TWI744848B - 包含具薄膜電晶體及電容感測之雙基板的數位微流體裝置 - Google Patents

包含具薄膜電晶體及電容感測之雙基板的數位微流體裝置 Download PDF

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TWI744848B
TWI744848B TW109110971A TW109110971A TWI744848B TW I744848 B TWI744848 B TW I744848B TW 109110971 A TW109110971 A TW 109110971A TW 109110971 A TW109110971 A TW 109110971A TW I744848 B TWI744848 B TW I744848B
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electrodes
digital microfluidic
microfluidic device
sensing
density
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伊恩 法蘭屈
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Abstract

一種介電質上電潤濕主動矩陣(AM-EWoD)裝置，其包含具薄膜電晶體(TFT)及電容感測之雙基板。此處所繪下基板包含第一複數個電極，用以推動各液滴穿過一微流體區域，而上基板包含第二複數個電極，其被構造成以電容感測詢問該等液滴。在一些實施例中，該上基板具高解析度感測區及低解析度感測區。

Description

包含具薄膜電晶體及電容感測之雙基板的數位微流體裝置
[相關申請案]
本申請案主張對2017.10.18申請之美國臨時專利申請案第62/573,846號的優先權。本說明書中參照之所有專利及專利申請案之全部內容均以參照的方式併入本文。
本發明係關於一種介電質上電潤濕主動矩陣(AM-EWoD)裝置，其包含具薄膜電晶體(TFT)及電容感測之雙基板。
數位微流體裝置利用獨立電極於受限環境下推進、分流及加入液滴，藉此提供「晶片實驗室(lab-on-a-chip)」。數位微流體裝置另稱之為介電質上電潤濕或「EWoD」，以進一步區隔此方法與仰賴電泳流動及/或微泵浦之競爭性微流體系統。Wheeler在2012年Annu. Rev. Anal. Chem (5:413-40)之「Digital Microfluidics」中提出2012電潤濕技術回顧，茲以參照方式將其全文併入本文。該技術允許以少量樣本及試劑實行樣本製備、分析及合成化學。近年來利用電潤濕之微流體單元中受控液滴操縱業具市場性；現已可自大型生命科學公司如Oxford Nanopore取得產品。
大部分的EWoD文獻報告涉及所謂的「被動矩陣」裝置(亦稱「分段」裝置)，藉此可以一控制器直接驅動十至二十個電極。雖然分段裝置易於製造，但是電極的數量受限於空間和驅動限制。因此，可於被動矩陣裝置中實行大量平行分析、反應等。相較於此，「主動矩陣」裝置(亦稱主動矩陣EWoD，或稱AM-EWoD)裝置可具有數千、數十萬甚或數百萬個可定址電極。該等電極一般係由薄膜電晶體(TFTs)切換，且液滴移動可經程式化使得AM-EWoD陣列可作為通用裝置，允許控制多液滴及執行同時分析處理之高自由度。
由於電場洩漏之限制性需求，大部分的先進AM-EWoD裝置係自多晶矽(polycrystalline silicon)(亦稱polysilicon，或稱poly-Si)建構。但多晶矽製造遠較非晶矽製造(即用於LCD顯示器業界之大量生產的主動矩陣TFT中使用的類型)價昂。多晶矽製程價昂之因在於用於伴隨多晶矽之獨特處理與製造步驟。全世界經構造來製造多晶矽裝置的設施亦較少。但由於多晶矽功能性之改良，Sharp公司已能達成在單一主動矩陣上含括推進、感測及加熱能力之AM-EWoD裝置。參見例如美國專利第8,419,273號、第8,547,111號、第8,654,571號、第8,828,336號及第9,458,543號，茲以參照方式將其等全文併入本文。一複雜的多晶矽AM-EWoD示例示如圖1。
