TW201244825A - Droplet manipulations on EWOD microelectrode array architecture - Google Patents

Droplet manipulations on EWOD microelectrode array architecture Download PDF

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TW201244825A
TW201244825A TW101105386A TW101105386A TW201244825A TW 201244825 A TW201244825 A TW 201244825A TW 101105386 A TW101105386 A TW 101105386A TW 101105386 A TW101105386 A TW 101105386A TW 201244825 A TW201244825 A TW 201244825A
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electrode
configuration
electrodes
excitation
droplet
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TW101105386A
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TWI510296B (en
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Gary Wang
Ching Yen Ho
Wen Jang Hwang
Wilson Wang
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Gary Wang
Ching Yen Ho
Hwang We Jang
Wilson Wang
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Priority claimed from US13/029,140 external-priority patent/US8815070B2/en
Priority claimed from CN201210034561.4A external-priority patent/CN102671722B/en
Priority claimed from CN201210034566.7A external-priority patent/CN102671724B/en
Application filed by Gary Wang, Ching Yen Ho, Hwang We Jang, Wilson Wang filed Critical Gary Wang
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0673Handling of plugs of fluid surrounded by immiscible fluid
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427Electrowetting

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

A method of manipulating droplet in a programmable EWOD microelectrode array comprising multiple microelectrodes, comprising: constructing a bottom plate with multiple microelectrodes on a top surface of a substrate covered by a dielectric layer; the microelectrode coupled to at least one grounding elements of a grounding mechanism, a hydrophobic layer on the top of the dielectric layer and the grounding elements; manipulating the multiple microelectrodes to configure a group of configured-electrodes to generate microfluidic components and layouts with selected shapes and sizes, comprising: a first configured-electrode with multiple microelectrodes arranged in array, and at least one second adjacent configured-electrode adjacent to the first configured-electrode, the droplet disposed on the top of the first configured-electrode and overlapped with a portion of the second adjacent-configured-electrode; and manipulating one or more droplets among multiple configured-electrodes by sequentially activating and de-activating one or more selected configured-electrodes to actuate droplets to move along selected route.

Description

201244825 六、發明說明: 【發明所屬之技術領域】 本發明係關於一種基於介質上電潤濕(EW0D)的微流體系統和 方法。更具體地,本發明特別係關於一種利用EW0D微電極陣列鈇 構技術進行液滴處理的方法和系統。 〜 相關申請的交叉參考 “本申請通過參照的方式併入2011年2月17日提交的名稱為 Droplet Manipulations on EWOD Microelectrode Array Architecture”的聯合待審美國專利申請N〇. 13,Q29J37_, 2011年2月17日提交的名稱為“Field_pr〇grammable Lab-on-a-Chip and Droplet Manipulations Based on EWOD Micro-Electrode Array Architecture” 的聯合待審美國專利申 ^ No·』3, 029,138—以及2011年2月17日提交的名稱為201244825 VI. Description of the Invention: [Technical Field] The present invention relates to a microfluidic system and method based on electrowetting (EW0D) on a medium. More specifically, the present invention relates in particular to a method and system for droplet processing using the EW0D microelectrode array architecture technique. 〜 CROSS-REFERENCE TO RELATED APPLICATIONS [This application is hereby incorporated by reference in its entirety in its entirety in its entirety in its entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire content Co-pending U.S. Patent Application No. 3, 029, 138, and February 2011, submitted under the name "Field_pr〇grammable Lab-on-a-Chip and Droplet Manipulations Based on EWOD Micro-Electrode Array Architecture" The name submitted on the 17th is

Microelectrode Array Architecture” 的聯合待審美國專利申 請No. 13, 029,140的令部内容。 【先前技術】 為了實現某些化學、物理或生物技術處理技術的可能性 流體技術在過去恃㈤賊紐。微流财的是财在微升到毫 微升範圍⑽微量越賴縱。祕實施小容量 裝置的使用由分析化學家首次提出,為了這—概念mg 使用了術語“小型化總化學分析系統,,UTAS}。來自分析化學 以外^很多學科的越來越多的研究者採納了仰】 理’作為-種開發化學和生物學應用的新研究工具的方 反映出這種擴展了的範圍,除了 WAS之外 廣 的術語“微流體”和“晶片實驗室(L〇c) ”。7丄吊使用更廣義 第-代微流體技術基於流經微細加卫的道 =液體流的激勵由外部壓力源、集成機械微型 構來貝現。連續流系統能滿足报多明確定義的、簡單 201244825 2 縱口==, ίϊ^ϊΐϊ^。這些技術可被分類成化學方法、熱測ί、 ΐίίίί^ΐΐ注在所有方法中,用以激勵液滴的電學方法 實驗(麵)是最f見的電學方法之—。諸如晶片 的圖案化陣列,頂板塗覆有連續的地電極。 (ITQ)的獅軸雜,使其在薄層中 透紐的組合概。塗财疏水朗介電絕緣體被 =到以降低表面的潤濕性並增加液滴與控制電極之間的 學樣品的液滴和填充媒介夹在板之間,同時液 部移動。為了移動液滴,向鄰近於液滴的電極施 力激勵控制輕,同時在賴正下方的電極去除激勵。 胜、j ’吊規的利用ew〇d技術的l〇c系、統至今仍然高度專用於 應用,有的L0C系統極其依賴於人工控制和生物測定優 w且’現有的E_-L0C系、、统中的應用和功能非常耗費時間並 〒貝的硬體設計、測試以及維護程式。現有的E_-L〇c系 大缺點是硬連線電極的設計。“硬連線,,是指電極控制器 沾二摄、尺寸、位置以及電子佈__完全受限於永久性餘刻 ^構。一旦電極被製造出,它們的形狀、尺寸、位置和執跡就 月b改變,而與它們的功能無關。因此,這可 臨 =程造價’以及限制更新推出或部分改裝L0C設計後的功能的能 力。 本領域存在對用於減少與利用液滴操縱產生數位微流體系統 201244825 力和成本的系統和方法的需要。EW0D微電極陣列結構 夠k供現場可程式設計能力,即所述電極和該既的整體 倾財設制。如果其固件(存·«錄記憶體, H被麟修改而無需拆卸或將其返回其製造商,據稱 件或m钱可以通過現場程式設計·上程式設 汁:由於能夠降低更換有問題或廢棄固件的費用和周轉時間,這 往往疋種極其理想的特性。在輸送、局部重新配置設計的部分 ^更新功能的能力以及相對於L〇C設計的較低的偶生工 將為报多應用提供優勢。 、 本領域將L0C設計提咼到應用級,從而將lqc巧許去們從车 動優化生物測定、耗時的硬齡計、#錢_試和^^= 放出來。 並且’基於新穎的EW0D微電極陣列結構,可以顯著改進L〇c 系統中的操縱液滴的技術。在基於既⑽微電極陣列結構的產生、 輸送、混合和切割過程中的先進的液滴操縱方面,本 各種實施对。 1 【發明内容】 本發明公開了 一種在包括多個微電極的可程式設計聊㈤微電 極陣列中操縱液滴的方法。在一實施方式中,該方法包括:(a) 構建包括多個微電極構成的陣列的底板,所述微電極設置在由介 電絕緣層覆蓋的基板的頂表面;其中,每個微電極與接地機構中 的至少一個接地元件連接;其中在介電絕緣層和接地元件的上部 設置有疏水層,以形成與液滴疏水的表面;(b)操縱所述多個微 電極以配置一組配置電極來產生微流體元件,並且按照選定的形. 狀和大小佈局’其中所述一組配置電極包括:第一配置電極,其 包括陣列佈置的多個微電極;以及至少一^個第二相鄰配置電極了 其與該第一配置電極相鄰;所述液滴設置在第一配置電極的頂部 並且與第二相鄰配置電極的部分重疊;以及(c)通過順序地施加 驅動電壓敖勵或去除激勵一個或多個選定的配置電極來順序地激 201244825 勵$去除激勵所選定的配置電極以驅動液滴沿選定的路徑移動, 來操縱多個配置電極之間的一個或多個液滴。 在另一實施方式中,一種在包括多個微電極的可程式設計 EW0D微電極陣列中操縱液滴的方法,該方法包括:(幻構建包括 微電極構成的陣列的底板,所述微電極設置在由介電絕緣層 覆蓋的基板的頂表面;其中,每個微電極與接地機構中的至少一 個接地元件連接;其中在介電絕緣層和接地元件的上部設置有疏 水層,以形成與液滴疏水的表面;(b)操縱所述多個微電極以^ 置一組配置電極來產生微流體元件,並且按照選定的形狀和大小 佈局,其中所述一組配置電極包括:第一配置電極,其包括陣列 佈置的多個微電極;以及至少一個第二相鄰配置電極,其與該第 配置電極相鄰,所述液滴設置在第一配置電極的頂部並且與第 二相鄰配置雜的部分重疊;(c)對第—配置電極去除激勵?及 ,第二相鄰配置電極進行激勵以將液滴從第一配置電極拉動到第 二配置電極上;錢⑷魏轉地施加购電驗勵或去除激 勵-個或多個選定的配置電極來順序地激勵或去除激勵所選定的 配置電極以驅動液滴沿選定的路徑移動,來操縱多個配置電極 間的一個或多個液滴。 再實%方式中,一種在包括多個微電極的可程式設計Ew〇d 微電極陣列中操縱液滴的方法,該方法包括:(a)構建包括多個 .微電極構朗P車列的底板’所賴電極設置在由介電絕緣層覆蓋 的基板的頂表面;其中,每個微電極與接地機構中的至少一個g 地元件連接,其中在介電絕緣層和接地元件的上部設置有疏水 層,以形成與液滴财的表面;⑻操縱所述多個微電極以配置 -組配置電極來產生微流體元件,並且按照選定的形狀和大小佈 局’ ^中所述-組配置電極包括:第一配置電極,其包括陣列佈 置的夕個微電極;以及至少__個第二相鄰配置電極,其與 一 配置電極相鄰;所述液滴設置在第一配置電極的頂部並且與第二 相=置,極的部分重疊;(c)配置不與該第—配置電極上的液 滴重邊的第二相鄰配置電極;以及⑷通過順序地施加驅動電壓 201244825 或多個選定的配置電極來順序地激勵或去除 ' _ 、-置電極以驅動液滴沿選定的路徑移動,來摔縱多 個配置電極,間的—個或多個液滴。 私縱夕 “在f Γ實施方式巾,本發明中的EW0D微電極陣列結構库用了 丄、^'可被㈤時被激勵/去除激勵以形成不同形狀和尺 寸的電極來付合場應用中的流體操作功能的需求。 個矜施中’所有的·⑽流體元件可以通過分组多 Ϊίΐ ίί ’包括但不現定於:貯液器(⑽㈣⑴、電極、 μ &至、液滴路技以及其他。此外,用於1/〇埠、貯液哭 路=及,網路的位置的L()c的物理饰局都可以通過配置二電 極貫,微電極在配置_配置後區別於常規的電極。’ 在另一貫施方式中,例如貯液器、電極、混合室 電=多種形狀和尺寸,以及用於微流體系統的I/O埠Γ 會路徑和電極網路的位置的L0C的物理佈局均能軟 Ξΐίΐ求。 以及現場程式設計以滿足場應用中的操作 *可ί 爐在縱他膽微電極陣列結構設計 上二it面結構’其中’由上頂板在系統中執行。 π丄f 一 ^施方式+ ’在液滴操縱中的_微電極陣列έ士禮的 =基於共_ ’其中__在—健崎以 不可ί二實=微陣列結構下通過共面結構利用 4 μ 自我"^的、透明頂板來容納最寬範圍齡心+ 積來產生以容納最寬範圍的液滴尺寸和體積的l〇C結構的方 _在二實1方式中,所有的典型的_微流體操作都处貌A 體择$ 控制“配置電極,,來實現。=微流 ”乍0括.將賴裝翻液滴微激勵器中;從源液滴=一 201244825 個或多個液滴;分裂、分 將液滴沿任何方向從^固液滴為兩個或更多個液滴; 液滴合併植合騎個2輸另—位置;將兩個或更多個 將液滴變形;將適; =佈置液滴;將液滴輸送出液滴二 it操ίΐ常!卜,’=極=極”的用以執行典型微流 滴;利用“臨時橋接,,拮對角線或义任何方向輸送液 清除殘留液、、翁Η 輸送液滴;利用電極列激勵輸送液滴; 4==—形下輸送液 刦.拙= 送液滴,執订精確的切割;執行對角線切 ;使賴形以加速混合; 速度;通過;娜*®齡狀進混合 德1改進混合速度;和/或上述的任何組合。 所屬領:::術C來是f發明的其它實施方式對於 明的示例性實施方式。應意識到,在不脫 t S神 的情況下,本發明在多個方面能夠有多種 =性Γ圖和詳細說明在性f上應#被視為示例性的而非 【實施方式】 凊f照目1A ’其圖示了現有的電潤濕微激勵結構(大小僅僅 為了圖示的目的)。基於EW0D的數位微流體元件1〇〇包括兩個 行的玻璃底板120和121,下底板121包括多個獨立可控電極13〇 的圖案化陣列’並且上底板塗覆有一連續的地電極⑽。優選地通 過諸如氧化銦錫(ΙΤ0)之類的材料形成電極,使其在薄層 導電性和透光性的組合特徵。將塗覆有諸如聚四氟乙婦AF曰之类員的 9 201244825 生物化學樣品的液滴150和油容二含有 f之間,以有助於液滴150在填充媒介内部的^送。為The content of the co-pending U.S. Patent Application Serial No. 13, 029,140 to Microelectrode Array Architecture. [Prior Art] In order to realize the possibility of certain chemical, physical or biotechnological processing techniques, fluid technology has been used in the past. The flow of money is in the range of microliters to nanoliters (10). The use of small-capacity devices is first proposed by analytical chemists. For this concept, the term “miniature total chemical analysis system, UTAS}. More and more researchers from many disciplines outside of analytical chemistry have adopted the role of Yang's as a new research tool for developing chemical and biological applications, reflecting the scope of this expansion, in addition to WAS. The terms "microfluidics" and "wafer labs (L〇c)". 7 丄 吊 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用 用The continuous flow system can meet the clearly defined and simple definition of the 201264425 2 vertical port ==, ίϊ^ϊΐϊ^. These techniques can be classified into chemical methods, thermal measurements, and ΐ ί ί ί 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 电 电 电 电 电 电 电A patterned array, such as a wafer, is coated with a continuous ground electrode. (ITQ)'s lion shaft miscellaneous, making it a combination of layers in a thin layer. The coated hydrophobic dielectric insulator is = to reduce the wettability of the surface and to increase the droplets of the sample between the droplet and the control electrode and the filling medium sandwiched between the plates while the liquid moves. In order to move the droplets, the excitation control is lightly applied to the electrodes adjacent to the droplets while the excitation is removed by the electrodes directly underneath. The l〇c system using the ew〇d technology of Sheng and j's slings is still highly dedicated to applications. Some L0C systems rely heavily on manual control and biometrics and the existing E_-L0C system, The applications and functions in the system are very time consuming and the hardware design, testing and maintenance programs of the mussels. The major drawback of the existing E_-L〇c system is the design of hardwired electrodes. "Hard connection, refers to the electrode controller's exposure, size, position, and electronic cloth __ is completely limited by the permanent residual structure. Once the electrodes are manufactured, their shape, size, position and obstruction The monthly b changes, regardless of their function. Therefore, this can be used to reduce the ability to introduce or partially modify the functions of the L0C design. There are fields in the field for reducing and utilizing droplet manipulation to generate digital digits. Microfluidic System 201244825 The need for systems and methods for force and cost. The EW0D microelectrode array structure is sufficient for field programmable capability, ie the electrodes and the overall cost of the package. If its firmware (Save Memory, H is modified by Lin without disassembling or returning it to its manufacturer. It is said that the piece or m money can be designed by on-site programming and programming: because it can reduce the cost and turnaround time of replacing the problem or scrapping the firmware, This tends to be extremely desirable. The ability to transport, partially reconfigure the part of the design, and the ability to update the function and the lower even workmanship relative to the L〇C design will be reported. Provide advantages. In this field, the L0C design is upgraded to the application level, so that lqc can be released from the vehicle optimization biometrics, time-consuming hard age meter, #钱_试 and ^^=. The novel EW0D microelectrode array structure can significantly improve the technique of manipulating droplets in the L〇c system. In terms of advanced droplet manipulation based on the generation, transport, mixing and cutting of both (10) microelectrode array structures, Various Embodiments 1 SUMMARY OF THE INVENTION The present invention discloses a method of manipulating droplets in a programmable (5) microelectrode array comprising a plurality of microelectrodes. In one embodiment, the method comprises: (a) constructing a bottom plate comprising an array of a plurality of microelectrodes disposed on a top surface of a substrate covered by a dielectric insulating layer; wherein each microelectrode is coupled to at least one grounding element of the grounding mechanism; wherein the dielectric is An upper portion of the insulating layer and the grounding element is provided with a hydrophobic layer to form a surface that is hydrophobic with the droplets; (b) manipulating the plurality of microelectrodes to configure a set of configuration electrodes to generate the microfluidic element And according to the selected shape and size layout, wherein the set of configuration electrodes comprises: a first configuration electrode comprising a plurality of microelectrodes arranged in an array; and at least one second adjacent configuration electrode The first configuration electrode is adjacent; the droplet is disposed on top of the first configuration electrode and overlaps with a portion of the second adjacent configuration electrode; and (c) is excited or removed by sequentially applying a driving voltage to excite one or more The selected configuration electrodes are sequentially energized to remove the selected configuration electrodes to drive the droplets to move along the selected path to manipulate one or more droplets between the plurality of configuration electrodes. In another embodiment A method of manipulating a droplet in a programmable EW0D microelectrode array comprising a plurality of microelectrodes, the method comprising: (a magical construction of a bottom plate comprising an array of microelectrodes disposed on a dielectric insulating layer a top surface of the covered substrate; wherein each of the microelectrodes is coupled to at least one of the grounding members; wherein the dielectric insulating layer and the grounding member are a hydrophobic layer is provided to form a surface that is hydrophobic with the droplets; (b) the plurality of microelectrodes are manipulated to set a set of configuration electrodes to create a microfluidic element, and arranged in a selected shape and size, wherein the The group configuration electrode includes: a first configuration electrode including a plurality of microelectrodes arranged in an array; and at least one second adjacent configuration electrode adjacent to the first configuration electrode, the droplets being disposed at the first configuration electrode a top portion and a portion overlapping the second adjacent configuration; (c) a first-disposition electrode removal excitation? and a second adjacent configuration electrode excitation to pull the liquid droplet from the first configuration electrode to the second configuration electrode Money (4) applies power purchase excitation or removes excitation - one or more selected configuration electrodes to sequentially energize or remove excitation of selected configuration electrodes to drive droplets to move along a selected path to manipulate multiple configurations One or more droplets between the electrodes. In a re-% mode, a method of manipulating a droplet in a programmable Ew〇d microelectrode array comprising a plurality of microelectrodes, the method comprising: (a) constructing a plurality of microelectrodes comprising a plurality of microelectrodes An electrode of the bottom plate is disposed on a top surface of the substrate covered by the dielectric insulating layer; wherein each of the microelectrodes is connected to at least one of the grounding mechanisms, wherein the upper portion of the dielectric insulating layer and the grounding member are disposed a hydrophobic layer to form a surface with a droplet; (8) manipulating the plurality of microelectrodes to configure a set of electrodes to create a microfluidic element, and arranging the electrodes in accordance with a selected shape and size arrangement a first configuration electrode comprising an array of argon microelectrodes; and at least __ second adjacent configuration electrodes adjacent to a configuration electrode; the droplets being disposed on top of the first configuration electrode and a second phase = set, a partial overlap of the poles; (c) a second adjacent configuration electrode that is not overlapped with the droplets on the first configuration electrode; and (4) a sequential application of a driving voltage 201244825 or a plurality of selected The electrodes are configured to sequentially energize or remove the ' _ , - the electrodes to drive the droplets to move along the selected path to sag the plurality of configuration electrodes, one or more droplets. In the case of the f Γ implementation, the EW0D microelectrode array structure library of the present invention uses 丄, ^' can be excited/removed by (5) to form electrodes of different shapes and sizes for use in a field application. The need for fluid handling functions. All of the '10' fluid components can be grouped into multiple Ϊίΐ ίί 'include but not limited to: reservoirs ((10)(4)(1), electrodes, μ & to, droplet routing and In addition, the physical decoration of L()c for 1/〇埠, liquid storage crying= and the position of the network can be configured by two electrodes, and the microelectrode is different from the conventional one after configuration_configuration. Electrodes. 'In another embodiment, such as reservoirs, electrodes, mixing chambers = various shapes and sizes, and the physical properties of the L0C for the I/O of the microfluidic system and the location of the electrode network The layout can be softly Ξΐ ΐ 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 以及 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场 现场One way + 'in droplet manipulation The _microelectrode array in the έ 礼 = = = based on the total _ 'where _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ A wide range of ages + accumulated to produce the widest range of droplet sizes and volumes of the l〇C structure. In the two real 1 mode, all typical _microfluidic operations are in the form of A. "Configure the electrode, to achieve. = microflow" 乍 0 bracket. Will be installed in the droplet micro-exciter; from the source droplet = a 201244825 or more droplets; split, split the droplet in any direction From the solid droplets to two or more droplets; the droplets merge and plant the ride 2 to the other position; the two or more will deform the droplets; will fit; = arranging the droplets; The droplets are transported out of the droplets. It is often used to perform typical microfluids; using "temporary bridging, anterior diagonal or any direction of transporting liquid to remove residual liquid, Weng输送 transport droplets; use the electrode column to stimulate the transport of droplets; 4 == - under the transport liquid robbery. 拙 = send droplets, set precise cutting; perform diagonal Cut; make the shape to accelerate the mixing; speed; pass; Na*® age into the mixed de 1 to improve the mixing speed; and / or any combination of the above. Owner:::C is the other embodiment of the invention Exemplary embodiments of the present invention. It should be appreciated that the present invention can be varied in many respects in various respects and detailed descriptions on the nature f are considered exemplary. [Embodiment] 凊f照目1A' illustrates the existing electrowetting micro-excitation structure (the size is only for the purpose of illustration). The EW0D-based digital microfluidic element 1〇〇 includes two rows of glass substrates 120 and 121, the lower substrate 121 includes a patterned array of a plurality of individually controllable electrodes 13A and the upper substrate is coated with a continuous ground electrode (10). The electrode is preferably formed by a material such as indium tin oxide (ITO) to combine characteristics of thin layer conductivity and light transmittance. The droplets 150 and the oil reservoirs of the 9 201244825 biochemical sample, which are coated with a member such as a polytetrafluoroethylene AF, are contained between f to facilitate the delivery of the droplets 150 inside the filling medium. for

