TW200813324A - Fluidic device and controlling method thereof - Google Patents
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- TW200813324A TW200813324A TW96125027A TW96125027A TW200813324A TW 200813324 A TW200813324 A TW 200813324A TW 96125027 A TW96125027 A TW 96125027A TW 96125027 A TW96125027 A TW 96125027A TW 200813324 A TW200813324 A TW 200813324A
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Abstract
Description
200813324 F6495001OTWC1 22169-1-twf.doc/006 九、發明說明: 【發明所屬之技術領域】 本描述關於流體裝置及其控制方法。 【先前技術】200813324 F6495001OTWC1 22169-1-twf.doc/006 IX. Description of the Invention: [Technical Field of the Invention] This description relates to a fluid device and a control method therefor. [Prior Art]
可使用許多類型之測試裝置來偵測化合物之存在或分 析生化反應。舉例而言,可使用沿長度方向具有—或多個 測試線之橫向流薄膜(Lateral flow membrane)來執行横向:、穿 檢定(Lateral Flow Assays)。具有溶解之試劑的流體藉由電 滲透(Electro osmosis)自薄膜的一端行進至測試線。讀取者 偵測測試線處是否發生反應,其指示試劑中存在或並不存 在某些粒子。作為另一實例,可使用具有一組微毛細管的 衣置來控制免疫檢定處理中的流體流動。試劑定位於沿微 毛細管之長度的多個位置處,使得當流體歸因於毛細管力 在微毛細管中流動時,流體與試劑相接觸。讀取者監控試 诏位於之位點以判定是否已發生反應。作為又一實例,藉 由控制流經多個通道以及腔室的流體流動,可使用微流^ 晶片來執行檢定。可與提供用以驅動流體之驅動力的外部 電源及/或泵一起使用微流體晶片。 【發明内容】 本發明提出一種用於執行檢定之流體裝置,包括諸如 '、工栗、氣體泵、斷開式打開閥(Broken open valves)” 以及自關閉閥(self-close valves),,之控制組件,其用於控 制流體裝置中的流體流動。 在本發明所提出之用於執行檢定之流體裝置,可使用 5 200813324 P6495001OTW Cl 22169-1-twf.doc/006 且可使用氣體泵 真空泵來沿特定方向牽引通道中的流體 來沿特定方向推動通道中的流體。 齡=,明所提出之用於執行檢定之流體裝置,可使用 =打開閥來連接由使用者控制的兩個獨立區域,且可 使用自關閥來在流體經過後自動密封通道。 =明:斤提出之用於執行檢定之流體裝置,真空 "ι之乱:斷開式打開闊以及自關閉閥可製造成體積甚 ^讀,使得流體裝置可製造為體積甚小且可攜帶的裝 道二:供_一 差,使得流體於所述通道中移動^於通迢中產生昼力 容器外部之氣體壓力的氣體壓力,或⑻包 :::離材料ΐ第—容器斷開前與-第二材 材料與第二材料相互:二擇以使得在第- 在第含通道以及第-容器。 生壓力差。A 賴時,第—容騎通道中產 界定第㈣第—容器⑴ 之氣體壓力的氣_力,或包括3於=容器外部 ==器斷開前與-第二材料相“= 弟-材料經選擇以使得第一材料與第二材料相互作^ 6 200813324 P64950010TWC1 22169小 twfdoc/006 後立即產生氣體。 本發明提供一種流體裝置,包含界定第一區域之第一 ^材料以f界定第二區域之第二材料,此第二區域與第-區 域相分離。而更包括連接器耦接於第一區域與第二區域 之間,此連接器包含脆性材料且具有開放端以及閉合端。 此開,端安置於第二區域中,而閉合端安置於第一區域 中。第一區域藉由連接器之閉合端與第二區域隔斷。連接 _ 裔經設定以使得當所述連接器之閉合端斷開時,連接器界 定自第一區域至第二區域的通路。 本發明提供一種流體裝置,包含膨脹部分的通道,此 膨脹部分具有大於通道之相鄰部分的直徑,而更包括安 置於膨脹部分中的材料。此材料具有在吸附流體前並不阻 斷流體之通路的體積。其中此材料吸附流體之部分後體積 立即膨脹以使得膨脹後材料阻斷額外流體經過通道的通 路。而此材料包含超級吸附劑聚合物。 本舍明^供一種流體裝置,包含含有第一流體之第一 ⑩ 儲集器、含有第二流體之第二儲集器、主通道、第一分枝 通道、第二分枝通道、第一單次使用泵以及第二單次使用 — 泵。此第一分枝通道耦接到第一儲集器至主通道。而第二 - 分枝通道耦接到第二儲集器至主通道。此第一單次使用泵 則當第一單次使用泵中之容器斷開時,此第—單次使用泵 產生壓力差以移動第一流體以及第二流體中之一者或兩 者。而當第二單次使用泵中之容器斷開時,第二單次使用 泵產生壓力差以移動第一流體以及第二流體中之一者或兩 7 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6 者。 本發明提供-種控制流體之方法,包括提/ 以使得能夠取樣預定量之流體。而每—吸管包括^吸: ^容器’此容器斷開時於通道中產生壓力差,而此 脆,材料製成。此容器界^容器内之㈣,此空間且ς 部之氣體壓力的氣體壓力’其中斷;通 =預定量之壓力差,以使得預定量之流體“衫 自第士 ί控制流體之方法,包含使得流體能夠 自=-£域^動至弟二區域,其中,此第_區域藉由具有 及閉合端之連接器輕接至第二區域,而此開放端 —。弟一區域中,而此閉合端安置於第一區域中。此第 由連接器之閉合端與第二區域隔斷,其中使得流 動包^斷開連接器之閉合端,以形成經過連接器 區域至第二區域的祕。藉由使用吸喊體後體積 =的材料’來吸附流經連接器之流體的部分,以及使用 !膨脹之材料來阻斷額外流體進一步流經連接器。 本發明提供一種控制流體之方法,包含使流體於通道 :動,而此通道包括吸附流體之部分後體積立即膨脹的 钮料,使流體於通道中流動包括使流體之第一部分流經材 ^且使用所述材料來吸附流體之第二部分,從而使得材料 、&積膨脹。而藉由使用經膨脹之材料來阻斷額外流體經過 通道的通路。 本發明提供一種控制流體之方法,包含使流體經過通 8 200813324 P6495001OTWC1 22169-1-twf.doc/006 道’此通道包括第一自關閉閥以及第二自關閉閥。此第一 自關閉閥與第二自關閉閥彼此間隔開,每一自關閉閥包含 吸附流體之部分後體積立即膨脹的流體吸附材料。藉由使 用第一自關閉閥以及第二自關閉閥中的流體吸附材料來吸 附流體之部分。膨脹流體吸附材料之體積以阻斷額外流體 進一步經過通道的通路,於通道之第一自關閉閥與第二自 關閉閥之間的部分中保持預定量之流體。Many types of test devices can be used to detect the presence of a compound or to analyze a biochemical reaction. For example, a lateral flow membrane having - or a plurality of test lines along the length direction can be used to perform lateral:, Lateral Flow Assays. The fluid with the dissolved reagent travels from one end of the membrane to the test line by electroosmosis. The reader detects if a reaction has occurred at the test line indicating the presence or absence of certain particles in the reagent. As another example, a garment having a set of microcapillaries can be used to control fluid flow in an immunoassay process. The reagent is positioned at a plurality of locations along the length of the microcapillary such that when the fluid flows in the microcapillary due to capillary forces, the fluid contacts the reagent. The reader monitors the location at which the test is located to determine if a reaction has occurred. As a further example, by controlling the flow of fluid through a plurality of channels and chambers, the microfluidic wafer can be used to perform the assay. The microfluidic wafer can be used with an external power source and/or pump that provides a driving force to drive the fluid. SUMMARY OF THE INVENTION The present invention provides a fluid device for performing an assay, including, for example, ', a work pump, a gas pump, a Broken open valve, and a self-close valve, a control assembly for controlling fluid flow in the fluid device. In the fluid device for performing the assay proposed by the present invention, 5 200813324 P6495001OTW Cl 22169-1-twf.doc/006 can be used and a gas pump vacuum pump can be used. Traction fluid in the channel in a particular direction to push the fluid in the channel in a particular direction. Age =, the proposed fluid device for performing the assay, can use the = open valve to connect two separate areas controlled by the user, A self-closing valve can be used to automatically seal the passage after the fluid passes. = Ming: The fluid device proposed for the execution of the test, the vacuum " ι mess: the open type wide and the self-closing valve can be made into a volume ^Reading, so that the fluid device can be made into a very small and portable tunnel 2: for a difference, so that the fluid moves in the passage and generates a gas outside the pressure vessel in the overnight The gas pressure of the body pressure, or (8) package::: from the material ΐ first - the container is disconnected before - the second material and the second material are mutually: two in order to make the first - in the first channel and the - container. Pressure difference. A Lai, the first - Rong riding channel produced the gas pressure of the gas pressure defining the (fourth) - container (1), or including 3 = = outside the container = = before the device is disconnected and - the second material phase " = brother - the material is selected such that the first material and the second material interact with each other immediately after the generation of the gas twfdoc/006. The present invention provides a fluidic device comprising a first material defining a first region to define a second material of the second region, the second region being separated from the first region. The connector further includes a connector coupled between the first region and the second region, the connector comprising a brittle material and having an open end and a closed end. This opening, the end is disposed in the second region, and the closed end is disposed in the first region. The first region is separated from the second region by the closed end of the connector. The connection is set such that when the closed end of the connector is broken, the connector defines a passage from the first region to the second region. The present invention provides a fluid device comprising a channel of an expanded portion having a diameter greater than an adjacent portion of the channel and further comprising a material disposed in the expanded portion. This material has a volume that does not block the passage of the fluid prior to adsorption of the fluid. Where the material adsorbs a portion of the fluid, the volume immediately expands such that the expanded material blocks the passage of additional fluid through the passage. This material contains a super adsorbent polymer. The present invention provides a fluid device comprising a first 10 reservoir containing a first fluid, a second reservoir containing a second fluid, a main channel, a first branch channel, a second branch channel, and a first Single use pump and second single use - pump. This first branch channel is coupled to the first reservoir to the main channel. The second-branch channel is coupled to the second reservoir to the main channel. The first single use pump then creates a pressure differential to move one or both of the first fluid and the second fluid when the container in the first single use pump is disconnected. And when the container in the second single use pump is disconnected, the second single use pump generates a pressure difference to move one of the first fluid and the second fluid or both. 7 200813324 P64950010TWC1 22169-l-twf.doc/ 〇〇6. The present invention provides a method of controlling a fluid comprising: lifting to enable sampling of a predetermined amount of fluid. Each of the straws includes a suction: ^Container' This container creates a pressure differential in the passage when it is disconnected, and this is brittle and made of material. (4) in the container boundary (4), the space and the gas pressure of the gas pressure of the ' part is interrupted; the pass = the predetermined amount of pressure difference, so that the predetermined amount of fluid "the method of controlling the fluid from the shishi, including The fluid can be moved from the range of the range to the second area, wherein the first area is lightly connected to the second area by the connector having the closed end, and the open end is in the middle area, and the The closed end is disposed in the first region. The first end of the connector is separated from the second region, wherein the flow packet is disconnected from the closed end of the connector to form a secret through the connector region to the second region. The portion of the fluid flowing through the connector is adsorbed by the use of the material after the volume of the body, and the expanded material is used to block further fluid flow further through the connector. The present invention provides a method of controlling a fluid, including Fluid in the channel: moving, and the channel includes a button that adsorbs the portion of the fluid immediately after the volume expands, causing the fluid to flow in the channel includes flowing a first portion of the fluid through the material and using the material to adsorb the fluid The second part, thereby causing the material, & expansion, to block the passage of additional fluid through the passage by using the expanded material. The present invention provides a method of controlling a fluid comprising passing a fluid through a pass 8 200813324 P6495001OTWC1 22169- 1-twf.doc/006 Road 'This passage includes a first self-closing valve and a second self-closing valve. The first self-closing valve and the second self-closing valve are spaced apart from each other, and each self-closing valve includes a portion that adsorbs fluid a fluid adsorbing material that expands immediately after the volume. The portion of the fluid is adsorbed by using the first self-closing valve and the fluid adsorbing material in the second self-closing valve. The expanding fluid adsorbs the volume of the material to block the passage of the additional fluid further through the passage. Maintaining a predetermined amount of fluid in a portion between the first self-closing valve of the passage and the second self-closing valve.