雖然多晶矽製造技術允許實現複雜的AM-EWoD裝置，多晶矽裝置製造的成本加上全球合適的製造設施之短缺，使得AM-EWoD技術難以廣泛運用。需要有可利用既有非晶矽製造容量優點的不同設計。此等裝置可以較低成本大量生產，使其成為常見診斷測試如免疫分析的理想選擇。
本發明藉由提供AM-EwoD用之一替代架構來解決先前技術的缺點，AM-EwoD極適於自非晶矽基板建構。在一例項中，本發明提供一種數位微流體裝置，其包括一第一基板、一第二基板、一間隔體及第一與第二控制器。該第一基板包括第一複數個電極，其耦合至一第一組薄膜電晶體，及包含覆蓋該第一複數個電極及該第一組薄膜電晶體兩者之一第一介電層。該第二基板包括第二複數個電極，其耦合至一第二組薄膜電晶體，及包含覆蓋該第二複數個電極及該第二組薄膜電晶體兩者之一第二介電層。該間隔體隔離該等第一及第二基板，及產生在該等第一及第二基板間之一微流體區域。該第一控制器操作耦合至該第一組薄膜電晶體及被構造成提供推進電壓至該第一複數個電極之至少一部分，而該第二控制器操作耦合至該第二組薄膜電晶體及被構造成判定在該第二複數個電極之至少一個電極與一驅動電極間之電容。在一些實施例中，該第一介電層係疏水性的，而在其他實施例中，該第二介電層係疏水性的。在較佳實施例中，該第一複數個電極配置成一陣列，例如包含每線性公分至少25個電極。在一些實施例中，該第二複數個電極與該驅動電極成交叉指形(interdigitated)。在一些實施例中，一信號源耦合至該驅動電極及被構造成提供一時變電壓至該驅動電極。在一些實施例中，該第二基板包含至少一個透光區域，其面積可為例如至少10mm2 。該數位微流體裝置可係自非晶或多晶矽建構。
在一些實施例中，一數位微流體裝置將具有不同電極密度之兩區域，亦即感測電極側用之一高密度(亦稱「高解析度(high-res)」)區及一低密度(亦稱「低解析度(low-res)」)區。此設計將允許使用者實行粒子詢問(亦即電容感測)以判定在裝置之一部分中的組成或尺寸，及接著簡單監測在裝置之另一部分中的粒子位置或存在。整體而言，此構造簡化了裝置製造，同時亦簡化了感測功能相關資料處理。
如上述，本發明提供一種介電質上電潤濕主動矩陣(AM-EWoD)裝置，其包含具薄膜電晶體(TFT)及電容感測之雙基板。此處所繪「下」基板包含複數個電極，用以推動各液滴穿過一微流體區域。「上」基板包含複數個電極，用以提供一信號及以電容感測偵測液滴之存在及/或尺寸及/或成分。使用「上」及「下」僅係依慣例，兩基板的位置可切換，且裝置可以多種方式定向，例如上下板可概略平行，而整體裝置經定向使得基板垂直於工作表面(相對於如圖所示的平行於工作表面)。上或下基板可包含額外功能如電阻性加熱及/或溫度感測。由於該等裝置併入基於TFT之感測器，故與已知被動裝置相較，該等裝置之敏感度與解析度高得多。此外，可以多晶矽進行設計，藉此降低生產成本至裝置係可拋式的程度。亦可下板採用a-Si TFT以取其較高操作電壓的優點，及poly-Si TFT為上板而具較高靈敏度感測。
一EWoD裝置之基本操作例示如圖2剖面影像。EWoD 200包含填充有油202及至少一個水溶液滴204之單元。單元間隙一般範圍在50至200µm，但間隙可更大些。在如圖2所示之一基本構造中，複數個推進電極205配置於一基板上，及單一上電極206配置於相對表面上。該單元另包含在接觸油層之表面上之疏水塗層207，及在推進電極205與疏水塗層207間之介電層208。(上基板亦可包含介電層，但未示於圖2中)。疏水層防止液滴潤濕表面。當相鄰電極間無施加電壓差時，液滴將維持球狀使得與疏水表面(油及疏水層)的接觸最小化。由於液滴不會潤濕表面，故除非需要該行為，較不可能汙染表面或與其他液滴交互作用。
雖然可以單一層針對介電及疏水功能兩者，但此等層一般需要厚的無機層(以避免針孔)，造成低介電常數，因而需要高於100V造成液滴移動。為達成低壓致動，較佳具有高電容且無針孔之薄的無機層，頂部是薄的有機疏水層。利用此組合可以具有電壓範圍在+/-10至+/-50V之(習知TFT陣列可供應範圍內)電潤濕操作。
當在相鄰電極間施加電壓差時，一電極上的電壓吸引在介電質對液滴介面處之液滴中的相反電荷，且該液滴移向此電極，如圖2所例示。可接受的液滴推進所需之電壓端視介電質與疏水層性質而定。AC驅動係用以降低液滴、介電質及電極因各種電化學而劣化。EWoD操作頻率範圍可在100Hz至1MHz，但較低頻之1kHZ或更低對於具操作速度限制之TFT之使用較佳。
