TWI275791B - Integrated electrospray microchip and manufacturing method therefor - Google Patents
Integrated electrospray microchip and manufacturing method therefor Download PDFInfo
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Ί275791 五、發明說明（1) 【發明所屬之技術領域】 本發明係關於一種整合式微電灑晶片及其製造方法，特 別疋關於由單一材質一體成型形成一微流體通道及一微電 灑噴頭，以提升電灑游離效能之整合式微電麗晶片及其製 造方法。 【先前技術】 近年來生物科技相關領域的蓬勃發展，利用質譜儀 〔mass spectrometer〕偵測技術對蛋白質體 〔proteome〕等生物大分子〔biological '•macro-molecule〕進行檢測以獲得蛋白質等生物結構訊 息’已逐漸成為蛋白質檢測方法之主流。質譜儀提供有效 之高敏感度檢測方法，並可克服生物體内之生物大分子 〔如蛋白質〕種類繁多、結構複雜、樣本量稀少、取得不 易、流程繁瑣耗時等相關問題。 實驗取得之生物大分子樣本通常數量極微少，因此習 i質譜儀分析架構必需先將生物微量樣本離子化，以提升 其檢測敏感度。在質譜儀之離子源可選擇的眾多技術中， 最常搭配使用一微電灑晶片進行電灑游離法 鲁〔electrospray ionization，ESI〕，其原因在於電灑游 離法具有下列諸多優點：可直接從溶液樣本中债測生物大 分子、可相容於液相層析儀、易於使用、靈敏度高、分析 快速等。 上述電灑法中所需使用的微電灑晶片係由玻璃或塑膠之 基質製成，其内部設有一微流體通道〔microfluidicΊ 275791 V. OBJECT OF THE INVENTION (1) The present invention relates to an integrated micro-electrospray wafer and a method of manufacturing the same, and more particularly to integrally forming a microfluidic channel and a micro-spraying nozzle from a single material. An integrated microelectronic wafer for improving the free performance of the electrospray and a method for manufacturing the same. [Prior Art] In recent years, biotechnology-related fields have flourished, using mass spectrometer detection technology to detect biological macromolecules such as proteome to obtain biological structures such as proteins. The message 'has gradually become the mainstream of protein detection methods. The mass spectrometer provides an effective high-sensitivity detection method, and can overcome various problems such as a wide variety of biological macromolecules (such as proteins) in the living body, a complicated structure, a small sample size, difficulty in obtaining, and cumbersome and time-consuming processes. The number of biomacromolecule samples obtained in the experiment is usually very small, so the analytical framework of the i-mass spectrometer must first ionize the biological micro-sample to improve its detection sensitivity. Among the many technologies that can be selected from the ion source of the mass spectrometer, the electrospray ionization (ESI) is most commonly used with a micro-discharge wafer. The reason is that the electrospray ionization method has the following advantages: In the sample of the solution, the biometric macromolecule is compatible with the liquid chromatograph, easy to use, high sensitivity, fast analysis, and the like. The micro-electrospray wafer required for the above electrospray method is made of a glass or plastic substrate, and a microfluidic channel is provided inside the microfluidic system.
•Ί275791 五、發明說明（2) 1•Ί275791 V. Invention description (2) 1
Channel〕，該微流體通道之一端為注入口，及宜另一 # 則為電灑游離喷嘴〔ESI nozzle〕。早期之電灌游離噴而 乃直接形成在由微電灑晶片之邊緣端面上[ref 1Ί，使 流體管道内之液態樣本利用所施加之電位差進行電作 用。然而，微電灑晶片t邊緣端面會因液體表面張力乍 造成液滴在電灑游離喷嘴〔即管道開口處〕累積’致 物分子ίί精準的依照分子大小電喷麗喷出微電麗晶片外 及進入貝瑨儀的入口，而造成質譜儀的檢測解析度降低。 為了改善上述缺點，目前微電灑晶片進一步選擇利用玻 >璃晶片[ref 3]、石夕晶片[ref 4]、PDMS高分子材料 5,6 ]等與一商業用毛細管喷頭作為組合，或先製作一噴頭晶 片再以毛細管連結微流體通道[r e f 11,12 ]。 然而，上述設計的技術問題在於：毛細管的管徑與微電 $晶片的微流體通道之管徑未實質相同、無法相配合，故 生一「死水區」〔dead vol ume，或稱滯留體 ^尸。此現象對於利用電滲透流或壓力流驅動之生物樣本 而言’將造成部份生物樣本停滯於死水區附近或僅可緩慢 流動’造成生物樣本未能有效依分子大小喷出微電灑晶片 _外’以致質譜檢測圖上的生物樣本區塊產生增長拖尾現 象，因而降低樣本分離的品質，影響質譜分析之解析度與 靈敏度。 一 此外’學者Schultz等人[ref 7]利用微機電製程技術以 多晶矽或氮化矽製作微管道及微喷頭，但此作法所製作之 喷頭結構甚小，反而限制其可應用之範圍。再者，學者Channel], one end of the microfluidic channel is an injection port, and the other one is a sprinkler free nozzle (ESI nozzle). The early electrospray free spray was formed directly on the edge end surface of the micro-sprayed wafer [ref 1Ί, so that the liquid sample in the fluid conduit was electrically operated by the applied potential difference. However, the edge of the edge of the micro-electroplated wafer t will be caused by the liquid surface tension, and the droplets will accumulate at the discharge nozzle (ie, the opening of the pipe). The precise molecular size of the wafer is ejected according to the molecular size. And entering the entrance of the Bellows, causing the detection resolution of the mass spectrometer to decrease. In order to improve the above disadvantages, the micro-electrospray wafer is further selected to be combined with a commercial capillary nozzle using a glass wafer [ref 3], a stone wafer [ref 4], a PDMS polymer material 5, 6 ], and the like. Or first make a nozzle wafer and then connect the microfluidic channel [ref 11, 12 ] with a capillary. However, the technical problem of the above design is that the diameter of the capillary tube and the microfluidic channel of the micro-powered wafer are not substantially the same and cannot be matched, so that a "dead volume" or a stagnant body is generated. corpse. This phenomenon is a phenomenon in which a biological sample driven by electroosmotic flow or pressure flow will cause some biological samples to stagnate near the dead water zone or only flow slowly, causing the biological sample to fail to effectively eject the micro-discharge wafer according to the molecular size. Externally, the biological sample block on the mass spectrometry detection pattern produces a growth tailing phenomenon, thereby reducing the quality of sample separation and affecting the resolution and sensitivity of mass spectrometry. In addition, the scholars Schultz et al. [ref 7] used microelectromechanical process technology to fabricate micro-pipes and micro-sprinklers with polysilicon or tantalum nitride. However, the structure of the nozzles produced by this method is very small, but limits its applicable range. Furthermore, scholars
