TW200811438A - Real-time hardened red blood cell detecting chip by using dielectrophoresis force - Google Patents

Real-time hardened red blood cell detecting chip by using dielectrophoresis force Download PDF

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TW200811438A
TW200811438A TW95131653A TW95131653A TW200811438A TW 200811438 A TW200811438 A TW 200811438A TW 95131653 A TW95131653 A TW 95131653A TW 95131653 A TW95131653 A TW 95131653A TW 200811438 A TW200811438 A TW 200811438A
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Taiwan
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red blood
substrate
blood cell
wafer
electrode
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TW95131653A
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Chinese (zh)
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Horn-Jiunn Sheen
Ching-Jiun Lee
Chia-Jui Hsu
Chen-Pang Liu
Tzu-Heng Wu
Chih Yu Huang
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Horn-Jiunn Sheen
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Publication of TW200811438A publication Critical patent/TW200811438A/en

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Abstract

A real-time hardened red blood cell detecting chip and the method of operating principle are provided. The real-time hardened red blood cell detecting chip comprises the first substrate and at least a parallel electrode array. The first substrate comprises at least a micro-channel. Electrodes are parallel arranged, and the parallel electrode array is disposed in the channel on the first substrate and is composed with a plurality of electrodes. Another real-time hardened red blood cell detecting chip comprising the first substrate, at least one of parallel electrode array and the second substrate having at least one of a micro-channel, is provided. The parallel electrode is disposed on the first substrate and is composed with a plurality of electrodes. The electrodes are also parallel arranged. The second substrate, comprising at least one of a micro-channel, is disposed on the first substrate. And the micro-channel passes through the parallel electrode array. By using the present real-time hardened red blood cell detecting chip, the red blood cells can be manipulated to adhere or move off the area of the parallel electrode array.

Description

200811438 九、發明說明: 【發明所屬之技術領域】 電技術所製作之應用 以及應用介電泳力之 本發明是有關於一種利用微機 介電泳力之脆性紅血球即時檢測晶片 脆性紅血球即時檢測方法。 【先前技術】200811438 IX. Description of the invention: [Technical field of invention] Application of electrical technology and application of dielectrophoretic force The present invention relates to an instant detection method for brittle red blood cells by using brittle red blood cells using a dielectrophoretic force of a microcomputer. [Prior Art]

血液是人體新陳代射最主要的成分之―,其成份由血 和血球(45%)所組成’由於血液的微小變動會反應出人體 的生理情況,因此在生醫檢測的領域中,金液分析是不可缺少 的步驟。許多疾病可由檢耻絲診_病情,在臨床實驗的 檢測中’血液測試幾乎是最具指標性的檢測方式。 、在人體血液循環中,血液是由心臟加壓送出經由動脈再漸 漸分支到微血管,最後由靜脈_心、臟,以達到輪送養分、排 除,物的功用。而血液在血管内的流動有—定的阻力,此阻力 乃是由血管本赖朗雜及血齡雜職定。社液中紅 血球的血容比(hematGerit)大大地影響血液的黏度,當血容 比,大血液就愈黏愈不易流動。正常人的血容比大約在4〇〜 45%,在這樣高濃度的狀態下,血液能維持順暢的流動通最主 要的原因是目為紅鱗具有強雜力,使得它可以依血 官的管徑大小,適當地調整形狀,以便它通過微血管。 紅血球是—個直徑約8哗,體積約9G 一,表面積約14〇 的扁平雙凹形;而相同體積的圓球形,表面積卻只有97 6 200811438 μιη ’由於紅血球具有相當大的表面積,故提供了紅血球自由 伸展的此力。細,它賴雜力仍是有—定限度的。紅企球 所能通過的最小微血管管徑約為Ζ7 μπι左右,人體内最細的 微血管約3〜4μιη。 當紅血球的彈性降低也就是紅血球細胞膜僵硬變脆時,會 使血球通·bk管更加_,甚至紅血球會產生破裂。例如在 、、、罔狀内皮組織裡,如肝藏等,由於這些組織的特殊構造,其内 部血官孔隙非常小,使得脆性紅血球不易通過而遭破壞。此 外,對於一些溶血性貧血,譬如遺傳性橢圓形紅血球症 (Hreditaty Elliptocytosis)、anthocytosis···等疾病,將會導致脆 1±紅A球過多,所以脆性紅血球的檢測,可輔助我們推測病患 是否有可能具有該疾病。 傳統的紅血球脆性試驗乃是利用不同濃度的低張溶液來 測定紅血球外膜的耐受性(脆性),來輔助診斷「遺傳性紅血球 症」(Hereditary spherocytic erythrocyte)等病變。尤其是遺傳性 紅血球症,其紅血球明顯對低張溶液的耐性降低,使得脆性測 試之檢驗的「開始溶血」和「完全溶血」的濃度值高於正常值, 可藉此判斷是否可能具有脆性血球的溶血性疾病。通常脆性測 試需要的血量較多(約4 ml),其過程檢測相當麻煩,且需要浪 費不少消耗性的醫療用具,一次完整測試需要至少56支試 管,4支含有EDTA採血管,加上採血的微量滴管不可重複使 7 200811438Blood is the most important component of the body's new generation of radiation, and its composition is composed of blood and blood cells (45%). Because of the slight changes in blood, it reflects the physiological condition of the human body. Therefore, in the field of biomedical testing, gold Liquid analysis is an indispensable step. Many diseases can be diagnosed by sputum _ _ disease, in the detection of clinical experiments ' blood test is almost the most indicative detection method. In the blood circulation of the human body, the blood is sent out by the heart and then gradually branches to the microvessels through the artery, and finally, the veins are _heart and dirty, so as to achieve the function of feeding nutrients and removing the substances. The flow of blood in the blood vessels has a certain resistance, which is determined by the blood vessels and the blood age. The blood volume ratio (hematGerit) of the red blood cells in the social fluid greatly affects the viscosity of the blood. When the blood volume ratio, the larger the blood, the more difficult it is to flow. The normal person's blood volume ratio is about 4 〇 to 45%. In such a high concentration state, the most important reason for the blood to maintain a smooth flow is that the red scale has a strong force, so that it can be bloody. The diameter of the tube is adjusted appropriately so that it passes through the microvessels. The red blood cell is a flat double concave with a diameter of about 8 哗, a volume of about 9G, and a surface area of about 14 ;. The same volume of the spherical shape, the surface area is only 97 6 200811438 μιη 'Because the red blood cells have a considerable surface area, it provides The red blood cell is free to stretch this force. Fine, it still has a certain limit. The minimum microvascular diameter that the red ball can pass is about μ7 μπι, and the smallest microvessel in the human body is about 3~4μιη. When the elasticity of the red blood cells is reduced, that is, the red blood cell membrane is stiff and brittle, the blood cell bb tube will be more _, and even the red blood cells will be broken. For example, in the sacral endothelium, such as the liver, etc., due to the special structure of these tissues, the internal blood sinus pores are very small, making the fragile red blood cells difficult to pass and being destroyed. In addition, for some hemolytic anemia, such as Hereditary Elliptocytosis, anthocytosis, etc., will lead to excessive 1 ± red A ball, so the detection of brittle red blood cells can help us speculate Is it possible to have the disease? The traditional red blood cell fragility test uses different concentrations of low-tension solution to measure the tolerance (brittleness) of the erythrocyte outer membrane to aid in the diagnosis of lesions such as Hereditary spherocytic erythrocyte. In particular, hereditary erythrocytosis, the red blood cells obviously reduce the tolerance to low-tension solution, so that the concentration values of "start hemolysis" and "complete hemolysis" of the test of brittleness test are higher than normal values, thereby judging whether it is possible to have brittle blood cells. Hemolytic disease. Usually the brittleness test requires more blood (about 4 ml), the process is quite troublesome, and it takes a lot of wasted medical equipment. At least 56 tubes are needed for a complete test, and 4 tubes contain EDTA blood collection tubes. The micropipette for blood collection cannot be repeated 7 200811438

