507046 座齊印窆慧讨轰苟員11肖費^乍土沪災 A7 B7 五、發明說明（/ ) 【發明之應用範疇】 本發明是關於一種微流體導引裝置，特別是關於一種外接式 伺服系統與受控晶片形成之無接點微流體驅動方法及裝置。 【發明背景】 能夠自動化操作核酸檢體處理及鹼基序列檢測之生物晶片、/ (biochip for DNA-based reaction )是目前世界各國競相發展的熱門 產品。在此類型的晶片中，導引檢體或生化試劑在晶片之通道内移 動的微流體驅動裝置是最重要的必備技術。而如何避免檢體或生化 試劑藉此驅動裝置交叉污染，則是設計上必須特別注意的重要考 量。 常見的設計策略可分三大類型：（一）晶片内建機械式微幫 浦（on-chip mechanical micropump );(二）晶片内建電極動力式 微幫浦（on-chip electrokinetic micropump );(三）晶片外接伺服 系統（external servo_system) 〇 分述如下： (一）機械式微幫浦 利用微加工技術（micro-machining)可直接在晶片上内建機械 式微幫浦。這種没计必須在晶片内佈置可動元件（111〇^^此1^31^)。 Roland Zengerie等人所發明的靜電式微幫浦（eiectr〇staticaUy driven diaphragmmicropmnp，美國專利第 5,529,465 號）即為一例。 微幫浦本體包括一個壓力艙，利用其二層結構之間的間歇靜 電吸引’配合流體通道上兩片早向被動閥（passive eheck valve )， 利用循環交換方式完成幫浦動作，工作流量大約是35〇V]/min。 FrankT.Hartley所發明的蠕動式微幫浦（micr〇madlined # 3 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公愛 — III----III -III----^--------- (請先閱讀背面之注意事項再填寫本頁) 507046 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（a ) peristaltic pump，美國專利第5,705,018號，是另一種較為簡潔的設 計。該發明在晶片之微通道内壁序列密植一塊塊可變形的導體帶 (flexible conductive strips)，當電壓脈波通過通道上方時，利用靜 電吸引導體帶一塊塊「循序」上舉，形成微通道的蠕動現象，藉此 推動通道内的流體前進。工作流量約為100#l/min。 在這種具有可動元件且微結構複雜的裝置中，要完全清除前 一次操作所殘留的檢體或生化試劑非常困難。因此若要應用為生物 晶片之驅動裝置，必須界定為可棄式晶片。然而内建交換式或内建 蠕動式微幫浦均涉及複雜的製程或昂貴的特殊材料，使得製造成本 大幅提高，並不適合應用在用完即丟的可棄式晶片上。 此外，尚有利用薄膜（membrane)方式製成之機械式幫浦。 但無論薄膜式或機械微幫浦產生流體驅動力的方法’均需利用闕門 或齒輪設計，並使用較大的外加能量（電力、磁力或熱力），其構 造複雜，製作及操作較為困難，成本也高，為其缺點。而且如果要 將微幫浦製成可驅動流體作雙向運動之雙幫浦，則更增加其複雜度 與困難度。 (二）電極動力微幫浦 電極動力微幫浦是一種非機械式微幫浦，裝置内無須佈置任 何可動元件。常見的操作原理有三種：電滲透（electroosmosis， EO );液電動力（electrohydrodynamics，EHD )及電泳(electrophorosis， EP) 〇 1997 年 Peter J· Zanzucchi 等人提出的發明·· Apparatus and methods for controlling fluid flow in microchannels (美國專利第 4 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -----------·震--------訂 ------!φ. (請先閱讀背面之注意事項再填寫本頁) 507046 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（9 ) 5,632,876號）是一種電滲透與液電動力的組合應用。該發明是在 晶片上的微管道内交錯佈置兩組、共四支電極。中間一組電極深入 微通道中。導通高電壓後，可帶動周遭流體逆電流方式流動，產生 液電動力效應（EHDpumping)。分置兩端的另一組電極僅接觸到 通道壁。導通高電壓後，首先造成管道壁的電性極化（electrical charged)及電荷堆積。此時流體内的帶電粒子因而產生逆電性滲 透’進而引發流體流動’此即電滲透效應（EOpumping)。此發 明整合兩種電極動力的微流體幫浦效果，藉此二力的消長產生推 進、斥退、停滯等微流體導引控制。507046 Block Qiyinhuihui discusses members 11 Xiao Fei ^ Zhutu Shanghai disaster A7 B7 V. Description of the invention (/) [Application scope of the invention] The present invention relates to a microfluidic guiding device, especially an external type Contactless microfluidic driving method and device formed by servo system and controlled wafer. [Background of the Invention] A biochip for DNA-based reaction capable of automating the processing of nucleic acid specimens and the detection of base sequences is a popular product that is currently being developed in countries around the world. In this type of wafer, a microfluidic drive device that guides a specimen or biochemical reagent to move within the channel of the wafer is the most important necessary technology. How to avoid cross-contamination of specimens or biochemical reagents to drive the device is an important consideration in the design. Common design strategies can be divided into three major types: (a) on-chip mechanical micropump; (b) on-chip electrokinetic micropump; (c) The external servo system of the chip (external servo_system) 〇 The details are as follows: (1) Mechanical micro-pumps Using micro-machining technology, mechanical micro-pumps can be built directly on the chip. In this case, a movable element (111〇 ^^ 1 ^ 31 ^) must be arranged in the wafer. An example is the electrostatic micropump (eiectróstaticaUy driven diaphragm micropmnp, US Patent No. 5,529,465) invented by Roland Zengerie et al. The micropump body includes a pressure chamber, which uses the intermittent electrostatic attraction between its two-layer structure to cooperate with two early-passive eheck valves on the fluid channel, and completes the pumping action by means of cyclic exchange. The working flow is approximately 35 ° V] / min. FrankT. Hartley's peristaltic micropump (micr〇madlined # 3 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 public love — III ---- III -III ---- ^- ------- (Please read the notes on the back before filling out this page) 507046 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (a) Peristaltic pump, US Patent No. 5,705,018, is Another