201141921 六、發明說明： 【發明所屬之技術頜城】 本發明是有關於一種於一基材上形成一分子拓印高分 子薄臈之方法，特別是指一種在塑膠基材上形成一供檢測 小分子麻醉劑之分子拓印咼分子薄膜之方法。 【先前技術】 分子拓印高分子薄膜（molecular imprinted polymer film，以下簡稱為「MIP薄膜」）的應用範圍相當廣泛’例 如分離（separation)、萃取（extraction)、人工抗體（artificial antibody)、觸媒（catalyst)以及生物感測器（biosensor)等。目 前MIP薄膜的製法主要是將「具有類似於目標分子（target molecule)之結構（特別是結構大小及所含之功能性基團）之模 板分子（target molecule)」、「功能性單體（functional monomers)」、「交聯劑（crosslinking agent)」及「起始劑 (initiator)」進行混合而形成一混合物，接著再將該混合物 塗佈於一基材上，再經聚合及固化反應，而於基材上形成 一固化薄膜，最後再以可溶解該模板分子之溶劑對該固化 薄膜進行萃取，以製得該MIP薄膜。 US 5,587,273揭示一種用於分子拓印一材料之方法，係 包含：（1)形成一溶液，該溶液含有一溶劑、一可與氮烯 (nitrene)進行加成反應之高分子、一交聯劑、一功能性單體 及一模板分子；（2)將溶液進行蒸發，以獲得一殘餘物；（3) 使該殘餘物曝露於一能源下，以藉此形成一經交聯之高分 子膜；及（4)使該經交聯之高分子膜進行萃取，以去除該模 201141921 板分子並獲得一 MIP薄膜。此專利並未就所製得之Mip薄 膜的性能[如吸附特異性（adsorption specificity)及後續應用 之線性度或靈敏度]進行深入研究。 在現有之MIP薄膜的各種製備方法中’為了有效提昇 MIP薄膜的吸㈣異性，f設法使MIp薄膜具❹數個孔 洞，以增加目標分子之接觸面積，且此等孔洞的尺寸大小 最佳只允許讓目標分子進入，俾有助於提昇Μιρ薄膜之吸 附特異性。目前增加孔洞的方式大多是將MIp薄膜進行研 • 磨’或者於製備MIP薄膜時加入孔洞調整劑，然而，上述 方式容易致使MIP薄膜之辨識結構受到破壞。由此可知， 現有之MIP薄膜之製備方法仍有待改進。 【發明内容】 因此本發明之目的，即在提供一種於一塑膠基材上 形成- A子拓印高分子薄膜之方&，此方法可讓該分子拓 印间/7子薄膜具有較適宜孔洞大小，在不同濃度之麻醉藥 中可展現不同的吸附特異性，且後續應用至微流體晶片並 鲁 仏丁檢測時’亦可展現較佳之靈敏度及線性度。 ^於是，本發明於一塑膠基材上形成一分子拓印高分子 薄膜之方法包含以下步驟：⑷將_反應混合物塗佈於該塑 膠基材上，其中，該反應混合物含有一作為模板分子之小 刀子麻醉劑、一功能性單體、一起始劑及一交聯劑，該功 月b丨生單體具有至少一個能與該小分子麻醉劑產生鍵結的官 月b基及小分子麻醉劑··該功能性單體〔該交聯劑··該起 始劑之莫耳比例範圍為1 : 4 : 30 : 〇 . 1 7〜1 : 4 : 30 : 201141921 3物(Γ在具有料範圍之曝光能量的光源下，使該反應 混』進仃曝光，以於該塑膠基材上形成—固化薄膜 移除該固化薄膜上之m 、刀子麻醉劑，以於該塑膠基材上形 成該分子拓印高分子薄膜。 本發明於-塑膠基材上形成—分子拓印高分子薄膜之 方法透過使用特定莫耳比例範圍之起始劑及特定範圍之曝 光能量’可讓所製得之分子拓印高分子薄膜具有較適宜之 孔洞大小，進而可提昇吸附特異性。 【實施方式】 請參閱圖1，本發明於一塑膠基材上形成一分子拓印高 分子薄膜之方法之一較佳具體例包含：⑷將一反應混合物 2塗佈於-塑膠基材！上[如圖1之⑷]，其中，該反應混合 物2含有一作為模板分子之小分子麻醉劑、一功能性單 體、一起始劑及一交聯劑，該功能性單體具有至少一個能 與該小分子麻醉劑產生鍵結的官能基，該小分子麻醉劑： 該功能性單體：該交聯劑：該起始劑之莫耳比例範圍為夏： 4 · 30 · 4 : 30 : 0.85 ; (b)在具有特定範圍之曝光 能量的光源下，使該反應混合物2進行曝光[如圖丨之⑺)]， 以於該塑膠基材1上形成一固化薄膜3 ;及（c)移除該固化 薄膜3上之小分子麻醉劑31[如圖1之（c)] ’以於該塑膠基 材1上形成一分子拓印高分子薄膜4。 該步驟（a)之塑膠基材1除了可提昇耐溶劑性之外，更 可大幅降低製造成本及有利於後續使用《較佳地，該塑膠 基材1具備較佳耐化性、較佳物理性質及高透光度，例如 201141921 由環稀烴共聚物（cyclic olefin copolymer，COC)所構成之基 材。 小分子麻醉劑係泛指液態麻醉劑。較佳地，小分子麻 醉劑為2,6-二異丙紛（propofol)。 該功能性單體具有至少一個能與小分子麻醉劑產生鍵 結的官能基。較佳地，該功能性單體為甲基丙烯酸。 該交聯劑可包含，但不限於乙二醇二甲基丙烯酸醋 (ethylene glycol dimethacrylate，EGDMA)及二乙烯基苯 (divinylbenzene，DVB) 〇 該起始劑可包含，但不限於2,2，_偶氮二異丁腈（2,2_ azobisisobutyronitrile，AIBN)及 1，1，-偶氮二環己腈（11， azobiscyclohexanecarbonitrile，ABCN)。於本發明之—具體 例中’該起始劑為AIBN。 該小分子麻醉劑：該功能性單體：該交聯劑：該起始 劑之莫耳比例範圍為1 : 4 : 30 : 0.17〜1 : 4 : 30 : 〇.85。較 佳地’該莫耳比例範圍為1 : 4 : 30 : 0.30〜1 : 4 : 30 . 0.50。於本發明之一具體例中，該莫耳比例為} : 4 : 〇/1。當該起始劑之莫耳t匕例小於017時，將#法讓薄膜 兀全固化，當該起始劑之莫耳比例大於〇85時將會致使 薄膜產生裂痕或類似晶體之構造，進而影響薄膜之透 度。 需注意的是’該反應混合物不含有甲苯或 劑。 較佳地’該步驟（b)之曝光能量範圍為16 J/cm2〜72 201141921 J/cm2 〇 較佳地，在忒步驟（b)中，該反應混合物2是在一具有 特定圖案之光罩下進行曝光。該光罩之圖案可依據後續所 需進行調整及變化。當使用具有多數個孔洞圖案的光罩， 於曝光固化後，由於只有在孔洞圖案下的反應混合物2會 進行固化，因此所形成之固化薄膜3將由多數個固化薄膜 單元所構成，藉此可在一次製程中製得由多數個MIp薄膜 單元所構成之MIP薄膜4。 該步驟（c)之移除方式可依據習知方式進行。較佳地， 該步驟⑷是以-試劑清洗該固化薄膜3，而完成小分子麻醉 劑31的移除《該試劑較佳為甲醇。 較佳地，該步驟（c)之分子拓印高分子薄膜4的厚度範 圍為 25~75 μιη。 較佳地，該步驟（c)之分子拓印高分子薄膜4具有多數 個直徑範圍為1 〇〜3〇 nm之孔洞。 本發明之方法不需研磨或者添加孔洞調整劑，便可於 該基材上形成具有多數個孔徑合宜之孔洞’因而可有效提 昇MIP薄膜之吸附特異性。 