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TW202217308A - Apparatus for accelerating and performing uniformly reaction of to-be-reacted substances and reactants contained in wettable substrate, system containing the apparatus, and coater - Google Patents

Apparatus for accelerating and performing uniformly reaction of to-be-reacted substances and reactants contained in wettable substrate, system containing the apparatus, and coater Download PDF

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TW202217308A
TW202217308A TW109137191A TW109137191A TW202217308A TW 202217308 A TW202217308 A TW 202217308A TW 109137191 A TW109137191 A TW 109137191A TW 109137191 A TW109137191 A TW 109137191A TW 202217308 A TW202217308 A TW 202217308A
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bottom plate
reactant
coating head
slit
wettable substrate
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TW109137191A
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TWI804766B (en
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王安邦
瞿嘉志
趙士懿
邱鴻年
陳俊安
張世宗
王貞仁
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國立臺灣大學
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Abstract

The present invention relates to an apparatus for accelerating and performing uniformly reaction of to-be-reacted substances and reactants contained in wettable substrate. The apparatus includes a machine body having a drainage plate for placing the wettable substrate and a coater configured on the top of the machine body, wherein the coater maintains a predetermined height for moving along the wettable substrate in horizon direction, and the coater has one or a plurality of slit. One end of the slit has an injection opening without limitation of arranged at the center of geometric symmetry, and the other end of the slits has a liquid discharge opening.

Description

使可潤濕基材上所含之被反應物與反應物加速並均勻反應之設備及含其之系統以及塗佈頭Equipment for accelerating and uniform reaction of reactants and reactants contained on wettable substrates, systems containing the same, and coating heads

本發明係關於一種加速可潤濕基材上反應之設備及系統,特別係可用於生化及免疫學反應試驗。The present invention relates to a device and system for accelerating reactions on wettable substrates, especially for biochemical and immunological reaction tests.

近年來生化檢測的市場需求持續上升且運用廣泛,其在醫檢方面之應用尤為顯著與重要。如何快速穩定的提供可靠的檢測結果則仍是一個多年尚未完全解決的課題;尤其爆發之新冠肺炎疫情,篩檢技術已成為世界各國公衛研發的首位目標之一。In recent years, the market demand for biochemical testing has continued to rise and it is widely used, and its application in medical testing is particularly significant and important. How to quickly and stably provide reliable test results is still a problem that has not been fully solved for many years; especially in the outbreak of the new crown pneumonia epidemic, screening technology has become one of the first goals of public health research and development in countries around the world.

許多快篩試片在追求低成本及快速搶攻市場之策略下,會藉由不斷改良試劑配方,以達到能完成快速篩檢疾病的目的。然而,在此策略下,常發生針對同一疾病而使用不同快篩試片,卻檢測出結果互相矛盾的情形,造成公衛上的防疫的困擾。Under the strategy of pursuing low cost and rapid market penetration, many rapid screening test tablets will continuously improve the reagent formula to achieve the purpose of rapid screening of diseases. However, under this strategy, it often happens that different rapid screening test pieces are used for the same disease, but the detection results are contradictory, which causes the problem of epidemic prevention in public health.

相較於快篩試片,實驗室篩檢方法的檢測結果雖可信度高,但操作上須耗費大量的時間及人力。以傳統西方墨點法為例,其前置準備作業繁瑣,且檢測時需使用相當量的抗體及試劑進行反應,反應等待時間長。倘若抗體濃度掌握不佳,造成背景值過高而無法分辨目標反應物,還則須重新進行檢測。Compared with the quick screening test piece, although the test results of the laboratory screening method are highly reliable, the operation requires a lot of time and manpower. Taking the traditional western blotting method as an example, its preparatory work is cumbersome, and a considerable amount of antibodies and reagents need to be used for the reaction, and the reaction time is long. If the antibody concentration is not well controlled, the background value is too high and the target reactant cannot be distinguished, and the detection must be repeated.