用’浪費之醫療成本相當可觀,另外還需要分光光度計 測,再經過正常血液之比對,所需的檢驗時間約卜2天檢驗報 告才可完成。由於這魏血性疾錢因為血料膜蛋白質的缺 陷而導致脆性紅血球的產生,峨性紅血球由於變形能力降 低,經職血管時容易破裂進而產生溶血現象,因此若血液中 脆性血球的量大料-正倾,财可視為擁有雜紅血球疾 病的可能’由於傳統的檢測技術需要的時間較長,因此經常無 法快速掌赌況延導致遲治__。本發明乃是藉由微機^ 製程技術製作-即時檢測晶片,细介電泳力使得脆性與正常 紅血球在平行電㈣達齡離效果,壯血球的㈣脆 提供一種參考方式。 J 運用微機電製程與介電泳力之原因,說明如下。 微機電製程起源於二十世紀八〇年代,其所開發出的製程 技術目前已被應躲料麵,在生醫檢測產業的翻方面, 其主要的特色是能製作出微小化的震置,以取代往日所使用的 武官、培養皿以及_裝置等。由於傳統生醫檢測乃是藉由隨 機碰撞與擴散來達成反應’因此需要數小時或數日才能^成= 種檢測。以往進行生物細胞檢測時都以群體為主,但是細胞 的尺寸剛好在微尺度範圍,而微機電之製程技術,恰好可以設 計出符合細胞大小之微結構,不但能增加對於個體細胞所收集 資訊的準確性’也能加速藥物與細胞的化學反應。因此透過微 8 200811438 機電製程所製作的生醫晶片的話,可以大幅度地提升檢測效 率。 在開發生醫檢測晶片時,需就待測細胞本身的特性進行考 量,以確保檢測結果的準確性,其中介電泳(dielectr〇phresis) 具有低電壓下,Sb成功操控細胞的特性,只要在晶片上陳列電 極、給予訊號源,就能隨意操控細胞而且不會損害細胞原有的 • 生物性質以及其結構。因此,利用介電泳力操控不同性質粒子 的移動,以檢測不同粒子,即成為微觀尺度下分辨粒子的方法 之一。介電泳之原理係說明如下,當一顆電中性的粒子放置在 電場中時,此電中性的粒子會因為電場之作用而產生偏極化 (electricalP〇larizati〇n)現象,並由此偏極化現象產生一誘導 祕矩,而這些電條且可被f場偏極絲刊狀為介電粒 子。此時,誘導耦極矩在電場中,會與電場相互作用而產生介 電泳力,使得粒子朝肖電場強度較強或較弱的區域移動。亦 除即,當粒子受到偏極化的程度大於週遭之流體時,粒子會往電 場強度較大的地方移動,而形成正介電泳。反之,當粒子受到 偏極化的程度小於週遭流體時,粒子會遠離電極或往電場強度 較小的區域移動,而形成負介電泳。一般介電泳之晶片即是利 用正介電泳與負介電泳之特性,將粒子移動至特定的區域。 另外,關於上述介電泳應用之實例係如下所述。2〇〇1年,The cost of medical waste is quite considerable. In addition, spectrophotometry is required, and after normal blood comparison, the required inspection time can be completed after 2 days of inspection report. Because this bloody disease causes the production of brittle red blood cells due to defects in the blood membrane protein, the sputum red blood cells are easily deformed due to the reduced deformability, and thus hemolysis is caused by the blood vessels, so if the amount of fragile blood cells in the blood is large - It is possible to have a red blood cell disease because of the long time required for traditional detection technology, so it is often impossible to quickly gamble and delay the treatment. The invention is made by a microcomputer-process technology - instant detection of the wafer, the fine dielectrophoretic force makes the brittleness and the normal red blood cells in parallel (four) ageing effect, and the strong blood cell (four) brittle provides a reference way. J The reasons for using the microelectromechanical process and dielectrophoretic force are as follows. The micro-electromechanical process originated in the 1920s, and the process technology developed by it has been evaded. In the aspect of the biomedical testing industry, its main feature is that it can produce a tiny shock. To replace the military officers, petri dishes, and equipment used in the past. Since traditional biomedical testing is achieved by random collision and diffusion, it takes hours or days to test. In the past, biological cell testing was dominated by populations, but the size of the cells was just in the microscale range, and the microelectromechanical process technology could just design a microscopic structure that fits the cell size, which not only increases the information collected for individual cells. Accuracy can also accelerate the chemical reaction between drugs and cells. Therefore, the biomedical wafers produced by the micro-2008 11438 electromechanical process can greatly improve the detection efficiency. When the medical test wafer is opened, it is necessary to consider the characteristics of the cell to be tested to ensure the accuracy of the test result. Among them, digelectr〇phresis has a low voltage, and Sb successfully manipulates the characteristics of the cell as long as it is on the wafer. By placing the electrodes on the display and giving the signal source, the cells can be manipulated at will without damaging the original biological properties and structure of the cells. Therefore, the use of dielectrophoretic force to manipulate the movement of particles of different properties to detect different particles is one of the methods for resolving particles at a microscopic scale. The principle of dielectrophoresis is as follows. When an electrically neutral particle is placed in an electric field, the electrically neutral particle will be polarized (electrical P〇larizati〇n) due to the action of the electric field. The polarization phenomenon produces an inducing secret, and these electric strips can be published as dielectric particles by the f-field polarized wire. At this time, the induced coupling moment is in the electric field, and interacts with the electric field to generate a dielectrophoretic force, so that the particles move toward a region where the electric field strength is strong or weak. In addition, when the particles are polarized to a greater extent than the surrounding fluid, the particles move to a place where the intensity of the electric field is large, and a positive dielectrophoresis is formed. Conversely, when the particles are polarized to a lesser extent than the surrounding fluid, the particles move away from the electrode or toward a region where the electric field strength is small, forming a negative dielectrophoresis. Generally, dielectrophoresis wafers use the characteristics of positive dielectrophoresis and negative dielectrophoresis to move particles to specific regions. In addition, examples of the above-described dielectrophoresis application are as follows. 2 years, 1 year,

Huang et aL針對五種生物分子細胞(丫邱贫(^11,;£ (;〇111^(^1^, 9 200811438 RBC,T-lymphocytes),區分在不同頻率下正負DEP所落的區 域,藉由同一輸入頻率範圍下,電極設計為5x5圓形陣列,不 同細胞擁有不同的DEP現象影響,細胞性質為正DEP的則被 吸附在電極陣列上達到收集,負的則被排斥到圓形電極外圍, 來達到分離不同種類的細胞,也能針對收集細胞的種類不同來 鎖定頻率範圍,達到兩種以上的細胞收集。Huang et aL is directed to five biomolecular cells ([11,; £ (; 〇111^(^1^, 9 200811438 RBC, T-lymphocytes), which distinguish between positive and negative DEPs at different frequencies, By the same input frequency range, the electrode is designed as a 5x5 circular array, and different cells have different effects of DEP. The cells with positive DOP are adsorbed on the electrode array for collection, while the negative ones are repelled to the circular electrode. In the periphery, to separate different types of cells, the frequency range can be locked for different types of collected cells, and more than two types of cells can be collected.

本發月乃疋利用介電泳力(也1沈仕〇沖如⑺簡稱DEP force)來分離脆性紅血球和正^紅血球。利用微機電製程技術 來氣作;I电永力脆性血球即時檢測晶片,搭配適當的流道, 可以達到㈣從錢巾分軸·紅姆:......This month, the sputum is used to separate fragile red blood cells and positive red blood cells by using dielectrophoretic force (also 1 Shen Shizhengru (7) for short). Using micro-electromechanical process technology to make gas; I electric permanent brittle blood cells to instantly detect the wafer, with appropriate flow channels, can reach (four) from the money towel split · red m: ...

