200912310 九、發明說明： 【發明所屬之技術領域】 本發月是有關於一種晶片，特別是指一種微流體生物 檢驗晶片。 【先命技術】 ;單株抗體技術與營光標定技術的逐漸成熟，利用 ^體會與特定抗原進行特異性反應，並配合螢光標定的光 學檢測技術，已逐漸被廣泛應用於各種檢驗方面。近年來 ，更發展出-種利用I面修飾固定有鍵結抗體之磁珠，來 抓取檢體中帶有特定抗原之檢測標的物（例如病毒、細菌 田胞等）的檢測方式，並於磁珠抓取該檢測對象後，以 可被激發出螢光之偵測抗體對檢測對象進行螢光標定，再 利用大型磁力架所產生之磁力將磁珠吸附固定試管之内壁 面進而將特疋抗原之檢測標的物一起固定於管壁，使得 該檢測標的物可與檢體中的其他物質分離，而達到分離、 純化與濃縮的目的。但因此種檢測方式所使用之儀器，均 為較大型儀器，且須人工多次操作，無法全程自動進行。 由於微流體檢測晶片具有高檢測效能、低樣品與檢體 消耗量、體積小…等優點，微型生物檢測晶片已逐漸被用以 取代傳統生物醫學檢測裝置。因此，若能發展出一種利用 混合磁珠抓取檢體中之特定檢測標的物，來達到分離、純 化與濃縮之目的，並可結合檢測標的物之螢光標定的光學 檢測晶片，將可大幅提高生物檢測之效能、速度，且能降 低檢體與樣品之使用量，進而相對降低檢測成本。 200912310 【發明内容】 因此，本發明之目的，即在提供一種可搭配用以抓取 檢體中之特定生物分子之磁珠，並可用以對該生物分子進 行螢光標定，而可方便利用光學檢測系統進行快速檢測之 生醫微流體晶片。 本發明之另一目的在於提供一種可搭配用以抓取檢體 中之特疋生物分子之磁珠，並可被通電而產生吸引磁珠之 磁力的生醫微流體晶片。 於是，本發明可快速偵測之生醫微流體晶片，可利用 磁珠抓取檢體中之特定生物分子，且適用於以勞光試劑對 該生物分子進行螢光標定，該生醫微流體晶片包含由下往 上依序疊接之-基板層、_流道層，及一幫浦層。該基板 層上被覆有一由金屬線圍繞構成之電磁線圈，且該電磁線 圈可被通電而產生吸附磁珠之磁力。 該流道層包括多數個可分別容裝螢光試劑、磁珠溶液 、檢體與緩衝液之注液孔、_凹設於其底面且與該等注液 連通而可供上述液體注入混合並流經該電磁線圈上方之 微流道'二分別設置於微流道相反侧並可供液體注入微流 道中而迫使位於微流道中磁珠匯聚於微流道中間的鞘流孔 、-位於電磁線圈上方與微流道連通之磁吸孔，及至少 ”微抓道連通並可收集來自微流道之檢測後液體的集液 孔。 ' 該幫浦層包括數量分別和流道層之該等注液孔、勒流 孔、磁吸孔與集液孔對應且連通之注液孔、鞘流孔、磁吸 200912310 孔和集液孔，更包括一可被驅動而封閉微流道之預定區段 的閥門機構’及一可被驅動而驅使微流道内之流體流動與 混合的幫浦機構。 於是’本發明可快速偵測之生醫微流體晶片，可搭配 用以抓取檢體中之特定生物分子之磁珠與對該生物分子進 行螢光標定之螢光試劑使用，並可安裝於一具有可產生吸 引磁珠之磁力的磁力區之檢測裝置上，該生醫微流體晶片 3由下在上依序疊接之一基板層、一可被推擠而局部彈 性變形之擠推層，及一流道層。該流道層包括多數個可分 別容裝螢光試劑、磁珠和檢體混合液與緩衝液之注液孔、 一凹設於其底面且與該等注液孔連通而可供上述液體注入 混合並流經該磁力區上方的微流道、二分別設置於微流道 相反侧並可供液體注入微流道中而迫使位於微流道中磁珠 匯聚於微流道中間的鞘流孔，及至少一與微流道連通並可 收集來自微流道之檢測後液體的集液孔。 該基板層包括一可被驅動而迫使擠推層局部彈性變形 而封閉微流道之預定區段的閥門機構，及一可被驅動而迫 使擠推層局部彈性變形而將該等注液孔中之液體推擠入微 流道内並朝集液孔流動的幫浦機構。 【實施方式】 有關本發明之前述及其他技術内容、特點與功效，在 以下配合參考圖式之二個較佳實施例的詳細說明中，將可 清楚的呈現。 在本發明被詳細描述之前，要注意的是，在以下的說 8 200912310 明内容中，類似的元件是以相同的編號來表示。 如圖1〜3所示，本發明可快速偵測之生醫微流體晶片 之第一較佳實施例，適用於設置於一光學檢測裝置2之承 接座21中，而可方便置入該檢測裝置2中進行光學檢測分 析，该生醫微流體晶片3包含由下往上依序疊接之一基板 層4、一流道層6,及一幫浦層7。 該基板層4為一透明玻璃片，具有一被覆於其頂面中200912310 IX. Description of the invention: [Technical field to which the invention pertains] This publication relates to a wafer, and more particularly to a microfluidic bioassay wafer. [Fat-skill technology]; The gradual maturity of the single-body antibody technology and the batching technique has been gradually applied to various inspections by using the specific reaction of the specific antigen and the optical detection technology. In recent years, it has been developed to use a magnetic bead immobilized with a binding antibody on the I surface to capture a detection method of a specific antigen (such as a virus, a bacterial cell, etc.) in a sample. After the magnetic bead grabs the detection object, the detection object is fluoresced by the detection antibody that can be excited by the fluorescent light, and then the magnetic force generated by the large magnetic frame is used to adsorb the magnetic beads to fix the inner wall surface of the test tube, and then the special feature is The detection target of the antigen is fixed together on the tube wall, so that the detection target can be separated from other substances in the sample to achieve the purpose of separation, purification and concentration. However, the instruments used in the various detection methods are all larger instruments, and must be manually operated multiple times, and cannot be automatically performed at all times. Micro-bioassay wafers have gradually been used to replace traditional biomedical detection devices due to their high detection efficiency, low sample and sample consumption, and small size. Therefore, if a hybrid magnetic bead can be used to grasp the specific detection target in the sample to achieve the purpose of separation, purification and concentration, and the optical detection wafer can be combined with the detection of the target object. Improve the efficiency and speed of bioassay, and reduce the amount of sample and sample used, thereby reducing the cost of detection. SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a magnetic bead that can be used to capture a specific biomolecule in a sample, and can be used to perform a cursor on the biomolecule, thereby facilitating the use of optics. The biomedical microfluidic wafer is tested by the detection system for rapid detection. Another object of the present invention is to provide a biomedical microfluidic wafer that can be used with magnetic beads for grasping specific biomolecules in a sample and that can be energized to generate a magnetic force that attracts the magnetic beads. Therefore, the present invention can quickly detect a biomedical microfluidic wafer, and can use a magnetic bead to grasp a specific biomolecule in the sample, and is suitable for performing a fluorescent cursor on the biomolecule with a lab light reagent, the biomedical microfluid The wafer includes a substrate layer, a channel layer, and a pump layer which are sequentially stacked from bottom to top. The substrate layer is covered with an electromagnetic coil surrounded by a metal wire, and the electromagnetic coil can be energized to generate a magnetic force for attracting the magnetic beads. The flow channel layer comprises a plurality of liquid injection holes respectively accommodating the fluorescent reagent, the magnetic bead solution, the sample and the buffer, and is recessed on the bottom surface thereof and connected to the liquid injection to allow the liquid to be injected and mixed. The microchannels 'flowing through the electromagnetic coils' are respectively disposed on opposite sides of the microchannels and are available for liquid injection into the microchannels to force the beads in the microchannels to converge in the middle of the microchannels. a magnetic hole communicating with the micro flow channel above the coil, and at least a "micro-grab line communicating with the liquid collecting hole of the detected liquid from the micro flow channel." The pump layer includes the number and the flow channel layer. The liquid injection hole, the flow hole, the magnetic hole and the liquid collecting hole correspond to and communicate with the liquid injection hole, the sheath flow hole, the magnetic hole 200912310 hole and