P282775 九、發明說明： 【發明所屬之技術領域】 本發明係關於一種微型喷嘴之製造方法，尤指一種適 用於半導體晶圓切割技術之微型噴嘴之製造方去 【先前技術】 由於蛋白質種類繁多、結構複雜、性質多變，導致蛋 白質分析的過程耗時費事。但是，近年來透過微機電技術 :生物科技的整合，可利用微製造技術將傳統的分析儀器 微小化，而提昇蛋白質分析的效率及精確性。目前，已成 功地開發出包括處理透析、層析及電泳程序的微流體晶片。 電摄離子化法是-種直接將溶液中的蛋白質在大氣壓 力之下經由電喷灑的過程轉換為氣相蛋白f離子，以供質 15 20 :儀進行债測的技術’目前已成為鑑定未知蛋白質化學結 要工具之一。然❿，應用於蛋白質的純化、分離的 ;=晶片可進：步透過微小化的電灑離子化器與質譜儀 作了 •而構成間易的蛋白質分析系統，使蛋白質分析工 作可一貫化作業。 4又私喷/鹿喷嘴與微流體晶片整合時，因晶片材質不 二：：別採用不同方法。舉例可如：先前有人以毛細管接 ;=的方式，將微流體晶片與毛細管接合後，在毛細 與毛二：:二電：而喷灑出氣相離子’但是微流體晶片 接合處仍有死角產生，對於較微量的分析物容易 以其峨雜訊比（S/Nratl。）下降，甚 5 1282775 刻的方法將二 ^M ^ 獲得+ tb 、有机體通這之尖嘴，雖然可 二V果良好之贺嘴，但製程上不僅費工亦費時。再者， 也有利用模具成型後接合 7Γ賈才再者， 兩片基板黏合，而形成—噴嘴'、:―尖鳴之模型與上下 使產口…一：成Ή易有接合錯位的缺點， 程，將日㈣心 眺用傳統㈣晶圓蝕刻製 ㈣成-具有㈣尺寸㈣嘴，然 相當費時。另外，並有直接 衣τ 口丨 現fe 有直接將貝鳴的出口處平面化並非呈 現-叙角’但Μ滴喷灑時，液珠^滑 =易於散佈在喷嘴處，造成較差的喷灑效果。此外 =人以微機電犧牲層之觀念，利用Ρ响e聚合物為材 15P282775 IX. Description of the Invention: [Technical Field] The present invention relates to a method for manufacturing a micro nozzle, and more particularly to a method for manufacturing a micro nozzle suitable for semiconductor wafer cutting technology. [Prior Art] Due to the wide variety of proteins, The structure is complex and the nature is variable, which leads to a time-consuming and laborious process of protein analysis. However, in recent years, through the integration of micro-electromechanical technology: biotechnology, micro-manufacturing technology can be used to miniaturize traditional analytical instruments to improve the efficiency and accuracy of protein analysis. Currently, microfluidic wafers including processing dialysis, chromatography and electrophoresis procedures have been successfully developed. Electro-acoustic ionization is a technique in which a protein in a solution is directly converted into a gas phase protein f ion by electrospraying under atmospheric pressure, and a technique for performing a debt measurement is performed. One of the unknown protein chemical knotting tools. Then, it is applied to the purification and separation of proteins; = the wafer can be stepped through a miniaturized electrospray ionizer and a mass spectrometer to form an easy protein analysis system, which enables the protein analysis work to be consistent. . 4 When the private spray/deer nozzle is integrated with the microfluidic chip, the material of the wafer is different:: Different methods are used. For example, some people have previously used a capillary connection; =, after the microfluidic wafer is bonded to the capillary, in the capillary and the hair:: two electricity: sprayed out of the gas phase ion 'but the microfluidic wafer joint still has a dead angle For a relatively small amount of analytes, it is easy to reduce with its noise-to-noise ratio (S/Nratl.), and even 5 1282775 engraved method will obtain 2 ^M ^ get + tb, the organism passes the tip of the mouth, although it can be two V fruits Good for the mouth, but the process is not only laborious but also time consuming. In addition, there are also the use of the mold to form the joints after the jointing, and the two substrates are bonded together to form the nozzle-type, the model of the squeaking and the upper and lower mouths of the product. The day (four) heart is made with the traditional (four) wafer etching system (four) into - with (four) size (four) mouth, but it is quite time consuming. In addition, there is a direct clothing τ mouth 丨 fe 有 有 有 有 有 有 有 fe fe fe , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , effect. In addition, people use the concept of micro-electromechanical sacrificial layer to use e-polymer as a material.
