TWI477321B - Micro flow mixing apparatus and method thereof - Google Patents
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Description
一種微流體混合裝置及其方法。A microfluidic mixing device and method therefor.
微流體系統，其係於各個單元中執行各種反應，以分析或處理一生物樣品溶液，現今係以一密封碟盤作為該微流體系統，該微流體系統係使用一離心力與磁性粒子，以執行所期望的任務。A microfluidic system that performs various reactions in each unit to analyze or process a biological sample solution, nowadays a sealed disk is used as the microfluidic system, the microfluidic system uses a centrifugal force and magnetic particles to perform The desired task.
該生物樣品中具有一目標生物材質能夠與該磁性粒子的表面官能團結合，以使該目標生物材質與該生物樣品相分離，然後再將磁性粒子與該目標生物材質相分離。The biological sample has a target biomaterial capable of combining with a surface functional group of the magnetic particle to separate the target biomaterial from the biological sample, and then separating the magnetic particle from the target biomaterial.
上述之檢測方式，其係用多個磁力，以使磁性粒子與生物樣品(以下稱為檢測流體)結合，再使檢測流體與磁性粒子分離，故進行微流體檢測的裝置中需要裝設附設個磁鐵，方能提供上述之磁力，但多個磁鐵係具有相當的重量，該重量係造成該裝置於運轉時的不順適。In the above detection method, a plurality of magnetic forces are used to combine the magnetic particles with the biological sample (hereinafter referred to as a detection fluid), and the detection fluid is separated from the magnetic particles, so that the apparatus for performing the microfluid detection needs to be provided with a plurality of attached devices. The magnet can provide the above-mentioned magnetic force, but the plurality of magnets have a considerable weight, which causes the device to be unsuitable during operation.
另外，多個磁鐵係具有相當的磁力，該磁力會影響提供離心力之馬達的運轉。並且現有之磁性粒子與流體混合的方式不易使磁性粒子均勻分散於流體之中，故使得混合效率不佳。In addition, the plurality of magnets have a relatively large magnetic force that affects the operation of the motor that provides the centrifugal force. Moreover, the manner in which the existing magnetic particles are mixed with the fluid is not easy to uniformly disperse the magnetic particles in the fluid, so that the mixing efficiency is not good.
如上所述，於現有的裝置中如何減少磁鐵的數量與重量，並且使磁鐵不影響馬達或裝置的運作，以及如何使磁性粒子在流體中均勻分散，就有可以討論的空間。As described above, there is room to discuss how to reduce the number and weight of magnets in existing devices, and to make the magnets do not affect the operation of the motor or device, and how to uniformly disperse the magnetic particles in the fluid.
於一實施例，本揭露之技術手段在於提供一種微流體混合裝置，其包含有：一卡匣單元，其具有：至少一儲存槽區，其係設於該卡匣單元的一面，該儲存槽區具有複數個儲存槽與複數個微針活動室，各微針活動室係位於該卡匣單元的另一面，各微針活動室與各儲存槽之間具有一微針針孔，以使各微針活動室與各儲存槽相通；至少一定量檢測室，其係相鄰於該儲存槽區，該定量檢測室係相通該儲存槽區；以及至少一廢液收集區，其係設於該卡匣單元的邊緣，並且相通於該定量檢測室；以及一卡匣載台，其係供該卡匣單元設置。In one embodiment, the technical means of the present disclosure is to provide a microfluidic mixing device, comprising: a cassette unit having: at least one storage tank region, which is disposed on one side of the cassette unit, the storage tank The area has a plurality of storage tanks and a plurality of microneedle activity chambers, and each microneedle activity chamber is located on the other side of the cassette unit, and a microneedle pin hole is formed between each microneedle activity chamber and each storage tank, so that each The microneedle activity chamber is in communication with each storage tank; at least a certain amount of detection chamber adjacent to the storage tank area, the quantitative detection chamber is connected to the storage tank area; and at least one waste liquid collection area is disposed at the The edge of the cassette unit is connected to the quantitative detection chamber; and a cassette carrier is provided for the cassette unit.
於一實施例，本揭露係提供一種微流體混合裝置，其包含有：一卡匣單元，其具有：至少一儲存槽區，其係設於該卡匣單元的一面，該儲存槽區具有複數個儲存槽與複數個微針活動室，各微針活動室係位於該卡匣單元的另一面，各微針活動室與各儲存槽之間具有一微針針孔，以使各微針活動室與各儲存槽相通；至少一定量檢測室，其係相鄰於該儲存槽區，該定量檢測室係相通該儲存槽區，該定量檢測室中具有磁性粒子；以及至少一廢液收集區，其係設於該卡匣單元的邊緣，並且相通於該定量檢測室；以及一卡匣載台，其係供該卡匣單元設置，該卡匣載台具有至少一滑槽，該滑槽中具有一磁性體。In one embodiment, the present disclosure provides a microfluidic mixing device, comprising: a cassette unit having: at least one storage tank region disposed on one side of the cassette unit, the storage tank region having a plurality of a storage tank and a plurality of microneedle activity chambers, each microneedle activity chamber is located on the other side of the cassette unit, and a microneedle pinhole is arranged between each microneedle activity chamber and each storage tank to enable each microneedle activity The chamber is in communication with each storage tank; at least a certain amount of detection chamber adjacent to the storage tank area, the quantitative detection chamber is in communication with the storage tank area, the quantitative detection chamber has magnetic particles; and at least one waste liquid collection area Provided at an edge of the cassette unit and communicating with the quantitative detection chamber; and a cassette carrier for the cassette unit, the cassette stage having at least one chute, the chute There is a magnetic body in it.