relatively simple design. The invention implants a series of flexible conductive strips on the inner wall of the microchannel of the wafer. When a voltage pulse passes through the channel, the conductors are attracted to each other in order. For example, the creeping phenomenon of the microchannel is formed, thereby pushing the fluid in the channel forward. The working flow rate is about 100 # l / min. In this kind of device with movable elements and complicated microstructure, it is necessary to completely remove the residues from the previous operation. The specimen or biochemical reagent is very difficult. Therefore, if it is to be used as the driving device of biochip, it must be defined as a disposable chip. However, the built-in exchange type or built-in peristaltic micropump involves complexities. Process or expensive special materials, which greatly increases the manufacturing cost, is not suitable for use on disposable wafers. In addition, there are still mechanical pumps made by the membrane method. But regardless of the membrane The method of generating fluid driving force by mechanical or mechanical micropumps requires the use of gates or gears, and uses large external energy (electricity, magnetic force or heat). The structure is complicated, the production and operation are difficult, and the cost is high. , Its disadvantages. And if the micropump is to be made into a dual-pump that can drive fluid for bidirectional motion, it will increase its complexity and difficulty. (II) Electrode power micropump Electrode power micropump is a kind of Non-mechanical micropumps do not require any movable components in the device. There are three common operating principles: electroosmosis (EO); electrohydrodynamics (EHD) and electrophorosis (EP). Peter J. 1997 The invention proposed by Zanzucchi et al. Apparatus and methods for controlling fluid flow in microchannels (U.S. Patent No. 4 Paper Standard Use Chinese National Standard (CNS) A4 specification (210 X 297 mm) ----------- · Zhen -------- Order ------! Φ. (Please first Read the notes on the back and fill in this page) 507046 A7 B7 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Invention Description (9) No. 5,632,876) is a combination application of electroosmosis and hydroelectric force. In the invention, two groups of four electrodes are arranged in a staggered manner in a microchannel on a wafer. The middle set of electrodes penetrates the microchannel. After the high voltage is turned on, the surrounding fluid can be driven to flow in a reverse current manner, resulting in a hydrodynamic effect (EHDpumping). The other set of electrodes at both ends of the split only touch the channel wall. After the high voltage is turned on, the electrical charging of the pipe wall and the accumulation of electric charges are caused first. At this time, the charged particles in the fluid will cause reverse electrical permeation ' and then cause fluid flow ' this is called the EO pumping effect. This invention integrates the microfluidic pumping effect of two kinds of electrode power, so that the fluctuation of the two forces produces microfluidic guidance control such as pushing, repulsion and stagnation.
Paul C· H· Li 與 D. Jed Harrison 於 1997 年提出之論文 「Transport，manipulation^ and reaction of biological cells on-chip using electrokinetic effects」（Anal· Chem· 1997, 69, 1564-1568 )則 是電滲透與電泳的組合應用。藉由交錯管道間之電泳與電滲透力量 間的差異，生物細胞即可輕易的被導引、轉向，甚至分類。不過電 滲透或電泳所移動的均是溶液中的帶電粒子而非溶液本身，因此該 研究的主要效應並不是微流體的導引，而是移動存在溶液中的生物 細胞（canineeiythrocyteetal·) 〇 就製程觀點而言，電極動力微幫浦的結構最簡單，製造成本 最低，然而在應用層面上卻有諸多限制。首先，管道内必須事先注 滿溶液，故無法將檢體或反應試劑導入空管道内。其次，EHD幫 浦能移動流體距離非常有限，而E0與EP幫浦的移動對象主要是 流體中的帶電粒子而非流體本身，因此無論何種方法，對於流體的 幫浦效果其實並不顯著（工作流量約1〇//1/min)。再者，三種作 5 本紙張尺度適用中國國豕標準（CNS)A4規格（210 X 297公爱） -----------裝--------訂--------- i (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 507046 A7 —~—-—---------- 五、發明說明（# ) 用力都必須在非常細微的管道内才能運作（直徑約1〇〇//π1)，且 必須在很近的距離内導通數百至數千伏的壓差，故其操作成本並不 低。最後’ EHD幫浦僅能適用於非極性的有機溶劑，而Ε〇與Ερ 幫浦僅能適用於極性溶液，且溶液中的離子濃度也會明顯影響幫浦 的推動效率，故一旦反應進行過程中離子濃度發生變化時，將使得 流體的導引變得難以控制。 (三）晶片外接伺服系統（external servo-system ) 將流體導引的工作交給晶片外接的伺服系統，晶片内無須任 何主動元件’其晶片結構必然簡單，製作成本亦低。且外接的伺服 系統不直接接觸檢體或反應試劑，故可重複使用。間題是在伺服系 統與晶片的介面（world-to-chip interface)，如何將一般尺寸之傳 輸導管（傳輸流體可為氣體或是試劑本身）連結到微觀尺寸的晶片 上，涉及一系列複雜的微加工技術。