嘴姓構内=光阻掏空後’而形成—軟質材料的懸空性喷 =構’其製料僅複雜且耗時。於上述習知技術内容中， :于去仍存在5午多尚待克服的問題，例如：流體管道的死 、費日守費工、製作複雜及產品可靠度差，甚至經濟效益 等。 、带因此，目前亟需一種製作穩定、製程簡單且可靠度高 =:貝灑介面，以改善習知缺點，並有利於電灑質譜儀進 行高通量（high throughput)微量樣品的分析。 20 【發明内容】 本發明可提供一種微型喷嘴之製造方法，包括下列步 驟：提供一具有至少一流道之基材、利用一刀具切割該基 材，使该基材形成一具有一 0角之角柱、以及利用該刀具 6 f282775 切割该角柱之0角處，以形成一具有厚度為D2之喷嘴，並 使該流道之一出口位於該喷嘴。其中，基材之厚度為Dl， 且流這底部距離基材表面之深度為D3 ;而0角不大於卯。。 此外，喷鳴之厚度A小於基材之厚度Di，·且流道之深度仏 小於基材之厚度。 3 本發明一較佳態樣中，流道之出口處可位於喷嘴上； 且流道之深度&可大於仏與仏兩者差值之一半。另一態樣The inside of the mouth name = the photoresist is hollowed out and formed - the suspended spray of the soft material = the construction of the material is only complicated and time consuming. In the above-mentioned conventional technical content, there are still many problems to be overcome in the past five years, such as the death of fluid pipelines, the cost of labor, the complexity of production, the poor reliability of products, and even economic benefits. Therefore, there is a need for a stable, simple process and high reliability =: a sprinkler interface to improve conventional disadvantages and facilitate the analysis of high-throughput microsamples by electrospray mass spectrometers. 20 SUMMARY OF THE INVENTION The present invention can provide a method for manufacturing a micro nozzle, comprising the steps of: providing a substrate having at least a first-class track, cutting the substrate with a cutter, and forming the substrate into a corner column having a 0-corner And using the cutter 6 f282775 to cut the corner of the corner post to form a nozzle having a thickness D2, and one of the outlets of the flow passage is located at the nozzle. Wherein, the thickness of the substrate is D1, and the depth of the bottom of the flow from the surface of the substrate is D3; and the 0 angle is not greater than 卯. . Further, the thickness A of the squirting is smaller than the thickness Di of the substrate, and the depth 仏 of the flow path is smaller than the thickness of the substrate. In a preferred aspect of the invention, the outlet of the flow channel may be located on the nozzle; and the depth & of the flow channel may be greater than one-half the difference between the 仏 and 仏. Another aspect
10 15 20 中，本發明之流道出口處可不限於喷嘴，且流道之 可小於仏與仏兩者差值之一半。 又3 一另外，於本發明中所適用之基材可為任何習知具有流 運之基材，且基材之製法可不限，較佳可由至少兩片以上L 基板所黏合組成的具有流道之基材。 ，較佳可介於 ’較佳可介於5 本發明之微型喷嘴，其基材厚度D1不限 5〇//m〜l5〇0/Zm之間；且噴嘴厚度a亦不限 // m〜500 // m之間。 ，本發明所提及之刀具可為習知任一種刀且 土可為-輪刀。於本發明中基材所適用的材不、^ 本卿、酋丄 物、塑膠或其組合等。In 10 15 20 , the outlet of the flow passage of the present invention may not be limited to the nozzle, and the flow passage may be smaller than one half of the difference between the 仏 and 仏. Further, in addition, the substrate to which the present invention is applied may be any conventionally flowable substrate, and the substrate may be produced by any method. Preferably, the substrate may be formed by bonding at least two or more L substrates. The substrate. Preferably, the micro-nozzle of the invention is preferably between 5 Å//m and 15 〇0/Zm; ~500 // m between. The tool referred to in the present invention may be any known knife and the soil may be a wheel cutter. In the present invention, the materials to which the substrate is applied are not, such as qing, mei, plastic or a combination thereof.