於一實施例，本揭露係提供一種微流體混合方法，其 包含有：提供一離心力驅動一工作流體，以流入一具有磁性粒子之定量檢測室；一導磁體帶動一磁性體遠離該定量檢測室；一轉動單元以一斷續性正逆旋轉，驅動該磁性粒子與該工作流體，於該定量檢測室內混合；該導磁體帶動該磁性體接近該定量檢測室，以將該磁性粒子吸引至該定量檢測室的一側；該轉動單元提供一離心力，使該工作流體進入一廢液收集區；以及以一偵測單元偵測該定量檢測室中之該工作流體，以進行一光判讀。In one embodiment, the present disclosure provides a microfluid mixing method, The method comprises: providing a centrifugal force to drive a working fluid to flow into a quantitative detection chamber having magnetic particles; a guiding magnet driving a magnetic body away from the quantitative detection chamber; and a rotating unit rotating the magnetic body in a intermittent positive and negative direction to drive the magnetic The particles and the working fluid are mixed in the quantitative detection chamber; the magnetic conductor drives the magnetic body to approach the quantitative detection chamber to attract the magnetic particles to one side of the quantitative detection chamber; the rotating unit provides a centrifugal force to The working fluid enters a waste collection area; and the detection fluid in the quantitative detection chamber is detected by a detecting unit to perform a light interpretation.
以下係藉由特定的具體實施例說明本揭露之實施方式，所屬技術領域中具有通常知識者可由本說明書所揭示之內容，輕易地瞭解本揭露。The embodiments of the present disclosure are described below by way of specific embodiments, and those skilled in the art can easily understand the disclosure by the contents disclosed in the specification.
請配合參考圖1及圖3所示，本揭露係一種微流體混合裝置之第一實施例，其包含有一卡匣單元1與一卡匣載台2。Referring to FIG. 1 and FIG. 3 together, the present disclosure is a first embodiment of a microfluidic mixing device comprising a cassette unit 1 and a cassette carrier 2.
請配合參考圖1及圖2所示，卡匣單元1為一圓盤體，卡匣單元1具有至少一儲存槽區10、至少一定量檢測室11、一第一排氣渠道12、一第二排氣渠道13與至少一廢液收集區14。Referring to FIG. 1 and FIG. 2, the cassette unit 1 is a disc body, and the cassette unit 1 has at least one storage tank area 10, at least a certain amount of detection chambers 11, a first exhaust channel 12, and a first Two exhaust channels 13 and at least one waste collection area 14.
儲存槽區10係設於卡匣單元1的一面，於本實施例 中，該儲存槽區10的數量為至少3個或一奇數，該些儲存槽區10係以卡匣單元1的中心為一圓心，而成一等角分佈。The storage tank area 10 is disposed on one side of the cassette unit 1 in the embodiment. The number of the storage tanks 10 is at least three or an odd number, and the storage tanks 10 are formed at an equiangular distribution with the center of the cassette unit 1 as a center.
該儲存槽區10具有複數個儲存槽100與複數個微針活動室101。The storage tank area 10 has a plurality of storage tanks 100 and a plurality of microneedle activity chambers 101.
各儲存槽100為一近似水滴型的槽體，舉例而言，該儲存槽100的數量為9個，則能夠以一第一儲存槽至一第九儲存槽說明，該數量能夠隨著不同測試，而予以增減。Each of the storage tanks 100 is an approximately water droplet type tank. For example, if the number of the storage tanks 100 is nine, it can be described by a first storage tank to a ninth storage tank, and the quantity can be tested according to different tests. And increase or decrease.
各微針活動室101係設於卡匣單元1的另一面，各微針活動室101係相鄰各儲存槽100，各微針活動室101與各儲存槽100之間具有一微針針孔102，以使各微針活動室101與各儲存槽100相通，各微針活動室101係朝向卡匣單元1的邊緣處，各微針活動室101進一步具有一流道103，該些流道103係相通。Each of the microneedle movable chambers 101 is disposed on the other side of the cassette unit 1. Each of the microneedle movable chambers 101 is adjacent to each of the storage tanks 100, and each of the microneedle movable chambers 101 and each of the storage tanks 100 has a microneedle pinhole. 102, so that each microneedle movable chamber 101 communicates with each storage tank 100, each microneedle movable chamber 101 is directed toward the edge of the cassette unit 1, and each microneedle movable chamber 101 further has a first-class track 103, and the flow paths 103 The system is connected.
各定量檢測室11係相鄰於該儲存槽區10，舉例而言，定量檢測室11的數量係等同儲存槽區10，該些定量檢測室11與係以該卡匣單元1的中心為一圓心，而成一等角分佈，各定量檢測室11進一步具有一緩衝室110，緩衝室110係相通流道103。Each of the quantitative detection chambers 11 is adjacent to the storage tank area 10. For example, the number of the quantitative detection chambers 11 is equivalent to the storage tank area 10, and the quantitative detection chambers 11 are connected to the center of the cassette unit 1 The center of the circle is formed in an equiangular distribution, and each of the quantitative detection chambers 11 further has a buffer chamber 110, and the buffer chamber 110 is connected to the flow passage 103.
各定量檢測室11進一步具有一突槽111，該突槽111係相通各定量檢測室11。Each of the quantitative detection chambers 11 further has a protrusion 111 that communicates with each of the quantitative detection chambers 11.
第一排氣渠道12與第二排氣渠道13分別為一環狀渠道，第一排氣渠道12與第二排氣渠道13係分別設於卡匣單元1具有微針活動室101的一面，第一排氣渠道12與第二排氣渠道13係位於卡匣單元1的中心與微針活動室101 之間。The first exhaust channel 12 and the second exhaust channel 13 are respectively an annular channel, and the first exhaust channel 12 and the second exhaust channel 13 are respectively disposed on one side of the cassette unit 1 having the microneedle activity chamber 101. The first exhaust channel 12 and the second exhaust channel 13 are located at the center of the cassette unit 1 and the microneedle activity chamber 101 between.
