensitivity on the microelectrode was 171.47 µA/cm2*mM from 0.01 to 0.2 mM MO. The imprinting efficiency and detection limit were 1.19 and 0.2 µM (S/N=3), respectively.中文摘要...................................................I 英文摘要.................................................III 致謝.......................................................V 目錄.....................................................VII 表目錄.....................................................X 圖目錄....................................................XI 符號說明................................................XVII 縮寫說明...............................................XVIII 第一章 緒論.............................................1 1-1 前言....................................1 1-2 分子模版之簡介..........................3 1-2-1 分子模版之表現性質之測定................8 1-2-2 分子模版技術之應用......................8 1-3 嗎啡特性及其感測發展...................13 1-3-1 嗎啡之特性.............................13 1-3-2 嗎啡之感測發展.........................16 1-4 嗎啡分子模版之文獻回顧.................21 1-4-1 膽固醇之特性...........................21 1-4-2 膽固醇之感測發展.......................25 1-5 研究動機與架構.........................35 第二章 原理............................................37 2-1 沈澱聚合法之原理.......................37 2-2 分子模版吸附分析.......................42 2-3 電流式感測原理.........................44 2-3-1 電極反應速率與電流的因素...............44 2-3-2 感測原理...............................45 2-4 電容式感測原理.........................50 第三章 實驗設備與方法..................................53 3-1 儀器設備...............................53 3-2 實驗藥品...............................55 3-3 實驗方法...............................57 3-3-1 嗎啡微球型分子模版之製備...............57 3-3-2 分子模版性質測試.......................58 3-3-3 MIP粉體模版修飾電極之製備..............58 3-3-4 嗎啡電流式感測.........................61 3-3-4-1 感測電位的選定.........................61 3-3-4-2 感測曲線...............................61 3-3-4-3 嗎啡干擾物之分析.......................62 3-3-5 MIP-PEDOTMO薄膜修飾電極之製備..........63 3-3-6 MIP-PEDOTMO薄膜修飾電極之電流感測......64 3-3-7 微電極感測器之製備.....................65 3-3-7-1 微電極製程.............................65 3-3-7-2 微感測器三極式製備.....................65 3-3-7-3 微電極之電流感測.......................66 3-3-8 膽固醇分子模版修飾電極之製備...........72 3-3-9 膽固醇間接電流式感測...................73 3-3-10 膽固醇電容式感.........................73 3-3-10-1 操作電位與頻率的尋.....................73 3-3-10-2 電容感測曲線...........................74 3-3-10-3 膽固醇類似物干擾物分...................74 第四章 結果與討論......................................75 4-1 分子模版微粒體之製備...................76 4-1-1 分子模版微粒體之粒徑分佈...............76 4-1-2 分子模版微粒體之表面積.................82 4-1-3 分子模版微粒體之表面型態...............84 4-1-4 分子模版吸附討.........................87 4-1-5 不同單體的分子模版與吸附討論...........93 4-2 嗎啡模版微粒修飾電極之電流式感.........96 4-2-1 感測電位的尋找.........................97 4-2-2 定電位電流式感測分析..................100 4-2-3 pH影響與嗎啡感測機制討論..............103 4-2-4 嗎啡之結構類似物對感測器之影響........107 4-3 MIP-PEDOTMO薄膜修飾電極之電流感測.....109 4-3-1 定電位電流感測........................114 4-3-2 嗎啡之結構類似物對感測器之影..........119 4-4 膽固醇分子模版修飾電極電流式感........121 4-4-1 膽固醇分子模版修飾電極製備與電流式設計122 4-4-2 定電位電流式感測分析與感測機制討......124 4-5 膽固醇分子模版修飾電極之電容式感......132 4-5-1 系統電容分析與感測電位與頻率的尋......132 4-5-2 電容式感測分..........................136 4-5-3 膽固醇之結構類似物對感測器之影響......141 4-6 分子模版應用於商用微電極感測嗎........143 4-6-1 商用微電極三極式製....................143 4-6-2 微電極電流感測行......................147 4-6-3 感測時間討............................151 4-7 分子模版應用於自製微電極感測嗎啡......153 4-7-1 自製微電極之三極式製..................153 4-7-2 不同流速對電流訊號的影................155 4-7-3 自製微電極電流感測行..................155 4-7-4 干擾物分..............................157 4-7-5 感測時間分............................158 4-8 綜合討................................168 第五章 結論與建議.....................................173 5-1 結論..................................173 5-2 建議..................................179 第六章 參考文獻.......................................181 附錄....................................................1952997200 bytesapplication/pdfen-US嗎啡膽固醇分子模版定電位電流感測電容感測微電極Morphinecholesterolmolecular imprinted polymer (MIP)amperometric detectioncapacitive detectionmicro- electrodethesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/52057/1/ntu-94-R92524022-1.pdf