本發明提供一種控制流體之方法,包含阻斷由脆性材 料製成之第一容器以於通道中產生壓力差,使得第一流體 自第一儲集器移動至通道之第一區段。此第一容器(a) 界定第一容器内之空間,此空間具有不同於第一容器外部 之氣體壓力的氣體壓力,或(b)包括第一材料,此第一材 料,第一容器斷開前與第二材料相分離,此第一材料以及 此第二材料經選擇以使得第一材料與第二材料相互作用後 立即產生氣體。阻斷由脆性材料製成之第二容ϋ,以於通 迢中,生壓力差,使得第—流體之至少部分轉 迢之第二區段。 《 口口本毛明提供-種控制流體之方法,包含同時操 一 泵以及第二單次使用泵’以吸取樣本流體之第一 口 P刀至弟一通這及吸取樣本流體之第二 道。阻斷第一單次使用泵中之第 弟一通 使得樣本流體之第—部分自 ς 生麗力差, 流體之第二部分自儲集器移動 斷第二單次使用泵㈣通f且阻 --^ - ‘ 產生麼力差,使得樣本 第二通道。同時操作第 9 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6 單次使用泵以及第四單次使用泵以吸取第一緩衝溶液至第 一通道及吸取第二緩衝溶液至第二通道。 ^ 【實施方式】 • 種用於執行檢定之流體裝置可包括諸如真空泵、氣 體泵 所開式打開閥(Broken open valves),,以及“自關 閉閥(self-d〇se valvesy,之控制組件,其用於控制流體裝置 中的流體流動。可使用真空泵來沿特定方向牽引通道中的 0 抓體且可使用氣體泵來沿特定方向推動通道中的流體。 可使用斷開式打關來連接由使用者控制兩個獨立區 域且可使用自關閉閥來在流體經過後自動密封通道。真 空泵、氣體泵、斷開式打開閥以及自關閉閥可製造為小的, 使得流體裝置可製造為小的且為可攜帶的。 在以下描述中,可首先引入個別控制組件,且隨後為 控制組2如何經組合以建構用於控制流體裝置中之流體的 模組化單元的描述。隨後將描述如何使用流體 生物性檢定。 τ 鲁 參看圖1Α’可藉由將容器1〇〇置放於由材料1〇2界定 之通道1〇6(或腔室)中來建構真空栗9〇。容器1〇〇封閉 區域104 ’區域1〇4為真空或具有與通道1〇6中之氣體壓 力相比較低的氣體愿力。 參看圖1Β,容器100可為(例如)玻璃毛細管,1在 ,加外力後立即斷開。當容器1〇〇斷開時,通道ι〇6 /中之 氣體流入真空區域104中’從而降低區域刚中之壓力。 以此方式產生可沿方向1〇8牽引流體以使其朝向區域刚 200813324 P6495001OTWC1 22169-1-twf.doc/006 的吸引力。 圖25A至圖25C展示使用置放於橡皮管中之玻璃毛 細管之真空泵的實例。圖25A展示氣體泵410的橫截面, 氣體泵410具有置放於橡皮管418中的真空玻璃毛細管 416,其中管418具有閉合端424以及開放端426。圖25B 展示氣體泵412的橫截面,氣體泵412類似於氣體泵410, 除了具有一帶有兩個開放端之橡皮管420之外。圖25C展 示連接至兩個橡皮管428的氣體泵412,其中橡皮管420 具有較大於橡皮管428的内徑(以容納玻璃毛細管416)。 圖26A以及圖26B展示使用置放於平面流體通道中之 玻璃毛細管之真空泵的實例。圖26A展示真空泵430的橫 截面,真空泵430具有置放於由平面基板434界定之流體 通道438中的真空玻璃毛細管416。流體通道438具有閉 合端440以及開放端442。平面基板434由剛性材料製成。 彈性層436後入於基板434中鄰近毛細管416之位置處, 使得允許使用者經由彈性層施加外力以斷開毛細管416。 圖26B展示真空泵432的橫截面,真空泵432類似於 真空泵430,除了流體通道438連接至具有較小橫截面之 兩個流體通道444之外。 可藉由加熱玻璃毛細管之一端以熔融玻璃而形成第一 閉合端來製成真空玻璃毛細管。使用真空泵來經由開放端 抽汲出玻璃毛細管中的空氣。在距第一閉合端一距離處加 熱破璃毛細管。熱量軟化玻璃,可捏縮或扭轉經軟化之玻 璃以形成第二閉合端。 11 200813324 P6495001OTWC1 22169-1-twf.doc/006 參看圖2A,可藉由將容器no置放於由材料1〇2界定 之通道106 (或腔室)中來建構氣體泵92。容器11〇封$ ' 區域112,區域Π2具有與容器11〇外部之通道1〇6中2 . 氣體壓力相比較高的氣體壓力。 參看圖2B,容器110可為(例如)玻璃毛細管,其在 施加外力後立即斷開。當容器110斷開時,原先在容器 内部之氣體流出容器110,從而增大了區域1〇6中之壓力。 • 以此方式產生可沿方向I14推動流體以使其遠離區域106 的力。 在此描述中,將使用術語“真空泵,,來泛指一種產生 牽的裝置,其可用以朝向裝置牽引流體;且將使用術 吾氣體泵來泛指一種產生推動力的裝置,其可用以推 動流體以使其遠離裝置。 存在用以建構氣體泵之替代方式。舉例而言,參看圖 3A,可藉由將部分填充有第一材料126的玻璃毛細管12〇 置放於含有第二材料128的通道124 (或腔室)中來製造 氣體泵94。選擇第一材料126以及第二材料128,使得當 • 材料126與材料128彼此混合時兩者將相互作用且產生一 或夕種,體=舉例而言,第一材料126可為碳酸鈉(Na2C〇3) 及/或碳酸氫鈉(NaHC〇3),且第二材料128可為乙酸 (CH2COOH)。 參看圖3B,當施加外力以斷開玻璃毛細管120時,第 材料^26與第—材料mg相互作用且產生氣體。在此實 例中,氣體為二氧化碳(C〇2)。發生之化學反應為·· 12 200813324 P64950010TWC1 22169-1 -twf.doc/006The present invention provides a method of controlling a fluid comprising blocking a first container made of a brittle material to create a pressure differential in the passage such that the first fluid moves from the first reservoir to the first section of the passage. The first container (a) defines a space within the first container, the space having a gas pressure different from the pressure of the gas outside the first container, or (b) including a first material, the first material, the first container being disconnected The front material is separated from the second material, and the first material and the second material are selected such that a gas is generated immediately after the first material interacts with the second material. The second volume made of a brittle material is blocked to create a pressure difference such that at least a portion of the first fluid is transferred to the second section. Oral Benjamin provides a method of controlling fluid, including simultaneously operating a pump and a second single use pump to draw a first P knife of the fluid to the second pass and a second sample of the sample fluid. Blocking the first pass of the first single use pump makes the first part of the sample fluid self-generated, and the second part of the fluid moves from the reservoir to break the second single use pump (four) through f and resistance - -^ - ' Produces a difference in force, making the sample the second channel. Simultaneous operation 9 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6 Single use pump and fourth single use pump to draw the first buffer solution to the first channel and draw the second buffer solution to the second channel. ^ [Embodiment] The fluid device for performing the verification may include, for example, a vacuum pump, a blown open valve of a gas pump, and a self-closing valve (self-d〇se valvesy, a control component, It is used to control fluid flow in a fluidic device. A vacuum pump can be used to pull the 0 gripper in the channel in a particular direction and a gas pump can be used to push the fluid in the channel in a particular direction. The user controls two separate zones and can use a self-closing valve to automatically seal the passage after the fluid has passed. The vacuum pump, gas pump, disconnect open valve, and self-closing valve can be made small so that the fluid device can be made small And in the following description, individual control components can be introduced first, and then a description of how the control group 2 can be combined to construct a modularized unit for controlling fluid in the fluidic device. How to use it will be described later Fluid bioassay. τ Lu can be constructed by placing the container 1 in the channel 1〇6 (or chamber) defined by the material 1〇2. The vacuum pump 9 〇. The container 1 〇〇 closed area 104 'area 1 〇 4 is vacuum or has a lower gas force than the gas pressure in the channel 1 〇 6. Referring to Figure 1 容器, the container 100 can be, for example, glass The capillary, 1 is disconnected immediately after the external force is applied. When the container 1 is disconnected, the gas in the channel ι 6 / flows into the vacuum region 104 'to reduce the pressure in the region just before. 1〇8 draws the fluid so that it faces the attraction of the region just 200813324 P6495001OTWC1 22169-1-twf.doc/006. Figures 25A-25C show an example of a vacuum pump using a glass capillary placed in a rubber hose. Figure 25A shows In cross-section of gas pump 410, gas pump 410 has a vacuum glass capillary 416 disposed in rubber tube 418, wherein tube 418 has a closed end 424 and an open end 426. Figure 25B shows a cross section of gas pump 412, similar to gas pump 412 The gas pump 410 has, in addition to having a rubber tube 420 with two open ends. Figure 25C shows a gas pump 412 coupled to two rubber tubes 428, wherein the rubber tube 420 has an inner diameter that is larger than the rubber tube 428 ( A glass capillary 416 is housed. Figures 26A and 26B show an example of a vacuum pump using a glass capillary placed in a planar fluid channel. Figure 26A shows a cross section of a vacuum pump 430 having a fluid placed on a planar substrate 434 The vacuum glass capillary 416 in the channel 438. The fluid channel 438 has a closed end 440 and an open end 442. The planar substrate 434 is made of a rigid material. The elastic layer 436 is post-into the substrate 434 adjacent the capillary 416, allowing the user An external force is applied via the elastic layer to break the capillary 416. Figure 26B shows a cross section of a vacuum pump 432 that is similar to vacuum pump 430 except that fluid passage 438 is coupled to two fluid passages 444 having a smaller cross section. A vacuum glass capillary can be made by heating one end of the glass capillary to melt the glass to form a first closed end. A vacuum pump is used to draw air out of the glass capillary via the open end. The glass capillary is heated at a distance from the first closed end. The heat softens the glass and can pinch or twist the softened glass to form a second closed end. 11 200813324 P6495001OTWC1 22169-1-twf.doc/006 Referring to Figure 2A, gas pump 92 can be constructed by placing container no in channel 106 (or chamber) defined by material 1〇2. The container 11 encloses the $' region 112, which has a higher gas pressure than the gas pressure in the channel 1〇6 outside the container 11〇. Referring to Fig. 2B, the container 110 can be, for example, a glass capillary that is broken immediately after an external force is applied. When the container 110 is disconnected, the gas originally inside the container flows out of the container 110, thereby increasing the pressure in the area 1〇6. • In this way a force is generated that can push the fluid in direction I14 away from region 106. In this description, the term "vacuum pump" will be used to refer to a device for generating a pull that can be used to pull fluid toward the device; and a gas pump will be used to refer to a device that generates a push force that can be used to push The fluid is moved away from the device. There is an alternative way to construct the gas pump. For example, referring to FIG. 3A, the glass capillary 12 partially filled with the first material 126 can be placed in the second material 128. A gas pump 94 is fabricated in the channel 124 (or chamber). The first material 126 and the second material 128 are selected such that when the material 126 and the material 128 are mixed with each other, the two will interact and produce one or the other species, body = For example, the first material 126 can be sodium carbonate (Na2C〇3) and/or sodium bicarbonate (NaHC〇3), and the second material 128 can be acetic acid (CH2COOH). Referring to Figure 3B, when an external force is applied to break When the glass capillary 120 is opened, the first material 26 interacts with the first material mg to generate a gas. In this example, the gas is carbon dioxide (C〇2). The chemical reaction that occurs is ·· 12 200813324 P64950010TWC1 22169-1 -twf .doc/006
Na2C03 + 2 CH2COOH + 2 NaCOOCH2 + H20 + C02Na2C03 + 2 CH2COOH + 2 NaCOOCH2 + H20 + C02
NaHC03 + CH2COOH NaCOOCH2 + H20 + C02 >一氧化奴增大通道124中之壓力,從而產生可用以推 動流體遠離斷開之毛細管120的力。 第一材料126可直接填充至毛細管12〇中。參看圖 27A,第一材料126亦可附著至導線450,隨後導線 與塗伟材料126 —起置放於毛細管12〇内部。圖27B展示 將玻璃毛細管120置放於橡皮管418内之通道124中的實 例。通道124含有第二材料128,當玻璃毛細管120斷開 時第二材料128可與第一材料126相互作用。圖27C展示 將玻璃毛細管120置放於平面裝置基板434内之流體通道 438中的實例。彈性層436嵌入於基板434申鄰近毛細管 120之位置處,使得允許使用者經由彈性層436施加外力 以斷開毛細管120。 參看圖4A,可藉由以下步驟來製造氣體泵96 :將化 合物130置放於玻璃毛細管132中、密封毛細管132、加 熱毛細官132、冷卻毛細管132且將毛細管132置放於通 迢106 (或腔室)中。將化合物13()選擇為在加熱後產生 氣體的材料。當加熱及冷卻毛細管132時,由化合物13〇 產生之氣體增大毛細管132内部的氣體壓力(與毛細管132 外部的氣體壓力相比較)。 化合物130之實例包括碳酸氫鈉(NaHC〇3)以及碳酸鈣 (CaC〇3)。此等化合物加熱時產生二氧化碳:NaHC03 + CH2COOH NaCOOCH2 + H20 + C02 > Monooxide increases the pressure in channel 124, creating a force that can be used to push the fluid away from the broken capillary 120. The first material 126 can be directly filled into the capillary 12〇. Referring to Fig. 27A, the first material 126 can also be attached to the wire 450, and the wire can then be placed inside the capillary 12〇 with the wei wei material 126. Figure 27B shows an example of placing a glass capillary 120 in a channel 124 in a rubber tube 418. Channel 124 contains a second material 128 that can interact with first material 126 when glass capillary 120 is broken. Figure 27C shows an example of placing glass capillary 120 in fluid channel 438 within planar device substrate 434. The elastic layer 436 is embedded in the substrate 434 adjacent to the capillary 120 such that the user is allowed to apply an external force via the elastic layer 436 to break the capillary 120. Referring to FIG. 4A, a gas pump 96 can be fabricated by placing the compound 130 in a glass capillary 132, sealing the capillary 132, heating the capillary 132, cooling the capillary 132, and placing the capillary 132 in the overnight 106 (or In the chamber). Compound 13 () was selected as a material which generates a gas after heating. When the capillary 132 is heated and cooled, the gas generated by the compound 13A increases the gas pressure inside the capillary 132 (compared to the gas pressure outside the capillary 132). Examples of the compound 130 include sodium hydrogencarbonate (NaHC〇3) and calcium carbonate (CaC〇3). These compounds produce carbon dioxide when heated:
NaHC03 NaOH + C〇2 13 200813324 P64950010TWC1 22169小 twf.doc/006NaHC03 NaOH + C〇2 13 200813324 P64950010TWC1 22169 small twf.doc/006