第一排氣渠道12與第二排氣渠道13之間具有複數個第一氣體流道120，該些第一氣體流道120係使第一排氣渠道12與第二排氣渠道13相通，各第一氣體流道120進一步具有一排氣孔121。A plurality of first gas flow channels 120 are disposed between the first exhaust gas channel 12 and the second exhaust gas channel 13 , and the first gas flow channels 120 are configured to communicate the first exhaust gas channel 12 with the second exhaust gas channel 13 . Each of the first gas flow passages 120 further has an exhaust hole 121.
第二排氣渠道13與流道103之間具有一第二氣體流道130，第二氣體流道130係使第二排氣渠道13與流道103相通。A second gas flow path 130 is formed between the second exhaust gas channel 13 and the flow channel 103, and the second gas flow channel 130 is connected to the flow channel 103 by the second exhaust gas channel 13.
廢液收集區14係設於卡匣單元1的邊緣，並且各廢液收集區14係相鄰於各微針活動室101，舉例而言，廢液收集區14的數量係等同儲存槽區10，該些廢液收集區14係以該卡匣單元1的中心為一圓心，而成一等角分佈。The waste collection area 14 is disposed at the edge of the cassette unit 1, and each waste collection area 14 is adjacent to each of the microneedle activity chambers 101. For example, the amount of the waste collection area 14 is equivalent to the storage tank area 10. The waste collection areas 14 are formed at an equiangular distribution with the center of the cassette unit 1 as a center.
各廢液收集區14進一步具有一第一排氣室140、一第二排氣室141、複數個廢液收集室142。Each waste liquid collection area 14 further has a first exhaust chamber 140, a second exhaust chamber 141, and a plurality of waste liquid collection chambers 142.
第一排氣室140係相鄰於定量檢測室11，並且第一排氣室140與定量檢測室11之間具有一導引槽143，導引槽143係使第一排氣室140與定量檢測室11相通，導引槽143為一具毛細作用之U型槽。The first exhaust chamber 140 is adjacent to the quantitative detection chamber 11, and a guiding groove 143 is defined between the first exhaust chamber 140 and the quantitative detecting chamber 11, and the guiding groove 143 is configured to make the first exhaust chamber 140 and the quantitative The detection chamber 11 is in communication, and the guiding groove 143 is a U-shaped groove with capillary action.
第二排氣室141係相鄰於第一排氣室140，第二排氣室141與第二排氣渠道13之間具有一第三氣體流道144，第三氣體流道144係使第二排氣室141與第二排氣渠道13相通。The second exhaust chamber 141 is adjacent to the first exhaust chamber 140, and the third exhaust passage 141 and the second exhaust passage 13 have a third gas flow passage 144. The third gas flow passage 144 is The second exhaust chamber 141 is in communication with the second exhaust passage 13.
廢液收集室142係相鄰於第二排氣室141、第一排氣室140與卡匣單元1的邊緣。The waste liquid collection chamber 142 is adjacent to the second exhaust chamber 141, the first exhaust chamber 140, and the edge of the cassette unit 1.
各廢液收集區14與第一排氣室140之間具有一第一排 液流道145，第一排液流道145係使廢液收集室142與第一排氣室140相通。There is a first row between each waste collection area 14 and the first exhaust chamber 140 The liquid flow path 145 and the first liquid discharge flow path 145 communicate the waste liquid collection chamber 142 with the first exhaust chamber 140.
各廢液收集室142之間具有一第二排液流道146，第二排液流道146係使各廢液收集室142相通。Each of the waste liquid collection chambers 142 has a second liquid discharge passage 146, and the second liquid discharge passage 146 communicates with each of the waste liquid collection chambers 142.
廢液收集室142與第二排氣室141之間具有至少一排氣流道147，排氣流道147係使廢液收集室142與第二排氣室141相通。There is at least one exhaust gas flow path 147 between the waste liquid collection chamber 142 and the second exhaust gas chamber 141, and the exhaust gas flow path 147 connects the waste liquid collection chamber 142 with the second exhaust gas chamber 141.
請配合參考圖3及圖4所示，卡匣載台2的一面具有一卡匣單元容槽20，卡匣單元容槽20係可供卡匣單元1設置。Referring to FIG. 3 and FIG. 4, one side of the cassette stage 2 has a cassette unit slot 20, and the cassette unit slot 20 is provided for the cassette unit 1.
卡匣載台2更具有至少一滑槽21，舉例而言，滑槽21的數量係等同定量檢測室11的數量，其外型可為弧線。The cassette stage 2 further has at least one chute 21. For example, the number of the chutes 21 is equivalent to the number of the quantitative detection chambers 11, and the shape thereof may be an arc.
各滑槽21的兩端朝向該卡匣單元容槽邊緣處延伸之方向分別具有一延伸槽210，而使各滑槽21形成一近似ㄇ型的槽，各滑槽21更具有一選擇性的視窗211，該視窗211係可設置或未設置，該視窗211係用於觀察下述之磁性體22於滑槽21中的位置，各視窗211係為一近似ㄟ型的孔，並且各視窗211的一端係延伸至其一延伸槽210中，並且該延伸槽210係相對於各定量檢測室11。Each of the two ends of each of the sliding slots 21 has an extending slot 210 in a direction extending toward the edge of the slot of the latching unit, so that each of the sliding slots 21 forms an approximately ㄇ-shaped slot, and each of the sliding slots 21 has a selective The window 211 is configurable or not. The window 211 is used to observe the position of the magnetic body 22 in the sliding slot 21, and each window 211 is an approximately ㄟ-shaped hole, and each window 211 One end extends into one of the extension slots 210, and the extension slot 210 is relative to each of the quantitative detection chambers 11.