the liquid collecting hole, and further comprise a predetermined area that can be driven to close the micro flow channel The valve mechanism of the segment and a pump mechanism that can be driven to drive the fluid flow and mixing in the microchannel. Thus, the invention can quickly detect the biomedical microfluidic wafer, which can be used for grasping the sample. Magnetic beads of a specific biomolecule and the biomolecule The fluorescent cursor is used for the fluorescent reagent, and can be mounted on a detecting device having a magnetic region capable of generating a magnetic force for attracting the magnetic beads, and the biomedical microfluidic wafer 3 is sequentially stacked on one of the substrate layers. a push-pull layer that can be pushed and partially elastically deformed, and a first-order layer. The flow channel layer includes a plurality of liquid injection holes that can respectively accommodate the fluorescent reagent, the magnetic beads, and the sample mixture and the buffer, a micro flow channel recessed on the bottom surface thereof and communicating with the liquid injection holes for allowing the liquid to be injected and mixed and flowing through the magnetic region, respectively, and disposed on the opposite side of the micro flow channel and allowing liquid to be injected into the micro flow channel Forcing the bead orifices in the microchannel to converge in the middle of the microchannels, and at least one liquid collecting hole communicating with the microchannels and collecting the detected liquid from the microchannels. The substrate layer includes a driveable layer And a valve mechanism for forcing the squeezing layer to be partially elastically deformed to close a predetermined section of the microchannel, and a drive mechanism for forcing the squeezing layer to be partially elastically deformed to push the liquid in the liquid injection hole into the microchannel Pump mechanism flowing toward the liquid collecting hole The above and other technical contents, features, and advantages of the present invention will be apparent from the following detailed description of the preferred embodiments of the present invention. It should be noted that similar elements are denoted by the same reference numerals in the following description of the contents of the above-mentioned 8 200912310. As shown in Figures 1 to 3, the present invention can quickly detect the first of the biomedical microfluidic wafers. The preferred embodiment is suitable for being disposed in the receiving seat 21 of an optical detecting device 2, and can be conveniently placed in the detecting device 2 for optical detection and analysis. The biomedical microfluidic chip 3 comprises a stack from bottom to top. a substrate layer 4, a first-order layer 6, and a pump layer 7. The substrate layer 4 is a transparent glass sheet having a coating on the top surface thereof.
間部位並由薄膜狀金屬線左右往復圍繞構成之電磁線圈51 ’該電磁、線® 51具有一位於基板層4底面中間部位之矩形 線圈部5U’及二分別延伸至基板層4底面左、右側之導電 部叫，該線圈部511是由—金屬線前後往復彎折所構成， 具有多數左右間隔且依序相連之區段512，且每—區段M2 亦左右往復彎折而構成多數前後依序相連之半圓環狀弧彎 部513 ’該等導電部514是分別電連接於線圈部511之兩相 反端。 另外，該微流體晶片3更包含一覆蓋該線圈部5ιι的局 部被覆於基板層4上之透明薄膜狀保護層52。 在本實施例中，該電磁線目5 j是利用微影技術（ Lithography)與化學電鍍技術沉積於該基板層4頂面，為 厚度約12 之金屬銅線，而該保護層52為厚度約Η" m之透明SU-.8光阻，但實施時，該電磁線圈51之設置方 式、分佈外型與材質 及該保護層52之材質皆不以此為限 該流道層6是由透明且具彈性之薄片狀二甲基石夕氧烧 200912310 (PDMS)製成’包括間隔分布於其前端部之—第一、一第 二與-第三注液孔61〜63、左右間隔地分佈於其後端部之一 第-與-第二集液孔64〜65、—凹陷於其底面且前後延伸的 連通於該等注液孔61〜63與集液孔64〜65間之微流道^、 二左右間隔且分別與微流道66連通之㈣孔Μ，及一與微 流道66連通之磁吸孔68。 該微流道66具有-自該第—注液孔61往後延伸之第 一匯流段660、分別自第二與第三注液孔62、63往後相向 延伸而與第一匯流段660連通之一第二與一 66卜662 一連通於該等匯流段⑽〜啦連通處與該磁= 68間之環狀混合段663、一自該磁吸孔68往後延伸且末端 部逐漸窄縮變細之聚焦段664、—自該聚焦段_末端往後 延伸之檢測段665、二分別與該等鞘流孔67連通且左右相 向地往後傾斜延伸而分別連通於聚焦段664末端部之鞘流 段666,及分別自檢測段665末端左右相背地往後延伸而^ 別與該等集液孔64、65連通之一第一與一第二分選段 667〜668。其中，該檢測段665與該等分選段667、668内 徑皆小於該聚焦段664，而僅可讓單一磁珠（圖未示）通過 該幫浦層7是由透明二甲基矽氧烷（PDMS)製成，包 括分別與流道層6之該等注液孔61〜63對應連通之一第四 、一第五與一第六注液孔71〜73、分別與該等集液孔64、 65對應連通之一第三與一第四集液孔74、75、二分別與該 等鞘流孔66連通之鞘流孔76，及一與該磁吸孔68連通之 10 200912310 磁吸孔77。該幫浦層7更包括-可被驅動而迫使流道層6 阻塞微々_L道66之預定部位的閥門機構78，及一可被驅動而 促使微流道66中之流體流動的幫浦機構79。 該閥門機構78具有五個閥門氣孔78〇與二個分選氣孔 781刀別凹陷於幫浦層7底面且分別與該等閥門氣孔780 連通並對應位於微流道66上方之—個第—閥門氣室爪、 一個第二閥門氣室783、—第三閥門氣室784與二個第四閥 門氣室785,及分別凹陷於f浦層7底面且分職該等分選 氣孔781連通並對應位於微流道66上方之一第一與一第二 分選氣室786、787。 其中，第一閥門氣室782是位於第一匯流段66〇與第 一注液孔61連通處上方，第二閥門氣室783是位於第三匯 f段662與第三注液孔63連通處上方，第三閥Η氣室· 是位於聚焦段664與磁吸孔68連通處上方，該等第四間門 氣室785是分別位於該等鞘流段666與鞘流孔^連通處上The electromagnetic coil 51 has a rectangular coil portion 5U' located at an intermediate portion of the bottom surface of the substrate layer 4 and two extending to the left and right sides of the bottom surface of the substrate layer 4, respectively. The conductive portion is formed by a reciprocating bending of the metal wire, and has a plurality of segments 512 which are spaced apart from each other in sequence, and each segment M2 is also reciprocally bent to form a majority of the front and rear. The semi-circular arc-shaped portions 513 ′ that are connected in series are electrically connected to opposite ends of the coil portion 511, respectively. Further, the microfluidic chip 3 further includes a transparent film-like protective layer 52 covering the substrate portion 4 with a portion covering the coil portion 5 ι. In this embodiment, the electromagnetic wire 5j is deposited on the top surface of the substrate layer 4 by using Lithography and electroless plating technology, and is a metal copper wire having a thickness of about 12, and the protective layer 52 is about a thickness. Η" m transparent SU-.8 photoresist, but in implementation, the arrangement of the electromagnetic coil 51, the distribution shape and material, and the material of the protective layer 52 are not limited thereto. The flow channel layer 6 is transparent. And the elastic flaky dimethyl oxysulfide 200912310 (PDMS) is made to include 'first, second and third liquid injection holes 61 to 63 spaced apart at the front end portion thereof, and distributed at right and left intervals The first-and-second liquid-collecting holes 64-65 at the rear end portion thereof are recessed on the bottom surface thereof