近於液滴的電極⑽施加控輸,同時:液^ 正下方的電極被去除激勵。 t长夜肩ibO 圖1B是概括說明在二維電極陣列190 圖。液滴150從電極130移動到被激=規_的頂視 呈黑色表鶴σ有控制電㈣WQDt=l電jt18G中。電極⑽ 體介面中,作用使4電荷積聚在液滴/絕緣 ΪΪΪ鄰電極130和180之間的間隙135上產生; ,張力梯度,械實職滴⑽的輸送 二 陣列的電位,可利用電潤濕來沿著此電 ;,在°:睛的範圍内調節控制電壓來控 f ί液滴可以W達2Gcm/s的速度移動。液滴151和152也可在 …而微型泵和微型_條件下,通過二維 的圖案在時鐘輕控制下輸送。 平⑽使用者限疋 基於EW0D的微流體元件使帅鄰電極 以激勵液滴。電極的設計包括每個電極 尺工以及,電極之間的間隙。在基於膽的設計中, =吊=在設計中連接不同區域的多個電極極可^ 送過程或者更複雜的操作,例如在液輪财 本發明_ 了“點矩陣印刷機,,的概念,即,_ ϋ,構中可祕職财_鮮體組件的 種微流體元件。根據客戶的需求ί個:ΐ 極可被視為成組的(grouped)並且可被同時 電極並執行微流體操作的“點’,。“激勵,, :=2 |的電壓’從而EWQD作用使得電荷積聚在液滴境^體介面中, 導致在相鄰電極之間的間隙上產生介面張力梯度,由此實現液滴 201244825 的輸送;或者DEP作用使得液體變得可極化並朝著較強電場 的區域流動。去除激勵”指的是去除施加到電極的電壓。又 .圖2描述了本發明EW0D微電極陣列結構技術的一個實施方 式。在本實施方式中,微電極陣列2〇〇包括多個(3〇χ23個 的微電極210。此微電極陣列2〇〇是基於標_電極規範 声 巧微電極210)以及獨立於最終的LQC應用和具體微流體操^ 气的製造技術製造的。換言之,此微電極陣列2〇〇是“空白、,,志 預配置L0C。然後,基於應用需要,此微電極陣 = =程式設計到期望的L0C中。如圖2所示,每個 包括100個微電極210 (即10><10個微電極)。“配置電極,, 是10x10個微電極210組合在一起以用作集成電極22〇,並且‘一 ί勵。通常來說’配置㈣存儲在非易失性 (比如ROM)中’並且可“在場中,,或在任何指定位置的“現 琢令被修改,而無需拆解裝置或將裝置返回其製造商 明液滴250位於中心配置電極220。 ° 如圖2所示,本發明配置電極的尺寸和形狀可基於應 ^计。尺寸受到控制的配置電極的例子是配置電極220和240。 4己"電極220具有1〇Xl0個微電極的尺寸,而配置電極240且有 S i微Ϊ極的尺寸。除了配置電極尺寸的配置,還可通過利用、ί 玉陣列來配置所述配置電極的不同形狀。盡配置管電極挪是 是230疋包括2x4個微電極的矩形。配置電極260 疋左側齒狀的方形,而配置電極270是圓形。 另外,如圖2所示,液滴250的體積與配置電極22〇的尺 Γ ί言之’通"^控制配置雜220的尺寸,液滴250的體 ^破Ρ艮制以與配置電極22〇的設計尺寸相適應,因此“配 的現場可程式設計性指岐對液滴體積的控 滴體積_態可程式設計控制是高度期 如圖3A所示’本發明配置電極的形狀可基於應用需要而設 11 201244825 計。配置電極的形狀可由多個微電極產生。根據設 作為組被配置和激勵,以形成期望形狀的配置電極本 配ί電極的形狀可以是方形、具有齒狀邊緣的方形、六 ϊ 匕形狀。參照圖3Α,輸送路徑340、檢測視窗350 和h合至的配置電極的形狀為方形。貯液器咖是確 的大尺寸配置電極。廢棄物貯存器32〇是四角形。 圖3B和雛說明圖3A中貯液器33〇的放大部分。關說明由傳 統的EWOD-LOC系統製造的物理钱刻貯液器結構測。該元件說明永 久性侧的貯液器331和4個永久性钱刻的電極37卜與圖3β(傳統 ’圖3C說明場程式設計L〇c結構,其具有類似尺寸的配 置貝了液斋332以及成組的電極372。配置貯液器332可通過將多個微 電極311組合細望的尺朴形狀來製造。雜的電極3 個微電極31卜 —在限疋了所需微流體組件的形狀和尺寸之後,還很重要的是 限定微流體元件的位置以及如何將這麵越元件連接在一起作 為電路或網路。圖3A說明這些微流體元件所處的物理位置以及這 些微流體元件如何連接在一起以用作功能L〇G:。這些微流體纟且件 為:配置電極370、貯液器330、廢棄物貯存器320、混合室36〇、 才^測視固350以及連接LOC的不同區域的輸送路徑34〇。如果是現 %可程式設計L0C,則在佈局設計之後,會有一些未使用的微電極 31^。在FPLOC被充分檢驗合格之後’設計者可以嘗試硬連線版本 以節約成本’然後未使用的微電極31〇可被移除。 常規的基於EWOD的LOC設計基於雙平面結構,其具有包含圖案 化電極陣列的底板以及塗覆有連續地電極的頂板。在本發明的二 個實施方式中,採用EW0D微電極陣列結構技術的L〇c裝置是基於共 面結構’其中激勵可發生在不具有頂板的單板配置中。共面設 可適應更寬範圍的不同體積尺寸的液滴,而不受頂板的限制。雙 平面結構在頂板之間具有固定間隙,並且在適應寬範圍的體積^ 寸的液滴方面存在限制。再在另一實施方式中,基於共面結構的、 採用EWOD微電極陣列結構技術的l〇C裝置仍可以增加用於密封測 Ο 12 201244825 试表面的無源頂板,以保護流體操作或者為了保護測試媒介具有 更長的上架保存(shelf storage)壽命的目的。 如圖4所示,在另一實施方式中,在用於EW0D微電極陣列的 共面結^中採用可拆卸的、可調節的和透明的頂板,以優化在如 圖4所示的頂板410與電極板420之間的間隙距離。電極板42〇 通過該EW0D微電極陣列結構技術來實現,其中用於液滴43〇的配 置電極的側視圖包括三個微電極(顯示為黑色)。用於液滴仏〇的 配置電極包括六個微電極,用於液滴45〇的配置電極包括十一個 微電極。本實施方式在諸如FPL〇c之類的應用中尤其有用。儘管 EW〇p微電極陣列結構在配置所述配置電極的形狀和尺寸時提供了 現場可程式設雜’但是健高度需要能_應最絲圍的^寸 j積的液滴㈣統結構。這是因為F隱可適應滴的尺寸 的範圍越寬,就可實現越多的應用。優化的間隙距離可被 合期望尺寸的液滴。在本發明中,優化的間隙可通過三 =式實現:首先’所有的液滴可在不接觸頂板41Q的條件下被 刼縱。這種方式通常應用於共面結構中。在第二種方式中, 通過接觸頂板41G被操縱,其中液滴夾在頂板410與電 之間。第二種方式通常應躲雙平面結構中。第三種方 3二ίί合併了共面結^以及在頂板41G與共面電極板420 二二心卩_的功能。這種混合方式可用於提供具有最寬範 如圖4所示,位於間_的液滴和液滴44〇可在 的條件下被操縱。液滴被操縱為夾在頂板· 本發明不限於腦微電極陣列結構技術,也 ^液献寸的可細顧可被_的啊細於其它常規的電 =極_結構賴電極的板結構可以通過使用 於目前流行配㈣_ 一的雙平面結構來設計 a ΐΐίτΓ種基於賊極結構⑷、僅是為了神丨的目的)的雙平 趁191。,中說明二個微電極130和兩個平行的板120和12卜 -板121包含了一組圖案化的單個可控電極13〇的陣列。頂板⑽ 13 201244825 覆有疏水膜160的介電絕緣層170 間的電i t 潤濕性並增加液滴和控制電極之 例如功f滴50包含被夾在板之間的生化樣品和填充介質, 油或者空氣,以便於液滴在填充介質内輸送。、 LOc/詈本一實施方式中,採用麵微電極陣列結構技術的 置中共激射發生林具有瓶的單= 頂板的二二更寬圍的不同體積尺寸的液滴,而不受 接結構在頂板之間具有固定間隙,並且在適應 “試S更 =ί二板命:目保:流體操作或者為了保 中物極板結構可以以很多方式尤其在共面結構 接地網”共面微電極結構,其包括一 λ #_時’驅動微電極510由此或方波 規電線與驅動微電極5ig處於相同的板上以實 見八面、、”構。間隙515用以確保在510與511之間無垂直重最。 和J 液滴操作單元,其包括永久性_的電二2〇 =,線531 (在垂直和水準方向上)。這兩個侧的電極52〇 直方向上的地線531分離。液滴540位於 =: ’㈣540太小m於不能接觸周圍的 也線531,並且不能執打液滴540的激勵。這可能 常觀察到的液滴操縱中的潛在問題。通常的補救措施是裝 ^大尺寸的液滴55〇,但是往往難以手動控制期望的液滴尺寸。 ^外,受常規系統中的地線531的限制,電極52〇和521不能具 有用於改善液滴操縱的交叉指型周邊。 罟說面結構中的本發明的改進的液滴操作單元。配 ^電極520紐多個現場可程式設計微電極⑽。配置電極可根 據液滴的尺寸通過軟體程式設計。在此實例中,配置電極52〇,包The electrode (10) near the droplet is controlled to be applied while the electrode directly below the liquid is removed and excited. t long night shoulder ibO Figure 1B is a schematic illustration of the two-dimensional electrode array 190. The droplet 150 moves from the electrode 130 to the top view of the excited = gauge _. The black crane σ has control power (four) WQDt = l electric jt18G. In the body interface of the electrode (10), the action causes 4 charges to accumulate on the gap 135 between the droplet/insulating electrode 130 and 180; the tension gradient, the mechanical droplet (10) transports the potential of the two arrays, and the electrowetting can be utilized. To follow this electricity; adjust the control voltage within the range of °: eye to control the movement of the droplets at a speed of 2 Gcm/s. The droplets 151 and 152 can also be transported under a light clock control by a two-dimensional pattern under the conditions of a micropump and a micro_. Flat (10) User Limits The EW0D-based microfluidic component allows the handsome neighboring electrodes to excite droplets. The design of the electrodes includes the spacing of each electrode and the gap between the electrodes. In a bile-based design, = hang = multiple electrodes in different regions of the design can be sent to the process or more complex operations, such as in the concept of a liquid crystal wheel, the concept of a dot matrix printer, That is, _ ϋ, a kind of microfluidic component that can be used as a secret component. According to the customer's needs, ΐ can be regarded as grouped and can be simultaneously electrode and perform microfluidic operation. "Point",. "Excitation,, :=2 | voltage' and thus EWQD acts to cause charge to accumulate in the droplet interface, resulting in an interface tension gradient across the gap between adjacent electrodes, thereby enabling delivery of droplets 201244825; Or the effect of DEP is such that the liquid becomes polarizable and flows toward the region of the stronger electric field. Removing the excitation means removing the voltage applied to the electrode. Further, Fig. 2 depicts an embodiment of the EW0D microelectrode array structure technique of the present invention. In the present embodiment, the microelectrode array 2A includes a plurality of (3〇χ23 microelectrodes 210. This microelectrode array 2〇〇 is based on the standard electrode specification microelectrode 210) and is independent of the final LQC. Applied and manufactured by specific microfluidic gymnastics. In other words, the microelectrode array 2 is "blank," and the pre-configured L0C. Then, based on the application requirements, the microelectrode array == is programmed into the desired L0C. As shown in Figure 2, each includes 100. The microelectrodes 210 (i.e., 10 < 10 microelectrodes). "The electrodes are arranged, and 10 x 10 microelectrodes 210 are combined to serve as the integrated electrode 22" and are 'excited. Generally, 'configuration (4) is stored in a non-volatile (such as ROM)' and can be "in the field, or at any given location, the current order is modified without disassembling the device or returning the device to its manufacture. The droplet 250 is located at the central configuration electrode 220. ° As shown in FIG. 2, the size and shape of the electrode of the present invention can be based on the measurement. An example of a configuration electrode whose size is controlled is to configure electrodes 220 and 240. The electrode 220 has a size of 1 〇 10 10 microelectrodes, and the electrode 240 is disposed and has a size of S i micro Ϊ. In addition to configuring the electrode size configuration, the different shapes of the configuration electrodes can also be configured by utilizing an array of electrodes. The configured tube electrode is a rectangle of 230 疋 including 2x4 microelectrodes. The electrode 260 is disposed to have a square shape on the left side of the tooth, and the arrangement electrode 270 is circular. In addition, as shown in FIG. 2, the volume of the droplet 250 is different from the size of the electrode 22 of the arrangement electrode 22, and the size of the droplet 250 is controlled to form a electrode. The 22-inch design size is compatible, so "the field-programmable design refers to the control of the droplet volume. The volume control mode is controlled by the height period. As shown in FIG. 3A, the shape of the electrode of the present invention can be based on The application needs to be set to 11. 201244825. The shape of the configuration electrode can be generated by a plurality of microelectrodes. The configuration of the electrode can be square and has a toothed edge according to the configuration and excitation of the electrode to form a desired shape. The square shape and the shape of the hexagonal crucible. Referring to Fig. 3, the shape of the arrangement electrode to which the conveying path 340, the detecting window 350 and the h are combined is a square shape. The liquid storage device is a large-sized electrode. The waste container 32 is a square shape. Fig. 3B and Fig. 3A illustrate an enlarged portion of the reservoir 33A of Fig. 3A. The description of the physical money reservoir structure manufactured by the conventional EWOD-LOC system illustrates the permanent side reservoir 331 and 4 permanent The magnetically engraved electrode 37b and FIG. 3β (traditional 'FIG. 3C illustrate the field programming L〇c structure, which has a similarly sized configuration, and a set of electrodes 372. The reservoir 332 can be configured by The plurality of microelectrodes 311 are fabricated in combination with a fine-grained ruler shape. The doped electrodes have three microelectrodes 31. After limiting the shape and size of the desired microfluidic component, it is also important to define the microfluidic components. The location and how the elements are connected together as a circuit or network. Figure 3A illustrates the physical location of these microfluidic components and how these microfluidic components are connected together for use as a function L〇G: These microfluidics The components are: the configuration electrode 370, the reservoir 330, the waste reservoir 320, the mixing chamber 36〇, the visual inspection 350, and the transport path 34〇 connecting the different regions of the LOC. If it is currently programmable L0C, after the layout design, there will be some unused micro-electrodes 31^. After the FPLOC is fully qualified, the designer can try the hard-wired version to save cost. Then the unused micro-electrodes 31 can be moved. except A conventional EWOD-based LOC design is based on a biplanar structure having a bottom plate comprising a patterned electrode array and a top plate coated with continuous electrodes. In two embodiments of the invention, an EW0D microelectrode array structure technique is employed. The L〇c device is based on a coplanar structure where the excitation can occur in a single-plate configuration without a top plate. The coplanar surface can accommodate a wider range of droplets of different volume sizes without being limited by the top plate. There is a fixed gap between the top plates, and there is a limit in adapting to a wide range of volumetric droplets. In another embodiment, a coplanar structure based on the EWOD microelectrode array structure technology A passive top plate for sealing the test surface can be added to protect the fluid operation or to protect the test medium for a longer shelf storage life. As shown in FIG. 4, in another embodiment, a detachable, adjustable, and transparent top plate is employed in the coplanar junction for the EW0D microelectrode array to optimize the top plate 410 as shown in FIG. The gap distance from the electrode plate 420. The electrode plate 42A is realized by the EW0D microelectrode array structure technique, in which the side view of the configuration electrode for the droplet 43A includes three microelectrodes (shown in black). The configuration electrode for the droplet enthalpy includes six microelectrodes, and the configuration electrode for the droplet 45 包括 includes eleven microelectrodes. This embodiment is especially useful in applications such as FPL〇c. Although the EW〇p microelectrode array structure provides on-site programmable design when configuring the shape and size of the configuration electrode, the health level requires a liquid crystal (four) structure that can be the most compact. This is because the wider the range of F-adaptable droplet sizes, the more applications can be achieved. The optimized gap distance can be matched to the desired size of the droplet. In the present invention, the optimized gap can be achieved by the three = formula: first, all of the droplets can be escaped without contacting the top plate 41Q. This approach is typically applied to coplanar structures. In the second mode, it is manipulated by contacting the top plate 41G, wherein the droplets are sandwiched between the top plate 410 and the electricity. The second way should usually be in a double plane structure. The third party 3 2 ί merges the coplanar junction ^ and the function of the second plate 卩 _ on the top plate 41G and the coplanar electrode plate 420. This mixing method can be used to provide the widest range of droplets and droplets 44 located between the sheets as shown in Fig. 4, which can be manipulated under the conditions. The droplets are manipulated to be sandwiched on the top plate. The present invention is not limited to the brain microelectrode array structure technology, and the liquid crystal layer can be carefully considered to be finer than other conventional electric poles. By using the biplane structure currently used in the (four)_ one to design a ΐΐίτΓ type based on the thief pole structure (4), only for the purpose of the gods). The two microelectrodes 130 and the two parallel plates 120 and 12 - the plate 121 comprise an array of patterned individual controllable electrodes 13A. Top plate (10) 13 201244825 Electrical iterability between dielectric insulating layers 170 coated with hydrophobic film 160 and increasing droplets and control electrodes, for example, the work droplets 50 contain biochemical samples and filling media sandwiched between the plates, oil Or air to facilitate delivery of the droplets within the filling medium. In the embodiment of LOc/詈, the centered eutectic occurrence forest adopting the surface microelectrode array structure technology has droplets of different volume sizes of the bottle 2 of the single plate of the top plate, and the unattached structure is There is a fixed gap between the top plates, and it is adapted to "test S more = ί2 plate life: eye protection: fluid operation or in order to protect the structure of the plate structure can be in many ways, especially in the coplanar structure grounding grid" coplanar microelectrode structure , which includes a λ #_' drive microelectrode 510 or the square wave gauge wire and the drive microelectrode 5ig are on the same board to see the eight sides, "the gap 515 is used to ensure that at 510 and 511 There is no vertical weight between the most. and J droplet operation unit, which includes the permanent _ electric 2 〇 =, line 531 (in the vertical and horizontal directions). The electrodes 52 on the two sides are in the vertical direction of the ground 531 Separation. Droplet 540 is located at =: '(4) 540 is too small to be in contact with the surrounding line 531 and cannot perform excitation of the droplet 540. This may often be a potential problem in droplet manipulation. Common remedies It is a large size droplet 55〇, but often The desired droplet size is manually controlled. ^Besides, limited by the ground line 531 in the conventional system, the electrodes 52A and 521 cannot have an interdigitated periphery for improving droplet manipulation. The improved droplet operation unit is provided with a plurality of field programmable microelectrodes (10). The configuration electrodes can be programmed by software according to the size of the droplets. In this example, the electrodes 52 are arranged,