一磁性體22係設於各滑槽21。在一實施例中，磁性體22之外型可為一扁平圓柱體；滑槽21之槽寬略大於磁性體22之直徑，藉由滑槽21之限制，以供磁性體22於滑槽21中進行平面移動。A magnetic body 22 is provided in each of the chutes 21. In one embodiment, the outer shape of the magnetic body 22 may be a flat cylinder; the groove width of the chute 21 is slightly larger than the diameter of the magnetic body 22, and is restricted by the chute 21 for the magnetic body 22 to be in the chute 21. Plane movement in the middle.
二選擇性之輔助磁性體23係設於卡匣載台2，並且分別設置於卡匣單元容槽20邊緣處與二延伸槽210之間，用 以將磁性體22磁吸於延伸槽210靠近卡匣單元容槽20邊緣處之一端。The second auxiliary magnetic body 23 is disposed on the cassette stage 2 and disposed between the edge of the cassette unit slot 20 and the two extending slots 210, respectively. The magnetic body 22 is magnetically attracted to one end of the extension groove 210 near the edge of the cassette unit slot 20.
該磁性體22與該輔助磁性體23能夠為一磁性物質或一導磁物質，如磁鐵或能夠磁性所吸引的物質。The magnetic body 22 and the auxiliary magnetic body 23 can be a magnetic substance or a magnetic conductive substance such as a magnet or a substance that can be attracted by magnetism.
當卡匣單元1設置於卡匣單元容槽20中時，滑槽21的其中一端以及對應之其中一延伸槽210相對緊鄰定量檢測室11，而滑槽21的另外一端以及對應之另外一延伸槽210相對遠離定量檢測室11。When the cassette unit 1 is disposed in the cassette unit slot 20, one end of the chute 21 and one of the corresponding extension slots 210 are relatively adjacent to the quantitative detection chamber 11, and the other end of the chute 21 and the corresponding other extension The trough 210 is relatively far from the quantitative detection chamber 11.
請配合參考圖5及圖6所示，本揭露之另一實施例之動作示意圖。Please refer to FIG. 5 and FIG. 6 for a schematic diagram of the operation of another embodiment of the present disclosure.
微流體混合裝置除包括至少一磁性體50(相當於前述之磁性體22)與設置於定量檢測室11內之磁性粒子52，更可包括至少一導磁體51與一設置於卡匣載台2外部之雙軸移動平台(圖中未示)，雙軸移動平台帶動導磁體51進行二維移動，進而以磁性吸引磁性體50於滑槽21中進行平面移動以進入或離開延伸槽210。雙軸移動平台例如可由氣壓缸或馬達等所組成。The microfluidic mixing device includes at least one magnetic body 50 (corresponding to the magnetic body 22 described above) and the magnetic particles 52 disposed in the quantitative detection chamber 11 , and may further include at least one magnetic conductive body 51 and one disposed on the cassette loading table 2 . An external biaxial moving platform (not shown) drives the magnetizer 51 to move in two dimensions, thereby magnetically attracting the magnetic body 50 to move in the slot 21 to enter or leave the extending slot 210. The biaxial moving platform may be composed of, for example, a pneumatic cylinder or a motor or the like.
於一實施例中，磁性體50為磁性物質，例如為磁鐵；導磁體51為導磁物質，例如為磁鐵、可導磁的金屬、電磁鐵等能夠被磁性所吸引的物質。In one embodiment, the magnetic body 50 is a magnetic substance, for example, a magnet, and the magnetic conductive body 51 is a magnetic conductive substance, and is, for example, a magnet, a magnetically permeable metal, or an electromagnet that can be attracted by magnetic properties.
至少一磁性體50(相當於前述之磁性體22)係可移動地設於卡匣載台的一側。At least one magnetic body 50 (corresponding to the magnetic body 22 described above) is movably provided on one side of the cassette stage.
當雙軸移動平台帶動導磁體51往底端(接近卡匣載台垂直方向)移動時，磁性體50受到導磁體51之磁性所吸引。When the biaxial moving platform drives the magnet 51 to move toward the bottom end (near the vertical direction of the cassette stage), the magnetic body 50 is attracted by the magnetism of the magnet 51.
如圖5所示，當磁性體50移動至卡匣載台的一側時， 受到磁性體50之磁性所吸引的磁性粒子52係朝向磁性體50方向聚集。As shown in FIG. 5, when the magnetic body 50 is moved to one side of the cassette stage, The magnetic particles 52 attracted by the magnetic properties of the magnetic body 50 are gathered toward the magnetic body 50.
導磁體51係可藉由雙軸移動平台帶動以移動地設於卡匣載台的一端，該端能夠為一頂端(遠離卡匣載台垂直方向)或一底端(接近卡匣載台垂直方向)。The magnet 51 can be movably disposed at one end of the cassette stage by a biaxial moving platform, and the end can be a top end (away from the vertical direction of the cassette stage) or a bottom end (close to the cassette stage vertical) direction).
如圖6所示，當雙軸移動平台帶動導磁體51朝向遠離卡匣載台水平方向移動時，受到導磁體51之磁性所吸引的磁性體50係朝向遠離卡匣載台方向平面移動。As shown in FIG. 6, when the biaxial moving platform drives the magnetizer 51 to move away from the cassette stage in the horizontal direction, the magnetic body 50 attracted by the magnetism of the magnetizer 51 moves toward the plane away from the cassette stage.
如圖6所示，若雙軸移動平台帶動導磁體51朝向接近卡匣載台水平方向移動時，受到導磁體51之磁性所吸引的磁性體50係朝向卡匣載台方向平面移動。As shown in FIG. 6, when the biaxial moving platform drives the magnetizer 51 to move in the horizontal direction toward the cassette stage, the magnetic body 50 attracted by the magnetism of the magnet 51 is moved toward the plane of the cassette stage.
