1336401 ,.. ' 補充，修正曰期：99年7月16曰 玖、發明說明： 、’ 【發明所屬之技術領域】 本發明係有關以數種化學分子的特性整合生物奈米自組裝技術，提出 一套具體程序方法進而製作並有效改變表面的親疏水性，可應用於生醫微 ' 流體晶片上的醫藥檢測和輸送。 • 【先前技術】 中華民國專利(1245771)—種微區域選擇性活化之疏水性晶片及其製 • 備方法。一種微區域選擇性活化之疏水性晶片/微陣列。其製備方法係將一 種疏水性材料及一種帶有一具有保護基保護之官能基的化合物，以混合、 ' 接枝或聚合的方式製備成一種疏水性聚合物，此疏水性聚合物塗覆於一基 底上，該疏水性聚合物經過選擇性的光顯活化形成與未活化的聚合物間隔 之具有功能活性之聚合物微區域。本發明之晶片適合用於製備高密度及高 效率之生物晶片/微陣列。中華民國專利(M287818)-具交錯式電極結構之 微流道。該專利爲一種微流道裝置包含親水性基板、微流道輸入端、輸出 端；一外加電源以及複數個交錯式電極單元。藉由該複數個呈交錯式排列 • 在該微流道單元側邊之電極，可有效增加流體溶液混合之均勻性並縮短流 體溶液混合之時間與距離。然而以上的專利在晶片表面上的親疏水性無法 進行調控，並且化學製作程序較爲複雜。而本專利提出以奈米自組裝的化 • 學合成技術，形成一特殊表面薄膜，並可利用磁場控制來調變其在表面上 • 的親疏水性。此外，本案設計可依檢測對象需求，採用多種不同之分子佈 植於表面，使晶片傳輸流道上具有多種不同親疏水性表面，此一技術可進 一步提供給生物晶片上，微流體與檢體輸送與檢測之設計。本技術之詳細 具體實施例將在後文陳述。 5 1336401 補充-修正日期：99年7月16日 【發明內容】 ‘ 根據數種化學分子的特性並利用奈米自組裝的技術，製作能夠改變表 面親疏水性之生化表面薄膜，並且提出相關合成技術、成分組成和製作步 驟。利用疏水性的長碳鏈分子一端固定在金箔表面上，另一端接上極性磁 球，利用磁場的力量來改變此表面的親疏水性，而此項製成技術能夠有效 控制和改變生化表面薄膜的親疏性程度，並可應用於生醫工程上的晶片檢 測和輸送。 下文藉由具體實施例配合所附的圖式詳加說明，更容易瞭解本發明的 目的、技術內容、特點及其所達成的功效。 【實施方式】 本發明提出一分子自組裝製作可控親疏水性介面之方法，主要提出最 佳實施例。第一個實施例的結構示意圖，如第1圖所示。 首先利用微機電微影製程在Pyrex 7740的玻璃基板（glass wafer ) (100) 上，製作液珠的傳輸路徑且製作一層金屬薄膜(101)，例如金箔，如第la圖 所示。第一個實施例所採用的生化分子是高分子聚合物之硫代十六醇酸 (C16H3202S)(1〇2)，如第lb圖所示。將特定濃度配製好的液態硫代十六醇酸， 塗上整片玻璃基板(glass wafer )正面’利用spin coater旋佈使玻璃基板(glass wafer)的表面上形成一層均勻的表面薄膜。此硫代十六醇酸本身屬於長碳 鏈，硫基(S)的一端將只與表面具有金屬薄膜的表面形成鍵結；而另一端則 是羧基(COOH)，此長碳鏈頂端與水滴接觸時屬於親水性模式但其側向爲斥 水性。其中，此生化分子之高分子聚合物的長鏈分子的尺寸介於100微米 6 1336401 • '' 補充、修正曰期：99年7月丨6曰 至3奈米之間。當塗佈上的硫代十六醇酸與表面形成鍵結後(i〇3a)，再用去 離子水(DI water)清洗掉殘餘在基板表面上未形成鍵結的硫代十六醇酸 (l〇3b)，如第lc圖所示。接下利用化學催化劑(EDCX104)以奈米自組裝的 技術，將具磁性的奈米磁球(1〇5)上的氨基(NH2)與硫代十六醇酸上的羧基 (COOH)形成鍵結，整體化學過程如第id圖所示。最後處理完成的表面， 如第le圖所示。因此’可利用此一技術對於表面的親疏水性進行改變，定 義具有硫代十六醇酸的表面薄膜爲親水性的接觸表面，如第2a圖所示液珠 • (2〇2)與該表面薄膜接觸角小於90度而當利用磁場裝置(207)加入磁場了之 . 後’奈米磁球(2〇4)被吸引而露出疏水性的長碳鏈分子表面，此薄膜則轉變 . 爲疏水性的接觸表面，如第2b圖所示液珠(206)與該表面薄膜接觸角大於 90度；其中由於磁性裝置能夠提供一作用場，此作用場係影響含高分子聚 合物之金屬薄膜的厚度範圍介於100微米至3奈米之間，且寬度範圍涵蓋 整個玻璃基板。以及在晶片流道表面上，利用生物自組裝技術定義不同親 疏水性之特定圖樣或面積，改變表面親疏水性程度，第2c圖所示。 ^ 另外，本發明所使用之基板的材料除了可爲上述玻璃基板之外，其材 質更可爲矽晶圓、金屬、高分子材料等之任一種或其組合。 7 1336401 補充、修正日期：99年7月丨6曰 【圖式簡單說明】 · 第la圖至第le圖係爲本發明以奈米自組裝技術製作生化表面薄膜過程示意 圖 第2a圖至第2c圖爲本發明之生化薄膜表面親疏水的改變原理與設計示意圖 【主要元件符號說明】 100 玻璃基板 101 金屬薄膜 102 硫代十六醇酸(c16h32o2s) 103 a 與表面金箔鍵結的硫代十六醇酸 103 b 未與表面金箔鍵結的硫代十六醇酸 104 連接奈米磁球與硫代十六醇酸的催化劑EDC 105 奈米磁球 200 玻璃基板 201 金屬薄膜 202 液珠的接觸角小於90度，爲親水性表面 203 硫代十六醇酸(c16h32o2s) 204 奈米磁球 205 疏水性表面 1336401 補充、修正曰期：99年7月丨6曰 206 液珠的接觸角大於90度’爲疏水性表面 207 磁場裝置1336401 ,.. ' Supplementary, revised period: July, 1996, 发明, invention description: , 'Technical field of invention> The present invention relates to the integration of bio-nano self-assembly technology by the characteristics of several chemical molecules, A specific procedure is proposed to make and effectively change the hydrophilicity of the surface, which can be applied to medical detection and delivery on biomedical micro-fluidic wafers. • [Prior Art] Republic of China Patent (1245771) - a micro-region-selectively activated hydrophobic wafer and its preparation method. A microregion selective activation hydrophobic wafer/microarray. The preparation method comprises the steps of: preparing a hydrophobic polymer and a compound having a functional group protected by a protecting group into a hydrophobic polymer by mixing, grafting or polymerizing, the hydrophobic polymer is coated on the first On the substrate, the hydrophobic polymer is selectively photoactivated to form a functionally active polymeric microdomain spaced from the unactivated polymer. The wafer of the present invention is suitable for use in the preparation of high density and high efficiency biochips/microarrays. Republic of China Patent (M287818) - Microchannel with staggered electrode structure. The patent is a microchannel device comprising a hydrophilic substrate, a microchannel input end, an output end, an external power supply, and a plurality of interleaved electrode units. By the plurality of interlaced arrays, the