血性貧血等病症。 【發明内容】Blood anemia and other diseases. [Summary of the Invention]

其包括1-基板與 脆性紅血球之即時檢戦供—個參考方式 泳力之脆性紅金球即時檢 L少一平行電極陣列。此第 200811438 一基板具有至少一微流道。平行電極陣列係配置於流道中 之第一基板上,且平行電極係由二個或多個電極構成,而 且電極係以垂直微流道方向平行排列。 依照本發明實施例之應用介電泳力之脆性紅血球即 時檢測晶片,例如更包括一第二基板配置於第一基板上, 以覆盍微流道,且第二基板之材質包括玻璃、石夕晶片、壓 克力、塑膠、聚甲基丙烯酸曱酯(PMMA)或聚二曱基矽 氧烷(PDMS)。 依照本發明實施例之應用介電泳力之脆性紅血球即. 時檢測晶片,更包括至少一注入構件配置於第二基板中, 以使液體可以進出微流道。其中,注入構件包括二注入管 與一傳輸管。注入管係連接微流道,而傳輸管係連接注入 管。 依照本發明實施例之應用介電泳力之脆性紅血球即 時檢測晶片,其中各電極平行排列,且各電極可不具有相 同寬度。 依照本發明實施例之應用介電泳力之脆性紅血球即 日守檢測晶片’例如更包括多個電極線,各電極線之一端係 連接至對應之各電極,且各電極線之另一端係連接至一電 極外部連接區。 依照本發明實施例之應用介電泳力之脆性紅血球即 時檢測晶片,其中第一基板之材質包括玻璃、矽晶片、壓 克力、塑膠、聚甲基丙烯酸甲酯(PMMA)或聚二曱基矽 氧烷(PDMS)。 11 200811438 依照本發明實施例之應时電泳力之脆性紅企球即 w檢測晶片’其中電極之材質包括黃金、白金、銘或鉻。 本發明再提出—種應用介電泳力之脆性紅血球即時 ^測晶片,其包括-第—基板、至少—平行_電極與具 至〉、微机道之-第一基板。平行陣列電極係配置於第 一基板上,且平行陣列電極係由二個或多個電極構成,而 且,係Μ直微流道方向平行制。具註少-微流道It includes 1-substrate and brittle red blood cells for immediate inspection - a reference method. The brittle red gold ball of the swimming force is immediately detected. L is a parallel electrode array. This 200811438 substrate has at least one microchannel. The parallel electrode array is disposed on the first substrate in the flow channel, and the parallel electrodes are composed of two or more electrodes, and the electrodes are arranged in parallel in the direction of the vertical microchannel. According to the embodiment of the present invention, the brittle red blood cell is used to detect the wafer, and the second substrate is disposed on the first substrate to cover the micro flow channel, and the material of the second substrate includes glass and stone wafer. , acrylic, plastic, poly(meth) methacrylate (PMMA) or polydimethyl decyl oxane (PDMS). According to an embodiment of the invention, a brittle red blood cell applying a dielectrophoretic force, that is, a time detecting wafer, further includes at least one injecting member disposed in the second substrate to allow liquid to enter and exit the microchannel. Wherein, the injection member comprises two injection pipes and a transmission pipe. The injection tube is connected to the microchannel, and the transfer tube is connected to the injection tube. A fragile red blood cell instant detecting wafer using dielectrophoretic force according to an embodiment of the present invention, wherein the electrodes are arranged in parallel, and each electrode may not have the same width. According to an embodiment of the present invention, a brittle red blood cell, which is a dice-positive detection wafer, for example, further includes a plurality of electrode lines, one end of each electrode line is connected to a corresponding electrode, and the other end of each electrode line is connected to one Electrode external connection area. According to an embodiment of the invention, a brittle red blood cell is applied to detect a wafer by using a dielectrophoretic force, wherein the material of the first substrate comprises glass, germanium wafer, acrylic, plastic, polymethyl methacrylate (PMMA) or polydimethyl fluorene Oxytomane (PDMS). 11 200811438 A brittle red ball, i.e., a w-detecting wafer, in response to an electrophoretic force in accordance with an embodiment of the present invention, wherein the material of the electrode comprises gold, platinum, or chrome. The present invention further proposes a brittle red blood cell instant measurement wafer using dielectrophoretic force, which comprises a -first substrate, at least - parallel_electrode and a substrate, and a first substrate. The parallel array electrode system is disposed on the first substrate, and the parallel array electrode is composed of two or more electrodes, and the straight micro flow path direction is parallel. Less note-micro flow channel