請配合參考圖7所示，本揭露係一種微流體混合方法，其具有：Please refer to FIG. 7 , which is a microfluid mixing method, which has:
步驟S1，舉例而言，如圖1及圖2所示，各儲存槽區10具有第一至第八儲存槽100，各儲存槽100依序儲存有以一密封膜封存之工作液體，該工作液體能夠為磁性粒子稀釋液、測試液體(如稀釋血液)、清洗液、偵測抗體稀釋液與色液。Step S1, for example, as shown in FIG. 1 and FIG. 2, each storage tank area 10 has first to eighth storage tanks 100, and each storage tank 100 sequentially stores a working liquid sealed by a sealing film. The liquid can be a magnetic particle diluent, a test liquid (such as diluted blood), a cleaning solution, a detection antibody dilution and a color liquid.
如圖1所示，若干磁性粒子設置於至少一定量檢測室11中，或者若干磁性粒子能夠於下述之混合過程前加入定量檢測室11中。As shown in FIG. 1, a plurality of magnetic particles are disposed in at least a certain amount of the detection chamber 11, or a plurality of magnetic particles can be added to the quantitative detection chamber 11 before the mixing process described below.
一刺膜單元係透過微針針孔102，以刺破位於第一儲存槽100之密封膜，而使工作流體得以流出，舉例而言，該工作流體為磁性粒子稀釋液。A lancet unit passes through the microneedle pinhole 102 to pierce the sealing film located in the first storage tank 100 to allow the working fluid to flow out. For example, the working fluid is a magnetic particle diluent.
在此步驟中，磁性粒子52受到磁性體50之磁性所吸 引而聚集。如圖5所示，於一實施例中，當磁性體50(相當於前述之磁性體22)位於卡匣載台的一側時，受到磁性體50之磁性所吸引的磁性粒子52係朝向磁性體50方向聚集，並吸引至定量檢測室11的一側，例如是突槽111中。於一實施例中，磁性體50留滯於相對緊鄰定量檢測室11之延伸槽210中，並受到輔助磁性體23之磁吸。In this step, the magnetic particles 52 are attracted by the magnetic properties of the magnetic body 50. Lead to gather. As shown in FIG. 5, in the embodiment, when the magnetic body 50 (corresponding to the magnetic body 22 described above) is located on one side of the cassette stage, the magnetic particles 52 attracted by the magnetic properties of the magnetic body 50 are oriented toward the magnetic body. The body 50 is gathered in the direction and attracted to one side of the quantitative detecting chamber 11, for example, in the protruding groove 111. In one embodiment, the magnetic body 50 is retained in the extending groove 210 of the quantitative detection chamber 11 and is magnetically attracted by the auxiliary magnetic body 23.
於一實施例中，延伸槽210自滑槽21朝向該卡匣單元容槽邊緣處延伸之深度約等於或大於磁性體22(亦即磁性體50)之直徑的1/2，如無上述之輔助磁性體23，則延伸槽210的深度亦可將磁性體22停留於該處。In an embodiment, the extending slot 210 extends from the sliding slot 21 toward the edge of the latching unit slot to a depth equal to or greater than 1/2 of the diameter of the magnetic body 22 (ie, the magnetic body 50). The auxiliary magnetic body 23, the depth of the extending groove 210 can also stay the magnetic body 22 there.
步驟S2，轉動單元提供一離心力驅動工作流體，以流入一具有磁性粒子之定量檢測室。In step S2, the rotating unit provides a centrifugal force to drive the working fluid to flow into a quantitative detection chamber having magnetic particles.
於一實施例中，轉動單元例如可為旋轉馬達，耦接於卡匣載台2，係藉由旋轉以提供一離心力驅動該工作流體，而使該工作流體流入定量檢測室，該轉動單元的轉速為1000至2500rpm，旋轉圈數為90至3000圈，時間為2至3000秒，較佳為轉速為2000rpm，旋轉圈數為100圈，時間為3秒，該工作流體的體積為61~65μl，較佳為63μl。In one embodiment, the rotating unit is, for example, a rotary motor coupled to the cassette carrier 2, and is driven to rotate to provide a centrifugal force to drive the working fluid, and the working fluid flows into the quantitative detection chamber. The rotational speed is 1000 to 2500 rpm, the number of revolutions is 90 to 3000 turns, the time is 2 to 3000 seconds, preferably the rotational speed is 2000 rpm, the number of revolutions is 100 turns, the time is 3 seconds, and the volume of the working fluid is 61-65 μl. Preferably, it is 63 μl.
如圖2所示，該磁性粒子稀釋液係經過流道103，以及緩衝室110的緩衝，而流入定量檢測室11中，以與該些磁性粒子混合，因導引槽143具有毛細作用，故部份之磁性粒子稀釋液會被吸入導引槽143中。As shown in FIG. 2, the magnetic particle dilution liquid is buffered by the flow path 103 and the buffer chamber 110, and flows into the quantitative detection chamber 11 to be mixed with the magnetic particles. Since the guide groove 143 has capillary action, the guide groove 143 has capillary action. A portion of the magnetic particle dilution is drawn into the guide groove 143.
在此步驟中，磁性粒子52仍受到磁性體50之磁性所吸引而聚集。In this step, the magnetic particles 52 are still attracted by the magnetic properties of the magnetic body 50 to aggregate.
步驟S3，導磁體51帶動磁性體50遠離定量檢測室11。In step S3, the magnetizer 51 drives the magnetic body 50 away from the quantitative detection chamber 11.