有鑒於上述缺點,本發明欲提供一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之設備,其包含塗佈頭及排液底板,二者藉由毛細力能減少試劑及反應物/被反應物(例如抗體)的用量、加速反應物及被反應物進行反應並減少反應時間,以改善習知篩檢須耗費大量的時間及人力。此外,本發明之設備可搭配系統模組及預先固定一或多種目標被反應物之試片,即時與客觀的提供有用的病況檢測資訊即受測者的病況發展與相對應臨床統計資訊,以協助醫事人員作出正確的診斷及處置。In view of the above-mentioned shortcomings, the present invention intends to provide a device for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate, which comprises a coating head and a liquid discharge bottom plate, both of which are provided by Capillary force can reduce the amount of reagents and reactants/reactants (such as antibodies), accelerate the reaction of reactants and reactants, and reduce the reaction time, so as to improve conventional screening tests, which require a lot of time and manpower. In addition, the device of the present invention can be matched with a system module and a test piece with one or more target reactants pre-fixed, so as to provide useful disease detection information, that is, the development of the patient's disease and the corresponding clinical statistical information in real time and objectively, to Assist medical personnel to make correct diagnosis and treatment.

是以,本發明之目的係提供一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之設備 ,其包含一機台本體及一塗佈頭。該機台本體具有供該可潤濕基材置放於上之一排液底板;該塗佈頭係設於該機台本體上方,並可維持一預設高度沿著該可潤濕基材以水平方向移動,該塗佈頭具有一或多個狹縫,該狹縫一端具有一注入開口,該狹縫的另一端具有一液體排出口。Therefore, the object of the present invention is to provide a device for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate, which comprises a machine body and a coating head. The machine body has a drain bottom plate for the wettable substrate to be placed on; the coating head is arranged above the machine body and can maintain a preset height along the wettable substrate Moving in the horizontal direction, the coating head has one or more slits, one end of the slit has an injection opening, and the other end of the slit has a liquid discharge port.

進一步地,該可潤濕基材可為多孔性材質。Further, the wettable substrate may be a porous material.

進一步地,該設備更包含一吸力產生裝置,該吸力產生裝置係連接於該排液底板,提供該可潤濕基材一負壓。Further, the apparatus further includes a suction generating device, which is connected to the drainage bottom plate to provide a negative pressure to the wettable substrate.

進一步地,該排液底板係一多孔性材質或一非多孔性材質,且當該排液底板為該非多孔性材質,該排液底板於其表面設有微流道。Further, the drain bottom plate is made of a porous material or a non-porous material, and when the liquid drain bottom plate is made of the non-porous material, the liquid drain bottom plate is provided with micro-channels on its surface.

進一步地,該微流道之溝槽深度具一梯度(gradient)。Further, the groove depth of the microchannel has a gradient.

進一步地,該排液底板下方進一步設有一震盪器。Further, an oscillator is further provided below the liquid discharge bottom plate.

進一步地,該排液底板與該吸力產生裝置之間進一步設有一廢液儲存槽。Further, a waste liquid storage tank is further provided between the liquid discharge bottom plate and the suction generating device.

進一步地,該塗佈頭進一步可與一清洗液儲存槽直接連接。Further, the coating head can be further directly connected to a cleaning liquid storage tank.

進一步地,該狹縫之兩側係非平行。Further, both sides of the slit are non-parallel.

進一步地,該排液底板的至少一側邊具有一塗佈準備區。Further, at least one side of the drain bottom plate has a coating preparation area.

本發明之另一目的係提供一種快速標定一被反應物之系統,其包含本發明之設備,以及一光學影像擷取分析模組。Another object of the present invention is to provide a system for rapidly calibrating a reactant, which includes the device of the present invention and an optical image capturing and analysis module.

進一步地,該光學影像擷取分析模組包含一攝像機,該攝像機可為CCD或CMOS等感光元件模組。Further, the optical image capturing and analyzing module includes a camera, and the camera can be a photosensitive element module such as CCD or CMOS.

進一步地,該系統包含與一預先固定一或多種目標被反應物之試片搭配使用。Further, the system includes use with a test strip pre-fixed with one or more target reactants.