请參閲圖2，本發明所製得之含有MIp薄膜4之塑膠 基材1後續可直接與具有微流道（micro-fluid channel)結構之 塑膠基材7進行熱壓接合，以製得微流體晶片(m—d chip)所製得之微流體晶片在進行感測時將具備不錯的靈 敏度、線性度等優點。此外，值得一提的是，在製作微流 體晶片時，由於含有薄膜4之塑膠基材i與具有微流 道結構之塑膠基材7皆為塑膠材質，因此不需要使用黏著 劑，便可直接運用熱壓方式進行接合。 本發明將就以下實施例來作進一步說明，但應瞭解的 是，該實施例僅為例示說明之用，而不應被解釋為本發明 實施之限制。 <實施例> [實施例1】 '«月參閱圖3，使二片基材1 (皆由環稀烴共聚物所製成） 夾置二塊厚度為25 μπι之聚醯亞胺（polyimide)墊片5，以 共同界定一容置空間。依據小分子麻醉劑（pr〇p〇f〇1):功能 I1生卓體（甲基丙稀酸）.交聯劑（EGDMA):起始劑（abCN)之 莫耳比例為1 : 4 : 30 : (Μ 1 ’配製一反應混合物2。將該 反應混合物2填入該容置空間[如圖3之步驟（a)所示]。接 著’利用一紫外光平行曝光機（Uv exp0sure syStem ,紫外 光波長為365 nm，曝光功率為20 mW/cm2，曝光時間為 2〇〇〇秒，即曝光能量為4〇 J/cm2)，在具有如圖4所示之特 定圖案之光罩6下，使該反應混合物2進行光固化反應， 以於基材1上形成一由多數個固化薄膜單元所構成之固化 薄膜3[如圖3之步驟（b)所示]。使該固化薄膜3浸泡於甲 醇中[如圖3之步驟⑷所示]，待24小時後，即移除該小分 子麻醉劑31，並形成一由多數個具有特定圖案之MIp薄膜 單元所構成之Mip薄膜4。201141921 VI. Description of the Invention: [Technology of the Invention] The present invention relates to a method for forming a molecularly-printed polymer thin crucible on a substrate, in particular to forming a test on a plastic substrate. A method of molecularly imprinting a molecular film of a small molecule anesthetic. [Prior Art] Molecular imprinted polymer film (hereinafter referred to as "MIP film") has a wide range of applications, such as separation, extraction, artificial antibody, and catalyst. (catalyst) and biosensor (biosensor). At present, the MIP film is mainly prepared by "a target molecule" having a structure similar to a target molecule (especially a structure size and a functional group contained therein), and "functional monomer" (functional monomer) ""," "crosslinking agent" and "initiator" are mixed to form a mixture, and then the mixture is applied to a substrate, followed by polymerization and curing reaction. A cured film is formed on the substrate, and finally the cured film is extracted with a solvent capable of dissolving the template molecule to obtain the MIP film. US 5,587,273 discloses a method for molecularly extruding a material comprising: (1) forming a solution containing a solvent, a polymer capable of undergoing addition reaction with nitrene, a crosslinking agent a functional monomer and a template molecule; (2) evaporating the solution to obtain a residue; (3) exposing the residue to an energy source to thereby form a crosslinked polymer film; And (4) extracting the crosslinked polymer film to remove the mold 201141921 plate molecule and obtaining a MIP film. This patent does not provide an in-depth study of the properties of the Mip film produced [such as adsorption specificity and linearity or sensitivity of subsequent applications]. In the various preparation methods of the existing MIP film, in order to effectively improve the absorption (four) anisotropy of the MIP film, f manages to make the MIp film have a plurality of holes to increase the contact area of the target molecules, and the size of the holes is optimal only Allowing the target molecule to enter, and helping to increase the adsorption specificity of the Μιρ film. At present, most of the ways of adding holes are to grind the MIp film or to add a hole adjusting agent when preparing the MIP