TW574130B - An innovative micro-fabrication for electroosmotic flow (EOF) control via a self-assembled monolayer by using a perpendicular electric potential - Google Patents
An innovative micro-fabrication for electroosmotic flow (EOF) control via a self-assembled monolayer by using a perpendicular electric potential Download PDFInfo
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574130574130
【發明所屬之技術領域】 本發明係有關於一錄i ®糜*也丨上、t *[Technical field to which the invention belongs] The present invention relates to a recording i ® Mi ** 丨 丨, t *
場效電場控制電滲流之微晶片製法,尤指 膜(sel f-assembled monolaye, SAM)作 的絕緣層,修飾於晶片基板之電極上,俾 成極薄的絕緣層、降低誘發電壓、縮小體 制電滲流〔Electroosmotic Flow; EOF〕 可電壓控制式之自組性薄膜 晶片製法」。 由於E〇F,〔電滲流〕具有易誘發·、平板.流曲線與無 須外加魔大的幫浦系統等特性,因此適合搭配微機電製程 應用於實驗室晶片化〔Lab-on-a-chip〕系統或微流體控 制系統中。在此領域中,毛細管電泳晶片搭配各式檢測系 統的應用是目前發展的最蓬勃、也最成熟的一環。近來’ 利用電滲流的特性,毛細管電泳晶片已成功的被用來做D N A的檢測、蛋白質的分析、環境或生化物質的快速檢驗 以及微泳道中細胞分離等用途。 相對之,本發明主要係提供一新式、方便製作、有效 控制與低耗能的電滲流控制技術平台,應用於微管道内之 流:體控制與毛細管電泳分離晶片。藉此,在不改變外加袖 向驅動電場的強度下,能夠即時控制電滲流的速度及方句 〇 【先前技術】 目前於生物微晶片(bioiicrochip)系統中’用來 574130 五、發明說明(2) 才呆控微流體的輸送方向與流速之技術,大致以氣壓驅動、 液壓驅動以及電驅動(electr〇kinectics)為主。特別是 電驅動乃透過電場作用力,驅使微泳道表面電雙層内的水 合離子移動;當水合陽(陰)離子受電場力作用時往負( 正)極移動,便能帶動微管道内液體的流動,此為電滲流 (electroosmotic f10W,EOF)的產生。然而,在傳統的 毛細管内當溶液pH>3時,表面會呈現強烈的負電,使e〇 F只能沿電場單方向移動,無法任意的作雙向流動。 請參閱第八圖所示,傳統的毛細管電參通道,由於管 壁(.4 )表面的石夕醇基(silanol group),在pH值大於3 的狀態下,會解離成帶負電的矽氧陰離子,使得毛細管的 管壁(4)内面呈負電狀態,此時,便吸引溶液中帶正電 的水合陽離子吸附於毛細管表面形成電雙層,在外加電場 的作用下產生電滲流(EOF)效應,有助於提升樣本的 分離。由於傳統的電滲流(E 0 F )會受到緩衝溶液的酸 鹼值、電解質溶液的離子強度與毛細管内表面的官能基不 同所影響’因此造成毛細管電泳道内液體流動速度與方向 的操控不易。1 9 9 0年’ Lee等人在毛細管外利用外加電壓 (radial external voltage),透過毛麵管.的管壁(4 )誘發極化而改變Γ電位(電雙層電彳立)的概念,來控制 E〇F的流向與流速。之後也有利用導電的溶^、離^化 的氣體與導電n分子當導體來改變^電位,然而這樣的裝 置有幾項缺點: 1. 一般毛細管的管壁(4)厚度大約數十到數百微米Field-effect electric field controlled microosmosis microchip manufacturing method, especially an insulating layer made of film (sel f-assembled monolaye, SAM), modified on the electrode of the wafer substrate, forming an extremely thin insulating layer, reducing induced voltage, reducing the system [Electroosmotic Flow; EOF] Voltage-controlled self-assembled thin-film wafer manufacturing method. " EOF, [electroosmotic flow] has characteristics such as easy to induce, flat plate, flow curve, and no need to add a large pump system, so it is suitable for laboratory waferization with MEMS process [Lab-on-a-chip] 〕 System or microfluidic control system. In this field, the application of capillary electrophoresis chips with various detection systems is currently the most vigorous and mature one. Recently, using the characteristics of electroosmotic flow, capillary electrophoresis chips have been successfully used for the detection of DNA, the analysis of proteins, the rapid detection of environmental or biochemical substances, and the separation of cells in microchannels. In contrast, the present invention mainly provides a new, easy-to-manufacture, effective control and low-energy-consumption electroosmotic flow control technology platform, which is applied to microfluidic flow: volume control and capillary electrophoresis separation wafers. In this way, without changing the intensity of the external sleeve driving electric field, the speed and the phrase of the electroosmotic flow can be controlled in real time. [Previous technology] Currently used in bioiicrochip systems' for 574130 V. Description of the invention (2 The technology that controls the direction and flow rate of microfluidics is mainly driven by air pressure, hydraulic pressure, and electric power (electricity). In particular, the electric drive drives the hydration ions in the electric double layer on the surface of the microchannel through the force of the electric field. When the hydrated positive (anion) ions are moved to the negative (positive) pole by the electric field force, the liquid in the microchannel can be driven. This is the generation of electroosmotic f10W (EOF). However, when the solution pH > 3 in the traditional capillary, the surface will show a strong negative charge, so that eOF can only move in one direction of the electric field, and can not arbitrarily do two-way flow. Please refer to Figure 8. As shown in the traditional capillary electrical parameter channel, due to the silanol group on the surface of the tube wall (.4), it will dissociate into negatively-charged silicon oxygen at a pH value greater than 3. The anion makes the inner surface of the capillary tube wall (4) in a negatively charged state. At this time, the positively charged hydrated cations in the solution are attracted to the capillary surface to form an electric double layer, which generates an electroosmotic flow (EOF) effect under the action