CaC03 CaO + C02 亦可使用自固態變化為氣態的昇華材料(例如,變為(^^的 乾冰)。圖4B之材料表中列出加熱時產生氣體的其他材^或 如NaN3加熱產生氮氣(2 NaN3 —> 2Na + 3N2) 〇 參看圖5A,可藉由將玻璃毛細管142置放於第一通道 148與第二通道150之間來製造斷開式打開閥i4〇。玻璃毛 細管142具有定位於第一通道148中的開放端144,以及 定位於第二通道150中的閉合端146。當玻璃毛細管完整 無損時’流體無法於第一通道148與第二通道15〇之間流 動。此稱為斷開式打開闊之“關閉,,狀態。 參看圖5B,當施加外力以斷開玻璃毛細管142時,連 接通道148與通道150之通路152形成了。此稱為斷開式 打開閥之“打開”狀態。斷開式打開閥14〇可用於允許兩 種流體(或一種流體以及一種固體)初始相分離,隨後在 由使用者控制之時刻相互作用。 圖28A以及圖28B展示使用斷開式打開閥來建構低成 本裝置的實例,低成本裝置用於執行其中用紫外(uv)光 輻射流體的檢定。玻璃毛細管142連接兩個塑膠通道46〇 以及462。初始,反應劑464包含於第一塑膠通道462中。 玻璃毛細管142斷開後,反應劑464立即流經玻璃毛細管 142至第二塑膠通道46〇。如圖28]B所示,當反應劑464 流經玻璃毛細管142時,UV光源466輻射反應劑464。偵 測器468偵測通過反應劑464的UV光。偵測器468所偵 測到之UV光的光譜可用於判定反應劑464中的化合物。 圖28C展示具有方形内周邊以及外周邊之玻璃毛細管 14 200813324 P6495001OTWC1 22169-1-twf.doc/006 的橫截面。方形内周邊以及外周邊允許UV光沿垂直於玻 璃毛細管之表面的方向通過玻璃毛細管。與毛細管具有圓 形橫截面相比較,毛細管具有方形橫截面之此方式允許更 多UV光達到玻璃毛細管中之流體,其中圓形橫截面可能 ’ 引起入射UV光沿遠離流體之方向反射或重定向。 參看圖6A以及圖6B ’可藉由將超級吸附劑聚合物 (Superabsorbent polymer,底下簡稱“sap”)162 置放 於通道164中來製造自關閉閥160。初始,SAP 162具有 較小體積且允許流體於通道164中之第一區域ι66與第二 區域168之間流動(圖6A)。此稱為自關閉閥之“打開” 狀態。當流體流經SAP 162時,SAP吸附流體之部分且體 積膨服’從而阻斷通道164 (圖6B ),藉此阻止流體於第 一區域166與第二區域168之間進一步流動。此稱為自關 閉閥之“關閉”狀態。 超級吸附劑聚合物可吸附且保持水或其他水溶液的大 體積。在某些實例中,SAP可由經化學改質之澱粉以及纖 ⑩ 維素以及其他聚合物製成,諸如,高親水性且對水呈有高 親和性的聚(乙烯醇)PVA、聚(氧化乙烯)pE〇/。'在= -些實例中,超級吸附劑聚合物可由部分中和且輕度交聯的 * 料丙烯酸)製成,部分中和且輕度交聯的聚(丙烯酸) 具有良好之效⑥相對成本的比率。聚合物可製造成具有低 固體含量,Pi後將聚合物乾燥且研磨為白色粒狀固體。在 水中,白色固體膨脹為在某些情況下可包括重量百分比古 達99%之水的橡膠凝膠。 ^ 15 200813324 P6495001OTWC1 22169-1-twf.doc/006 參看圖7A ’自關閉閥170可包括通道164,通道刚 具有擴大部分172以容納超級吸附劑聚合物162 ,使得超 ^ 級吸附劑聚合物162在膨脹前並不限制流體的流動。為^ 製造自關閉閥no,可將黏附劑塗覆至擴大部分172的内 ^ 壁,以粉末形態的SAP 162隨後被推動至通道164中, 得SAP 162粉末黏附至擴大部分172處之内壁。 參看圖7B,當流體流經超級吸附劑聚合物162時,超 φ 級吸附劑聚合物162吸附流體之部分且體積膨脹,從而^ 斷通道164,藉此阻止流體進一步流經膨脹之聚合物162。 參看圖8A以及圖8B,超級吸附劑聚合物162可附著 至導線180,隨後置放於通道164中。通道164可具有凹 座區域182,凹座區域182中塗覆有黏附劑以將導線18〇 緊固於預界定位置處。 參看圖8C,當流體流經超級吸附劑聚合物162時,聚 合物162吸附流體之部分且體積膨脹,從而阻斷通道164, 藉此阻止流體進一步流經膨脹之聚合物162。 • 可藉由用SAP塗佈導線、隨後將經塗佈之導線置放於 • 通道或管中來製造自關閉閥。可藉由用SAP塗佈平面基 板、隨後將經塗佈之基板置放於平面流體裝置中之平面通 • 運中來製造用於平面流體裝置的自關閉閥。 ^參看圖9A至圖9C,可藉由使用玻璃毛細管142以及 1位於毛細管142外部且鄰近毛細管142之SApi62來製 以,關開閥190。毛細管142與SAP 162皆定位於具有第 一區域166以及第二區域168的通道164中。使用玻螭毛 16 200813324 P64950010TWC1 22169-l-twf.doc/006 細管142以及SAP類似於使用斷開式打開閥與自關閉閥之 組合。開關開閥190使得使用者能夠藉由允許、隨後阻斷、 且隨後允許流體經過特定位置而控制流體流經通道中之特 定位置的流動。 . ,參看圖9A,初始,SAP 162具有較小體積且並不阻斷 通道,從而允許流體於第一區域166與第二區域168之間 流動。 _ 參看圖9B,當流體經過時,流體之部分被SAp 162 吸附,從而使得SAP 162體積增大,藉此阻斷流體於第一 區域166與第二區域168之間的進一步流動。 參看圖9C,當施加外力以斷開玻璃毛細管142時,產 生通路152以允許流體於第一區域166與第二區域168之 間流動。 參看圖10A至圖l〇c,可藉由使用玻璃毛細管142以 及定位於毛細管142内部之SAP 162來製造關開關闊 200。毛細管142具有開放端144以及閉合端146。開放端 • I44定位於第一通道148中,且閉合端146定位於第二通 道150巾。玻璃毛細管142以及SAp 162執行類似於斷開 - 式打開閥與自關閉閥之組合的功能。關開關閥2〇〇使得使 - 用者能夠藉由阻斷、隨後允許、且隨後阻斷流體經過特定 位置而控制流體流經通道中之特定位置的流動。 參看圖10A,當玻璃毛細管142完整無損時,第一 道148與第二通道150並不相連接。 參看圖10B ’當施加外力靖開玻璃毛細管142時, 17 200813324 P6495001OTWC1 22169-1-twf.doc/006 形成通路152,從而允許流體於通道148與15〇之間流動。 SAP 162初始具有較小體積且並不阻斷流體於通路152中 的流動。 參看圖10C ’當流體流經通路152時,流體之部分被 SAP 162吸附,從而使得SAP體積增大且阻斷通路152, 藉此阻止流體進一步流經通路152。 參看圖11A至圖11D,可藉由使用玻璃毛細管142、 • 定位於毛細管I42内部之SAP 212,以及定位於毛細管142 外部之SAP 214來製造開關開關閥(〇n_〇ff_〇n_〇ff valve)。玻璃毛細管142、SAP 212,以及SAP 214置放於 通道164中。玻璃毛細管142、SAP212,以及SAp2M執 行類似於斷開式打開閥與兩個自關閉閥之組合的功能。開 關開關閥210使得使用者能夠藉由允許、隨後阻斷、隨後 允許、且隨後阻斷流體經過特定位置而控制流體流經通道 中之特定位置的流動。 參看圖11A,初始,SAP 214具有較小體積且允許流 攀 體於通道164之第一區域166與第二區域168之間流動。 參看圖11B,當流體經過時,流體之部分被SAp 214 吸附,從而使得SAP 214體積增大,藉此阻斷流體於第_ , 區域166與第二區域168之間的進一步流動。 參看圖lie,當施加外力以斷開玻璃毛細管142時, 开成通路152以允許流體於弟一區域166與第二區域168 之間流動。 參看圖11D,當流體流經SAP 212時,流體之部分被 18 200813324 P64950010TWC1 22169-l-twf.doc/006 =T吸附:從而使得SAp 212體積增大且阻斷通路 152,猎此阻止流體進一步流經通路。 ί看圖12’可藉由使用_接至吸管管體224的真* =2來建構用於吸取預定量之流體的計量吸管(跑咖 ipette)22〇。真空泵222包括置放於吸管球體挪中的真 毛細f削。為了使用計量奸挪,咖玻璃毛細 S 100以產生將流體吸取至吸管管體224中的吸引力。CaC03 CaO + C02 can also be used as a sublimation material that changes from a solid state to a gaseous state (for example, it becomes a dry ice of (^^). The material table of Fig. 4B lists other materials which generate gas when heated or nitrogen gas generated by heating like NaN3 ( 2 NaN3 -> 2Na + 3N2) 〇 Referring to Fig. 5A, a break open valve i4〇 can be fabricated by placing a glass capillary 142 between the first passage 148 and the second passage 150. The glass capillary 142 has positioning The open end 144 in the first passage 148 and the closed end 146 positioned in the second passage 150. When the glass capillary is intact, the fluid cannot flow between the first passage 148 and the second passage 15〇. For the open type, the "closed, state" is shown. Referring to Fig. 5B, when an external force is applied to break the glass capillary 142, the connecting passage 148 is formed with the passage 152 of the passage 150. This is called a "disconnected opening valve". Open "state. Disconnected open valve 14" can be used to allow initial separation of the two fluids (or a fluid and a solid) and then interact at a time controlled by the user. Figures 28A and 28B show the use of breakaway An example of a low cost device is opened by opening a valve for performing a test in which a fluid is irradiated with ultraviolet (uv) light. A glass capillary 142 connects the two plastic channels 46 and 462. Initially, the reactant 464 is included in the first In the plastic channel 462. After the glass capillary 142 is broken, the reactant 464 immediately flows through the glass capillary 142 to the second plastic channel 46. As shown in Figure 28]B, when the reactant 464 flows through the glass capillary 142, the UV light source 466 Radiation Reagent 464. Detector 468 detects UV light passing through Reagent 464. The spectrum of UV light detected by detector 468 can be used to determine the compound in Reagent 464. Figure 28C shows a square inner perimeter And a cross section of the outer periphery of the glass capillary 14 200813324 P6495001OTWC1 22169-1-twf.doc/006. The inner circumference of the square and the outer periphery allow UV light to pass through the glass capillary in a direction perpendicular to the surface of the glass capillary. Compared to the cross-section, the capillary has a square cross-section which allows more UV light to reach the fluid in the glass capillary, where a circular cross-section may 'cause The UV light is reflected or redirected away from the fluid. Referring to Figures 6A and 6B, a self-closing valve can be fabricated by placing a Superabsorbent Polymer ("sap") 162 in the channel 164. 160. Initially, the SAP 162 has a smaller volume and allows fluid to flow between the first zone ι 66 and the second zone 168 in the channel 164 (Fig. 6A). This is referred to as the "open" state of the self-closing valve. As the fluid flows through the SAP 162, the SAP adsorbs a portion of the fluid and expands to block the passage 164 (Fig. 6B), thereby preventing further flow of fluid between the first region 166 and the second region 168. This is referred to as the "off" state of the self-closing valve. Supersorbent polymers adsorb and retain the bulk of water or other aqueous solutions. In certain instances, SAP can be made from chemically modified starches as well as cellulose 10 and other polymers, such as poly(vinyl alcohol) PVA, poly (oxidized) which is highly hydrophilic and has a high affinity for water. Ethylene) pE〇/. 'In some examples, supersorbent polymers can be made from partially neutralized and lightly crosslinked acrylic acid, partially neutralized and lightly crosslinked poly(acrylic acid) with good efficiency 6 relative cost The ratio. The polymer can be made to have a low solids content, and after the Pi, the polymer is dried and ground to a white granular solid. In water, the white solid swells to a rubber gel which in some cases may comprise up to 99% by weight of the water. ^ 15 200813324 P6495001OTWC1 22169-1-twf.doc/006 Referring to Figure 7A, the self-closing valve 170 can include a channel 164 having a flared portion 172 to accommodate the super-adsorbent polymer 162 such that the super-adsorbent polymer 162 The flow of fluid is not limited prior to expansion. To make the self-closing valve no, an adhesive can be applied to the inner wall of the enlarged portion 172, and the SAP 162 in powder form is then pushed into the passage 164, and the SAP 162 powder is adhered to the inner wall at the enlarged portion 172. Referring to Figure 7B, as the fluid flows through the supersorbent polymer 162, the super-φ adsorbent polymer 162 adsorbs a portion of the fluid and expands in volume, thereby breaking the passage 164, thereby preventing further flow of fluid through the expanded polymer 162. . Referring to Figures 8A and 8B, supersorbent polymer 162 can be attached to lead 180 and subsequently placed in channel 164. Channel 164 can have a recessed region 182 that is coated with an adhesive to secure wire 18〇 at a predefined location. Referring to Figure 8C, as fluid flows through the supersorbent polymer 162, the polymer 162 adsorbs a portion of the fluid and expands in volume, thereby blocking the passage 164, thereby preventing further flow of fluid through the expanded polymer 162. • Self-closing valves can be fabricated by coating the wires with SAP and then placing the coated wires in a channel or tube. Self-closing valves for planar fluidic devices can be fabricated by coating a planar substrate with SAP and subsequently placing the coated substrate in a planar communication in a planar fluidic device. Referring to Figures 9A through 9C, the valve 190 can be closed by using a glass capillary 142 and a SApi 62 located outside of the capillary 142 and adjacent to the capillary 142. Capillary 142 and SAP 162 are both positioned in channel 164 having a first region 166 and a second region 168. Use of glass wool 16 200813324 P64950010TWC1 22169-l-twf.doc/006 The thin tube 142 and SAP are similar to the combination of a disconnected open valve and a self-closing valve. Switching the open valve 190 allows the user to control the flow of fluid through a particular location in the channel by allowing, subsequently blocking, and then allowing fluid to pass through a particular location. Referring to Figure 9A, initially, SAP 162 has a smaller volume and does not block the passage, allowing fluid to flow between first region 166 and second region 168. Referring to Figure 9B, as the fluid passes, a portion of the fluid is adsorbed by SAp 162, thereby increasing the volume of SAP 162, thereby blocking further flow of fluid between first region 166 and second region 168. Referring to Figure 9C, when an external force is applied to break the glass capillary 142, a passage 152 is created to allow fluid to flow between the first region 166 and the second region 168. Referring to Figures 10A through 10c, the switch width 200 can be fabricated by using a glass capillary 142 and an SAP 162 positioned inside the capillary 142. Capillary 142 has an open end 144 and a closed end 146. Open End • I44 is positioned in the first channel 148 and the closed end 146 is positioned in the second channel 150. The glass capillary 142 and the SAp 162 perform a function similar to the combination of the open-type open valve and the self-closing valve. Turning off the switching valve 2〇〇 enables the user to control the flow of fluid through a particular location in the channel by blocking, subsequently allowing, and then blocking fluid flow through a particular location. Referring to Figure 10A, when the glass capillary 142 is intact, the first track 148 is not connected to the second channel 150. Referring to Fig. 10B', when an external force is applied to the glass capillary 142, 17 200813324 P6495001OTWC1 22169-1-twf.doc/006 forms a passage 152 to allow fluid to flow between the passages 148 and 15〇. The SAP 162 initially has a small volume and does not block the flow of fluid in the passage 152. Referring to Figure 10C', as fluid flows through passage 152, portions of the fluid are adsorbed by SAP 162, causing the SAP volume to increase and block passage 152, thereby preventing fluid from flowing further through passage 152. Referring to Figures 11A through 11D, the switch-on/off valve can be manufactured by using a glass capillary 142, an SAP 212 positioned inside the capillary I42, and a SAP 214 positioned outside the capillary 142 (〇n_〇ff_〇n_〇 Ff valve). Glass capillary 142, SAP 212, and SAP 214 are placed in channel 164. The glass capillary 142, SAP 212, and SAp2M perform a function similar to the combination of a disconnected open valve and two self-closing valves. Switching on and off the switching valve 210 allows the user to control the flow of fluid through a particular location in the channel by allowing, subsequently blocking, subsequently allowing, and subsequently blocking fluid flow through a particular location. Referring to Figure 11A, initially, the SAP 214 has a relatively small volume and allows flow to flow between the first region 166 and the second region 168 of the passage 164. Referring to Figure 11B, as the fluid passes, a portion of the fluid is adsorbed by SAp 214, thereby increasing the volume of SAP 214, thereby blocking further flow of fluid between the first, region 166 and second region 168. Referring to Fig. lie, when an external force is applied to break the glass capillary 142, the passage 152 is opened to allow fluid to flow between the first region 166 and the second region 168. Referring to Figure 11D, as the fluid flows through the SAP 212, the portion of the fluid is adsorbed by 18 200813324 P64950010TWC1 22169-l-twf.doc/006 = T: thereby increasing the volume of the SAp 212 and blocking the passage 152, which prevents the fluid from furthering Flow through the passage. Referring to Figure 12', a metering straw 22 can be constructed for drawing a predetermined amount of fluid by using the true * = 2 connected to the pipette body 224. The vacuum pump 222 includes a true capillary fry placed in the suction ball. In order to use the metering, the glass capillary S 100 is used to create an attractive force for drawing fluid into the straw body 224.