and extend in the front-rear direction to communicate with the microfluids between the liquid-injecting holes 61-63 and the liquid collecting holes 64-65. The channel is connected to the microchannel 13 and is connected to the microchannel 66, and a magnetic aperture 68 is connected to the microchannel 66. The microchannel 66 has a first confluence section 660 extending rearward from the first liquid injection hole 61, and extending backward from the second and third liquid injection holes 62, 63, respectively, to communicate with the first confluence section 660. One of the second and one of the 66 662 is in communication with the confluent section (10)-to-the intersection of the junction and the magnetically-integrated section 663, and extends backward from the magnetic aperture 68 and the end portion is gradually narrowed. The tapered focusing section 664, the detecting sections 665 and 2 extending from the end of the focusing section _ are respectively connected to the sheath flow holes 67, and are inclined obliquely to the left and right and are respectively connected to the end portions of the focusing segments 664. The sheath flow section 666 extends from the end of the detection section 665 to the left and right, and is connected to the first and second separation sections 667 to 668 in communication with the liquid collection holes 64 and 65, respectively. Wherein, the detection section 665 and the inner diameters of the sorting sections 667, 668 are smaller than the focusing section 664, and only a single magnetic bead (not shown) passing through the pumping layer 7 is made of transparent dimethyl decane. (PDMS), comprising a fourth, a fifth and a sixth liquid injection holes 71 to 73 respectively corresponding to the liquid injection holes 61 to 63 of the flow channel layer 6, respectively, and the liquid collection holes 64, 65 corresponding to one of the third and fourth liquid collecting holes 74, 75, two sheath flow holes 76 respectively communicating with the sheath flow holes 66, and a magnetic connection with the magnetic holes 68 10 200912310 magnetic attraction Hole 77. The pumping layer 7 further includes a valve mechanism 78 that can be driven to force the flow channel layer 6 to block a predetermined portion of the microchannels 66, and a pumping mechanism that can be driven to cause fluid flow in the microchannels 66. 79. The valve mechanism 78 has five valve air holes 78 〇 and two sorting air holes 781 which are recessed on the bottom surface of the pump layer 7 and communicate with the valve air holes 780 respectively and corresponding to the first valve located above the micro flow path 66 a chamber chamber claw, a second valve chamber 783, a third valve chamber 784 and two fourth valve chambers 785, and are respectively recessed in the bottom surface of the p-pull layer 7 and are connected to the sorting holes 781 and correspondingly One of the first and a second sorting chambers 786, 787 located above the microchannel 66. Wherein, the first valve chamber 782 is located above the first confluence section 66〇 and the first injecting hole 61, and the second valve chamber 783 is located at the junction of the third sinking section 662 and the third injecting hole 63. Above, the third valve Η chamber is located above the communication between the focusing section 664 and the magnetic absorbing hole 68, and the fourth door plenum 785 is located at the intersection of the sheath flow section 666 and the sheath flow hole respectively.
方。第—分選氣室786是位於第—分選段⑹與檢測段奶 連通處上方，第二分選氣室787是位於第二分選段⑽與 檢測段665連通處上方。可分別經由該等氣孔780、781對 該等氣室勝787可分別被灌注高壓氣體，分別迫使該等 乳室782〜787所涵蓋之流道層6部位，往下陷入微流道66 中並阻塞微流道66。 該幫浦機構79具有四間隔分右+封丄 男间&刀布之幫浦氣孔791，及分 別凹陷於幫浦層7底面且分別盥該箄暂 第一、一第 I、〇表导幫浦氣孔791連通之 第三與一第四幫浦氣室792〜795。該等 200912310square. The first sorting chamber 786 is located above the junction of the first sorting section (6) and the detecting section, and the second sorting chamber 787 is located above the junction of the second sorting section (10) and the detecting section 665. The gas chambers 787 can be respectively infused with high pressure gas via the pores 780, 781, respectively, forcing the flow channel layer 6 covered by the chambers 782 to 787, respectively, into the microchannel 66 and The micro flow path 66 is blocked. The pumping mechanism 79 has four spaced apart right + sealed male men's & knife cloth sump 791, and respectively sunken on the bottom of the pumping layer 7, respectively, respectively, the first, the first, the first The pump vent 791 is connected to the third and a fourth pump chamber 792~795. The 200912310
幫浦氣室792〜795是對應位於微流道66之環狀混合段μ〕 上方，並沿該混合段663間隔排列成環狀，且該等幫浦氣 室792〜795可分別被灌注高壓氣體，而迫使其所涵蓋之流 道層部ό位往下凹陷並阻塞下方之混合段663部位。 L 在本實施例中，本發明可快速偵測之生醫微流體晶片3 使用時，需先將該生醫微流體晶片3組裝於該光學檢測裝 置2中，並使該電磁線圈51之該等導電部與檢測裝置 2電連接，且將該等氣孔78〇、781、791分別與空壓機（圖 未示）組接，而可透過空壓機將高壓氣體注入該等氣室 782〜787、792〜795巾，且該等鞘流孔67、76會與一可輸出 同壓液體之儀器組接’而可經由該等鞘流# 666左右相向 地將高壓液體注入聚焦段664末端部。 開始檢測前，需先驅使空壓機作動，而對第一〜第四閥 門氣至782〜785充填高壓氣體，使流道層6之該等相對應 部位分別陷阻塞於該等匯流段66〇、663、聚焦段664與鞘 又666中，並對該等第一〜第四幫浦氣室792〜795充氣， I使"IL道層6之該等相對應部位分別凹陷而阻塞混合段 。接者，便可將表面修飾有預定鍵結抗體之磁珠與具有待 測生物物g (例如病毒、細菌、酵母菌或細胞..等）之溶液 起庄入相連通之第二與第五注液孔62、72中，而於相連 通之第與第四注液孔61、71中注入清洗用緩衝液，再於 相連通之第二與第六注液孔63、73中注人可被激發出螢光 之偵測抗體試齊丨。 70成上述準備步驟後’便可啟動該檢測裝置2開始進 12 200912310 行待測物質之制。該制裝置2會先將㈣層7之磁吸 孔77開口氣密封閉，並依序地釋放掉第—第四幫浦氣室 792〜795之氣體’此時’原本凹陷阻塞混合段⑹之該等流 道層6部位會依序往上彈性復原，而產生用以將第-注^ 孔61中之混合液體吸人混合段⑹中的負壓吸力，並可藉 由依序對該等幫浦氣室792〜795進行灌氣、㈣之方式，曰 使該混合溶液於混合段663中流動，促使磁珠之鍵結抗體 可逐漸抓住待測物質。並於混合數次後，該檢測裝置2會 打開磁吸孔77開口，並先對第一幫浦氣室792注氣，再同 日年對第二與第四幫浦氣室793、795注氣，最後對第三幫浦 氣室794注氣，將混合段663中之混合液擠人該等磁吸孔 68 、 77 中。 然後，再洩掉第二閥門氣室783之高壓氣體，使第三 匯流段662與第三注液孔63連通，並以依序洩掉第一、第 二與第三幫浦氣室792〜794之高壓氣體，再依序對第一〜第 三幫浦氣室792〜794灌氣的方式，使第一〜第三幫浦氣室 792〜794和流道層6之該等被擠壓凹陷部位相配合構成一蠕 動幫浦作用’而持續將第三注液孔63中之㈣抗體試劑輸 送至磁吸孔68、77中，而與待測物進行結合。實施時，亦 可以反向驅動第一〜第三幫浦氣室792〜794的方式，將磁吸 孔68、77中之混合液體一起輸送回該等注液孔62、63、72 、73中，然後再送回磁吸孔68、77中，藉以達到充分混合 ，但實施時不以此為限。 元成上述之混合動作後，該檢測裝置2會對該電磁線 13 200912310 圏5!通電，驅使該電磁線圈51之線圈部5ιι產生磁力，將 位於磁吸孔68、77中之磁珠往下吸附於保護層52上。秋 後’再封閉磁吸孔77開口’刪一與第三閥門氣室782 、784之氣體’並對第—分選氣室m灌注高錢體，而封 閉檢測段665與第-分選段667連通處。