of an external electric field. , Help to improve the separation of samples. The traditional electroosmotic flow (E 0 F) is affected by the pH value of the buffer solution, the ionic strength of the electrolyte solution, and the functional groups on the inner surface of the capillary ’, which makes it difficult to control the flow rate and direction of the liquid in the capillary electrophoresis channel. In 1990, Lee et al. Used the external external voltage on the capillary tube to change the concept of the Γ potential (electrical double-layered electrical standing) by inducing polarization through the tube wall (4) of the matte tube. To control the flow direction and flow rate of E0F. Later, there is also the use of conductive dissolved and ionized gases and conductive n molecules as conductors to change the potential, but this device has several disadvantages: 1. The thickness of the tube wall (4) of a general capillary is about tens to hundreds Micron
574130 五'發明說明(3) (micrometer),新命从 足夠的誘發電場。"的外加電壓需高達數千伏才能產生 以負2的電由參於:(細二的△面在pH值大於3時會呈負電性^ ^ 達到控制流向的U向與電場方向相反)無法產生,無法 3 ·毛細管較不古為:^ network)以達到樣太&相連接形成一微流體的網路( 由於上述的方法都輪;V切換、混合與分離的功能。 中也能達到控C 毛細管設計,為能在微管道 s—等人H 寇請;閲第九圖所示, )結構,再使用陽極接合;“ = =微管道(: 控二:…6)的表面電位,進而操 控電上"L動方向’同時外加的誘發閘極電屋(+ MV〜 最大可^可控1 ί '速,其系統所誘發之雙向電滲流的速 |^产一3~^1"¥^1〇4(環境溶液^3.6);但在 衣,洛液pH大於3.6 (環境溶液ρΗ45)時,由於外加誘發 電堃所造成的場效電場·無法克服微管道 =面負電荷,故只能誘發出單向之正電渗流;】。斤; 後也有利用玻璃為絕緣層(5)(厚度為5〇微米)在玻璃 =㈣合的晶片中控制E 〇F或利用二氧化石夕為絕緣層 (5 )(尽度為2微米)在P DMS與梦為基材 五、發明說明 I該 得所需的 就無法任 生物實驗 只能操控 2·在 電製程才 3. 再 米至數十 下,所誘 4. 由 慮未來在 【發 (4) 絕緣層 電壓須 意的控 之環境 與電場 絕緣膜 能形成 者,所 微米, 發出之 此可知 商品化 明内容 (5 )的 高達數百 制E 0 F 溶液pH值 同向之電 (5 )的 此膜。 形成之絕 故愈厚的 場效電場 ,其所控 與可攜性 ] 厚度與微管道(6)的材質,使 =伏特,在PH值大於3時使 大流逮。況且,-般傳統 大为在7· 〇左右,故在此條件下 渗μ ’無法產生雙向之控制。 製作方面上,需利周繁複的微機 緣膜(5)的厚度通常達數百奈 絕緣膜(5 )在相同的閘極電壓 則相對越小。 制之雙向電滲流效能不高,若考 的應用性上有其相當的困難性。574130 Five 'invention description (3) (micrometer), new life from sufficient induced electric field. " The applied voltage needs to be up to several thousand volts in order to generate an electric charge of minus two: (The △ plane of the thin second will be negatively charged when the pH value is greater than 3 ^ The U direction to control the flow direction is opposite to the electric field direction) Can't produce, can't. 3 · Capillaries are less ancient: ^ network) to achieve a sample & connection to form a microfluidic network (because the above methods are all round; V switching, mixing and separation functions. C capillary design is achieved, in order to be able to be used in the micro-channel s — et al. H; please see the ninth figure,) structure, and then use anodic bonding; "= = surface potential of the micro-channel (: control two: ... 6) , And then control the electric direction of "L moving direction" at the same time plus the induced gate electric house (+ MV ~ maximum controllable 1 controllable speed, the speed of the two-way electroosmosis induced by its system | ^ produce 3 ~ ^ 1 " ¥ ^ 1〇4 (environmental solution ^ 3.6); but when the pH of the solution is higher than 3.6 (environmental solution ρΗ45), the field-effect electric field caused by the externally induced electric field cannot be overcome. Therefore, it can only induce a unidirectional positive electroosmotic flow;]. Jin; there is also the use of glass as an insulating layer (5) (thickness of 5 〇micron) control E 〇F in the glass = coupling wafer or the use of dioxide as the insulating layer (5 micron as much as possible) in the P DMS and dream as the substrate If you need it, you ca n’t do any biological experiment. You can only manipulate it. 2. Only in the electrical process. 3. Induced by a few meters to dozens of times. 4. You should consider the future and the insulation of the electric field in [发 (4) The insulation layer voltage must be controlled. The film can be formed by the micrometer, and it can be known that the commercialized content (5) of this film can reach hundreds of E 0 F solutions with the same pH value (5). This film has a thicker field effect. Electric field, its control and portability] Thickness and the material of the micro-channel (6), so that = volts, so that when the pH value is greater than 3, the large current catches. Moreover,-the general tradition is about 7 · 〇, so Under these conditions, the infiltration μ 'cannot produce bidirectional control. In terms of fabrication, the thickness of the microcomputer edge film (5), which needs to be complicated, usually reaches several hundred nanometers, and the insulating film (5) has a relatively smaller voltage at the same gate voltage. The efficiency of the two-way electroosmosis system is not high, and it has considerable difficulties in application.