Γ:二:可為習知各種形狀，較佳可為U形、V 形等：且流道之孔徑尺寸可不限，較佳 可=22大2:中，本發明中所提及之角柱， 不限J角之大小，且θ角之較佳角度可介於r 此外，本發明一態樣中 噴嘴之用途可不限，較佳可 7 1282775 吸取一液體、氣體、膠體或其組合等。另外，噴嘴亦可噴 灑或排放一液體、氣體、膠體或其組合等。一較佳態樣中j 本發明噴嘴内含的流道可具有層析功能，使樣品可於微型 喷嘴中進行純化、分離、濃縮等步驟。Γ: two: can be various shapes, preferably U-shaped, V-shaped, etc.: and the aperture size of the flow channel can be unlimited, preferably = 22 large 2: in the corner column mentioned in the present invention, It is not limited to the size of the J angle, and the preferred angle of the angle θ may be between r. In addition, the nozzle may be used in any aspect of the invention, and preferably, the liquid may be sucked by a liquid, a gas, a colloid or a combination thereof. Alternatively, the nozzle can be sprayed or discharged with a liquid, gas, gel or combination thereof. In a preferred embodiment, the flow channel contained in the nozzle of the present invention can have a chromatography function, so that the sample can be purified, separated, concentrated, and the like in the micro nozzle.
10 1510 15
20 本發明所製造之噴嘴其應用領域可不限，其可應用於 =物醫學檢測、蛋白質分子量測定及有機分子測 定之相關研究領域，較佳可整合於一電喷灑質譜儀，並 將帶測物電m離子化後，㈣儀μ行㈣物之測試分析。 本發明可利用習知半導體製程上晶圓的機械切割 (wafer dicing)技術，針對本發明之基材進行多軸的精密切 削而產生微米尺寸的結構與流體噴嘴，並在微體流道末 端處建構類似毛細管的突出嘴嘴（n()zzle)，以利於整合微流 K牛與電噴灑離子化質譜（eleetn)spray疆izad〇n _ sp⑽職ete〇。此整合步驟不僅能整合分析樣品的純化、 漢縮、分離、及電灑離子化步驟，並可與質譜儀相連，完 成極微量的-貫化分析，以簡化與加速樣品的分析時間。 【實施方式】 實施例一 ®所不’為本發明_較佳實施例微型喷嘴之 程圖。首先’提供—具有樣品注射孔η之基板10a 有流道12之基板⑽，並將兩者相黏合，以形成一 品注射孔u與流道12之基材ig。其中，流道η 面可為任何形狀，在本實施例中為半圓形；且基材 8 1282775 =的厚w ’而本實施狀基材1G厚度為12醜。 者利用-半導體切割晶圓之刀具（本實施例為刀， t圖未示）將基材10切割成一具有Θ角之角柱20,且本實 了角* 30。最後’於角柱之0角處，沿著基材 幾…下切割兩刀；即利用-輪刀，亦在與流道12 ^垂直的橫截面方向，上下切割出一具有厚度為A之喷 本實施例中喷嘴厚度D2為281.5# m，且流道12之 出口即位於噴嘴3〇上。經由 丰〜+ 由上迹步驟’即可完成本發明微 10 15 20 /、寸之贺嘴。圖2即為本實施例之微型喷嘴側面之示意 圖’其中〇,乃為基材之厚度；1>2乃為喷嘴之厚度；且d 乃為流道之深度。 3 參照圖3,為本實施例喷嘴於掃描式電子顯微鏡下之斜 視照片圖，由圖中可得知本發明之製造方法可獲得一突出 且具有銳角之喷嘴，圖中可顯示此突出之噴嘴乃呈現三角 柱形，其喷嘴出口距離刀具所切割之截面約為5—，且 圖中可觀察噴嘴處具有一流道出口。 實施例二 本實施例係利时施例—所製成的微型噴嘴作為綠 逢先蛋白質分子（GFP’Green Flu〇rescent卜心⑷電 育麗離子化之用，並將微型噴嘴與f譜儀相連後，即可進 行此綠螢光蛋白分子之分子量分析。首先，提供—已純化 之樣品㈣蛋白質分子’將其置入—注射針筒中，且針筒末 端係以膠管連結至微型喷嘴之樣品注射孔，施予一焊力即 可將樣品GFP蛋白質分子注人本發明之微型噴嘴中。ς然， 9 1282775 本實施例中係採用針筒注 限於此。本實施例中 J ，、樣品注入方式可不 < 务明之喷嘴相連於質譜儀，並在 ^ 處施予一電虔，當液相蛋白質分子喷嘴出口處 時，經由電喷灑的過程奋韓 所;、担胃轉換成軋相蛋白質離子，並喷入 貝邊儀中騎分析。本實_巾所使料電錢離子化質 講儀型號為廳roMass ’所待測GFp樣品條件漠度為ι〇 fmole且此貝sf儀分析的結果圖譜可參照圖情示。圖中 可知，本實驗係獲得GFP蛋白質分子的穩定訊號，並清楚指 出其分子量之分佈。因此’本實施例可證實本發明之微型 喷嘴確實能整合於電魏離子化質譜儀，並能有效地將溶 液中的蛋白質分子轉換成氣相的蛋白質離子，以供質譜儀 進行偵測，並可獲得穩定的偵測訊號。 、曰 上述實施例僅係為了方便說明而舉例而已，本發明所 15 主張之權利範圍自應以申請專利範圍所述為準，而非僅限 於上述貫施例。