接著，再驅使第 —第三幫浦氣室792〜794產生螺動幫浦作用，將第一與第 、液孔61 71中之緩衝液傳送經過磁吸孔68、77 ,而將 磁吸孔68、77 t未被磁力吸住之雜f帶往第二集液孔65 中。 如圖2、4、5所示，待緩衝液作用一段時間後，停止 驅動該等幫浦氣室792〜794,並封閉第—匯流段_，且於 關閉—電磁線圈51而使磁珠刚脫離後，再次驅動該等第一 第二幫浦氣室792〜794作動，將含有磁珠1〇〇之溶液1〇 ' /聚’、、、#又664，並逐漸聚集而進入聚焦段之窄縮端部 t，於此同時，打開該等鞘流段666，並經由該等鞘流段 666將高壓緩衝液u注入聚焦段_中且左右相向地迫 使磁珠1〇〇逐漸聚集於聚焦段664中間部位，而逐顆排列 地依序進入細窄之檢測段665中。 此時，該檢測裝置2會對該檢測段665發射激發偵測 抗體發出螢光之雷射’而開始進行光學檢測，且該檢測裝 置2 s於接收到螢光訊號後，關閉第二分選段，並使第 I分選段667和檢測段665連通，使檢測後之含磁珠1〇〇 办液10收集至第一集液孔64、74中，而達到分離、純化 與濃縮之目的。 14 200912310 實靶蚪，流道層6與幫浦層7之該等注液孔6丨〜63、 =與集液孔64〜65、74〜75數量與設置位置皆可依需要 文I而幫浦機構79之該等幫浦氣室792~795數量亦可 序要而調整，另外’該微流道66亦可僅設置第-分選段 ;而對應不设置該等分選氣孔781與分選氣室786、787 /閥門機構78則不以設置該等第四閥門氣室785為必要 —、X保4層52亦非必要’且可將該電磁線圈51被覆固 疋於基板^ 4底面，同樣可達到通電而產生吸附磁珠之磁 、处9另外，當檢測裝置2具有可產生吸附磁珠之磁 力功此時，則可不需使用該電磁線圈51，但實施時，皆不 以上述外型為限。 再者，實施時，亦可透過增加生醫微流體晶片3之注 液孔與集Μ之數量，並配合使时難财㈣鍵結抗 體之磁珠的方式，制具有不同特異性免疫反應之磁珠來 抓住不同之病以後’相不同之㈣抗體分別對不同之 病原麵進行螢先# + 县 祆不最後，再配合閥膜機構78與幫浦機 79之作動設計’即可分別對不同螢光之磁珠進行檢測， 可將不同螢光之磁珠分選輸送至不同之集液孔中，但實 施時不以此為限。 、 如圖6〜8所示，本發明可快速㈣之生醫微流體晶片 的第二較佳實施例與第一實施例差異處在於：本 生醫微流體W 3未設置電磁線圈51，且整體結構亦不同 _: 說月以下僅針對本實施例第-實施例差異處進 15 200912310 在本實施例中，該生醫微流體晶片3包含由下往上依 序疊接之一基板層4、一彈性擠推層8,及一流道層6。該 擠推層8是由具彈性之薄片狀二甲基矽氧烷（PDMS)製成 ，可被擠推而彈性變形。 在本實施例中，該流道層6是由較厚之二甲基矽氧烷 (PDMS)製成，且具有左右間隔地分布於其前端部之一第 ' 二與一第三注液孔62〜63、左右間隔地分布於其後端部之一 第一與一第二集液孔64〜65、一位於其中間區段右側之廢液 孔69、二間隔分布於其中間區段之鞘流孔67，及一前後延 伸且連通於該等注液孔61〜63、集液孔64〜65、廢液孔69 與鞠流孔67間之微流道66。 該微流道66是凹設於流道層6底面，並具有左右相向 延伸之一第二匯流段661與一第三匯流段662、一連通於該 等匯流段661、662相向端間並貫穿流道層6頂底面之圓形 混合段663、一自混合段663往後延伸且後端部之左右寬度 窄縮的聚焦段664、一自聚焦段664後端往後延伸之檢測段 i 665、二左右相向地往後彎曲延伸且分別連通於聚焦段664 後端部左右側之鞠流段666，及分別自該檢測段665後端左 右相背地往後延伸之一第一分選段667與一第二分選段668 〇 其中，第二注液孔62是與第二匯流段661左端連通， 第三注液孔63是與第三匯流段662右端連通，該等集液孔 64、65是分別與該等分選段667、668後端連通，該等鞘流 孔67是分別與該等鞠流段666前端連通。 16 200912310 該基板層4包括一幫浦機構400，及一閥門機構4〇1。 該幫浦機構400具有分別凹設於其頂面且分別與擠推層8 相配合界定出一密閉空間之一第一幫浦氣室41、二第二幫 浦氣室42、一第三幫浦氣室43、二第四幫浦氣室44，及多 數分別貫穿其頂底面之且分別與該等幫浦氣室41〜44連通 之幫浦氣孔40。 该4繁浦氣室41〜44可分別被灌The pump chambers 792-795 are located above the annular mixing section μ of the microchannel 66, and are arranged in a ring shape along the mixing section 663, and the pump chambers 792-795 can be respectively filled with high pressure. The gas, forcing the flow channel layer covered by it to be depressed downward and blocking the lower portion of the mixing section 663. In the present embodiment, when the biomedical microfluidic chip 3 can be quickly detected, the biomedical microfluidic wafer 3 is first assembled into the optical detecting device 2, and the electromagnetic coil 51 is The conductive portions are electrically connected to the detecting device 2, and the air holes 78〇, 781, and 791 are respectively connected to an air compressor (not shown), and the high pressure gas can be injected into the air chambers 782 through the air compressor. 787, 792-795, and the sheath orifices 67, 76 are coupled to an instrument capable of outputting a liquid of the same pressure, and the high pressure liquid can be injected into the end of the focusing section 664 via the sheath flow #666. . Before starting the test, it is necessary to first drive the air compressor to operate, and the first to fourth valve gases are filled with high pressure gas to 782 to 785, so that the corresponding portions of the flow channel layer 6 are respectively trapped in the confluence section 66. , 663, the focusing segment 664 and the sheath 666, and inflating the first to fourth pumping chambers 792 to 795, and causing the corresponding portions of the "IL layer 6 to be respectively recessed to block the mixing section . Alternatively, the magnetic beads having the surface modified with the predetermined binding antibody and the solution having the biological substance g to be tested (for example, virus, bacteria, yeast or cells, etc.) can be connected to the second and fifth. In the liquid injection holes 62 and 72, the cleaning buffer is injected into the fourth and fourth liquid injection holes 61 and 71 which are in communication, and the second and sixth liquid injection holes 63 and 73 are connected to each other. The detection antibody that is excited by the fluorescence is tested. After 70% of the above preparation steps, the detection device 2 can be started to start the process of the test substance. The device 2 firstly seals the opening of the magnetic hole 77 of the (four) layer 7 and sequentially releases the gas of the fourth to fourth plenums 792-795, which is the original recessed block mixing section (6). The portions of the flow channel layer 6 are elastically restored in order, and the negative pressure suction force for sucking the mixed liquid in the first injection hole 61 into the mixing section (6) is generated, and the same can be obtained by sequentially The gas chambers 792 to 795 are filled with gas, and (4), the mixed solution is caused to flow in the mixing section 663, so that the bonded antibodies of the magnetic beads can gradually grasp the substance to be tested. After mixing a plurality of times, the detecting device 2 opens the opening of the magnetic suction hole 77, first injects the first pumping chamber 792, and injects gas into the second and fourth pumping chambers 793 and 795 in the same day. Finally, the third pumping chamber 794 is inflated, and the mixture in the mixing section 663 is squeezed into the magnetic holes 68, 77. Then, the high pressure gas of the second valve chamber 783 is discharged, the third bus portion 662 is connected to the third liquid inlet 63, and the first, second and third pump chambers 792 are sequentially discharged. 