electrodes on the side of the microchannel unit can effectively increase the uniformity of mixing of the fluid solution and shorten the time and distance of mixing of the fluid solution. However, the above-mentioned patents are not capable of regulating the hydrophobicity on the surface of the wafer, and the chemical production process is complicated. However, this patent proposes a special surface film formed by nano-self-assembly chemical synthesis technology, and can use magnetic field control to modulate its hydrophilicity on the surface. In addition, the design of the case can be carried on the surface by using a variety of different molecules according to the requirements of the test object, so that the wafer transport flow channel has a plurality of different hydrophilic and hydrophobic surfaces. This technology can be further provided to the biochip, the microfluid and the sample transport and Design of the test. Detailed embodiments of the present technology will be described later. 5 1336401 Supplementary-Revised Date: July 16, 1999 [Invention>] Based on the characteristics of several chemical molecules and using nano-self-assembly technology, biochemical surface films capable of changing the surface hydrophobicity are prepared, and related synthetic techniques are proposed. , composition of ingredients and production steps. The hydrophobic long carbon chain molecule is fixed on the surface of the gold foil at one end and connected to the polar magnetic ball at the other end, and the strength of the magnetic field is used to change the hydrophilicity of the surface, and the preparation technology can effectively control and change the biochemical surface film. The degree of affinity, and can be applied to wafer inspection and transportation in biomedical engineering. The objects, technical features, features, and effects achieved by the present invention will become more apparent from the detailed description of the appended claims. [Embodiment] The present invention proposes a method for self-assembly of a molecule to prepare a controllable hydrophilic and hydrophobic interface, and the most preferred embodiment is proposed. A schematic structural view of the first embodiment is shown in Fig. 1. First, a micro-electromechanical lithography process was used to fabricate a droplet transfer path on a Pyrex 7740 glass wafer (100) and a metal film (101) such as gold foil was formed, as shown in FIG. The biochemical molecule used in the first embodiment is a high molecular weight thiohexadecanol (C16H3202S) (1〇2) as shown in Figure lb. The liquid thiohexadecanol acid prepared at a specific concentration was applied to the front side of a whole glass wafer. A spin coater was used to form a uniform surface film on the surface of the glass wafer. The thiohexadecanol acid itself belongs to a long carbon chain, and one end of the sulfur group (S) will only form a bond with a surface having a metal thin film on the surface; and the other end is a carboxyl group (COOH), the end of the long carbon chain and the water droplet It is hydrophilic in contact but is water repellent in the lateral direction. Among them, the long-chain molecules of the biopolymer of the biochemical molecule have a size of 100 μm 6 1336401 • '' Supplementary, modified flood season: July 丨 6曰 to 3 nm. When the coated thiohexadecanol is bonded to the surface (i〇3a), the thiohexadecanol remaining on the surface of the substrate is not washed away with DI water. (l〇3b), as shown in Figure lc. Next, using a chemical catalyst (EDCX104) in nano-self-assembly technology, the amino group (NH2) on the magnetic nanosphere (1〇5) and the carboxyl group (COOH) on the thiohexadecanolate form a bond. The overall chemical process is shown in Figure id. The finished surface is finally processed, as shown in the figure lee. Therefore, this