有鑑於此,發明人為改善上述習知技術之缺失,遂一 孜不倦之精神,藉由其豐富之專業知識及多年之實務 、所辅佐’並歷經多方巧思及多番試驗,終精心研擬出 本創作。 '' β ▲本=明係有關於一種可電壓控制式之自組性薄膜誘發 琢效電~控制電滲流之微晶片製法,該微晶片係由底板及 頂板對應結合而成;該底板係於基板中間具設間極電極, ^極電極表面形成一極薄之S Α μ〔自組性薄膜〕以作為 、’、巴緣層’頂板底侧凹具一比閘極電極略窄小的微泳道,微 士道内可供填充緩衝溶液;使用時,係於微泳道兩端加給 向壓電源正負端以作為產生電滲流的電場,並對閘極電極In view of this, the inventor has worked tirelessly to improve the lack of the above-mentioned conventional techniques. With his rich professional knowledge and years of practice, he has been assisted by many ingenuity and many experiments, and finally researched carefully. Draft this creation. '' β ▲ Ben = Ming is a microchip manufacturing method related to a voltage-controllable self-assembled thin film-induced electricity-controlling electroosmotic flow. The microchip is a corresponding combination of a bottom plate and a top plate; the bottom plate is An intermediate electrode is provided in the middle of the substrate, and an extremely thin S Α μ [self-organizing film] is formed on the surface of the electrode, which serves as a recess that is slightly narrower than the gate electrode at the bottom of the top plate. Swim lanes, microchannels can be filled with buffer solution; when in use, they are connected to the positive and negative ends of the directional power supply at the two ends of the microswim lane as an electric field generating electroosmotic flow, and the gate electrode
第9頁 574130 五、發明說明(5) 加給誘發電壓以使絕緣骐產生電極化效應,進而控制電滲 流之方向與速虞;由於上述絕緣層係以S A Μ〔自組性薄 膜〕構成,故<達到製作容易、厚度薄,益可降低誘發電 壓、縮小體積,且無論微泳道的溶液為酸性或中性皆可任 意控制電滲流方向及流速等功效。 【實施方武】 為使本發明所運用之技術手段與達成功效易於明瞭, 茲配合圖式說明如下: 首先,請參閱第 圖所示’本發明的微晶片’係由底 板(1)及頂板(2)所組成。 該底板(1 )係於基板(1 1 )中間具設極薄的長形 閘極電極(1 2 ),閘極電極(1 2 )表面具有絕緣層( 13)。再者,底板(1 )頂側結合頂板(2 ),頂板( 2 )底側凹具〆比電極略窄小的長形微泳道(2 1 ),微 泳道(2 1 )怜罩合於絕緣層(1 3 )頂側。其中,頂板 (2 )於微泳道(2 1 )兩端分別具設與其連通之孔洞以 作為可填充缓衡溶液的儲存槽(22),微泳道(21) 可藉此填充緩衝溶液。 使用時,係於微泳道(2 1 )兩端加給高壓電源正負 端以、作為產生電滲流(electroosmotic fl〇w,EQF)的電 場’並對閘極電極(1 2 )加給誘發場效電場的電壓〔即 為閑極電壓,V g〕,以控制微泳道(2 1 )底側絕緣層( 1 3 )表面電位,進而控制電雙層電位即可操控電滲流( E〇F)的流動方向及速度。Page 9 574130 V. Description of the invention (5) The induced voltage is applied to make the insulating plutonium produce an electrodetic effect, thereby controlling the direction and speed of the electroosmotic flow; since the above-mentioned insulating layer is composed of SAM [self-organizing film], < Easy production, thin thickness, which can reduce the induced voltage and volume, and can control the direction and flow rate of the electroosmotic flow arbitrarily regardless of whether the solution of the microchannel is acidic or neutral. [Embodiment Fangwu] In order to make the technical means used in the present invention and achieve the effect easy to understand, it is explained with drawings as follows: First, please refer to the 'microchip of the present invention' shown in the figure is composed of the bottom plate (1) and the top plate (2) Composition. The bottom plate (1) is provided with an extremely thin and long gate electrode (1 2) in the middle of the substrate (1 1). The surface of the gate electrode (1 2) has an insulating layer (13). In addition, the top side of the bottom plate (1) is combined with the top plate (2), and the bottom side of the top plate (2) is recessed with an elongated micro-swim lane (2 1) slightly narrower than the electrode, and the micro-swim lane (2 1) is sealed to the insulation Layer (1 3) on the top side. The top plate (2) is provided with holes communicating with the micro-swim lane (21) at both ends thereof as storage tanks (22) for filling the slow balance solution, and the micro-swim lane (21) can be used for filling the buffer solution. In use, it is connected to the positive and negative ends of the high-voltage power supply at both ends of the micro-swim lane (2 1) as an electric field to generate electroosmotic flow (EQF), and the gate electrode (1 2) is added to the induced field effect electric field. The voltage (that is, the idler voltage, V g) is used to control the surface potential of the bottom insulation layer (1 3) of the micro-swim lane (2 1), and then to control the electric double-layer potential to control the flow direction of the electroosmotic flow (EOF). And speed.