5Q V' 〆 14 201244825 ==H)微電極51〇。在圖5C.中,液滴54ι錄配置電 的尺寸。在上Γ,的目的,液滴541類似於液滴540 (圖5B) 本配置電極520’包括多條具有橫截面的地線 物理重ίΓΓΙ於液滴541與配置電極520’ *多條地線511 置因此可實現有效的液滴操縱。 個接組接地(g卿giOunding)(在®6b中有21 - ί=ΐ„651重疊),其比常規實施方式的基本-對 的個液滴僅依賴—個接地焊盤,則液滴 焊盤之 管液滴的尺+二Ί。大里的接地知盤不存在這種限制;不 聚的的驅動i基本與在偏置的激勵電極和接地焊盤上^ 成比二Hi吊,電荷積聚也與電極和接地焊盤的表面積 鹿用遍2寸接鱗盤將對鶴力敍縣崎低侧,除非 這將使製造;藝 33„_極的中點㈣達到均衡。因此,存在Ϊ滴: • Ϊ尤盤叫致不可靠的液滴操縱的可能性。 ί絡的一致重疊保證了可靠的液滴操作。此ί,ί 本發明中,微型微電極(通常小於·xlG(W)超出了卜二 可行^因此需要源自轉體積體電路製造的微細加工技I 方々圖月程式設計接地谭盤,,共面微電極結構的另一實施 ϋί微雜_的板上不具有地線祕地賴。而是,、-些微電極用作接地焊盤以實現共面電極結構。圖7Α說明^個同 15 201244825 中,7i0 ’在微電極之間具有間隙715 °在本實施方式 作地電極m7ii可f配置為通過物理連接為電性接地3 極爪。相比常本規貫&方式的微電極710被配置為地電 具有群組接地上:上中的目的電極和接地機構,本發明 751只能在f轴也7f/、能在X軸方向上移動,且液滴 激勵的的分佈,液滴伽將位於被 以這種方激勵’並對相鄰電極730進行激勵; ΐ f2ewqw轉_的共面表面 移動。當臨時“配置電極”脱被激勵 763 ί Π 勵)將液滴752沿對角線拉到“配置電極” 了例示的目的’每個“配置電極”㈣具有在ίΓ角上 電後的臨時步驟’以達到液滴操縱的最佳結果。 施方式中,採用EW0D微電極陣列結構技術的 ί合祕構,射雜可發Μ共祕置或雙平面 置中。圖8說明開關81〇,其可被控制為在共面模式和雙平面模 極結構。在共面模式中,在蓋板82〇上的連 it 2雙平面模式中,電極板821上的接地網88〇連 η ‘ίί的地電極_與地斷開連接。在另-實施 工’接也網可被如前面的段落中描述的“接地焊盤,,或 201244825 地[代替。此外’在-個實施方式中,共面接 帶來任何問題K 只要額外的接地不會給雙平面結構操作 載入滴操縱中的液滴產生過程。樣品和試劑從輸入埠 得液滴者出。貯液器可以按照使 二實程是最關鍵的元件。該系統由於在流體輸入璋 升量與微升量甚至毫微升量規模的樣品之間 和試劑載义到1 可以改善液滴產生過程的設計。將樣品 的介ί載織财置和料Α賴裝置之間 的通孔上的於入造通常該介面由安裝在頂板915和貯液器920 液器中,之^ ϋ組成。樣品和試劑930從此輸入埠裝入到貯 ί,ί 成的液滴_在貯液器中產生。在晒 髒的 傳統的方法可能由於人為失誤引入錯誤的或者 褒载ί是絲共雜構,射树品或試劑 纺cwi α上之後了添加盍,因而不需要固定的輸入埠。浐對於 微電極陣舰構尤其重要,_該結翻現射程式対 貯液器和該収的輸人埠的形狀、尺寸和位式9 j =針960將樣品950直接裝載到共面電極板 的 必Ϊ常精確,因為貯液器的位置可根據需要由軟體 5十進行調節,以補償物理梦#值#。园Qr主_ 田软體私式5又 至電_ _^=差°圖9C表不在將樣品咖裝載 -化f"另一實施方式中’刪)微電極陣列結構的靈活㈣汽细 =褒載的樣品或,劑相對於貯液器的位置的成為可能。 二=避免對精確定位輸人埠的需要以及避免經輪人埠將ϋ 者+罔 匕們都未精確定位於貯液器941 爲也方式_,液滴952不必能與貯液器941重疊。對於^編^, 17 201244825 難以將液滴952重定位到貯液器941中。 柄缺I 式中丄即使樣品液滴952被裝載遠離貯液器941, — d動广位。這可以通過激勵臨時配置電極961來將液滴 液器941重疊來實現。接下來,去除激勵臨日ίΐί ==液_。在酬中’樣品液滴953可以被準確ΐ 過浐°圖10代表在ew〇d微電極陣列結構下的液滴產生 巾’特殊形狀的贿器聰和重疊的電極1035 貯滴:在本發明中’重疊的電極1035不必存在。 ιοίΓ= ”為方形的貯液器1015,而不需要重疊的電極 —貫施方式中’貯液器⑹5的形狀可以通過設計微電 設計需,為任何其它形狀。如_所示,液滴= 產,trf^015產生出液滴1050的過程。為了啟動液滴 先激勵臨時雜聰作為拉回(pul卜baGk)電極, ,的配置,1_ ’從貯液器1〇15提取出液體指狀物(ii_ “Si切?ΐ產生液滴1050。每個_電極1040由配置的4x4個 成。在—個實施方式中,配置電極的尺寸可以 形、圓形或其式中,貯液11可以是方 糟雷;Ξ田述了 ‘‘液滴等分’’產生過程的實施方式。通過操縱 沾士 勵配置電極1120。每個小液滴1115都大約與配置電極 ra 田,以至於能夠從貯液器Hl〇中提取出。如圖11Α所示, 凉。組微電極的配置電極1120被激勵以收集所需量的液 W二滴尺寸近似於電極的尺寸’並不存在用以控制液 頦斟π龙挪七確的方式。本發明中,液滴等分產生系統可用於實 積的更精顧控制。此外,在另一實施方式中,通過 1130的體積來計算從液滴1130產生的更小的液滴 圖11B描述了採用液滴等分工藝來製備樣品的另一實施方5Q V' 〆 14 201244825 ==H) The microelectrode 51〇. In Figure 5C., the droplet 54 is sized to configure electricity. For the purpose of the upper cymbal, the droplet 541 is similar to the droplet 540 (Fig. 5B). The configuration electrode 520' includes a plurality of ground lines having a cross section, the physical weight of the droplet 541 and the arrangement electrode 520' * a plurality of ground lines 511 thus enables efficient droplet manipulation. Grounding (g giOunding) (21 - ί = 651 651 overlap in ® 6b), which relies on only one ground pad for the base-to-drop droplet of the conventional embodiment, then droplet soldering The diameter of the tube is +2 Ί. There is no such limitation in the grounding knives of the large one; the non-polymerized drive i is basically compared with the biased excitation electrode and the grounding pad, and the charge is accumulated. Also with the surface area of the electrode and the grounding pad, the deer uses a 2-inch scale to connect the scale to the lower side of the Heliqi County, unless this will make the manufacturing; Art 33„_ pole midpoint (four) reach equilibrium. Therefore, there are tricks: • The possibility of unreliable droplet manipulation. The consistent overlap of the layers ensures reliable droplet operation. In the present invention, the micro microelectrode (usually less than ·xlG(W) is beyond the feasibility of the second method. Therefore, it is required to use the microfabrication technology from the manufacture of the revolving volume circuit. Another implementation of the surface microelectrode structure does not have a ground line. Instead, some microelectrodes are used as ground pads to achieve a coplanar electrode structure. Figure 7Α illustrates the same 15 201244825 Wherein, 7i0' has a gap of 715 ° between the microelectrodes. In the present embodiment, the ground electrode m7ii can be configured to be electrically grounded by a physical pole 3 pole. The microelectrode 710 is compared with the conventional method. Configured as grounding with group grounding: upper target electrode and grounding mechanism, the present invention 751 can only move in the x-axis and 7f/, can move in the X-axis direction, and the distribution of droplet excitation, droplet gamma Will be located in this side excited 'and excite the adjacent electrode 730; ΐ f2ewqw turn _ coplanar surface movement. When the temporary "configuration electrode" is de-energized 763 ί Π) the droplet 752 along the diagonal Pull to "configure the electrode" for the purpose of the illustration 'each' Step electrode interim "(iv) has, on the electrical angle after ίΓ 'to achieve the best results droplet manipulation. In the application method, the EW0D microelectrode array structure technology is used for the structure, and the hybrid can be co-secured or double-planar. Figure 8 illustrates switch 81A, which can be controlled to be in coplanar mode and biplanar mode structure. In the coplanar mode, in the connected it 2 biplane mode on the cover 82, the ground grid 88 on the electrode plate 821 is disconnected from the ground electrode _ ί. In another implementation, the network can be as described in the previous paragraph "grounding pad, or 201244825 ground [instead of. In addition - in an embodiment, the coplanar connection brings any problems K as long as additional grounding The double-plane structure operation is not loaded into the droplet generation process in the drop manipulation. Samples and reagents are drawn from the input droplets. The reservoir can be based on the two components that are the most critical components. Entering the amount of soaring between the sample and the microliter or even the nanoliter scale of the sample and the reagent loading to 1 can improve the design of the droplet generation process. The sample is placed between the device and the device. The through-hole is usually formed by the top plate 915 and the liquid reservoir 920, and the sample and reagent 930 are loaded from the input port to the reservoir. It is produced in the liquid. The traditional method of drying in the sun may introduce a wrong or a miscellaneous structure due to human error. After the tree or reagent is spun cwi α, the crucible is added, so no fixed input is required.浐For the micro-electrode array Importantly, the shape, size and position of the 翻 翻 対 対 対 対 和 和 9 9 9 9 9 9 9 9 960 960 960 960 960 960 960 960 960 960 960 960 960 960 960 The position of the liquid can be adjusted by the soft body according to the need to compensate for the physical dream # value#. Park Qr main _ field software private 5 and then _ _ ^ = difference ° Figure 9C is not loading the sample coffee f"In another embodiment, the 'deletion' of the microelectrode array structure is flexible (4), the steam sample = the sample or the position of the agent relative to the reservoir. 2 = avoid the need to accurately locate the input and It is not necessary to accurately position the sputum + 罔匕 in the reservoir 941. In other ways, the droplet 952 does not have to overlap with the reservoir 941. For ^编^, 17 201244825 It is difficult to drop 952 Relocating to the reservoir 941. The stalk is in the middle of the sputum. Even if the sample droplet 952 is loaded away from the reservoir 941, the d is moved wide. This can overlap the liquid droplet 941 by exciting the temporary configuration electrode 961. To achieve. Next, remove the incentive pro ίΐί == liquid _. In the remuneration 'sample droplet 953 can be approved ΐ ΐ 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图 图= "The square reservoir 1015, without the need for overlapping electrodes - the shape of the reservoir (6) 5 can be used in any other shape by designing a micro-electric design. As indicated by _, droplet = yield, trf^015 produces a droplet 1050. In order to activate the droplets, the temporary miscellaneous is excited as a pullback (pulbbaGk) electrode, and the configuration, 1_', extracts the liquid fingers from the reservoir 1〇15 (ii_“Si cut?” produces droplets 1050. Each of the _ electrodes 1040 is formed by 4×4 pieces. In one embodiment, the size of the arrangement electrode may be shaped, circular or in the formula, and the liquid storage 11 may be a square slag; An embodiment of the process of aliquoting. The electrode 1120 is configured by manipulating the smear. Each of the small droplets 1115 is approximately fieldd with the electrode, so that it can be extracted from the reservoir H1〇. Show, cool. The set electrode 1120 of the microelectrode is energized to collect the required amount of liquid W. The size of the droplet is approximately the size of the electrode. There is no way to control the liquid helium. In the present invention The droplet halving generation system can be used for more sophisticated control of the actual product. Further, in another embodiment, the smaller droplets generated from the droplet 1130 are calculated by the volume of 1130. Figure 11B depicts the use of droplets. Another implementation of the aliquot process to prepare the sample