如圖2所示，上電極206係單一導電層，一般設定為0伏特或共用電壓值(VCOM)，其考量推進電極205上因用以切換電極上電壓之TFT之電容回踢(kickback)造成的偏移電壓(見圖3)。上電極亦可具有經施加以增加液體兩端電壓之方波。此配置允許對TFT連接之推進電極205使用較低推進電壓，因為上板電壓206係TFT供應之電壓外之額外電壓。
如圖3所示，推進電極之一主動矩陣可經配置而以資料與閘極(選擇)線驅動，非常類似於液晶顯示器中之主動矩陣。閘極(選擇)線係以一次一線定址方式掃描，而資料線攜載待傳送至推進電極用於電濕潤操作之電壓。若無需移動，或若液滴會自一推動電極遠離，則將施加0V至該(非標定)推進電極。若液滴會移向推進電極，則將施加一AC電壓至該(標定)推進電極。
非晶矽、TFT切換之推動電極之架構示如圖4。介電質408須夠薄且介電常數與低壓AC驅動相容，諸如自LCD顯示器用之習知影像控制器可得者。例如介電層可包括一層上塗布有200-400 nm電漿沉積矽氮化物之近乎20-40 nm SiO2 。或者，介電質可包括介於2與100 nm厚之原子層沉積之Al2 O3 ，較佳介於20與60 nm厚。TFT係藉由沿著各電極線產生不同摻雜之a-Si結構之交替層而建構，其方法係熟悉此技術者所週知。疏水層407可自材料如Teflon® AF (Sigma-Aldrich, Milwaukee, WI)及Cytonix (Beltsville, MD)之FlurorPelTM 塗布建構，其等可經旋塗布於介電層408上。
在本發明中，具TFT功能之第二基板經建構以提供電容感測能力，且以一間隔體分離兩層，在該兩層間產生微流體區。液滴之電容感測利用兩電極，示如圖6。AC信號一般施加於驅動電極506，藉此AC信號在相鄰感測電極505上產生電容耦合電壓。電容耦合信號係由外部電路測量，且信號改變指示驅動電極506與感測電極505間的材料。例如，耦合電壓將因油202或水溶液滴204是否介於電極間而顯著不同，此係因材料間相對介電常數不同所致。(矽油之相對介電常數係εr = 2.5，乙醇之相對介電常數係εr = 24，及水之相對介電常數係εr = 80。)
非晶矽感測層的架構，包含TFT切換之感測電極505與驅動電極506，示如圖5。驅動電極用之AC信號水平移動，且一次僅一線被啟動以將對讀取線及「關閉(OFF)」感測電極之電容耦合最小化。TFT並非完美開關，即使在「關閉」狀態下仍具有小量導電性。亦即大量的關閉線會具有與一「導通(ON)」像素類似的信號。因此較佳係藉由僅在被驅動之列上具有ac電壓而將來自其上下列的ac電壓之電容信號降至最低。
如圖6所示，感測與驅動電極產生一共面間隙單元。一主要優點在於兩板無需精確對齊，或甚至具有相同的像素間隔，因而簡化了兩板系統之製造。利用交叉指形間隙單元之液滴用電容感測的額外細節見於例如「Capacitance Variation Induced by Microfluidic Two-Phase Flow across Insulated Interdigital Electrodes in Lab-On-Chip Devices」(T. Dong, C Barbosa, Sensors , 15, 2694-2708, (2015))，茲以參照方式將其全文併入本文。用於偵測電容信號之電路可包含各種電器組件，包含放大器、多工開關等。先進設計可包含耦合至多通道電荷感測器之a-Si TFT陣列，諸如用於數位x射線成像。見於G. De Geronimo 等人在Nuclear Instruments and Methods in Physics Research A (471 pp. 192–199, (2001))中之「Front-end electronics for imaging detectors」，茲以參照方式將其全文併入本文。
在一些實施例中，無需針對AC信號提供多個獨立驅動電極。如圖7所示，驅動電極可經配置為連續，但與感測電極呈交叉指形。(圖7中所示之所有電極均在同一金屬層中，但以不同顏色展示以彰顯其功能。)在圖7中，提供跨越表面以水平傳輸之AC信號至單一驅動電極，同時跨越陣列「讀取」各感測電極。一般一次僅啟動一感測器線，以將來自驅動電極之AC信號與處於「關閉」模式之感測電極間的電容耦合降至最低。沒有此類逐線讀取，來自多個感測電極之具「空」狀態(例如耦合至油)之信號將較適當者大，降低正確感測電極之信雜比。在一替代實施例中，上基板可包含驅動電極、感測電極及一接地閘極。驅動與感測電極可用於液滴感測，如上述，而接地閘極提供相對於推進電極之一電極表面區域，其具有對電氣接地之低阻抗。