,製造-批計量吸管22〇時,球體226以及玻璃毛細 官1〇〇之尺寸可製成相同的。球體226以及玻璃毛細管⑽ 、、^計以當使用者按壓球體226以斷開玻璃毛細管1〇〇 時,引起玻璃毛細f 1〇〇斷開所需要之施予球體226的變 形量對於所有計量吸管220而言為大體相同的。以此方 式’使用者可使用計量吸管22G來在無f監控莖狀物— 中之流體含量的情況下快速吸取預定量之流體。 舉例而言,參看圖21A以及圖21B,可使用計量吸管 220來快速自患者取樣預定量之血液a?。。 爹看圖13,計量吸管230之另一實例包括真空泵222 ,及氣體泵232。真空泵222類似於圖12所示之真空泵。 氣體泵232包括玻璃毛細管12〇,玻璃毛細管12〇'填充有 %α)3且置放於含有CH2C〇〇H之吸管球體说卜當玻 螭毛細管120斷開時,NhCOs與CH2C〇〇H相互作用:產 生c〇2,從而增大球體234中之氣體壓力。真空泵222允 許使用者快速吸取預定量之流體至吸管23〇中。氣體泵232 允許使用者將流體施配至吸管230之外。 19 200813324 P64950010T WC1 22169-1 -twf.doc/006 使用氣體泵232之優勢在於:當Na2C〇3與CH2COOH 之間的反應產生C〇2氣體時,可在受控之一段時間期間施 配管體228中之流體。以此方式,使用者無需小心監控施 配流體時流體的流出。 參看圖14A,計量吸管240之另一實例包括球體242、 中間部分244以及吸管管體246。中間部分244由可變形 材料建構。開關開閥248定位於中間部分244中。開關開 閥248包括玻璃毛細管142以及定位於毛細管142外部之 SAP 162,此類似於圖9A至圖9C所示之裝置。 參看圖14A,為了使用吸管240,使用者擠壓且釋放 球體242以吸取流體至管體246以及中間部分244中。 參看圖14B,當流體達到中間部分244且開始與SAP 248相接觸時,流體之部分被sAp 248吸附,從而使得sap 248體積膨脹且阻斷sAP 248之另一側的流體通路。以此 方式,預定量之流體被吸取至吸管240中6 參看圖14C,為了自吸管240施配流體,使用者按壓 中間部分244 (由可變形材料製成)以斷開玻璃毛細管 142’從而形成經過斷開之毛細管142的通路。使用者隨後 播壓球體242以迫使流體流出吸管240。 當製造一批吸管240時,管體240以及中間部分244 之尺寸為相同的,且中間部分244内之開關開閥248的位 置為相同的,使得使用者可使用吸管240來在i需精宓臣6 控吸管240中之液體含量的情況下快速吸取大體同= 流體。 里气 20 200813324 P6495001OTWC1 22169-1-twf.doc/006 參看圖15A,用於收集預定量之流體的計量裝置26〇 包括玻璃毛細管262,玻璃毛細管262具有兩個分枝266a 以及266b、兩個自關閉閥268a以及268b,以及兩個斷開 式打開閥270a以及270b。自關閉閥268a以及268b中之 每一者具有吸附流體後立即膨脹的SAP。初始,自關閉閥 268a以及268b處於打開狀態,且斷開式打開閥27〇a以及 270b處於關閉狀態。自關閉閥268a以及268b可類似於圖 φ 6A至圖8C所示之自關閉閥。斷開式打開閥27〇a以及27% 可類似於圖5A以及圖5B所示之斷開式打開閥。 在操作中,歸因於毛細管力,流體274被吸取至毛細 管262中,且流經自關閉閥268a以及268b。參看圖15B, 當流體274流經自關閉閥268a以及268b時,流體274之 部分被自關閉閥268a以及268b中之SAP吸附,從而使自 關閉閥268a以及268b變化為關閉狀態,藉此阻斷流體274 的進步ml動。以此方式導致流體274佔據毛細管之自關 閉閥268a與268b之間的區段264。 • 藉由將斷開式打開閥27〇a以及270b自關閉狀態改變 為打開狀態且施加吸引力或推動力來移動流體274,流體 274可經過分枝266a或266b自區段264移動至其他位置。 • 計量裝置260之優勢在於:計量裝置260可在無需使用 者小心監控的情況下快速取樣預定體積之流體。因為毛細 管具有小直徑’所以計量裝置260可用於精確取樣 體。 參看圖16A,可自樣本池282獲取三種不同量之流體 21 200813324 P6495001 〇TWC 1 22169小 twf.doc/006 ,計量裝置280包括三個毛細管284a、28牝以及28牝。 每一毛細管在一端具有自關閉閥(例如,286a、286b或 286c)且另一端具有真空閥(例如,288a、288b或288c)。 每-真空泵具有真空玻璃毛細管。初始,自關關處於打 開狀態。 參看圖16B,當使用者斷開真空泵288a中之真空玻璃 毛細管時,產生吸引力來吸取預定量之液體至毛細管284a 中。當流體經過自關閉閥286a時,自關閉閥286a中之SAp 膨脹,從而使自關閉閥286a進入關閉狀態,藉此阻止流體 進步移動而經過自關閉閥286a。類似,藉由阻斷真空泵 288b以及288c中之真空毛細管,預定量之流體可被吸取 至毛細官284b以及284c中。被吸取至毛細管284a至284c 中之流體量由真空泵288a至288c中之毛細管的體積來判 定,被吸取至毛細管284a至284c中之流體量可為相同或 不同的。 參看圖17A,可藉由使用真空泵、斷開式打開閥、自 關閉閥之組合來製造用於兩步驟檢定的裝置29〇,兩步驟 檢定要求在快速結合試劑後用緩衝液進行清洗。通道3〇2 之一端經過自關閉閥296搞接至樣本池300,且通道302 之另一端耦接至第一真空泵292a。通道302連接至通道 308,通道308經過斷開式打開閥294耦接至緩衝液298。 通道302亦連接至通道304,通道304耦接至第二真空泵 292b以及第三真空泵292c。通道304包括結合及/或感測 區306,結合及/或感測區3〇6包括用於結合或感測樣本3〇〇 22 200813324 P64950010TWC1 22169-l-twf.doc/006 中之化合物的試劑。 以一方式操作裝置290以使得朝向結合以及感測區 306吸取樣本300以使反應發生,隨後朝向結合以及感測 £ 306吸取緩衝液298以清洗結合以及感測區。 麥看圖17B,啟動真空泵292a以產生朝向真空泵292a 吸取樣本300且將樣本300吸取至真空泵292a與自關閉閥 296之間的通道302之部分的吸引力。當樣本3〇〇流經自 關閉閥296時,樣本之部分被自關閉閥296中之SAP吸 附,從而使自關閉閥296進入關閉狀態。 參看圖17C,啟動斷開式打開閥294以使閥294改變 為打開狀態。啟動真空泵292b以產生朝向真空泵292b吸 取樣本300與緩衝液298的吸引力。真空粟292a以及292b 經設計以使得在啟動泵後,樣本300將停止於結合以及感 測區306處。在一段時間後,啟動真空泵292c以移動樣本 300至區306之外,且使缓衝液298流經區306及清洗區 306 〇 上述實例提供培養時間(incubation time)以允許在缓 衝液290清洗結合以及感测區306之前樣本300中之化合 物與區306中之試劑進行反應。若區306處之反應為快且 培養時間為不必要的,則真空泵292b可製得較大且可省略 真空泵292c。當啟動真空泵292b時,樣本迅速流經結合 以及感測區306,隨後由缓衝液298清洗結合以及感測區 306 〇 參看圖18A,可藉由使用真空泵、斷開式打開閥、自 23 200813324 P6495001OTWC1 22169小 twf.doc/006 關閉閥以及氣體泵之組合來製造用於兩步驟檢定的裝置 310 ’兩步驟檢定要求在缓慢結合試劑後用缓衝液進行清 洗。類似於裝置290之裝置310具有通道302,通道302 連接至兩個通道304以及308。通道302經過自關閉閥296 、 耦接至樣本300。通道308經過斷開式打開閥294耦接至 緩衝液298。通道304包括結合以及感測區306。通道304 之一端耦接至斷開式打開閥312。氣體泵314耦接至缓衝 • 液 298。 裝置310與裝置290之間的差別在於:裝置310並非使 用真空栗292b來朝向結合以及感測區306吸取樣本300 以及緩衝液298,而是使用氣體泵314來朝向區306推動 樣本300以及缓衝液298。 參看圖18B,為了執行兩步驟檢定,啟動真空泵292& 以吸取樣本300至通道中。在樣本流經自關閉闕2%後閥 296進入關閉狀態。 參看圖18C,啟動斷開式打開閥294以及312以使閥改 • 變為打開狀態。啟動氣體泵314以在一段時間期間產生氣 體,從而推動樣本300以及缓衝液298經過纯合以及感: ^ 區306。因為氣體泵314在一段時間期間產^氣體(1生 - 氣體之化合物之間的反應耗費一定量之時間來穿成),样士 300可緩慢經過結合以及感测區3〇6,從而緩慢發生結: 應。 又X 口口久 參看圖19A,可藉由添加第二緩衝液324以及通道幻2 至圖17A所示之結構來製造用於三步驟檢定的裝置32〇, 24 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6 三步驟檢定要求在快速結合試劑後用兩種缓衝液進行清 洗。為了執彳亍多步驟檢定,啟動真空果292a以使樣本300 流動至通道302。當樣本300流經自關閉閥296時,閥296 改變為關閉狀態。 參看圖19B,啟動斷開式打開閥294以使其改變為打 開狀恶’且啟動真空栗292b以使朝向結合以及感測區306 吸取樣本300以及第一緩衝液298。 參看圖19C,啟動斷開式打開閥326以使其改變為打 開狀態’且啟動真空泵292c以使朝向結合以及感測區306 吸取樣本300、第一緩衝液298以及第二缓衝液324。以此 方式,可用兩種不同缓衝液清洗區306處之反應。 可藉由麵接額外緩衝液或樣本且添加對應數目個真空 泵至通道304之末端來建構用於要求三步驟以上之步驟之 檢定中的裝置。 參看圖20,可建構模組330來執行多重分析物檢定。 模組包括用於固持樣本300的樣本池282以及三個腔室 332a、332b以及332c,每一腔室含有用於結合且感測樣本 300中之化合物的分析物。以下描述用以執行與腔室332a 中之第一分析物相關之檢定的組件。 腔至332a經過通道342a以及自關閉閥344a麵接至樣 本池282。通道342a經過自關閉閥346a以及斷開式打開 閥348a耦接至第一缓衝液350a。通道342a經過自關閉二 352a以及斷開式打開閥354a耦接至第二緩衝液356a。通 道342a經過自關閉閥358a以及斷開式打開閥36〇&耦接至 25 200813324 P6495001OTWC1 22169-1 -twf.doc/006 第三缓衝液362a。腔室332a亦連接至真空泵33如、336a、 338a 以及 340a。 為了執行檢定,啟動真空泵334a以朝向腔室332a吸 取樣本300,以使得允許樣本300中之化合物與分析物332a 進行反應。在一定量之樣本流經自關閉閥344a之後,閥 344a改變為關閉狀態。藉由啟動斷開式打開閥348a (將闊 改變為打開狀態)以及第二真空泵336a,第一缓衝液350a 沖洗過腔室332a。在一定量之第一緩衝液35〇a流經自關 閉閥346a之後,閥346a改變為關閉狀態。 藉由啟動斷開式打開閥354a (將閥改變為打開狀態) 以及第三真空泵338a,第二缓衝液356a沖洗過腔室332a。 在一定量之第二緩衝液356a流經自關閉閥352a之後,閥 352a改變為關閉狀態。 #、以此類似方式,藉由啟動斷開式打開閥360a (將閥改 k為打開狀態)以及第四真空泵340a,第三缓衝液362a 冲洗過腔室332a。在一定量之第三緩衝液362a流經自關 閉閥j58a之後,閥358公改變為關閉狀態。 人〜可以類似於執行與腔室332a中之第一分析物相關之 =定的方式執行與腔室332b以及幻乂中之第二以及第三 物相關之檢定。可同時執行與腔室332a、332b以及 、之第、弟—以及第三分析物相關之檢定。 =下為執行生物性檢定之真空泵以及氣體泵之應用。 狀¥ π A以及圖展示用於執行快速反應比色檢定的 0衣置380包括通道384,通道384之一端搞接至 26 200813324 P64950010TWC1 22I69-l-twf.doc/〇〇6 tir 端輛接至真空果90。樣本池382可固持 ==賴一化合物後立即改變顏色的測試= 可快速吸取樣本池382中之流體經過測試區 386。耩_取賴社純,制者可快速败流體中存 在或並不存在某一化合物。When the manufacturing-batch metering pipette is 22 inches, the size of the sphere 226 and the glass capillary can be made the same. The ball 226 and the glass capillary tube (10) are used to measure the amount of deformation of the application sphere 226 required to break the glass capillary f1〇〇 when the user presses the ball 226 to break the glass capillary 1〇〇 for all metering straws. 220 is roughly the same. In this manner, the user can quickly draw a predetermined amount of fluid using the metering straw 22G to monitor the fluid content of the stem without f. For example, referring to Figures 21A and 21B, a metering pipette 220 can be used to quickly sample a predetermined amount of blood a from a patient. . Referring to Figure 13, another example of a metering straw 230 includes a vacuum pump 222, and a gas pump 232. The vacuum pump 222 is similar to the vacuum pump shown in FIG. The gas pump 232 includes a glass capillary 12〇, the glass capillary 12〇' is filled with %α)3 and placed in a straw sphere containing CH2C〇〇H. When the glass capillary 120 is disconnected, NhCOs and CH2C〇〇H are mutually Effect: Generate c〇2 to increase the gas pressure in the sphere 234. The vacuum pump 222 allows the user to quickly draw a predetermined amount of fluid into the straw 23. Gas pump 232 allows the user to dispense fluid out of straw 230. 19 200813324 P64950010T WC1 22169-1 -twf.doc/006 The advantage of using gas pump 232 is that when a reaction between Na2C〇3 and CH2COOH produces C〇2 gas, tube 228 can be dispensed during a controlled period of time. Fluid in the middle. In this way, the user does not have to carefully monitor the flow of fluid as it is being dispensed. Referring to Figure 14A, another example of a metering straw 240 includes a ball 242, a middle portion 244, and a straw body 246. The intermediate portion 244 is constructed of a deformable material. Switch open valve 248 is positioned in intermediate portion 244. The switch open valve 248 includes a glass capillary 142 and an SAP 162 positioned outside of the capillary 142, similar to the device shown in Figures 9A-9C. Referring to Figure 14A, in order to use the suction tube 240, the user squeezes and releases the ball 242 to draw fluid into the body 246 and the intermediate portion 244. Referring to Figure 14B, when the fluid reaches the intermediate portion 244 and begins to contact the SAP 248, a portion of the fluid is adsorbed by the sAp 248, causing the sap 248 to expand in volume and block the fluid passage on the other side of the sAP 248. In this manner, a predetermined amount of fluid is drawn into the suction tube 240. Referring to Figure 14C, in order to dispense fluid from the suction tube 240, the user presses the intermediate portion 244 (made of a deformable material) to break the glass capillary 142' to form The passage through the broken capillary 142. The user then squashed the ball 242 to force fluid out of the straw 240. When a plurality of suction tubes 240 are manufactured, the tubular body 240 and the intermediate portion 244 are the same size, and the position of the switch opening valve 248 in the intermediate portion 244 is the same, so that the user can use the suction tube 240 to be precise. In the case of the liquid content in the control tube 240, the fluid is substantially aspirated.里气20 200813324 P6495001OTWC1 22169-1-twf.doc/006 Referring to Figure 15A, a metering device 26 for collecting a predetermined amount of fluid includes a glass capillary 262 having two branches 266a and 266b, two from Valves 268a and 268b are closed, as well as two open-ended valves 270a and 270b. Each of the self-closing valves 268a and 268b has an SAP that expands immediately after adsorbing the fluid. Initially, the self-closing valves 268a and 268b are in an open state, and the disconnected open valves 27A and 270b are in a closed state. Self-closing valves 268a and 268b can be similar to the self-closing valves shown in Figures φ 6A through 8C. The break open valve 27A and 27% can be similar to the open open valve shown in Figures 5A and 5B. In operation, fluid 274 is drawn into capillary tube 262 due to capillary forces and flows through self-closing valves 268a and 268b. Referring to Figure 15B, as fluid 274 flows through self-closing valves 268a and 268b, portions of fluid 274 are adsorbed by SAP in shut-off valves 268a and 268b, thereby changing self-closing valves 268a and 268b to a closed state thereby blocking The progress of fluid 274 is moving. In this manner, fluid 274 occupies a section 264 between the self-closing valves 268a and 268b of the capillary. • The fluid 274 can be moved from section 264 to other locations via branches 266a or 266b by changing the disconnected open valves 27A and 270b from the closed state to the open state and applying an attractive or urging force to move the fluid 274. . • The advantage of the metering device 260 is that the metering device 260 can quickly sample a predetermined volume of fluid without careful monitoring by the user. Because the capillary has a small diameter', the metering device 260 can be used to accurately sample the body. Referring to Figure 16A, three different amounts of fluid can be taken from the sample cell 282. 