794 of the high-pressure gas, and then sequentially injecting the first to third pump chambers 792 to 794, so that the first to third pump chambers 792 to 794 and the runner layer 6 are squeezed. The recessed portions cooperate to constitute a peristaltic pumping action' while the (four) antibody reagent in the third liquid injection hole 63 is continuously transported into the magnetic holes 68, 77 to be combined with the analyte. In practice, the first to third pumping chambers 792 to 794 may be reversely driven to transport the mixed liquid in the magnetic holes 68, 77 together into the liquid filling holes 62, 63, 72, and 73. Then, it is sent back to the magnetic holes 68, 77, so as to achieve sufficient mixing, but the implementation is not limited thereto. After the above-mentioned mixing operation, the detecting device 2 energizes the electromagnetic wire 13 200912310 圏5! to drive the coil portion 5 ι of the electromagnetic coil 51 to generate a magnetic force, and the magnetic beads located in the magnetic holes 68, 77 are turned down. Adsorbed on the protective layer 52. After the autumn, 'reclose the magnetic aperture 77 opening' to delete the gas of the third valve chamber 782, 784 and inject the high-volume body into the first-selection chamber m, while the closed detection section 665 and the first-selection section 667 Connected. Then, the third to third chambers 792 to 794 are driven to generate a screwing action, and the buffers in the first and the first liquid holes 61 71 are transmitted through the magnetic holes 68 and 77, and the magnetic holes are 68, 77 t is not magnetically attracted by the impurity f to the second liquid collection hole 65. As shown in Figures 2, 4, and 5, after the buffer solution is applied for a period of time, the driving of the pump chambers 792 to 794 is stopped, and the first bus bar _ is closed, and the electromagnetic coil 51 is turned off to make the magnetic beads After the detachment, the first second pumping chambers 792 to 794 are again driven to operate, and the solution containing the magnetic beads 1 〇 ' / poly ', , # # 664, and gradually gathers into the focus segment The narrowed end portion t, at the same time, opens the sheath flow segments 666, and injects the high pressure buffer u into the focus segment _ via the sheath flow segments 666 and forces the magnetic beads 1 〇〇 to gradually concentrate on the focus. The middle portion of the segment 664 is sequentially arranged into the narrow detection segment 665 one by one. At this time, the detecting device 2 starts to perform optical detection by emitting a laser that emits a fluorescent light by exciting the detecting antibody, and the detecting device 2s closes the second sorting segment after receiving the fluorescent signal. And the first sorting section 667 and the detecting section 665 are connected to each other, so that the detected magnetic beads-containing liquid 10 is collected into the first liquid collecting holes 64, 74 to achieve separation, purification and concentration. 14 200912310 The actual target 蚪, the flow layer 6 and the pump layer 7 of the injection holes 6丨~63, = and the collection holes 64~65, 74~75 number and setting position can be helped according to the need The number of these pump chambers 792~795 of the Puzhou 79 can also be adjusted in order, and the 'micro-channel 66 can also only set the first-sorting section; and the corresponding sorting holes 781 and sorting are not set accordingly. The gas chambers 786, 787 / valve mechanism 78 are not necessary to provide the fourth valve chamber 785 - X protection 4 layer 52 is not necessary ' and the electromagnetic coil 51 can be covered and fixed on the bottom surface of the substrate ^ 4 Similarly, the magnetization of the magnetic beads can be generated by energization. In addition, when the detecting device 2 has a magnetic force capable of generating an adsorbing magnetic bead, the electromagnetic coil 51 can be omitted, but in practice, none of the above is performed. Type is limited. Furthermore, in practice, it is also possible to increase the number of injection holes and collections of the biomedical microfluidic wafer 3, and to form a magnetic reaction with different specific immunological reactions in a manner that makes it difficult to bond the magnetic beads of the antibody. After the magnetic beads are used to grasp different diseases, the different antibodies (four) are respectively used to carry out the different pathogens. #+ County is not the last, and then the valve membrane mechanism 78 and the pump machine 79 are designed to operate separately. The detection of different fluorescent magnetic beads can be carried out by differently filtering the magnetic beads into different liquid collecting holes, but the implementation is not limited thereto. As shown in FIG. 6 to FIG. 8 , the second preferred embodiment of the biomedical microfluidic wafer of the present invention can be distinguished from the first embodiment in that the biomedical microfluidic W 3 is not provided with the electromagnetic coil 51, and The overall structure is also different _: The following is only for the difference of the first embodiment of the present embodiment. 15 200912310 In the present embodiment, the biomedical microfluidic wafer 3 includes a substrate layer 4 sequentially stacked from bottom to top. , an elastic extrusion layer 8, and a first-class layer 6. The squeezing layer 8 is made of elastic flaky dimethyl methoxy oxane (PDMS) which can be pushed and elastically deformed. In the present embodiment, the flow channel layer 6 is made of thicker dimethyl methoxy oxane (PDMS) and has a left and right spaced distribution at one of its front end portions, a second and a third liquid injection hole. 62 to 63, distributed at right and left at one of the rear end portions of the first and second liquid collecting holes 64 to 65, a waste liquid hole 69 located on the right side of the middle portion thereof, and two spaced apart in the middle portion thereof The sheath flow hole 67 and a micro flow path 66 extending forward and backward and communicating with the liquid injection holes 61 to 63, the liquid collection holes 64 to 65, and the waste liquid holes 69 and the flow holes 67. The microchannel 66 is recessed on the bottom surface of the flow channel layer 6 and has a second confluence section 661 and a third confluence section 662 extending in the right and left direction, and is connected to the opposite ends of the confluence sections 661 and 662. A circular mixing section 663 of the top surface of the flow channel layer 6 , a focusing section 664 extending from the mixing section 