…1275791 專五、發明說明（3) --—...1275791 Special 5, invention description (3) ---
Shui等人[ref 8]利用不鏽鋼細管直接作為微喷頭之結構， 其優點為為導電容易，但不鏽鋼細管不易與其他微流體系 統整合為其缺點。另外，亦有學者R〇hner等人[ref 9]利用 塑膠基材直接以準分子雷射〔excimer laser〕加工製作 微電灑晶片之微流體通道及喷嘴，或有學者Arscott等人 [ref 1G]直接利用光阻蝕刻法由負型光阻劑su — 8光蝕刻形 成说流體通道及喷嘴結構。上述方法雖均具有其優點，然 而其大多需要使用昂貴之設備或複雜之製程，方可順利製 作该微電灑晶片’不符合低成本大量製造之商業化需求。 •基於上述因素，確實仍有必要進一步改良上述整合式微電 灑晶片及其製造方法。 有鑑於此，本發明改良上述之缺點，其利用塑膠基材、 抽拉模桿及硬化膠材製作一微電灑晶片，該微電灑晶片由 材質一體成型形成一微流體通道與一微電灑喷頭，該 灑晶片可組合一微型霧化裝置，共同用以對液相生物 樣本進行霧化，使生物樣本能直接進入質譜儀中進行分 析。該微電灑喷頭可有效避免習用微電灑晶片之微流體通 道與玻璃毛細官連接時所造成的「死水區」衍生問題，同 鲁時亦可藉由提供微流體通道内壁與電灑喷頭之間的材料一 致性’以減少生物樣本在管道中傳送時因不同材料間吸附 力不同所造成之檢測困擾，進而降低微電灑晶片製造成 本、加速及簡化其製程、提升電灑游離法的效能及蜇雄公 析的解析度。 ' 【發明内容】Shui et al. [ref 8] use a stainless steel capillary tube directly as the structure of the micro-nozzle, which has the advantage of being easy to conduct, but the stainless steel thin tube is not easy to integrate with other microfluidic systems. In addition, some scholars R〇hner et al. [ref 9] use a plastic substrate to directly process microfluidic channels and nozzles of micro-electrospray wafers using excimer lasers, or scholars Arscott et al. [ref 1G] Directly using photoresist etching to form a fluid channel and nozzle structure by photo-etching of a negative photoresist su-8. Although the above methods all have their advantages, most of them require the use of expensive equipment or complicated processes in order to smoothly manufacture the micro-electroplated wafers, which does not meet the commercialization requirements of low-cost mass production. • Based on the above factors, it is indeed necessary to further improve the above-described integrated micro-electrode wafer and its manufacturing method. In view of the above, the present invention improves the above-mentioned disadvantages, and uses a plastic substrate, a drawing die rod and a hardened rubber material to form a micro-electrospray wafer, which is integrally formed by a material to form a microfluidic channel and a micro-electricity. The sprinkler head can be combined with a micro atomizing device for atomizing the liquid phase biological sample so that the biological sample can directly enter the mass spectrometer for analysis. The micro-electrospray nozzle can effectively avoid the problem of "dead water zone" derivation caused by the micro-fluid channel of the micro-electrospray wafer and the glass capillary officer. The same time can also provide the micro-fluid channel inner wall and the electric sprinkler. The material consistency between the heads is used to reduce the detection of the difference in adsorption between different materials when the biological sample is transported in the pipeline, thereby reducing the manufacturing cost of the micro-spray wafer, accelerating and simplifying the manufacturing process, and improving the electrospray free method. The performance and the resolution of the protagonist. 'Content of the invention】
'1275791'1275791
" 要目的係提供一種整合式微電灑晶片之製造方 法、:其利用塑膠基材、抽拉模桿及硬化膠材快速製備一微 電灑曰曰片，使泫微電灑晶片由單一材質一體成塑形成一微 流體通道及-微電灑喷頭，使得本發明具有降低製造成本 及加速簡化製程之功效。 本發明次要目的係提供一種整合式微電灑晶片，其中一 微電灑晶片係由單一材質一體成型形成一微流體通道及一 微電灑喷頭，使得本發明具有提升電灑游離效能及增加質 譜分析解析度之功效。 鲁本發明另一目的係提供一種整合式微電灑晶片，其中一 微電灑晶片由單一材質一體成型形成一微流體通道及一微 電灑喰頭’該微電灑晶片選擇組合使用一微型霧化裝置， 以分別提供帶電液滴及霧化樣本，以供進行生物樣本之質 ’使得本發明可進行基質辅助雷射脫附游離法 女I )之生物樣本分析法，以獲取不同於£ s I之質譜分 析訊號。並可具有提升電灑游離效能及增加質譜分析解析 度之功效。 根據本發明之整合式微電灑晶片及其製造方法，其包含 _下列步驟··製造一微電灑晶片，其設有至少一微流體通 道，該微流體通道在該微電灑晶片之一端面形成至少一開 口端；製造一抽拉模桿’將該抽拉模桿之一端預置在該微 電灑晶片之微流體通道内，並使該抽拉模桿之另一端裸露 於該微流體通道的開口知’调配一硬化膠材，將該硬化腰 材塗覆於該微流體通道的開口端；及在該硬化膠材完全固" The aim is to provide a method for manufacturing an integrated micro-electro-spray wafer: a plastic substrate, a drawing die and a hardened rubber material are used to rapidly prepare a micro-electrostatic sprinkler film, so that the micro-electro-spray wafer is made of a single material. The integrated molding forms a microfluidic channel and a micro-electrospray nozzle, so that the invention has the effects of reducing manufacturing cost and speeding up the process. A secondary object of the present invention is to provide an integrated micro-electrospray wafer in which a micro-electrospray wafer is integrally formed from a single material to form a microfluidic channel and a micro-electrospray nozzle, so that the present invention has the function of improving the sprinkler free performance and increasing The efficiency of mass spectrometry resolution. Another object of the invention is to provide an integrated micro-electrospray wafer in which a micro-electrospray wafer is integrally formed from a single material to form a microfluidic channel and a micro-electric sprinkler head. a bio-sample analysis method for providing charged droplets and atomized samples for the quality of the biological sample to enable the substrate to be subjected to matrix-assisted laser desorption of free female I to obtain a different biological value I mass spectrometry signal. It can also improve the performance of electrospray free performance and increase the resolution of mass spectrometry. An integrated micro-electrospray wafer and a method of fabricating the same according to the present invention, comprising the steps of: manufacturing a micro-electrospray wafer provided with at least one microfluidic channel at one end of the micro-discharge wafer Forming at least one open end; manufacturing a pull mold rod's one end of the pull mold rod is preset in the microfluidic channel of the micro-electrospray wafer, and the other end of the pull mold rod is exposed to the microfluid The opening of the passage is configured to dispense a hardened rubber material, the hardened waist material is applied to the open end of the microfluidic channel; and the hardened rubber material is completely solidified