21 200813324 P6495001 〇TWC 1 22169 small twf.doc/006, the metering device 280 includes three capillaries 284a, 28A and 28A. Each capillary has a self-closing valve (e.g., 286a, 286b, or 286c) at one end and a vacuum valve (e.g., 288a, 288b, or 288c) at the other end. Each vacuum pump has a vacuum glass capillary. Initially, the self-closing is in the open state. Referring to Fig. 16B, when the user turns off the vacuum glass capillary in the vacuum pump 288a, an attractive force is generated to draw a predetermined amount of liquid into the capillary 284a. As the fluid passes through the self-closing valve 286a, the SAp in the self-closing valve 286a expands, thereby causing the self-closing valve 286a to enter a closed state, thereby preventing fluid from moving through the self-closing valve 286a. Similarly, by blocking the vacuum capillaries in vacuum pumps 288b and 288c, a predetermined amount of fluid can be drawn into capillaries 284b and 284c. The amount of fluid sucked into the capillary tubes 284a to 284c is determined by the volume of the capillary in the vacuum pumps 288a to 288c, and the amount of fluid sucked into the capillary tubes 284a to 284c may be the same or different. Referring to Fig. 17A, a device 29 for a two-step assay can be fabricated by using a combination of a vacuum pump, a disconnected open valve, and a self-closing valve. The two-step assay requires cleaning with a buffer after rapid binding of the reagent. One end of the passage 3〇2 is engaged to the sample cell 300 through the self-closing valve 296, and the other end of the passage 302 is coupled to the first vacuum pump 292a. Channel 302 is coupled to channel 308, which is coupled to buffer 298 via a disconnect open valve 294. Channel 302 is also coupled to channel 304, which is coupled to second vacuum pump 292b and third vacuum pump 292c. Channel 304 includes a binding and/or sensing region 306 that includes reagents for binding or sensing a compound in sample 3〇〇22 200813324 P64950010TWC1 22169-l-twf.doc/006 . Device 290 is operated in a manner such that sample 300 is aspirated toward bonding and sensing region 306 to cause a reaction to occur, followed by aspiration buffer 298 toward bonding and sensing £306 to clean the bonding and sensing regions. Referring to Figure 17B, vacuum pump 292a is activated to generate an attractive force that draws sample 300 toward vacuum pump 292a and draws sample 300 to a portion of passage 302 between vacuum pump 292a and self-closing valve 296. When the sample 3 〇〇 flows through the self-closing valve 296, a portion of the sample is attracted by the SAP in the self-closing valve 296, thereby bringing the self-closing valve 296 into a closed state. Referring to Figure 17C, the break open valve 294 is actuated to change the valve 294 to the open state. The vacuum pump 292b is activated to generate an attractive force for drawing the sample 300 and the buffer 298 toward the vacuum pump 292b. The vacuum mills 292a and 292b are designed such that after the pump is started, the sample 300 will stop at the bonding and sensing zone 306. After a period of time, vacuum pump 292c is activated to move sample 300 out of zone 306 and buffer 298 is flowed through zone 306 and wash zone 306. The above examples provide incubation time to allow for buffer 290 cleaning and bonding. The compound in sample 300 prior to sensing zone 306 is reacted with the reagent in zone 306. If the reaction at zone 306 is fast and the incubation time is unnecessary, vacuum pump 292b can be made larger and vacuum pump 292c can be omitted. When the vacuum pump 292b is activated, the sample rapidly flows through the bond and sensing region 306, and then the bond is cleaned by the buffer 298 and the sensing region 306 is shown in Fig. 18A, which can be opened by using a vacuum pump, a disconnected valve, and from 23 200813324 P6495001OTWC1 22169 Small twf.doc/006 A combination of a shut-off valve and a gas pump to make a device for a two-step assay. The 'two-step assay requires cleaning with a buffer after slowly combining the reagents. Device 310, similar to device 290, has a channel 302 that is connected to two channels 304 and 308. Channel 302 passes through self-closing valve 296 and is coupled to sample 300. Channel 308 is coupled to buffer 298 via a disconnect open valve 294. Channel 304 includes a bond and sense region 306. One end of the passage 304 is coupled to the break open valve 312. Gas pump 314 is coupled to buffer liquid 298. The difference between device 310 and device 290 is that device 310 does not use vacuum pump 292b to draw sample 300 and buffer 298 toward bonding and sensing region 306, but instead uses gas pump 314 to push sample 300 and buffer toward zone 306. 298. Referring to Figure 18B, in order to perform a two-step assay, vacuum pump 292 & is activated to draw sample 300 into the channel. Valve 296 enters a closed state after the sample has flowed through self-closing 阙 2%. Referring to Fig. 18C, the open type open valves 294 and 312 are actuated to cause the valve to be changed to an open state. Gas pump 314 is activated to generate gas over a period of time to push sample 300 and buffer 298 through homozygous and sense: ^ region 306. Since the gas pump 314 produces gas during a period of time (the reaction between the compounds of the raw gas and the gas takes a certain amount of time to pass through), the sample 300 can slowly pass through the bonding and the sensing region 3〇6, thereby slowly occurring. Conclusion: Yes. Further, with reference to Fig. 19A, the apparatus for three-step verification can be manufactured by adding the second buffer 324 and the structure shown in Fig. 17A to Fig. 17A, 24 200813324 P64950010TWC1 22169-l-twf. The doc/〇〇6 three-step assay requires two buffers to be washed after rapid reagent binding. To perform the multi-step assay, vacuum fruit 292a is activated to cause sample 300 to flow to channel 302. When the sample 300 flows through the self-closing valve 296, the valve 296 changes to the closed state. Referring to Fig. 19B, the break open valve 294 is actuated to change it to open and the vacuum pump 292b is activated to draw the sample 300 and the first buffer 298 toward the bond and sensing region 306. Referring to Fig. 19C, the open type open valve 326 is actuated to change to the open state' and the vacuum pump 292c is activated to draw the sample 300, the first buffer 298, and the second buffer 324 toward the bonding and sensing region 306. In this manner, the reaction at zone 306 can be washed with two different buffers. The means for verifying the steps of the three or more steps can be constructed by attaching additional buffers or samples and adding a corresponding number of vacuum pumps to the ends of the channels 304. Referring to Figure 20, a module 330 can be constructed to perform multiple analyte assays. The module includes a sample cell 282 for holding the sample 300 and three chambers 332a, 332b, and 332c, each chamber containing an analyte for binding and sensing a compound in the sample 300. The components used to perform the assay associated with the first analyte in chamber 332a are described below. Cavity 332a is flanked to sample reservoir 282 via passage 342a and self-closing valve 344a. The passage 342a is coupled to the first buffer 350a via a self-closing valve 346a and a disconnected open valve 348a. Channel 342a is coupled to second buffer 356a via self-closing two 352a and disconnected open valve 354a. The passage 342a is coupled to the third buffer 362a via a self-closing valve 358a and a disconnected open valve 36〇& to 25 200813324 P6495001OTWC1 22169-1 -twf.doc/006. The chamber 332a is also connected to vacuum pumps 33 such as 336a, 338a and 340a. To perform the assay, vacuum pump 334a is activated to draw sample 300 toward chamber 332a to allow the compound in sample 300 to react with analyte 332a. After a certain amount of sample flows through the self-closing valve 344a, the valve 344a changes to the closed state. The first buffer 350a is flushed through the chamber 332a by actuating the open type open valve 348a (changing the width to the open state) and the second vacuum pump 336a. After a certain amount of the first buffer 35〇a flows through the self-closing valve 346a, the valve 346a is changed to the closed state. The second buffer 356a is flushed through the chamber 332a by actuating the open type open valve 354a (changing the valve to the open state) and the third vacuum pump 338a. After a certain amount of the second buffer 356a flows through the self-closing valve 352a, the valve 352a is changed to the closed state. #, In a similar manner, the third buffer 362a is flushed through the chamber 332a by activating the open type opening valve 360a (changing the valve to the open state) and the fourth vacuum pump 340a. After a certain amount of the third buffer 362a flows through the self-closing valve j58a, the valve 358 is changed to the closed state. The person ~ can perform an assay associated with the chamber 332b and the second and third objects in the illusion, similar to performing the determination associated with the first analyte in the chamber 332a. Verifications associated with chambers 332a, 332b and the first, third, and third analytes can be performed simultaneously. = The application for vacuum pumps and gas pumps for performing biological tests. Figure ¥ π A and the figure shows that the 0 set 380 for performing the fast response colorimetric check includes the channel 384, and one end of the channel 384 is connected to 26 200813324 P64950010TWC1 22I69-l-twf.doc/〇〇6 tir end to Vacuum fruit 90. The sample cell 382 can hold the test after changing the color immediately after the compound == The sample in the sample cell 382 can be quickly sucked through the test zone 386.耩 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