film. However, the above method easily causes the identification structure of the MIP film to be damaged. It can be seen that the preparation method of the existing MIP film still needs to be improved. SUMMARY OF THE INVENTION Therefore, the object of the present invention is to provide a square-amplified polymer film formed on a plastic substrate, which can make the molecular rubbing/7 sub-film more suitable. The size of the pores can exhibit different adsorption specificities in different concentrations of anesthetics, and the subsequent application to the microfluidic wafer and the Lumin detection can also exhibit better sensitivity and linearity. Thus, the method of the present invention for forming a molecularly imprinted polymeric film on a plastic substrate comprises the steps of: (4) applying a reaction mixture to the plastic substrate, wherein the reaction mixture contains a template molecule. a knives anesthetic, a functional monomer, a starter, and a cross-linking agent, the gongs and b-monogens having at least one official b-based and small-molecule anesthetic capable of binding to the small molecule anesthetic agent·· The functional monomer [the crosslinking agent··the starting agent has a molar ratio range of 1:4:30: 〇. 1 7~1 : 4 : 30 : 201141921 3 (the exposure in the range of materials) Under the light source of energy, the reaction is mixed and exposed to form a cured film on the plastic substrate to remove m and a knife anesthetic on the cured film to form the molecular topography on the plastic substrate. Molecular film. The method for forming a molecularly-printed polymer film on a plastic substrate by using a specific molar range of the initiator and a specific range of exposure energy can make the prepared molecular printing polymer The film is suitable The size of the pores can further enhance the adsorption specificity. [Embodiment] Referring to Figure 1, a preferred embodiment of the method for forming a molecularly-printed polymer film on a plastic substrate comprises: (4) a reaction mixture 2 is coated on a plastic substrate! (Fig. 1 (4)), wherein the reaction mixture 2 contains a small molecule anesthetic as a template molecule, a functional monomer, a starter and a crosslinking agent. The functional monomer has at least one functional group capable of binding to the small molecule anesthetic, the small molecule anesthetic: the functional monomer: the crosslinking agent: the molar ratio of the starting agent ranges from summer: 4 · 30 · 4 : 30 : 0.85 ; (b) The reaction mixture 2 is exposed to light having a specific range of exposure energy [Fig. 7(7)) to form a cured film on the plastic substrate 1. 