於一實施例中，如圖7所示，雙軸移動平台帶動導磁體51往底端(接近卡匣載台垂直方向)移動並朝向遠離卡匣載台水平方向移動時，受到導磁體51之磁性所吸引的磁性體50(亦即磁性體22)係朝向遠離卡匣載台方向平面移動，此時定量檢測室11內之磁性粒子52因來自於磁性體50之磁力被移除或減弱而無法保持聚集的狀態。於一實施例中，磁性體50受到導磁體51之吸引並克服輔助磁性體23之磁吸，而離開相對緊鄰定量檢測室11之延伸槽210，並進入滑槽21中。In one embodiment, as shown in FIG. 7, the biaxial moving platform drives the magnet 51 to move toward the bottom end (near the vertical direction of the cassette stage) and move toward the horizontal direction away from the cassette stage, and is guided by the magnet 51. The magnetic body 50 (i.e., the magnetic body 22) attracted by the magnetic body moves toward the plane away from the cassette stage, and at this time, the magnetic particles 52 in the quantitative detection chamber 11 are removed or weakened by the magnetic force from the magnetic body 50. Unable to maintain the state of aggregation. In one embodiment, the magnetic body 50 is attracted by the magnetizer 51 and overcomes the magnetic attraction of the auxiliary magnetic body 23, and is separated from the extending groove 210 of the quantitative detection chamber 11 and enters the chute 21.
步驟S4，轉動單元以一斷續性正逆旋轉，驅動磁性粒子52與工作流體，於定量檢測室內混合。In step S4, the rotating unit rotates in a discontinuous forward and reverse direction to drive the magnetic particles 52 and the working fluid to be mixed in the quantitative detection chamber.
於一實施例中，轉動單元以一斷續性正逆旋轉，驅動磁性粒子稀釋液與磁性粒子混合時，藉由導磁體51於水平方向之移動，以帶動磁性體50由滑槽21進入並留滯於相對遠離定量檢測室11之延伸槽210中，並受到輔助磁性體23之磁吸。此時定量檢測室11內之磁性粒子52因來自於磁性體50之磁力被移除或更為減弱，而使該些磁性粒子係能夠與磁性粒子稀釋液充分混合均勻。In one embodiment, the rotating unit rotates in a intermittent positive and negative direction to drive the magnetic particle dilution liquid to mix with the magnetic particles, and the magnetic body 50 moves in the horizontal direction to drive the magnetic body 50 into the sliding groove 21 and It is retained in the extending groove 210 relatively far from the quantitative detecting chamber 11, and is attracted by the auxiliary magnetic body 23. At this time, the magnetic particles 52 in the quantitative detection chamber 11 are removed or weakened by the magnetic force from the magnetic body 50, so that the magnetic particles can be sufficiently mixed with the magnetic particle diluent.
步驟S5，導磁體51帶動磁性體50接近定量檢測室11，以將磁性粒子52吸引至該定量檢測室11的一側。於一實施例中，如圖6所示，雙軸移動平台帶動導磁體51朝向接近卡匣載台方向水平移動時，受到導磁體51之磁性所吸引的磁性體50係朝向卡匣載台方向平面移動。In step S5, the magnetizer 51 drives the magnetic body 50 close to the quantitative detection chamber 11 to attract the magnetic particles 52 to one side of the quantitative detection chamber 11. In one embodiment, as shown in FIG. 6, when the biaxial moving platform drives the magnetizer 51 to move horizontally toward the cassette stage, the magnetic body 50 attracted by the magnetism of the magnet 51 is oriented toward the cassette stage. Plane movement.
如圖5所示，當磁性體50移動至接近卡匣載台的一側時，受到磁性體50之磁性所吸引的磁性粒子52係朝向磁性體50方向聚集，並至下述之S6或S7。As shown in FIG. 5, when the magnetic body 50 is moved to the side close to the cassette stage, the magnetic particles 52 attracted by the magnetic properties of the magnetic body 50 are gathered toward the magnetic body 50, and to the following S6 or S7. .
於一實施例中，如圖4所示，磁性粒子52係被磁性體50吸引至定量檢測室11的一側，如突槽111中，若該卡匣載台2具有輔助磁性體23，磁性體50(亦即磁性體22)係受到輔助磁性體23的吸引，而留滯於相鄰於定量檢測室11的位置。In one embodiment, as shown in FIG. 4, the magnetic particles 52 are attracted to the side of the quantitative detection chamber 11 by the magnetic body 50, such as in the protrusion 111, and if the cassette stage 2 has the auxiliary magnetic body 23, the magnetic The body 50 (i.e., the magnetic body 22) is attracted by the auxiliary magnetic body 23 and stays at a position adjacent to the quantitative detection chamber 11.
於一實施例中，磁性體50先受到導磁體51之吸引並克服輔助磁性體23之磁吸，而離開相對遠離定量檢測室11之延伸槽210，並進入滑槽21中。而後繼續藉由導磁體51於水平方向之移動，以帶動磁性體50由滑槽21進入並留滯於相對緊鄰定量檢測室11之延伸槽210中。In one embodiment, the magnetic body 50 is first attracted by the magnetizer 51 and overcomes the magnetic attraction of the auxiliary magnetic body 23, and leaves the extending groove 210 relatively far from the quantitative detecting chamber 11 and enters the chute 21. Then, the movement of the magnet 51 in the horizontal direction is continued to drive the magnetic body 50 into the slot 21 and stay in the extending slot 210 of the quantitative detection chamber 11 .
步驟S6，轉動單元提供一離心力，使工作流體進入一廢液收集區。In step S6, the rotating unit provides a centrifugal force to cause the working fluid to enter a waste collection area.
於一實施例中，如圖2所示，等待一時間，該等待時間為30秒，轉動單元再藉由旋轉以提供一離心力，而將磁性粒子稀釋液排入廢液收集區14，並重複上述之S1至S5，該轉動單元的轉速為1800至6000rpm，旋轉圈數為90至3000圈，時間為25至35秒，較佳為轉速為2000pm，旋轉圈數為100圈，時間為30秒。In one embodiment, as shown in FIG. 2, waiting for a time, the waiting time is 30 seconds, and the rotating unit further rotates to provide a centrifugal force, and the magnetic particle dilution liquid is discharged into the waste liquid collection area 14 and repeated. In the above S1 to S5, the rotating unit has a rotational speed of 1800 to 6000 rpm, a number of revolutions of 90 to 3000 turns, a time of 25 to 35 seconds, preferably a rotational speed of 2000 pm, a number of revolutions of 100 turns, and a time of 30 seconds. .