圖23A以及圖23B展示用於取樣經過濾之流體的裝置 390。裝置390包括通道384,通道384 ㈣且另-爾靡线。職_== 本池382中。真空泵90啟動時可快速吸取樣本池刈2中之 流體(例如,血液)經過過濾薄膜392,從而產生被吸取 至通道384中的經過濾之流體(血漿)。 圖24A至圖24C展示用於缓慢之比色檢定的裝置 400。裝置400包括樣本池402,樣本池402耦接於氣體泵 404與通道384之間。通道384具有測試區386,測試區 386具有偵測到某一化合物後立即改變顏色的測試線。為 了使用裝置400,將樣本流體406置放於樣本池402中。 密封帶408密封樣本池之開口。啟動氣體泵404以產生推 動樣本流體406經過測試區386的氣體。因為氣體泵404 在一段時間期間產生氣體,所以樣本流體406在一段時間 期間行進經過測試區,從而允許執行緩慢之比色檢定。 本發明之一具體實施例,則請參照圖29A與29B,可 藉由使用自關閉閥(SLV)與斷開式打開閥(BOV)之組合來 製造用於對A液樣本進行抗體(Antibody)檢定的裝置 27 200813324 P64950010TWC1 22169-1 -twf.doc/006 500。此裝置5〇〇包括血液樣本池即00(15&111卩16\¥611)5〇1、 沖洗緩衝液池(Washing buffer well)503、計量區域與標誌抗 體(Metering zone and labeled antibody)區域 505、診斷法區 域(Diganostic Zone)(抗體陣列 Antibody array)507、斷開式 打開閥(BOV)509、廢棄物池(Waste well)511與自關閉閥 (SLV)513。此計量區域與標誌抗體區域505具有一通道連 通血液樣本池501與沖洗缓衝液池5〇3,而自關閉閥 (SLV)513則是位於此通道之間。而診斷法區域5〇7則是具 有另一通道,一端連接到計量區域與標誌抗體區域5〇5之 中心位置,而另一端則通過斷開式打開閥(B〇V)5〇9連接到 廢棄物池(Waste well)511。 此裝置500對血液樣本進行抗體(Antibody)檢定的方 法,請參照圖30A、30B與30C所示。首先,將血液樣本 502載入血液樣本池501内,而後,使用本發明前述實施 例中所提出之自關閉閥(SLV)513,利用毛細管力(Capillary force)將企液吸入此計量區域與標誌抗體區域505的通道 内,如圖30A所示之502a。而後,載入沖洗缓衝液到沖洗 緩衝液池503内,而此時沖洗缓衝液也會流入計量區域與 標誌抗體區域505的通道内,如圖3〇B之504a,而此時血 液會被擠入診斷法區域507内,如圖之502b。 而後,請參考圖30C,將斷開式打開閥(b〇V)509斷開 後,則將血液進一步吸入而經過診斷法區域507,如圖所 示之502c,此時在此診斷法區域507内的抗體陣列 (Antibody array)將會與企液内的抗原(Antigent)結合,而沖 28 200813324 P64950010TWC1 22169-l.twf.doc/006 洗緩衝液則將沒有作用的血液沖到廢棄物池511。 本發明之又一具體實施例,而參看圖31所示。可藉由 一 使用自關閉閥(SLV)與斷開式打開閥(BOV)之組合來製造 用於對血液樣本進行抗體(Antibody)檢定的裝置。而此裝置 包括血液樣本池、沖洗緩衝液池、診斷法區域(内含抗體陣 列)、斷開式打開閥(BOV)、廢棄物池與自關閉閥。而此血 液才水本池則包含具有移除血細胞(Bl〇〇(J ceii rein〇val)之薄 • 膜,可利用血液樣本在吸入時即可過濾掉血細胞。 此#斷法區域具有一通道連通金液樣本池與沖洗缓衝 液池,而另一端則通過斷開式打開闊(B0V)連接到廢棄物 池。自關閉閥(SLV)則是位於血液樣本池進入此通道之前, 可控制流入診斷法區域之血液量,並且防止血液倒流至血 液樣本池。 當斷開式打開閥(BOV)斷開後,將金液先經過可移除 血細胞之薄膜過濾後,進一步吸入診斷法區域内,此時在 #斷法區域内的抗體陣列(Antibody array)將會與血液内的 釀抗原(Antigent)結合,而沖洗緩衝液則將沒有作用的血液沖 到廢棄物池中。 上述的超級吸附劑聚合物(Superabsorbent polymer,“SAP”)可吸附且保持水或其他水溶液的大體 積。在某些實例中,SAP可由經化學改質之澱粉以及纖維 素以及其他聚合物製成,諸如,高親水性且對水具有高親 和性的聚(乙烯醇)PVA、聚(氧化乙烯)ΡΕ〇Γ在某些 只例中,超級吸附劑聚合物可由部分中和且輕度交聯的聚 29 200813324 P6495001OTWC1 22169-1-twf doc/006 (丙烯酸)製成,部分中和且輕度交聯的聚(丙烯酸)具 有良好之效能相對成本的比率。 ‘ 而在自關閉閥中使用超級吸附劑聚合物,因為聚合物 的凝膠時間(Gelling Time)約數秒,較適用於真空泵搭配應 , 用。在毛細力(Capillary Force)與離心力(CentrifugalF〇rce) 驅動的應用時,流體流速小於SAP的凝膠時間,因此僅有 阻止流體流動,無法允許流體於通道中之流動。因此,本 鲁 發明所^出自關閉閥的應用,可藉由加入時間延滞層的設 計,延緩SAP自關閉閥的“關閉”時間,另外,此延滯層可 選擇不影響檢測標的物的材料製作即可,即可達到適用慢 流速的應用領域,在此稱為時間延滯閥(Time]Lag Valve)。 在此實施例中,利用可溶性材質配置在自關閉閥通道 中,介於超級吸附劑聚合物SAP與流體之間,在檢測溶液 流經此通道時,SAP吸附且保持水或其他水溶液的大體積 的速度會受到可溶性材質的延滯而膨脹凝膠的速度趨緩,、 此即可達到慢流速的要求。 • 茶看圖32A,自關閉閥550可包括通道552,通道552 具有擴大部分554以容納超級吸附劑聚合物556,使得超 級吸附劑聚合物556在膨脹前並不限制流體的流動。為了 . 製造自關閉闊550,可將黏附劑塗覆至擴大部分554的内 壁,以粉末形態的SAP 556隨後被推動至通道552中,使 得SAP 5S6粉末黏附至擴大部分554處之内壁。而利用可 洛性材質所製成的延滯層558則可置於通道552在擴大部 分554的流體流通的通道内。參看圖32β ,當流體在流通 30 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6 日守,必須等到延縣558溶解後,超級吸附劑聚合物MS 才開始吸附流體之部分而體積膨脹,從而阻斷通道552, 藉此阻止流體進一步流經膨脹之聚人 此延滯層材質的選擇,以可溶ς材質為主,在一實施 例中,可以選擇水溶性材料為主,例如嚴糖塊(零rcube) 或嚴糖片(sugar sheet),厚度介於〇 〇1〜2麵間,塾覆於流 迢與超級㈣齡合物(SAP)材帥。#水絲體流經流道 時’先與韻麵進行簡作用,阻止SAp的吸收水分, 當嚴糖-邊溶解賴㈣”容許SAp —邊吸水賴。當 糖浴解元畢後’ SAP方能完全阻絕流道,完成“關閉,,的作 動。此延料贿錢㈣厚度增加而延長,此可根據需 求而没計。另外’不同延滞層材質的選擇也會具有不同的 延滯時間效果。 在另外實施例中,自_閥55〇的通道说可以不需 要擴大部分554’而取而代之的是可以將超級吸附劑聚合 物556粉末黏附至通道552處之内壁,而此超級吸附劑聚 合物556粉末可以# SAP材料固定後’進行熔融糖漿的浸 泡式塗佈(dlp-eGating)、滾筒式塗佈(Rq11 c⑽㈣或旋轉式 塗佈(Spin Coating)等製程’將輯層材纽合在超級吸附 劑聚合物556粉末内,例如圖33A與33B所示,分別顯示 局部塗佈或全©的塗佈。而此時,SAp材料吸附且保持^ 或其他水溶液的大體積的速度將會有所遲滯,此亦達到此 目的。 上述的時間延滞閥設計,可運用在多個例子中,例如 31 200813324 P6495001OTWC1 22169-1-twf.doc/006 圖34A與34B所繪式抗體(Antibody)檢定的裝置。在此抗 體檢定裝置600中,包括檢體流通通道610以及相連接的 標記抗體槽(Labeled Antibody Well)620、樣品槽(Sample Well)630、沖洗液槽(Washing Buffer Well)640。而此檢體流 通通道610與標記抗體槽620及樣品槽630之間分別具有 兩個上述的時間延滯閥622與632。檢體流通通道610上 包括一步階區域612、抗體陣列區域(Antibody Array Area)614 與斷開式打開閥(Broken Open Valve)616。 此步階區域612主要是配合時間延滯閥622與632的 設計。檢體流通通道610的流道管徑如圖34B沿著剖面 圖AA’所示之步階設計,由較大流道管徑611轉而改 變為其次的流道管徑613,而後轉為較小流道管徑 615。此種漸縮流道管徑的設計可以有效的增加下游 毛細力的大小。以步階(step)設計,配合時間延滯閥 622與632的使用,當液槽流入特定管道區間時,亦 可達到液體定體積的功能。 使用如圖34A的抗體檢定裝置600的抗體檢定方法, 在一實施例中,對例如A液樣本進行抗體檢定,其梦驟如 圖35A、35B、35C與35D所示。此抗體檢定裝置600包 括檢體流通通道610、標記抗體槽620、樣品槽630、沖洗 液槽640、第一時間延滯閥622與第二時間延滯閥632。而 檢體流通通道610包括步階區域612、抗體陣列區域614 與斷開式打開閥616。此步階區域612包括不同流道管徑 的區域611、613與615。而上述區域hi具有較大 32 200813324 P64950010TWC1 22169-l-twf.doc/006 的流道管徑,而區域613則具有較小的流道管徑,例 如小於上述區域611的流道管控。 首先,如圖35A所示,將血液樣本635載入樣品槽630 内,而後,血液樣本635會經由第二時間延滯閥632慢速 地流到區域613,隨後此第二時間延滯閥632將關閉而 不再讓血液樣本635流入檢體流通通道610内。而由於檢 體流通通道610的區域613内流道管徑固定,因此可 以得到定體積的血液樣本635。 而後,如圖35B所示,將標記抗體625載入標記抗體 槽620内,而後,標記抗體625會經由第一時間延滯閥622 慢速地流到區域611,隨後此第一時間延滯閥622將關 閉而不再讓標記抗體625流入檢體流通通道610内。而由 於檢體流通通道610的區域611内流道管徑固定,因此 可以得到定體積的標記抗體625。 而後’如圖35C所示,將沖洗液645加入沖洗液槽640 中,隨後,如圖35D所示,將斷開式打開閥616打斷後, 產生及附力’將檢體流通通道610内的沖洗液645、位於 區域611内的標記抗體625與位於區域613内的血液樣 本635吸附並經過抗體陣列區域614,即可達到抗體檢定 的效果。 上述的抗體檢定方法中,檢體流通通道内的流道管徑 漸縮而增加下游毛細力,並以步階(step)設計,配合 時間延滯閥,當液槽流入特定管道區間,達到液體定 體積功能。在依序注入樣品於樣品槽中,標記抗體於 33 200813324 P6495001OTWC1 22169-1 -twf.doc/006 標記抗體槽以及沖洗液於沖洗液槽後,打開斷開式打 開閥,.液體因毛細力的驅動,依序流經抗體陣列區, 進行結合(binding)、標記與冲洗等程序。 上述的時間延滯閥設計,也可運用在例如圖36A與 36B所繪示藉由離心力進行血液細胞分離的裝置中。在圖 36A與36B配置時間延滞閥的全血分離裝置660中,包括 全血分離道管662。在全血分離道管662内部侧壁上配 _ 置一時間延滯閥664。而此全血分離道管662則是根據一 轉軸666旋轉,在一離心力方向(Centrifugal Direction)668 產生離心力(Centrifugal Force)。在全血分離道管662内 則注入一全血樣品(Whole Blood Sample)661,當高速離心 時’全企樣品661的jk球會往離心的區域集中,產生 企球區(Blood Cell Area)663 與血漿區(Blood Plasma23A and 23B show apparatus 390 for sampling filtered fluid. The device 390 includes a channel 384, a channel 384 (four) and another line. Job _== This pool 382. When the vacuum pump 90 is activated, the fluid (e.g., blood) in the sample cell 2 can be quickly aspirated through the filter membrane 392 to produce filtered fluid (plasma) that is drawn into the channel 384. Figures 24A through 24C show an apparatus 400 for a slow colorimetric assay. The device 400 includes a sample cell 402 coupled between the gas pump 404 and the channel 384. Channel 384 has a test zone 386 that has a test line that changes color immediately after detecting a compound. To use device 400, sample fluid 406 is placed in sample cell 402. A sealing strip 408 seals the opening of the sample cell. Gas pump 404 is activated to generate a gas that pushes sample fluid 406 through test zone 386. Because gas pump 404 produces gas over a period of time, sample fluid 406 travels through the test zone over a period of time, allowing for a slow colorimetric assay to be performed. Referring to Figures 29A and 29B, an antibody for the A liquid sample can be manufactured by using a combination of a self-closing valve (SLV) and a disconnected open valve (BOV). Calibrated device 27 200813324 P64950010TWC1 22169-1 -twf.doc/006 500. The device 5 includes a blood sample pool, ie, 00 (15 & 111 卩 16 \ 611 611) 5 〇 1, Washing buffer well 503, Metering zone and labeled antibody region 505 A Diagnostic Zone (antibody array) 507, a disconnected open valve (BOV) 509, a waste well 511, and a self-closing valve (SLV) 513. The metering region and marker antibody region 505 have a channel for communicating with the blood sample cell 501 and the flush buffer pool 5〇3, and a self-closing valve (SLV) 513 is located between the channels. The diagnostic method area 5〇7 has another channel, one end is connected to the center of the metering area and the marker antibody area 5〇5, and the other end is connected to the center of the marker opening valve (B〇V) 5〇9. Waste well 511. The apparatus 500 performs an antibody assay on a blood sample, as shown in Figs. 30A, 30B and 30C. First, the blood sample 502 is loaded into the blood sample cell 501, and then, using the self-closing valve (SLV) 513 proposed in the foregoing embodiment of the present invention, the capillary force is used to draw the liquid into the metering area and the mark. Within the channel of antibody region 505, 502a is shown in Figure 30A. Then, the rinsing buffer is loaded into the rinsing buffer tank 503, and at this time, the rinsing buffer also flows into the channel of the metering region and the marker antibody region 505, as shown in Fig. 3B, 504a, and the blood is squeezed at this time. Into the diagnostics area 507, as shown in Figure 502b. Then, referring to FIG. 30C, after the disconnected open valve (b〇V) 509 is disconnected, the blood is further drawn in through the diagnostic area 507, as shown in FIG. 502c, at this time in the diagnostic area 507. The internal antibody array will bind to the antigen in the medicinal solution (Antigent), while the rushing 28 200813324 P64950010TWC1 22169-l.twf.doc/006 wash buffer will flush the inactive blood to the waste pool 511 . Yet another embodiment of the present invention is shown in FIG. A device for performing an antibody assay on a blood sample can be made by using a combination of a self-closing valve (SLV) and a disconnected open valve (BOV). The device includes a blood sample cell, a flush buffer pool, a diagnostic zone (containing an antibody array), a disconnected open valve (BOV), a waste reservoir, and a self-closing valve. The blood water pool contains a thin membrane that removes blood cells (B 〇〇 J J , , , , , , , , , , , , , , , , , 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液 血液The gold liquid sample pool and the flush buffer pool are connected, and the other end is connected to the waste pool through the open open (B0V). The self-closing valve (SLV) is located before the blood sample pool enters the channel and can control the inflow. Diagnosing the amount of blood in the area and preventing blood from flowing back to the blood sample pool. When the disconnected open valve (BOV) is disconnected, the gold liquid is filtered through a membrane of removable blood cells and further inhaled into the diagnostic area. At this point, the antibody array in the #断法 region will bind to the antigen in the blood, and the flushing buffer will flush the inactive blood into the waste pool. Superabsorbent polymer ("SAP") can adsorb and maintain a large volume of water or other aqueous solutions. In some instances, SAP can be chemically modified starch and cellulose as well as other polymers. Poly(vinyl alcohol) PVA, poly(ethylene oxide) ruthenium, such as high hydrophilicity and high affinity for water. In some cases, the super sorbent polymer can be partially neutralized and lightly distributed. Made of poly 29 200813324 P6495001OTWC1 22169-1-twf doc/006 (acrylic), partially neutralized and lightly crosslinked poly(acrylic acid) with good performance versus cost ratio. 