3; and (c) removing the small molecule anesthetic agent 31 on the cured film 3 [Fig. 1 (c)] ' to form a molecularly-printed polymer film 4 on the plastic substrate 1. In addition to improving solvent resistance, the plastic substrate 1 of the step (a) can greatly reduce the manufacturing cost and facilitate subsequent use. Preferably, the plastic substrate 1 has better chemical resistance and better physical properties. Properties and high transparency, such as 201141921 A substrate composed of a cyclic olefin copolymer (COC). Small molecule anesthetics are generally referred to as liquid anesthetics. Preferably, the small molecule anesthetic is 2,6-dipropofol. The functional monomer has at least one functional group capable of binding to a small molecule anesthetic. Preferably, the functional monomer is methacrylic acid. The crosslinking agent may include, but is not limited to, ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB). The initiator may include, but is not limited to, 2, 2, _Azobisisobutyronitrile (AIBN) and 1,1,-azobiscyclohexanecarbonitrile (ABCN). In the embodiment of the invention - the initiator is AIBN. The small molecule anesthetic: the functional monomer: the crosslinking agent: the molar ratio of the initiator is 1: 4: 30: 0.17~1: 4: 30: 〇.85. Preferably, the molar ratio ranges from 1:4:30:0.30~1:4:30.0.50. In one embodiment of the invention, the molar ratio is: : 4 : 〇 /1. When the molybdenum of the initiator is less than 017, the film is fully cured, and when the molar ratio of the initiator is greater than 〇85, the film may be cracked or crystal-like. Affect the transparency of the film. It should be noted that the reaction mixture does not contain toluene or an agent. Preferably, the exposure energy of the step (b) ranges from 16 J/cm 2 to 72 201141921 J/cm 2 . Preferably, in the step (b), the reaction mixture 2 is in a mask having a specific pattern. Under the exposure. The pattern of the reticle can be adjusted and varied as needed. When a photomask having a plurality of hole patterns is used, after the exposure curing, since only the reaction mixture 2 under the hole pattern is cured, the formed cured film 3 is composed of a plurality of cured film units, whereby A MIP film 4 composed of a plurality of MIp film units is produced in one process. The removal method of the step (c) can be carried out according to a conventional manner. Preferably, the step (4) is to wash the cured film 3 with a reagent to complete the removal of the small molecule anesthetic agent 31. The reagent is preferably methanol. Preferably, the molecularly-printed polymer film 4 of the step (c) has a thickness ranging from 25 to 75 μm. Preferably, the molecularly-printed polymer film 4 of the step (c) has a plurality of pores having a diameter ranging from 1 〇 to 3 〇 nm. The method of the present invention can form a plurality of pores having a suitable pore diameter on the substrate without grinding or adding a pore adjusting agent, thereby effectively increasing the adsorption specificity of the MIP film. Referring to FIG. 2, the plastic substrate 1 containing the MIp film 4 prepared by the present invention can be directly subjected to thermocompression bonding with a plastic substrate 7 having a micro-fluid channel structure to obtain micro The microfluidic wafer prepared by the m-d chip will have good sensitivity, linearity and the