之一第二基板佩置料—基板上,且微流道係通過平行 陣列電極。 士依照本發明實施例之應用介電泳力之脆性紅血球即 時檢測晶片,例如更包括至少一注入構件配置於第二基板 t,以使液體可以進出微流道。其中注入構件包括一注入 官,一傳輸管。注入管係連接微流道,而傳輸管係連接注 入管。 士依知本發明實施例之應用介電泳力之脆性紅血球即 日守檢測晶片,其中各電極平行排列,且各電極可不具一相 同寬度,。 、 ^ 依本發明實施例之應用介電泳力之脆性紅血球即 日守檢測晶片,例如更包括多個電極線,各電極線之一端係 連接至對應之各電極,且各電極線之另一端係連接至一電 極外部連接區。 士依照本發明實施例之應用介電泳力之脆性紅血球即 ^檢測晶片’其中第一基板或第二基板之材質包括玻璃、 石夕晶片、壓克力、塑膠、聚甲基丙烯酸甲酯(PMMA)或 12 200811438 聚二甲基矽氧烷(PDMS)。 士依照本發明實施例之應用介電泳力之脆性紅血球即 知檢測晶片,其中電極的材質例如為黃金、白金、銘或鉻。 本發明提出一種介應用介電泳力之脆性紅血球即時 =之方法’首先係提供上狀應时料力之脆性紅血 球即時檢測晶片,且該晶片之電極的數目為m*n個,其中 =表示,,η表示每-組之電極數目,且4 • ―“接著,注入一液體進入微流道中。之後,對電極施加 ,源汛5虎,且電源訊號在每一組之相鄰二電極之間的相 位差為2π/η,以使液體中之多個介電粒子於平行陣列電極 之區域移動。 ±依照本發明實施例之應用介電泳力之脆性紅血球即 1檢利之方法,其中上述之介電粒子包括電中性且可被電 ^ 場偏極化之介電粒子。 士依舨本發明實施例之應用介電泳力之脆性紅血球即 馨 =檢剃之方法,上述之介電粒子例如為高分子聚合物粒 具細胞膜之生物粒子、細胞、酵母菌、血球或DNA。 依照本發明實施例之介電泳力脆性紅血球即時檢測 方法上述之電源訊號例如為6〜4〇 Vpp之交流電。 、本發明提供一種應用介電泳力之脆性紅血球即時檢 則曰曰片,利用其具有的平行陣列電極與微流道之設計,並 配合在相鄰二電極之間導入具有一相位差之電源訊號,而 使传介電粒子可以於平行陣列電極區域移動。此應用介電 冰力之脆性紅血球即時㈣晶片在生醫制方面之應用可 13 200811438 利用介電泳原理來操控電中性之微小粒子,在微尺度之卞 使微粒子產生各種不同的轨跡運動,並在低電壓的情况之 下,供給等相位差的訊號產生非均勻電場,電中性微粒子 隨著電場提供方式的變化,而產生多樣的粒子操控方式。 並針對生醫檢測晶片之中待測細胞的尺寸,設計微流道以 及平仃電轉列,麵者相互搭配下,使㈣晶片具有操 控粒子的效果,並可时電泳力來進行雜紅血球的即時 檢測。 *為讓本發明之上述和其他目的、特徵和優點能更明顯 易If,下文特舉較佳實施例,並配合所附圖式,作詳細說 明如下。 【實施方式】 第一實施例 圖1繪示為流道位於第一基板上之應用介電泳力之脆 性紅血球即時檢測晶片的示意圖,圖1A繪示為圖1中之 應用介電泳力之脆性紅血球即時檢測晶片沿AA,剖面線之 剖面示意圖。 曰請共同參照圖1與圖1A,第一實施例之微粒子混合 曰曰片100包括一第一基板110以及至少一平行陣列電極 120。其中,第一基板110具有至少一微流道112,且平行 陣列電極120係位於微流道112中之第一基板n〇上,且 平行陣列電極120係由多個電極122構成,而且電極122 係以垂直微流道112方向平行排列。 14 200811438 睛參照圖1A’在-較佳實施例中,此介電泳力 之脆性紅血球即時檢測晶片卿例如更包括一第二基板 130配置於第-基板11〇上,以覆蓋微流道⑴,且第二基 板130之材質例如為玻璃、石夕晶片、壓克力、塑膠、聚甲 基丙烯酸=(ΡΜΜΑ)或聚二甲基魏烧(pDMS)。One of the second substrates is placed on the substrate, and the microchannels pass through the parallel array electrodes. According to an embodiment of the present invention, a brittle red blood cell instant detecting wafer using a dielectrophoretic force, for example, further comprising at least one injecting member disposed on the second substrate t to allow liquid to enter and exit the microchannel. The injection member includes an injection unit and a transfer tube. The injection tube is connected to the microchannel, and the delivery tube is connected to the injection tube. According to the embodiment of the present invention, the brittle red blood cell using the dielectrophoretic force is a day-care wafer, wherein the electrodes are arranged in parallel, and the electrodes may not have the same width. According to the embodiment of the present invention, a brittle red blood cell, which is a dice-killing detection wafer, which includes a plurality of electrode lines, each of which is connected to a corresponding electrode, and the other end of each electrode line is connected. To the external connection area of an electrode. According to the embodiment of the present invention, a brittle red blood cell using a dielectrophoretic force is used to detect a wafer. The material of the first substrate or the second substrate includes glass, stone wafer, acrylic, plastic, polymethyl methacrylate (PMMA). ) or 12 200811438 Polydimethyloxane (PDMS). According to an embodiment of the present invention, a brittle red blood cell using a dielectrophoretic force is known to detect a wafer, wherein the material of the electrode is, for example, gold, platinum, or chrome. The invention provides a method for immediately detecting a brittle red blood cell by using a dielectrophoretic force. The first method is to provide a brittle red blood cell instant detection wafer with a top-loading force, and the number of electrodes of the wafer is m*n, wherein = , η represents the number of electrodes per group, and 4 • ― “Next, a liquid is injected into the microchannel. After that, the electrode is applied, the source is 5, and the power signal is between the adjacent two electrodes of each group. The phase difference is 2π/η, so that a plurality of dielectric particles in the liquid move in a region of the parallel array electrode. ± A method for applying brittle red blood cells using a dielectrophoretic force according to an embodiment of the present invention, wherein The electric particles include dielectric particles which are electrically neutral and can be polarized by the electric field. The method for applying the dielectrophoretic force of the brittle red blood cell, ie, the method of shaving, according to the embodiment of the present invention, the dielectric particles are, for example, The polymer particle has a cell membrane biological particle, a cell, a yeast, a blood cell or a DNA. The instant detection method of the dielectrophoretic brittle red blood cell according to the embodiment of the present invention is, for example, 6 to 4 Vpp alternating current. The present invention provides a brittle red blood cell instant detection smear using dielectrophoretic force, which has a parallel array electrode and a micro flow channel design, and is matched with a phase between adjacent two electrodes. Poor power signal, so that the dielectric particles can move in the parallel array electrode area. This application of dielectric ice force brittle red blood cells in real time (four) wafer application in biomedical applications 13 200811438 using dielectrophoresis principle to control electrical neutrality The tiny particles, at the micro-scale, cause the micro-particles to produce various trajectory movements, and in the case of low voltage, the signals of equal phase difference produce a non-uniform electric field, and the electric neutral particles change with the way the electric field is supplied. And produce a variety of particle manipulation methods. And for the size of the cells to be tested in the biomedical detection wafer, design the micro-flow channel and the flat-turn electric transfer, and the faces are matched with each other, so that the (four) wafer has the effect of manipulating the particles, and Simultaneous detection of red blood cells by electrophoretic force. * To make the above and other objects, features and advantages of the present invention clearer The following is a detailed description of the preferred embodiments, and the following is a detailed description of the following: [Embodiment] FIG. 1 illustrates the brittleness of the dielectrophoretic force applied to the first substrate by the flow channel. Schematic diagram of the red blood cell detecting the wafer immediately, FIG. 1A is a schematic cross-sectional view of the brittle red blood cell using the dielectrophoretic force in FIG. 1 along the line AA, and the cross-sectional line is taken. Referring to FIG. 1 and FIG. 1A together, the first embodiment The microparticle mixing cymbal 100 includes a first substrate 110 and at least one parallel array electrode 120. The first substrate 110 has at least one microchannel 112, and the parallel array electrode 120 is located in the first substrate of the microchannel 112. The upper array electrode 120 is composed of a plurality of electrodes 122, and the electrodes 122 are arranged in parallel in the direction of the vertical microchannels 112. 14 200811438 Eyes Referring to FIG. 1A', in a preferred embodiment, the dielectrophoretic brittle red blood cell instant detection wafer, for example, further includes a second substrate 130 disposed on the first substrate 11A to cover the micro flow channel (1), The material of the second substrate 130 is, for example, glass, stone wafer, acrylic, plastic, polymethacrylic acid = (ΡΜΜΑ) or polydimethyl Wei (pDMS).