Ί275791 五、發明說明（5) 化前，將該抽拉模桿拉出該微電灑晶片外，以便該硬化膠 材由該微流體通道的開口端向外一體延伸形成一微電灑喷 頭。 ’ 【實施方式】 為了讓本發明之上述及其他目的、特徵、優點能更明顯 易懂，下文將特舉本發明較佳實施例，並配合所附圖式， 作詳細說明如下。 請參照第1及2A至2F圖所示，本發明第一實施例之整合 式微電灑晶片之製造方法包含下列步驟：〔1〕、製造一 丨模板1，其設有至少一微流體通道之互補凸模丨丨；〔2〕、 製造一第一塑性基板2，利用該模板1熱壓處理該第一塑性 基板2，使其形成至少一微流體通道21 ;〔 3〕、製造一第 二塑性基板3，其對應該微流體通道21鑽設至少一孔3 i ; 免4 、製造一抽拉模桿4 ’將該抽拉模桿4之一端預置在 該第/一塑性基板2之微流體通道21内；〔5〕、由該第一及 第二塑性基板2、3結合形成一微電灑晶片丨〇，並使該抽拉 模桿4之另一端裸露於該微流體通道2丨的開口端；〔6〕、 調配一硬化膠材6，將談硬化膠材6塗覆於該微流體通道21 灸的開口端；及〔7〕、在該硬化膠材6完全固化前，將該抽 3桿4拉出該微電灑晶片1〇外’以便該硬化 由該微 流體通道21的開口端向外一體延伸形成一微電麗喷頭61。 睛參照第1及2 A圖所示，本發明筮 杏# /1 & ^ ^ n … 私乃第一貫施例之整合式微 電麗晶片之製造方法第一步驟：勢拌 / 泉造一模板1，：ii母右泛 少一微流體通道之互補凸模U。太恭ηη λ : /、卩又有主 本發明較佳利用玻璃等堅Ί 275791 V. Invention Description (5) Before the chemical extraction, the drawing die rod is pulled out of the micro-electrospray wafer, so that the hardened rubber material integrally extends outward from the open end of the microfluidic channel to form a micro-electric sprinkler nozzle . The above and other objects, features, and advantages of the present invention will become more apparent from the claims. Referring to FIGS. 1 and 2A to 2F, the manufacturing method of the integrated micro-electrospray wafer according to the first embodiment of the present invention comprises the following steps: [1] manufacturing a template 1 having at least one microfluidic channel. a complementary punch 丨丨; [2], a first plastic substrate 2 is fabricated, and the first plastic substrate 2 is hot pressed by the template 1 to form at least one microfluidic channel 21; [3], a second is fabricated The plastic substrate 3 is drilled with at least one hole 3 i corresponding to the microfluidic channel 21; free of 4, a drawing die rod 4' is formed, and one end of the drawing die rod 4 is preset on the first plastic substrate 2 a microfluidic channel 21; [5], the first and second plastic substrates 2, 3 are combined to form a micro-discharge wafer crucible, and the other end of the drawing die 4 is exposed to the microfluidic channel 2 The open end of the crucible; [6], a hardened rubber material 6 is prepared, and the hardened rubber material 6 is applied to the open end of the microfluidic channel 21; and [7], before the hardened rubber material 6 is completely cured, Pulling the pumping rod 4 out of the micro-spraying wafer 1 'so that the hardening is outward from the open end of the microfluidic channel 21 Li extended to form a micro-electro nozzle 61. Referring to Figures 1 and 2A, the present invention is a method for manufacturing an integrated micro-electric wafer of the first embodiment: the first step: the potential mixing / the spring making The template 1, , ii, is a complementary convex U of a microfluidic channel. Taigong ηη λ : /, 卩 has a main body. The present invention preferably utilizes glass and the like.
…:[275791 ' 五、發明說明（6) " ^ 硬基材製成該模板1，其較佳藉由標準之光蝕刻顯影程序 處理該模板1。首先，利用適當光阻劑定義該微流體通道 之圖案。接著，對該模板1利用BOE (HF :40 = 1: 6)蝕刻液進 行蝕刻，以逐步形成該微流體通道之互補凸模丨丨。蝕刻過 程中，每五分鐘便將該模板1轉換浸泡於丨M的HC1溶液中i 〇 :秒，重複此步驟，直至該互補凸模11達到所需結構高度或 深度。 / 請參照第1及2 B圖所示，本發明第一實施例之整合式微 電灑晶片之製造方法第二步驟··製造一第一塑性基板2， 鲁利用該模板1熱壓處理該第一塑性基板2，使其形成至少一 微流體通道21。本發明較佳利用熱塑性高分子基材製成該 第一塑性基板2，例如聚甲基丙烯酸甲酯 〔poly-methylmethacrylate，PMMA，俗稱有機玻璃或壓 奢,】〕、聚本乙烯〔polystyrene，PS〕、聚碳酸酯塑膠 flr^ycarbonate，PC〕或聚對苯二曱酸乙二醇酯塑膠 i polyethylene terephthalate，PET〕等塑膠 ° 接著， 利用熱壓成型技術’將該模板1之互補凸模丨丨熱壓於該第 一塑性基板2上，如此該第一塑性基板2即可互補形成該微 _流體通道2 1。該微流體通道21之一端貫穿露出該第一塑性 基板2之一端面’而成為開口端。接著，取下該模板1，該 模板1可重複用於熱壓製作該第一塑性基板2，該第一塑性 基板2則用於製作該微電灑晶片丨〇。再者，依使用需求， 該第一塑性基板2可選擇製作一電極5，該電極5之一端鄰 接於該微流體通道21之管壁。依不同應用需求，該電極5...: [275791 ' V. Invention Description (6) " ^ The substrate 1 is made of a hard substrate, which is preferably processed by a standard photolithography development process. First, the pattern of the microfluidic channel is defined using a suitable photoresist. Next, the template 1 is etched using a BOE (HF: 40 = 1: 6) etching solution to gradually form a complementary punch 丨丨 of the microfluidic channel. During the etching process, the template 1 is immersed in the HCl solution of 丨M every five minutes for i 〇 : seconds, and this step is repeated until the complementary punch 11 reaches the desired structural height or depth. / Referring to Figures 1 and 2B, the second step of the method for manufacturing the integrated micro-electrospray wafer according to the first embodiment of the present invention is to manufacture a first plastic substrate 2, which is heat-treated by the template 1 A plastic substrate 2 is formed to form at least one microfluidic channel 21. The present invention preferably utilizes a thermoplastic polymer substrate to form the first plastic substrate 2, such as poly-methylmethacrylate (PMMA, commonly known as plexiglass or embossed), and polystyrene (PS). 