like when sensing. In addition, it is worth mentioning that, in the production of the microfluidic wafer, since the plastic substrate i containing the film 4 and the plastic substrate 7 having the micro flow channel structure are both made of plastic material, it is possible to directly use the adhesive without using an adhesive. Bonding is performed by hot pressing. The invention is further illustrated by the following examples, which are to be construed as illustrative and not restrictive. <Examples> [Example 1] '«月 Referring to Fig. 3, two sheets of substrate 1 (all made of a ring-diffusing hydrocarbon copolymer) were sandwiched between two polyimides having a thickness of 25 μm ( The gasket 5 is used to define a housing space. According to the small molecule anesthetic (pr〇p〇f〇1): function I1 bio-organism (methyl acrylic acid). Crosslinking agent (EGDMA): the molar ratio of the initiator (abCN) is 1: 4 : 30 : (Μ 1 'Prepare a reaction mixture 2. Fill the reaction mixture 2 into the accommodating space [as shown in step (a) of Figure 3]. Then use a UV parallel exposure machine (Uv exp0sure syStem, UV The light wavelength is 365 nm, the exposure power is 20 mW/cm2, and the exposure time is 2 〇〇〇 seconds, that is, the exposure energy is 4 〇J/cm 2 ). Under the reticle 6 having the specific pattern as shown in FIG. 4 , The reaction mixture 2 is subjected to a photocuring reaction to form a cured film 3 composed of a plurality of cured film units on the substrate 1 [shown in step (b) of FIG. 3]. The cured film 3 is immersed in In methanol [as shown in step (4) of Figure 3], after 24 hours, the small molecule anesthetic agent 31 is removed, and a Mip film 4 composed of a plurality of MIp film units having a specific pattern is formed.
【實施例2〜10J 除了依據下表！改變聚醯亞胺墊片5之厚度以及曝光 201141921 時間之外，實施例2〜10之MIP 致相同，最後分別獲得實施例2〜 專嗅之製程與實施例1大 薄膜。 表1[Examples 2 to 10J except according to the following table! The MIP of Examples 2 to 10 was changed except that the thickness of the polyimide film 5 was changed and the exposure time was 201141921. Finally, the process of Example 2 to the scent and the film of Example 1 were respectively obtained. Table 1
[實施例11][Example 11]
除了將小分子麻醉劑：功能性單體：交聯劑：起始劑 之莫耳比例改變為1 : 4: 30: 〇.17之外，實施例u之 MIP薄膜之製程與實施例丨大致相同，最後分別獲得實施 例11之MIP薄膜。 [測試】實施例1〜10(在表2及3中標註為Εχ1~Εχ1〇)之 ΜΙΡ薄膜分別進行以下測試： 1.固化薄膜3之外觀觀察：利用掃描式電子顯微鏡在實 施例1的製備過程中，觀察步驟（b)所形成之固化薄膜 3的外觀’所得結果如圖5所示。 2· MIP薄膜4之外觀觀察：利用掃描式電子顯微鏡對實 施例1及實施例3所形成之MIP薄膜4進行觀察，所 10 201141921 〜果々ϋ 6(a)及⑻所示’其中圖6⑷為實施例i之 、D果’圖6(b)為實施例3之結果。 、又（〇) ·刀別取出實施例2〜1〇之Mip薄膜，再分 、气X下透光率測試一以兩片石英晶圓夾置該MIP ^ 接著再利用紫外線光譜儀進行透光度測試，所 t結果整理於下表2。透光度希望越高越佳。 4.縮減率（％):分別取出實施例2〜1〇之MIP薄膜，再分 j進行以下透光率測試―以兩片聚烯烴共聚物基材央 f該MIP薄膜，以數位相機操取相片後再由以响 办像程式（美國Nati〇nal Institmes 〇f肠仙所開發）進 仃面積的量測’再利用以下公式計算縮減率：⑽P薄 膜面積/光罩之每一單元圖案的面積）xl00%，所得結果 整理於下表2。縮減率希望越高越佳。 膨脹率（/〇).分別取出實施例2〜1 〇之MIP薄獏，再分 別進行以下膨脹率測試…將MIP薄膜浸泡於甲醇中， 以獲得完全濕潤之MIP薄膜，再利用上述縮減率之測 忒過程進行量測，最後利用以下公式計算膨脹率：（完 全濕潤後之MIP薄膜面積/上述縮減率測試所獲得之 MIP薄膜面積）xl00%，所得結果整理於下表縮減 率希望越高越佳。 6.及附i (Mg/mm ):分別取適量之pr〇p〇f〇1溶解於甲醇 中，以獲得濃度為0.7918、7.918及19.795 |ag/mL之 pr〇P〇f〇l溶液。