'And used in self-closing valves Super sorbent polymer, because the gelling time of the polymer is about several seconds, which is more suitable for vacuum pumping. When using Capillary Force and Centrifugal F〇rce, the fluid flow rate It is smaller than the gel time of SAP, so it only prevents the fluid from flowing and cannot allow the fluid to flow in the channel. Therefore, the application of the self-closing valve can be delayed by the design of the time delay layer. The "off" time of the valve, in addition, the retardation layer can be selected to not affect the material of the detection target, and can reach the application field suitable for slow flow rate, which is referred to herein as In this embodiment, a soluble material is disposed in the self-closing valve passage between the super adsorbent polymer SAP and the fluid, and when the detection solution flows through the passage, The rate at which SAP adsorbs and maintains the bulk of water or other aqueous solutions is retarded by the soluble material and the rate of swelling of the gel slows down, which results in slow flow rates. • Tea See Figure 32A, self-closing valve 550 A channel 552 is included that has an enlarged portion 554 to accommodate the super sorbent polymer 556 such that the super sorbent polymer 556 does not restrict the flow of fluid prior to expansion. In order to manufacture the self-closing width 550, an adhesive agent may be applied to the inner wall of the enlarged portion 554, and the SAP 556 in powder form is then pushed into the channel 552, so that the SAP 5S6 powder adheres to the inner wall at the enlarged portion 554. A retardation layer 558 made of a corrugated material can be placed in the passage of the fluid passage of the passage 552 in the enlarged portion 554. Referring to Fig. 32β, when the fluid is in circulation 30 200813324 P64950010TWC1 22169-l-twf.doc/〇〇6, the super adsorbent polymer MS must start to adsorb the part of the fluid and expand in volume after the dissolution of Yanxian 558. Blocking the passage 552, thereby preventing the fluid from flowing further through the expanded aggregate. The selection of the material of the retardation layer is mainly based on the soluble material. In one embodiment, the water-soluble material may be selected, for example, a sugar block. (zero rcube) or sugar sheet, the thickness is between 〇〇1~2, and it is covered with rogue and super (four) age compound (SAP). #水丝体流流流流's first action with the rhyme to prevent the absorption of water by SAp, when the sugar is dissolved - (4) "allows SAp - while absorbing water. When the sugar bath is dissolved, 'SAP side Can completely block the flow channel and complete the "close," action. This extension of bribes (4) is increased by the increase in thickness, which can be calculated according to the demand. In addition, the choice of different retardation layer materials will have different delay time effects. In other embodiments, the passage from the valve 55A says that the enlarged portion 554' may not be required and instead the supersorbent polymer 556 powder may be adhered to the inner wall at the passage 552, and the super adsorbent polymer 556 Powder can be #SAP material fixed after 'dip-eGating of molten syrup (dlp-eGating), drum coating (Rq11 c (10) (four) or spin coating (Spin Coating) and other processes 'to laminate the layer in the super adsorption In the powder of the polymer 556, as shown, for example, in Figures 33A and 33B, respectively, the coating of the partial coating or the full coating is shown. At this time, the velocity of the large volume of the SAp material adsorbed and maintained or other aqueous solution will be delayed. This also achieves this purpose. The above-described time delay valve design can be used in a number of examples, for example, 31 200813324 P6495001OTWC1 22169-1-twf.doc/006 The apparatus for the antibody assay depicted in Figures 34A and 34B. In the antibody assay device 600, a sample flow channel 610 and a labeled labeled antibody well 620, a sample well 630, and a Washing Buffer Well 640 are included. There are two time delay valves 622 and 632 respectively between the sample flow channel 610 and the labeled antibody tank 620 and the sample tank 630. The sample flow channel 610 includes a step-by-step region 612 and an antibody array region (Antibody Array Area). 614 and Broken Open Valve 616. This step area 612 is mainly designed with the time delay valves 622 and 632. The flow path diameter of the sample flow passage 610 is as shown in Fig. 34B along the sectional view AA. 'The step design shown is changed from the larger runner diameter 611 to the second runner diameter 613 and then to the smaller runner diameter 615. The design of the tapered runner diameter can be Effectively increase the size of the downstream capillary force. With the step design, with the use of the time delay valves 622 and 632, when the liquid tank flows into the specific pipeline section, the liquid volume function can also be achieved. In the antibody assay method of the antibody assay device 600, in one embodiment, an antibody assay is performed on, for example, a liquid sample A, as shown in Figures 35A, 35B, 35C and 35D. The antibody assay device 600 includes a sample flow channel. 610, labeled antibody tank 6 20. Sample tank 630, rinse tank 640, first time delay valve 622 and second time delay valve 632. Sample flow path 610 includes step area 612, antibody array area 614 and open open valve 616. This step area 612 includes areas 611, 613 and 615 of different flow path diameters. The above region hi has a larger diameter of the flow path of 32 200813324 P64950010TWC1 22169-l-twf.doc/006, and the area 613 has a smaller flow path diameter, for example, less than the flow path control of the above-mentioned area 611. First, as shown in FIG. 35A, the blood sample 635 is loaded into the sample well 630, and then the blood sample 635 is slowly flowed to the region 613 via the second time delay valve 632, followed by the second time delay valve 632. The blood sample 635 will no longer flow into the sample flow channel 610. Since the diameter of the flow path in the region 613 of the sample flow channel 610 is fixed, a blood sample 635 of a fixed volume can be obtained. Then, as shown in Fig. 35B, the labeled antibody 625 is loaded into the labeled antibody tank 620, and then the labeled antibody 625 is slowly flowed to the region 611 via the first time delay valve 622, and then the first time delay valve 622 will be turned off and the labeled antibody 625 will no longer flow into the sample flow channel 610. On the other hand, since the flow path diameter is fixed in the region 611 of the sample flow channel 610, a fixed volume of the labeled antibody 625 can be obtained. Then, as shown in Fig. 35C, the rinsing liquid 645 is added to the rinsing liquid tank 640, and then, as shown in Fig. 35D, after the disconnecting opening valve 616 is broken, the generating and attaching force 'will be in the sample flow passage 610. The rinsing solution 645, the labeled antibody 625 located in the region 611, and the blood sample 635 located in the region 613 are adsorbed and passed through the antibody array region 614 to achieve the effect of antibody assay. In the above antibody assay method, the flow path diameter in the sample flow channel is tapered to increase the downstream capillary force, and is designed in steps, with a time delay valve, when the liquid tank flows into a specific pipeline section to reach a liquid Fixed volume function. The sample is sequentially injected into the sample tank, and the labeled antibody is labeled at 33 200813324 P6495001OTWC1 22169-1 -twf.doc/006. After the antibody buffer and the rinsing liquid are labeled in the rinsing liquid tank, the open type open valve is opened, and the liquid is caused by capillary force. Drive, sequentially flow through the antibody array area, and perform binding, labeling, and rinsing procedures. The above-described time delay valve design can also be applied to a device for performing blood cell separation by centrifugal force as shown, for example, in Figs. 36A and 36B. In the whole blood separation device 660 in which the time delay valve is disposed in Figs. 36A and 36B, a whole blood separation tube 662 is included. A time delay valve 664 is disposed on the inner side wall of the whole blood separation tube 662. The whole blood separation tube 662 is rotated according to a rotation axis 666, and a centrifugal force is generated in a centrifugal direction 668 (Centrifugal Force). In the whole blood separation tube 662, a Whole Blood Sample 661 is injected, and when the high-speed centrifugation is performed, the jk ball of the whole sample 661 is concentrated in the centrifugal region to generate a Blood Cell Area 663. And plasma zone (Blood Plasma
Area)665。在高速離心過程中,時間延滯閥664外層 水溶性延滯層會進行溶解,分離後待超吸收樹脂 (SAP)吸收部份水後會膨脹,並可阻止血球區663與 • 血漿區665之間的擴散混合。 儘官上文已論述某些實例,但其他實施以及應用亦屬 - 於以下申請專利範圍之範疇。舉例而言,在圖1A以及圖 ^ 比之真空泵90中,容器1〇〇可含有低壓力區域而並非含 有真空區域。只要容器100内部之氣體壓力較低於容器1〇〇 外邛之氣體壓力,當谷裔100斷開時,容器}⑽外部之區 域⑽中之壓力將下降嗜而產生沿一方向朝向容器励 吸取流體的吸引力。上文描述之毛細管可由用其他脆性材 34 200813324 P64950010TWC1 22169-I-tw£doc/006 料製成之毛細管來替代,諸如脆性塑膠、石英以 【圖式簡單說明】 〜 - 圖1A以及圖1B為真空泵的示意圖。 、 圖2A以及圖2B為氣體果的不意圖。 圖3A以及圖3B為氣體泵的示意圖。 圖4A為氣體泵的示意圖。 圖4B為材料之表。 鲁 圖5A以及圖5B為斷開式打開閥的示意圖。 圖6A、圖6B、圖7A、圖7B以及圖8A至圖8C為自 關閉閥的示意圖。 _ 圖9A至圖9C為開關開閥的示意圖。 圖10A至圖10C為關開關閥的示意圖。 圖11A至圖11D為開關開關閥的示意圖。 圖12為計量吸管的示意圖。 圖13為計量吸管的示意圖。 圖14A至圖14C為計量吸管的示意圖。 鲁 圖15A以及圖1 SB為計量裝置的示意圖。 圖16A以及圖16B為計量裝置的示意圖。 圖17A至圖17C為用於兩步驟檢定之裝置的示音固 - 圖18A至圖18C為用於兩步驟檢定之裝置的示专固。 圖19A至圖19C為用於三步驟檢定之裝置的示音固 圖20為用於多重分析物檢定之模組的示意圖。W 圖21A以及圖21B展示正用於自患者取樣血液的計量 吸管。 35 200813324 P6495001OTWC1 22169- l-twf.doc/006 圖22A以及圖22B為用於執行快逮反 應比色檢定之裝 置的示意圖。Area) 665. During high-speed centrifugation, the water-soluble retardation layer of the time delay valve 664 is dissolved, and after being separated, the superabsorbent resin (SAP) absorbs part of the water and then expands, and blocks the blood cell region 663 and the plasma region 665. Diffusion mixing between. Some examples have been discussed above, but other implementations and applications are also within the scope of the following patent application. For example, in Fig. 1A and Fig. 2, the container 1〇〇 may contain a low pressure region rather than a vacuum region. As long as the gas pressure inside the vessel 100 is lower than the gas pressure of the vessel 1 outside the vessel, when the Gu 100 is disconnected, the pressure in the region (10) outside the vessel (10) will drop and the attraction will be induced toward the vessel in one direction. The attraction of fluids. The capillaries described above may be replaced by capillaries made of other brittle materials 34 200813324 P64950010TWC1 22169-I-tw£doc/006, such as brittle plastic, quartz [simplified illustration] ~ - Figure 1A and Figure 1B Schematic diagram of the vacuum pump. 2A and 2B are not intended to be gas fruits. 3A and 3B are schematic views of a gas pump. 4A is a schematic view of a gas pump. Figure 4B is a table of materials. Lutu 5A and Fig. 5B are schematic views of a disconnected open valve. 6A, 6B, 7A, 7B and 8A to 8C are schematic views of the self-closing valve. _ Figures 9A to 9C are schematic views of the valve opening and closing. 10A to 10C are schematic views of the switch-off valve. 11A to 11D are schematic views of a switch-on/off valve. Figure 12 is a schematic illustration of a metering straw. Figure 13 is a schematic illustration of a metering straw. 14A to 14C are schematic views of a metering straw. Lu Figure 15A and Figure 1 SB are schematic views of the metering device. 16A and 16B are schematic views of a metering device. 17A to 17C are illustrations of the apparatus for the two-step assay - Figs. 18A to 18C are diagrams showing the apparatus for the two-step assay. 19A through 19C are schematic diagrams of a sound map 20 for a three-step assay device for a module for multiple analyte assays. W Figure 21A and Figure 21B show a metering straw being used to sample blood from a patient. 35 200813324 P6495001OTWC1 22169-l-twf.doc/006 Figures 22A and 22B are schematic diagrams of an apparatus for performing a fast-reaction colorimetric assay.