Q 18 201244825 傭步驟之—是從全企中去除企細胞,以獲取用於 ίίΐΐ 3:體。如® 11β所示,經由微_1140利用液滴 然後經由小尺寸的麵猶‘=小^ 可右⑷15Q °液鱗分技術和小間隙的組合 以㈣更大ι^ϋ145從貯液器/液滴1160經通道1170移動, •擔血細胞1180。這裡的物理阻擔 s ΐϊΐ ㈣液滴°它並不用作去除血細胞的主 ϊίϊ哲等分技術,此樣品製備發明不僅能從液滴 去=❿且犯約製備用於診斷測試的合適尺寸的液滴。 方^_微電極陣列結構的液滴輸送。在一實施 Ξί:配ΐIt 置電極1231,1232到1239。每個配置電 配置恭極1235 ϋ個微電極’因而為方形。液滴位於中心 置i本祕的—個實财式巾,通過操縱配 ^ 1234 If f+j5〇JD北和東西方向輸送。例如,通過激勵配置電 f5去除激勵’將使液滴從配置電極1235 ,-電極1234上。在另一個實施方式中,根據使用者的雲 極123定肖線輸送。例如’液滴1250可沿對角線從配置電 才f 1235輸送到任一個配置電極123卜1233、1237或1239上,卽 1231 ' 1233 ' 1237 °為了沿對角線移動液滴1250,一個實施方式是作A辟 if/ °如圖12所示’液滴·可在方形電極 j所有8個方向移動,即南北、東西、西北 以便於液施方式十,臨時配置電極1260的形狀可以改變 =8 。在另一個實施方式尹’液滴的輸送i 供π吝吐if方向。果相鄰配置電極處於這8個方向之外,則 和激勵臨時配置電極以將液滴輸送到目的地。 、 19 201244825 圖13A-13C描述了採用包含臨時橋接技術的EW0D微電極陣列結 構的液滴輸送和移動的另一實施方式。通過液滴切割和液滴自然 蒸發’液滴太小而不能夠被電極可靠地驅動。圖13A說明由間隙 1360彼此分離的兩個配置電極1330、1340。液滴1350位於配置電 極1330的左側。兩配置電極1330和1340之間的間隙1360足夠寬, 能夠將兩配置電極1330和1340隔開。液滴1350位於配置電極1330 左側,將不會接觸到接下來相鄰的配置電極。 在圖13A中,由於在液滴1350和電極1340之間沒有物理重疊來 改變表面張力,因此液滴1350不能直接從電極133〇移動到接下來 相鄰的電極1340。這種問題在現有的^^(见輸送中經常看到。圖13β 描述了將圖13A中的液滴1350輸送到期望的配置電極134〇的一實 =式。在該過程中,被“齒狀”區域覆蓋的電極·被激勵。 w狀配置電極1370局部覆蓋左側配置電極133〇、間隙136〇以 =目鄰配置電極·。如圖13B所示,“齒狀,,配置電極盘液 西己詈ϊΐίίΐΐ重豐。觸發配置細370的激勵將使液滴1350在 。圖既描述了完成向期望的配置電極 ‘‘去此,液滴輸送。在㈣135Q輸送到期望的配置雜1370之後, 以二然後,配置電極1340被激勵, 以將液滴1·佈置和定蝴财的方觀置電簡 r方極㈣結構來進行㈣輸送和移_另一個實 式包括電極列激勵操縱。通過液 ,小得多,並且在液滴⑽和 二 =1 電極_中,因此液滴容不能被移動到 的-個實施方式S糊電極列激勵:、在 t地枝枯留液滴 多列以執行電極列激勵。在-個實施:广激勵電極佈置成 包括1x10搬電極。三瓶”㈣删配置電極列 勵’如U14B中標記為黑色的部分所_、、’且^ 起以執行電極列激 極,但是取錄細也可岐紅彳二默J侧寬奴-讎電 、 數里。在另一個實施方式中, 〇 20 201244825 ^效的電極列激齡具有―組電極列,其寬度獻於液滴剛 =禮。在另—個實施方式中,列的長度取決於朗,通常情況 下越長越好。 圖14β說明三列配置電極列如何被操縱以促進液滴的輸送。 ^首位的配践刻讀,電酬·被激勵,尾隨 的配置電極歹U422被去除激勵。在此實施方式中,不管液滴的尺 寸如何’三列配置電極列總是提供最大有效長度的接觸線。結果, ,滴1450能夠有效、平滑地移動,因為液滴145〇上的毛細力是 =致的並且被最大化。因此’㈣丨能在比纽Ε_液滴操 作中的驅動電壓低得多的驅動電慶下移動。這種電極列驅動技術 ^用於通ρ在低得多的驅動電壓下的平滑移動來輸送液滴。此 外’由於這種技術的一致的毛細力,通過以低速推進配置電極列, 可以實現對液滴速度(尤其在低速情形中)的控制。在另一實施 方式中,在臨界驅動電壓下,可應用電極列驅動以驅動液滴。再 f另實施方式中,已經觀察到:在低於8Vp-p 1kHz方波驅動電 壓並且在80/zm的間隙的條件下,在i〇cst石夕油中緩慢但平穩地 移動DI水滴(1.1mm直徑)。再在另一實施方式中,配置的電極列 的長度可以被配置為L0C的總長度。電極列驅動的單次沖刷可以 洗刷掉L0C中的所有無效液滴(dea(i droplet)。圖14C說明在激 勵配置的電極列(以黑色表示)保持朝右移動並最終移出配置電 極1410時,小液滴1450也移出配置電極141〇。 一圖UA-15C說明在EW0D微電極陣列結構下執行液滴的典型的 三電極切割的一個實施方式。圖15Λ說明水準排列的三個^置電 極1510、1511和1512。待切割的液滴1550位於中心的配置電極 151卜在圖15Α中’配置電極1511被激勵以控制住液滴155〇。液 滴1550與部分的相鄰配置電極1510和1512重疊。圖15β說明通 過同時激勵配置電極1510和1512,而對配置電極1511去除激勵 來切割液滴的階段。通過電極操縱,液滴1550朝著左右方向被拉 至電極1510和1512。在一個實施方式中,兩個外部配置電極丨51〇 和1512引發的親水力拉伸液滴,同時中央的疏水力將液體夾斷為 21 201244825 兩個子液滴1551’和1552’ ,如圖15C所示。 圖16A-16C描述了液滴切割的一個實施方式。圖l6A_i6 說明三個水準湖在-_配置_丨⑽、1611和1612。待 τα 1611 ^ ° f 液滴1650,利用電極列驅動技術來朝 ^配置=」610 * 1612緩慢但穩固地拉動液滴删,如圖16八 貫二方Λ^,ί、用並激勵兩組配置電極列1615和1616 己為’色來拉開液滴。兩組配置電極列中的每 一,,且us 5列電極。圖ι6Β描述了通過一 一^ 5 ίί5〇 ίΐίΐΐ Λ朝方向移動。兩組電極列組1615和ΐ6ΐ6引 1650 0 1615 ^1616 ^電極刪和1612的外緣時,所有配置電 去除激勵。配置電極161〇釦lm9 an ^ 子液滴福和·,戶^激勵’以將液體失斷為兩個 的一 _微電極陣列結構執行對角線切割 電極πιο、nu、1713和17t 圖17A +的四個配置 勵,並且配置電極mo和配置電極^配^電極1712被去除激 拉伸到液體柱中,如圖Γ7Β所二勵,因此將液滴1750 配置電極和mi _角去除激勵斷為兩個子液滴, 生必要的疏水力。圖17c說明L形‘電m50的m 再次激勵,=== 由於兩個拉動電極擁有較長的電極接觸,因此液滴的對角線切 22 201244825 ,是高效和有利的。液滴上的拉動毛細力比傳統的 此,可以降低切割電壓並且可以實現更 二要大。因 統的切割,需要超過飽和電壓的電塵(例如對接對於傳 更:靠義液滴====: 了寻南要更加小心、’所以不要超過餘和賴。因此 = 切醜選方案’以保持切割電壓低域和電 任何大小滴。 ㈣鎌切職乎可以切割 劫施方式中’在ew〇d微電極陣列結構下,在敞開的夺面 1870^:ίΧ2 二刪仏的士寬宝,的液體柱。接下來’激勵兩個預選的配置電極18二 =,:切割液滴1870並將其中心定位到這兩細己置電極i謂 ===圖」8C所示。共面鱗咖鍵在於在賴與外部的 之i有足夠的重疊,以便具有足夠的毛細力來克 °在一個實施方式中,當液體柱1删由 被切割成多個液滴時,姐被動切割。在另 ϋϊϊϋΓΐΐ和主動切割都被本發明採用。在液滴被拉伸 成兩個、ij的;r、L時2利用被動力或主動力來將起始液滴斷開 主利用被動力時,對液體柱長度的計算很重 時’優化的長度並不重要。不管是被動切割還 ϋΐΐ 割過程的最後步驟,配置電極_和被 23 1 Γ由激?二後將液滴定位到期望的配置電極中。在另一實施 方式中,被動4主動切割過裎通過利用麵微電極陣列結構在敞 201244825 開的表面下進行。圖18C說明當液滴被切割成兩個子液 1870時完成切割。 。圖19A-19B說明在EW0D微電極陣列結構下執行基本合併和混 合操作的一個實施方式。在本發明中,術語“合併,,和“混人” 可互換地使用,用以表示兩個或更多個液滴的組合。這是因&人 併兩個液滴並不總是直接或立即地導致初始分離的㈣的成分二 完全混合。在圖19A中,兩個液滴1950和1951初始分別位於 個對應的配置電極1910和1912上,並由至少一個位於其間的配 置電極j911分離。兩個液滴1950和1951與中心配置電'極1911 部分重疊。如圖19B所示,通過對兩個配置電極191〇和1912去 除激勵,對中心配置電極進行激勵,液滴195〇和1951在中心配 置電極1911上相互移動,然後合併成一個更大的液滴1953。 在EWOD微電極陣列結構中,分析物和試劑混合是一個決定性的 步驟。液滴充當實體混合室,通過將兩個液滴輸送到同一'個電極 來產生混合。利用最小的空間迅速混合液滴大大提高了生產能 力。通常地,有效的液滴混合需要8 (2 X 4)個電極以在這8個^ 極之間沿確定的路徑移動該混合的液滴,以加速混合。因此混合 操作中,急需一種不需要大的、用於混合操作的場所的、有效混 合液滴的方式。然而,隨著微流體裝置正在接近該替代的毫微升 模式’降低的體積流速和非常低的雷諾數將難以在合理的時間範 圍内實現液體混合。改善混合取決於兩個原則:在如此小的範圍 内產生渦流的能力,或者可選擇地,產生多層以實現快速混合的 能力。該EWOD微電極陣列結構可提供比通過擴散的被動混合1少 快一個數量級的基於液滴主動的混合。 圖20A-20C描述了基於EWOD微電極陣列結構通過不均勻幾何運 動以產生渦流來實現液滴操縱的主動混合過程。如圖2〇a所示,液 滴2050、2070可通過操縱配置電極而變形為所需的形狀。如圖2〇β 所示,通過激勵配置電極2051和2071,液滴說明為液滴2051,和 液滴2070’ 。然後,激勵中心配置電極2060以將液滴2050’ 、 2070,拉到混合配置電極2060 (標記為黑色)中,如圖2〇C所示。 p 24 201244825 在圖2GBt,H區域表示雜被激麟配置雜㈣和綱。這 些被激勵的電極可用於使這兩個液滴2〇5〇,和2〇7〇,變形,並且 將它們拉動到中心配置電極2060中。圖2〇B所示的這種臨日^激勵步 驟也有助於兩個液滴的平滑混合移動。圖2〇B_2〇ct的黑色區域和 變形液滴的形狀僅為例*的目的。在另一個實施方式中,這些形 狀根據需要可以為任意類型。 一 ^圖和21B描述了用於改善混合速度的微電極陣列混合 器。在=實施方式中,可使用不均勻的往復混合器來加速液滴的 混合。這可通過激勵一組微電極以產生不可逆轉圖案來實現,其 中不可逆轉圖案破壞了兩個迴圈的對稱性以改進混合速度。初^ 狀態在圖21A中說明,其中液滴2150包含樣品和試劑,並位於配 置電極2140的頂部。用於不均勻往復混合的第一個步驟是激勵配 置電極2160以使液滴2150朝著圖21B中所示的箭頭方向變形。 然後,配置電極2160被去除激勵,並且配置電極214〇被激勵以 將液滴拉回到圖21A所示的初始位置。往復混合可執行多次,以 實現優化的混合效果。此外,圖21A和圖21B中的配置電極2140 和變形液滴的形狀僅為例示的目的。在一個實施方式中,這些形 狀可以為任意類型的設計,只要它們具有產生渦流的能力,或可 選地,具有產生多層的能力。 在基於EWOD的液滴混合過程的另一實施方式中,圖22說明 用於改善混合速度的迴圈混合器。這可通過激勵更小的微電極組 的序列以產生不可逆轉水準迴圈來實現,其中不可逆轉水準迴圈 破壞了垂直層迴圈的對稱性以加速混合。如圖22所示的一個實施 方式是形成包圍液滴2290的八個配置電極(2210、2220、2230、 2240、2250、2260、2270和2280),然後以迴圈的方式順序地逐 個激勵配置電極。例如’在第一步驟中,配置電極2210被激勵較 短的時間段’以導致表面張力改變並且在配置電極2210上的液滴 2290的内部產生迴圈。接下來,配置電極2210被去除激勵,隨後 激勵下一個相鄰配置電極2220。通過全部八個配置電極(2210到 2280)重複迴圈激勵過程’以在液滴2290内部產生水準迴圈。此 25 201244825 迴圈流激勵可根據需要執行Μ。在另-個實施方式中,迴圈流 可按照順時針、逆時針或者這_方式的交替混合純行,以實 ,最佳混合效果。再在另—個實施方式中,配置電極22iq到㈣ 的形狀可為其他類型以及·的形狀僅為例示的目的一 個實施方式中,這種迴圈混合可岐任何纏的設計,只要它們 具有產生渦流的能力,或可選地,具有產生多層的能力。 在個貫把方式中,在EW0D微電極陣列結構中實現小尺寸 (2x2個配置電極)的混合器產生多層以加速混合的 層,合器對於低縱橫比(aspect rati〇) (<1)的情形尤其有用。 縱橫比,指電極板和接地板之間關隙與電極尺寸的比。低縱橫 比意味著更難以在液朗部產生渦流,因而產生多層的能力變^ 更加重要。®23A-23E說明-個實施方式,在此具體混合器中利用 對角線混合和對角線切割。在圖23A中,在配置電極2314處的黑色 液滴2351與在配置電極2311處的白色液滴235〇混合。臨時配置電 極2310將成為混合室,並將被激勵以拉入兩液滴2351和235〇。為 了啟動多層混合’第-個步驟是沿對角線合併兩個液滴。液滴合 併的對角線方向可以是45度或135度,但是隨後對角線切割的方向 需要垂直於合併操作。圖23B表示將液滴2351和液滴2350第一次合 =成為黑白液滴2352。由於低雷諾數和低縱橫比,液滴2352具有 單純基=擴散的靜態混合,其導致較長的混合時間,因此混合的 液滴顯示為一半為白色,一半為黑色,第二個步驟是要執行對角 線·^割,如圖23C所示,與起始的液滴2352的對角線混合呈9〇度。 在臨時配置電極2310被去除激勵的同時,配置電極2312和2313以 及其它臨時配置電極被激勵,以將液滴2352沿對角線切割成兩個 子液滴2353和2354,如圖23C所示。對角線切割的細節已在前面的 對角線切割過程中討論。由於低混合率,因此兩個子液滴2353和 2354在對^線切割之後以相同的方位保持黑/白疊層。然後,多層 混合的第三個步驟是將兩個液滴移回到起始配置電極上,以重^ 對角線混合和切割。在圖23D中,液滴2354從配置電極2312移動到 下一個相鄰配置電極2311上。液滴2353從配置電極2313移動到下 26 201244825 極2314上。可對電極2311和2314進行激勵並對電 韻。f要考躺是在雜的啊避免液滴 Z能會導致兩個液滴2353和2354在移_同時發生物理接觸: 後兩個液滴可能會合並在一起。在一個實施方式令,臨時配 =15和2316?先被激勵’以在兩個液滴之間產生保護區'用以 在兩個液滴朝著期望的電極移動的同時防止出現任何音。 在液滴編和移_配置電極咖和2315巾之後Γ將:個液 滴移動到配置電極2311和2314中。此程可以重複以產 力二速混合的必要數量的多層。作為重複從第—錄獅 =),2353和2354沿對角線合併成為液㈣咖 。圖職明轉複多層混合的迴圈之後^到的 滴微流體操作。連續微流體操作在控制方 ί谈讀操財缺供轉姐的途徑。圖 綱中產生確定體積的㈣。如= _之間的橋2415。當橋2415和目標配置電電 激= 置,極2460中。廷裡橋疋一條微電極線 續流和基於液滴的系統的特點。它具有通道的所有優點置‘;有, 旦橋配置電極被激勵,液體就將通過 對 考慮。同時它也“== 到貯液器i者目^置 (dead ν〇1·)。一旦目:配7雪0=在 配置電極2460的液體填滿是自動化的,即,斷旦橋^配置斤= 所有微電極被液體填滿,則將停止從貯液器細流出液體,因= 27 201244825 j過程的時雜織不重要。可通·纔適當㈤ 间的中斷點來精確地控制液體2430的產生。如 ° 微電極2416去除激勵然後對橋去除激勵,液體2Γ30 ί 10斷開。這個過程將確絲成橋的大部分液體將被拉回 數ΐίϊϋ0地液&24930將通過配置電極2460的微電極的 中’配置電極2460包括1議個 ,電極。可定義配置電極的其它尺寸和形狀以產生Q 18 201244825 The commission step is to remove the cell from the whole enterprise to obtain the ίίΐΐ 3: body. As shown by ® 11β, the droplets are transferred via micro-1140 and then via a small-sized surface. The shape is still small. The right (4) 15Q ° liquid scale technique and a small gap are combined to (4) larger ι^ϋ145 from the reservoir/liquid Drop 1160 moves through channel 1170, • blood cell 1180. Here, the physical resistance s ΐϊΐ (4) droplets. It is not used as the main 去除 ϊ 等 等 去除 去除 去除 去除 去除 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , drop. The droplet delivery of the microelectrode array structure. In one implementation, Ξί: ΐIt sets electrodes 1231, 1232 to 1239. Each configuration is electrically arranged with 1235 microelectrodes' and thus square. The droplet is located in the center of the secret - a real money towel, by manipulating with ^ 1234 If f + j5 〇 JD north and east-west direction. For example, removing the excitation by energizing the configuration f5 will cause the droplets to pass from the configuration electrode 1235, the -electrode 1234. In another embodiment, the cloud 123 is routed according to the user's cloud 123. For example, 'droplet 1250 can be transported diagonally from the configuration electrode f 1235 to any of the configuration electrodes 123, 1233, 1237 or 1239, 卽1231 '1233' 1237 ° in order to move the droplets 1250 along the diagonal, an implementation The way is to make A asif / ° as shown in Figure 12 'droplet · can move in all eight directions of square electrode j, that is, north-south, east-west, northwest to facilitate liquid application mode ten, the shape of temporary configuration electrode 1260 can be changed = 8 . In another embodiment, the delivery of the ink droplets is provided by the π 吝 if direction. If the adjacent configuration electrodes are outside these eight directions, then the excitation temporarily configures the electrodes to deliver the droplets to the destination. 19 201244825 Figures 13A-13C depict another embodiment of droplet delivery and movement using an EW0D microelectrode array structure including a temporary bridging technique. By droplet cutting and natural evaporation of droplets, the droplets are too small to be reliably driven by the electrodes. Figure 13A illustrates two configuration electrodes 1330, 1340 separated from each other by a gap 1360. Droplet 1350 is located on the left side of configuration electrode 1330. The gap 1360 between the two configuration electrodes 1330 and 1340 is sufficiently wide to separate the two configuration electrodes 1330 and 1340. Droplet 1350 is located to the left of configuration electrode 1330 and will not contact the next adjacent configuration electrode. In Fig. 13A, since there is no physical overlap between the droplet 1350 and the electrode 1340 to change the surface tension, the droplet 1350 cannot be directly moved from the electrode 133 到 to the next adjacent electrode 1340. This problem is often seen in the prior art (see Transport). Figure 13β depicts a real version of the delivery of the droplet 1350 in Figure 13A to the desired configuration electrode 134. In the process, it is "toothed". The electrode covered by the "region" is excited. The w-shaped electrode 1370 partially covers the left side of the electrode 133, and the gap 136 is arranged to be adjacent to the electrode. As shown in Fig. 13B, "toothed, the electrode plate is disposed. The excitation of the trigger configuration 370 will cause the droplet 1350 to be in. The figure depicts both the completion of the desired configuration of the electrode '', the droplet delivery. After the (iv) 135Q is delivered to the desired configuration 1370, Secondly, the configuration electrode 1340 is energized to perform the (4) transport and transfer of the liquid crystal 1· arrangement and the square view of the electric square. The other real type includes the electrode column excitation manipulation. , much smaller, and in the droplet (10) and two = 1 electrode _, so the droplet volume can not be moved to - an embodiment S paste electrode column excitation: Electrode column excitation. In one implementation: wide excitation electrodes are arranged Including 1x10 electrode. Three bottles "(4) delete the electrode column excitation" as in the U14B marked black part _,, 'and ^ to perform electrode column excitation, but the fine can also be 岐 red 彳 two silent J side In another embodiment, the electrode array of the 〇20 201244825 efficiency has a group electrode column, the width of which is provided for the droplet just = rit. In another embodiment, The length of the column depends on the lang, which is usually as long as possible. Figure 14β illustrates how the three columns of the electrode array are manipulated to facilitate the transport of droplets. ^The first reading of the fit, the recharge, the excitation, the trailing configuration electrode歹U422 is removed for excitation. In this embodiment, regardless of the size of the droplets, the three-column arrangement electrode column always provides the contact line of the largest effective length. As a result, the droplet 1450 can move efficiently and smoothly because the droplet 145 The capillary force on the cymbal is = and is maximized. Therefore, '(4) 丨 can move under the driving power of the driving voltage in the operation of the droplets. The electrode column driving technology is used for Pass ρ at a much lower drive voltage Smooth movement to deliver droplets. Furthermore, due to the consistent capillary forces of this technique, control of droplet velocity (especially in low speed situations) can be achieved by propagating the electrode columns at low speeds. In another embodiment, At the critical drive voltage, the electrode column drive can be applied to drive the droplets. In another embodiment, it has been observed that at a voltage below 8 Vp-p 1 kHz square wave drive voltage and at a gap of 80/zm, The DI water droplets (1.1 mm diameter) are slowly but smoothly moved in i〇cst. In another embodiment, the length of the configured electrode columns can be configured as the total length of the L0C. All invalid droplets (dea(i droplet) in the L0C can be washed away. Figure 14C illustrates that droplets 1450 also move out of configuration electrode 141A while the electrode column (shown in black) in the energized configuration remains moving to the right and eventually moves out of configuration electrode 1410. A diagram UA-15C illustrates one embodiment of performing a typical three-electrode cut of droplets under an EW0D microelectrode array structure. Fig. 15A illustrates three levels of electrodes 1510, 1511 and 1512 arranged in a level. The droplet 1550 to be cut is located at the center of the configuration electrode 151. In Fig. 15A, the configuration electrode 1511 is energized to control the droplet 155. Droplet 1550 overlaps portions of adjacent configuration electrodes 1510 and 1512. Fig. 15 is a view showing a stage of cutting off the droplets by removing the excitation of the arrangement electrodes 1511 by simultaneously energizing the arrangement electrodes 1510 and 1512. The droplets 1550 are pulled to the electrodes 1510 and 1512 in the left-right direction by electrode manipulation. In one embodiment, the two externally configured electrodes 丨51〇 and 1512 induce a hydrophilic force to stretch the droplets while the central hydrophobic force pinches the liquid into 21 201244825 two sub-droplets 1551' and 1552', as shown in the figure 15C is shown. Figures 16A-16C depict one embodiment of droplet cutting. Figure l6A_i6 