進一步地,該系統包含一非暫態機器可讀媒體,其儲存一程式用以判讀該試片經反應後之結果,該非暫態機器可讀媒體可選自任一項或二種以上由以下模組所組成之群組:一影像判讀模組、一定量模組、一參照資料庫模組及一比對模組。該影像判讀用以判讀該試片經反應後之影像;該定量模組用以定量該試片之目標被反應物之含量;該參照資料庫模組係儲存該試片之該目標被反應物之檢測圖譜及相關臨床症狀;該比對模組係用以將該影像與檢測圖譜進行比對,以確定該試片反應後之結果。Further, the system includes a non-transitory machine-readable medium, which stores a program for interpreting the result of the test strip after the reaction, and the non-transitory machine-readable medium can be selected from any one or two or more from the following: A group composed of modules: an image interpretation module, a certain amount of modules, a reference database module and a comparison module. The image interpretation is used to interpret the reacted image of the test piece; the quantitative module is used to quantify the content of the target reactant of the test piece; the reference database module is used to store the target reactant of the test piece The detection map and related clinical symptoms; the comparison module is used to compare the image with the detection map to determine the result after the test piece reacts.

本發明之另一目的係提供一塗佈頭,其具有一或多個狹縫,該狹縫一端具有一無需限制置於幾何對稱中心的注入開口,該狹縫的另一端具有一液體排出口。於較佳實施態樣,該狹縫之兩側係非平行。Another object of the present invention is to provide a coating head, which has one or more slits, one end of the slit has an injection opening located at the center of geometric symmetry without restriction, and the other end of the slit has a liquid discharge port . In a preferred embodiment, the two sides of the slit are non-parallel.

相較於先前技術,本發明之優勢為:Compared with the prior art, the advantages of the present invention are:

本發明之設備,搭配係本發明之塗佈頭並可視需要為手動或電動方式移動,並可搭配不同材質及設計的排液底板並視需求搭配該吸力產生裝置,透過加裝震盪器等方式,降低所需之操作時間。The equipment of the present invention is matched with the coating head of the present invention and can be moved manually or electrically as needed, and can be matched with liquid discharge bottom plates of different materials and designs and matched with the suction generating device as required, by adding an oscillator or the like. , reducing the required operating time.

本發明之系統利於一站式快速完成篩檢及呈像,能作為具有高精準度及高效的生醫檢測系統,不同於習知的西方墨點法進行時需要多站式、長時間且耗人力;此外,系統搭配的試片及非暫態機器可讀媒體中的參照資料庫中因存有檢測圖譜對應的相關臨床症狀,取代目前僅有單項被反應物單純判斷是否有感染的快篩。因此,本發明之系統能利於在各種情況下,能夠即時與客觀的提供有用的病況檢測資訊,即受測者的病況發展與相對應臨床統計資訊,以協助醫事人員作出正確的診斷及處置。The system of the present invention facilitates one-stop rapid screening and imaging, and can be used as a biomedical detection system with high accuracy and efficiency, which is different from the conventional western ink dot method, which requires multi-station, long time and time-consuming. manpower; in addition, the test strips matched with the system and the reference database in the non-transitory machine-readable media contain the relevant clinical symptoms corresponding to the detection pattern, replacing the current rapid screening that only judges whether there is infection by a single reactant. . Therefore, the system of the present invention can provide useful disease detection information in real time and objectively under various circumstances, that is, the development of the patient's disease and the corresponding clinical statistical information, so as to assist medical personnel to make correct diagnosis and treatment.

本發明之塗佈頭可設計為一或多個狹縫,且可不需額外的動力即可利用毛細力及重力,使液體平均往兩側及往下分散,且若為多個狹縫,可同時測試多種不同反應物是否能與可潤濕基材上吸附的被反應物反應,大幅提升檢測效率。The coating head of the present invention can be designed as one or more slits, and the capillary force and gravity can be used to disperse the liquid evenly to both sides and downward without additional power. Simultaneously test whether a variety of different reactants can react with the reactants adsorbed on the wettable substrate, which greatly improves the detection efficiency.

以下將參照所附圖式說明本發明之實施形態以敘述本發明。在圖式中,相同的元件符號表示相同的元件,並且為求清楚說明,元件之大小或厚度可能誇大顯示。Embodiments of the present invention will be described below to describe the present invention with reference to the accompanying drawings. In the drawings, the same reference numerals denote the same elements, and the size or thickness of the elements may be exaggerated for clarity of illustration.