本發明將利用耦合至上驅動與感測電極之電路提供電容感測，藉此允許裝置追蹤由裝置操縱之液滴位置。但來自液滴之電容感測之透過一小感測電極之信號亦相當小，因此可能需要一至三百條感測電極線來獲得可接受的信雜比。提供跨越整個裝置之此高密度感測電極將係價昂且非必要的。因此，對於較大陣列而言(諸如組合化學)，較佳係在用於微粒尺寸調整之上板上具有具高密度感測像素之小局部化區域，而其他用於移動感測處則係低密度。
如圖8所示，可由在上板上各位置處具不同密度的感測電極產生AM-EWoD裝置。在圖8之實施例中，在用於液滴尺寸測量之陣列上具有200 dpi高解析度區域，及用於追蹤液滴移動之10 dpi解析度區域。在圖8中，對於100條測量線，感測器將係181.61 mm寬。若感測板下之TFT EWoD推進基板具有200 dpi之均勻解析度(每英寸的電極數)，則將具有1430列推進電極用於控制液滴之移動、混合等。相對地，受限於跨越整個裝置具180 dpi解析度的一百個感測列之裝置，將僅係14.1 mm寬，造成僅111列推進電極；對於複雜陣列可能過小。因此，藉由提供不同密度，一較大裝置可由所有的需求感測容量產生。概言之，低解析度區域每線性公分將包含1到15個電極，而高解析度區域每線性公分將包含20到200個電極。一般具較低密度(亦稱「低解析度」)之感測電極的總面積(長x寬)大於具較高密度(亦稱「高解析度」)之感測電極的總面積。例如相較於高解析度面積s，低解析度面積可為三倍以上。例如可具5倍以上的低解析度面積。例如相較於高解析度面積，低解析度面積可為十倍以上。
利同密度感測電極的額外優點在於部分上板可具可穿透或可透光區域，以允許進一步液滴詢問。例如可藉由以一光源透過上基板照射液滴而觀察到螢光標記，及接著利用一偵測器及彩色濾波器(選用)透過上基板觀察所得螢光。在其他實施例中，光可穿過上與下基板兩者，以允許在IR、UV或可見光波長之吸收測量。或者，可利用經衰減(經擾動)之總體內反射光譜探測系統中液滴內含物或位置。
此系統之一實施例示如圖9，其中在感測電極905間的間隙910係約2 mm，允許光915自物件920穿過以照射一通過中的液滴930。在一實施例中，液滴930包含螢光分子，且所得螢光信號經收集回穿物件920並利用雙色濾波器(未顯示)分波而以偵測器偵測之(未顯示)。因此，該設計允許不同類型資訊如電容及光譜資訊在液滴移動穿過系統時，被液滴收集。
如參考圖8所述，用以達成低解析度感測的最簡單方式將係具有如高解析度區域之感測像素設計。此概念例示如圖10中的不同實施例。利用圖10的設計，液滴將可通過低解析度感測像素間，而可將液滴控制演算法寫入以確保液滴恆定穿過感測像素，允許監視液滴尺寸與成分。如圖10所例示，低解析度像素的均勻分布使其得以大幅增加可感測區域，同時允許使用市售驅動器。替代地，在任一垂直感測線上的感測像素數量可為定值，而感測像素交錯，示如圖11。亦可採用其他圖案如虛擬隨機式，將與液滴之交互作用最大化，同時降低須製造及稍後定址之實際感測TFT數量。
亦可利用不同外形電極產生低解析度與高解析度感測區域，示如圖12與13。圖12顯示在高解析度感測區域中的正方形像素及在低解析度感測區域之較大的矩形感測像素。此設計將可有效率地感測上下移動陣列，亦即在長型電極間移動。可實行與此相同技術製作水平與垂直長型電極兩者，提供以低解析度追蹤之液滴。圖13顯示具垂直與水平矩形感測像素之低解析度區域，以偵測液滴的垂直與水平移動。其他幾何形狀設計如螺旋狀，亦可用以促進以較少電極及較少TFT進行位置感測。如圖12與13所示，易於自低密度區域(在該處發生液滴產生、分開或混合)將液滴移動至高密度區域(在該處可評估液滴的尺寸及成分)。
自前述可知本發明可提供低成本晶片上實驗功能。尤其是藉由使用上述架構，可利用非晶矽製造設施及較低成本驅動電子元件產生介電系統上的電潤濕。本發明可有效利用EWoD裝置上下兩者之可用表面，但無需在上下表面上對齊電極。
熟悉此技術者將知可在不背離本發明的範疇下，對上述本發明的特定實施利進行多種改變與修改。因此，前述之整體應解譯為例示性而無限制之意。