第10頁 574130 五、發明說明(6) 製造底板(1)時,係將其一材質的化學分子製成溶 液,再將具有閘極電極(;[2 )的基板(丄丄)浸置於溶 液中,經一時間〔如18 — 24小時〕後,其一材質的化學分 子恰可與閘極電極(1 2 )的表面相互作用,使其一材質 的化學分子於閘極電極(i 2 )上形成s A M (自組性的 薄膜)以作為絕緣層(1 3 ) ,·藉此,即製成底板(1 ) 。由於該絕緣層(1 3 )為一單分子層,故非常薄,此亦 為本發明的主要訴求重點。 上述其一材質的化學分子於閘極電極(1 2 )上形成 S A Μ (自組性缚膜)的,方法,大致可分四類: .1·其一材質的化學分子為碳長鏈脂肪酸〔aikan〇ic acids(CnH2n+1C00H)〕對表面具有金屬陽離子的閘極電極 (12)〔如氧化鋁或銀的表面〕; 2·其一材質的化學分子為有機梦的衍生物 (organosilicon derivatives)〔如烷基氣矽烷 (alkylchlorosi lane)、烷基胺矽烷(alkylaminosi lane) 與烧基炫醇石夕烧(alkyalkoxysilane)〕對表面具氫氧基 (hydroxyl)的閘極電極(12); 3 ·其一材質的化學分子為有機硫〔如烧基硫化物 (n-alkyl sulfide)、硫酚(thiophenol)、一硫二浠伍圜 (thiophene)等〕對屬於過渡金屬(transition metal)的 閘極電極(1 2 )加以吸附形成,如碳長鏈硫醇在金或銀 閘極電極(1 2 )表面加以吸附形成; 4·其一材質的化學分子為烷基(alkyl)在以矽製成的Page 10 574130 V. Description of the invention (6) When manufacturing the bottom plate (1), a chemical molecule of one material is made into a solution, and then the substrate (丄 丄) with the gate electrode (; [2) is immersed in In the solution, after a period of time (such as 18-24 hours), a chemical molecule of one material can just interact with the surface of the gate electrode (1 2), so that a chemical molecule of one material is on the gate electrode (i 2 ) S AM (self-organizing film) is formed as an insulating layer (1 3), and thus a base plate (1) is made. Since the insulating layer (1 3) is a monomolecular layer, it is very thin, which is also the main claim of the present invention. The chemical molecules of one of the above materials form SA Μ (self-organizing binding film) on the gate electrode (1 2). The methods can be roughly divided into four categories: .1. The chemical molecules of one material are carbon long-chain fatty acids. [Aikan〇ic acids (CnH2n + 1C00H)] Gate electrode with metal cations on the surface (12) [such as the surface of alumina or silver]; 2. One of the chemical molecules is an organic dream derivative (organosilicon derivatives) ) [Such as alkylchlorosi lane, alkylaminosi lane and alkyalkoxysilane] gate electrode (12) with hydroxyl group on the surface; 3 · One of the chemical molecules is organic sulfur (such as n-alkyl sulfide, thiophenol, thiophene, etc.) to the transition metal gate. Electrode (1 2) is formed by adsorption, such as carbon long chain thiol is formed by adsorption on the surface of gold or silver gate electrode (1 2); 4. One of the chemical molecules is alkyl, which is made of silicon. Into
第11頁 574130 五、發明說明(7) 閘極電極(1 2 )表面加以吸附形成。 製造頂板(2 )時,可選用能製成具彈性且軟質頂板 (2 )之材質為之,如聚二f基矽氧烷 〔P〇ly(dimethylsiloxane),PDMS〕材質。如此,將頂板 (2)置於四周平整之底板(1)上後,僅要略為壓合, 該頂板(2 )即可因凡得瓦爾力之物理特性而與底板(1 )自然吸附結合。 以下依一實施例說明本發明之製法·· 首先’於製造底板(1)時’以屬於有機硫的Page 11 574130 V. Description of the invention (7) The surface of the gate electrode (12) is formed by adsorption. When manufacturing the top plate (2), a material that can be made into a flexible and soft top plate (2) can be used, such as polydimethylsiloxane (PDMS). In this way, after placing the top plate (2) on the flat bottom plate (1) around it, the top plate (2) can be naturally adsorbed and combined with the bottom plate (1) due to the physical characteristics of Van der Waals force. The following describes the manufacturing method of the present invention according to an embodiment. First, when the bottom plate (1) is manufactured, it is classified as organic sulfur.
1 -oct:adecanethiol(ODT,Aldrich)的化學分子作為其一材 質,溶於约9 9 · 5 %的無水酒精成約2 m Μ的溶液,再將具有 金閘極電極(1 2 )之玻璃晶片基板(1 1 )浸置於上述 溶液中;其中,基板(1 1 )係以玻璃製成,為於玻璃晶 片上形成金閘極電極(12),可先於玻璃晶片上蒸鍍鉻 作為黏著層,再於鉻上蒸鍍金,金/鉻厚约為l〇〇/3〇nm ,其長皆約為1 · 2cm,寬皆约為1 〇 〇 # m,此乃屬習知技術1-oct: adecanethiol (ODT, Aldrich) chemical molecule is used as a material, dissolved in about 99.5% anhydrous alcohol into a solution of about 2 m, and then a glass wafer with a gold gate electrode (1 2) The substrate (1 1) is immersed in the above solution; wherein, the substrate (1 1) is made of glass. In order to form a gold gate electrode (12) on a glass wafer, chrome can be evaporated on the glass wafer as an adhesion layer. Gold is then vapor-deposited on chromium. The thickness of gold / chromium is about 100/30 nm, its length is about 1.2 cm, and its width is about 100 #m. This is a conventional technology.