上述之S5與S6可如上述之說明依序進行，或者S6可以先進行，再進行S5，或者S5與S6能夠同時進行。The above S5 and S6 may be sequentially performed as described above, or S6 may be performed first, then S5 may be performed, or S5 and S6 may be simultaneously performed.
承上所述，於一實施例中，如圖2所示，刺膜單元係刺破位於第二槽100之密封膜，並且轉動單元係提供一離 心力，以使另一工作流體得以流入定量檢測室11中，並與磁性粒子充分混合，該混合方式與各實施例中之排氣方式與磁性體的移動方式係可見於上述之S1至S5中，故不再贅述。As described above, in an embodiment, as shown in FIG. 2, the lancet unit pierces the sealing film located in the second groove 100, and the rotating unit provides a separation. The force is applied to allow another working fluid to flow into the quantitative detection chamber 11 and be thoroughly mixed with the magnetic particles. The mixing mode and the manner of moving the exhaust gas and the magnetic body in each embodiment can be found in the above S1 to S5. Therefore, it will not be repeated.
承上所述，舉例而言，該轉動單元的轉速為2000rpm，旋轉圈數為100圈，時間為3秒，該工作流體能夠為一測試液體，如稀釋血液，該工作流體的體積為60~64μl，較佳為62μl。As described above, for example, the rotational speed of the rotating unit is 2000 rpm, the number of revolutions is 100 turns, and the time is 3 seconds. The working fluid can be a test liquid, such as diluted blood, and the working fluid has a volume of 60~ 64 μl, preferably 62 μl.
轉動單元係再提供一離心力，以使該工作流體流入廢液收集區中；再回到S1，並重複S1至S6的步驟，且依序刺破第三儲存槽至第七儲存槽，而使各槽的工作流體能夠流入定量檢測室中，並與磁性粒子混合後，再排出定量檢測室，第三儲存槽、第四儲存槽、第六儲存槽與第七儲存槽的工作流體為一清洗液，該清洗液係用於清洗磁性粒子與該定量檢測室，第五儲存槽的工作流體為偵測抗體稀釋液。The rotating unit further provides a centrifugal force to flow the working fluid into the waste collection area; return to S1, and repeat the steps S1 to S6, and sequentially pierce the third storage tank to the seventh storage tank, thereby The working fluid of each tank can flow into the quantitative detection chamber, mix with the magnetic particles, and then discharge the quantitative detection chamber, and the working fluids of the third storage tank, the fourth storage tank, the sixth storage tank and the seventh storage tank are cleaned. The cleaning liquid is used for cleaning magnetic particles and the quantitative detection chamber, and the working fluid of the fifth storage tank is a detection antibody dilution liquid.
於一實施例中，當磁性粒子稀釋液排入廢液收集區14時，磁性粒子稀釋液係先進入第一排氣室140，再由第一排液流道145、第二排液流道146流入各廢液收集室142，各廢液收集室142的空氣係經由排氣流道147流入第二排氣室141。In one embodiment, when the magnetic particle dilution liquid is discharged into the waste liquid collection area 14, the magnetic particle dilution liquid first enters the first exhaust chamber 140, and then the first liquid discharge flow path 145 and the second liquid discharge flow path. 146 flows into each of the waste liquid collection chambers 142, and the air in each of the waste liquid collection chambers 142 flows into the second exhaust chamber 141 via the exhaust gas flow path 147.
位於第二排氣室141的空氣係由第三氣體流道144流至第二排氣渠道13、第一氣體流道120與第一排氣渠道12，並由排氣孔121排出至外部。The air located in the second exhaust chamber 141 flows from the third gas flow path 144 to the second exhaust gas flow path 13, the first gas flow path 120 and the first exhaust gas flow path 12, and is discharged to the outside by the exhaust gas holes 121.
如圖4所示，於一實施例中，於工作液體排入廢液收 集區14時，磁性體22係位於相鄰於定量檢測室31之延伸槽210中；若無延伸槽210，則磁性體22係移動至相鄰於定量檢測室31。As shown in FIG. 4, in an embodiment, the waste liquid is discharged into the working liquid. In the collecting zone 14, the magnetic body 22 is located in the extending groove 210 adjacent to the quantitative detecting chamber 31; if there is no extending groove 210, the magnetic body 22 is moved adjacent to the quantitative detecting chamber 31.
步驟S7，承上述之S5，刺膜單元係刺破第八儲存槽的密封膜，並使工作流體流入定量檢測室中，而與磁性粒子充分混合，該工作流體之流入方式與混合方式係如上述之步驟所述，待混合完畢後，磁性體係將磁性粒子吸引至定量檢測室的一側，如S3所述，但於此步驟中，工作液體係未排出定量檢測室，一偵測單元係偵測定量檢測室中之工作流體，以進行一光判讀，該光判讀能夠為一吸收光判讀、一螢光判讀或一冷光判讀。Step S7, in accordance with S5 above, the lancet unit pierces the sealing film of the eighth storage tank, and flows the working fluid into the quantitative detection chamber to be sufficiently mixed with the magnetic particles, and the inflow mode and the mixing mode of the working fluid are as follows. In the above steps, after the mixing is completed, the magnetic system attracts the magnetic particles to one side of the quantitative detection chamber, as described in S3, but in this step, the working fluid system does not discharge the quantitative detection chamber, and a detection unit is The working fluid in the quantitative detection chamber is detected to perform a light interpretation, which can be an absorption light interpretation, a fluorescence interpretation or a cold light interpretation.