此=,第二基板130例如更包括至少一注入構件i4〇 2於第—基板13G巾,以使液體可以進綠流道112。 Γ中:注入構件140包括一注入管142與一傳輸管144。 ^入官142係連接微流道112,而傳輸f I44係連接注入 ^42。在-較佳實施例中,例如配置兩個注人構件⑽ ,弟二基板13G巾…為越進人微流道112之路徑,一 為流體排出之路徑。 請繼續參照圖卜在-較佳實施例中,平行陣列電極 U0之各電極122具有-寬度。特別是,當啟動晶片時, 紅血球會麵經平行雜___,因本身技為脆性紅 血球’_而受獨介電泳力的影響,產生遠離電極或是吸附於電 極的行為,即在使用此微粒子操控晶#綱時,流經平行 陣列電極120之液财的紅血雜子,會因本妓否為脆 、、血球*有&離或是吸附於電極的行為,進*達到即時檢 测的效果。 此外,如圖1所繪示,應用介電泳力之脆性紅血球即 ^测晶片100例如更包括多個電極線150,各電極線15〇 ^係連接至對應之各電極122,且各電極線之另 15 200811438 ^—端係遠技5 主一電極外部連接區160,此電極外部連接區 二為70王令焊點之設計,且可簡易地外接到一匯流排 、、’:達到晶片隨插即用的功能。 參照圖1A,在一較佳實施例中,第一基板110 t材貝例如為破壤、石夕晶片、壓克力、塑膠、聚甲基丙稀 §曰(PMMA)或聚二甲基石夕氧烧(PDMS),且電極122 ^材貝例如為頁金、白金、鋁或鉻。第-基板110與第二 _ 土板130之材質可相同也可不相同。 第二實施例 圖1B繪不為流道位於第二基板上之應用介電泳力之 脆性=血球即時檢測晶片的剖面示意圖。 請共同參照圖1與圖1B,第二實施例之應用介電泳 力之脆性紅血球即時檢測晶片1〇2例如包括一第一基板 no、至少一平行陣列電極12〇與具有至少一微流道 之一第二基板130。 鲁 平行陣列電極12〇係配置於第一基板11〇上,且平行 陣列電極120係由多個電極122構成,而且電極122係以 垂=微流道132方向平行排列。具有至少一微流道132之 第一基板130係配置於第一基板11〇上,且 32 係通過平行陣列電極12〇。 /於此,第二實施例中與第一實施例相同或相類似的構 =係標示以相同之標號,在此將不再予以贅述。不過,值 得主思的疋,在第二實施例中,流道132之位置係配置於 16 200811438 第二基板130中。也就是說,在應用介電泳力之脆性紅血 球即時檢測晶片100中’流道可與平行陣列電極設置於同 一基板或是不同之基板。 此外,在一較佳實施例中,第一實施例或第二實施例 中之平行陣列電極120亦可使用陣列(army )型態之設計, 具體而言,在流道112、132中係以陣列型態設置多個平行 狀電極120,如此一來,能夠增加脆性紅血球遠離或是吸附 • 於電極的範圍,可使脆性紅金球的檢測更為容易,以提升 應用介電泳力之脆性紅血球即時檢測晶片之功能與效率。For example, the second substrate 130 further includes at least one injecting member i4 〇 2 on the first substrate 13G so that liquid can enter the green flow path 112. Γ中: The injection member 140 includes an injection tube 142 and a transfer tube 144. ^Into the official 142 is connected to the microchannel 112, and the transmission f I44 is connected to the injection ^42. In the preferred embodiment, for example, two injection members (10) are disposed, and the second substrate 13G is a path for the fluid passage. With continued reference to the preferred embodiment, each of the electrodes 122 of the parallel array electrode U0 has a width. In particular, when the wafer is activated, the red blood cell meets through the parallel ___, which is affected by the single-dielectrophoretic force due to its own technique as a brittle red blood cell, and acts to move away from the electrode or adsorb to the electrode, that is, to use the microparticle. When the crystal# is manipulated, the red blood miscellaneous particles flowing through the parallel array electrode 120 may be immediately detected due to whether the sputum is brittle, the blood cell* is & or is adsorbed to the electrode. Effect. In addition, as shown in FIG. 1 , the brittle red blood cell using the dielectrophoretic force, that is, the test wafer 100 further includes a plurality of electrode lines 150 , and each electrode line 15 is connected to the corresponding electrode 122 , and each electrode line is Another 15 200811438 ^—Terminal technology 5 main electrode external connection area 160, this electrode external connection area 2 is 70 Wang solder joint design, and can be easily externally connected to a bus, ': to achieve wafer insertion Ready-to-use features. Referring to FIG. 1A, in a preferred embodiment, the first substrate 110 t is, for example, a broken soil, a stone wafer, an acrylic, a plastic, a polymethyl methacrylate (PMMA) or a polydimethyl stone. Oxygen burn (PDMS), and the electrode 122 ^ is, for example, sheet gold, platinum, aluminum or chromium. The materials of the first substrate 110 and the second earth plate 130 may be the same or different. SECOND EMBODIMENT Fig. 1B is a schematic cross-sectional view showing the brittleness of the application dielectrophoretic force of the flow path on the second substrate = the blood cell immediate detection wafer. Referring to FIG. 1 and FIG. 1B together, the brittle red blood cell instant detection wafer 1 2 using the dielectrophoretic force of the second embodiment includes, for example, a first substrate no, at least one parallel array electrode 12 and at least one micro flow channel. A second substrate 130. The parallel array electrode 12 is disposed on the first substrate 11A, and the parallel array electrode 120 is composed of a plurality of electrodes 122, and the electrodes 122 are arranged in parallel in the direction of the vertical/microchannel 132. The first substrate 130 having at least one microchannel 132 is disposed on the first substrate 11A, and the 32 is passed through the parallel array electrode 12A. The same or similar reference numerals are used in the second embodiment to designate the same reference numerals, and will not be described again. However, it is worthwhile to think that in the second embodiment, the position of the flow path 132 is disposed in the second substrate 130 of 16 200811438. That is to say, in the brittle red blood cell immediate detecting wafer 100 to which dielectrophoretic force is applied, the flow path can be disposed on the same substrate or a different substrate as the parallel array electrode. Moreover, in a preferred embodiment, the parallel array electrode 120 of the first embodiment or the second embodiment may also use an array design, specifically, in the flow paths 112, 132. The array type is provided with a plurality of parallel electrodes 120, so that the brittle red blood cells can be increased away or adsorbed in the range of the electrodes, and the detection of the brittle red gold balls can be made easier to enhance the brittle red blood cells applying the dielectrophoretic force. Instantly detect the function and efficiency of the chip.

電極晶片200之製作請參照圖^ ^Please refer to the figure for the fabrication of the electrode wafer 200 ^ ^

乍一金屬層220於基板210 且金屬層220之材質例如為 17 200811438 ,來’如圖2C〜2F所緣示,對於金屬層22〇進 案化衣程,此圖案化製程之過程例如採取下述步驟十 如圖2C所示之塗佈光阻23〇的步驟;進行如圖2D所示Γ ^用光罩240進行曝光的步驟;進行 頁 步以得到圖案化光阻層230a;進行如圖2以^ 圖”化光阻層2地為罩幕侧金屬層22 =G:/之去除圖案化光阻層23°3的步驟而= 之電極W。上述之步驟為-般 技術者所週知,於此不再贅述。 〜為料,亥項 請參甲基^氧_廳)層遍的製作 微粒。清ΪΙτ;:序’財除基板31G上之污染物或 清洗法、妓细氣體錢4高温真空之乾式 上。^一=2。於基板”❹ 細進行曝井以^ 利用一先罩330對於此光阻層 有一圖案化光阻屌:等製程’之後形成如圖3D所示之具 半導體製程,因^上之f模340。上述之步驟為一般的 術者所此砰=㈣之詳_料熟習該項技 -聚二^基石夕3E ’在此圖案化光阻層320a上塗佈 方法與條件例如,亚加熱供烤使其固化。加熱之 馬玫置在加熱板上,以10(rc加熱3〇分鐘。 200811438 白孙ίΐή請參照圖3F,將固化之聚二甲基魏烧層300 母=上剝離,而完成具有微流道搬之聚 氧烷層3⑽的製作。 τ ι yThe metal layer 220 is on the substrate 210 and the material of the metal layer 220 is, for example, 17 200811438. As shown in FIG. 2C to FIG. 2F, for the metal layer 22, the process of the patterning process is taken, for example, Step 10: the step of coating the photoresist 23〇 as shown in FIG. 2C; performing the step of exposing with the photomask 240 as shown in FIG. 2D; performing the page step to obtain the patterned photoresist layer 230a; 2, the photoresist layer 2 is the mask side metal layer 22 = G: / the step of removing the patterned photoresist layer 23 ° 3 = the electrode W. The above steps are the general technical week I know, I will not repeat them here. ~ For the material, please refer to the methyl ^ oxygen _ hall for the production of particles in the layer. Clear τ;: Precise the removal of contaminants on the substrate 31G or cleaning method, fine gas On the dry side of the high temperature vacuum of the money 4, ^1 = 2. On the substrate, the exposure is performed finely. Using a squeegee 330, there is a patterned photoresist for the photoresist layer: the process is formed as shown in Fig. 3D. It has a semiconductor process, because of the f-mode 340. The above steps are the general practitioner's 砰 = (4) details _ familiar with the technology - poly bismuth stone eve 3E 'coating method and conditions on the patterned photoresist layer 320a, for example, sub-heating for baking It cures. The heated horse is placed on a hot plate and heated at 10 (rc for 3 〇 minutes. 200811438 白孙ίΐή Please refer to Figure 3F, the cured polydimethyl Wei burnt layer 300 mother = upper stripped, and finished with micro flow channel Production of a polyoxyalkylene layer 3 (10). τ ι y