illustrates three levels of lakes in -_configuration_丨(10), 1611, and 1612. Wait for τα 1611 ^ ° f droplet 1650, using the electrode column drive technology to configure the filter to slowly and firmly pull the droplets, as shown in Figure 16, the two-way Λ^, ί, use and stimulate the two groups The electrode columns 1615 and 1616 are configured to 'color to pull the droplets apart. Each of the two sets of electrode columns is arranged, and us 5 columns of electrodes. Figure ι6Β describes moving in the direction of one by one ^ 5 ίί5〇 ίΐίΐΐ. When the two sets of electrode columns 1615 and ΐ6ΐ6 lead 1650 0 1615 ^1616 ^ electrode cut and the outer edge of 1612, all configurations are electrically removed. The electrode 161 is configured to perform the diagonal cutting electrodes πιο, nu, 1713, and 17t by the lm9 an ^ sub-drops and the stimulators to break the liquid into two. The four configurations are energized, and the configuration electrode mo and the configuration electrode ^electrode 1712 are removed and stretched into the liquid column, as shown in Fig. 7 ,, so the droplet 1750 configuration electrode and the mi _ angle removal excitation are broken. Two sub-droplets, generating the necessary hydrophobic force. Figure 17c illustrates that the L-shaped 'm50 of the electric m50 is re-energized, === since the two pulling electrodes have longer electrode contacts, the diagonal cut of the droplets 22 201244825 is efficient and advantageous. The pulling capillary force on the droplets is lower than the conventional one, which can lower the cutting voltage and can be made even larger. Due to the cutting of the system, it is necessary to exceed the saturation voltage of the electric dust (for example, docking for transmission: relying on the drop ====: to find the South to be more careful, 'so do not exceed Yu and Lai. So = cut the ugly option' In order to keep the cutting voltage low and electric any drop. (4) Cut the job can be cut in the way of robbing in the ew〇d micro-electrode array structure, in the open face 1870^: Χ 2 2 仏 仏 士 士 士 士The liquid column. Next, 'exciting two preselected configuration electrodes 18==: cutting the droplet 1870 and positioning its center to the two thin electrodes i said === Fig. 8C. The coffee key is that there is sufficient overlap between the outer and outer i to have sufficient capillary force to be in a certain embodiment. When the liquid column 1 is cut into a plurality of liquid droplets, the sister passively cuts. The other method and the active cutting are both adopted by the present invention. When the droplet is stretched into two, ij; r, L, when the power or the main power is used to disconnect the starting droplet from the main utilization power, When the length of the liquid column is very heavy, the 'optimized length is not important. Whether it is The dynamic cutting also performs the final step of the cutting process, arranging the electrodes _ and being positioned by 23 1 激 to position the droplets into the desired configuration electrode. In another embodiment, the passive 4 active cutting passes through the surface The microelectrode array structure is performed under the open surface of Open 201244825. Figure 18C illustrates the completion of the cut when the droplet is cut into two sub-liquids 1870. Figures 19A-19B illustrate the basic merging and mixing operations performed under the EW0D microelectrode array structure. One embodiment of the invention. In the present invention, the terms "merging," and "mixing" are used interchangeably to mean a combination of two or more droplets. This is due to & It is not always possible to directly or immediately cause the initial separation of the component(s) of (4) to be completely mixed. In Fig. 19A, two droplets 1950 and 1951 are initially located on corresponding configuration electrodes 1910 and 1912, respectively, and at least one is located therebetween. The configuration electrode j911 is separated. The two droplets 1950 and 1951 are partially overlapped with the centrally disposed electrical 'pole 1911. As shown in Fig. 19B, the excitation is performed on the two configuration electrodes 191 and 1912, and the electrode is placed in the center. Excitation, droplets 195 and 1951 move across each other on central configuration electrode 1911 and then merge into a larger droplet 1953. In the EWOD microelectrode array structure, analyte and reagent mixing is a decisive step. A solid mixing chamber that produces mixing by delivering two droplets to the same 'electrode. Rapid mixing of droplets with minimal space greatly increases productivity. Typically, effective droplet mixing requires 8 (2 x 4) The electrode moves the mixed droplets along the determined path between the 8 electrodes to accelerate the mixing. Therefore, in the mixing operation, there is an urgent need for an effective mixing of droplets that does not require a large space for the mixing operation. the way. However, as the microfluidic device is approaching the alternative nanoliter mode, the reduced volumetric flow rate and very low Reynolds number will make it difficult to achieve liquid mixing within a reasonable time frame. Improving mixing depends on two principles: the ability to create eddy currents in such a small range, or alternatively, the ability to create multiple layers for fast mixing. The EWOD microelectrode array structure provides an order of magnitude active droplet-based mixing that is one order of magnitude faster than passive mixing by diffusion. 20A-20C depict an active mixing process that implements droplet manipulation based on an EWOD microelectrode array structure by non-uniform geometric motion to create eddy currents. As shown in Fig. 2a, the droplets 2050, 2070 can be deformed into a desired shape by manipulating the electrode. As shown in Fig. 2A, the droplets are illustrated as droplets 2051, and droplets 2070' by energizing the arrangement electrodes 2051 and 2071. The excitation center then configures electrode 2060 to pull droplets 2050', 2070 into hybrid configuration electrode 2060 (labeled black) as shown in FIG. p 24 201244825 In Figure 2GBt, the H region indicates the heterogeneous configuration of the heterogeneous (four) and the outline. These energized electrodes can be used to deform the two droplets 2〇5〇, and 2〇7〇, and pull them into the central configuration electrode 2060. The temporary excitation step shown in Fig. 2B also contributes to the smooth mixing movement of the two droplets. The black area of Figure 2B_2〇ct and the shape of the deformed droplets are only for the purpose of Example*. In another embodiment, these shapes may be of any type as needed. A map and 21B depict a microelectrode array mixer for improving the mixing speed. In an embodiment, a non-uniform reciprocating mixer can be used to accelerate the mixing of the droplets. This can be accomplished by energizing a set of microelectrodes to create an irreversible pattern, wherein the irreversible pattern destroys the symmetry of the two loops to improve the mixing speed. The initial state is illustrated in Figure 21A, wherein the droplet 2150 contains the sample and reagent and is located on top of the configuration electrode 2140. The first step for uneven reciprocal mixing is to energize the configuration electrode 2160 to deform the droplet 2150 in the direction of the arrow shown in Figure 21B. Then, the configuration electrode 2160 is de-energized, and the configuration electrode 214 is energized to pull the droplet back to the initial position shown in Fig. 21A. Reciprocating mixing can be performed multiple times to achieve an optimized blending effect. Further, the shapes of the arrangement electrodes 2140 and the deformed droplets in FIGS. 21A and 21B are for illustrative purposes only. In one embodiment, these shapes may be of any type as long as they have the ability to create eddy currents or, alternatively, have the ability to create multiple layers. In another embodiment of the EWOD based droplet mixing process, Figure 22 illustrates a loop mixer for improving mixing speed. This can be accomplished by exciting a sequence of smaller microelectrodes to create an irreversible level loop, where the irreversible level loop destroys the symmetry of the vertical layer loop to accelerate mixing. One embodiment as shown in Fig. 22 is to form eight configuration electrodes (2210, 2220, 2230, 2240, 2250, 2260, 2270, and 2280) surrounding the droplets 2290, and then sequentially align the arrangement electrodes one by one in a loop manner. . For example, 'in the first step, the configuration electrode 2210 is energized for a shorter period of time' to cause a change in surface tension and a loop is generated inside the droplet 2290 on the configuration electrode 2210. Next, the configuration electrode 2210 is de-energized, and then the next adjacent configuration electrode 2220 is energized. The loop excitation process is repeated by all eight configuration electrodes (2210 to 2280) to create a level loop inside the droplet 2290. This 25 201244825 loop current excitation can be performed as needed. In another embodiment, the loop flow can be mixed in a clockwise, counterclockwise or alternate manner to achieve the best mixing effect. In still another embodiment, the shape of the arrangement electrodes 22iq to (4) may be other types and the shape of the shape is only for the purpose of illustration. In this embodiment, the loop mixing may be any winding design as long as they have a generation The ability to vortex, or alternatively, the ability to create multiple layers. In the coherent mode, a mixer of small size (2x2 configuration electrodes) is realized in the EW0D microelectrode array structure to generate multiple layers to accelerate the mixed layer, and the combiner is for low aspect ratio (<1) The situation is especially useful. Aspect ratio refers to the ratio of the gap between the electrode plate and the ground plate to the electrode size. A low aspect ratio means that it is more difficult to generate eddy currents in the liquid slab, and thus the ability to produce multiple layers becomes more important. ® 23A-23E illustrates an embodiment in which diagonal blending and diagonal cutting are utilized. In Fig. 23A, the black droplet 2351 at the arrangement electrode 2314 is mixed with the white droplet 235 在 at the arrangement electrode 2311. The temporary configuration electrode 2310 will become the mixing chamber and will be energized to pull in two droplets 2351 and 235〇. In order to initiate multi-layer mixing, the first step is to merge two droplets along the diagonal. The diagonal direction of the droplets may be 45 degrees or 135 degrees, but then the direction of the diagonal cut needs to be perpendicular to the merge operation. Fig. 23B shows that the first drop of the droplet 2351 and the droplet 2350 becomes black and white droplet 2352. Due to the low Reynolds number and low aspect ratio, the droplet 2352 has a static mixing of simple base = diffusion, which results in a longer mixing time, so the mixed droplets are shown as half white and half black, the second step is The diagonal cut is performed, as shown in Fig. 23C, and the diagonal of the starting droplet 2352 is mixed at 9 degrees. While the temporary placement electrode 2310 is de-energized, the configuration electrodes 2312 and 2313 and other temporary configuration electrodes are energized to cut the droplet 2352 diagonally into two sub-droplets 2353 and 2354, as shown in Fig. 23C. The details of the diagonal cut have been discussed in the previous diagonal cutting process. Due to the low mixing rate, the two sub-droplets 2353 and 2354 maintain a black/white stack in the same orientation after the wire is cut. Then, the third step of multi-layer mixing is to move the two droplets back to the starting configuration electrode to blend and cut diagonally. In Fig. 23D, the droplet 2354 is moved from the arrangement electrode 2312 to the next adjacent arrangement electrode 2311. The droplet 2353 moves from the placement electrode 2313 to the lower 26 201244825 pole 2314. The electrodes 2311 and 2314 can be energized and electronically illuminated. f is to be lying in the miscellaneous to avoid droplets Z can cause two droplets 2353 and 2354 to physically contact at the same time: the latter two droplets may merge together. In one embodiment, the temporary assignments = 15 and 2316 are first energized 'to create a guard zone between the two droplets' to prevent any sound from occurring while the two droplets are moving toward the desired electrode. After the droplet editing and shifting of the electrode coffee and the 2315 towel, a liquid droplet is moved into the arrangement electrodes 2311 and 2314. This process can be repeated to multiply the necessary number of layers at the second rate of productivity. As a repetition from the first - recorded lion =), 2353 and 2354 merged along the diagonal into a liquid (four) coffee. Figure shows the microfluidic operation after the multi-layer mixed loop. Continuous microfluidic operation in the control side of the way to talk about the lack of money for the transfer of sisters. The figure (4) is produced in the figure. Such as = _ bridge 2415. When the bridge 2415 and the target are configured to be electrically charged, the pole 2460 is in the middle. The Terry Bridge is characterized by a micro-electrode line and a droplet-based system. It has all the advantages of the channel ‘; there is, the bridge configuration electrode is energized, the liquid will pass through the consideration. At the same time, it also "== to the liquid receiver i (dead ν〇1·). Once the head: with 7 snow 0 = the liquid filling in the configuration electrode 2460 is automated, that is, the broken bridge ^ configuration斤 = All microelectrodes are filled with liquid, it will stop the fine flow of liquid from the reservoir, because = 27 201244825 j process is not important. Can pass the appropriate (5) break point to accurately control the liquid 2430 The resulting microelectrode 2416 removes the excitation and then removes the excitation from the bridge, and the liquid 2Γ30 ί 10 is disconnected. This process will make sure that most of the liquid that will be bridged will be pulled back to the ΐίϊϋ0 ground solution &24930 will pass through the configuration electrode 2460 The 'electrode' of the microelectrode 2460 includes a number of electrodes, which can define other sizes and shapes of the electrodes to be produced.