如果伺服系統與晶片間的介面 問題能夠解決，微流體的導引設計採用外接伺服系統，搭配低成 本、無主動元件的可棄式晶片，將會是最為可行的策略。 因此目前實有必要提供一種新穎的微流體導引裝置，以提供 微流體在管道内行進之驅動力。 * 同時也有必要提供一種簡化且製作容易的微流體導引裝置。 此外’目前也有必要提供一種新穎的外接式微流體導引裝 置，可以引導微流體在管道内作雙向行進。 【發明之目的】 本發明之目的即在提供一種新穎的微流體導引裝置，以提供 微流體在管道内行進之驅動力。 6 ---II------------ (請先閲讀背面之注意事項再填寫本頁) 川/U46 經濟部智慧財產局員工消費合作社印製 A7 —^ ----— B7___ 五、發明說明（丈） 本發明之目的也在提供一種簡化且製作容易的微流體導引裝 置。 本發明之目的也在提供一種新穎的外接式微流體導引裝置， 可以引導微流體在管道内作雙向行進。 本發明之目的也在提供一種新穎的微流體雙向導引方法。 本發明之目的也在提供—一種新穎的微流體雙向導引系統。 【發明之簡述】 依據本發明之微流體導引裝置，係具有一個可以製作在晶片 上之微流體導引平台，包括二個或以上之微小化文氏（Venturi)幫 浦及至少一微流體管道，以及製作於管道内之微混合器或微反應 器，一組可變換氣體大小的外接氣流供應控制模組，可以產生至少 二道可變速、變頻的氣流，·以及連接該微流體導引平台及該氣流供 應控制模組之介面裝置。其中，該氣流供應控制模組所供應氣流， 經由該介面裝置而選擇性地變速、變頻分別進入該至少二個文氏幫 浦’驅動連結至該至少二個文氏幫浦的微流體管道内之微流體作不 同速度的前進、後退、停滯等動作，以完咸流體輸送、混合或反應 等效果。 上述及其他本發明之目的及優點，可由以下詳細說明並參照 下列圖式而更形清楚。 【圖式之說明】 第1圖表示本發明微流體導引裝置之一實施例之方塊圖。 第2圖表示一種適用在本發明微流體導引裝置之微流體導引 平台平面結構示意圖。 7 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 1 -----ill --------^ —AVI (請先閱讀背面之注意事項再填寫本頁) 五、發明説明（A ) 第3圖表示一種適用在本發明微流體導引裝置之介面裝置結構 圖。 第4圖表示一種適用在本發明微流體導引裝置之微流體導引平 台製法流程圖。其中（a)表示矽晶片上形成氧化層，（b)表晶片與 電阻層，（c)為在晶片上形成之蝕刻罩幕，（d)表示晶片深蝕刻後 的情形，（e)為晶片與玻璃板接合後的情形。 第5圖顯示本發明中驅動氣體流量與測試流體流速關係表。 【發明之詳細說明】 依據本發明之微流體導引裝置，係具有一個可以製作在晶片上 之微流體導引平台，包括二個或以上之微小化文氏（Venturi)幫浦 及至少一微流體管道，以及製作於管道内之微混合器或微反應器；一 組可變換氣體大小的外接氣流供應控制模組，可以產生至少二道可變 速、變頻的氣流；以及連接該微流體導引平台及該氣流供應控制模組 之介面裝置。其中，該氣流供應控制模組所供應氣流，經由該下面装 置而選擇性地變速、變頻分別進入該至少二個文氏幫浦，驅動連結至 該至少二個文氏幫浦的微流體管道内之微流體作不同速度的前進、後 退、停滯等動作，以完成流體輸送、混合或反應等效果。 經濟部智慧財產局員工消費合作社印製 以下说明本發明微流體導引裝置之構造。第1圖表示本發明微 流體導引裝置之一種實施例平面圖。如圖所示，本發明之微流體導引 裝置主要包括一個微流體導引平台（10)及一個驅動氣體供應控制模 組（2)。該導引平台（10)具有一個微流體管道（11)及二個文氏 (Venturi)幫浦（12) (13)。微流體通道（11)兩端連接該二個 文氏幫浦（12) (13)。 驅動氣體供應控制模組（20)具有一氣流源（21),以氣體 HP my docimiente/itri/Dbsp-lZSB ^ 507046 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（7 ) 管道（22) (23)分別對該文氏幫浦（12) (13)供應驅動氣體。 在氣體管道（22) (23)上各設置流量控制器（24) (25)。利用 一個微電腦控制器（未圖示），可控制該流量控制器（24) (25)， 而控制任一時點供應於各文氏幫浦（12) (13)之氣體其流量。 請參閱第2圖。第2圖表示一種適用在本發明微流體導引裝置 的微流體導引平台（10)之平面結構示意圖。如圖所示，文氏幫浦 (12) (13)各為一中央較窄，兩端較寬的氣體通道。當通過該通 道之氣體速率達到一定程度時，即可在該通道之較窄部份產生一低 氣壓’而吸引連接該較窄部份之管道内（如該微流體管道）之流體 流出。此種現象稱為白努力效應（BernoulliEffect)。因此，當向 第1文氏幫浦（12)供應氣體，而不對第2文氏幫浦（13)供應氣 體時，位於微流體通道（11)内之流體，即流向該第1文氏幫浦端 (12)。反之亦然。同時對2個文氏幫浦（12) (13)供應氣體時， 微流體管道（11)内之流體即可緩慢前進、後退或停滯。交替對2 個文氏幫浦（12 )(13 )供應氣體時，即可使該微流體在管道（11) 内混合。 在該微流體管道（11)内可以設置反應（例如加熱器，未圖 示），即可使微流體在管道（11)内進行所欲之反應。 在上述微流體導引平台（10)中，微流體之控制常需考慮微 流體之表面張力以及其對管道（11 )壁之吸附力。此為微流體導引 系統與大尺寸流體導引系統不同之處。 在上述微流體導引平台（10)中，可設一流體進出井（14)。 在此加入流體，並對第2文氏幫浦（13)供應氣體，即可使流體進 9 本紙張尺度適用中國國家標準（CNS)A4規格（21〇 x 297公 —----——^------—^ (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 507046 A7 ______B7____ 五、發明說明（<?) 入管道（11)中。 為提供該氣體供應控制模組（20)與該微流體導引平台（10) 間良好之介接，本發明特別設計一個介面裝置（30)。第3圖即顯 示該介面裝置之結構示意圖。如圖所示，該介面裝置具有一個上蓋 (31)及一下蓋（32)。在下蓋（32)則設有一個微流體導引平台 座（33)，在該導引平台座（33)相對應於該導引平台（1〇)之文 氏幫浦（12) (13)氣體入口處，設有二氣體導引口（34) (35)。 在該上蓋（31)相對該二氣體導引口（34) (35)之處，則設二氣 體入口（36) (37)。該氣體入口（36) (37)可供氣體供應控制 模組（20)之氣體通道（22) (23)之接頭（未圖示）插入。將該 上、下盍（31) (32)接合，即可完成該介面裝置（3〇)。使用時， 將氣體供應控制模組（20)之氣體通道（22) (23)以接頭接至該 介面裝置（30)之氣體入口（36) (37),並將該形成晶片之微流 體導引平台（10)礙入該導引平台座（33)，即可對該導引平台（1〇) 之管道（11)内之流體進行導引。 在該微流體導引平台（10)之製作方面，可以利用微系統 技術進行。第4圖即顯示一種本發明微流體導引裝置之微流體導 引平台製作方法流程圖。如圖所示，於步驟⑷將石夕晶片先經 爐管產生熱氧化層，當作深_用的罩幕。於㈨_準的黃 光微影，並於⑷魏化物侧製程，定義歧體通道圖案。 於（d)經ICP深侧石夕到所需深度。最後於⑷與玻璃作陽極 接合並切割成所要的晶片大小。 在降低成本的可棄式晶片細上，可使用PM·等高分子 10 ▼裝—— (請先閱讀背面之注意事項再填寫本頁)The paper "Transport, manipulation ^ and reaction of biological cells on-chip using electrokinetic effects" proposed by Paul C. H. Li and D. Jed Harrison in 1997 (Anal. Chem. 1997, 69, 1564-1568) is electrical Combined application of osmosis and electrophoresis. With the difference between electrophoretic and electroosmotic forces between staggered channels, biological cells can be easily guided, diverted, and even classified. However, the electrophoresis or electrophoresis moves the charged particles in the solution rather than the solution itself. Therefore, the main effect of this study is not the guidance of the microfluid, but the movement of biological cells (canineeiythrocyteetal) in the solution. From a viewpoint, the structure of the electrode powered micropump is the simplest and the manufacturing cost is the lowest, but there are many restrictions on the application level. First, the pipe must be filled with the solution in advance, so the specimen or reaction reagent cannot be introduced into the empty pipe. Secondly, EHD pumps can move fluids at very limited distances, while E0 and EP pumps are mainly driven by charged particles in the fluid rather than the fluid itself, so no matter what method is used, the pumping effect on the fluid is actually not significant ( Working flow is about 10 // 1 / min). In addition, three paper sizes of 5 paper sizes are applicable to China National Standard (CNS) A4 (210 X 297 public love) ----------- installation -------- order --- ------ i (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 507046 A7 — ~ —-—---------- V. Invention Note (#) The force must be operated in a very fine pipe (approximately 100 // π1 in diameter), and a pressure difference of hundreds to thousands of volts must be conducted in a short distance, so its operating cost is Not low. Finally, the EHD pump can only be applied to non-polar organic solvents, while the E0 and Eρ pumps can only be applied to polar solutions, and the ion concentration in the solution will obviously affect the efficiency of the pump, so once the reaction progresses When the ion concentration changes, it will be difficult to control the guidance of the fluid. (3) External servo-system The external servo-system is used to transfer the work of fluid guidance to the external servo system of the chip. There is no need for any active components in the chip. The chip structure must be simple and the manufacturing cost is low. And the external servo system does not directly contact the specimen or reaction reagent, so it can be reused. The problem is how to connect a general-sized transmission tube (the transmission fluid can be a gas or the reagent itself) to a micro-sized chip in the world-to-chip interface of the servo system and the chip, involving a series of complex Micromachining technology. If the interface between the servo system and the chip can be solved, the microfluidic guidance design uses an external servo system, and it is the most feasible strategy to use a low-cost, disposable chip with no active components. Therefore, it is really necessary to provide a novel microfluidic guiding device to provide the driving force for the microfluid to travel in the pipeline. * It is also necessary to provide a simplified and easy-to-manufacture microfluidic guiding device. In addition, it is also necessary to provide a novel external microfluidic guiding device which can guide the microfluid to travel in both directions in the pipeline. [Objective of the Invention] The object of the present invention is to provide a novel microfluidic guiding device to provide a driving force for the microfluid to travel in a pipeline. 6 --- II ------------ (Please read the notes on the back before filling out this page) Chuan / U46 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 — ^ ---- — B7___ 5. Description of the Invention (Zhang) The object of the present invention is also to provide a microfluidic guiding device that is simplified and easy to make. The object of the present invention is also to provide a novel external microfluidic guiding device that can guide microfluids to travel in both directions in a pipeline. The object of the present invention is also to provide a novel microfluidic bidirectional guiding method. The object of the invention is also to provide a novel microfluidic two-way guidance system. [Brief description of the invention] The microfluidic guiding device according to the present invention has a microfluidic guiding platform that can be fabricated on a wafer, including two or more micro Venturi pumps and at least one micro Fluid pipeline and micro-mixer or micro-reactor made in the pipeline, a set of external air supply control modules that can change the size of the gas, can generate at least two variable-speed, variable-frequency air streams, and connect the micro-fluid guide Interface device for guiding platform and air supply control module. Wherein, the airflow supplied by the airflow control module is selectively shifted and frequency-converted through the interface device into the at least two Venturi pumps and connected to the microfluidic pipes of the at least two Venturi pumps. The microfluid performs forward, backward, and stagnation actions at different speeds to complete the effects of salty fluid transport, mixing, or reaction. The above and other objects and advantages of the present invention will be made clearer by the following detailed description and with reference to the following drawings. [Explanation of the drawing] Fig. 1 is a block diagram showing an embodiment of the microfluidic guiding device of the present invention. Fig. 2 is a schematic diagram showing a planar structure of a microfluidic guiding platform applicable to the microfluidic guiding device of the present invention. 7 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1 ----- ill -------- ^ —AVI (Please read the precautions on the back before filling this page 5. Description of the Invention (A) FIG. 3 shows a structural diagram of an interface device applicable to the microfluidic guiding device of the present invention. Fig. 4 shows a flowchart of a microfluidic guiding platform manufacturing method applicable to the microfluidic guiding device of the present invention. Among them, (a) indicates the formation of an oxide layer on a silicon wafer, (b) a surface wafer and a resistance layer, (c) an etching mask formed on the wafer, (d) indicates a situation after the wafer is deeply etched, and (e) indicates a wafer. After bonding to a glass plate. FIG. 5 is a table showing the relationship between the driving gas flow rate and the test fluid flow rate in the present invention. [Detailed description of the invention] The microfluidic guiding device according to the present invention has a microfluidic guiding platform that can be fabricated on a wafer, including two or more micro Venturi pumps and at least one micro Fluid pipelines, and micro-mixers or micro-reactors made in the pipelines; a set of external air supply control modules that can change the size of the gas can generate at least two variable-speed, variable-frequency air flows; and connect the micro-fluid guide Platform and interface device of the air supply control module. Wherein, the airflow supplied by the airflow control module is selectively shifted and frequency-converted into the at least two venturi pumps through the lower device, and is driven into the microfluidic pipeline connected to the at least two venturi pumps. The microfluid moves forward, backward, and stagnates at different speeds to complete the effects of fluid transportation, mixing, or reaction. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs The structure of the microfluidic guiding device of the present invention will be described below. Fig. 1 is a plan view showing an embodiment of the microfluidic guiding device of the present invention. As shown in the figure, the microfluidic guiding device of the present invention mainly includes a microfluidic guiding platform (10) and a driving gas supply control module (2). The guiding platform (10) has a microfluidic tube (11) and two Venturi pumps (12) (13). The two ends of the microfluidic channel (11) are connected to the two Venturi pumps (12) (13). The driving gas supply control module (20) has a gas source (21), which uses the gas HP my docimiente / itri / Dbsp-lZSB ^ 507046, printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (7) Pipe (22) (23) Supply driving gas to the Venturi pump (12) (13), respectively. Flow controllers (24) (25) are provided on the gas pipes (22) (23). A microcomputer controller (not shown) can be used to control the flow controller (24) (25), and control the flow rate of the gas supplied to each Venturi pump (12) (13) at any time. See Figure 2. Fig. 2 shows a schematic plan view of a microfluidic guiding platform (10) applicable to the microfluidic guiding device of the present invention. As shown in the figure, the venturi pumps (12) and (13) each have a narrow gas channel at the center and wide at both ends. When the velocity of the gas passing through the channel reaches a certain level, a low pressure can be generated in the narrower part of the channel to attract the fluid flowing out of the pipe (such as the microfluidic pipe) connected to the narrower part. This phenomenon is called the Bernoulli Effect. Therefore, when gas is supplied to the first Venturi pump (12), but not