’同’於玻璃晶片基板(1 1 )兩端亦蒸鍍形成源極電 極(1 4 )、洩極電極(1 5 )以作為電場的兩高壓電源 ,入端、’且於基板(1 1 )上形成一與閘極電極(1 2) 連接之導線(1 6 )以作為誘發電場的電壓輸入端;繼之 ’於上述將基板(1 1 )浸置於溶液約1 8 — 2 4小時後取出 ,其材質的化學分子便會於閘極電極(1 2)上形成一 S A Μ (自組性薄膜)的絕緣層(i 3 ),藉此製成底板'Same' is also formed on the glass wafer substrate (1 1) at both ends by forming a source electrode (1 4) and a drain electrode (1 5) as two high-voltage power sources for the electric field. ) To form a wire (16) connected to the gate electrode (12) as a voltage input terminal for inducing an electric field; and then 'immerse the substrate (1 1) in the solution for about 18 to 2 4 hours as described above. After taking out, the chemical molecules of the material will form an SA Μ (self-organizing film) insulating layer (i 3) on the gate electrode (1 2), thereby making the bottom plate
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再者,請參閱第四圖所示,製造頂板(2)時,係以 才示準光微影银刻技術(standard lithography)於發基板上 製出一高約13# m、寬50#瓜、長約1· 5cm的長形凸條(3 1)作為母模(3),再將聚二甲基矽氧烷 〔poly(dimethylsi l〇xane),PDMS〕單體及固化劑以約 1 0 : 1的比例混合均勻,繼倒 9 0 °C,1小時,使其固化; 模(3 ◦)上剝離取下,即 之頂板(2)。另請參閱第 微泳道(2 1 )兩端挖孔, 槽(2 2 ) 〇 請參閱第一〜三圖所示 )時,將頂板(2)置於底 製成的頂板(2)具彈性且 1 )表面平整,故僅要再以 會因凡得瓦爾力之物理特性 附結合,即製成微晶片。 於上述母模(3),並加熱約 待PDMS固化後,將其自母 為一具有長形微泳道(2 1 ) 一圖所示,再於頂板(2)之 以作為可填充缓衝溶液的健存 ’組合底板(1)及頂板(2 板(1)上,由於以 軟質’而以玻璃製成的底板( 手略為壓合,則頂板(2 )便 而與平整的底板(1 )自然吸Furthermore, please refer to the fourth figure. When manufacturing the top plate (2), the standard lithography technology was used to produce a height of about 13 # m, a width of 50 #, and a length on the hair substrate. Approximately 1.5 cm long convex strips (31) were used as the master mold (3), and then poly (dimethylsi loxane) (PDMS) monomer and curing agent were used for about 10: The ratio of 1 is mixed uniformly, and then it is poured at 90 ° C for 1 hour to cure it. The mold (3 ◦) is peeled off and removed, that is, the top plate (2). Also refer to dig holes at the two ends of the micro lane (2 1), and the groove (2 2) (see the first to third figures), when the top plate (2) is placed on the bottom, the top plate (2) is elastic. And 1) the surface is flat, so it only needs to be combined with the physical characteristics of Van der Waals force to form a microchip. After the master mold (3) is heated, and the PDMS is cured, the master mold is shown as a picture with an elongated microchannel (2 1), and then the top plate (2) is used as a fillable buffer solution. Jian's' combined bottom plate (1) and top plate (2 plate (1), because of the softness of the bottom plate made of glass (the hand is slightly pressed, the top plate (2) and the flat bottom plate (1) Suck naturally
請參閲第一、二、五圖所示,使用時,於上述可 儲存槽(2 2 )的源極電極(工4 )與洩極電極(〉 加給南壓源正負端以作為產生電滲流的電場,並對上2 壓,藉由誘發電壓來控制sam絕二 0.8V〜-UV 值:誘發電壓範圍為+ 田閘極電壓值為正時,所誘發產生的正Please refer to the first, second, and fifth figures. In use, the source and drain electrodes (> 4) and the drain electrode (> 2 of the storable tank (2 2)) are applied to the positive and negative ends of the south pressure source to generate electroosmotic flow. The electric field is controlled by the induced voltage to control the sam absolute value of 0.8V ~ -UV by the induced voltage: when the induced voltage range is + field gate voltage is positive, the induced positive
574130 五、發明說明 表面電位 而形成電 場反向, 示〕,反 向稱為正 可決定流 實驗 為了 此分別採 分子〇D A 〔表面 基板(1 層(1 3 成之頂板 兩微晶片 電渗流的 1 2 )施 (9) 會吸引 雙層, 此時所 之,藉 向電滲 速快慢 例: 驗證本 用皆屬 T ·〔.表 官能基 1 )之 ),再 (21 之微泳 電場, 予誘發 於微泳道(2 1 )中的缓衝溶液之陰離子 於上述外加高壓電源下,電滲流與電泳電 產生的方向稱為反向電滲流〔如第五圖所 誘發閘極電壓值為負時,電滲流與電場同 流。另外,利用調控誘發電壓的大小,即 發明能 有機硫 面·官能 為羧基 金閘極 將藉此 )結合 道(2 約80 V 電壓+ 有效控制電滲流的方向與 具有不同官能基之其一材 量為曱基(me thy 1,-CH3)〕 (carboxy1,-C00H)〕,於 電極(12)上形成SA 製成之底板(1)配合P 成不同之兩微晶片。