寸^狀。圖2C說明液體橋的消失,並且_激= 和配置電極2460產生液體2430。 履a»Z4iU ㈣Ϊ圖24D所示’在一實施方式中,可利用液體的相同產生過 =激勵之後,橋配勵2417和目標配置 ,體從橋流到湖的區域中。對橋配置電極241 勵献 置電極_和2471進行激勵’使得液體斷裂並形 子液體2470和2430 ’如® 24E所示。只要配置電極2461和2471 的尺寸被預先計算為期望的尺寸,這種切割處理就可產生不同尺 寸的兩種子液體。 —在另-實施方式中,圖25A-25C說明通過連續流微流體操作 貫施的混合過程。圖25A說明通過激勵橋2515和2525以及激勵 配置電極2516和2526 ’液體從貯液器2510和252〇經橋流到混合 室2530中。這裡,與配置電極2516和2526相關聯的液體在形狀 上發生改變以便進行更好的混合,此外液體的尺寸也不同以便進 行比例混合(ratio mixing)。在配置電極2516和2526之間具有 間隙,以防止過早混合。一旦液體填滿了配置電極2516和2526, 則配置電極2530 (10x10個微電極)被激勵,兩種液體將被混合, 如圖25B所示。然後,兩個橋電極被去除激勵,如圖25C所示。 〇在這種簡單的混合微流體操作中,實際上所有的基礎微流體 操作被解釋為·( 1)產生:液體2516和2526以精確的方式自貯 液器2510和2520產生;(2)切割:液體2516與液體2510被切 斷,液體2526與液體2520被切斷;(3)輸送:橋2515和2525Inch ^ shape. 2C illustrates the disappearance of the liquid bridge, and the _excitation = and configuration electrode 2460 produces a liquid 2430.履 a»Z4iU (four) 所示 Figure 24D shown in an embodiment, the same can be generated using the same liquid = after the excitation, the bridge with the excitation 2417 and the target configuration, the body flows from the bridge into the area of the lake. The bridge configuration electrode 241 is energized to energize the electrodes _ and 2471 to cause the liquid to break and the liquid liquids 2470 and 2430' are as shown in the ® 24E. This cutting process produces two sub-liquids of different sizes as long as the dimensions of the configuration electrodes 2461 and 2471 are pre-calculated to the desired size. - In another embodiment, Figures 25A-25C illustrate a mixing process that is performed by continuous flow microfluidic operation. Figure 25A illustrates the flow of liquid from the reservoirs 2510 and 252 through the bridges 2515 and 2525 and the excitation configuration electrodes 2516 and 2526' to the mixing chamber 2530. Here, the liquid associated with the configuration electrodes 2516 and 2526 is changed in shape for better mixing, and in addition, the size of the liquid is also different for ratio mixing. There is a gap between the configuration electrodes 2516 and 2526 to prevent premature mixing. Once the liquid fills the configuration electrodes 2516 and 2526, the configuration electrode 2530 (10 x 10 microelectrodes) is energized and the two liquids will be mixed as shown in Figure 25B. Then, the two bridge electrodes are removed and excited as shown in Fig. 25C. In this simple hybrid microfluidic operation, virtually all of the basic microfluidic operations are interpreted as (1) production: liquids 2516 and 2526 are produced from reservoirs 2510 and 2520 in a precise manner; (2) cutting : liquid 2516 and liquid 2510 are cut, liquid 2526 and liquid 2520 are cut; (3) transport: bridges 2515 and 2525