分別測試實施例1及3之MIP薄膜於 上述二種不同濃度下之吸附量，流程如下：將]VIIP薄 11 201141921 膜放入2 g之propofol溶液中，待吸附15分鐘後，再 量測Propofol溶液之濃度，再透過以下公式計算吸附 量，結果整理於表3中： 吸附量（pg/mm2)=[(propofol溶液之原有濃度一propofol溶液 之吸附後濃度)x2]/MIP薄膜之面積 7. 特異結合率（％):分別將實施例1及3之步驟（b)所製 得之固化薄膜依據上述吸附量之測試方法進行測試， 再分別依據以下公式計算特異結合率，結果整理於表 3中： 特異結合率（％)=(MIP薄膜之吸附量/步驟（b)之固化薄 膜的吸附量）xl〇〇% 表2 編號 透光度(％) 縮減率(％) 膨脹率(％) Ex2 88.87 87.57 106.19 Ex3 90.55 84.93 108.30 Ex4 89.80 86.59 107.41 Ex5 88.45 80.05 113.61 Ex6 90.19 85.57 107.06 Ex7 90.39 88.18 107.01 Ex8 87.98 88.24 108.52 Ex9 88.91 90.89 104.62 ExlO 88.70 88.24 107.35 12 201141921 表3 Exl Ex3 在右列濃度（pg/mL)之 propofol 的吸附量 (pg/mm2) 0.7918 0.00233 0.00098 7.918 0.02330 0.00607 19.795 0.05521 0.02137 在右列濃度（pg/mL)之 propofol的特異結合率 (%) 0.7918 191.53 455.82 7.918 164.84 246.09 19.795 269.56 138.40 在圖5中，實施例丨則可獲得完全固化之薄膜。由此 s登明起始劑之莫耳比例會影響薄膜之固化程度，因此需特 別控制起始劑之莫耳比例。 在圖6(a)中，可發現實施例1之MIP薄膜具有多數個 孔洞’且孔洞直控約為1〇〜25 nm。在圖6(b)中，實施例3 之MIP薄膜同樣具有多數個孔洞’且孔洞直徑約為丨3 8 nm。由上述結果可證明本發明之方法確實可讓MIp薄膜具 有多數個孔洞，更可有效縮小孔洞直徑（約1〇〜25 。 在表2中，可發現實施例2〜丨〇之Mip薄膜皆具有符合 業界需求之透光度、縮減率及膨脹率。 由表3之結果可知，實施例丨及3在不同濃度之 propofol溶液下分別具有不同吸附量（〇 〇〇〇98〜〇 〇552ι pg/mm2) ’以及特異結合率（164.84%〜455·82〇/。），證明本發明 方法所形成之MIP薄膜在不同濃度之小分子麻醉劑溶液中 可展現不同吸附量及特異結合率，顯示確實適合用於檢測 小分子麻醉劑，且在後續製作成微流體晶片並應用於麻醉 13 201141921 劑$測時，更可展現靈敏度、線性度等優點。 八^上所述，本發明於—塑膠基材上形成—分子拓印高 膜的方法透過使用特^比例之起始劑及特定範圍之 二光能量，可於該基材土形成一具有較適 子拓印高分子薄膜。 直仏之刀 、准以上所述者，僅為本發明之較佳實施例而已，當不 月匕以此限疋本發明實施之範圍’即大凡依本發明_請專利 範圍及發明說明内容所作之簡單的等效變化與修飾，皆仍 屬本發明專利涵蓋之範圍内。 【圖式簡單說明】 圖1流程示意圖，說明本發明於一塑勝基材上形 成一分子拓印高分子薄膜之方法的__較佳具體例之連續步 圖2是一流程示意圖，說明本發明方法所製得之含有 -分子拓印高分子薄膜之基材在後續製作為一微流體晶片 的步驟； 圖3疋一 /’IL程示意圖，說明本發明於一塑膠基材上形 成一分子拓印高分子薄膜之方法的一實施例之連續步驟； 圖4是一俯視圖，說明本發明方法之步驟（1))所使用之 光罩的一態樣； 圖5是電子顯微鏡照片，說明實施例丨之反應混合物 的固化情形；及 圖6(a)及（b)疋電子顯微鏡照片，說明實施例1及3之 MIP薄膜的外觀，其中圖6(a)為實施例1之結果及圖6(b)為 14 201141921 實施例3之結果。 201141921 【主要元件符號說明】 1…… •…塑膠基材 4 ·· …分子拓印高分子薄膜 2…… .....反應混合物 5…·. …··聚醯亞胺墊片 3…… …··固化薄膜 6…. …··光罩 31·.·. ••…小分子麻醉劑 7 .· …具有微流道結構之塑膠基材The process of the MIP film of Example u was substantially the same as that of the Example except that the molar ratio of the small molecule anesthetic: functional monomer: crosslinking agent: initiator was changed to 1: 4: 30: 〇.17. Finally, the MIP film of Example 11 was obtained separately. [Test] The films of Examples 1 to 10 (labeled as Εχ1 to Εχ1〇 in Tables 2 and 3) were subjected to the following tests: 1. Appearance observation of cured film 3: Preparation in Example 1 by scanning electron microscope In the process, the appearance of the cured film 3 formed in the step (b) was observed. The results obtained are shown in Fig. 5. 2. Observation of the appearance of the MIP film 4: The MIP film 4 formed in the first embodiment and the third embodiment was observed by a scanning electron microscope, and 10201141921~fruits 6(a) and (8) are shown in Fig. 6(4). For the example i, the result of Fig. 6(b) is the result of the embodiment 3. And (〇) · remove the Mip film of Example 2~1〇, and then divide the light transmittance test by gas X. Place the MIP on two quartz wafers. Then use UV spectrometer for transmittance. Test, the results are summarized in Table 2 below. The higher the transmittance, the better. 