本發明中,術語「可潤濕基材」係指生化或免疫反應中可吸附被反應物之膜,通常為多孔性,例如但不限於西方墨點法所使用的基材薄膜,材料可例如但不限於聚偏二氟乙烯膜(poly(vinylidene fluoride, PVDF)或硝化纖維膜(Nitrocellulose, NC)。In the present invention, the term "wettable substrate" refers to a membrane that can adsorb reactants in biochemical or immune reactions, usually porous, such as but not limited to the substrate film used in Western blotting. The material can be, for example, But not limited to poly(vinylidene fluoride, PVDF) or nitrocellulose (Nitrocellulose, NC).

本發明中,術語「被反應物」係指吸附或固定於可潤濕基材的標靶物質(例如但不限於抗體或抗原、組織細胞等),供後續與其對應之抗原或抗體或其他可與其交互反應之另一化學物質作用。「反應物」係指藉由塗佈頭塗佈至該可潤濕基材而能與該附著於可潤濕基材上之標靶物質相互作用者(例如但不限於抗原或抗體、藥物、病原體、體液、環境收集液等)。In the present invention, the term "reactant" refers to a target substance (such as but not limited to antibodies or antigens, tissue cells, etc.) adsorbed or immobilized on a wettable substrate for subsequent antigens or antibodies or other The effect of another chemical substance with which it interacts. "Reactant" refers to a substance (such as, but not limited to, antigens or antibodies, drugs, drugs, pathogens, body fluids, environmental collection fluids, etc.).

本發明中,吸力產生裝置包括「負壓真空裝置」與具毛細力之吸液材料等;「吸力產生裝置」係指會產生負壓的裝置,該負壓可產生抽取力抽取液體。由於抽取力方向及塗佈頭塗佈方向不平行,因此會產生一強制對流,迫使塗佈在有孔性材質上的反應物往被反應物方向移動。In the present invention, the suction generating device includes a "negative pressure vacuum device" and a liquid absorbing material with capillary force; the "suction generating device" refers to a device that generates a negative pressure, which can generate a suction force to extract the liquid. Since the direction of the extraction force and the coating direction of the coating head are not parallel, a forced convection is generated, forcing the reactant coated on the porous material to move toward the direction of the reactant.

如圖1至4所示,本發明之一實施態樣為一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之設備,其包含一機台本體1、一塗佈頭2及一吸力產生裝置3;該機台本體1具有供該可潤濕基材M置放於上之一排液底板101,該塗佈頭2係設於該機台本體1上方,並可維持一預設高度沿著該可潤濕基材M以水平方向移動;如圖2及3所示,該塗佈頭2可具有一或多個狹縫201,該狹縫201一端具有一注入開口202,該狹縫201的另一端具有一液體排出口203,且該狹縫201之兩側係非平行;如圖1所示,該吸力產生裝置3係連接於該排液底板101(經管線P連通),提供該可潤濕基材M一向下吸力。As shown in FIGS. 1 to 4 , an embodiment of the present invention is an apparatus for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate, which includes a machine body 1 , a coating head 2 and a suction generating device 3; the machine body 1 has a liquid discharge bottom plate 101 for the wettable substrate M to be placed on, and the coating head 2 is arranged on the machine body 1, and can maintain a preset height to move in a horizontal direction along the wettable substrate M; as shown in FIGS. 2 and 3, the coating head 2 can have one or more slits 201, the slits One end of 201 has an injection opening 202, the other end of the slit 201 has a liquid discharge port 203, and both sides of the slit 201 are non-parallel; as shown in FIG. 1, the suction generating device 3 is connected to the row The liquid bottom plate 101 (connected via line P) provides a downward suction for the wettable substrate M.