繼之 1 )兩端施予高壓電源, / cm之軸向電場,並對閘574130 V. Description of the invention The surface potential creates an electric field reversal, as shown in the figure. The reverse is called the positive determinable flow experiment. For this purpose, molecules are used respectively. [DA] [surface substrate (1 layer (13% of the top plate of two microchips of electroosmotic flow 1 2) Shi (9) will attract the double layer, so at this time, the speed of the electroosmosis is taken as an example: verify that this application belongs to T · [. Table functional group 1)), and then (21 micro swimming electric field, In the pre-induced anion of the buffer solution in the micro-channel (2 1), under the above-mentioned externally applied high-voltage power supply, the direction of the electroosmotic flow and the electrophoretic electricity is called reverse electroosmotic flow [as shown in the fifth figure, the gate voltage is negative At the same time, the electroosmotic flow co-current with the electric field. In addition, the size of the induced voltage is controlled, that is, the organic sulfur surface and the functional carboxyl gold gate will be used to combine the channel (2 about 80 V voltage + effectively control the direction of the electroosmotic flow) It is different from a base material (1) with different functional groups which is a fluorenyl group (me thy 1, -CH3)] (carboxy1, -C00H)], which is made of SA on the electrode (12). Two microchips. 1) High voltage power is applied to both ends, / cm of the axial electric field, and
0· 8 V 0 . 8 V。如此 流速,於 質的化學 或M U D 玻璃晶片 Μ之絕緣 D M S製 ,分別對 作為產生 極電極( 於微泳道 (2 1 )内填充ρΗ6· 0或3· 0的緩衝溶液,施予不同大小與 極.性的誘發電壓,觀察電滲透流遷移率(# eQf)與誘發閘極 電壓(gate voltage,Vg)之間的關係,如第六、七圖所示 。由於ODT表面與PD MS製成的微泳道(2 1)表面 皆為甲基,所以不受溶液pH值的影響,透過閘極電壓的大 小與極性可完全的控制# eQf〔電滲流移動率〕的大小與方 向。若以MUDA形成絕緣層(1 3)時,表面的羧基在0 · 8 V 0.8 V. At such a flow rate, a buffer solution of qualitative chemical or MUD glass wafer M made of insulating DMS is used to generate a polar electrode (filling ρΗ6 · 0 or 3 · 0 in the microchannel (2 1)) with different sizes and polarities. .Sexually induced voltage, observe the relationship between the electroosmotic flow mobility (#eQf) and the induced gate voltage (Vg), as shown in Figures 6 and 7. Due to the ODT surface and PD MS The surface of the microchannel (2 1) is all methyl, so it is not affected by the pH of the solution. The size and polarity of the gate voltage can be completely controlled. # EQf [Electroosmotic flow rate] The size and direction. If it is formed by MUDA When the insulating layer (1 3), the carboxyl group on the surface is
第14頁 574130 五、發明說明(10) PJI6· 〇時,會解離成帶負電的表面,以當閘極電壓為負值 日守’可加強此絕緣層(1 3 )的負表面電位,所以量得的 A -比〇D T的更大,然而當閘極電壓為正時,所誘發出 的正表面電位無法克服原表面的負電性,以總和上還是呈 現負表面電位,使# e〇f無法呈現反向的控制广且大^較〇 D 丁的更小,但當ΡΗ3· 0時,表面並不會解離,所以又可 控制# ecf的方向與大小。 ,此,於下列表一中,將上述於先前技術中所提到的 、’研九與本發明相比較V eof的誘發效率。其中,比較 自/1 9 9 9 ·年,第一次使用光微影钱刻技術製作出可控制式 的微流體晶片的發展與進度,比較的結果明顯的顯示以s A 2做絕緣層所誘發出# ecf的控制範圍最好,其大小與方 向皆可受誘發電壓〔閘極電壓,Vg〕的大小與極性做線性 的控制’甚至在緩衝溶液ρΗ6· 〇也具有同樣的特性。所需 誘發的閑極電漫(vs)最小但其誘發的控制指數(control factor )為其他研究的一百倍,證明此發明可有效的以低 電壓(< 1 · 〇 V )達到完全控制微流體的流速與方向的目的 表一 降考文獻 氺 1 黑,液 絕緣層 誘發電聖 Vg (V) 飞八 e( mmmmm "eof (XiaW/Vs) )r〜 〜 … 广 控制指數 Δ /Zeof/ AVg (X104cm2/V2s) 材質 厚度 (nm) 1 Ί mi]X6~~~— (Si3N4) 390 25 〜-37 -2·0 〜1.5 5.6 1 43 (Si3N4) 390 50〜-50 4.3 〜6.0 1.7 L 3 ί (Si〇2) 50000 172〜52 -1.1-1.9 4.0 (SiOd 2000 460〜-300 -0.9^2.9 0.5 D (SiOJ 2000 460〜-300 1.2^3.4 0.3 本發明 (ODT) 2.9 0.8—0.8 -3.1-3.3 400.0 本發明 (ODT) 2.9 0.8 〜-0.8 -3.1 〜3·4 406.3Page 14 574130 V. Description of the invention (10) When PJI6 · 〇, it will dissociate into a negatively charged surface, and when the gate voltage is negative, it will strengthen the negative surface potential of this insulating layer (1 3), so The measured A-is larger than 〇DT. However, when the gate voltage is positive, the induced positive surface potential cannot overcome the negative electrical property of the original surface, and the negative surface potential appears as a sum, so that # e〇f Can not show the reverse control is wider and smaller than 0D, but the surface will not dissociate when ρ3.0, so you can control the direction and size of #ecf. Therefore, in Table 1 below, the efficiencies of V eof compared with the above-mentioned “Yan Jiu” in the prior art are compared with the present invention. Among them, comparing the development and progress of making a controllable microfluidic wafer for the first time using lithography and photoengraving