20 The nozzle manufactured by the invention can be applied in any field, and can be applied to the related research fields of physical medicine detection, protein molecular weight measurement and organic molecular measurement, preferably integrated into an electrospray mass spectrometer and tested. After the ionization of the material m, the test of the (four) instrument (four) is tested. The invention can utilize the mechanical dicing technique of the wafer on the conventional semiconductor process to perform multi-axis precision cutting on the substrate of the invention to produce a micro-sized structure and a fluid nozzle, and at the end of the micro-fluid channel A capillary-like protruding nozzle (n()zzle) was constructed to facilitate integration of microfluidic K-bovine with electrospray ionization mass spectrometry (eleetn) spray izad〇n _ sp(10) ete 〇. This integration step not only integrates the purification, Hans, separation, and electrospray ionization steps of the analytical sample, but can be coupled to the mass spectrometer to perform a very small amount of analysis to simplify and accelerate the analysis time of the sample. [Embodiment] Embodiment 1 is not a process diagram of the micro nozzle of the present invention. First, the substrate 10a having the sample injection hole η has a substrate (10) having a flow path 12, and the two are bonded to each other to form a substrate ig of the injection hole u and the flow path 12. Wherein, the flow channel η face can be any shape, which is semi-circular in this embodiment; and the substrate 8 1282775 = thickness w ′ and the substrate 1G of the embodiment has a thickness of 12 ug. The substrate 10 is cut into a corner post 20 having a corner by a tool for cutting a wafer by a semiconductor (not shown in the present embodiment), and the angle is 30. Finally, at the 0 corner of the corner post, two knives are cut along the substrate; that is, using a - wheel cutter, also in the cross-sectional direction perpendicular to the flow channel 12 ^, a spray having a thickness of A is cut up and down. In the embodiment, the nozzle thickness D2 is 281.5# m, and the outlet of the flow path 12 is located on the nozzle 3〇. The micro 10 15 20 /, the inch of the mouth can be completed by the Feng ~ + step by step. Fig. 2 is a schematic view of the side surface of the micro-nozzle of the present embodiment, wherein 〇 is the thickness of the substrate; 1> 2 is the thickness of the nozzle; and d is the depth of the flow path. 3 is a squint photograph of the nozzle under the scanning electron microscope according to the embodiment of the present invention. It can be seen from the figure that the manufacturing method of the present invention can obtain a nozzle having a sharp angle and an acute angle, and the nozzle can be displayed in the figure. It has a triangular prism shape, and its nozzle exit is about 5° from the section cut by the cutter, and there is a first-class exit at the observable nozzle in the