663 and narrowing the left and right widths of the rear end portion, and a detecting section i 665 extending backward from the rear end of the focusing section 664 And a second turbulent section 666 extending backward and backward oppositely to the left and right sides of the rear end portion of the focusing section 664, and a first sorting section 667 extending backward from the rear end of the detecting section 665 a second sorting section 668, wherein the second liquid injection hole 62 is in communication with the left end of the second confluence section 661, and the third liquid injection hole 63 is in communication with the right end of the third confluence section 662, and the liquid collection holes 64, 65 are They are respectively connected to the rear ends of the sorting sections 667 and 668, and the sheath flow holes 67 are respectively connected to the front ends of the turbulent sections 666. 16 200912310 The substrate layer 4 includes a pump mechanism 400 and a valve mechanism 4〇1. The pumping mechanism 400 has a first pumping chamber 41, a second pumping chamber 42 and a third gang which are respectively recessed on the top surface thereof and respectively cooperate with the squeezing layer 8 to define a closed space. The pump chamber 43, the second and fourth pump chambers 44, and a plurality of pump air holes 40 respectively penetrating the top and bottom surfaces thereof and communicating with the pump chambers 41 to 44, respectively. The 4 Fanpu air chambers 41~44 can be separately filled
迫使其正上方所涵蓋之擠推層8部位往上彈性變形而擠入 微机道66中，其中，弟一幫浦氣室41是對應位於混合段 663下方，該等第二幫浦氣室42是分別對應位於第二與第 三匯流段661、662下方，第三幫浦氣室43是位於聚焦段 664前端部下方’該等第四幫浦氣室44是分關應位於第 -與第二分選段667、668下方。第一幫浦氣室Μ具有二 前後間隔且對應位於混合段663下方之半圓形氣室部川， 及連通於該等氣室部411間且較内徑窄小之連通部化， ::、第三與第四幫浦氣室42〜44則分別具有四個相間隔 刀U/f對應之微流道66區段延伸方向間 = h41’及三分別連通於該等氣室部421〜441間且= 車父乍小之連通部422〜442，該箄瞽、者# π j 等幫°亥等幫浦風孔4〇則是分別與該 幫浦軋至41〜44之最外侧氣室部4ιι〜441連通。 該閥門機構401可被驅動而迫使 而封M h 更擠推層局部彈性變形 封閉“道之預定區段’且具有一第 第二閥η氣室46、一第三間門氣室47 5 - ’及多數分別書空甘λ s 弟四閥門氣室48 貫穿頁底且分別與該等閥門氣室45〜48 17 200912310 連通人之閥H氣孔49。第氣室45是對應位於聚焦段 "於其窄縮端部與該廢液段669間之部位下方、該第二 閥=室46是對應位於廢液段_下方，該第三與第四間 門氣室47、48是對應位於該等分選段667、66 測段665連通處下方。 ' 本實施例之生醫微流體晶片3同樣可用以搭配接種有 鍵。抗體之磁珠進行生物分子檢測旦因本實施例生醫微 流體晶片3上並未設置電磁線圈，所以需搭配—可產生吸 引磁珠之磁力的檢測裝置（圖未示）一起使用。 該生醫微流體晶》3使料，需先將該生醫微流體晶 片3組裝於該檢測裝置中，且同樣需將該等氣孔4〇、49分 別與二壓機（圖未不）組接。並先將含有可被激發產生螢 光之偵測抗體（圖未示）的溶液注入第三注液孔63中將 緩衝液注入第二注液孔62與該等鞘流孔67中，再將含有 已接種鍵結抗體之磁珠與病源菌之混合液直接注入混合段 663 中。 然後’便可啟動該檢測裝置，針對第一幫浦氣室41間 歇地省注鬲壓流體，使高壓流體自前側氣室部4 η經由窄小 之連通部412流至後側氣室部411，藉由該等氣室部4丨〗被 注滿尚壓流體之時間差，與泄除高壓流體之時間差，來與 擠推層8相配合產生嫣動式幫浦作用，迫使擠推層8位於 §亥專氣室部411上方之局部部位，間歇地往上突擠入混合段 663中，促使混合段663中之溶液在其前半區與後半區間往 復流動’使病源菌可充分與磁珠上之鍵結抗體產生鍵結。 18 200912310 如圖8~11所示，混合一段時間後，該檢測裝置會產生 吸附磁珠之磁力，將磁珠往下吸附靠抵於混合段663内 擠推層8頂面，然後’便可洩除第二閥門氣室46的高壓： 體’使廢液孔69與混合段663連通，接著，再間歇地對= 第三幫浦氣室43與第二匯流段661上方之第二幫浦氣室Λ 灌注高壓流體，藉由該等氣室部421被填滿高屋流體之時2 間差：使該等氣室部421迫使擠推層8產生罐動幫浦作用 ，將第二注液孔62内之緩衝液注入混合段063中’將多餘 病源菌與雜質沖洗掉，並將沖洗後之廢液導引至廢液孔69 内集中’待清洗—敢時間後，停止第二幫浦氣室42之續 動幫浦作用，且再次驅使第二閥門氣室46作動而封住 段669 。 狀 接著’檢測裝置會解除吸引磁珠之磁力，然後便可驅 使位於第三匯流段662下方之第二幫浦氣室“與擠推層8 :位產生螺動幫浦作用，將含有㈣抗體之溶液打入混合 段663巾，同時驅動第一幫浦氣室41產生螺動幫浦作用， 使伯測抗體可充分與磁珠上之病源菌鍵結，待屍合一段時 間後，重複上料洗方式，❹餘❹m 中至廢液孔69中。 貝心无票 待完成病源菌與㈣抗體之接種後，便可 、 第三與第四閥門氣室45、47、 你 ...壓抓體，使聚焦段 與該等分選段667、_導通，㈣驅使該等第四幫浦 軋室44與相對應擠推層 。生蝶動幫浦作用，持續將 " 7中之緩衝液自聚焦段咖的窄縮端部左右側 19 200912310 注入中。於此同時’檢測裝置會料磁力作用，並驅使第 三幫浦氣室43與相對應擠推層8部位產生螺動幫浦作用， 持續將混合段663中之磁珠溶液沿聚焦段咖推移流動， 並會被朝流段666的緩衝液壓縮集中，而單顆排列地依序 進入檢職665中，並經檢測裝置激發檢測偵測抗體之發 光訊號後，該檢測裝置會依訊後號類型，驅使第三或第四 閥門氣室47、48作動而分別封閉第一或第二分選段μ?、 668 ’使通過檢測段665之磁珠可被導引至預定之第一或第 二集液孔64、65中，以便進行後續分析鍵結於磁珠1〇2上 之病源菌類型。歸納上述’透過上述生醫微流體晶Μ 3之 結構設計，使該生醫微流體晶片3適用於應用在光學檢測 裝置中，並可搭配接種有鍵結抗體之磁珠與進行標定之偵 測抗體，來快速抓住待測檢體中之病源菌等生物分子，並The portion of the squeezing layer 8 covered by the upper portion thereof is forced to be elastically deformed upwardly and squeezed into the micro-machine path 66, wherein a pumping chamber 41 is correspondingly located below the mixing section 663, and the second pumping chamber 42 Correspondingly located below the second and third confluence sections 661, 662, respectively, the third pumping chamber 43 is located below the front end of the focusing section 664. The fourth pumping chamber 44 is located at the first and the third The second is divided into sections 667 and 668 below. The first pump chamber has two semi-circular air chambers spaced apart from each other and corresponding to the semi-circular air chamber portion below the mixing portion 663, and a communication portion between the air chamber portions 411 and having a narrow inner diameter, :: The third and fourth pump chambers 42 to 44 respectively have four phase spacing knives U/f corresponding to the micro flow passages 66. The section extending direction = h41' and three are respectively connected to the plenum portions 421~ 441 and = car father 乍 small communication part 422 ~ 442, the 箄瞽, the # π j, etc. ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ The chambers are connected to each other at 4 ι to 441. The valve mechanism 401 can be driven to force the seal Mh to be more elastically deformed to partially close the "predetermined section of the track" and has a second valve η plenum 46 and a third dam chamber 47 5 - 'And the majority of the book is empty λ s brother four valve plenum 48 through the bottom of the page and respectively with the valve chamber 45~48 17 200912310 connected to the valve H vent 49. The plenum 45 is corresponding to the focus segment " Below the portion between the narrow end portion and the waste liquid portion 669, the second valve=chamber 46 is correspondingly located below the waste liquid section, and the third and fourth door air chambers 47, 48 are correspondingly located The sub-segment 667, 66 is below the junction of the measuring section 665. The biomedical microfluidic wafer 3 of the present embodiment can also be used to match the inoculated key. The magnetic beads of the antibody are used for biomolecule detection. There is no electromagnetic coil on the 3, so it needs to be used together with a detection device (not shown) that can generate magnetic force to attract the magnetic beads. The biomedical microfluidic crystal 3 requires the biomedical microfluidic chip to be used first. 