technology since 199 · 9 · year, the comparison results clearly show that s A 2 is used as the insulating layer. Induced #ecf has the best control range, and its size and direction can be controlled linearly by the magnitude and polarity of the induced voltage [gate voltage, Vg] 'even in the buffer solution ρΗ6 · 〇. The induced idler diffusion (vs) is required to be the smallest but the control factor (induced) is one hundred times that of other studies, which proves that the invention can effectively achieve full control with low voltage (<1 · 〇V) The purpose of the velocity and direction of the microfluidics is shown in Table 1. 黑 1 Black, liquid-insulated layer induces electrical voltage Vg (V) Feiba e (mmmmm " eof (XiaW / Vs)) r ~ ~… Wide control index Δ / Zeof / AVg (X104cm2 / V2s) Material thickness (nm) 1 Ί mi] X6 ~~~ — (Si3N4) 390 25 ~ -37 -2 · 0 ~ 1.5 5.6 1 43 (Si3N4) 390 50 ~ -50 4.3 ~ 6.0 1.7 L 3 (Si〇2) 50000 172 ~ 52 -1.1-1.9 4.0 (SiOd 2000 460 ~ -300 -0.9 ^ 2.9 0.5 D (SiOJ 2000 460 ~ -300 1.2 ^ 3.4 0.3 The present invention (ODT) 2.9 0.8- 0.8 -3.1-3.3 400.0 The present invention (ODT) 2.9 0.8 ~ -0.8 -3.1 ~ 3.4 406.3
第15頁 574130 五、發明說明(π) *參考文獻 1.R.B.M.Schasfoort, S. Schlautmann, J. Hendr i kse, A. van den Berg, Science 28 6, 942(1999). 2.N.A.Poison, M.A.Hayes, Anal, Chem. 72, 1088(2000)· 3 · J · S · B u c h,P · - C · W a n g,D · L · D e v o e,C · S · L e e,Page 15 574130 V. Description of the invention (π) * References 1. RBMSchasfoort, S. Schlautmann, J. Hendr i kse, A. van den Berg, Science 28 6, 942 (1999). 2. NAPoison, MA Hayes, Anal, Chem. 72, 1088 (2000) · 3 · J · S · Buch, P · -C · Wang, D · L · D evoe, C · S · L ee,
Electrophoresis 22,3 9 0 2 ( 20 0 1 ). 由上述說明可知本發明嫁具如下優點: 1 · S A Μ (自組性薄膜)絕緣層(丄3 )的製成與修 飾容易,只需浸泡即可自發性的進行化學吸附與共鍵結形 成;另,透過不同官能基的選用即可改變修= 位與親疏水性。 胃的表面電 2.SAM絕緣層(1 3)的厚度極薄, 奈米以内,因此所需之相對誘發電壓小於丨、 可,而誘發電壓的大小可用一個乾電池來押 以下皆 成本更可縮小系統體積。 工制’不但精減Electrophoresis 22, 3 9 0 2 (2 0 1). From the above description, it can be seen that the present invention has the following advantages: 1 · SA Μ (self-organizing film) insulation layer (丄 3) is easy to make and modify, only need to soak That is, the chemical adsorption and co-bond formation can be performed spontaneously; in addition, the modification position and the hydrophilicity can be changed through the selection of different functional groups. The surface of the stomach 2. The thickness of the SAM insulation layer (1 3) is extremely thin, within nanometers, so the required relative induced voltage is less than 丨, and the magnitude of the induced voltage can be charged with a dry battery, and the cost can be reduced. System volume. Working system ’not only cuts
3·被誘發的表面電位所控制的電雙層 potential)可任意的控制電滲流的方向曰與户f ( uta 酸性或中性溶液下,可作為微管道中、速,無論在 幫浦。 儆S道中推動液體流動之液體 4·被誘發的表面電位所控制的電雙層電位r (Zet a3. The electric double-layer potential controlled by the induced surface potential can arbitrarily control the direction of the electroosmotic flow, and it can be used as a medium and low speed microtubule under the acid or neutral solution, regardless of the pump. 浦The liquid that pushes the liquid in S channel 4. The electric double-layer potential r (Zet a) controlled by the induced surface potential
574130 五、發明說明(12) :0:>]ed'任意控制微泳道内所檢測標的溶液中,所 ίΓ!ίϊ採樣及蛋白質採樣分析,因其測得信號= ^放=準確性的問題…,具有濃度之聚增產生 L唬放大的效果。 日庄王 5 ·因S A Μ〔自组性簿膜%丑,丄、 很小,故運用於生物晶片之〕微7^ 性疾病組織所在位置:么;=慕…植入人體之慢574130 V. Description of the invention (12): 0: >] ed 'Controls the detection of the target solution in the micro-lane. The sampling and protein sampling analysis, because the measured signal = ^ put = accuracy problem …, It has the effect of increasing the concentration and increasing the amplification. King of Zhuangzhuang 5 · Since SAM [Self-organizing membrane is ugly, ugly, very small, so it is used in biochips] Micro 7 ^ Sexual disease tissue location:?; = Mu ... Slowness of implantation into the human body