figure. EXAMPLE 2 This example is a micro-nozzle prepared as a green protein protein (GFP' Green Flu〇rescent (4) electro-producing ionization, and the micro-nozzle and f spectrometer Once connected, the molecular weight analysis of the green fluorescent protein molecule can be performed. First, the purified sample (4) protein molecule is placed in the injection syringe, and the end of the syringe is connected to the micro nozzle by a hose. The injection hole can be injected into the micro-nozzle of the present invention by applying a welding force. ς然, 9 1282775 In this embodiment, the syringe is limited to this. In this embodiment, J, the sample is injected. The method may not be: the nozzle is connected to the mass spectrometer, and an electric sputum is applied at the outlet of the liquid protein molecule. When the liquid protein protein nozzle is at the outlet, the process is performed by electrospraying; Ion, and spray into the edge of the instrument to ride the analysis. The actual _ towel made the electricity money ionization quality lecturer model for the hall roMass 'the GFp sample conditionality to be measured is ι〇fmole and this sf instrument analysis The result map can be referenced As shown in the figure, it can be seen that this experiment obtains the stabilization signal of the GFP protein molecule and clearly indicates the molecular weight distribution. Therefore, this example can confirm that the micro nozzle of the present invention can be integrated into the electric Wei ionization mass spectrometer. And can effectively convert the protein molecules in the solution into protein ions in the gas phase for detection by the mass spectrometer, and obtain a stable detection signal. The above embodiments are merely examples for convenience of explanation. The scope of the claims of the present invention is determined by the scope of the patent application, and is not limited to the above embodiments.
20 10 ¢282775 【圖式簡單說明】 二糸本發明一較佳實施例之微型噴嘴之製造流程圖。 :::發明一較佳實施例之微型噴嘴側面之示意圖。 斜視照片圖。 、、知描式笔子顯微鏡下之 圖4係本發明微型喷嘴整合於 測試結果圖。 ^離子化貝譜儀之實驗20 10 ¢ 282775 [Simple Description of the Drawings] A flow chart for manufacturing a micro nozzle according to a preferred embodiment of the present invention. ::: A schematic view of the side of the micronozzle of a preferred embodiment. Strabismus photo. Figure 4 shows the micro-nozzle of the present invention integrated into the test result. ^Ionized Bay Spectrometer Experiment
【主要元件符號說明】 10b 基板 20角柱 D2噴嘴厚度 10基材 l〇a基板 11樣品注射孔 12流道 3〇喷嘴 Di基材厚度 D3流道深度 10[Main component symbol description] 10b substrate 20 corner column D2 nozzle thickness 10 substrate l〇a substrate 11 sample injection hole 12 flow path 3〇 nozzle Di substrate thickness D3 flow path depth 10