於完成之電極晶片200與具有微流道302之聚二甲基矽 氧烧層300將繼續進行一封裝接合製程,請參照圖4A〜 4F。首,,提供一如圖4A所示之具有微流道3〇2之聚二 曱基石夕氧院層300。接著,請參照圖4B,在聚二甲基石夕氧 烷層300上鑽鑿流體注入孔304。 再參照圖4C,將電極晶片200與具有微流道 3和机體入孔304之聚二甲基矽氧烷層300放入氧氣 電聚儀之環境4GG中處理。之後,請參_ 4D,自氧氣電 漿儀之環境400中取出電極晶片和具有微流道搬和 流體注入孔304之聚二曱基魏烧層議,並將兩者接合。 繼之,請參照圖4E,將兩個注入構件51〇插入聚二 基石夕氧烧層3GG之流體注人孔3()4。每—注人構件51_ 如更包括注入管512與傳輸管514,且傳輸管5 在注入管512上。 之後,請參照圖4F,將注入管512與流體注入孔3〇4 之接合處再以聚二甲基魏烧層汹或是其他黏合劑如 AB膠等賊’加熱並待其,至此即完成制介電泳 力之脆性紅血球即時檢測晶片的製作。 第四實施例 圖5係利用本發明之應用介電泳力之脆性紅血球即時 200811438 電源訊號的相位變化以檢測脆性紅血球之測 4…果,圖6則為介電泳力操控結果,正介電 象’負介電泳為排斥現象。請參照圖1、圖5,首^提供 =:;rrri2〇之應用介電心^ 檢H在-較佳實施例中,平行陣列電極120之 设计係先書一組平行雷搞,P卩拓如, 並平銘t 一 ’再將原電極複製 μηΜ ,凡成第二組電極,再重複此步驟即可完 成平行陣列排列。 乂哪丨J凡 雷^1ί卜2用介電泳力之脆性紅血球即時檢測晶片中的 電f 22的數目為心個,其中m表示組數,η表示 =電極122數目,且m與η為正整數。在—實施例中, 圖1所繪不,將8條電極分成4組(122a〜mb),每 組具有2條電極。 ^著,注人液體進人流道中,此液體中具有多數個介 電粒子,而此所謂的介電粒子於此是指本身為電中性且可 3場偏極化之粒子。在本實關中,介錄子為紅血球, 包議性紅血球與正常紅血球。在另—實施例中,介電粒 子=如為具細胞膜之生物粒子、細胞、酵母、DNA或高分 子聚合物粒子。·本發明之㈣介電減性紅血球檢測 晶片可用於生醫檢測系統。 之後、,對電極122施加一電源訊號,且電源訊號在每 、、且之相鄉一電極122之間的相位差為2π/η,以使液體中 之多個介電粒子產生遠離或是吸附於電極的行為。其中,電 源訊说例如為6〜2GVpp之交流電,以提供上述之平行陣 20 200811438 列電極120對於介電粒子之操控。根據圖5的測試結果, 當輸入頻率為2MHz時,新鮮紅血球為正介電泳,脆性紅 血球為負;|電,永’因此啟動晶#時,紅▲球會在流經平行電 極陣歹丨的區域% ’因本身是否為脆性紅*球,而受不同介電泳 力的衫響’產生mi球遠離電極且新鮮紅i球吸附於電極 的行為,即在使耻即時檢測晶w⑼時,流經平行陣列 電極120之液體巾的紅血球粒子,會因本身是否為脆性紅The completed electrode wafer 200 and the polydimethyl oxynitride layer 300 having the microchannels 302 will continue to be subjected to a package bonding process, with reference to Figs. 4A to 4F. First, a polydioxin-based compound 300 having a microchannel 3〇2 as shown in Fig. 4A is provided. Next, referring to Fig. 4B, a fluid injection hole 304 is drilled in the polydimethylalkaline layer 300. Referring again to Figure 4C, electrode wafer 200 and polydimethyloxane layer 300 having microchannels 3 and body inlets 304 are placed in an environment 4GG of an oxygen cell. Thereafter, in the environment 400 of the oxygen plasma meter, the electrode wafer and the polydithiocarbeene layer having the microchannel and fluid injection holes 304 are taken out and joined. Next, referring to Fig. 4E, the two injection members 51 are inserted into the fluid injection hole 3 () 4 of the polysulfide oxide layer 3GG. Each of the injection members 51_ further includes an injection tube 512 and a transfer tube 514, and the transfer tube 5 is on the injection tube 512. After that, referring to FIG. 4F, the joint between the injection tube 512 and the fluid injection hole 3〇4 is heated and waited for by a dimethyl squid or other adhesive such as AB glue, and then completed. Preparation of a brittle red blood cell for the detection of dielectrophoretic force. Fourth Embodiment FIG. 5 is a graph showing the phase change of a brittle red blood cell instant 200811438 power signal using the dielectrophoretic force of the present invention to detect a brittle red blood cell 4, and FIG. 6 is a dielectrophoretic force manipulation result, a positive dielectric image Negative dielectrophoresis is a phenomenon of rejection. Referring to FIG. 1 and FIG. 5, the first application provides a dielectric core for detecting the voltage of the device. In the preferred embodiment, the design of the parallel array electrode 120 is a set of parallel lightning. For example, and Pingming t a 'reproduce the original electrode μηΜ, where the second group of electrodes, then repeat this step to complete the parallel array arrangement.乂 丨 丨 凡 雷 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ Integer. In the embodiment, as shown in Fig. 1, eight electrodes are divided into four groups (122a to mb) each having two electrodes. ^, the injection of liquid into the human channel, the liquid has a plurality of dielectric particles, and the so-called dielectric particles here refers to particles that are themselves electrically neutral and can be polarized in three fields. In this real customs, the mediators are red blood cells, encapsulated red blood cells and normal red blood cells. In another embodiment, the dielectric particles are, for example, biological particles, cells, yeast, DNA or polymer polymer particles having a cell membrane. - (IV) Dielectric Reduced Red Blood Cell Detection of the Invention The wafer can be used in a biomedical detection system. Thereafter, a power signal is applied to the electrode 122, and the phase difference of the power signal between each of the electrodes 122 is 2π/η, so that the plurality of dielectric particles in the liquid are generated or adsorbed. The behavior of the electrodes. The power source is, for example, an AC of 6 to 2 GVpp to provide the above-described parallel array 20 200811438 column electrode 120 for manipulation of dielectric particles. According to the test results of Figure 5, when the input frequency is 2MHz, the fresh red blood cells are positive dielectrophoresis, and the brittle red blood cells are negative; |Electric, Yong' so when starting the crystal #, the red ▲ ball will flow through the parallel electrode array The area % 'because it is a brittle red * ball, and the shirt is excited by different dielectrophoretic forces' produces a mi ball away from the electrode and the fresh red i ball is adsorbed on the electrode, that is, when the shame is detected immediately, the crystal w(9) flows through The red blood cell particles of the liquid towel of the parallel array electrode 120 may be brittle red due to itself.