technique can be used to change the hydrophilicity of the surface, and define a surface film having thiohexadecanoic acid as a hydrophilic contact surface, such as the liquid bead shown in Fig. 2a (2〇2) and the surface. The film contact angle is less than 90 degrees and the magnetic field is added by the magnetic field device (207). After the 'nano magnetic ball (2〇4) is attracted to expose the surface of the hydrophobic long carbon chain molecule, the film is transformed. The contact surface of the liquid, as shown in Fig. 2b, has a contact angle of more than 90 degrees with the surface film; wherein the magnetic field can provide an action field, and the action field affects the metal film containing the polymer. The thickness ranges from 100 microns to 3 nanometers and the width ranges from the entire glass substrate. And on the surface of the wafer runner, a specific pattern or area of different hydrophilicity is defined by bio-self-assembly techniques, and the degree of surface hydrophobicity is changed, as shown in Fig. 2c. Further, the material of the substrate used in the present invention may be any one or a combination of a germanium wafer, a metal, a polymer material, or the like, in addition to the glass substrate. 7 1336401 Supplementary, Amendment Date: July, 1999 丨6曰 [Simple description of the diagram] · The first to the first diagrams are the schematic diagrams of the process of making biochemical surface film by nano self-assembly technology. 2a to 2c The figure shows the principle and design of the surface hydrophobicity change of the biochemical film of the present invention. [Main component symbol description] 100 glass substrate 101 metal film 102 thiohexadecanol (c16h32o2s) 103 a thio sixteen bonded to the surface gold foil Alkyd 103 b thiohexadecanol acid 104 not bonded to the surface gold foil 104 Catalyst connecting nanomagnetic ball with thiohexadecanol acid EDC 105 Nano magnetic ball 200 Glass substrate 201 Metal film 202 Contact angle of liquid bead Less than 90 degrees, hydrophilic surface 203 thiohexadecanol (c16h32o2s) 204 nano magnetic ball 205 hydrophobic surface 1364401 Supplementary, modified flood season: July 1999 丨6曰206 The contact angle of the liquid bead is greater than 90 degrees 'For hydrophobic surface 207 magnetic field device
η7月16曰修召 拾、申請專利範圍： 1. 一種奈米粒子及長鏈分子自組裝製作可控親疏水性介面之方法，其包 • 括： (a) 在一基板上製作液珠傳輸路徑並形成—金屬薄膜； (b) 在該金屬薄膜表面上塗佈一層硫代十六醇酸，使該硫代十六醇酸 之硫基端與該金屬薄膜產生鍵結； (c) 去除該金屬薄膜上未形成鍵結之該硫代十六醇酸；以及 (d) 利用催化劑以奈米自組裝技術’將奈米磁球與該硫代十六醇酸之 羧基形成鍵結。 _ 2.如申請專利範圍第1項所述之方法，其中該奈米磁球係藉由磁性裝置的 作用，進而調控該金屬薄膜之表面親疏水特性。 3. 如申請專利範圍第1項所述之方法’其中該基板之材料可爲矽晶圓、玻 璃、金屬、高分子材料等之任一種或其組合。 4. 如申請專利範圍第1項所述之方法，其中該高分子聚合物之分子的長鏈 分子的尺寸介於100微米至3奈米之間。 5. 如申請專利範圍第2項所述之方法，其中該磁性裝置能夠提供一作用 場，該作用場係影響含該高分子聚合物之該金屬薄膜的厚度範圍介於 9η July 16 曰 召 、 、 、 、 、 、 、 、 、 、 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. 1. Forming a metal film; (b) coating a surface of the metal film with a layer of thiohexadecanol to bond the sulfur-based end of the thiohexadecanol to the metal film; (c) removing the The thiohexadecanol acid which is not bonded to the metal thin film; and (d) the nano magnetic ball is bonded to the carboxyl group of the thiohexadecanolate by a nano-self-assembly technique using a catalyst. 2. The method of claim 1, wherein the nanomagnetic ball controls the surface hydrophobicity of the metal film by the action of a magnetic device. 3. The method of claim 1, wherein the material of the substrate is any one or a combination of germanium wafers, glass, metal, polymer materials, and the like. 4. The method of claim 1, wherein the polymer of the polymer has a long chain molecule having a size between 100 micrometers and 3 nanometers. 5. The method of claim 2, wherein the magnetic device is capable of providing an action field that affects the thickness of the metal film containing the polymer to be in the range of 9