3 is assembled in the detecting device, and the same holes 4〇, 49 are also required respectively The second pressure injection hole 63 is injected into the third liquid injection hole 63 to inject the buffer into the second liquid injection hole, and the solution containing the detection antibody (not shown) which can be excited to generate fluorescence is first injected into the second injection hole. 62 and the sheath holes 67, the mixture of the magnetic beads containing the inoculated antibody and the pathogenic bacteria is directly injected into the mixing section 663. Then, the detection device can be activated for the first pump chamber. 41 intermittently injecting the rolling fluid, so that the high-pressure fluid flows from the front side air chamber portion 4n through the narrow communication portion 412 to the rear side air chamber portion 411, and the gas chamber portion is filled with the pressure. The time difference between the fluid and the time difference between the high pressure fluid and the squeezing layer 8 are combined to produce a turbulent pumping action, forcing the squeezing layer 8 to be located at a local portion above the 412 chamber, intermittently upward. Suddenly squeezing into the mixing section 663 causes the solution in the mixing section 663 to reciprocate in the first half and the second half of the section, so that the pathogenic bacteria can fully bond with the bound antibody on the magnetic beads. 18 200912310 As shown in Figures 8-11 It is shown that after mixing for a period of time, the detecting device generates a magnetic force for adsorbing magnetic beads. The magnetic beads are sucked down against the top surface of the squeezing layer 8 in the mixing section 663, and then 'the high pressure of the second valve plenum 46 can be vented: the body' connects the waste liquid hole 69 with the mixing section 663, and then And intermittently injecting the high pressure fluid to the second pump chamber 43 above the second pump chamber 43 and the second bus portion 661, and the difference between the two chambers 421 is filled with the high chamber fluid : causing the plenum portions 421 to force the squeezing layer 8 to generate a canister action, injecting the buffer in the second liquid injection hole 62 into the mixing section 063 to 'wash out excess pathogenic bacteria and impurities, and after rinsing The waste liquid is guided to the waste liquid hole 69 to concentrate 'to be cleaned|after dare time, the second pump chamber 42 is stopped, and the second valve chamber 46 is driven again to seal the segment 669. . Then, the detecting device will release the magnetic force of the attracting magnetic beads, and then the second pumping chamber located below the third confluent section 662 can be driven to generate a screwing action with the pushing layer 8 to contain the (four) antibody. The solution is driven into the mixing section 663 towel, and at the same time, the first pumping chamber 41 is driven to generate a screwing function, so that the test antibody can be fully bonded to the pathogenic bacteria on the magnetic beads, and after repeated for a period of time, repeat The method of washing the material, the remaining ❹ m to the waste liquid hole 69. The heart of the heart is not completed after the inoculation of the pathogenic bacteria and (4) antibodies, the third and fourth valve chambers 45, 47, you... Grasping the body, causing the focusing segment to be connected to the sorting segments 667, _, and (4) driving the fourth pumping chamber 44 and the corresponding squeezing layer. The butterfly moving pump acts to continue the buffer of " The left and right sides of the narrowed end of the self-focusing section coffee 19 200912310 are injected. At the same time, the detecting device will magnetically act and drive the third pumping chamber 43 and the corresponding pushing layer 8 to generate a screwing action. , continuously flowing the magnetic bead solution in the mixing section 663 along the focusing section, and will The buffer of the flow segment 666 is compressed and concentrated, and the single array sequentially enters the inspection 665, and after detecting the illuminating signal of the detection antibody by the detecting device, the detecting device drives the third type according to the type of the post-signal. Or the fourth valve chambers 47, 48 are actuated to respectively close the first or second sorting sections μ?, 668' so that the magnetic beads passing through the detecting section 665 can be guided to the predetermined first or second collecting holes 64, 65, in order to carry out subsequent analysis of the pathogenic bacteria type bonded to the magnetic beads 1〇2. The above-mentioned structural design through the above-mentioned biomedical microfluidic crystal 3 is made, so that the biomedical microfluidic wafer 3 is suitable for application in optics. In the detecting device, the magnetic beads inoculated with the binding antibody and the detecting antibody for calibration can be used to quickly grasp the biological molecules such as pathogenic bacteria in the sample to be tested, and