t球而有祕或是吸附於電極的行為,進而達到檢測的效 果0 為了證明本發明確實可行,圖7係對上述之應用介電 =之脆性紅血球㈣檢測晶片騎試驗,並拍攝微流道 中液體之紅血球移動之情形。 2發明之應时電泳力之祕紅血球即時檢測晶 於所需的電壓僅在2G伏特左右,且仙時間僅需數 t鐘=所需的能量可由—般攜帶型電池提供,配合適當 遠接曰、二可將電池的直流電訊號轉換成交流電訊號, 於、目丨’本發明u介電泳力之雜紅血球即時 電泳力之脆性紅血球即時檢測方法,至 檢測曰(發明之應用介電泳力之脆性紅血球即時 區域二έ II電冰微粒子操控方法,能夠使流經在電極 '中的、、工血球粒子遠離或是吸附在電極表面,因此達到 21 200811438 脆性紅血球即時檢測的目的。 (2) 本發明之應用介電泳力之脆性紅i球即時檢測 晶片為完全零焊點與隨插即用之設計,可提升應用介電泳 力之脆性紅jk球即時檢測晶片之操作穩定性與使用方便 性,並可配合一般攜帶型電池與適當轉換電路,將電池的 直流電訊號轉換成交流電訊號,連接晶片中的電極後,成 為一可攜式應用介電泳力之脆性紅血球即時檢測晶片。 (3) 本發明之應用介電泳力之脆性紅企球即時檢測 晶片可利用微影蝕刻製程,設計並製作品質良好以及操作 穩定之平行陣列電極。此外利用聚二甲基矽氧烷層之翻模 製作方式可大量製作微流道,此方式具有成本低廉並可大 量製作之優點。 雖然本發明已以較佳實施例揭露如上,然其並非用以 限^本發明,任何熟習此技藝者,在不脫離本發明之精神 =範圍内,當可作些許之更動與潤飾,因此本發明之保護 範圍當視後附之申請專利範圍所界定者為準。 【圖式簡單說明】 圖1繪示為流道位於第一基板上之應用介電泳力之脆 性紅血球即時檢測晶片的示意圖。 囷A、、、曰示為圖1中之應用介雷洗力之脆性紅血球即t ball and secret or adsorption to the electrode, and then achieve the effect of detection 0 In order to prove that the present invention is indeed feasible, Figure 7 is the application of dielectric = brittle red blood cells (four) detection wafer riding test, and shooting in the micro-channel The situation in which the red blood cells of the liquid move. 2 The invention of the electrophoresis force of the secret red blood cell for immediate detection of the crystal required voltage is only about 2G volts, and the time is only a few t clock = the required energy can be provided by the general portable battery, with appropriate distance 曰And the second can convert the DC signal of the battery into an AC signal, and witness the instant detection method of the brittle red blood cell of the instant electrophoresis force of the dielectrophoretic force of the present invention, to detect the sputum (the application of the dielectrophoretic brittle red blood cell) The instant zone II II electric ice particle manipulation method can make the flow of the blood cell particles in the electrode 'is away from or adsorb on the electrode surface, thereby achieving the purpose of the instant detection of the brittle red blood cell of 21 200811438. (2) The invention The application of dielectrophoretic brittle red i-ball instant detection chip is completely zero solder joint and plug-and-play design, which can improve the operational stability and ease of use of the brittle red jk ball for the application of dielectrophoretic force. With the general portable battery and appropriate conversion circuit, the DC signal of the battery is converted into an AC signal, and the electrodes in the wafer are connected to become Portable application of dielectrophoretic brittle red blood cells for immediate detection of wafers. (3) The application of the dielectrophoretic brittle red ball instant detection wafer of the present invention can utilize the lithography etching process to design and fabricate parallel arrays of good quality and stable operation. In addition, the microchannels can be produced in a large number by means of a mold-making method of a polydimethylsiloxane layer, which has the advantages of low cost and mass production. Although the invention has been disclosed above in the preferred embodiment, It is not intended to limit the invention, and those skilled in the art can make some modifications and refinements without departing from the spirit and scope of the invention, and the scope of the invention is defined by the scope of the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS [Simplified Schematic] FIG. 1 is a schematic diagram of a brittle red blood cell instant detection wafer using a dielectrophoretic force on a first substrate. 囷A, , and 曰 are shown in FIG. Brittle red blood cells

圖1B繪示為流道位於第 脆性紅血球即時檢測晶片的 於第二基板上之應用介電泳力之 的剖面示意圖。 22 200811438 圖2A〜2G繪示為電極晶片製作流程圖。 圖3A〜3F為微流道製作流程圖。 圖4A〜4F 流程圖。 緣示為電極晶片與微流道封裝接合之製作 圖5係利用本發明之應用介電泳力之脆性紅企球即時 檢測晶片配合電源訊號的相位變化以檢測脆性紅血球之測 試結果。Fig. 1B is a schematic cross-sectional view showing the application of dielectrophoretic force on the second substrate of the first brittle red blood cell detecting wafer in the flow path. 22 200811438 FIGS. 2A to 2G illustrate a flow chart of electrode wafer fabrication. 3A to 3F are flow charts for making a micro flow path. 4A to 4F are flowcharts. The production of the electrode wafer and the microchannel package is shown in Fig. 5. The test results of the brittle red blood cells are detected by using the brittle red ball of the dielectrophoretic force of the present invention to detect the phase change of the wafer with the power signal.

圖6為介電粒子流經平行電極時所產生的現象,正介 電泳為吸附於電極上,負介電泳則為排斥現象遠離電極。 圖7係利用本發明之應用介電泳力之脆性紅血球即時 檢測晶片實際檢測脆性紅血球之測試結果。 【主要元件符號說明】 100、102:應用介電泳力之脆性紅血球即時檢測晶片 110 :第一基板 112 ' 132 ·微流道 120 :平行陣列電極 122 ·電極 122a、122b、122c、122d :電極組 130 :第二基板 140、510 :注入構件 142、512 :注入管 144 ' 514 =傳輸管 150 :電極線 160 :電極外部連接區 23 200811438 200 :電極晶片 210、310 :基板 220 :金屬層 220a:圖案化金屬層 230 :光阻 230a :圖案化光阻層 240、330 :光罩 300、520 :聚二曱基矽氧烷層 302 :微流道 304 ··流體注入孔 320 :光阻層 340 :母模 400 ··氧氣電漿儀之環境Figure 6 shows the phenomenon that dielectric particles flow through a parallel electrode. Positive dielectric electrophoresis is adsorbed on the electrode, and negative dielectrophoresis is a repulsive phenomenon away from the electrode. Fig. 7 shows the test results of the actual detection of fragile red blood cells by the use of the dielectrophoretic brittle red blood cells of the present invention. [Main component symbol description] 100, 102: Brittle red blood cell instant detection wafer 110 using dielectrophoretic force: First substrate 112 '132 · Micro flow channel 120: Parallel array electrode 122 · Electrode 122a, 122b, 122c, 122d: Electrode group 130: second substrate 140, 510: injection member 142, 512: injection tube 144 ' 514 = transfer tube 150: electrode line 160: electrode external connection region 23 200811438 200: electrode wafer 210, 310: substrate 220: metal layer 220a: Patterned metal layer 230: photoresist 230a: patterned photoresist layer 240, 330: photomask 300, 520: polydioxanoxane layer 302: microchannel 304 · fluid injection hole 320: photoresist layer 340 : Mother mold 400 · · Oxygen plasma environment

24twenty four

Claims (1)