〕, polycarbonate plastic flr^ycarbonate, PC] or polyethylene terephthalate plastic i polyethylene terephthalate, PET] and other plastics ° Next, using the hot press forming technology 'the complementary punch of the template 1 丨The crucible is pressed against the first plastic substrate 2 such that the first plastic substrate 2 can complementarily form the micro-fluid channel 2 1 . One end of the microfluidic channel 21 is formed to open the end surface of the first plastic substrate 2 to become an open end. Next, the template 1 is removed, and the template 1 can be repeatedly used for hot pressing to fabricate the first plastic substrate 2, and the first plastic substrate 2 is used to fabricate the micro-electroplated wafer cassette. Furthermore, the first plastic substrate 2 can be selectively fabricated with an electrode 5, one end of which is adjacent to the wall of the microfluidic channel 21, depending on the needs of use. According to different application requirements, the electrode 5
C:\L0G0-5\FIVE CONTINENTSXPK9738.ptd 第12頁 …1275791 五、發明說明（7) 可選擇電性連接高壓端或接地端。例如，在質 negative mode時，該電極5可做為接地端；在質譜= P〇S1t1Ve mode時，該電極5可電性連接高壓端。、我為 請參照第1及2C圖所示，本發明第一實施例之整合 電灑晶片之製造方法第=牛咪.制、生 咕 σ式i放 衣每刀成乐_步驟·製造一第二塑性基 其對應該微流體通道21鑽設至少一孔31。本’ PMMA等熱塑性高分子基材製成該第二塑性基板2 ’ 用 範圍相同於該第一塑性基板2之塑性基材。接著，利t 當鑽孔技術，使該第二塑性基板3對應該第一塑性美^ »微流體通道21鑽設形成至少一該孔31。該孔31後續^ ^ 微電麗晶片1〇之注入口，以供注入液相樣本或緩衝以该 請參照第1及2C圖所示，本發明第一實施例之整合式微 電灑晶片之製造方法第四步驟：製造一抽拉模桿4，將ζ ff]模桿4之一端預置在該第一塑性基板2之微流體通道^ 内本發明較佳利用不鏽鋼、金屬、合金或高分子等勒性 線材製成該抽拉模桿4。同時，在該第一塑性基板2形成該 微流體通道21後，先將該抽拉模桿4之一端預置在該第一/ 塑性基板2之微流體通道21内，以便後續抽拉製作該微電 ，灑喷頭61。再者，為了方便後續進行抽拉動作，本發明亦 可選擇先將該抽拉模桿4以潤滑油處理其表面，再將該抽 拉模桿4對位置入該第一塑性基板2之微流體通道2丨内。另 一方面，本發明亦可先製備該微電灑晶片1 〇，再將該抽拉 模桿4之一端預置在該微電灑晶片1 〇之微流體通道2丨内， 並使該抽拉模桿4之另一端裸露於該微流體通道21的開口C:\L0G0-5\FIVE CONTINENTSXPK9738.ptd Page 12 ...1275791 V. INSTRUCTIONS (7) Electrical connection of high voltage or ground terminal is optional. For example, in the negative mode, the electrode 5 can be used as a ground terminal; in the mass spectrum = P〇S1t1Ve mode, the electrode 5 can be electrically connected to the high voltage end. For the sake of reference, please refer to the first and second embodiments. The manufacturing method of the integrated electrospray wafer according to the first embodiment of the present invention is the same as that of the method of manufacturing the electrospray wafer. The second plastic base is formed with at least one hole 31 corresponding to the microfluidic channel 21. A thermoplastic polymer substrate such as PMMA is made of a plastic substrate having the same extent as the second plastic substrate 2'. Next, when drilling, the second plastic substrate 3 is drilled to form at least one of the holes 31 corresponding to the first plastic channel. The hole 31 is followed by an injection port of the micro-electrode wafer for injection into a liquid phase sample or buffer. Referring to FIGS. 1 and 2C, the integrated micro-electrospray wafer of the first embodiment of the present invention is manufactured. Method of the fourth step: manufacturing a drawing die rod 4, presetting one end of the 模 模 模 模 模 4 in the microfluidic channel of the first plastic substrate 2, preferably using stainless steel, metal, alloy or polymer The drawing rod 4 is made of a linear wire. At the same time, after the first plastic substrate 2 forms the microfluidic channel 21, one end of the drawing die 4 is preset in the microfluidic channel 21 of the first/plastic substrate 2 for subsequent drawing. Micro-electric, sprinkler 61. Furthermore, in order to facilitate the subsequent pulling operation, the present invention may also choose to first treat the drawing die rod 4 with lubricating oil, and then position the drawing die rod 4 into the first plastic substrate 2 The fluid channel is inside 2丨. On the other hand, in the present invention, the micro-electroplated wafer 1 can be prepared first, and then one end of the drawing die 4 is preset in the microfluidic channel 2 of the micro-discharge wafer 1 and the pumping is performed. The other end of the die bar 4 is exposed to the opening of the microfluidic channel 21
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五、發明說明（8) 端。 請參照第1、2 C及2 D圖所示，本發明第一實施例之整合 式微電灑晶片之製造方法第五步驟··由該第一及第二塑性 基板2、3結合形成一微電灑晶片1 〇，並使該抽拉模桿4之 另一端裸露於該微流體通道2 1的開口端。本發明較佳利用 化學藥劑進行化學低溫接合，以便由該第一及第二塑性基 板2、3結合形成該微電灑晶片1 0。低溫接合之優點在於& 少高溫導致該微流體通道21變形之機率。在結合後，該抽 拉模桿4之另一端裸露於該微流體通道21的開口端，以便 鲁後續抽拉製作該微電灑喷頭61。 睛參照第1及2 E圖所示，本發明第 貫施例之整合式微 電灑晶片之製造方法第六步驟··調配一硬化膠材6，將嗦 硬化膠材6塗覆於該微流體通道21的開口端。本發明較^ ^相^自市購可得之各種商用硬化膠材6，其較佳屬於埶 性」高分子材料，例如PMMA膠、環氧樹脂〔ep〇xy〕、& 類〔resin〕、丙烯酸脂類〔acrylates〕 曰 6〔=膠〕可利用適當有物 Ϊ ^ 溫下，先將該硬化膠材6〔 PMMA膠〕調製 产句後，靜置三分鐘使其猶微固化。 巧衣 於該微流體通道21開：端 受到該硬化膠材6之包覆。同時此該該抽硬 模桿4之外周面及微流體通初之内壁面部份毛:者滲亥入抽該拉V. Description of the invention (8). Referring to FIGS. 1 , 2 C and 2 D, the fifth step of the method for manufacturing the integrated micro-electrospray wafer according to the first embodiment of the present invention is formed by combining the first and second plastic substrates 2 and 3 to form a micro The wafer 1 is sprinkled and the other end of the drawing die 4 is exposed to the open end of the microfluidic channel 21. The present invention preferably utilizes a chemical agent for chemical low temperature bonding to form the microelectrospray wafer 10 by the combination of the first and second plastic substrates 2, 3. The advantage of low temperature bonding is that & low temperature causes the microfluidic channel 21 to deform. After the bonding, the other end of the drawing die 4 is exposed to the