承上所述，本揭露係一種能夠廣泛地應用於密閉式或開放式反應空間(定量檢測室)的混合機構與方法，其係利用可移動式的磁性體，於需要磁力時方使該磁性體移動，並於分散磁性粒子時停用，並配合一轉動單元，以使反應空間產生正轉或逆轉的往復運動，於慣性與角速度作用，而使該些磁性粒子能夠均勻分散於反應空間，以提升反應效率。In view of the above, the present disclosure is a hybrid mechanism and method that can be widely applied to a closed or open reaction space (quantitative detection chamber), which utilizes a movable magnetic body to make the magnetic force when a magnetic force is required. The body moves and is deactivated when dispersing the magnetic particles, and cooperates with a rotating unit to cause the reaction space to generate a forward or reverse reciprocating motion, which acts on the inertia and the angular velocity, so that the magnetic particles can be uniformly dispersed in the reaction space. To improve the efficiency of the reaction.
另外，本揭露係於有限的磁性體的情況下，以減輕磁性體的重量與數量，並使磁性體的磁力無法影響轉動單元之運作。Further, the present disclosure is in the case of a limited magnetic body to reduce the weight and number of the magnetic body, and the magnetic force of the magnetic body cannot affect the operation of the rotating unit.
惟以上所述之具體實施例，僅係用於例釋本揭露，而非用於限定本揭露之可實施範疇，於未脫離本揭露上揭之精神與技術範疇下，任何運用本揭露所揭示內容而完成之等效改變及修飾，均仍應為下述之申請專利範圍所涵蓋。However, the specific embodiments described above are only used to illustrate the disclosure, and are not intended to limit the scope of the disclosure, and may be disclosed without departing from the spirit and scope of the disclosure. Equivalent changes and modifications to the content are still covered by the scope of the patent application below.
1‧‧‧卡匣單元1‧‧‧ cassette unit
10‧‧‧儲存槽區10‧‧‧ Storage tank area
100‧‧‧儲存槽100‧‧‧ storage tank
101‧‧‧微針活動室101‧‧‧microneedle activity room
102‧‧‧微針針孔102‧‧‧Microneedle pinhole
103‧‧‧流道103‧‧‧ flow path
11‧‧‧定量檢測室11‧‧‧Quantitative testing room
110‧‧‧緩衝室110‧‧‧ buffer room
111‧‧‧突槽111‧‧‧Slot
12‧‧‧第一排氣渠道12‧‧‧First exhaust channel
120‧‧‧第一氣體流道120‧‧‧First gas flow path
121‧‧‧排氣孔121‧‧‧ venting holes
13‧‧‧第二排氣渠道13‧‧‧Second exhaust channel
130‧‧‧第二氣體流道130‧‧‧Second gas flow path
14‧‧‧廢液收集區14‧‧‧ Waste collection area
140‧‧‧第一排氣室140‧‧‧First Exhaust Chamber
141‧‧‧第二排氣室141‧‧‧Second exhaust chamber
142‧‧‧廢液收集室142‧‧‧ Waste collection room
143‧‧‧導引槽143‧‧‧ guiding slot
144‧‧‧第三氣體流道144‧‧‧ third gas flow path
145‧‧‧第一排液流道145‧‧‧First drain channel
146‧‧‧第二排液流道146‧‧‧Second drain channel
147‧‧‧排氣流道147‧‧‧Exhaust runner
2‧‧‧卡匣載台2‧‧‧Card loading platform
20‧‧‧卡匣單元容槽20‧‧‧Card unit slot
21‧‧‧滑槽21‧‧‧Chute
210‧‧‧延伸槽210‧‧‧Stretching slot
211‧‧‧視窗211‧‧‧Window
22‧‧‧磁性體22‧‧‧ magnetic body
23‧‧‧輔助磁性體23‧‧‧Assistive magnetic body
50‧‧‧磁性體50‧‧‧ magnetic body
51‧‧‧導磁體51‧‧‧Bolt magnet
52‧‧‧磁性粒子52‧‧‧Magnetic particles
S1至S7‧‧‧步驟S1 to S7‧‧‧ steps
圖1為本揭露之一種微流體混合裝置之一卡匣單元之第一實施例之立體外觀圖。1 is a perspective view of a first embodiment of a cassette unit of a microfluidic mixing device according to the present disclosure.
圖2為本揭露之卡匣單元之仰視示意圖。2 is a bottom view of the card unit of the present disclosure.
圖3為本揭露之微流體混合裝置之一卡匣載台之第一實施例之俯視示意圖。3 is a top plan view of a first embodiment of a cassette carrier of one of the microfluidic mixing devices of the present disclosure.
圖4為本揭露之卡匣載台之立體示意圖。4 is a perspective view of the cassette carrier of the present disclosure.
圖5為本揭露之磁性體之一實施例之動作示意圖。FIG. 5 is a schematic view showing the operation of an embodiment of the magnetic body according to the present disclosure.
圖6為本揭露之磁性體之又一實施例之動作示意圖。FIG. 6 is a schematic view showing the operation of still another embodiment of the magnetic body according to the present disclosure.
圖7為本揭露之一種微流體混合方法之流程示意圖。FIG. 7 is a schematic flow chart of a microfluid mixing method according to the present disclosure.
S1至S7‧‧‧步驟S1 to S7‧‧‧ steps
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| CN112986148A (en) * | 2019-12-12 | 2021-06-18 | 杭州微策生物技术股份有限公司 | Biological fluid detection device, detection system and detection method |
| CN111715314B (en) * | 2020-06-29 | 2023-05-12 | 京东方科技集团股份有限公司 | Microfluidic system and mixing method |
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| CN103913582B (en) | 2016-04-27 |
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