28 201244825 將液體輸送到混合室:以芬 處混合。很明顯,這種合推液體_和㈣在2530 小尺寸微電極。、月確的方式執行,因為精度的解析度取決於 在本ί明 =實中施的理上可以不同的方式實施。 中之-被突出顯示為f脱描述了方形微電極陣列,且其 個f極形成配置電極26t4、,中在^== 6 旁㈣在又實知方式中,圖26c 中的方形微電極的陣列,其中的一 ^=局 六邊形微電極的交叉翻邊緣在沿著配置電極之間 有優勢,但這只發生在χ轴上。還可實酿 微電極三而不僅限於這裡所討論的三種形狀。 、/狀的 儘管已經參照優選實施方式描述了本發明, 人員,意識到,在不脫離本發明的精神和範 和細卽上作出各種改變。 J在^/式 【圖式簡單說明】 圖1Α是概括說明常規的夾置的EW〇D系統的橫截面 圖1B是概括說明在二維電極陣列上的常規抓⑽ 圖2是說明微電極陣列的圖,其中微電極陣列中的^ ^搞 (configured-electrode)可被配置成各種形狀和尺寸。 p 3A疋不同形狀的配置電極和利用微電極陣列結構的[ο。 局的不意圖; w 圖3B是傳統的物理钱刻的結構的圖; 圖3C是配置電極的圖,其中說明貯液器和配置電極的放大部 29 201244825 分。 圖4是朗混合彡、赌構_,射混合 =積可調節的並且透明的頂板’用以適應最寬範圍⑽ 圖5A、5B和5C是說明接地網(gr〇undgrid)共面钍 =和6B是接地焊盤(ground _)的共“益:圖, ^ A曰、7B和7C是可程式料接地職的共面結構=: 圖8疋說明混合板的圖; 罔’ 圖9A、9B和9C說明樣品的载入; 圖9D和9E說明載入的樣品在貯液器上自定 圖10是說明在EW0D微電極陣列結構下產生液目仃疋位); 圖11A是說明利用液滴等分技術產生液滴的圖;固, 圖11B是說明通過液滴等分技術製備樣品的圖; 圖12是說明基於膽微電極陣列結構進行液 方向被激勵的能力的圖; 】之和&所有 圖13A、13B和13C是說明利用基於Ε_微電極 時橋接技術輸送液滴的圖; 早構的 圖14A、14B和14C是說明在_微電極陣歹 列激勵的圖; 再<卜的電極 割的^咖15B和^是說明基於麵微電極陣列結構的液滴切 確切^圖獅脱說明基於麵微電極陣列結構的液滴的精 圖17A、17B、17C和17D是說明基於_微 液滴的對躲切_圖; w I桃σ構的 面切圖1齡18C是說明基於膽微電極陣列結構的液滴共 、人圖19A和19B是說明基於_微電極陣列結構的兩液滴合併/ 混合的圖; 圖2〇A、2〇B和20C是說明基於讎微電極陣列結構通過非均 30 201244825 勻幾何移動來實現液滴快速混合的圖; EW〇D ^ 圖22疋顯不基於麵微電轉列結構的迴圈混合器是示音 圖; 〜 圖23A、23B、23C、23D、23E和23F是說明基於EW0D微電極 陣列結構的多層混合器的圖; 圖24A、24B和24C是通過連續流的激勵以說明產生液滴的圖; 圖24D和24E是通過練習流驅動切割流體的說明圖示; 圖25A、25B和25C是通過連續流驅動的液滴合併/混合的圖示; 圖26A說明方形微電極陣列;圖26β說明六邊形微電極陣列; 以及 圖26C說明佈置在牆碑佈局中的方形微電極的陣列。 【主要元件符號說明】 100微流體元件 120、121玻璃底板 121下底板 130可控電極 140地電極 160疏水膜 170介電絕緣體 180、371、372、720、730、1030、1035、1410、1411、2604、 2606電極 200電極陣列200 210、311、510、520、52卜 610、710、1140、2416、2605 微電極 220、230、240、260、270、760、76卜 762、763、790、 1040、1120、123卜 1232、1233、1234、1235、1237、1239、1260、 1330、1340、1370、1510、15U、1512、1610、16Η、1612、1615、 31 201244825 1616、1710、17U、1712、1713、1714、1715、1716、1820、1840、 1910、1911、1912、205卜 2071、2060、2140、2160、2210-2280、 2310、23Η、2312、2313、2314、2315、2316、2417、2460、2461、 2471、2516、2526、2530、2601、2602 配置電極 150、15卜 152、250、430、440、450、540、54iL、550、65卜 750、75卜 752、940、95卜 952、953、1050、1115、1130、1145、 1150、1160、1250、1350、1450、1550、1551’ 、1552’ 、1650、 1651、1652、1750、175卜 1752、1850、1870、1950、195卜 1953、 2050、2070、2050’ 、2051’ 、2060、2070’ 、2150、2290、2350、 2351、2352、2353、2354、2355、2356 液滴 320、330、33卜 332、920、941、1015、1030、2410、2510、 2520貯液器 340輸送路徑 350檢測視窗 360、2530混合室 410頂板 420電極板 511、531 地線 515、615、715、1170、1360 間隙 611接地焊盤 711、840地電極 740箭頭 810開關 820蓋板 821電極板 880接地網 915頂板 910輸入璋 930試劑 950樣品28 201244825 Transport liquid to the mixing chamber: Mix in fen. It is obvious that this combination of liquid _ and (d) is in the 2530 small size microelectrode. The implementation of the monthly method, because the resolution of the accuracy depends on the implementation of this method can be implemented in different ways. Among them, the square microelectrode array is described as being f, and its f pole forms the configuration electrode 26t4, which is in the vicinity of ^==6 (4). In a known manner, the square microelectrode in Fig. 26c The array, in which one of the intersecting edges of the hexagonal microelectrodes, has an advantage along the configuration electrode, but this only occurs on the x-axis. It is also possible to brew the microelectrode three without being limited to the three shapes discussed herein. The present invention has been described with reference to the preferred embodiments thereof, and it is appreciated that various changes may be made without departing from the spirit and scope of the invention. J is in the form of a simple description of the drawing. Fig. 1A is a cross-sectional view schematically showing a conventional sandwiched EW〇D system. Fig. 1B is a schematic view showing a conventional grasping on a two-dimensional electrode array (10). Fig. 2 is a view showing a microelectrode array. The figure in which the configured-electrode in the microelectrode array can be configured in various shapes and sizes. p 3A 疋 differently shaped configuration electrodes and utilizing the microelectrode array structure [ο. Figure 3B is a diagram of a conventional physical engraving structure; Figure 3C is a diagram of a configuration electrode illustrating an amplifying portion of the reservoir and the configuration electrode 29 201244825 points. Figure 4 is a mixture of 彡, _ _, shot mixing = product adjustable and transparent top plate 'to accommodate the widest range (10) Figure 5A, 5B and 5C is a description of the ground grid (gr〇undgrid) coplanar 钍 = and 6B is the common ground of the ground pad (ground _): Figure, ^ A 曰, 7B and 7C are coplanar structures of the programmable grounding == Figure 8疋 illustrates the diagram of the hybrid board; 罔' Figure 9A, 9B And 9C illustrate the loading of the sample; Figures 9D and 9E illustrate that the loaded sample is self-determined on the reservoir. Figure 10 is a view showing the formation of liquid mesh under the EW0D microelectrode array structure; Figure 11A is a diagram illustrating the use of droplets. The aliquot technique produces a map of the droplets; solid, FIG. 11B is a diagram illustrating the preparation of the sample by the droplet halving technique; FIG. 12 is a diagram illustrating the ability of the liquid direction to be excited based on the biliary microelectrode array structure; 13A, 13B, and 13C are diagrams illustrating the use of the Ε-microelectrode-based bridging technique to deliver droplets; the early configurations of Figures 14A, 14B, and 14C are diagrams illustrating the excitation of the _microelectrode array; < The electrode cutting of the electrode 15B and ^ is to illustrate the droplet cutting based on the surface microelectrode array structure. The fine images 17A, 17B, 17C, and 17D of the droplets based on the surface microelectrode array structure are illustrative of the _ microdroplet-based occlusion graph; the surface morphogram of the w I peach σ structure is shown in Fig. 1 FIG. 19A and FIG. 19B are diagrams illustrating the merging/mixing of two droplets based on the _microelectrode array structure; FIGS. 2A, 2B and 20C are diagrams illustrating the structure based on the 雠 microelectrode array Non-uniform 30 201244825 Plane moving to achieve rapid mixing of droplets; EW〇D ^ Figure 22 shows the loop mixer not based on the surface micro-electrical structure is a sound map; ~ Figure 23A, 23B, 23C, 23D 23E and 23F are diagrams illustrating a multilayer mixer based on the EW0D microelectrode array structure; Figs. 24A, 24B and 24C are diagrams illustrating the generation of droplets by excitation of a continuous flow; Figs. 24D and 24E are driving fluids driven by a flow of practice 25A, 25B, and 25C are diagrams of droplet merging/mixing by continuous flow driving; FIG. 26A illustrates a square microelectrode array; FIG. 26β illustrates a hexagonal microelectrode array; and FIG. 26C illustrates An array of square microelectrodes in a wall monument layout. DESCRIPTION OF SYMBOLS] 100 microfluidic element 120, 121 glass bottom plate 121 lower bottom plate 130 controllable electrode 140 ground electrode 160 hydrophobic film 170 dielectric insulator 180, 371, 372, 720, 730, 1030, 1035, 1410, 1411, 2604, 2606 electrode 200 electrode array 200 210, 311, 510, 520, 52 610, 710, 1140, 2416, 2605 microelectrode 220, 230, 240, 260, 270, 760, 76 762, 763, 790, 1040, 1120 , 123 1232, 1233, 1234, 1235, 1237, 1239, 1260, 1330, 1340, 1370, 1510, 15U, 1512, 1610, 16Η, 1612, 1615, 31 201244825 1616, 1710, 17U, 1712, 1713, 1714 , 1715, 1716, 1820, 1840, 1910, 1911, 1912, 205, 2071, 2060, 2140, 2160, 2210-2280, 2310, 23Η, 2312, 2313, 2314, 2315, 2316, 2417, 2460, 2461, 2471 215, 2526, 2526, 2530, 2601 1115, 1130, 1145, 1150, 1160, 1250, 1350, 1450, 1550, 1551', 1552', 1650, 1651, 1652, 1750, 175, 1752, 1850, 1870, 1950, 195, 1953, 2050, 2070, 2050', 2051', 2060, 2070', 2150, 2290, 2350, 2351, 2352, 2353, 2354, 2355, 2356 Droplets 320, 330, 33, 332, 920, 941, 1015, 1030, 2410, 2510, 2520 reservoir 340 transport path 350 detection window 360, 2530 mixing chamber 410 top plate 420 electrode plates 511, 531 ground lines 515, 615 , 715, 1170, 1360 gap 611 ground pad 711, 840 electrode 740 arrow 810 switch 820 cover 821 electrode plate 880 grounding grid 915 top plate 910 input 璋 930 reagent 950 sample