open end of the microfluidic channel 21, so that the micro-spraying nozzle 61 can be subsequently drawn. Referring to Figures 1 and 2E, the sixth step of the method for manufacturing the integrated micro-electrospray wafer according to the first embodiment of the present invention is to apply a hardened rubber 6 to apply the hardening adhesive 6 to the microfluid. The open end of the passage 21. The invention is more suitable for various commercial hardened rubber materials 6 which are commercially available, and is preferably a bismuth polymer material such as PMMA glue, epoxy resin [ep〇xy], & Acrylates [acrylates] 曰6 [= glue] can be prepared by using appropriate materials 温 ^, the hardened rubber 6 [PMMA glue] is prepared and then allowed to stand for three minutes to make it cure. The delicate fluid is opened on the microfluidic channel 21: the end is covered by the hardened rubber 6. At the same time, the outer peripheral surface of the hard die rod 4 and the inner wall surface of the microfluid-passing initial wall are:
Ϊ275791 五、發明說明（9) 微流體通道21内。 請參照第1及2F圖所示，本發明第一實施 電灑晶片之劁i生太、、表筮 > 本_ 、 之正&式微 曰曰月之裟仏方法第七步驟··在該硬化膠材6完 脒从將該抽拉模桿4拉出該微電灑晶片丨〇 =二微道，開口端向外-體延二= 杈# 土；成形口口質之考量，本發明較佳藉由步進 杈伸程序〔Wmin〕將該抽拉模桿4逐步向外拉伸至：進 mm。此乃利用該抽拉模桿4與硬化膠材6〔 膠〕之門 =附著力，使該硬化膠材6隨著該抽拉模桿4之拉伸，而^ -^之錐狀體。依需求，亦可以定速或變速之拉伸程J 仃。在拉伸過程中，由於該硬化膠材6〔 pMMA膠〕會聚 口口，收縮，因此最終可製得長度約丨· 3 的微電灑喷頭 。冩後，可利用適當之抽氣幫浦將該微流體通道2丨中殘 潤滑油吸除，並以去離子水〔de—ionized water〕對 該微電灑晶片1 0進行清洗動作。 印參照第3 A、3 Β及3 C圖所示，其揭示本發明第一實施例 之微電灑晶片1 0之實體影像及電子顯微影像，該微電灑晶 片1 〇主要包含該微流體通道21、電極5及微電灑喷頭61三 •個部份。由第3B及3C圖之電子顯微影像可知，利用本發明 所製作之微電灑喷頭6 1，其内徑約為3 〇以m，外徑約為1 5 0 〆m ’長度約為1 5 0 0 " m，因此本發明確實可使製得之該微 電灑喷頭61具有足夠内徑，以免發生通道阻塞之問題。利 用上述製造方法，本發明確實能降低該微電灑晶片1 〇之製 造成本，並加速及簡化其製程。 C:\LOGO-5\FIVE CONTINENTSXPK9738. ptd 第15頁 1275791 五、發明說明（ίο) ___ 請參照第4及4A圖所示，| 流體通道21 ’及毛細管7之局^揭示習用微電灑晶片1 〇，之微Ϊ 275791 V. Description of the invention (9) Inside the microfluidic channel 21. Referring to FIGS. 1 and 2F, in the first embodiment of the present invention, the seventh step of the method of immersing the wafer, the 筮, and the _ After the hardened rubber material 6 is completely pulled out from the drawing die rod 4, the micro-electrospray wafer 丨〇=two micro-channels, the open end is outward-body extension two=杈# soil; the quality of the forming mouth is considered, Preferably, the drawing die rod 4 is gradually stretched outward to: mm by a step stretching process [Wmin]. This is the use of the pull-out mold 4 and the door of the hardened rubber material 6 [adhesive] = adhesion, so that the hardened rubber material 6 is stretched with the drawing mold rod 4, and the cone-shaped body. According to the demand, the stretching process can also be fixed or variable speed J 仃. During the stretching process, since the hardened rubber material 6 [pMMA glue] condenses into the mouth and shrinks, a micro-electrospray nozzle having a length of about 丨·3 can be finally obtained. After the crucible, the residual lubricating oil in the microfluidic channel 2 can be removed by a suitable pumping pump, and the micro-spraying wafer 10 is cleaned by de-ionized water. Referring to FIGS. 3A, 3A and 3C, the physical image and electron microscopic image of the micro-sprayed wafer 10 of the first embodiment of the present invention are disclosed. The micro-electroplated wafer 1 〇 mainly includes the micro Three parts of the fluid channel 21, the electrode 5 and the micro-electrospray nozzle 61. It can be seen from the electron microscopic images of Figs. 3B and 3C that the micro-electrospray nozzle 6 1 manufactured by the present invention has an inner diameter of about 3 〇m and an outer diameter of about 150 〆m. 1 5 0 0 " m, so the present invention can indeed make the micro-electrospray nozzle 61 have a sufficient inner diameter to avoid the problem of channel blockage. With the above manufacturing method, the present invention can indeed reduce the manufacturing cost of the micro-electroplated wafer 1 and accelerate and simplify the process thereof. C:\LOGO-5\FIVE CONTINENTSXPK9738. ptd Page 15 1275791 V. INSTRUCTIONS (ίο) ___ Please refer to Figures 4 and 4A, | Fluid Channel 21' and Capillary 7 to disclose the conventional micro-discharge wafer 1 〇, the slightest
圖所示·，其揭示本發明第二=示意圖。另請參照第5及5 A 體通道2 1及微電灑噴頭6 j舄施例之微電灑晶片1 0之微流 如第4及4A圖所示，習用局部示意圖。 21，連接該毛細管7時，當田—電灑晶片1 〇 ’之微流體通道 管徑不相配合，而產生一「一毛細管7與微流體通道21，之 樣本之後續質譜分析效率。f ^區」，進而容易影響生物 微電麗晶片之微電灑ί頭二第5及5A圖所示，本發明之 員6 1係利用步進拉伸女腺好 >6〔 PMMA膠〕所形成。在拉伸租伸'亥硬化膠材 f ’並完整包覆其内壁面。經由步進拉伸 的程序，、該硬化膠材6沿著該微流體通道21之内壁面依序 向外形成一弧錐面6 2、一喷纟貞# g A q $ 〇a p 貝頌逋道及一開口 64，並使該 微觀輕喷頭61形成細長之錐狀體。該微流體通道以之内壁 面、弧錐面62及喷頭通道63係依序平滑的一體相接，且該 弧錐面62係呈漏斗形，因此可有效防止液相樣本流經該微 μ體通道21及微電灑喷頭6 1之交界處發生堵塞或遞延拖尾 現象’在清洗該微流體通道21時也不易有溶液殘留於交界 .處。 請參照第6 A、6 B及6 C圖所示，本發明之微電灑晶片1 〇係 利用一質譜儀8〔Bruker Esquire 3000 口1115商用質譜 儀〕進行測試，以驗證其質譜分析應用之效能。該質譜儀 8設有一樣本入口 81〔不使用該質譜儀8本身内建之喷 頭〕。