本發明之設備於塗佈時,視需要可任意採人工方式利用定量工具或採電動方式以注射幫浦,將反應物注入該塗佈頭2,即從該注入開口202進入到該狹縫201中;該反應物藉由毛細力、重力及慣性力,在該液體排出口203及該可潤濕基材M之間自然形成液橋;當該塗佈頭2水平方向移動時,利用反應物的黏滯力、毛細力、重力及慣性力間的平衡,可將該反應物的液橋橫向拉出進行塗佈。一般認為塗佈頭2需要在兩平板內形成導流結構,才能使注入之液體往下流動;然而,經發明人實驗發現,該塗佈頭2只需要以兩平板形成狹縫201,且較佳該狹縫201之兩側非平形,則可不需額外的動力(例如注射幫浦提供動力),即可利用毛細力及重力,使液體平均往兩側及往下分散。於圖1的實施態樣中,包含了吸力產生裝置3可進一步縮短反應時間並降低非專一性結合所導致的雜訊,但經實驗,於另一實施態樣中,可以省略下方的吸力產生裝置3,塗佈頭2內的反應物仍可藉由毛細力及重力即使液體可平均往兩側及往下分散,平均分佈於1吸附有被反應物之可潤濕基材M之上。When the apparatus of the present invention is used for coating, if necessary, a quantitative tool or an electric injection pump can be used arbitrarily to inject the reactant into the coating head 2, that is, from the injection opening 202 to the slit 201. In; the reactant naturally forms a liquid bridge between the liquid discharge port 203 and the wettable substrate M by capillary force, gravity and inertial force; when the coating head 2 moves horizontally, the reactant is used The balance between the viscous force, capillary force, gravity and inertia force of the reactant can be pulled out of the liquid bridge of the reactant laterally for coating. It is generally believed that the coating head 2 needs to form a diversion structure in the two flat plates so that the injected liquid can flow downward; however, the inventor's experiment found that the coating head 2 only needs to form the slit 201 with the two flat plates, and it is relatively If the two sides of the slit 201 are not flat, the capillary force and gravity can be used to disperse the liquid evenly to both sides and downward without additional power (such as the power provided by an injection pump). In the embodiment of FIG. 1, the suction generating device 3 is included to further shorten the reaction time and reduce the noise caused by non-specific binding, but through experiments, in another embodiment, the lower suction generation can be omitted. In the device 3, the reactants in the coating head 2 can still be distributed evenly on the wettable substrate M on which the reactants are adsorbed by capillary force and gravity even though the liquid can be evenly dispersed to both sides and downwards.

該塗佈頭2可以有一或多個狹縫,圖3之塗佈頭2顯示僅有一個狹縫201,狹縫201之側面位置有一注入開口202,下方有液體排出口203,該注入開口202並無需限制在幾何對稱中心,即無特別位置限定,雖然圖中顯示注入開口202位於塗佈頭2之側面位置,但該注入開口202只要能使液體流通至狹縫201即可,因此也可設置於塗佈頭2上方或側方表面等;又該液體排出口203係在塗佈頭2之狹縫201下方形成整面的開口,以使塗佈頭2內的反應物可均勻的塗佈於可潤濕基材M之上;圖2之塗佈頭2之態樣則為多個狹縫201,該多個狹縫201為獨立的通道彼此不連通,每個狹縫201上端均有一注入開口202,每個狹縫201下端均有一液體排出口203,由於該多個狹縫201彼此不連通,因此可在每個注入口202注入不同的反應物,故可於一次的反應中,測試多種不同反應物是否能與可潤濕基材M上吸附的被反應物反應,大幅提升檢測效率。The coating head 2 may have one or more slits. The coating head 2 shown in FIG. 3 has only one slit 201. The side of the slit 201 has an injection opening 202 and a liquid discharge port 203 below. The injection opening 202 It does not need to be limited to the center of geometric symmetry, that is, there is no special position limitation. Although the drawing shows that the injection opening 202 is located at the side of the coating head 2, the injection opening 202 only needs to enable the liquid to flow to the slit 201, so it can also be used. Set on the top of the coating head 2 or on the side surface, etc.; and the liquid discharge port 203 forms an entire opening under the slit 201 of the coating head 2, so that the reactants in the coating head 2 can be uniformly coated. cloth on the wettable substrate M; the state of the coating head 2 in FIG. 2 is a plurality of slits 201, the plurality of slits 201 are independent channels that are not connected to each other, and the upper end of each slit 201 is There is an injection opening 202, and the lower end of each slit 201 has a liquid discharge port 203. Since the plurality of slits 201 are not communicated with each other, different reactants can be injected into each injection port 202, so that one reaction can be performed in one reaction. , testing whether a variety of different reactants can react with the reactants adsorbed on the wettable substrate M, greatly improving the detection efficiency.