圖2SA至圖2SC為真空泵的示意圖。 圖26A以及圖26B為真空泵的示意圖。 圖27A至圖27C為自關閉閥的示意圖。 圖28A以及圖28B為斷開式打開閥的示意圖。 的橫截面。 圖28C展示具有方形内周邊以及外周邊之玻璃毛細管 圖29A與29B說明本發明具體實施例之藉由使用自 閉閥(SLV)與斷開式打開閥(Β〇ν)之組合來製造用於 液樣本進行抗體(Antibody)檢定的裝置。 圖30A、30B與30C說明圖29A之對血液樣本進行抗 體檢定裝置操作示意圖。 圖31說明本發明另一具體實施例之藉由使用自關閉 閥(SLV)與斷開式打開閥(Β〇ν)之組合來製造用於對血液 樣本進行抗體檢定的裝置。 彳 圖32A、32B為具有遲滯層的自關閉閥示意圖。 圖33A與33B所示’分別顯示局部塗佈或全面的塗佈 圖3 4 A與3 4 B繪示本發明所提出具有時間延滯閥的抗 體檢定裝置的一實施例。 36 200813324 P6495001OTWC1 22169-1 -twf.doc/006 圖35A、35B、35C與35D繪示本發明所提出具有時 間廷滯閥的抗體檢定方法。 圖3 6 A與3 6 B繪示本發明所提出具有時間延滯閥的企 液離心裝置實施例。 ^ 【主要元件符號說明】 90 ··真空泵 92 :氣體泵 94 :氣體泵 96 :氣體栗 100 :容器 102 :材料 104 ··區域 106 :通道 108 :方向 110 :容器 112 :區域 • 114 :方向 120 :玻璃毛細管 Λ 124 :通道 ★ 126 :第一材料 128 :第二材料 130 :化合物 132 :玻璃毛細管 140 :斷開式打開閥 37 200813324 P6495001OTWC1 22169-1 -twf.doc/006 142 ··玻璃毛細管 144 :開放端 146 :閉合端 148 :第一通道 “ 150 :第二通道 152 :第二通道 160 :自關閉閥 162 :超級吸附劑聚合物(SAP) 164 :通道 166 :第一區域 168 :第二區域 170 :自關閉閥 172 :擴大部分 180 ·導線 182 ·凹座區域 190 :開關開閥 • 210 :開關開關閥 212 :超級吸附劑聚合物(SAP) ~ 214 :超級吸附劑聚合物(SAP) , 220 :計量吸管 222 :計量吸管 224 ··吸管管體 226 :球體 228 :管體 38 200813324 P6495001OTWC1 22169-1 -twf.doc/006 230 :吸管 232 :氣體泵 234 :吸管球體 240 :計量吸管 ^ 242 :球體 244 :中間部分 246 :吸管管體 248 :吸管管體 • 260 :計量裝置 262 ·•玻璃毛細管 264 :區段 266a :分枝 266b :分枝 268a :自關閉閥 268b :自關閉閥 270a :斷開式打開閥 • 270b ··斷開式打開閥 274 :流體 • 280 :計量裝置 , 282 :樣本池 284a :毛細管 284b :毛細管 284c ··毛細管 286a :自關閉閥 39 200813324 P6495001OTWC1 22169-1 -twf.doc/006 286b :自關閉閥 286c :自關閉閥 288a ··真空闕 288b :真空閥 Λ 288c ··真空閥 290 :裝置 292a :第一真空泵 292b :第二真空泵 ® 292c :第三真空泵 294 :斷開式打開閥 296 :自關閉閥 298 :缓衝液 300 :樣本池 302 :通道 304 :通道 306 :結合及/或感測區 • 308 ··通道 310 :裝置 Λ 314 :氣體泵 . 320 :裝置 322 :通道 324 :第二緩衝液 326 :斷開式打開閥 330 :模組 200813324 P64950010TWC1 22169- l-twf.doc/0062A to 2SC are schematic views of a vacuum pump. 26A and 26B are schematic views of a vacuum pump. 27A to 27C are schematic views of a self-closing valve. 28A and 28B are schematic views of a disconnected open valve. Cross-section. Figure 28C shows a glass capillary having a square inner perimeter and an outer perimeter. Figures 29A and 29B illustrate the use of a combination of a self-closing valve (SLV) and a break-open valve (Β〇ν) for the fabrication of the embodiment of the present invention. The liquid sample is subjected to an antibody (antibody) assay device. Figures 30A, 30B and 30C illustrate a schematic view of the operation of the blood test device for the blood sample of Figure 29A. Figure 31 illustrates a device for making an antibody assay for a blood sample by using a combination of a self-closing valve (SLV) and a disconnected open valve (Β〇ν) in accordance with another embodiment of the present invention.彳 Figures 32A and 32B are schematic views of a self-closing valve having a hysteresis layer. Figures 33A and 33B show a partial coating or a full coating, respectively. Figures 34A and 3BB illustrate an embodiment of the antibody assay device of the present invention having a time delay valve. 36 200813324 P6495001OTWC1 22169-1 -twf.doc/006 Figures 35A, 35B, 35C and 35D illustrate an antibody assay method of the present invention having a timed valve. Figures 3 6 and 3 6 B illustrate an embodiment of a liquid centrifuge device having a time delay valve as proposed by the present invention. ^ [Main component symbol description] 90 · Vacuum pump 92: Gas pump 94: Gas pump 96: Gas pump 100: Container 102: Material 104 · · Area 106: Channel 108: Direction 110: Container 112: Area • 114: Direction 120 : glass capillary Λ 124 : channel ★ 126 : first material 128 : second material 130 : compound 132 : glass capillary 140 : open type open valve 37 200813324 P6495001OTWC1 22169-1 -twf.doc / 006 142 · · glass capillary 144 Open end 146: closed end 148: first passage "150: second passage 152: second passage 160: self-closing valve 162: super adsorbent polymer (SAP) 164: passage 166: first region 168: second Zone 170: self-closing valve 172: enlarged portion 180 • wire 182 • recessed area 190: switch open valve • 210: switch on and off valve 212: super adsorbent polymer (SAP) ~ 214: super adsorbent polymer (SAP) , 220: metering straw 222: metering straw 224 · straw tube 226: sphere 228: tube body 38 200813324 P6495001OTWC1 22169-1 -twf.doc / 006 230: straw 232: gas pump 234: straw sphere 240: metering straw ^ 242: Sphere 244: Middle Section 246: Suction Tube Body 248: Suction Tube Body • 260: Metering Device 262 • Glass Capillary 264: Section 266a: Branch 266b: Branch 268a: Self-closing Valve 268b: Self-closing Valve 270a: Disconnected Open Valve • 270b • Disconnected open valve 274: Fluid • 280: Metering device, 282: Sample cell 284a: Capillary 284b: Capillary 284c • Capillary 286a: Self-closing valve 39 200813324 P6495001OTWC1 22169-1 -twf.doc/006 286b : self-closing valve 286c: self-closing valve 288a · vacuum 288b: vacuum valve Λ 288c · vacuum valve 290: device 292a: first vacuum pump 292b: second vacuum pump® 292c: third vacuum pump 294: open-open valve 296: self-closing valve 298: buffer 300: sample cell 302: channel 304: channel 306: bonding and/or sensing zone • 308 • channel 310: device Λ 314: gas pump. 320: device 322: channel 324: Second buffer 326: open type open valve 330: module 200813324 P64950010TWC1 22169- l-twf.doc/006
332a :腔室 332b :腔室 332c :腔室 334a ··真空泵 336a :第二真空泵 338a :第三真空泵 340a :第四真空泵 342a :通道 344a :自關閉閥 346a ··自關閉閥 348a :斷開式打開閥 350a :第一緩衝液 352a :自關閉閥 354a :斷開式打開閥 356a :第二緩衝液 358a :自關閉閥 360a ··斷開式打開閥 362a :第三缓衝液 370 :血液 380 :裝置 382 :樣本池 384 :通道 3 8 6 ·測試區 390 :裝置 41 200813324 P6495001OTWC1 22169-1 -twf.doc/006 392 :過濾薄膜 400 :裝置 402 :樣本池 404 :氣體泵 ^ 406 :樣本流體 408 :密封帶 410 :氣體泵 412 :氣體泵 416 ··真空玻璃毛細管 418 :管 420 ··橡皮管 424 :閉合端 426 :開放端 428 :閉合端 430 :真空泵 432 :真空泵 ⑩ 434 :平面基板 436 :彈性層 • 438 :流體通道 . 440 ··閉合端 442 :開放端 444 :流體通道 450 :導線 460 :塑膠通道 200813324 P6495001OTWC1 22169-1 -twf.doc/006 462 :塑膠通道 464 :反應劑 466 : UV光源 468 :偵測器 5〇〇:用於對血液樣本進行抗體檢定的裝置 5〇1,血液樣本池(Blood sample well) 503 ·沖洗缓衝液池(Washing buffer well) 505 ·計量區域與標誌、抗體(Metering zone and labeled antibody)區域 507 ·診斷法區域(Diganostic Zone)(抗體陣列 Antibody array) 509 :斷開式打開閥 511 :廢棄物池(Waste well) 513 :自關閉閥(SLV) 550 ··自關閉閥 552 ·通道 554 β•擴大部分 556 :超級吸附劑聚合物 558 :延滯層 600 :抗體檢定裝置 610 :檢體流通通道 612 :步階區域 614 ·抗體陣列區域(Antib〇dy Array Area) 616 ·斷開式打開閥(Broken Open Valve) 43 200813324 P6495001OTWC1 22169-1-twf.doc/006 620 :標記抗體槽(Labeled Antibody Well) 630 :樣品槽(Sample Well) 640 :沖洗液槽(Washing Buffer Well) 622 :第一時間延滯閥 632 ·弟二時間延滯閥 625 ·標§己抗體 635 ··金液樣本 660 :配置時間延滯閥的全血分離裝置 662 ··全血分離道管 664 :時間延滯閥 666 :轉轴 668 ·離心力方向(Centrifugal Direction) 661 ·全金樣品(whole Blood Sample) 663 :金球區(Blood Cell Area) 665 ·血襞區(Bi〇〇d Plasma Area)332a: chamber 332b: chamber 332c: chamber 334a · vacuum pump 336a: second vacuum pump 338a: third vacuum pump 340a: fourth vacuum pump 342a: channel 344a: self-closing valve 346a · self-closing valve 348a: disconnected Open valve 350a: first buffer 352a: self-closing valve 354a: open type open valve 356a: second buffer 358a: self-closing valve 360a · disconnected open valve 362a: third buffer 370: blood 380: Device 382: sample cell 384: channel 3 8 6 · test zone 390: device 41 200813324 P6495001OTWC1 22169-1 -twf.doc/006 392: filter membrane 400: device 402: sample cell 404: gas pump ^ 406: sample fluid 408 : sealing tape 410 : gas pump 412 : gas pump 416 · vacuum glass capillary 418 : tube 420 · rubber tube 424 : closed end 426 : open end 428 : closed end 430 : vacuum pump 432 : vacuum pump 10 434 : planar substrate 436 : Elastic layer • 438 : fluid channel. 440 · · closed end 442 : open end 444 : fluid channel 450 : wire 460 : plastic channel 200813324 P6495001OTWC1 22169-1 -twf.doc / 006 462 : plastic channel 464 : reagent 466 : UV Light source 468: detector 5〇 〇: Device for antibody testing of blood samples 5〇1, Blood sample well 503 · Washing buffer well 505 · Metering zone and labeled antibody Area 507 · Diagnostic Zone (antibody array) 509 : Disconnected open valve 511 : Waste well 513 : Self-closing valve (SLV) 550 · Self-closing valve 552 · Channel 554 β•Expanded portion 556: Super adsorbent polymer 558: retardation layer 600: Antibody assay device 610: Sample flow channel 612: Step region 614 • Antibody array region (Antib〇dy Array Area) 616 • Disconnected open Valve (Broken Open Valve) 43 200813324 P6495001OTWC1 22169-1-twf.doc/006 620 : Labeled Antibody Well 630 : Sample Well 640 : Washing Buffer Well 622 : First Time delay valve 632 · Di two time delay valve 625 · Standard § antibody 635 · · Gold sample 660 : Whole blood separation device 662 with time delay valve · · Whole blood separation tube 664 : Time delay valve 666: Rotary shaft 668 · Centrifugation Forcerifugal Direction 661 · Whole Blood Sample 663 : Blood Cell Area 665 · Bi〇〇d Plasma Area
4444
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| TW95142968A TWI336781B (en) | 2006-07-17 | 2006-11-21 | Fluidic device and controlling method thereof |
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| CN103529195B (en) * | 2013-10-24 | 2014-08-06 | 山东大学 | Detection method applied to measurement of trace target materials |
| AU2016306713C1 (en) * | 2015-08-12 | 2023-06-01 | University Of Tasmania | Liquid collection device |
| JP6529667B2 (en) * | 2016-01-22 | 2019-06-12 | ヒューレット−パッカード デベロップメント カンパニー エル.ピー.Hewlett‐Packard Development Company, L.P. | Fluid detection with control of particle aggregation in the detection area |
| CN111110951A (en) * | 2020-01-09 | 2020-05-08 | 中国人民解放军总医院 | Micro-control orbital vein quantitative blood taking, injection and analysis device |
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| DE60031540T2 (en) * | 1999-06-28 | 2007-05-16 | California Institute Of Technology, Pasadena | MICROMECHANICAL PUMP AND VALVE SYSTEMS |
| US6521188B1 (en) * | 2000-11-22 | 2003-02-18 | Industrial Technology Research Institute | Microfluidic actuator |
| US6527003B1 (en) * | 2000-11-22 | 2003-03-04 | Industrial Technology Research | Micro valve actuator |
| US6453928B1 (en) * | 2001-01-08 | 2002-09-24 | Nanolab Ltd. | Apparatus, and method for propelling fluids |
| EP1490601B1 (en) * | 2002-03-23 | 2007-08-15 | Starbridge Systems Limited | Micromechanical components |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |