TWI290850B - Microfluidic volume control system - Google Patents

Microfluidic volume control system Download PDF

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Publication number
TWI290850B
TWI290850B TW95123103A TW95123103A TWI290850B TW I290850 B TWI290850 B TW I290850B TW 95123103 A TW95123103 A TW 95123103A TW 95123103 A TW95123103 A TW 95123103A TW I290850 B TWI290850 B TW I290850B
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Taiwan
Prior art keywords
feed
flow path
end point
passive valve
interface element
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TW95123103A
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Chinese (zh)
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TW200800399A (en
Inventor
Bi-Chu Wu
Chung-Kai Chen
Gin-Shu Young
Mei-Ya Wang
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Ind Tech Res Inst
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Publication of TW200800399A publication Critical patent/TW200800399A/en

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Abstract

The present invention relates to a microfluidic volume control system. The invention achieves single- or multiple-sample volume control by special fluid channel design and the use of one or more passive valves, caps and air vents. Furthermore, the microfluidic volume control system can process a plurality of samples and/or reagents by using single negative-pressure source.

Description

Ι29085Ό * 九、發明說明: 【發明所屬之技術領域】 本發明係關於一種微流體進料體積控制系統,更進一步 地,本發明係關於一種微流體多重進料體積控制系統,尤 其適用於微流體晶片内之流道設計。 【先前技術】 許多臨床生化檢測應用均著眼於特定生物、化學物質 ^ 或病原體的偵測,藉由偵測的結果可以得知該生化物質或 病原體的存在與否或含量多寡,而反映出患病程度、患者 的健康狀態或醫藥處理的療效。此外,生物、化學物質或 病原體的偵測也可用於藥物檢測、工業製程監測、環境監 ~ 測、植物或動物的檢測等應用。 . 近年來,由於機電技術之發展,使得許多原本龐大之 元件得以微小化,人類也逐漸可以藉由微小化之設備,從 事先前所無法進行之實驗,例如:細胞之操控以及快速蛋 白質或DNA之分離等應用。微流體生醫檢測晶片具有高檢 φ 測效能、低樣品或試劑消耗量、體積小以及成本低等優點, 尤其以整合微流體操作及檢測功能於同一晶片上之設計, 最具發展潛力以及市場價值,因此,除了具有微型化之優 勢外,更免除了複雜及昂貴之檢測設備,使得單一晶片便 具有完整之檢測功能。 在微流體晶片的設計中,由於樣品或試劑的量之多少 • 對於分析結果具有最直接的影響,因此必須考慮檢體或試 . 劑的體積控制單元。可用於控制微量液體體積之方法大致 分為三類:1. Off-chip dispenser :市面上的產品可用於控制 微量液體體積常見者有微量分注器(pipette ), 1290850 drop-on_demand dispenser,contact dispenser等。微量分注器 為手動,後兩者則可整合於自動化系統之中, drop-on-demand dispenser,例如ink-jet head 技術雖已成熟, 但機構複雜、製作成本高。至於Contact type dispenser,典 型的應用例如DNA晶片的點片機,其變異係數(coefficient of variation,CV)較高,此二者皆為〇ff-chip dispenser,難 與晶片整合,在操作流程的連貫性、操作品質的一致性及 避免污染等考量之下,並非微流體晶片之最佳選擇;2· On-chip dispenser with active component:這一類的方法可以 整合dispenser於晶片上,但其中與體積控制相關的動作則牽 涉到主動元件(active component的)使用,以主動式結構控制 液體的通過或攔阻。例如以on-Chip主動式可啟閉的薄膜控 制液體流動,而US 6929030則以彈性主動加壓裝置控^ on-chip液體流動。0n_chip主動裝置雖然有可能達到流&體 積控制的需求,但在材質的使用上卻受到極大的限=。有 些設計使用Si為基材,需以微影製程加工。有些設$兩 上金屬層做為電極,或加上特殊合金以配合磁性=而口 加上壓電材料做為制動裝置。這純料上的限制使^ 成本及製㈣用大為提高,難以達到低成本的。、” 这些複雜的製程在實用性及製作品質的重複性 驗,因此至今雖有許多文獻討論實驗 ^ 件,但能達到商業化量產規格的產品仍作,主動元 裝置控制液體的流動’例如us 692903 1以主動 量,有些主動式裂置需另加感測或迴授裝▲有::度的考 配流體的特性,才能達到體積控制的目的 <則需搭 dispe· based 〇n passive valve :這一類的· ―叫機制於晶片h液體的驅動也可以有仏整: 6 Ι29085Ό • 主要是以被動閥(passive valve)執行液體定位,達到體積 控制的目的。在許多情況下,以被動閥執行液體定位具有 不必感測器及迴授裝置做液體定位的好處,但缺點是目前 這一類方法必需使用較多的外加輔助裝置,例如使用多個 外加驅動源及多個可動式連接頭或外加閥,才能達到體積 " 控制的目的。當所需控制體積的液體種類增加時,則需另 外增加更多外加閥或泵浦做調控,既增加成本,又可能增 加裝置失效的風險。 φ 因此,微流體檢測晶片有許多應用必需具有多種液體同 時進行體積控制的需求。如何進行有效而低成本的液體體 積控制而不必外加太多輔助裝置,是許多微流體檢測晶片 應用共同的需求。 • 【發明内容】 有鑑於習知技術的缺失,本發明之目的,在提供一種 為微流體進料體積控制系統,透過構造簡易的元件設計與 操作步驟,達到微量流體體積控制的目的。 • 為達上述目的,本發明之微流體體積控制系統係包 含:一進料控制流道,其係具有一進料流道與一通氣流道, 其中前述進料流道具有兩端點,其第一端點係為進料端 點,第二端點係為出口端點;該進料端點係與一液體槽連 接,該液體槽係可藉由一液體槽界面元件控制與大氣之接 觸或隔絕;前述進料流道之前述兩端點間具有一第一被動 閥;前述通氣流道具有兩端點,其第一端點係為一通氣孔, ^ 該通氣孔可藉由一通氣孔界面元件控制;第二端點位於前 述進料流道第一端點與第一被動閥間,通氣流道上靠近第 , 二端點處具有一第二被動閥;及一負壓提供裝置,該裝置 7 1290850 係可由前述進料流道之出口端提供一負壓。 其中,透過操作前述負壓提供裝置、液體槽界面元件 及通氣孔界面元件,可由液體槽内取第一被動閥與第二被 動閥間之液體並由出口端移出。 本發明同時也提供一種微流體多重進料體積控制系 統,係包含:至少二組進料控制流道,該進料控制流道係 獨立具有一進料流道與一通氣流道,其中:前述進料流道 具有兩端點,其第一端點係為進料端點,第二端點係為出 口端點;該進料端點係與一液體槽連接,該液體槽係可藉 由一液體槽界面元件控制與大氣之接觸或隔絕;前述兩端 點間具有一第一被動閥;前述通氣流道具有兩端點,其第 一端點係為通氣孔,該通氣孔可藉由一通氣孔界面元件控 制;第二端點位於前述進料流道第一端點與第一被動閥 間,通氣流道上靠近第二端點處具有一第二被動閥;前述 各進料流道之出口端點係匯集於一總出口端;及一負壓提 供裝置,該裝置係可由前述各進料控制流道之總出口端提 供一負壓。 其中,透過操作前述負壓提供裝置、與各組液體槽界 面元件及通氣孔界面元件,使系統輸出上述各組進料控制 流道中,各組第一被動閥與第二被動閥間之液體,並由總 出口端移出。 本發明同時另提供一種微流體多重進料體積控制系 統,係包含:一主進料控制流道,其係具有一主進料流道 與一主通氣流道,其中前述主進料流道具有兩端點,其第 一端點係為主進料端點,第二端點係為出口端點;該主進 料端點係與一液體槽連接,該液體槽係可藉由一液體槽界 面元件控制與大氣之接觸或隔絕;前述主進料流道之前述 1290850 * 兩端點間具有一主進料流道被動閥;前述主通氣流道具有 兩端點,其第一端點係為一主通氣孔,該通氣孔可藉由一 通氣孔界面元件控制;第二端點位於前述主進料流道第一 ^ 端點與主被動閥間,主通氣流道上靠近第二端點處具有一 主通氣流道被動閥;一負壓提供裝置,該裝置係可由前述 主進料流道之出口端點提供一負壓;及至少一組次進料控 制流道,其係具有一次通氣流道被動閥,一次進料流道與 一支通氣流道,其中前述次通氣流道被動閥設於主通氣流 Φ 道上,位於主通氣流道被動閥與主通氣孔之間;前述次進 料流道具有兩端點,其第一端點係為次進料端點,該進料 端點係與一液體槽連接,該液體槽係可藉由一液體槽界面 元件控制與大氣之接觸或隔絕,次進料流道之第二端點與 • 主通氣流道相接,位於主通氣流道被動閥與次通氣流道被 . 動閥之間;前述支通氣流道具有兩端點,其第一端點係為 一支通氣孔,該支通氣孔可藉由一通氣孔界面元件控制; 第二端點與主通氣流道相接,位於前述主通氣流道被動閥 與次進料流道之第二端點間,支通氣流道上靠近第二端點 φ 處具有一支通氣流道被動閥。 其中,透過操作前述負壓提供裝置、液體槽界面元件及 通氣孔界面元件,可由主通氣流道及主進料流道内取得液 體並由出口端移出。 【實施方式】 本發明之微流體體積控制系統主要係利用負壓與被動 閥元件之搭配操作達到流體體積的控制,被動閥係可用於 流體之攔阻或前進。被動閥之具體實施態樣之一係為一局 , 部流道截面積之變化,使流體臨近不同截面積之流道時有 9 1290850 - 攔阻的作用。另一實施態樣係為一局部流道親疏水性之變 化,使流體臨近不同親疏水性之流道時有攔阻的作用。關 於被動閥之實施態樣示意圖可參考第四A圖、第四B圖、第 五A圖與第五B圖,其中第四A圖及第四B圖係為流道截面改 變態樣之被動閥。第五A圖及第五及圖係為流道材質改變態 樣之被動閥。參考第四A圖及第五A圖,當提供一較弱負壓 PL於流道時,流體會沿管道流動至被動閥處,第四A圖之被 動閥處係指流道截面積較窄處,第五A圖之被動閥處係指流 φ 道材質改變處,例如中間區段,若Pl之絕對值低於一臨界值 Pth時,流體將受被動閥之限制而無法再繼續前進。參考第 四B圖及第五B圖,若使負壓變強至PH之絕對值〉Pth時,流 體即可通過被動閥開始流動。被動閥之技術概念係為本技 術領域具通常知識者所知悉,流道截面變化、材質選用及 • Pl、PH值係可視應用需求選擇而有不同而無須限定之。 利用前述被動閥運作概念之本發明之微流體體積控制 系統100之示意圖係可參考第一 A圖,其係包含進料控制流 道50,其係具有一進料流道10與一通氣流道20,其中前述 _ 進料流道10具有兩端點,其第一端點係為進料端點11,第二 端點係為出口端點12;該進料端點u係與一液體槽13連接, 该液體槽13係可藉由一液體槽界面元件14控制與大氣之接 觸或隔絕;前述進料流道1〇之前述兩端點間具有一第一被 動閥15 ;前述通氣流道20具有兩端點,其第一端點係為一 ^ 通氣孔21,該通氣孔21可藉由一通氣孔界面元件22控制; 第二端點位於前述進料流道第一端點11與第一被動閥15 間,通氣流道20上靠近第二端點處具有一第二被動閥23, 另本微流體進料體積控制系統具有一負壓提供裝置3〇,該 • 裝置係可由前述進料流道10之出口端點12提供一負壓。 10 1290850 、 當液體槽界面元件14為開啟狀態(即與大氣壓力連 通)’而通氣孔界面元件22為關閉狀態(即與大氣壓力不連 通)’利用負壓提供裝置3〇由出口端點12提供進料流道1〇一 弱=負壓時,可由液體槽13内之將液體樣品由液L體槽13 d。t出,但因為弟一被動閥Μ設置使得液體樣品只能充滿 區段及d,區段之流道内,如第一B圖所示。 接著將液體槽界面元件14關閉,再將通氣孔界面元件 ^開啟,然後將負壓提供裝置3〇提供較強的負壓h時,此 守口液體樣品將無法由液體槽13内被吸出,但因通氣孔21 開啟的緣故,d區段流道内的液體樣品將通過第一 口端點移動,如第一C圖所示,而d,區段流道内之液體 樣品則不會移動而停滯原地。 與、、=第—B圖及第—c圖及上述操作說明可知,本發明之 一机體進料體積控制系統可透過液體槽界面元件14、通氣 面控制元件22及負壓提供裝置3〇的操作,達到固定體 積〜體(d區段流道體積)的進料。 可在部分實施態樣中,紐槽中的液體樣品亦 而精由負壓匕的導引下由液體槽中自行移動出直至 及d’區段’此係肇因於構成系統各科之材料與液體 ^兩者特性之偶合(例如毛細現象造成液體自行前 =負壓提供裝置只需在液體樣品已充滿d區段及d,區段 供較強的負壓PH使d區段流道内的液體樣品通過第一 閥I5往出口端點移動即可。 破動 /在部分的實施態樣中,本發明之微流體進料體積 糸統100係、可進-步包含—樣品檢測流道4G如第= 不,該樣品檢職道40係具有兩端點,其―端點係盘ς斤 進料流道U)之出口端點12相通U點與前述負壓= 1290850 裝置30相通’以應用於樣品檢測。樣品檢測的方式包含, 但不限於本技術領域具通常知識者所知悉之可見光或不可 見光仏測、抗原抗體檢測、光學吸收波峰及/或吸收值檢測、 • 導電度檢測、聲學檢測及磁性檢測等。 本發明所稱之「液體槽界面元件」及「通氣孔界面元 件」係為一控制與大氣接觸與否之界面,亦可為一提供正 壓或負壓之壓源裝置,藉由控制流道内各區段之壓力導引 液體樣品之流動,例如液體槽界面元件及通氣孔界面元件 _ 係可為一使流道封閉或開啟之膠布。 本發明之負壓提供裝置係用以提供微流體體積控制系 統中之各流道負壓之裝置,例如係可為一抽氣幫浦。本發 明之微流體體積控制系統100之進料控制流道50係可位於 • 一晶片上,晶片之材質包含親水性材質或疏水性材質而無 - 需限制。 Μ 而當可輕易理解的是,本發明之微流體體積控制系統 100中之流道區段d (即第二被動閥23至第一被動閥15間之 流道區段)係為單次進料之液體樣品體積,當透過微機電 Φ 工程製得不同可替換之流道區段元件時(例如具螺紋可裝 卸之中空流道元件),即可適用於不同進料體積之需求。 更進一步地,本發明之微流體體積控制系統係可應用 於多種樣品之進料,亦即如第二A圖所示,本發明提供一種 微流體多重體積控制系統200,係包含二組進料控制流道50 及50’,該進料控制流道50及50’係獨立具有一進料流道1〇及 • 1〇’與一通氣流道20及20,。以進料控制流道50這一組為例, , 其進料流道10具有兩端點,其第一端點係為進料端點11,第 二端點係為出口端點12 ;該進料端點11係與一液體槽13連 _ 接,該液體槽13係可藉由一液體槽界面元件14控制與大氣 12 Ι29085Ό • 之接觸或隔絕;前述進料流道ίο之前述兩端點間具有一第 一被動閥15 ;前述通氣流道20具有兩端點,其第一端點係 為一通氣孔21,該通氣孔21可藉由一通氣孔界面元件22控 制;第二端點位於前述進料流道10第一端點η與第一被動閥 15間,通氣流道20上靠近第二端點處具有一第二被動閥23。 • 二組進料控制流道之各進料流道10及1〇’之出口端點12 及12,係匯集於一總出口端16,另本微流體體積控制系統具 有一負壓提供裝置30,該裝置30係可由前述總出口端16提 ^ 供一負壓。 9 當液體槽界面元件14及14’為開啟狀態,而通氣孔界面 元件22及22’為關閉狀態,利用負壓提供裝置30由總出口端 點16提供進料流道10及1〇’一較弱負壓PL時,可由液體槽13 及13,内分別將液體樣品由液體槽其中”吸出’’,但因為第一 . 被動閥15及15’的設置使得液體樣品只能分別充滿dl區段、 dl’區段及d2區段、d2’區段之流道内如第二B圖所示。 接著將液體槽界面元件14及14’關閉,再將通氣孔界面 元件22及22’開啟,然後將負壓提供裝置30提供的負壓調強 ❿ 至Ph時,此時因液體樣品將無法由液體槽13及13,内被吸 出,且因通氣孔21及21’開啟的緣故,dl及d2區段流道内的 液體樣品將分別通過其第一被動閥15及15 ’往總出口端點矛多 動如第二C圖所示,而dl’區段及d2,區段流道内之液體樣品 則不會移動停滯原地。 °° 由第二B圖及第二C圖及上述操作說明可知,本發明之 • 微流體多重進料體積控制系統可透過液體槽界面元件14、 , 通氣孔界面控制元件22及負壓提供裝置30的操作,達函 定體積流體(dl及d2區段流道體積)的進料。 古 當可輕易理解的是:本發明之微流體多重體積控制系 1290850 統200中,第一組進料控制流道5〇之液體槽衣 氣孔界面元件22之啟閉動作可以與第二组胃進疋件Η與通 之液體槽界面元件14,及通氣孔界面元件22,=^制流道50’ 時擷取兩種液體體積,也可以不同步操作,°』W呆作,以同 各自擷取兩種液體體積。 本’以在不同時間 本發明之微流體多重體積控制系統2〇〇中 槽^面”」1「通氣孔界面元件」及「負壓“裝置1 几件之功能、態樣及材料係同前述。 、置」專 當可輕易理解的{,本發明之微〉 衷體多 統200中之流道區段dl&d2係為單次進料之^ ^糸 積,當透過微機電工程製得不同可替換之 (例如具螺紋可裝卻之中空流道元件即可適用 之區=二同步體也積_係可為不同流道體積 在部分的實施態樣中,通氣孔21及21,係可為同 :L ’並藉由單一之通氣孔界面元件來控 “乳 f即液體槽界面元件或通氣孔界面元件係為一控 ^觸與否之界面、各自壓源裝置或共壓源裝置三者中^ ^動而液體槽界面元件或通氣孔界面元件,係可各自控;; 成總點12及12,係可接於-槽或匯集成1管口形 本發明之微流體多重體積控制系統係可包含 之進料控做道,其連接方—可參第二⑽,各= =、?類似「並聯」概念方式連接,達到單次= 除了所逑並聯態樣之微流體多重體積控制系統外,本 14 Ι29085Ό - 發明也提供一種類似「串聯」概念之微流體多重進料體積 控制系統300如第三A圖所示,其係包含一主進料控制流道 60,該流道係具有一主進料流道70與一主通氣流道80,其 & 中前述主進料流道70具有兩端點,其第一端點係為主進料 端點71,第二端點係為出口端點72 ;該主進料端點71係與 < 一液體槽73連接,該液體槽73係可藉由一液體槽界面元件 74控制與大氣之接觸或隔絕;前述主進料流道70之前述兩 端點間具有一主進料流道被動閥75 ;前述主通氣流道80具 φ 有兩端點,其第一端點係為一主通氣孔81,該通氣孔81可 藉由一通氣孔界面元件82控制;第二端點位於前述主進料 流道70第一端點71與主進料流道被動閥75間,主通氣流道 80上靠近第二端點處具有一主通氣流道被動閥83 ; —負壓 • 提供裝置76,該裝置76係可由前述主進料流道70之出口端 . 點72提供一負壓;及一組次進料控制流道90,其係具有一 次通氣流道被動閥91,一次進料流道92與一支通氣流道 95,其中前述次通氣流道被動閥91設於主通氣流道80上, 位於主通氣流道被動閥83與主通氣孔81之間;前述次進料 φ 流道92具有兩端點,其第一端點係為次進料端點,該進料 端點係與一液體槽連接93,該液體槽93係可藉由一液體槽 界面元件94控制與大氣之接觸或隔絕,次進料流道92之第 二端點與主通氣流道80相接,位於主通氣流道被動閥83與 次通氣流道被動閥91之間;前述支通氣流道95具有兩端 點,其第一端點係為一支通氣孔96,該支通氣孔96可藉由 • 一通氣孔界面元件97控制;第二端點與主通氣流道80相 、 接,位於前述主通氣流道被動閥83與次通氣流道被動閥91 之間,支通氣流道95上靠近主通氣流道80處具有一支通氣 流道被動閥98。 1290850 =著操作液體槽界面元件74、82、94及97開啟或關閉 ψ、怨’以及填充液體槽73、93的次序及時間點,可衍生 出不同進料次序的效果。實施態樣之一請參考第三Β圖,操 ★ 作方式係將液體槽介面元件74調整於關閉狀態,只讓液體 槽介面元件94調整為開啟狀態,而通氣孔界面元件82及97 為關閉狀態,利用負壓提供裝置76由出口端點72提供負壓 Pl時,d2’及d2區段流道會先充滿液體槽93内的液體樣品, 然後再將液體槽介面元件74調整於開啟狀態,這時液體槽 φ 73内液體樣品被導引進入dl,區段及dl區段流道中,形成如 第三B圖的狀態。而在調整為較強負壓至匕前,係先將液體 槽界面元件74及94都調整為關閉狀態,然後將通氣孔μ之 通氣孔界面元件82調整於開啟狀態(此時的之通氣孔%之 A 通氣孔界面元件97係處於關閉狀態),這時再將負^提供裝 置76提供之負壓由PL調強至PH,這時dl區段及们γ^ 内的液體樣品即會在負壓ΡΗ的引導下向出口端點二移動, 形成如第三C圖所不之狀態。 其他實施態樣亦包括藉著操作液體槽界面元件74、 φ 82、94及97開啟或關閉的狀態,以及填充液體样73、93的 次序及時間點,造成dl’區段及dl區段個別進料^吱果。 本發明之微流體多重體積控制系統3〇〇中所稱>之「液體 槽界面元件」、「通氣孔界面元件」及「負壓提供裝置\等 元件之功能、態樣及材料係同前述。 當可輕易理解的是’本發明之微流體多重體積控制系 '統3〇〇中之流道區段d^d2係為單次進料之液體樣品體 ,積,當透過微機電工私製得不同可替換之流道區段元件時 (例如具螺紋可裝卸之中线道元件),即可適用於不同進 料體積之需求’更進一步地,dmd2係可為不同流道體積 16 Ι29085Ό • 之區段,無需限制於相同體積。 本發明之微流體多重進料體積控制系統係可包含一会 以上之進料控制流道,其連接方式係可參第三D圖, = . 進料控制流道係以類似「串聯」概念方式連接,達^ ^ 多重樣品的進料。 ’早次 \ 在系統100、200及300的部分實施態樣中,液體槽中 液體樣品可在不需藉由負壓pL的導引下由液體槽中自行移 動出直至充滿對應之d區段、d,區段、dl區段、dl,區段 ❿區段及们,區段,此係肇因於構成系統各元件之材料^液^ 樣品兩者特性之偶合,此一現象在系統100及200中並不影 ,系統的可實施性,相反地,負壓提供裝置只需在液體= 品已充滿d區段及d,區段(或者dl區段、dl,區段、d2區段及 d2’區段)後,再提供一壓力值p強於Pth之負壓,即可讓^區 段(或dl區段及d2區段之液體樣品被導引向出口端;然而 同前系統300之操作狀況,若dl,區段流道被液體槽乃内之液 體樣品填滿,但d2,及d2區段流道尚未被液體槽93内之液體 樣品填滿時,則需透過支通氣流道95、支通氣孔96及通氣 • 孔界面元件97之開啟,使d2,及d2區段流道之氣體得以泡出。 0 綜合上述,本發明之微流體進料體積控制系統藉由簡 單的流道的設計以及被動閥與通氣孔的設置達到精準的進 料體積控制,更進一步,透過本發明之微流體多重進料體 積控制系統及其操作,可使微流體晶片只需使用單一負壓 ^供裝置即可進行複數樣品及試劑的進料混和,降低使用 複數驅動裝置所需的高成本以及可能造成的誤差。 甚^實施熊樣 、 在本說明書中所揭露的所有特徵都可能與其他方法結 Ι29085Ό 合,本說明書中所揭露的每一個特徵都可能選擇性的以相 同、相等或相似目的特徵所取代,因此,除了特別顯著的 特徵之外,所有的本說明書所揭露的特徵僅是相等或相似 特徵中的一個例子。 雖然本發明已以較佳實施例揭露如上,然其並非用以 限定本發明,任何熟悉此技藝者,在不脫離本發明之精神 和範圍内,當可作各種之更動與潤飾。 !29〇85〇 【圖式簡單說明】 ,一 Α圖係為本發明之微流體體積控制系統示意圖。 第一 B圖係為本發明之微流體體積控制系統之操作流 裎分解圖,其係為第一階段。 第一 裎分解圖Ι29085Ό* IX. DESCRIPTION OF THE INVENTION: FIELD OF THE INVENTION The present invention relates to a microfluidic feed volume control system, and more particularly to a microfluidic multiple feed volume control system, particularly for microfluidics Flow channel design within the wafer. [Prior Art] Many clinical biochemical testing applications focus on the detection of specific organisms, chemical substances or pathogens. The results of the detection can be used to know the presence or absence of the biochemical substance or pathogen, and reflect the disease. The degree of illness, the health status of the patient, or the efficacy of the medical treatment. In addition, detection of biological, chemical or pathogens can be used for applications such as drug testing, industrial process monitoring, environmental monitoring, and plant or animal testing. In recent years, due to the development of electromechanical technology, many of the original large components have been miniaturized, and human beings have been able to carry out experiments that were previously impossible, such as cell manipulation and rapid protein or DNA, through miniaturized devices. Separation and other applications. Microfluidic biomedical test wafers have the advantages of high detection efficiency, low sample or reagent consumption, small size, and low cost, especially in the design of integrated microfluidic operation and detection functions on the same wafer, with the most development potential and market. Value, therefore, in addition to the advantages of miniaturization, the elimination of complex and expensive testing equipment, so that a single wafer has a complete detection function. In the design of microfluidic wafers, due to the amount of sample or reagent • The most direct impact on the results of the analysis, the volume control unit of the specimen or reagent must be considered. The methods that can be used to control the volume of trace liquids can be broadly classified into three categories: 1. Off-chip dispenser: Commercially available products can be used to control trace volume of liquids. Commonly used are micropipettes (pipette), 1290850 drop-on_demand dispenser, contact dispenser Wait. The micro-dispenser is manual, and the latter two can be integrated into the automation system. The drop-on-demand dispenser, such as the ink-jet head technology, is mature, but the mechanism is complicated and the production cost is high. As for the Contact type dispenser, a typical application such as a DNA chip spotting machine has a high coefficient of variation (CV), both of which are 〇ff-chip dispensers, which are difficult to integrate with the wafer, and are consistent in the operation flow. The best choice for microfluidic wafers, such as the consistency of the quality of the operation, the avoidance of contamination, etc.; 2· On-chip dispenser with active component: This type of method can integrate the dispenser on the wafer, but with volume control Related actions involve the use of active components to control the passage or blocking of liquids in an active configuration. For example, the on-Chip active openable membrane controls liquid flow, while the US 6929030 controls the on-chip liquid flow with an elastic active pressurizing device. Although the 0n_chip active device is likely to meet the requirements of flow & volume control, it is extremely limited in the use of materials. Some designs use Si as the substrate and require lithography. Some have $2 on the metal layer as the electrode, or a special alloy to match the magnetic = and the piezoelectric material is used as the brake device. This restriction on the pure material makes the cost and system (4) greatly improved, and it is difficult to achieve low cost. " These complex processes