測試時，將該微電灑晶片1 〇固定在可三維移動之一The figure shows a second = schematic view of the invention. Please refer to the 5th and 5th A channel 2 1 and the micro-spraying nozzle 6 j舄. The micro-flow of the micro-discharge wafer 10 as shown in Figures 4 and 4A. 21, when the capillary 7 is connected, when the microfluidic channel diameter of the field-discharge wafer 1 〇' does not match, a "sample 7 and microfluidic channel 21 are generated, and the subsequent mass spectrometry efficiency of the sample is .f ^ The region, which is easy to affect the micro-electricity of the bio-micro-electricity wafer, is shown in Figures 5 and 5A, and the member of the present invention is formed by step-stretching female gland >6 [PMMA] . Stretch the 'hardened rubber f' and stretch the inner wall surface. Through the step of step stretching, the hardened rubber material 6 sequentially forms an arc-shaped surface along the inner wall surface of the microfluidic channel 21, and a sputum # g A q $ 〇ap An opening 64 is formed and the microscopic light nozzle 61 is formed into an elongated tapered body. The microfluidic channel is integrally connected by the inner wall surface, the arc cone surface 62 and the nozzle channel 63 in a smooth manner, and the arc cone surface 62 is funnel-shaped, thereby effectively preventing the liquid sample from flowing through the micro-μ At the junction of the body passage 21 and the micro-electrospray nozzle 61, a clogging or deferring smearing phenomenon occurs. When the microfluidic channel 21 is cleaned, it is also difficult for a solution to remain at the junction. Referring to Figures 6A, 6B and 6C, the micro-electrospray wafer 1 of the present invention is tested using a mass spectrometer 8 [Bruker Esquire 3000 1115 commercial mass spectrometer] to verify its mass spectrometry application. efficacy. The mass spectrometer 8 is provided with the same inlet 81 (the nozzle built in the mass spectrometer 8 itself is not used). When testing, the micro-electroplated wafer 1 〇 is fixed in one of three-dimensional movement
C:\LOGO-5\FIVE CONTINENTS\PK9738.ptdC:\LOGO-5\FIVE CONTINENTS\PK9738.ptd
…1275791 ' 五、發明說明（11) " " "' ""~- 調整台82上，調整至該微電灑喷頭61距離該質譜儀8之樣 本入口 8j約〇· 5 mm，使該微電灑晶片10之電極5接地，及 由該質缙儀8提供—4〇〇〇v之高電壓。接著，將一液相樣本 •、〔未、”a示〕由5亥彳政電灑晶片1 〇之孔31主入縱向的微流金通 1 一端’同時將一緩衝液由該微電灑晶片1 0之孔3 1注入 :橫向的微流體通道21 —端。例如，以咖啡因〔c〇f f ine， /辰度1 0 Μ〕之液相樣本進行電喷灑，咖哪因中混合少量醋 酸以助其解離。該質譜儀8另將訊號傳送至一電腦83進行 分析’其結果如第6Β圖所示，所得圖譜訊號清晰，且各峰 值〔peak〕幾乎無遞延拖尾之雜訊，此可證明本發明之微 電灑喷頭61之電灑效率良好。另外，如第6C圖所示，亦可 進行肌紅蛋白〔my〇globiri，濃度10-5jj〕之液相樣本的電 喷灑。此肌紅蛋白之蛋白質溶液為質譜儀標準測試溶液， 才肌紅蛋白之液相樣本由該微電灑喷頭61進行喷灑20 上’游離後的液滴以帶電荷之多寡依序呈高斯分 佈，其結果同樣可得到高解析之檢測質譜圖。...1275791 ' V. Invention description (11) """""~- Adjusting the stage 82, adjusting to the micro-electrospray nozzle 61 from the mass spectrometer 8 sample inlet 8j about 〇·5 Mm, the electrode 5 of the micro-discharge wafer 10 is grounded, and the high voltage of -4 〇〇〇V is supplied by the mass spectrometer 8. Next, a liquid phase sample, [not, "a" is introduced from the hole 31 of the 5 彳 电 电 晶片 主 主 主 主 主 主 主 主 主 主 ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 主 主 主 主 主 主 主The hole 10 1 of the wafer 10 is injected: the end of the microfluidic channel 21 in the lateral direction. For example, the liquid phase sample of caffeine [c〇ff ine, /chenness 10 Μ] is electrically sprayed, and the mixture is mixed. A small amount of acetic acid is used to help dissociate. The mass spectrometer 8 transmits the signal to a computer 83 for analysis. The result is as shown in Fig. 6, and the obtained signal is clear, and each peak has almost no delay and tail. This can prove that the electrospray nozzle 61 of the present invention has good electrospray efficiency. In addition, as shown in Fig. 6C, a liquid phase sample of myoglobin (my〇globiri, concentration 10-5jj) can also be performed. Electrospraying. The protein solution of myoglobin is the standard test solution of the mass spectrometer, and the liquid phase sample of myoglobin is sprayed by the micro-spraying nozzle 61 on the 20's free droplets to be charged. The Gaussian distribution is sequentially obtained, and the result is also a high-resolution detection mass spectrum.
再者’本發明的微電灑晶片不僅可應用於典型之電喷灑 游離法 ^ 谱分析（eleCtr〇Spray i〇niZati〇n/maSS •spectrometry，ESI-MS )，且亦可應用於類似基質輔助雷 射脫附游離法〔matr i X-ass i sted 1 aser desorpt i on ionization，MALDI〕系統之脫附游離質譜分析Furthermore, the micro-discharge wafer of the present invention can be applied not only to typical electrospray ionization analysis (eleCtr〇Spray i〇niZati〇n/maSS •spectrometry, ESI-MS), but also to similar substrates. Desorption free mass spectrometry analysis of the system of assisted laser desorption free method [matr i X-ass i sted 1 aser desorpt i on ionization, MALDI]
(desorption ionization masss pectrometry，DI-MS )’以適用於不同生物樣本偵測之需求。 請參照第7圖所示，本發明第二實施例之整合式微電灑(desorption ionization masss pectrometry, DI-MS)' is suitable for the detection of different biological samples. Referring to FIG. 7, the integrated micro-electric shower of the second embodiment of the present invention
1275791 、發明說明（12) 晶片及其製造方法。相對於第一實施例，第二實施例係藉 由步進拉伸程序在同一片該微電灑晶片i 〇上製作多組該微 電灑喷頭6 1。藉此，該微電灑晶片丨〇可利用多組該微電灑 ^頭6 1分別〔或同步〕進樣至該質譜儀8之樣本入口 8丨連 績偵測多種液相樣本。此微電灑晶片丨〇可應用於生物醫學 領域之快速疾病檢測，可利用多組該微電灑喷頭6丨快速進 行多位病患之蛋白質檢測，且因本晶片製作成本低廉、製 迅速、分析效率良好，可同時商業化大量生產，故實屬 適合應用於疾病檢測之可拋棄式〔或重複使用式〕檢測晶 •片。 請參照第8A及8B圖所示，其揭示本發明第三實施例之整 =式微電灑晶片及其製造方法。相較於第一實施例，第三 貫施例之微電灑晶片1 〇係組合使用一微型霧化裝置9。該 化裝置9包含一本體91、一樣本霧化槽92、一壓電 3、一霧化驅動電路94及一電源供應器95。組合使 用時，先將該微電灑晶片1 〇定位於該本體2丨上。接著，將 液相樣本注入該樣本霧化槽92内。接著，由該電源供應器 95提供12V直流電源予該霧化驅動電路94，再由該霧化驅 _動電路9 4產生高頻震盪訊號予該壓電霧化片，使該壓電 霧化片93產生高頻震動而霧化該樣本霧化槽92内之液相樣 本，液相樣本形成極微小之液滴，並漂浮於該質譜儀8之 樣本入口 81前方。另一方面，該微電灑晶片丨〇之微流體通 道2 1注入適當液體’並藉由該微電灑喷頭6丨喷出，以提供 離子電荷。