200:介電質上電潤濕 202:油 204:液滴 205:推進電極 206:上電極 207:疏水塗層 208:介電層 405:電極 407:疏水層 408:介電層 505:感測電極 506:驅動電極 507:疏水層 508:介電層 905:感測電極 910:間隙 915:光 920:物件 930:液滴
圖1顯示一先前技術EwoD裝置，其包含在相同主動矩陣上的推進及感測兩者； 圖2繪示藉由在相鄰電極上提供不同電荷狀態而在相鄰電極間移動水相液滴； 圖3顯示本發明之一EwoD裝置之複數個推進電極用的一TFT架構； 圖4係第一基板的一部分之簡圖，其包含一推進電極、一薄膜電晶體、一儲存電容器、一介電層及一疏水層； 圖5係第二基板的一部分之簡圖，其包含一感測電極、一驅動電極、一薄膜電晶體、一介電層及一疏水層； 圖6顯示一感測電極及一驅動電極用之一TFT架構，其構造成用於電容感測及評估微流體液滴； 圖7例示一實施例，其中該感測電極及該驅動電極呈交叉指形為第二電極的一部分； 圖8例示一數位微流體裝置頂視圖，其中感測電極配置成具有高低密度的變化區。在圖8中所示電極配置提供許多分析功能所需功能性(液滴尺寸判定及移動追蹤)，同時降低裝置複雜性及生產成本； 圖9例示一替代實施例，其包含一透光區域，在該處可以電磁輻射(亦及光)詢問液滴。可以理解的是，探測光及所得信號兩者可進入/離開通過相同透光區域； 圖10顯示感測電極之一替代配置，其配置成具有高低密度變化區； 圖11顯示感測電極之一替代配置，其配置成具有高低密度變化區； 圖12顯示一替代配置，其包含配置成具有高低密度變化區之長型感測電極； 圖13顯示一替代配置，其包含配置成具有高低密度變化區之長型感測電極。
200:介電質上電潤濕
202:油
204:液滴
205:推進電極
206:上電極
207:疏水塗層
208:介電層

Claims (15)

  1. 一種數位微流體裝置，其包括：一第一基板，其包括第一複數個電極，其耦合至第一組薄膜電晶體，及包含覆蓋該第一複數個電極及該第一組薄膜電晶體兩者之一第一介電層；一第二基板，其包括一驅動電極及第二複數個電極，該第二複數個電極耦合至第二組薄膜電晶體，該第二基板包含覆蓋該第二複數個電極及該第二組薄膜電晶體之一第二介電層；一間隔體，其隔離該等第一及第二基板，及產生在該等第一及第二基板間之一微流體區域；及一第一控制器，其操作耦合至該第一組薄膜電晶體及被構造成提供推進電壓至該第一複數個電極之至少一部分。
  2. 如請求項1之數位微流體裝置，其中該第一介電層係疏水性的。
  3. 如請求項1之數位微流體裝置，其中該第二介電層係疏水性的。
  4. 如請求項1之數位微流體裝置，其進一步包括覆蓋該第一介電層之一第一疏水層及覆蓋該第二介電層之一第二疏水層。
  5. 如請求項1之數位微流體裝置，其中該第一複數個薄膜電晶體或該第二複數個薄膜電晶體包括非晶矽。
  6. 如請求項1之數位微流體裝置，其中該第一複數個電極或該第二複數個電極配置成一陣列。
  7. 如請求項1之數位微流體裝置，其進一步包括一信號源，其耦合至該驅動電極且被構造成提供一時變電壓至該驅 動電極。
  8. 如請求項1之數位微流體裝置，其中該第二基板包含至少一個透光區域。
  9. 如請求項8之數位微流體裝置，其中該透光區域之面積至少為10mm2。
  10. 如請求項1之數位微流體裝置，其中該該第二複數個電極係以一第一密度及一第二密度配置，及該第一密度包含每100mm2至少三倍於該第二密度之電極。
  11. 如請求項10之數位微流體裝置，其中該第二複數個電極之該第一密度包含每線性公分20至200個電極。
  12. 如請求項10之數位微流體裝置，其中該第二複數個電極之該第二密度包含每線性公分1至15個電極。
  13. 如請求項10之數位微流體裝置，其中該對應於該第一密度之該裝置之面積小於對應於該第二密度之該裝置之面積。
  14. 如請求項13之數位微流體裝置，其中該裝置之對應於該第二密度的面積係該裝置之對應於該第一密度的面積的至少三倍。
  15. 如請求項1之數位微流體裝置，其中該第二複數個電極之每個電極與該驅動電極成交叉指形(interdigitated)。
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