200811438 十、申請專利範園·· L一種應用介電泳力之脆性紅血球即時檢測晶片,包 括·· 一第一基板,該第一基板具有至少一微流道;以及 至少一平行陣列電極,配置於該微流道中之該第一基 板上)且該平行陣列電極係由多數個電極構成,而且該些 電極係以垂直微流道方向平行排列。 1如申凊專利範圍第1項所述之應用介電泳力之脆性 紅血球即時檢測晶片,更包括一第二基板配置於該第一基 板上,以覆蓋該微流道。 1如申請專利範圍第2項所述之應用介電泳力之脆性 紅血球即時檢測晶片,其中該第二基板之材質包括玻璃、 矽晶片、壓克力、塑膠、聚甲基丙烯酸曱酯(PMMA)或 聚二曱基矽氧烷(PDMS)。 4·如申請專利範圍第2項所述之應用介電泳力之脆性 紅血球即時檢測晶片,更包括至少一注入構件配置於該第 二基板中,以使液體可以進出該微流道。 5·如申請專利範圍第4項所述之應用介電泳力之脆性 紅血球即時檢測晶片,其中該注入構件包括: 二注入管,連接該微流道;以及 一傳輸管,連接該注入管。 6·如申請專利範圍第1項所述之應用介電泳力之脆性 紅血球即時檢測晶片,其中各該電極具有一寬度,相鄰區 域互相平行排列。 25 200811438 7. 如申請糊範圍第1項所述之朗介電泳力之 紅血^即時檢測晶片,更包括多數個電極線,各該電極線 之-端係連接至對應之各該電極,且各該電極線之 係連接至一電極外部連接區。 8. 如申請專利範圍第1項所述之應用介電泳力之脆性 紅血球即時檢測晶片,其中該第—基板之材質包括玻璃、 矽晶片、壓克力、塑膠、聚甲基丙烯酸甲酯(PMMA)或 聚二甲基矽氧烷(PDMS)。 一 9:如申請專利範圍第1項所述之應用介電泳力之脆性 紅血球即時檢測晶片,其中各該電極之材質包括黃金、白 金、铭或鉻。 、 1〇· 一種應用介電泳力之脆性紅血球即時檢測晶片,包 括: 一第一基板; 至少一平行陣列電極,配置於該第一基板上,且該平 行陣列電極係由多數個電極構成,而且該些電極係以垂直 微流道方向平行排列;以及 具有至少一微流道之一弟二基板,配置於該第一基板 上’且該微流道係通過該平行陣列電極。 11·如申請專利範圍第10項所述之應用介電泳力之脆 性紅血球即時檢測晶片,更包括至少二注入構件配置於該 第二基板中,以使液體可以進出該流道。 12·如申請專利範圍第π項所述之應用介電泳力之脆 性紅血球即時檢測晶片,其中該注入構件包括: 26 200811438 二注入管,連接該微流道;以及 一傳輸管,連接該注入管。 13·如申請專利範圍第丨〇項所述之應用介電泳力之跪 性紅血球即時檢測晶片,更包括多數個電極線,各該電極 線之一端係連接至對應之各該電極,且各該電極線之另一 端係連接至一電極外部連接區。200811438 X. Application for Patent Park·· L A brittle red blood cell instant detection wafer using dielectrophoretic force, comprising: a first substrate having at least one microchannel; and at least one parallel array electrode disposed at The first substrate in the microchannel) and the parallel array electrode are composed of a plurality of electrodes, and the electrodes are arranged in parallel in a vertical microchannel direction. The application of the dielectrophoretic brittle red blood cell detection chip according to the first aspect of the invention, further comprising a second substrate disposed on the first substrate to cover the micro flow channel. 1 The method for detecting a brittle red blood cell using a dielectrophoretic force as described in claim 2, wherein the material of the second substrate comprises glass, germanium wafer, acrylic, plastic, polymethyl methacrylate (PMMA) Or polydidecyloxyne (PDMS). 4. The fragile red blood cell instant detection wafer using dielectrophoretic force as described in claim 2, further comprising at least one injection member disposed in the second substrate to allow liquid to enter and exit the microchannel. 5. The fragile red blood cell instant detection wafer using dielectrophoretic force as described in claim 4, wherein the injection member comprises: a second injection tube connected to the micro flow channel; and a transfer tube connected to the injection tube. 6. The fragile red blood cell instant detection wafer using dielectrophoretic force as described in claim 1, wherein each of the electrodes has a width, and adjacent regions are arranged in parallel with each other. 25 200811438 7. If the red blood of the Langsei electrophoresis force described in the first paragraph of the application is applied, the wafer is further detected, and further includes a plurality of electrode lines, and the ends of the electrode lines are connected to the corresponding electrodes, and Each of the electrode lines is connected to an electrode external connection region. 8. The instant detection chip for brittle red blood cells using dielectrophoretic force as described in claim 1, wherein the material of the first substrate comprises glass, germanium wafer, acrylic, plastic, polymethyl methacrylate (PMMA) Or polydimethyl siloxane (PDMS). A 9: A brittle red blood cell instant detection wafer using dielectrophoretic force as described in claim 1 of the patent application, wherein the material of each electrode comprises gold, platinum, inscription or chromium. The invention relates to a method for detecting a wafer of a brittle red blood cell by using a dielectrophoretic force, comprising: a first substrate; at least one parallel array electrode disposed on the first substrate, wherein the parallel array electrode is composed of a plurality of electrodes, and The electrodes are arranged in parallel in the direction of the vertical microchannel; and the substrate having at least one microchannel is disposed on the first substrate and the microchannel passes through the parallel array electrode. 11. The fragile red blood cell instant detection wafer using dielectrophoretic force according to claim 10, further comprising at least two injection members disposed in the second substrate to allow liquid to enter and exit the flow channel. 12. The method of claim 1, wherein the injection member comprises: 26 200811438 two injection tubes connecting the microchannels; and a transfer tube connecting the injection tubes . 13) The method for detecting a wafer of a red blood cell using a dielectrophoretic force as described in the scope of the patent application, further comprising a plurality of electrode lines, one end of each of the electrode lines being connected to the corresponding one of the electrodes, and each of the electrodes The other end of the electrode line is connected to an electrode external connection region. 14·如申請專利範圍第1〇項所述之應用介電泳 性紅血球即時檢測晶片,其中該第—基板或該第二其之 材貝包括玻璃、石夕晶片、壓克力、塑膠、聚酸 醋(職A)或聚二甲基魏烧(pDMS)。丙純甲 15·如申請專利範圍第1〇項所述之應用介電 ^紅血球即時檢測晶片,其中該電極之材質包括黃金、白 金、銘或絡。 16·—種介電泳力脆性紅血球即時檢測之方法,包括· 提供㈣利申請朗第Μ項任 庫 φ , 一 m η個,其中m表示組數,11表示每一:^之 電極數目,且(母、、且之 注入一液體進入該微流道中;以及 對該些電極施加一電源訊號 二r極,相位差為2二=二 檢測的子進㈣離或是畴於電極_移動而達到 申π專利㈣第16項所述之介電泳力脆性紅血 27 200811438 球即時檢測之方法,复 電場偏極化之介電粒u些介電粒子包括電中性且可被 18·如申請專利範圍繁 … 性紅i球即時檢测之方、項所述之應用介電泳力之脆 膜之生物粒子、細的 f’其中該些介電粒子包括具細胞 物粒子。 母菌、血球、DNA或高分子聚合 19·如申請專利範園14. The application of a dielectrophoretic red blood cell instant detection wafer according to the first aspect of the patent application, wherein the first substrate or the second material comprises a glass, a stone wafer, an acrylic, a plastic, a polyacid. Vinegar (job A) or polydimethyl Wei (pDMS).丙纯甲15·Applicable to the application of dielectric ^ red blood cell instant detection wafer as described in the first paragraph of the patent application, wherein the electrode material comprises gold, platinum, Ming or network. 16·—A method for the immediate detection of brittle red blood cells by dielectrophoresis, including · providing (4) applying for the finite item φ, a m η, where m represents the number of groups, and 11 represents the number of electrodes of each: (mother, and inject a liquid into the microchannel; and apply a power signal to the electrodes to the r pole, the phase difference is 2 2 = the detection of the sub-input (four) or the domain _ movement to reach Shen π patent (4) Item 16 of the dielectrophoresis force brittle red blood 27 200811438 ball instant detection method, complex electric field polarized dielectric particles u some dielectric particles including electrical neutral and can be patented The range is complex... The real-time detection of the sexual red i-ball, the biological particles of the brittle membrane using the dielectrophoretic force, and the fine f', wherein the dielectric particles include cell particles. Mother bacteria, blood cells, DNA Or polymer polymerization 19·such as applying for a patent garden 性紅血球即時檢测之方、6項所述之應用介電泳力之脆 Vpp之交流電。 法其中該電源訊號包括6〜20The immediate detection of the red blood cells, the six applications of the dielectrophoretic force of the brittle Vpp AC. The power signal includes 6~20 2828
TW95131653A 2006-08-29 2006-08-29 Real-time hardened red blood cell detecting chip by using dielectrophoresis force TW200811438A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112334234A (en) * 2018-07-04 2021-02-05 罗伯特·博世有限公司 Device for dielectrophoretic trapping of particles

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112334234A (en) * 2018-07-04 2021-02-05 罗伯特·博世有限公司 Device for dielectrophoretic trapping of particles
US11975340B2 (en) 2018-07-04 2024-05-07 Robert Bosch Gmbh Device for dielectrophoretic capture of particles

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