本發明設備中,該塗佈頭2可藉由手動或自動方式進行水平方向移動。如圖1所示,本發明之一實施態樣為,本發明之設備可進一步包含一清洗液儲存槽5,該塗佈頭2係連接至該清洗液儲存槽5,該塗佈頭2可藉由該清洗液儲存槽5下方的滑軌6進行水平方向移動,該滑軌6的驅動力可來自電動馬達或人工手動操作,本發明並不予以限制滑軌6之設置位置及驅動方式。較簡便且具彈性,該塗佈頭2為手動方式進行水平方向移動,省去水平位移電動馬達及周邊控制輔助系統設備,以降低成本並增加操作便捷性。In the apparatus of the present invention, the coating head 2 can be moved in the horizontal direction manually or automatically. As shown in FIG. 1 , in one embodiment of the present invention, the apparatus of the present invention may further comprise a cleaning liquid storage tank 5 , the coating head 2 is connected to the cleaning liquid storage tank 5 , and the coating head 2 can The sliding rail 6 under the cleaning liquid storage tank 5 is moved horizontally. The driving force of the sliding rail 6 can come from an electric motor or manual operation. The present invention does not limit the setting position and driving method of the sliding rail 6 . Simple and flexible, the coating head 2 is manually moved in the horizontal direction, eliminating the need for a horizontal displacement electric motor and peripheral control auxiliary system equipment, thereby reducing costs and increasing operational convenience.

本發明之設備的另一實施態樣如圖4所示,本發明設備中,該塗佈頭2可藉由手動或自動方式在該可潤濕基材M上進行水平方向塗佈,而後輔以手動或自動方式將該可潤濕基材M移至一搖動清洗槽、一超音波清洗槽或一光學影像擷取分析模組周邊輔助系統設備,以降低成本並增加操作便捷性。Another embodiment of the apparatus of the present invention is shown in FIG. 4 . In the apparatus of the present invention, the coating head 2 can perform horizontal coating on the wettable substrate M by manual or automatic methods, and then auxiliary The wettable substrate M is manually or automatically moved to a shaking cleaning tank, an ultrasonic cleaning tank, or a peripheral auxiliary system equipment of an optical image capture and analysis module to reduce costs and increase operational convenience.