to the second Venturi pump (13), the fluid located in the microfluidic channel (11) flows to the first Venturi pump. Urata (12). vice versa. When two Venturi pumps (12) (13) are supplied with gas at the same time, the fluid in the microfluidic pipe (11) can slowly advance, retreat or stagnate. When two Venturi pumps (12) (13) are alternately supplied with gas, the microfluid can be mixed in the pipe (11). A reaction (for example, a heater, not shown) can be provided in the microfluidic pipe (11), so that the microfluidic can perform a desired reaction in the pipe (11). In the above-mentioned microfluidic guiding platform (10), the control of the microfluid often needs to consider the surface tension of the microfluid and its adsorption force on the wall of the pipeline (11). This is the difference between a microfluidic guidance system and a large-sized fluid guidance system. In the above microfluidic guiding platform (10), a fluid inlet and outlet well (14) may be provided. Add fluid here, and supply gas to the second Venturi pump (13), you can make the fluid into 9 paper sizes apply the Chinese National Standard (CNS) A4 specifications (21〇x 297) —----—— ^ ------— ^ (Please read the precautions on the back before filling out this page) Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs Employee Cooperatives 507046 A7 ______B7____ V. Invention Description (<?) Into the pipeline (11) In order to provide a good interface between the gas supply control module (20) and the microfluidic guiding platform (10), the present invention specially designs an interface device (30). Figure 3 is a schematic diagram showing the structure of the interface device As shown in the figure, the interface device has an upper cover (31) and a lower cover (32). A microfluid guide platform base (33) is provided on the lower cover (32), and the guide platform base (33) Corresponding to the gas inlet of the Venturi pump (12) (13) corresponding to the guiding platform (10), two gas guiding ports (34) (35) are provided. The upper cover (31) is opposite to the two gases At the guide port (34) (35), there are two gas inlets (36) (37). The gas inlet (36) (37) can be used for the gas supply control module The connector (not shown) of the gas channel (22) (23) of 20) is inserted. The upper and lower cymbals (31) (32) are joined to complete the interface device (30). When in use, the gas The gas channel (22) (23) of the supply control module (20) is connected to the gas inlet (36) (37) of the interface device (30) with a connector, and the microfluid guide platform (10) forming the wafer By obstructing the guide platform base (33), the fluid in the pipeline (11) of the guide platform (10) can be guided. In the production of the microfluid guide platform (10), it can be used Micro system technology is performed. Figure 4 shows a flowchart of a method for manufacturing a microfluidic guiding platform of the microfluidic guiding device of the present invention. As shown in the figure, in step 夕, the Shi Xi wafer is first passed through a furnace tube to generate a thermal oxide layer. It is used as a mask for depth. The yellow light lithography by Yu Z_, and the process on the Weiwei side, define the pattern of the divergent channel. (D) Pass the ICP deep side to the desired depth. Finally, Yu and Yu Glass is anodically bonded and cut to the desired wafer size. For cost-effective disposable wafers, polymers such as PM · can be used. 10 ▼ Loading-(Please read the precautions on the back before filling this page)
I 考I test
507046 經濟部智慧財產局員工消費合作社印製 A7 五、發明說明 ， 材料，叙程方法為類LIGA製程。可利用上面完成的石夕深_結 構或厚光組結構，經電鍍成模與壓模技術即可完成所需的下層 PMMA結構，再與上層以黏著劑接合即可完成低成本的可丟棄 高分子晶片。 【實施例】 製作一個包括微流體通道及其上、下兩文氏幫浦之晶片，其 規格如下： 晶片外觀大小：30 mm (L) X 15 mm (W) X 525 um (H) , L : 長，W :寬，Η :厚或高，D :深度。 文氏幫浦尺寸·氣體進出通道口截面2 (w) X 300 mn (D)，進氣3 mm後經内縮角〜25。斜度轉成抽氣通道L0皿n (L) x 1·0 mm (W) x 300 um (D)，再經外張角〜1〇。斜度轉成截面2 mm (W) x 300 um (D)出氣通道，與流體連接開口為3〇〇胍(w) x 300 um (D) 〇 微流體通道：截面300 um (W) x 300 um (D),長度婉蜒共約 15 cm 〇 測試液體：藍色鋼筆墨水約4.3 μΐ。 使用切割妤的矽玻璃(長30mm^i5mm，高525 um)接合微流 體晶片。矽玻璃上位於上文氏幫浦處挖一注入口。將藍墨水置於 試劑注入口，藍墨水會因表面張力自動導入流體通道，至張力平 衡停止。此時啟動下文氏幫浦對流體產生白努力效應（Bemoullis effect)的向下吸力（前進），到適當距離再啟動上文氏幫浦產 生向上吸力。當向上吸力與向下吸力平衡時流體停滯。當向上吸 11 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） I----------裝--------訂·---11---- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 A7 ^-- 五、發明說明（（〇 ) 力大於向下吸力時，流體反向運動（後退）。調好上下相對吸力， 藉由電磁閥控制，即可達到上下來回的雙向微流體導引。當氣體 流量愈大對流體的吸力也愈大。控制上下兩文氏幫浦的氣流大小 與時序，即可對流體產生變速變頻的微流體雙向運動特性。 實驗結果當氣體流量為2.7 slpm時，對4·3μ1的藍墨水推動速 度約為9.5 mm/sec，換算成流體體積速度為〇·86 uJ/sec。更大氣 流量，可產生更高流體速度。 實驗結果顯示，測試液體之流速/流量隨氣流大小增加而 增加。第5圖顯示驅動氣體流量與測試液體流速關係表。視應用 需要’可藉氣流量調整不同流體速度達成所需功能。 【發明之效果】 本發明所使用之氣動伺服系統構造簡單、操作容易，比起傳 統機械式微幫浦或電極動力式微幫浦動辄數百至數千伏高壓電源 供應器、甚至現有之各類型晶片外接伺服系氣之運作成本都低。且 容易完成雙向流體導引功能，在多幫浦組合於微流體的運用上，極 具潛力。 本發明之氣體供應控制模組與微流體導引平台之間無須任何 管道連結，使得微反應模組上不必另外設計管道連結介面 (world-to-chip coupler) 〇 在任何工作模式之下，所有氣流均送人微流體導引模組再吹 出系統外。氣體供應與微反應模組之間無任何管道連結，故微反應 模組承載的檢體或生化試劑不會回溯污染伺服系統。 微反應模組部份無須搭配任何可動元件即可完成前進、後 12 -----· —---- 丨訂·--------線 (請先閱讀背面之注音？事項再填寫本頁)507046 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 V. Description of Invention The materials and narrative method are LIGA-like processes. You can use the Shi Xishen structure or thick light group structure completed above, and the required lower PMMA structure can be completed by electroplating and stamping technology, and then bonded with the upper layer with an adhesive to complete the low cost disposable high Molecular wafer. [Example] A wafer including a microfluidic channel and its upper and lower Venturi pumps was fabricated with the following specifications: Appearance of the wafer: 30 mm (L) X 15 mm (W) X 525 um (H), L : Length, W: width, Η: thick or high, D: depth. Venturi pump size · Cross section of gas inlet and outlet channel 2 (w) X 300 mn (D), after 3 mm of air intake, it has a receding angle of ~ 25. The inclination is converted into a suction channel L0 n (L) x 1.0 mm (W) x 300 um (D), and then the opening angle is ~ 10. The slope turns into a 2 mm (W) x 300 um (D) outlet channel with a cross section of 300 guanidine (w) x 300 um (D). The microfluidic channel: 300 um (W) x 300 um (D), about 15 cm in length. Test liquid: Blue pen ink is about 4.3 μΐ. Microfluidic wafers were bonded using diced silica glass (length 30mm ^ 5mm, height 525um). An inlet was dug on the silica glass at the above pump. Place the blue ink in the reagent injection port, and the blue ink will be automatically introduced into the fluid channel due to the surface tension until the tension balance stops. At this time, the downward pumping of the Biaulli effect (Bemoullis effect) on the fluid is started (forward), and the above pump is started to generate an upward suction at a proper distance. The fluid stagnates when the upward suction is balanced with the downward suction. When sucking up 11 This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) I ---------- Installation -------- Order · -11- --- (Please read the notes on the back before filling this page) A7 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ^-V. Description of the invention ((〇) When the force is greater than the downward suction, the fluid moves in reverse ( Backward.) Adjust the upper and lower relative suction, and control the solenoid valve to achieve two-way microfluidic guidance. When the gas flow rate is greater, the suction force of the fluid is greater. Control the flow of the upper and lower Venturi pumps With the timing, the microfluidic bidirectional motion characteristics of variable speed and frequency conversion can be generated for the fluid. Experimental results When the gas flow rate is 2.7 slpm, the pushing speed of the blue ink of 4 · 3μ1 is about 9.5 mm / sec, which is converted into the fluid volume velocity. · 86 uJ / sec. More atmospheric flow rate can produce higher fluid velocity. The experimental results show that the flow rate / flow rate of the test liquid increases with the increase of the air flow. Figure 5 shows the relationship between the drive gas flow rate and the test liquid flow rate. Depending on the application Need to be able to adjust different fluids by air flow Speed achieves the required function. [Effects of the invention] The pneumatic servo system used in the present invention has a simple structure and easy operation. Compared with traditional mechanical micropumps or electrode-powered micropumps, hundreds to thousands of volts of high-voltage power supplies are used. And even the existing various types of chips have low operating costs for external servo system gas. It is easy to complete the two-way fluid guidance function and has great potential in the application of multi-pump combination to microfluidics. The gas supply control module of the present invention There is no need for any pipeline connection with the microfluidic guiding platform, so there is no need to design another pipeline connection interface (world-to-chip coupler) on the micro-reaction module. 