are reproducible in practicality and quality of production. So many documents have been discussed so far, but products that can achieve commercial mass production specifications are still in place. Active element devices control the flow of liquids'. Us 692903 1 With active quantity, some active splitting needs to be separately sensed or feedbacked. ▲ There is:: the degree of the fluid to be tested, in order to achieve the purpose of volume control<1) need to take the dispe·based 〇n passive Valve: This type of ―called mechanism on the wafer h liquid drive can also be adjusted: 6 Ι 29085 Ό • mainly through the passive valve (passive valve) to perform liquid positioning, to achieve volume control purposes. In many cases, passive Valves perform liquid positioning with the benefit of not requiring sensors and feedback devices for liquid positioning, but the disadvantage is that this type of method currently requires the use of more external aids, such as the use of multiple external drive sources and multiple movable connectors or With the addition of a valve, the purpose of volume control can be achieved. When the type of liquid required to control the volume increases, additional valves or pumps are required. Doing regulation increases the cost and increases the risk of device failure. φ Therefore, there are many applications for microfluidic detection wafers that require multiple liquids for simultaneous volume control. How to perform effective and low-cost liquid volume control without having to add too much Multiple auxiliary devices are a common requirement for many microfluidic detection wafer applications. SUMMARY OF THE INVENTION In view of the deficiencies of the prior art, it is an object of the present invention to provide a microfluidic feed volume control system that transmits a simple component Design and operation steps to achieve the purpose of microfluid volume control. For the above purposes, the microfluidic volume control system of the present invention comprises: a feed control flow passage having a feed flow passage and a through air passage. Wherein the feed flow passage has two end points, the first end point is a feed end point, and the second end point is an outlet end point; the feed end point is connected to a liquid tank, and the liquid tank system can be Contacting or isolating from the atmosphere by a liquid trough interface element; the first end of the feed flow path has a first The movable air passage has a two-end point, the first end of which is a vent hole, and the vent hole is controlled by a vent interface element; the second end point is located at the first end of the feed flow path The first passive valve is adjacent to the first air passage, and has a second passive valve at the second end; and a negative pressure providing device, wherein the device 12 1290850 can provide a negative pressure from the outlet end of the feed flow passage. By operating the aforementioned negative pressure providing device, the liquid tank interface element and the vent interface element, the liquid between the first passive valve and the second passive valve can be taken from the liquid tank and removed from the outlet end. The present invention also provides a microfluid. The multiple feed volume control system comprises: at least two sets of feed control flow passages, the feed control flow passage independently having a feed flow passage and a through air flow passage, wherein: the feed flow passage has two ends, The first end point is the feed end point, and the second end point is the outlet end point; the feed end point is connected to a liquid tank, and the liquid tank can be controlled by the liquid tank interface element and the atmosphere Contact or separation A first passive valve is disposed between the two ends; the through air flow passage has two end points, and the first end point is a vent hole, and the vent hole can be controlled by a vent interface element; the second end point is located at a first passive valve is disposed between the first end of the feed flow passage and the first passive valve, and a second passive valve is disposed on the air flow passage near the second end; the outlet end points of each of the feed flow passages are collected at a total outlet end; And a negative pressure providing device capable of providing a negative pressure from the total outlet end of each of the aforementioned feed control flow passages. The system is configured to output the liquid between the first passive valve and the second passive valve in each group of the feed control flow passages by operating the negative pressure supply device, the liquid reservoir interface elements and the vent interface components, And removed from the total exit end. The invention also provides a microfluidic multiple feed volume control system comprising: a main feed control flow passage having a main feed flow passage and a main flow passage, wherein the main feed passage has The two end points, the first end point is the main feed end point, and the second end point is the outlet end point; the main feed end point is connected to a liquid tank, and the liquid tank can be connected by a liquid tank The interface element controls contact or isolation from the atmosphere; the aforementioned 1290850 of the main feed flow path has a main feed flow path passive valve between the two end points; the main flow path has two end points, and the first end point thereof a main vent hole, the vent hole can be controlled by a vent hole interface element; the second end point is located between the first end point of the main feed flow path and the main passive valve, and the main air flow path is near the second end point Having a primary airflow passage passive valve; a negative pressure providing device capable of providing a negative pressure from an outlet end of the aforementioned main feed flow passage; and at least one set of secondary feed control flow passages having a primary passage Air passage passive valve, one feed flow passage and one passage The air flow passage, wherein the aforementioned secondary air flow passage passive valve is disposed on the main air flow Φ channel, between the main air flow passage passive valve and the main vent hole; the second feed flow passage has two end points, and the first end point thereof For the secondary feed end, the feed end is connected to a liquid tank that can be contacted or isolated from the atmosphere by a liquid tank interface element, and the second end of the secondary feed flow path • The main airflow path is connected, and is located between the main airflow passage passive valve and the secondary airflow passage and the movable valve; the foregoing branch airflow passage has two end points, and the first end point is a vent hole, The vent hole can be controlled by a vent interface element; the second end is connected to the main air flow path, and is located between the main air flow path passive valve and the second end point of the secondary feed flow path, and the branch air flow path is close to The second end point φ has a through air passage passive valve. Wherein, by operating the negative pressure supply means, the liquid tank interface means