離子電荷立即結合霧化後之液相樣本，使液相1275791, invention description (12) wafer and its manufacturing method. With respect to the first embodiment, the second embodiment fabricates a plurality of sets of the micro-spraying nozzles 61 on the same piece of the micro-electroplated wafer i by a step stretching process. Thereby, the micro-electrospray wafer cassette can be used to detect a plurality of liquid phase samples by using a plurality of sets of the micro-electrospray heads 61 respectively (or synchronously) to sample inlets of the mass spectrometer 8. The micro-electrospray wafer crucible can be applied to rapid disease detection in the biomedical field, and multiple sets of the micro-electrospray nozzle 6 can be used to quickly perform protein detection of a plurality of patients, and the wafer is inexpensive to manufacture and rapidly manufactured. The analysis is efficient and can be mass-produced at the same time. Therefore, it is suitable for use in disease detection and disposable (or reusable) detection of crystal chips. Referring to Figures 8A and 8B, there is disclosed a micro-discharge wafer of the third embodiment of the present invention and a method of fabricating the same. In contrast to the first embodiment, the micro-spraying wafer 1 of the third embodiment is combined with a micro-atomizing device 9. The device 9 comprises a body 91, a similar atomization groove 92, a piezoelectric element 3, an atomization drive circuit 94 and a power supply 95. When used in combination, the micro-discharge wafer 1 is first positioned on the body 2''. Next, a liquid phase sample is injected into the sample atomization tank 92. Then, the power supply 95 supplies a 12V DC power supply to the atomization drive circuit 94, and the atomization drive circuit 94 generates a high frequency oscillation signal to the piezoelectric atomization sheet to make the piezoelectric atomization. The sheet 93 generates high frequency vibrations to atomize the liquid phase sample in the sample atomization tank 92. The liquid phase sample forms very minute droplets and floats in front of the sample inlet 81 of the mass spectrometer 8. On the other hand, the microfluidic channel 2 1 of the micro-discharge wafer is filled with a suitable liquid ' and ejected by the micro-spraying nozzle 6 to provide an ion charge. The ionic charge is immediately combined with the atomized liquid sample to make the liquid phase
1275791 .五、發明說明（13) 樣本帶電進入該質譜儀8之樣本入口81進行檢測。此外， 本發明亦可整合使用一針筒注射型幫浦〔syringe pump， 未繪不〕’由該針筒注射型幫浦推送液相樣本進入該樣本 ：霧化槽9 2 ’以便該微型霧化裝置9及微電灑晶片1 〇連續進 樣，以供該質譜儀8做長時間分析檢測。 : 如上所述，相較於第4及4 A圖之習用微電灑晶片1 〇，，第 5及5A圖之本發明微電灑晶片丨〇直接在該微流體通道21之 開口端利用該硬化膠材6 —體成型形成該微電灑喷頭61， 其確實能有效改善習用微電灑晶片1 〇的死水區問題，進而 丨•提升電灑游離法的效能及質譜分析的解析度。 參考文獻： 〔1〕、Q· Xue, F. Foret, Υ· Μ· Dunayevskiy, P. M|^^Fracky> Ν· E· McGruer , B. L. Karger, channel Microchip Electrospray Mass Spectrometry1丨，Anal· Chem·，69，426-430(1997). C 2 ] ' R. S. Ramsey and J. M. Ramsey, "Generating Electrospray from Microchip Devices •Using E1ectroosmot i c Pumping" , Anal. Chem. , 69， 1174-1178(1997). 〔3〕、B. Zhang, F. Foret, B. L. Karger, ’丨 High-Throughput Microfabricated CE/ESI-MS: Automated Sampling from a Microwell Plate", Anal. Chem·2001， 73， 2675-2681.1275791 . V. Description of the Invention (13) The sample is charged into the sample inlet 81 of the mass spectrometer 8 for detection. In addition, the present invention can also integrate the use of a syringe injection pump (not drawn). The syringe injection pump pushes a liquid sample into the sample: the atomization tank 9 2 ' so that the micro mist The chemical device 9 and the micro-electrospray wafer 1 are continuously injected for the long-term analysis and detection of the mass spectrometer 8. As described above, the micro-electrospray wafer of the present invention according to FIGS. 5 and 5A is directly used at the open end of the microfluidic channel 21 as compared with the conventional micro-sprayed wafer 1 of FIGS. 4 and 4A. The hardened rubber material 6 is integrally formed to form the micro-electrospray nozzle 61, which can effectively improve the problem of the dead water area of the conventional micro-electrospray wafer 1 , and further improve the performance of the electrospray free method and the resolution of mass spectrometry. References: [1], Q· Xue, F. Foret, Υ· Μ· Dunayevskiy, P. M|^^Fracky> Ν· E· McGruer, BL Karger, channel Microchip Electrospray Mass Spectrometry1丨, Anal·Chem·, 69, 426-430 (1997). C 2 ] 'RS Ramsey and JM Ramsey, "Generating Electrospray from Microchip Devices • Using E1ectroosmot ic Pumping", Anal. Chem., 69, 1174-1178 (1997). [3] B. Zhang, F. Foret, BL Karger, '丨High-Throughput Microfabricated CE/ESI-MS: Automated Sampling from a Microwell Plate", Anal. Chem. 2001, 73, 2675-2681.
C:\L0G0-5\FIVEC0NTINENTS\PK9738.ptd $ 10 胃 1275791 五、發明說明（14) 〔4〕、P. Tabourier，C. Druon，C. Rolando，P. Lefebvre， M On-Chip Micro fluidics For Proteom i c Ana lysis by Electrospray Ionization/Mass Spectrometry", Proc. IEEE EMBS, .2000, 439-444. 〔5〕 、Y. Jiang, P. C. Wang, L. E. Locascio, C. :S. Lee, MIntegrated Plastic Microfluidic Devices with ESI-MS for Drug Screening and Residue Analysis”，Anal· Chem.2001，73, 2048-2053· 〔6〕、W. C. Sung, S. Y. Huang, P. C. Liao, G.C:\L0G0-5\FIVEC0NTINENTS\PK9738.ptd $10 Stomach 1275991 V. Description of Invention (14) [4], P. Tabourier, C. Druon, C. Rolando, P. Lefebvre, M On-Chip Micro fluidics For Proteom ic Ana lysis by Electrospray Ionization/Mass Spectrometry", Proc. IEEE EMBS, .2000, 439-444. [5] , Y. Jiang, PC Wang, LE Locascio, C. :S. Lee, MIntegrated Plastic Microfluidic Devices with ESI-MS for Drug Screening and Residue Analysis", Anal·Chem. 2001, 73, 2048-2053· [6], WC Sung, SY Huang, PC Liao, G.