可利用該等鞘流段666與聚焦段664結構設計，促使帶有 待測物質之磁珠可被聚集而陸續通過檢測段665，進而方便 光學檢測裝置2進行螢光光學檢測分析，而可達到分離、 純化、濃縮，且便於進行光學檢測之目的。再者，還可透 過該基板層4底面設有可被通電產生磁力之電磁線圈51設 汁，以及該閥門機構78與幫浦機構79之結構設計，使得 s亥生醫微流體晶片3可被通電驅動而自行產生吸引磁珠之 磁力’而可適用於無法產生磁力之光學檢測裝置，因此相 當方便實用。 惟以上所述者，僅為本發明之二較佳實施例而已，當 不能以此限定本發明實施之範圍，即大凡依本發明申請專 20 200912310 利fe圍及發明說明内容所作之簡簞 皆 谷所作之間早的等效變化與修飾 仍屬本發明專利涵蓋之範圍内。 【圖式簡單說明】 土圖！是本發明可快速制之生醫微流體晶片之第一較 佳實施例與—光學檢測裝置搭配使用之的立體示意圖； 圖2是該第一較佳實施例的立體分解圖； 圖3是該第—較佳實施例之基板層的局部放大俯視圖 說明一電磁線圈之外型； ίThe structure of the sheath flow segment 666 and the focusing segment 664 can be utilized to facilitate the magnetic beads with the substance to be tested to be collected and successively passed through the detecting segment 665, thereby facilitating the optical detecting device 2 to perform fluorescent optical detection and analysis. It is isolated, purified, concentrated, and convenient for optical detection. Furthermore, the bottom surface of the substrate layer 4 is provided with a solenoid 51 capable of being energized to generate a magnetic force, and the valve mechanism 78 and the pump mechanism 79 are designed so that the micro-fluid wafer 3 can be It is easy to use and can be applied to an optical detecting device that does not generate magnetic force when it is driven by electric power, and it can be applied to an optical detecting device that cannot generate magnetic force. However, the above is only the preferred embodiment of the present invention, and the scope of the present invention cannot be limited thereto, that is, the application according to the present invention is not limited to the scope of the invention. Early equivalent changes and modifications between the two are still within the scope of the invention. [Simple description of the map] Earth map! FIG. 2 is a perspective exploded view of the first preferred embodiment of the first preferred embodiment; FIG. 3 is a perspective view of the first preferred embodiment of the present invention; A partially enlarged plan view of a substrate layer of the first preferred embodiment illustrates an electromagnetic coil profile;
圖4是該第一較佳實施例之組合俯視圖； 圖5是該較佳實施例之局部俯視示意圖，說明多數磁 珠自聚焦段流至檢測段時的情形； 圖6疋本發明生醫微流體檢測晶片之第二較佳實施例 的立體分解圖； 、 疋α亥第一較佳實施例之一基板層的局部立體放大 圖8該第二較佳實施例之組合俯視圖； 圖9是該較佳實施例之局部侧視剖面示意圖，說明一 第L室之其中二氣室部被充填高壓流體時的情況； 〜圖10是類似圖9之視圖，說明第二幫浦氣室之其中三 氣至部被充填高壓流體時的情況；及 圖11是類似圖10之視圖，說明第二幫浦氣室之該等氣 至部皆被充填高壓流體時的情況。 21 200912310 【主要元件符號說明】 10 ...·· ....溶液 51 ..... ……電磁線圈 100.... 511.... 11 ..… ....缓衝液 512.... ,....區段 2....... 513.... ,....弧彎部 21 .···· ....承接座 514.... ....導電部 3....... ....生醫微流體晶片 52 ..... ....保護層 4....... —基板層 6....... ....流道層 400·..· ....幫浦機構 61 … ....第一注液孔 40 ..... —幫浦氣孔 62 ….· ....第二注液孔 41 ..... ....第一幫浦氣室 63 …·· .…第二注液孔 411.... ....氣室部 64 ····. ....第一集液孔 412.... ....連通部 65 ··._· …·第二集液孔 42 … ....第二幫浦氣室 66 ….· ....微流道 421.... ....氣室部 660.... .…第一匯流段 422.... ....連通部 661.... …·第二匯流段 43 ..... ....第=幫浦氣室 662.... ....第=匯流段 431···. ....氣室部 663.·.· ....混合段 432...· ....連通部 664.... ....聚焦段 44 .··.· ....第四幫浦氣室 665.... 441.... ....氣室部 666...· ....鞘流段 442·.·· ....連通部 667.... .…第一分選段 401·.·. ....閥門機構 668.··. …·第二分選段 45 ..... ....第一閥門氣室 669·... ....廢液段 46 ..... ....第二閥門氣室 67 ….· ....鞘流孔 47 ...... ....第二閥門氣室 68 …·· ....磁吸孔 48 ...... ....第四閥門氣室 69 …·. ....廢液孔 49 ...... ....閥門氣孔 7....... ....幫浦層 22 200912310 71 ..… ·.·.第四注液孔 784··.. ....第二閥門氣室 72 …·. ....第五注液孔 785.... •…第四閥門氣室 73 …·. ....第六注液孔 786·.·. ....第一分選氣室 74…… .…第二集液孔 787..·. ....第二分選氣室 75 …· …·第四集液孔 79 ....幫浦機構 76 …·. ....鞘流孔 791.··. ....幫浦氣孔 77 ....磁吸孔 792·... ....第一幫浦氣室 78 …·· .…閥門機構 793..·. ....第二幫浦氣室 780·.·. —閥門氣孔 794·..· ....第二幫浦氣室 781.... ....分選氣孔 795.... •…第四幫浦氣室 782.... ....第一閥門氣室 8....... ....推擠層 783·..· ....第二閥門氣室 234 is a top plan view of the first preferred embodiment; FIG. 5 is a partial top plan view of the preferred embodiment, illustrating a situation in which most of the magnetic beads flow from the focusing section to the detecting section; An exploded perspective view of a second preferred embodiment of a fluid detecting wafer; a partial enlarged view of a substrate layer of a first preferred embodiment of FIG. 1; a combined top view of the second preferred embodiment; FIG. A partial side cross-sectional view of a preferred embodiment illustrating a case where a second chamber portion of a chamber L is filled with a high pressure fluid; FIG. 10 is a view similar to FIG. 9 illustrating three of the second pump chambers The case where the gas is filled with the high pressure fluid; and Fig. 11 is a view similar to Fig. 10, illustrating the case where the gas to the second pump chamber is filled with the high pressure fluid. 21 200912310 [Explanation of main component symbols] 10 ...·· ....Solution 51 ..... ......Electromagnetic coil 100.... 511.... 11 ..... .... Buffer 512 .... ,.... Section 2....... 513.... ,....Arc bend 21 ..···.... socket 514.... ...the conductive portion 3......... biomedical microfluidic wafer 52 ..... .... protective layer 4....... - substrate layer 6... ..... runner layer 400·..·.. pump mechanism 61 ..... first injection hole 40 ..... - pump vent 62 ..... ... The second liquid injection hole 41 ..... .... the first pump gas chamber 63 ..... .... the second liquid injection hole 411 ..... gas chamber portion 64 ···· . . . first collecting liquid hole 412..... communicating portion 65 ···_· ...· second liquid collecting hole 42 .... second pumping gas chamber 66 ..... .... micro flow channel 421..... air chamber portion 660..... first confluence segment 422..... communication portion 661.... ... second Confluence section 43 ..... ....第=帮浦气室662.....第=汇汇段431···.....Air chamber section 663.·.. .. .. mixing section 432...·..communication section 664.....focus section 44.··.. .... fourth pump chamber 665.... 441.. .. .... air chamber part 666...·.. sheath flow section 442·.·....communication section 667.....first sorting section 401·..... Valve mechanism 668.··....·Second sorting section 45 ..... .... First valve chamber 669·.... Waste section 46 ..... .... The second valve plenum 67 ..... .... sheath flow hole 47 ..... second valve plenum 68 ..... .... magnetic suction hole 48 ... ....fourth valve air chamber 69 ...·. .... waste liquid hole 49 ... .... valve air hole 7....... .... pump layer 22 200912310 71 ..... ···.The fourth injection hole 784··.....the second valve plenum 72 ...·.....the fifth injection hole 785.... Air chamber 73 ..... .... sixth liquid injection hole 786 ·...... first sorting gas chamber 74 ... .... second liquid collecting hole 787..·. .... Two sorting chamber 75 ...· ...· fourth liquid collecting hole 79 .... pumping mechanism 76 ...·. .... sheath flow hole 791.··. .... pumping air hole 77 ... Magnetic suction hole 792·....First pump air chamber 78 ...··..Valve mechanism 793..·.....Second pump chamber 780·.·.—Valve vent 794·..·....Second pump chamber 781..... Sorting vents 79 5.... •...The fourth pump air chamber 782.....The first valve air chamber 8.........Pushing layer 783·..... .The second valve chamber 23