and the vent interface element, the liquid can be taken from the main air flow path and the main feed flow path and removed from the outlet end. [Embodiment] The microfluidic volume control system of the present invention mainly utilizes a combination of a negative pressure and a passive valve element to achieve fluid volume control, and a passive valve system can be used for fluid blocking or advancement. One of the specific implementations of the passive valve is a one-stage, the change in the cross-sectional area of the flow passage, so that the fluid is adjacent to the flow passage of different cross-sectional areas when there is 9 1290850 - blocking effect. Another embodiment is a change in the hydrophilicity of a local flow channel that causes the fluid to block as it approaches a different hydrophilic and hydrophobic channel. For a schematic diagram of the implementation of the passive valve, reference may be made to the fourth A diagram, the fourth B diagram, the fifth A diagram, and the fifth B diagram, wherein the fourth A diagram and the fourth B diagram are passive of the flow path cross section change state. valve. The fifth A diagram and the fifth diagram are the passive valves whose flow path material changes. Referring to the fourth A diagram and the fifth diagram A, when a weak negative pressure PL is provided in the flow passage, the fluid flows along the pipeline to the passive valve, and the passive valve at the fourth A diagram refers to the narrow cross-sectional area of the flow passage. At the passive valve of Figure 5A, the material of the flow φ is changed, for example, the middle section. If the absolute value of Pl is lower than a critical value Pth, the fluid will be restricted by the passive valve and cannot continue to advance. Referring to Figures 4B and 5B, if the negative pressure is increased to the absolute value of PH > Pth, the fluid can begin to flow through the passive valve. The technical concept of passive valves is known to those of ordinary skill in the art. Flow path cross-section changes, material selection, and • Pl, pH values vary depending on the application requirements and need not be limited. A schematic diagram of the microfluidic volume control system 100 of the present invention utilizing the aforementioned passive valve operation concept can be referred to the first A diagram, which includes a feed control flow passage 50 having a feed flow passage 10 and a flow passage 20 Wherein the aforementioned feed channel 10 has two end points, the first end of which is the feed end point 11 and the second end point is the outlet end point 12; the feed end point u is a liquid tank 13 The liquid tank 13 is controlled to be in contact with the atmosphere by a liquid tank interface element 14; a first passive valve 15 is disposed between the two ends of the feed flow passage 1; the through air passage 20 The first end point is a vent hole 21, and the vent hole 21 can be controlled by a vent interface element 22; the second end point is located at the first end point 11 of the feed flow path and the first end Between the passive valve 15, the second air passage 20 has a second passive valve 23 near the second end point, and the microfluidic feed volume control system has a negative pressure providing device 3, which can be fed by the foregoing The outlet end 12 of the flow passage 10 provides a negative pressure. 10 1290850, when the liquid trough interface element 14 is in an open state (ie, in communication with atmospheric pressure) and the vent interface element 22 is in a closed state (ie, not in communication with atmospheric pressure) 'utilizing the negative pressure providing device 3' from the outlet end point 12 When the feed flow path is provided as a weak = negative pressure, the liquid sample from the liquid tank 13 can be passed from the liquid L body groove 13d. t out, but because of the passive valve setting, the liquid sample can only fill the section and the channel of the d, section, as shown in Figure B. Then, when the liquid tank interface element 14 is closed, and then the vent interface element is turned on, and then the negative pressure supply device 3 〇 provides a strong negative pressure h, the snorkel liquid sample cannot be sucked out by the liquid tank 13, but Due to the opening of the vent hole 21, the liquid sample in the d-section flow path will move through the first port end point, as shown in the first C-picture, and d, the liquid sample in the segment flow path will not move and stagnant. Ground. It can be seen that the body feed volume control system of the present invention can pass through the liquid tank interface member 14, the venting surface control member 22 and the negative pressure providing device 3〇. The operation achieves a fixed volume ~ body (d segment runner volume) feed. In some implementations, the liquid sample in the new tank is also moved by the liquid pressure tank under the guidance of the negative pressure 直至 to the d' section, which is due to the materials constituting the various sections of the system. Coupling with the characteristics of the liquid ^ (for example, capillary phenomenon caused by the liquid itself = negative pressure supply device only needs to fill the d section and d in the liquid sample, the section provides a strong negative pressure PH to make the d section flow path The liquid sample can be moved to the outlet end point through the first valve I5. Broken/in part of the embodiment, the microfluidic feed volume system 100 of the present invention can be further included - the sample detection flow path 4G If the number = no, the sample inspection lane 40 has two end points, and the outlet end point 12 of the "end point ς 进 feed channel U) communicates with the U point and the aforementioned negative pressure = 1290850 device 30. Used in sample testing. The method of sample detection includes, but is not limited to, visible or invisible light detection, antigen-antibody detection, optical absorption peak and/or absorption detection, and conductivity detection, acoustic detection and magnetic detection, which are known to those skilled in the art. Wait. The term "liquid tank interface element" and "vent hole interface element" as used in the present invention is an interface for controlling contact with the atmosphere, and may also be a pressure source device for providing positive or negative pressure by controlling the flow path. The flow of the pressure-directed liquid sample of each zone, such as the liquid trough interface element and the vent interface element, may be a tape that closes or opens the flow path. The negative pressure providing device of the present invention is a device for providing a negative pressure of each flow path in a microfluidic volume control system, for example, an evacuation pump. The feed control flow path 50 of the microfluidic volume control system 100 of the present invention can be located on a wafer, and the material of the wafer contains a hydrophilic material or a hydrophobic material without limitation. Μ It can be easily understood that the flow path section d (i.e., the flow path section between the second passive valve 23 and the first passive valve 15) in