〇In any working mode, all air flows are sent to the microfluidic guidance. The module is blown out of the system. There is no pipeline connection between the gas supply and the micro-reaction module, so the specimen or biochemical reagent carried by the micro-reaction module will not trace back to pollute the servo system. The micro-reaction module does not need to be equipped with any movable The components can complete the forward and backward 12 ----- · —---- 丨 order · -------- line (please read the phonetic on the back? Matters before filling out this page)
507046 A7 ___B7 五、發明說明（// ) 退、停滯等微流體運動控制，相較於機械式微幫浦需搭配使用可動 元件（如各類型主動或被動微閥，microvalve)顯然更加精簡。 本發明之工作原理與被驅動流體之極性或離子濃度無關，故 其適用範圍比電極動力式微幫浦寬廣。 綜合言之，本發明提供之氣動伺服系統可適用在製程簡單、 低成本的微流體晶片，故可在操作生化檢測反應之可棄式晶片内提 供微流體驅動。例如在操作核酸檢體處理及鹼基序列檢測之生物晶 片内，導引病人血液、痰檢體進入檢體前處理模組中；或導引核酸 分子進入驗基定序探針陣列(gene pr〇be array)等。對於進一步擴大 規模至可自動化連續生化實驗步驟之晶片實驗室(Lab 〇n a Chip) 而言，本發明亦具備了雄厚的發展潛力。 以上是對本發明微流體導引裝置實施例之說明。習於斯藝之 人士不難由上述說明，了解本發明之精神，並據以作出各種變化與 衍伸。惟無論如何，均屬於本發明之範圍内。 【元件符號之說明】 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 (10) 微流體導引平台 (11) 微流體通道 (12)-(13) 文氏幫浦 (14) 流體進出井 (20) 氣體供應控制模組 (—21) 氣流源 (22)-(23) 氣體管道 (24)-(25) 流量控制器 13 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 507046 A7 B7 五、發明說明（Μ) (30) 介面裝置 (31) 介面裝置之上蓋 (32) 介面裝置之下蓋 (33) 微流體導引平台座 (34)-(35) 氣體導引口 (36)-(37) 氣體入口 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作钍印製 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐）507046 A7 ___B7 V. Description of the Invention (//) Microfluidic motion control such as retreat and stagnation is obviously more streamlined than the use of movable components (such as various types of active or passive microvalves) with mechanical micropumps. The working principle of the present invention has nothing to do with the polarity or ion concentration of the driven fluid, so its application range is wider than that of electrode powered micropumps. In summary, the pneumatic servo system provided by the present invention can be applied to a microfluidic wafer with a simple manufacturing process and low cost, so it can provide microfluidic drive in a disposable wafer that operates a biochemical detection reaction. For example, in a biochip that handles nucleic acid sample processing and base sequence detection, guide the patient's blood and sputum samples into the sample preprocessing module; or direct nucleic acid molecules into the test sequence sequencing probe array (gene pr 〇be array) and so on. For the Lab Lab (Lab On Chip), which can further expand the scale to automate continuous biochemical experiment steps, the present invention also has strong development potential. The above is the description of the embodiment of the microfluidic guiding device of the present invention. Those skilled in the arts can easily understand the spirit of the present invention from the above description, and make various changes and extensions based on it. However, it is within the scope of the present invention. [Explanation of component symbols] (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (10) Microfluidic Guide Platform (11) Microfluidic Channels (12)-(13) Venturi pump (14) Fluid inlet and outlet well (20) Gas supply control module (-21) Air source (22)-(23) Gas pipeline (24)-(25) Flow controller 13 This paper size is applicable to China Standard (CNS) A4 specification (210 X 297 mm) 507046 A7 B7 V. Description of invention (M) (30) Interface device (31) Interface device cover (32) Interface device cover (33) Microfluidic guide Platform base (34)-(35) Gas guide (36)-(37) Gas inlet (Please read the precautions on the back before filling this page) Consumer cooperation of Intellectual Property Bureau of the Ministry of Economic Affairs China National Standard (CNS) A4 specification (210 X 297 mm)