峰運用㈣〔自組性薄膜〕與小電壓1.0V :f (Zeta P〇tential)對人體的無危害之特性,來測 、病理級織所分泌的分泌物, 微泳道内治療標的藥劑的輪“,,信號來控制另一 物所造成對人體副作;輪出劑夏,…改善以往因藥 6·因SAM〔自組性薄臈〕在小雷 核誘發時,在pH3,具有相當2U1·,下的間極電 值影響,故SAM〔自組性薄膜7二二不受人體體液Μ 影響其效果。 不易被人體之體液所破壞,而 綜上所述,本發明實施例確能達到所 ,又其所揭露之具體構造,不僅未治# =翊之使用功效 亦去鉍八Μ於由社-Γ ^ σ m本9見諸於同類產品中, ,羑:i:出發;i利之申:全符合專利法之規定與要求 利懇請惠予審查,並賜准專 574130 圖式簡單說明 【圖式簡單 第一圖 第二圖 第三圖 第四圖 第五圖 第六圖 第七圖 第八圖 第九圖 〔參照圖號 <本發 (1 ) (12) (14) (16) (21) (3 ) <習知 (4 ) (6 ) 板立體分解示意圖 板組合側面剖視圖 板組合端面剖視圖 時的示意圖 滲流產生機制示意圖 電滲流移動率與誘發電壓 為 S A Μ〕 電滲流移動率與誘發電壓 Α 為 S A Μ〕 電滲流產生機制 電滲流產生機制 說明】 本發明之底板及頂 本發明之底板及頂 本發明之底板及頂 本發明於製造頂板 本發明微泳道内電 本發明經實驗後的 關係圖〔以〇D T :本發明經實驗後的 關係圖〔以M U D :其一習知微管道内 :其二習知微管道内 ) 明>The peak uses the self-organizing film and a small voltage of 1.0V: f (Zeta Potential) to harm the human body to measure the secretions secreted by pathological tissues, and the round of the target drug in the micro lane ", The signal to control the side effects of another thing caused by the human body; rotation of the agent Xia, ... to improve the past due to drugs 6. · SAM [self-organizing thin 臈] when induced by the small thunder nucleus, at pH 3, has a considerable 2U1 ·, The influence of the lower inter-electron value, so SAM [self-organizing film 7 222 is not affected by the body fluid M of the body. It is not easy to be damaged by the body fluid of the body, and in summary, the embodiment of the present invention can indeed achieve Therefore, the specific structure disclosed is not only untreated # = 翊 's use effect but also bismuth VIII Yu Youshe-Γ ^ σ m This 9 is found in similar products, 羑: i: departure; i profit Shen: It fully complies with the requirements and requirements of the Patent Law, and is grateful for your review, and will give Zhunzhu 574130 a simple explanation of the diagram. [Schematic diagram 1st diagram 2nd diagram 3rd diagram 4th diagram 5th diagram 6th diagram 7th diagram Eighth picture Ninth picture [Refer to the drawing number < The present (1) (12) (14) (16) (21) (3) < Know (4 ) (6) Dimensional decomposition of the plate Schematic view of the combination of the side view of the plate and the cross-section of the end surface of the plate. Schematic of the seepage generation mechanism. The electroosmotic flow rate and the induced voltage are SA M.] The electroosmotic flow rate and the induced voltage A are SA M.) The electroosmotic flow generation mechanism. Description of electroosmotic flow generation mechanism] The bottom plate of the present invention and the bottom plate of the present invention and the bottom plate of the present invention and the bottom plate of the present invention The relationship diagram after the experiment (with MUD: one of them is known in the micro-pipeline: the other is in the micro-pipeline).
> 底板 ( 1 1 ) 基板 閘極電極 ( 1 3 ) 絕緣層 源極電極 ( 1 5 ) 浅極電極 導線 ( 2 ) 頂板. 微泳道 ( 2 2 ) 儲存槽 母模 ( 3 1 ) 凸條 管壁 ( 5 ) 絕緣層 微管道 第18頁> Bottom plate (1 1) Substrate gate electrode (1 3) Insulation layer source electrode (1 5) Shallow electrode wire (2) Top plate. Micro-swim lane (2 2) Storage tank female mold (3 1) convex tube Wall (5) Insulated micropipes 第 18 页
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US10527626B2 (en) | 2013-07-05 | 2020-01-07 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
US11982678B2 (en) | 2009-04-13 | 2024-05-14 | University Of Washington Through Its Center For Commercialization | Ensemble-decision aliquot ranking |
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US11982678B2 (en) | 2009-04-13 | 2024-05-14 | University Of Washington Through Its Center For Commercialization | Ensemble-decision aliquot ranking |
US10527626B2 (en) | 2013-07-05 | 2020-01-07 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
TWI691724B (en) * | 2013-07-05 | 2020-04-21 | 美國華盛頓大學商業中心 | Apparatus for detecting particle in fluid sample and method for isolating aliquot of fluid sample within microfluidic chip |
US11480575B2 (en) | 2013-07-05 | 2022-10-25 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
US11808767B2 (en) | 2013-07-05 | 2023-11-07 | University Of Washington Through Its Center For Commercialization | Methods, compositions and systems for microfluidic assays |
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