the microfluidic volume control system 100 of the present invention is a single pass. The liquid sample volume of the material can be adapted to different feed volume requirements when different alternative flow channel segment components are produced through MEMS Φ engineering (eg, threaded removable hollow runner components). Furthermore, the microfluidic volume control system of the present invention is applicable to the feeding of a plurality of samples, that is, as shown in FIG. 2A, the present invention provides a microfluidic multi-volume control system 200 comprising two sets of feeds. The flow passages 50 and 50' are controlled to have a feed flow path 1〇 and 1〇' and a flow passage 20 and 20, respectively. Taking the group of feed control flow passages 50 as an example, the feed flow passage 10 has two end points, the first end point being the feed end point 11 and the second end point being the outlet end point 12; The feed end point 11 is connected to a liquid tank 13 which is controlled by a liquid tank interface element 14 to be in contact with or isolated from the atmosphere 12 ; 29085 ; • the aforementioned two ends of the feed flow path ίο There is a first passive valve 15 between the points; the through air flow path 20 has two end points, and the first end point is a vent hole 21, and the vent hole 21 can be controlled by a vent hole interface element 22; the second end point is located at The first end point η of the feed channel 10 is connected to the first passive valve 15, and the second air passage 20 has a second passive valve 23 near the second end. • The outlet ends 12 and 12 of each of the feed channels 10 and 1' of the two feed control channels are collected at a total outlet end 16, and the microfluidic volume control system has a negative pressure supply device 30. The device 30 can be provided with a negative pressure from the aforementioned total outlet end 16. 9 When the liquid trough interface elements 14 and 14' are in an open state and the vent interface elements 22 and 22' are in a closed state, the negative flow providing means 30 provides the feed flow paths 10 and 1' from the total outlet end point 16. When the weak negative pressure PL is used, the liquid sample can be "sucked out" from the liquid tank by the liquid tanks 13 and 13, respectively, but because the first passive valve 15 and 15' are arranged, the liquid sample can only be filled with the d1 area, respectively. The flow path of the segment, the dl' segment, and the d2 segment and the d2' segment is as shown in the second B. The liquid channel interface elements 14 and 14' are then closed, and the vent interface elements 22 and 22' are opened. Then, when the negative pressure provided by the negative pressure supply device 30 is adjusted to Ph, the liquid sample will not be sucked out by the liquid tanks 13 and 13, and the vent holes 21 and 21' are opened, and The liquid sample in the d2 section flow path will be moved through the first passive valves 15 and 15' to the total outlet end point respectively as shown in the second C diagram, while the dl' section and d2, the liquid in the section flow path The sample will not move to the original position. °° It can be seen from the second and second C diagrams and the above operation instructions. The microfluidic multiple feed volume control system of the present invention is permeable to the volumetric fluid (d and d2 section flow path volumes) through the operation of the liquid tank interface element 14, the vent interface control element 22 and the negative pressure supply device 30. The feed can be easily understood. In the microfluidic multi-volume control system 1290850 of the present invention, the opening and closing action of the liquid trough interface element 22 of the first group of feed control channels 5 can be With the second group of gastric inlets and the liquid channel interface element 14, and the vent interface element 22, = 2 flow channel 50', two liquid volumes can be taken, or can be operated asynchronously. In order to extract two liquid volumes from each other, the present invention uses the microfluidic multi-volume control system of the present invention at different times, and the "ventilating interface element" and the "negative pressure" device 1 The functions, aspects and materials of several pieces are the same as above. It is easy to understand, and the flow section dl&d2 in the multi-system 200 is a single-feeding ^^ accumulation, which is made by micro-electromechanical engineering. It can be replaced (for example, the area where the hollow flow channel element with thread can be installed can be applied = the second synchronization body is also accumulated. The system can be different flow volume in part of the embodiment, the vent holes 21 and 21 can be The same as: L ' and controlled by a single vent interface element "milk f, that is, the liquid trough interface element or the vent interface element is a control interface, the respective pressure source device or the common pressure source device three The liquid trough interface element or the vent interface element can be controlled separately; the total points 12 and 12 can be connected to the trough or integrated into a 1-port shape. The microfluidic multi-volume control system of the present invention The system can include the feed control, the connection side - can refer to the second (10), each = =, ? similar to the "parallel" conceptual connection, to achieve a single = in addition to the parallel state of the microfluidic multi-volume control system In addition, Ben 14 Ι 29085 Ό - The invention also provides a microfluidic multiplicity similar to the concept of "series" The feed volume control system 300, as shown in FIG. 3A, includes a main feed control flow passage 60 having a main feed flow passage 70 and a main flow passage 80, in & The foregoing main feed flow path 70 has two end points, the first end point being the main feed end point 71 and the second end point being the exit end point 72; the main feed end point 71 is < a liquid The tank 73 is connected, and the liquid tank 73 can be controlled to be in contact with the atmosphere by a liquid tank interface member 74; the main feed passage 70 has a main feed passage passive valve 75 between the two ends; The first main air flow path 80 has φ having two end points, and the first end point thereof is a main vent hole 81, and the vent hole 81 can be controlled by a vent hole interface member 82; the second end point is located in the foregoing main feed stream Between the first end 71 of the passage 70 and the main feed passage passive valve 75, the main passage air passage 80 has a main passage air passage passive valve 83 near the second end point; - a negative pressure supply means 76, the device The 76 series may be provided by the outlet end of the aforementioned main feed flow path 70. Point 72 provides a negative pressure; and a set of secondary feed control flow paths 90 having a primary ventilation. The flow passage passive valve 91, the primary feed flow passage 92 and the one passage air passage 95, wherein the secondary passage air passage passive valve 91 is disposed on the main air passage 80, located in the main air passage passive valve 83 and the main vent hole 81; the foregoing secondary feed φ flow channel 92 has two end points, the first end point of which is the secondary feed end point, and the feed end point is connected with a liquid tank 93, the liquid tank 93 can be borrowed Contact or isolation with the atmosphere is controlled by a liquid bath interface element 94. The second end of the secondary feed flow path 92 is in contact with the main air flow path 80, and is located in the main air flow path passive valve 83 and the secondary air flow path passive valve. 91; the foregoing branch air passage 95 has two end points, and the first end point is a vent hole 96, and the vent hole 96 can be controlled by a vent interface element 97; the second end point and the main The air flow path 80 is connected, and is located between the main air flow passage passive valve 83 and the secondary air flow passage passive valve 91. The branch air flow passage 95 is adjacent to the main air flow passage 80 and has a through air passage passive valve 98. . 1290850 = The effect of different feed sequences can be derived by operating the liquid trough interface elements 74, 82, 94, and 97 to open or close the order, time, and time of filling the liquid reservoirs 73, 93. For one of the implementations, please refer to the third diagram, which is to adjust the liquid trough interface element 74 to the closed state, only the liquid trough interface element 94 is adjusted to the open state, and the vent interface elements 82 and 97 are closed. In the state, when the negative pressure P1 is supplied from the outlet end point 72 by the negative pressure supply device 76, the d2' and d2 segment flow paths are first filled with the liquid sample in the liquid tank 93, and then the liquid tank interface member 74 is adjusted to the open state. At this time, the liquid sample in the liquid tank φ 73 is guided into the flow path of the dl, the section and the dl section to form a state as shown in the third B diagram. Before adjusting to a strong negative pressure to the crucible, the liquid trough interface elements 74 and 94 are first adjusted to the closed state, and then the vent hole interface element 82 of the vent hole μ is adjusted to the open state (the vent hole at this time) %A vent interface element 97 is in the off state), then the negative pressure provided by the negative supply device 76 is adjusted from PL to PH, and the liquid sample in the dl segment and γ^ will be under negative pressure. Under the guidance of ΡΗ, it moves to the exit end point 2, forming a state as shown in the third C diagram. Other embodiments also include the state in which the liquid trough interface elements 74, φ 82, 94, and 97 are opened or closed, and the order and time at which the liquid samples 73, 93 are filled, resulting in individual dl' segments and dl segments. Feeding ^ fruit. The functions, aspects and materials of the components such as "liquid tank interface element", "vent hole interface element" and "negative pressure supply device" referred to in the microfluidic multi-volume control system 3 of the present invention are as described above. It can be easily understood that the flow path section d^d2 in the microfluidic multi-volume control system of the present invention is a liquid sample body of a single feed, which is obtained by computer electrical engineering. Different replacement flow channel segment components (eg threaded removable intermediate track components) can be adapted to different feed volume requirements. Further, the dmd2 system can be a different flow channel volume of 16 Ι 29085 Ό • The segment is not limited to the same volume. The microfluidic multiple feed volume control system of the present invention may include more than one feed control flow channel, and the connection mode thereof may be referred to the third D diagram, =. Feed control flow channel Connected in a similar "series" concept to achieve multiple feeds of multiple samples. 'Early time' In some embodiments of systems 100, 200 and 300, the liquid sample in the liquid tank can be moved by the liquid tank without being guided by the negative pressure pL until it is filled with the corresponding d section. , d, section, dl section, dl, section ❿ section, and section, this section is due to the coupling of the characteristics of the material ^ liquid ^ sample constituting each component of the system, this phenomenon is in the system 100 And 200 does not affect the system's implementability. Conversely, the negative pressure supply device only needs to be in the liquid = product has been filled with d segment and d, segment (or dl segment, dl, segment, d2 segment And after the d2' section), a pressure value p is stronger than the negative pressure of Pth, so that the liquid section of the section (or the dl section and the d2 section is guided to the outlet end; however, the same system 300 operating conditions, if dl, the section flow channel is filled by the liquid sample in the liquid tank, but the d2, and d2 section flow channels have not been filled by the liquid sample in the liquid tank 93, then the through-pass The air passage 95, the branch vent 96, and the venting/hole interface member 97 are opened to allow the gas in the flow channels of the d2 and d2 sections to be bubbled out. The microfluidic feed volume control system of the present invention achieves precise feed volume control by simple flow channel design and passive valve and venting arrangement, and further, through the microfluidic multiple feed volume control system of the present invention and The operation allows the microfluidic wafer to be mixed with a plurality of samples and reagents using a single negative pressure supply device, reducing the high cost and possible errors required to use the complex drive unit. All of the features disclosed in this specification may be combined with other methods, and each of the features disclosed in this specification may be selectively replaced with the same, equal or similar purpose features, and therefore, except for the particularly significant In addition to the features, all of the features disclosed in the present specification are only one of the equivalent or similar features. Although the present invention has been disclosed in the preferred embodiments as above, it is not intended to limit the invention, any one skilled in the art, It is possible to make various changes and retouches without departing from the spirit and scope of the present invention. !29〇85〇[图BRIEF DESCRIPTION OF THE DRAWINGS A schematic diagram of a microfluidic volume control system of the present invention is shown in Fig. 1. The first B diagram is an operational flow decomposition diagram of the microfluidic volume control system of the present invention, which is the first stage. Exploded view

C圖係為+本發明之微流體體積控制系統之操作流 ,其係為第二階段。 /;IL 統具有檢測 、第一 D圖係為本發明之微流體體積控制系 流道設計之系統示意圖。Figure C is the operating flow of the microfluidic volume control system of the present invention, which is the second stage. /; IL system has detection, the first D picture is the system schematic diagram of the microfluidic volume control system flow channel design of the invention.

第二A圖 似並聯態樣)。 係為本發明之微流體多重體積控制系統The second A picture is like a parallel pattern). Microfluidic multi-volume control system of the present invention

第二B圖係為本發明之並聯式微流體多重體 統之操作流程分解圖,其係為第一階段。 、卫削糸 第二C圖係為本發明之並聯式微流體多重體 統之操作流程分解圖,其係為第二階段。 、卫,、 一第二D圖係為本發明之並聯式微流體多重體積 統示,圖,其係為三組以上之進料控制流道態樣。、工’、The second B diagram is an exploded view of the operation flow of the parallel microfluidic multi-system of the present invention, which is the first stage. The second C-picture is an exploded view of the operation flow of the parallel microfluidic multi-system of the present invention, which is the second stage. The second D diagram is the parallel microfluidic multi-volume system of the present invention, and is a diagram of three or more groups of feed control flow passages. ,work',

第三A圖係為本發明之微流體多重體積控李 似串聯態樣)。 H先(類 第三B圖係為本發明之串聯式微流體多重體 統之操作流程分解圖,其係為第一階段。 、二J糸 第三C圖係為本發明之串聯式微流體多重體 統之操作流程分解圖,其係為第二階段。 貝控制糸 一第三D圖係為本發明之串聯式微流體多重體 統不意圖,其係為三組以上之進料控制流道態樣。 ’、 弟四A圖被動閥操作流程分解圖(第一階段)。 ,四B圖被動閥操作流程分解圖(第二階段)。 第五A圖被動閥操作流程分解圖(第一階段)。 19 Ι29085Ό - 第五B圖被動閥操作流程分解圖(第二階段)。 [主要元件符號對照說明] 100 微流體體積控制系統 10、10’ 進料流道 ¥ 、11、11, 進料端點 12、 12’出口端點 13、 13’液體槽 _ 14、14’液體槽界面元件 15、15’第一被動閥 20、 20’ 通氣流道 21、 21’ 通氣孔 ^ 22、22,通氣孔界面元件 23、23,第二被動閥 30 負壓提供裝置 50、50’、50” 進料體積控制流道 200 微流體多重體積控制系統(並聯式) | 16 總出口端 300 微流體多重體積控制系統(串聯式) 60 主進料控制流道 70 主進料流道 71 主進料端點 72 出口端點 73 液體槽 . 74 液體槽界面控制元件 75 主進料流道被動閥 76 負壓提供裝置 20 1290850 80 主通氣流道 81 通氣孔 82 通氣孔界面元件 83 主通氣流道被動閥 90 次進料控制流道 91 次通氣流道被動閥 92 次進料流道 93 液體槽 94 液體槽界面元件 95 支通氣流道 96 支通氣孔 97 支通氣孔界面元件 98 支通氣流道被動閥The third A picture is the microfluidic multi-volume controlled Lie-like series of the present invention). H first (the third B-like diagram is the operational flow decomposition diagram of the tandem microfluidic multi-body system of the present invention, which is the first stage. The second J diagram is the series microfluidic multi-system of the invention. The operational process decomposition diagram is the second stage. The shell control and the third D diagram are the series microfluidic multi-systems of the present invention, which are three or more groups of feed control flow patterns. Decomposition diagram of the passive valve operation flow of the fourth A diagram (Phase 1)., Figure 4 is an exploded view of the passive valve operation process (Phase II). Figure 5A is an exploded view of the passive valve operation process (Phase 1). 19 Ι29085Ό - Figure 5 is an exploded view of the passive valve operation flow (second stage). [Main component symbol comparison description] 100 microfluid volume control system 10, 10' feed flow path ¥, 11, 11, feed end point 12, 12' outlet end point 13, 13' liquid tank_14, 14' liquid tank interface element 15, 15' first passive valve 20, 20' air flow path 21, 21' vent hole 22, 22, vent interface element 23, 23, second passive valve 30 negative pressure supply 50, 50', 50" feed volume control flow channel 200 microfluidic multi-volume control system (parallel) | 16 total outlet end 300 microfluidic multi-volume control system (series) 60 main feed control runner 70 main Feed runner 71 Main feed end 72 Outlet end 73 Liquid tank. 74 Liquid tank interface control element 75 Main feed runner Passive valve 76 Negative pressure supply 20 1290850 80 Main air passage 81 Vent 82 Vent Interface element 83 Main air flow passage Passive valve 90 times Feed control flow path 91 Passing air flow path Passive valve 92 Feed flow path 93 Liquid tank 94 Liquid tank interface element 95 Support air flow passage 96 Support vent hole 97 Support vent hole Interface element 98 branch air passage passive valve

Claims (1)

1290850 十、申請專利範圍: 1. 一種微流體體積控制系統,係包含: 一進料控制流道,其係具有一進料流道與一通氣 流道,其中前述進料流道具有兩端點,其第一端點係為進 料端點,第二端點係為出口端點;該進料端點係與一液體 ^ 槽連接,該液體槽係可藉由一液體槽界面元件控制與大氣 之接觸或隔絕;前述進料流道之前述兩端點間具有一第一 被動閥;前述通氣流道具有兩端點,其第一端點係為一通 ^ 氣孔,該通氣孔可藉由一通氣孔界面元件控制;第二端點 位於前述進料流道第一端點與第一被動閥間,通氣流道上 靠近第二端點處具有一第二被動閥;及 一負壓提供裝置,該裝置係可由前述進料流道之 - 出口端提供一負壓; 其中,透過操作前述負壓提供裝置、液體槽界面 元件及通氣孔界面元件,可由液體槽内取第一被動閥與第 二被動閥間之液體並由出口端移出。 2. 如申請專利範圍第1項所述之系統,其中更包括一樣 φ 品檢測流道,其係具有兩端點,其一端點係與前述進料流 道之出口端點相通,另一端點與前述負壓提供裝置相通, 以應用於樣品檢測。 3. 如申請專利範圍第1項所述之系統,其中液體槽界面 元件或通氣孔界面元件係為一控制與大氣接觸與否之界面 或一壓源裝置兩者中之一者。 ^ 皂如申請專利範圍第1項所述之系統,其中前述負壓提 . 供裝置係包含一抽氣幫浦。 5.如申請專利範圍第1項所述之系統,其中前述進料控 制流道係位於一晶片上。 22 Ι29085Ό 〜 6.如申請專利範圍第5項所述之系統,其中前述晶片之 材質包含親水性材質或疏水性材質。 7. 如申請專利範圍第1項所述之系統,其中前述液體槽 界面元件係包含一可封住液體槽之膠布。 r 8. 如申請專利範圍第1項所述之系統,其中前述通氣孔 # 界面元件係包含一可封住通氣孔之膠布。 9. 如申請專利範圍第1項所述之系統,其中前述被動閥 係包含一局部流道截面積之變化,使不同於臨近流道之截 • 面積。 10. 如申請專利範圍第1項所述之系統,其中前述被動閥 係包含一局部流道親疏水性之變化,使不同於臨近流道之 親疏水性。 - 11.一種微流體多重體積控制系統,係包含: 至少二組進料控制流道,該進料控制流道係獨立 具有一進料流道與一通氣流道,其中:前述進料流道具有 兩端點,其第一端點係為進料端點,第二端點係為出口端 點;該進料端點係與一液體槽連接,該液體槽係可藉由一 • 液體槽界面元件控制與大氣之接觸或隔絕;前述兩端點間 具有一第一被動閥;前述通氣流道具有兩端點,其第一端 點係為通氣孔,該通氣孔可藉由一通氣孔界面元件控制; 第二端點位於前述進料流道第一端點與第一被動閥間,通 氣流道上靠近第二端點處具有一第二被動閥;前述各進料 流道之出口端點係匯集於一總出口端;及 r 一負壓提供裝置,該裝置係可由前述各進料控制 . 流道之總出口端提供一負壓; ‘其中,透過操作前述負壓提供裝置、與各組液體 槽界面元件及通氣孔界面元件,使系統輸出上述各組進料 23 1290850 • 控制流道中,各組第一被動閥與第二被動閥間之液體,並 由總出口端移出。 12. 如申請專利範圍第11項所述之系統,其中各組進料 控制流道更包括一樣品檢測流道,其係具有兩端點,其一 端點係與前述進料流道之出口端點相通,另一端點與前述 ’ 負壓提供裝置相通,以應用於樣品檢測。 13. 如申請專利範圍第11項所述之系統,其中該總出口 端,係可為一槽或一出管口中之一者。 φ 14.如申請專利範圍第11項所述之系統,其中液體槽界 面元件或通氣孔界面元件係為一控制與大氣接觸與否之界 面、各自壓源裝置或共壓源裝置三者中之一者。 15. 如申請專利範圍第11項所述之系統,其中該各液體 槽界面元件或通氣孔界面元件,係可各自控制作動。 16. 如申請專利範圍第11項所述之系統,其中前述負壓 提供裝置係包含一抽氣幫浦。 17. 如申請專利範圍第11項所述之系統,其中前述進料 控制流道係位於一晶片上。 • 18.如申請專利範圍第11項所述之系統,其中前述晶片 之材質包含親水性材質或疏水性材質。 19. 如申請專利範圍第11項所述之系統,其中前述液體 槽界面元件係包含一可封住液體槽之膠布。 20. 如申請專利範圍第11項所述之系統,其中前述通氣 孔界面元件係包含一可封住通氣孔之膠布。 ’ 21.如申請專利範圍第11項所述之系統,其中前述被動 . 閥係包含一局部流道截面積之變化,使不同於臨近流道之 截面積。 22.如申請專利範圍第11項所述之系統,其中前述被動 24 1290850 * 閥係包含一局部流道親疏水性之變化,使不同於臨近流道 之親疏水性。 23. —種微流體多重體積控制系統,係包含: 一主進料控制流道,其係具有一主進料流道與一 主通氣流道,其中前述主進料流道具有兩端點,其第一端 ’ 點係為主進料端點,第二端點係為出口端點;該主進料端 點係與一液體槽連接,該液體槽係可藉由一液體槽界面元 件控制與大氣之接觸或隔絕;前述主進料流道之前述兩端 φ 點間具有一主進料流道被動閥;前述主通氣流道具有兩端 點,其第一端點係為一主通氣孔,該通氣孔可藉由一通氣 孔界面元件控制;第二端點位於前述主進料流道第一端點 與主被動閥間,主通氣流道上靠近第二端點處具有一主通 氣流道被動閥; 一負壓提供裝置,該裝置係可由前述主進料流道 之出口端點提供一負壓;及 至少一組次進料控制流道,其係具有一次通氣流 道被動閥,一次進料流道與一支通氣流道,其中前述次通 φ 氣流道被動閥設於主通氣流道上,位於主通氣流道被動閥 與主通氣孔之間;前述次進料流道具有兩端點,其第一端 點係為次進料端點,該進料端點係與一液體槽連接,該液 體槽係可藉由一液體槽界面元件控制與大氣之接觸或隔 絕,次進料流道之第二端點與主通氣流道相接,位於主通 氣流道被動閥與次通氣流道被動閥之間;前述支通氣流道 具有兩端點,其第一端點係為一支通氣孔,該支通氣孔可 . 藉由一通氣孔界面元件控制;第二端點與主通氣流道相 接,位於前述主通氣流道被動閥與次進料流道之第二端點 間,支通氣流道上靠近第二端點處具有一支通氣流道被動 25 1290850 閥; 其中,透過操作前述負壓提供裝置、液體槽界面 元件及通氣孔界面元件,可由主通氣流道及主進料流道内 取得液體並由出口端移出。 24. 如申請專利範圍第23項所述之系統,其中各進料控 制流道更包括一液體檢測流道,其係具有兩端點,其一端 點係與前述進料控制流道第二端相接,另一端點與前述負 壓提供裝置相接,以應用於液體檢測。 25. 如申請專利範圍第23項所述之系統,其中該界面元 件係為一控制與大氣接觸與否之界面或一壓源裝置兩者中 之一者。 26. 如申請專利範圍第23項所述之系統,其中前述進料 控制流道係位於一晶片上。 27. 如申請專利範圍第23項所述之系統,其中前述液體 槽界面元件係包含一可封住液體槽之膠布。 28. 如申請專利範圍第23項所述之系統,其中前述通氣 孔界面元件係包含一可封住液體槽之膠布。 29. 如申請專利範圍第23項所述之系統,其中前述被動 閥係包含一局部流道截面積之變化,使不同於臨近流道之 截面積。 30. 如申請專利範圍第23項所述之系統,其中前述被動 閥係包含一局部流道親疏水性之變化,使不同於臨近流道 之親疏水性。 261290850 X. Patent Application Range: 1. A microfluidic volume control system comprising: a feed control flow passage having a feed flow passage and a through air passage, wherein the feed flow passage has two end points, The first end point is the feed end point, and the second end point is the outlet end point; the feed end point is connected to a liquid tank, and the liquid tank can be controlled by the liquid tank interface element and the atmosphere Contacting or isolating; a first passive valve is disposed between the two ends of the feed flow passage; the through air flow passage has two end points, and the first end point is a through hole, and the vent hole can be passed through a venting interface element is controlled; a second end point is located between the first end of the feed flow path and the first passive valve, a second passive valve is disposed on the air flow path near the second end point; and a negative pressure providing device The device may provide a negative pressure from the outlet end of the feed flow channel; wherein, by operating the negative pressure supply device, the liquid tank interface component and the vent interface element, the first passive valve and the second passive may be taken from the liquid tank Valve room By the end of the outlet body moves. 2. The system of claim 1, further comprising the same φ product detection flow path having two end points, one end of which is in communication with the outlet end of the feed flow path, and the other end It is in communication with the aforementioned negative pressure supply device for application to sample detection. 