32 201244825 970共面電極板 980無源蓋 1180血細胞 1420、1421、1422、1615、1616 電極列 1860液體柱 2470、2430、2516、2526 液體 2415 、 2515 、 2525 橋 2603微電極陣列 3332 201244825 970 coplanar electrode plate 980 passive cover 1180 blood cells 1420, 1421, 1422, 1615, 1616 electrode column 1860 liquid column 2470, 2430, 2516, 2526 liquid 2415, 2515, 2525 bridge 2603 microelectrode array 33

Claims (1)

201244825 七、申請專利範圍: 操縱可程雜計圓D微雜陣列中 置微電極構成的陣列的底板,所述微電極設 =2=層覆盖的基板的頂表面;其中,每個微電極與接 二一個接地兀件連接;其中在介電絕緣層和接地元 件的今巧置有疏水層,以形成與液滴疏水的表面; μ 多個微電極魏置—組配置賴來產生微流體 的形狀和大小佈局,其中所述-組配置電極 铺第η置電極’其包括陣列佈置的多個微電極;以及至少 其與該第—配置電極相鄰;所述液滴設 以及置電極的頂部並且與第二相鄰配置電極的部分重疊; 定的驅動電壓激誠去除激勵—個或多個選 ^沿選定的雜義,麵料他置電極之咖-個或多ξ 減L、-如清Ί1所述的方法,更包括操縱配置電極的多個微電 極的數罝,以控制液滴的尺寸和形狀。 π佩电 電極3。、如請求項2所述的方法,其中所述配置電極包括至少一微 元件其中所述一組配置電極的麵 滴路經和指定功能電極/"σ至、檢測視窗、廢棄物貯存器、液 於入5/21求,4=述的方法’其中所述微流體元件的佈局包括 :二和電i二:J分:合室、檢測窗口、廢棄物貯存器、 操縱可程_ E_電極陣列中 (a)構建包括多個微電極構成的陣列的底板,所述微電極設201244825 VII. Patent application scope: Manipulating the bottom plate of the array formed by the microelectrodes in the D-micro-array array, the micro-electrodes are set = 2 = the top surface of the substrate covered by the layer; wherein each micro-electrode Connecting two grounding members; wherein the dielectric insulating layer and the grounding member are provided with a hydrophobic layer to form a surface hydrophobic with the droplet; μ plurality of microelectrodes are disposed to form a microfluid Shape and size layout, wherein the -group configuration electrode lays an n-th electrode' comprising a plurality of micro-electrodes arranged in an array; and at least adjacent to the first-arrangement electrode; the droplet arrangement and the electrode The top portion and the portion of the second adjacent configuration electrode overlap; the predetermined driving voltage is violently removed from the excitation - one or more selections along the selected ambiguity, and the fabric is placed on the electrode - one or more 减 minus L, - The method of cleaning 1 further includes manipulating the number of microelectrodes of the configuration electrode to control the size and shape of the droplets. π electric electrode 3. The method of claim 2, wherein the configuring electrode comprises at least one micro-element, wherein the set of configuration electrodes has a surface drip path and a designated functional electrode/"σ to, a detection window, a waste reservoir, The solution is in 5/21, 4=the method described] wherein the layout of the microfluidic component includes: two and electric i: J: room, detection window, waste storage, manipulation process _ E_ In the electrode array, (a) constructing a bottom plate including an array of a plurality of microelectrodes, the microelectrode 34. 201244825 置在由介魏緣層覆蓋的基板的 地元件連接,·其中^電二= 疏水層,以形成與液滴疏水的表面; 元件,並/ίίίίΓ微電極魏置—絲產生微流體 牛、’按…、、疋的形狀和大小佈局,其中所述一袓配置帝搞 1笛第Π己置電極,其包括陣列佈置的多個微電極;以及i少 電極,其與該第—配置電極相鄰;所述:i 置在第-配置電極_部並錢第二相鄰配置電極崎分重疊; ⑹料-配置電極去除激勵,輯第二柳配置電極進 激勵以將液滴從第-配置電極拉動到第二配置電極;以及 —(d)通過順序地施加驅動電壓激勵或去除激勵一個或多個選 j配極來順序地激勵或去除激勵所敎的配置電極以驅動 液滴沿k定的路徑移動,來操縱多個配置電極之間的一個或 液滴。 ,7、如請求項6所述的方法,更包括通過利用三個配置電極分 裂所述液滴,其巾在處於巾㈣第—配置電極上絲的液滴大致 與兩個第二相鄰配置電極重疊,包括: 、(〇配置兩個臨時配置電極,所述臨時配置電極包括覆蓋裝 載於該第一配置電極上的液滴的多條微電極線; (ii)激勵所述的兩個臨時配置電極; fiii)逐行地激勵以朝著所述兩個第二相鄰配置電極方向移 動,並且對與中心最接近的線去除激勵,以大致朝著所述兩個第 二相鄰配置電極拉動液滴;以及 (iv)去除激勵兩個臨時配置電極,激勵所述兩個第二相鄰配 置電極。 8、如請求項6所述的方法’更包括通過利用三個配置電極分 裂所述液滴,其中液滴裝載在處於中心的第一配置電極上,並且 兩個相鄰配置電極不與液滴重疊,包括: (a)配置兩個臨時配置電極’所述臨時配置電極包括覆蓋裝 載於該第一配置電極上的液滴的多條微電極線; 35 201244825 (b) 激勵所述的兩個臨時配置電極; (c) 逐行地激勵以朝著兩個所述第二相鄰配置電極移動, 且對與中心最接近的線去除激勵,以大致朝著兩個所述第二. 配置電極拉動液滴;以及 # (d) 去除激勵兩個臨時配置電極,激勵所述兩個第二 置電極。 π 9、 如請求項6所述的方法,更包括通過利用三個配置 裂,述液滴,其中在處於中坤第—配置電極上对的液滴 個弟-相鄰配置電極部分地重疊,包括: (i) 去除激勵第一配置電極;以及 液商(ii)激勵所述兩個第二相鄰配置電極從而大致拉動和切割 10、 如請求項7所述的方法,更包括沿對角線分裂液滴, 括: l (0將液滴設置在第一配置電極上; (ii) 對所述第一配置電極去除激勵,並對與所述第一配 重疊的兩個沿對角線佈置的第二相鄰配置電極進行激 朝著兩個沿對角線佈置的所述第二相鄰配置電極拉動液滴;以及 (111)對所述第一配置電極與兩個沿對角線佈置的所述m _ =配置電極之間的重疊區域去除激勵,以將麵峽為兩個子 中,^括如請求項6所述的方法,更包括將液滴重定位到貯液器 都八產生臨時配置電極,其中該臨時配置電極與貯液器的-冲刀重i,並且液滴的一部分不與所述貯液器重疊; 器至重該=配及置電極,以拖動液滴,使液滴與所述貯液 «將’並麟猶液料行激勵, 12、一種在包括多個微電極的可程式設計EW〇D微電極陣列中34. 201244825 is placed on the ground element of the substrate covered by the interlayer of the Wei-Wei layer, where ^^2 = hydrophobic layer to form a surface that is hydrophobic with the droplets; component, and /ίίίίΓ micro-electrode Wei-filament to produce micro-fluid cattle Layout according to the shape and size of the ..., 所述, 所述 帝 搞 搞 1 1 1 1 1 1 1 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , The electrodes are adjacent; the: i is placed in the first-configured electrode portion and the second adjacent configuration electrode is overlapped; (6) the material-disposing electrode removes the excitation, and the second will configure the electrode to be excited to move the droplet from the first Configuring the electrode to pull to the second configuration electrode; and - (d) sequentially energizing or removing the energized configuration electrode to drive the droplet edge by sequentially applying a driving voltage excitation or removing the excitation one or more selected j-poles The path of k is moved to manipulate one or a droplet between a plurality of configuration electrodes. 7. The method of claim 6, further comprising splitting the droplet by using three configuration electrodes, the droplet of the towel on the first (disposed) electrode of the towel (four) being substantially adjacent to the two second adjacent configurations The electrodes overlap, comprising: (〇 configuring two temporary configuration electrodes, the temporary configuration electrode comprising a plurality of microelectrode lines covering the droplets loaded on the first configuration electrode; (ii) exciting the two temporary Configuring electrodes; fiii) exciting row by row to move toward the two second adjacent configuration electrodes, and removing excitation from the line closest to the center to substantially align toward the two second adjacent configuration electrodes Pulling the droplets; and (iv) removing the excitation of the two temporary configuration electrodes, energizing the two second adjacent configuration electrodes. 8. The method of claim 6 further comprising splitting the droplet by utilizing three configuration electrodes, wherein the droplet is loaded on the first configuration electrode at the center, and the two adjacent configuration electrodes are not associated with the droplet Overlapping, comprising: (a) configuring two temporary configuration electrodes 'the temporary configuration electrode comprising a plurality of microelectrode lines covering droplets loaded on the first configuration electrode; 35 201244825 (b) stimulating the two Temporarily arranging the electrodes; (c) exciting the rows one by one to move toward the two of the second adjacent configuration electrodes, and removing the excitation from the line closest to the center to substantially align the electrodes toward the two of the second. Pulling the droplets; and # (d) removing the excitation of the two temporary configuration electrodes, energizing the two second electrodes. π 9. The method of claim 6, further comprising: by using three configuration cracks, wherein the droplets are partially overlapped, and wherein the droplets in the Zhongkang-configuration electrode are partially overlapped, Included: (i) removing the excitation first configuration electrode; and liquid quotient (ii) exciting the two second adjacent configuration electrodes to substantially pull and cut 10, as described in claim 7, further including diagonally a line splitting droplet, comprising: l (0 sets the droplet on the first configuration electrode; (ii) removing the excitation from the first configuration electrode, and two diagonal lines overlapping the first alignment Arranging a second adjacent configuration electrode to excite the droplets toward the two second adjacent configuration electrodes arranged diagonally; and (111) pairing the first configuration electrode with two diagonal lines The m _ = arrangement of overlapping regions between the electrodes removes the excitation to have the face gorge into two sub-ranges, including the method of claim 6, and further includes relocating the droplets to the reservoir Eight produces a temporary configuration electrode, wherein the temporary configuration electrode and the reservoir - punch Heavy i, and a portion of the droplet does not overlap with the reservoir; the device is heavy to the counter = the electrode is placed to drag the droplet, so that the droplet and the liquid reservoir «will be combined with the liquid Excitation, 12, in a programmable EW〇D microelectrode array comprising a plurality of microelectrodes 36 201244825 操縱液滴的方法,該方法包括: 要士 構建包括多個微電極構成的陣列的底板,所述微電極設 ^在由;I f絕緣層覆蓋的基板的職面;其中,每個微電極與接 =構中的至少-健地元件連接;其巾在介和接地元 牛的上部設置有疏水層,以形錢絲疏水的表面; (b)操縱所述多個微電極則&置—組配置電極來產生微流體 ίί ·’ ΐ且按照選定的形狀和大小佈局,其巾所述—組配置電極 匕f够第—配置電極’其包括陣列佈置的多個微電極;以及至少 二相鄰配置電極’其與該第—配置電極相鄰;所述液滴設 置在第-配置雜的頂部纽與第二相鄰配置電極的部分重疊; (C)配置不與該第一配置電極上的液滴重疊的第三相鄰配 置電極,以及 1,(Ϊί過f序地施加驅動電壓激勵或去除激勵一個或多個選 j配^電極來順序地激勵或去除激勵所選定的配置電極以驅動 選糾路徑移動’來操縱多個配置電極之間的—個 液滴。 法,=中Γί求項12所述的方法,更包括沿對角線移動液滴的方 配置ϋ鼓與部分液難疊的科配置馳,和產生第三相鄰 來將除第一配置電極和激勵該臨時配置電極 對角線輸送到所述第三相鄰配置 極。(出)去除激勵該臨時配置電極’並激勵該第三相鄰配置電 方法其項12所述的方法,更包括沿所有方向移動液滴的 ⑴產生與部分液滴重疊的臨時配置電極,和產生第三相鄰 37 201244825 配置電極; _ ( ii)通過去除激勵該第一配置電極和激勵該臨時配置電極 來將液滴從該第一配置電極輸送到該第三相鄰配置電極上;以及 (11〇去除激勵該臨時配置電極,並激勵該第三相鄰配置電 極。 16、如請求項6所述的方法,更包括共面分裂的方法,其中 包括: (i) 配置與液滴重疊的薄帶式臨時配置電極; (ii) 去除激勵該第一配置電極並激勵該薄帶式臨時配置電 極; (ill)去除激勵該臨時配置電極;以及 (iv)激勵第一配置電極和該第二相鄰配置電極。 Π、如請求項6所述的方法,更包括通過利用三個配置電極 將兩液滴合併的方法,其中兩個第一配置電極被該第二相鄰配置 電極分隔開,包括: (i) 去除激勵所述兩個第一配置電極;以及 (II) 激勵中間的該第二相鄰配置電極。 18、如請求項17所述的方法,更包括變形混合的方法,包括: (〇產生兩個臨時配置電極以使兩個液滴的形狀變形; (ii) 去除激勵所述兩個第一配置電極,並激勵所述兩個 時配置電極;以及 (III) 去除激勵所述兩個臨時配置電極並激勵中間的 相鄰配置電極。 琢第一 19、如請求項6所述的方法,更包括通過使 加速液_部混合的綠,其巾包‘ ①狀义形來 Ο)產生該臨時配置電極以使液滴形狀變形; 以 及 (ii)去除激勵該第一配置電極並激勵該臨時配置電極; (Hi)去除激勵該臨時配置電極並激勵該第一配置電極 iv)重複對該臨時配置電極和該第一配置電極的去除激勵36 201244825 A method of manipulating a droplet, the method comprising: constructing a bottom plate comprising an array of a plurality of microelectrodes, the microelectrodes being disposed on a surface of a substrate covered by an insulating layer; The microelectrode is connected to at least the geotechnical element in the structure; the towel is provided with a hydrophobic layer on the upper part of the grounding and the grounded bull to form a hydrophobic surface; (b) manipulating the plurality of microelectrodes Setting the electrodes to produce microfluids ' ΐ 布局 ΐ 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照At least two adjacent arrangement electrodes 'which are adjacent to the first-arrangement electrode; the droplets are disposed at a portion of the first-position impurity top and the second adjacent arrangement electrode; (C) the configuration is not the first Configuring a third adjacent configuration electrode on which the droplets on the electrode overlap, and 1, (using a driving voltage excitation or removing the excitation one or more selected electrodes to sequentially excite or remove the excitation selected Configuring electrodes to drive The correcting path moves to manipulate a droplet between the plurality of configuration electrodes. The method of claim 12, wherein the method of moving the droplet along the diagonal line configures the drum and the partial liquid stack And arranging a third adjacent to deliver the diagonal of the first configuration electrode and the excitation of the temporary configuration electrode to the third adjacent configuration pole. (Exiting the excitation of the temporary configuration electrode 'and exciting The method of item 12, further comprising: moving the droplets in all directions (1) generating a temporary configuration electrode overlapping with a portion of the droplets, and generating a third adjacent 37 201244825 configuration electrode; _ ( Ii) transporting droplets from the first configuration electrode to the third adjacent configuration electrode by removing the excitation of the first configuration electrode and exciting the temporary configuration electrode; and (11) removing the excitation of the temporary configuration electrode and exciting The third adjacent configuration electrode. The method of claim 6, further comprising a method of coplanar splitting, comprising: (i) configuring a thin strip temporary configuration electrode overlapping the droplet; (ii) removing Exciting the first configuration electrode and exciting the thin strip temporary configuration electrode; (ill) removing the temporary configuration electrode; and (iv) exciting the first configuration electrode and the second adjacent configuration electrode. Π, as in claim 6 The method further includes a method of merging two droplets by using three configuration electrodes, wherein the two first configuration electrodes are separated by the second adjacent configuration electrode, comprising: (i) removing the excitation of the two The first configuration electrode; and (II) the second adjacent configuration electrode in the middle of the excitation. 18. The method of claim 17, further comprising the method of deforming mixing, comprising: (〇 generating two temporary configuration electrodes to Deforming the shape of the two droplets; (ii) removing the excitation of the two first configuration electrodes and stimulating the two when the electrodes are configured; and (III) removing the excitation of the two temporary configuration electrodes and exciting the middle Arrange the electrodes adjacent to each other. The method of claim 6, further comprising: generating the temporary arrangement electrode to deform the shape of the droplet by causing the accumulating liquid to be mixed with green, the towel package is shaped like a 1 shape; (ii) removing the excitation of the first configuration electrode and exciting the temporary configuration electrode; (Hi) removing the excitation of the temporary configuration electrode and exciting the first configuration electrode iv) repeating the removal excitation of the temporary configuration electrode and the first configuration electrode 38 201244825 和激勵。 加速括通過使液滴内部迴圈來 ⑴產^多舰時配置電極以環驗滴;以及 方法,包ΪΓ切6所述的方法,更包括產生賴的多層混合的 個第=)置1料雜_極,包卿—嫩置上的兩 電極ω)產生位於所述2χ2陣列的配置電極的中心的臨時配置 第一酉極_勵,絲自所述兩個 上的t ΐΐΐΞΐ電極去除激勵,並對在第二對角位置 二液ί)對所述臨時配置電極去除激勵,靖液滴_成兩個第 第 外的臨時配置電極進行激勵將兩個所述 =所述額外的臨時配置電極去除激勵並對在所述I 一對 上的兩個第—配置電極進行激勵,以完成輸送;㈣對角位置 第—激勵,以合併來自兩個所述 (V111)重複對角線分裂、輸送和對角線合併。 3、如請求項6所述的方法,更包括塑造液滴的方 (1)在所述貯液器中配置第一臨時配置電極·, (1〇自裝載有液體的貯液器配置相鄰配置電極線·, 39 201244825 (iii) 產生與所述貯液器中的液體重 配置電極重疊的第二臨時配置電極; 、,、取近的相鄰 (iv) 對所述第一臨時配置電極進行激勵; (v) 對所述第二臨時配置電極去除激並 置電極進行激勵;以及 並對最近的相鄰配 f前一被激勵的相鄰配置電極去除激勵,並對後庠π 中的,-相鄰配置電極進行激勵,直到產生液滴為止。博序列 生二=求:所述的方法,更包括利用液滴等分技術來產 (i) 產生用於期望液滴尺寸的目標配置電極; (ii) 自裝載有液體的貯液器配置小尺寸相 ==到所述目標配置電極,其中所述小電 極線的兩埏與所述貯液器和所述目標配置電極重疊; 電 (III) 對所述目標配置電極進行激勵; (IV) 沿著從貯液器側到所述目標配置電極的路徑,一 載有微等分液滴的每一個小尺寸相鄰配置電極進 订激勵和去除激勵;以及 适 、、(V)重複小尺寸相鄰配置電極的激勵和去除激勵順序,以 所述目標配置電極中產生期望的液滴。 25、 如請求項24所述的方法,更包括執行預先計算 分液滴的數量的步驟。 ^ 26、 如請求項6所述的方法,更包括糊液料分技術計算 裝载在所述第-配置電極上的液滴的體積的方法,包括: (i)產生存儲配置電極; (1〇在所述第一配置電極的内部配置臨時配置電極; (111)自裝載有與所述存儲配置電極連接的液滴的第一配置 1極配置小尺寸相鄰配置電極線,其中所述小尺寸相鄰配置電極 線的兩端與所述第一配置電極和所述存儲配置電極重疊; Civ)對所述臨時配置電極進行激勵; Cv)對所述存儲配置電極進行激勵; 201244825 電極進行激勵和去除激勵;以及 )母個小尺寸相鄰配置 計算戶 配置電極的激勵和去除激勵順序,以 緣=、、十-t請求項12所述的方法’更包括利用所述第-配置带搞 置‘電極包括所述第三相鄰配 進行i); ΪΓ第—配置電極去除激勵,並對所述橋配置電極 電極额s_極絲絲,並酬蜂三相鄰配置 的方^ =求項6所述的方法,更包括利用列激勵來移動液滴 (i)配置包括多列微電極的列配置電極;以及 和去軸娜行激勵 有己置電極包括多列微電極並具 (11 )通過沿著目標方向對所述列配置電極的 =激勵’來沖撕述舰置電極上的所有殘留液滴。 =、如請求項6所述的方法,其中貯液器財液體。 懈尺生不同 υ配置用於期望液體尺寸和雜的目標配置電極 •i)配置橋配置電極,所述橋配置電極包括微電極線並連 41 201244825 接到所述貯液器和所述目標配置電極; 及(山)對所述橋配置電極和所述目#配置電極進行激勵;以 最近橋f置電極的、與所述目標配置電極 32、如=3^ +勵’來對所述橋配置電極去除激勵。 和分f比ί述的方法,更包括利用連續流以受控尺寸 體二=將液體分裂搞種子㈣的方法,其情液器裝載有液 狀的第樓崎—侧尺寸和形 標配配置具有紋義的第二子液體尺寸和形狀的、第二目 (VI)對所述第一目標配置電極進行激勵。 ㈣6所賴方法,更包括利料續如受控尺寸、 包括和。併比來合併兩種液_方法,其愤液器裝載有液體, (i)配置混合配置電極; 第二目所述混合配置電極重疊的第-目_ 搞綠in配置第—橋配置電極’所述第—橋配置電極包括微雷 極線並連接_述第-目標配置電極和第-液體源 L括微電 ㈣ϋ配置第二橋配置電極’所述第二橋配置電極包括科雷 極線並連接到所述第二目標配置電極和第二液源匕括微電 第一目一橋酉1置巧和戶斤述第二橋配置電極以及所述 第目私配置電極和所述第二目標配置電極進行激勵· (vi)對所述第一橋配置電極和所述第二橋配置電極去除激 42 201244825 勵;以及 (νι〇對所述混合配置電極進行激勵。 構的mi項1所述的方法,其中所述接地機構在雙平面結 底板之間具^隙所述頂板位於底板上方並且在所述頂板與所述 職:法,其中所述接地機構為具有無源 網的求項1所賴錢,其情述接地機構為具有接地 焊盤1麟的綠,其情述躺結縣具有接地 38、如請求項}所述的方法, 設計的接地焊_共面結構。 娜為具杨式 制求項1所述的方法’其情述接地機構為利用可選 擇開關將雙平通構與共面結構組合的混合結構。 ^ 器中4的0方^請=:6所述的方法’更包括將液體裝載到所述貯液 (0將液體襄載到共面結構上;以及 (ii)在液體上放置無源蓋。 4卜如請求項1所述的方法,更包括適應寬範圍的、且 ^尺’其中該接地機構在雙平面結構的頂 k該頂板位於底板社方且它們之間具有間隙;包括: ,(1 置^所述頂板與所述底板之間的間隙距離的高度· (⑴配置所述配置電極的尺寸,以控制液滴的 ^ 滴接觸所述頂板和所述底板;以及 使液 、(iii)、配置所述配置電極的尺寸,以控制液滴的尺寸 滴僅接觸所述底板。 使液 ϋίΐίΐ 1所述的方法’其中所述微電極可以以陣列料 佈置為大致圓形、方形、六邊蜂窩狀或疊碑形。皁歹冰式 4338 201244825 and incentives. Acceleration includes the method of arranging the electrode to loop back by (1) arranging the electrode during the production of the multi-ship; and the method of the method of the splicing, and the method of the multi-layer mixing a plurality of electrodes ω) on the matte-initial arrangement to generate a temporary configuration of the first drain _ excitation at the center of the arrangement electrode of the array of 2 χ 2, the filaments being de-energized from the two tw-electrodes on the two And exciting the temporary configuration electrode at the second diagonal position, and exciting the two temporary externally disposed electrodes to the two of the additional temporary configuration electrodes The excitation is removed and the two first-arranged electrodes on the pair of I are energized to complete the transport; (iv) the diagonal position first-excited to combine the diagonal splitting and transport from the two (V111) repeats Combined with the diagonal. 3. The method of claim 6, further comprising: shaping the droplets (1) arranging the first temporary configuration electrode in the reservoir, (1) from the reservoir with the liquid being placed adjacent to the reservoir Configuring Electrode Wires, 39 201244825 (iii) generating a second temporary arrangement electrode overlapping the liquid reconfiguration electrode in the reservoir; ,, approaching adjacent (iv) to the first temporary configuration electrode Exciting; (v) exciting the second temporary configuration electrode removal excitation parallel electrode; and removing the excitation from the nearest adjacent configuration of the adjacent excitation element, and after 庠π - Adjacently arranged electrodes are energized until droplets are generated. The method described further includes the use of droplet halving techniques to produce (i) generating target configuration electrodes for desired droplet sizes. (ii) a reservoir from which the liquid is loaded is configured with a small size phase == to the target configuration electrode, wherein two turns of the small electrode line overlap the reservoir and the target configuration electrode; III) stimulating the target configuration electrode (IV) along the path from the reservoir side to the target-arranged electrode, each small-sized adjacent configuration electrode carrying micro-aliquoted droplets is programmed to excite and remove excitation; and (V) Exciting and removing the excitation sequence of the small-sized adjacent configuration electrodes to generate the desired droplets in the target configuration electrode. 25. The method of claim 24, further comprising the step of performing pre-calculation of the number of droplets The method of claim 6, further comprising a method for calculating a volume of a droplet loaded on the first-arrangement electrode by a paste liquid fraction technique, comprising: (i) generating a storage configuration electrode; Disposing a temporary arrangement electrode inside the first arrangement electrode; (111) arranging a small-sized adjacent arrangement electrode line from a first configuration 1 pole loaded with droplets connected to the storage arrangement electrode, wherein Both ends of the small-sized adjacent arrangement electrode line overlap with the first configuration electrode and the storage configuration electrode; Civ) exciting the temporary configuration electrode; Cv) exciting the storage configuration electrode; 201244825 The electrode performs excitation and removal excitation; and) the mother small-sized adjacent configuration calculates the excitation and removal excitation sequence of the household configuration electrode, and the method described by the edge=,, the ten-t request item 12 further includes utilizing the first Configuring the tape to perform the 'electrode including the third adjacent arrangement for i); ΪΓ first - arranging the electrode to remove the excitation, and arranging the electrode electrode for the bridge s_ pole wire, and paying for the three adjacent configurations ^ = the method of claim 6, further comprising moving the droplets by column excitation (i) configuring a column-arranged electrode comprising a plurality of columns of micro-electrodes; and exciting the self-excited electrode comprising a plurality of columns of micro-electrodes together with the de-axis (11) All residual droplets on the ship's electrode are punctured by arranging the = excitation of the electrodes along the target direction. The method of claim 6, wherein the liquid reservoir is a liquid. Different configurations for the desired liquid size and miscellaneous target configuration electrodes • i) configuration of the bridge configuration electrode, the bridge configuration electrode including the microelectrode wire and connected 41 201244825 to the reservoir and the target configuration And the (mountain) excitation of the bridge configuration electrode and the target #configuration electrode; the bridge with the nearest bridge f and the target configuration electrode 32, such as =3^ + excitation Configure the electrode to remove the stimulus. And the method of sub-f, and the method of using the continuous flow to control the size of the body 2 = splitting the liquid into the seed (four), the liquid appliance is loaded with the liquid Dazaki - side size and shape standard configuration The second target (VI) having a second sub-liquid size and shape of the sense is used to excite the first target configuration electrode. (4) The method of 6 reliance, including the continued dimensions such as controlled size, including and. And the two liquid_methods are combined, the liquid in which the liquid in the liquid is loaded, (i) the mixed configuration electrode is arranged; the second item is mixed with the first electrode of the mixed arrangement electrode _ greening in the configuration - the bridge configuration electrode The first bridge configuration electrode includes a micro lightning line and is connected to the first-target configuration electrode and the first liquid source L includes a micro-electric (four) ϋ configuration second bridge configuration electrode 'the second bridge configuration electrode includes a Kole line And connecting to the second target configuration electrode and the second liquid source, including the micro-electric first mesh-bridge 1 and the second bridge configuration electrode, and the first-purpose private configuration electrode and the second target Configuring the electrodes for excitation (vi) deactivating the first bridge configuration electrode and the second bridge configuration electrode; and (νι〇 exciting the hybrid configuration electrode. The method, wherein the grounding mechanism has a gap between the two-plane junction bottom plate, the top plate is located above the bottom plate, and the top plate is in the same manner as the method, wherein the grounding mechanism is a passive network 1 The money is based on the grounding mechanism There is a green grounding pad 1 lining, and its method of lying in the county has a grounding 38, as described in the request, the grounding welding _ coplanar structure is designed. Na is the method described in the article 1 'The description of the grounding mechanism is a hybrid structure that combines the double flat and the coplanar structure with a selectable switch. ^ The method of 0 in the middle of the device =: 6 The method further includes loading the liquid into the a stock solution (0 loading the liquid onto the coplanar structure; and (ii) placing a passive cover on the liquid. 4 The method of claim 1 further comprises adapting to a wide range and The grounding mechanism is at the top k of the biplanar structure. The top plate is located at the floor of the bottom plate and has a gap therebetween; and includes: (1) a height of a gap between the top plate and the bottom plate ((1) configuring the configuration The electrode is sized to contact the droplet of the droplet to contact the top plate and the bottom plate; and to liquefy, (iii) configure the size of the configuration electrode to control the droplet size to contact only the bottom plate. Liquid ϋ ΐ ΐ ΐ 其中 其中 其中 其中 其中 其中 其中 其中 其中 其中 其中 其中Arranged in a generally circular, square, hexagonal or honeycomb-shaped stack tablet. Soap bad ice type 43
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US13/029,138 US8685325B2 (en) 2010-03-09 2011-02-17 Field-programmable lab-on-a-chip based on microelectrode array architecture
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