Lee, C. W. Li, S. H. Chen, 丨,Poly(dimethylsiloxane) - based micro fluidic device with electrospray ionization-mass spectrometry interface for protein identification丨丨， E^：|jLijophoresis 20 0 3，24，3 648-36 54· iSi/] >G. A. Schultz, T. N. Corso, S. J.Lee, CW Li, SH Chen, 丨, Poly(dimethylsiloxane) - based micro fluidic device with electrospray ionization-mass spectrometry interface for protein identification丨丨, E^:|jLijophoresis 20 0 3,24,3 648-36 54· iSi /] >GA Schultz, TN Corso, SJ
Prosser, S. Zhang,丨,A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry", Anal· Chem·2000，72,4058-4063· > 〔8〕、W. Q. Shui, Y. L. Yu, X. J. Xu, Z. Y.Prosser, S. Zhang, 丨, A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry", Anal·Chem·2000, 72, 4058-4063· > [8], W. Q. Shui, Y. L. Yu, X. J. Xu, Z. Y.
Huang, G. B. Xu, P. Y. Yang, "Micro-e1ectrospray with stainless steel emitters", Rapid Commun. Mass Spectrom. 2003; 17: 1541 -1547. C9 ] ^ T. C. Rohner, J. S. Rossier, Η. H.Huang, G. B. Xu, P. Y. Yang, "Micro-e1ectrospray with stainless steel emitters", Rapid Commun. Mass Spectrom. 2003; 17: 1541 -1547. C9 ] ^ T. C. Rohner, J. S. Rossier, Η. H.
Girault, "Polymer Microspray with an IntegratedGirault, "Polymer Microspray with an Integrated
C:\L0G0-5\FIVE CONTINENTSXPK9738.ptd 第20頁 1275791 ' 五、發明說明（15)C:\L0G0-5\FIVE CONTINENTSXPK9738.ptd Page 20 1275791 ' V. Description of invention (15)
Thick-FilmMicroelectrode", Anal. Chem.2001, 73, 5353-5357. 〔10〕、S. Ar sco 11, S· L. Gac, C. Druon, P. Tabouri er, C. Rolando, "A planar on-chip micro-nib * interface for NanoESI-MS microfluidic ；applications", J. M i cromech. M i croeng. 1 4 (2004) 〔11〕、美國公開第 2005/00065 02 號「Integrated monolithic microfabricated dispensing nozzle and liquid chromatography-electrospray system and •method」 〔12〕、美國公開第 2004/0072337 號「Integrated monolithic microfabricated electrospray and liquid chromatography system and method 」 〔13〕、美國公開第 2003/0 1 60 1 66 號「Electrospray iUfi^tion device」 雖然本發明已利用前述較佳實施例詳細揭示，然其並非 用以限定本發明，任何熟習此技藝者，在不脫離本發明之 _精神和範圍内，當可作各種之更動與修改，因此本發明之 保護範圍當視後附之申請專利範圍所界定者為準。Thick-FilmMicroelectrode", Anal. Chem. 2001, 73, 5353-5357. [10], S. Ar sco 11, S. L. Gac, C. Druon, P. Tabouri er, C. Rolando, "A planar On-chip micro-nib * interface for NanoESI-MS microfluidic ;applications", J. M i cromech. M i croeng. 1 4 (2004) [11], US Publication No. 2005/00065 02 "Integrated monolithic microfabricated regional nozzle And liquid chromatography-electrospray system and •method” [12], US Published No. 2004/0072337, "Integrated monolithic microfabricated electrospray and liquid chromatography system and method" [13], US Publication No. 2003/0 1 60 1 66 "Electrospray Although the present invention has been disclosed in detail using the foregoing preferred embodiments, it is not intended to limit the invention, and may be used in various ways without departing from the spirit and scope of the invention. The scope of protection of the present invention is defined by the scope of the appended claims.
C:\L0G0-5\FIVE CONTINENTSXPK9738. ptd 1275791 '圖式簡單說明 【圖式簡單說明】 第1圖：本發明整合式微電灑晶片之製造方法之流程方 塊圖。 第2A至2F圖：本發明第一實施例之整合式微電灑晶片之 •製造方法之各步驟示意圖。 : 第3 A至3 C圖：本發明第一實施例之整合式微電灑晶片之 實體影像及電子顯微影像。 第4及4 A圖··習用微電灑晶片之上視圖及局部剖視圖。 第5及5 A圖：本發明第一實施例之整合式微電灑晶片之 jp上視圖及局部剖視圖。 第6A至6C圖：本發明第一實施例之整合式微電灑晶片整 合使用質譜儀之使用示意圖及質譜曲線圖。 第7圖··本發明第二實施例之整合式微電灑晶片之實體C:\L0G0-5\FIVE CONTINENTSXPK9738. ptd 1275791 'Simple description of the drawing [Simplified description of the drawing] Fig. 1 is a block diagram showing the process of manufacturing the integrated micro-electroplated wafer of the present invention. 2A to 2F are views showing the steps of the manufacturing method of the integrated micro-electrospray wafer of the first embodiment of the present invention. : Figures 3A to 3C: Solid image and electron microscopic image of the integrated micro-electrospray wafer of the first embodiment of the present invention. 4th and 4th drawings. A top view and a partial cross-sectional view of a micro-electrospray wafer. 5 and 5A are a top view and a partial cross-sectional view of the integrated micro-sprayed wafer of the first embodiment of the present invention. 6A to 6C are schematic diagrams showing the use of the integrated micro-electrode wafer in the first embodiment of the present invention using a mass spectrometer and a mass spectrum. Figure 7 is an entity of the integrated micro-electrospray wafer of the second embodiment of the present invention
第8A及8B圖：本發明第三實施例之整合式微電灑晶片整 合使用質譜儀及微型霧化裝置之實體影像及使用示意圖。 【主要元件符號說明 10 微電灑晶片 10, 微電灑晶片 2 第一塑性基板21 微流體通道 3 第二塑性基板31 孔 5 電極 6 硬化膠材 62 弧錐面 63 喷頭通道 7 毛細管 8 質譜儀8A and 8B are diagrams showing the physical image and use of the integrated micro-spray wafer integrated with the mass spectrometer and the micro-atomizing device according to the third embodiment of the present invention. [Main component symbol description 10 micro-spray wafer 10, micro-spray wafer 2 first plastic substrate 21 microfluid channel 3 second plastic substrate 31 hole 5 electrode 6 hardened rubber 62 arc cone surface 63 nozzle channel 7 capillary 8 mass spectrometry instrument
I 模板 II 互補凸模 21 微流體通道 4 抽拉模桿 61 微電灑喷頭 64 開口I Template II Complementary Punch 21 Microfluidic Channel 4 Pulling Rod 61 Micro Electrospray Nozzle 64 Opening
一 1275791 圖式簡單說明 調整台 83 電腦 本體 9 2 樣本霧化槽 霧化驅動電路9 5 電源供應器 81 樣本入口 82 9 微型霧化裝置9 1 93 壓電霧化片 94 # _A 1275791 Schematic description of the adjustment table 83 computer body 9 2 sample atomization tank atomization drive circuit 9 5 power supply 81 sample inlet 82 9 micro atomization device 9 1 93 piezoelectric atomization film 94 # _
C:\L0G0-5\FIVE CONTINENTS\PK9738.ptd 第23頁C:\L0G0-5\FIVE CONTINENTS\PK9738.ptd Page 23
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