3. The system of claim 1, wherein the liquid trough interface element or the vent interface element is one of an interface for controlling contact with the atmosphere or a source device. The soap system of claim 1, wherein the negative pressure supply device comprises a pumping pump. 5. The system of claim 1, wherein the feed control flow path is on a wafer. The system of claim 5, wherein the material of the wafer comprises a hydrophilic material or a hydrophobic material. 7. The system of claim 1, wherein the liquid trough interface element comprises a tape that seals the liquid trough. The system of claim 1, wherein the venting port interface component comprises a tape that seals the venting opening. 9. The system of claim 1, wherein the passive valve comprises a change in a cross-sectional area of the partial flow path that is different from the cross-sectional area of the adjacent flow path. 10. The system of claim 1, wherein the passive valve comprises a change in the hydrophilicity of a partial flow channel that is different from the hydrophilicity of the adjacent flow channel. - 11. A microfluidic multivolume control system comprising: at least two sets of feed control flow paths independently having a feed flow path and a flow path, wherein: said feed flow path has The two end points have a first end point as a feed end point and a second end point as an outlet end point; the feed end point is connected to a liquid tank, and the liquid tank can be connected by a liquid tank interface The component controls contact or isolation with the atmosphere; a first passive valve is disposed between the two ends; the through airflow passage has two end points, and the first end is a vent hole, and the vent hole can be connected by a vent hole interface component Controlling; a second end point is located between the first end of the feed flow path and the first passive valve, and a second passive valve is disposed on the air flow path near the second end point; the outlet end point of each of the feed flow channels is Collecting at a total outlet end; and r a negative pressure supply device, which can be controlled by each of the foregoing feeds. The total outlet end of the flow channel provides a negative pressure; 'where, through the operation of the aforementioned negative pressure supply device, and each group Liquid tank interface element and vent Surface elements, the system outputs the groups 23 1290850 • control the feed flow channel, the liquid between the respective groups of the first passive valve and the second passive valve and removed from the total outlet end. 12. The system of claim 11, wherein each group of feed control flow paths further comprises a sample detection flow path having two end points, one end of which is connected to the outlet end of the feed flow path The points are in communication and the other end is in communication with the aforementioned 'negative pressure supply device' to apply to sample detection. 13. The system of claim 11, wherein the total outlet end is one of a trough or an outlet. Φ 14. The system of claim 11, wherein the liquid trough interface element or the vent interface element is an interface for controlling contact with the atmosphere, a respective pressure source device or a common pressure source device. One. 15. The system of claim 11, wherein the liquid trough interface elements or vent interface elements are each controllable. 16. The system of claim 11, wherein the aforementioned negative pressure providing device comprises a pumping pump. 17. The system of claim 11, wherein the feed control flow path is on a wafer. The system of claim 11, wherein the material of the wafer comprises a hydrophilic material or a hydrophobic material. 19. The system of claim 11, wherein the liquid trough interface element comprises a tape that seals the liquid trough. 20. The system of claim 11, wherein the vent interface element comprises a tape that seals the vent. 21. The system of claim 11, wherein the passive valve system comprises a variation in a cross-sectional area of the partial flow path that is different from the cross-sectional area of the adjacent flow channel. 22. The system of claim 11, wherein the passive 24 1290850 * valve system comprises a change in the hydrophilicity of the partial flow channel to distinguish it from the hydrophilicity of the adjacent flow channel. 23. A microfluidic multivolume control system comprising: a main feed control flow path having a main feed flow path and a main flow air flow path, wherein said main feed flow path has two end points, The first end 'point is the main feed end point, and the second end point is the outlet end point; the main feed end point is connected to a liquid tank, and the liquid tank can be controlled by a liquid tank interface element Contact or isolation from the atmosphere; the main feed channel has a main feed passage passive valve between the two ends φ point; the main flow passage has two ends, and the first end is a main passage a vent hole, the vent hole being controllable by a venting port interface element; the second end point being located between the first end of the main feed flow path and the active and passive valve, and having a main air flow adjacent to the second end point on the main air flow path a passive valve; a negative pressure providing device that provides a negative pressure from an outlet end of the aforementioned main feed flow passage; and at least one set of secondary feed control flow passages having a primary flow passage passive valve a feed flow path and a through air flow path, wherein the aforementioned Passing φ air passage passive valve is disposed on the main air flow passage between the main air passage passive valve and the main vent hole; the secondary feed flow passage has two end points, and the first end point is the secondary feed end point The feed end is connected to a liquid tank, and the liquid tank can control contact or isolation with the atmosphere by a liquid tank interface element, and the second end of the secondary feed flow channel is connected to the main air flow passage Between the main air flow passage passive valve and the secondary air flow passage passive valve; the aforementioned branch air flow passage has two end points, and the first end point is a vent hole, and the vent hole can be through a vent hole The interface element is controlled; the second end point is connected to the main air flow path, and is located between the first main air flow path passive valve and the second end point of the secondary feed flow path, and the branch air flow path has a branch near the second end point Passing the air passage passive 25 1290850 valve; wherein, by operating the negative pressure providing device, the liquid tank interface element and the vent interface element, the liquid can be taken from the main air flow passage and the main feed flow passage and removed from the outlet end. 24. The system of claim 23, wherein each of the feed control flow paths further comprises a liquid detection flow path having two end points, one end of which is associated with the second end of the feed control flow path In connection, the other end is connected to the aforementioned negative pressure supply device for application to liquid detection. 25. The system of claim 23, wherein the interface element is one of an interface for controlling contact with the atmosphere or a source device. 26. The system of claim 23, wherein the feed control flow path is on a wafer. 27. The system of claim 23, wherein the liquid trough interface element comprises a tape that seals the liquid trough. 28. The system of claim 23, wherein the venting interface element comprises a tape that seals the liquid bath. 29. The system of claim 23, wherein the passive valve system comprises a variation in a cross-sectional area of the partial flow path that is different from the cross-sectional area of the adjacent flow channel. 30. The system of claim 23, wherein the passive valve system comprises a change in the hydrophilicity of a partial flow channel that is different from the hydrophilicity of the adjacent flow channel. 26
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