4. Reduction rate (%): The MIP films of Examples 2 to 1 were respectively taken out, and the following transmittance test was carried out by sub-j. The MIP film was taken with two pieces of polyolefin copolymer substrate, and was taken by a digital camera. The photo is then measured by the image of the image (developed by Nati〇nal Institmes, USA). The reduction rate is calculated using the following formula: (10) P film area / area of each unit pattern of the mask ) xl00%, the results are summarized in Table 2 below. The reduction rate is expected to be higher and better. Expansion ratio (/〇). The MIP sheets of Examples 2 to 1 were respectively taken out, and the following expansion ratio tests were carried out separately... The MIP film was immersed in methanol to obtain a completely wet MIP film, and the above reduction rate was utilized. The measurement process was measured, and finally the expansion ratio was calculated by the following formula: (MIP film area after complete wetting/MIP film area obtained by the above reduction rate test) x l00%, and the results were summarized in the table below. good. 6. and attached i (Mg/mm): Dissolve an appropriate amount of pr〇p〇f〇1 in methanol to obtain a solution of pr〇P〇f〇l at concentrations of 0.7918, 7.918 and 19.795 |ag/mL. The adsorption amounts of the MIP films of Examples 1 and 3 at the above two different concentrations were tested separately. The procedure was as follows: [VIIP thin 11 201141921 film was placed in 2 g of propofol solution, and after 15 minutes of adsorption, Propofol was measured. The concentration of the solution was calculated by the following formula, and the results were summarized in Table 3: Adsorption amount (pg/mm2) = [(original concentration of propofol solution - concentration after adsorption of propofol solution) x2] / area of MIP film 7. Specific binding rate (%): The cured films prepared in the steps (b) of Examples 1 and 3 were respectively tested according to the above-mentioned adsorption amount test method, and the specific binding rates were calculated according to the following formulas, respectively. In Table 3: Specific binding rate (%) = (adsorption amount of MIP film / adsorption amount of cured film of step (b)) x l 〇〇 % Table 2 No. Transmittance (%) Reduction rate (%) Expansion ratio ( %) Ex2 88.87 87.57 106.19 Ex3 90.55 84.93 108.30 Ex4 89.80 86.59 107.41 Ex5 88.45 80.05 113.61 Ex6 90.19 85.57 107.06 Ex7 90.39 88.18 107.01 Ex8 87.98 88.24 108.52 Ex9 88.91 90.89 104.62 ExlO 88.70 88.24 107.35 12 201141921 3 Exl Ex3 Adsorption capacity of propofol in the right column concentration (pg/mL) (pg/mm2) 0.7918 0.00233 0.00098 7.918 0.02330 0.00607 19.795 0.05521 0.02137 Specific binding rate (%) of propofol in the right column concentration (pg/mL) 0.7918 191.53 455.82 7.918 164.84 246.09 19.795 269.56 138.40 In Figure 5, the Example 可获得 obtains a fully cured film. Therefore, the molar ratio of the starting agent affects the degree of curing of the film, so the molar ratio of the initiator is specifically controlled. In Fig. 6(a), the MIP film of Example 1 was found to have a plurality of holes ' and the holes were directly controlled to be about 1 〇 to 25 nm. In Fig. 6(b), the MIP film of Example 3 also has a plurality of holes ' and a hole diameter of about 丨38 nm. From the above results, it can be confirmed that the method of the present invention can make the MIp film have a plurality of holes, and the hole diameter can be effectively reduced (about 1 〇 to 25 Å. In Table 2, it can be found that the Mip film of Example 2 to 丨〇 has According to the results of Table 3, the examples 丨 and 3 have different adsorption amounts under different concentrations of propofol solution (〇〇〇〇98~〇〇552ι pg/). Mm2) 'and specific binding rate (164.84%~455.82〇/.), which proves that the MIP film formed by the method of the present invention can exhibit different adsorption amount and specific binding rate in different concentrations of small molecule anesthetic solution, and the display is indeed suitable. It is used to detect small-molecule anesthetics, and it can exhibit the advantages of sensitivity, linearity, etc. when it is subsequently fabricated into a microfluidic wafer and applied to anesthesia 13 201141921. The above invention is on the plastic substrate. The method of forming a molecularly-printed high-film film can form a relatively good-developing polymer film on the substrate soil by using a special ratio of the initiator and a specific range of light energy. The knives and the above are only the preferred embodiments of the present invention, and the scope of the present invention is not limited to the scope of the present invention. The equivalent changes and modifications are still within the scope of the present invention. [Simplified Schematic] FIG. 1 is a schematic flow chart showing the method for forming a molecularly-printed polymer film on a plastic substrate. __Continuous Steps of a Preferred Example FIG. 2 is a schematic flow chart showing the steps of preparing a substrate containing a molecularly-printed polymer film prepared by the method of the present invention into a microfluidic wafer; FIG. / 'IL path diagram illustrating a sequential step of an embodiment of the method of forming a molecularly imprinted polymeric film on a plastic substrate; FIG. 4 is a top plan view showing the steps (1) of the method of the present invention Figure 5 is an electron micrograph showing the curing of the reaction mixture of Example ;; and Figure 6 (a) and (b) 疋 electron micrographs illustrating the MIP of Examples 1 and 3. Thin film Concept, where FIG. 6 (a) Results of Example 1 and the embodiment of FIG. 6 (b) the result of Example 3 14 201 141 921 embodiment. 201141921 [Explanation of main component symbols] 1...... •...Plastic substrate 4 ···Molecular rubbing polymer film 2............Reaction mixture 5...·.···Polyimide gasket 3... ...··cured film 6....·······························································
1616