本發明之設備中,該排液底板101係指可供放置上述該可潤濕基材M的基板,該排液底板101之材料可為多孔性材質或非多孔性材質;如該排液底板101為多孔性材質(例如陶瓷、泡棉、紙、多孔纖維等),則該排液底板101因其多孔而具有向下吸引作用,可將該可潤濕基材M上含反應物之液體向下吸引,抑制反應物橫向擴散,促進反應物及被反應物持續產生動態反應,同時減少塗佈後所需等待反應之時間;如該排液底板101為非多孔性材質,則其材料可例如玻璃、金屬、壓克力、聚合物、矽膠、塑料或其等之組合等,且較佳實施態樣中,則該排液底板101可如圖5至7所示,該排液底板101為具有該微流道1011;該微流道1011細小而具毛細力,且於較佳實施態樣中,其微流道1011之溝槽深度具有一梯度(換言之,溝槽深度可由淺至深或由深至淺),提供該微流道101內的液體可因毛細力高低差而流動,而相對低處係位在具有該排液口1012之一端,該排液口1012係用以將液體排出,其中該排液口1012可為一或二個以上,如圖5所示,具有二個排液口1012;在另一實施態樣,該排液口1012可連接吸力產生裝置;較佳地,該排液口1012係設置在該微流道1011之溝槽深度的低處;較佳地,該塗佈頭2在塗佈時,係由該微流道1011之溝槽深度的高處往低處方向進行塗佈;藉由毛細力及流道的高低差,該微流道1011中的液體流動時具方向性(即朝具有該排液口1012之一端流動),不僅可便於收集流下的液體外,此液體流動的方向性亦可驅使該可潤濕基材M上的反應物之液體被向下吸引。進一步地,當該排液底板101搭配該吸力產生裝置3所產生的負壓時,具有抽吸力,即可加乘此向下吸引作用,更進一步加速反應物及被反應物的反應時間。In the apparatus of the present invention, the drain bottom plate 101 refers to a substrate on which the wettable substrate M can be placed, and the material of the drain bottom plate 101 can be a porous material or a non-porous material; for example, the drain bottom plate 101 is a porous material (such as ceramics, foam, paper, porous fibers, etc.), then the drainage bottom plate 101 has a downward suction effect due to its porousness, and can wet the liquid containing the reactant on the substrate M. Suction downward, inhibit the lateral diffusion of the reactants, promote the continuous dynamic reaction of the reactants and the reactants, and reduce the waiting time for the reaction after coating; if the drain bottom plate 101 is a non-porous material, the material can For example, glass, metal, acrylic, polymer, silicone, plastic or a combination thereof, etc., and in a preferred embodiment, the drain bottom plate 101 can be as shown in FIGS. 5 to 7 , the drain bottom plate 101 It has the micro-channel 1011; the micro-channel 1011 is small and has capillary force, and in a preferred embodiment, the groove depth of the micro-channel 1011 has a gradient (in other words, the groove depth can be from shallow to deep (or from deep to shallow), the liquid in the microchannel 101 can flow due to the difference in capillary force, and the relatively low part is located at one end with the liquid discharge port 1012, and the liquid discharge port 1012 is used to Liquid discharge, wherein the liquid discharge port 1012 can be one or more than two, as shown in FIG. 5, there are two liquid discharge ports 1012; in another embodiment, the liquid discharge port 1012 can be connected to a suction generating device; Preferably, the liquid discharge port 1012 is disposed at the lower part of the groove depth of the micro-channel 1011; Coating is carried out in the direction from high to low; due to the capillary force and the height difference of the flow channel, the liquid in the micro-channel 1011 flows in a directional direction (that is, it flows towards the end with the liquid discharge port 1012), which not only can In addition to facilitating the collection of the flowing liquid, the directionality of the liquid flow can also drive the liquid of the reactant on the wettable substrate M to be attracted downward. Further, when the drainage bottom plate 101 is matched with the negative pressure generated by the suction force generating device 3, it has a suction force, which can be multiplied by the downward suction effect, thereby further accelerating the reaction time of the reactants and the reacted objects.

於較佳實施例中,該排液底板101較佳亦可為非多孔性材質。該排液底板101為多孔性材質(例如泡棉、紙、多孔性纖維、金屬網等)之時,由於該多孔性材質本身具有孔隙故具有吸力,則該排液底板101整體持續吸收該可潤濕基材M上的液體,可潤濕基材M無法保持一定的濕潤度,故若未及時處理,恐影響後續判讀結果;此外,該多孔性材質的孔隙容易有反應物殘留,無法清洗後重複使用;雖然如此,多孔性材質之排液底板101仍可用於拋棄性且可即時判讀的反應程序中。相較之下,該排液底板101為非多孔性材質之時,如圖5至7所示,由於該微流道1011係藉由毛細力及梯度高低差,將反應物之液體流向該排液口1012後排出,該排液底板101整體不具孔隙故並不會快速吸收該可潤濕基材M上含反應物之液體,因此不會發生可潤濕基材M濕潤度不足的狀況(即維持在含有液體但液體不會消失太快的狀態),此外,該非多孔性材質之排液底板101可清洗後重複使用更具環保概念。因此,該排液底板101也可視使用者需求選用其適宜的材質、或做成可拆解模組以方便裝置及更換。另外,如圖2所示,該排液底板101可進一步設置一塗佈準備區1013,該塗佈頭2可由該塗佈準備區1013形成穩定液橋後,再水平移動至該可潤濕基材M上進行塗佈,以維持設定之塗佈間距、並避免塗佈頭2直接接觸可潤濕基材M產生污染。該塗佈準備區1013可以係與該排液底板101一體成型所完成、或額外設置該塗佈準備區1013於該排液底板101所完成。In a preferred embodiment, the drain bottom plate 101 can also preferably be made of non-porous material. When the drainage bottom plate 101 is made of a porous material (such as foam, paper, porous fiber, metal mesh, etc.), since the porous material itself has pores and thus has suction, the drainage bottom plate 101 as a whole continues to absorb the liquid. Wetting the liquid on the substrate M, the wettable substrate M cannot maintain a certain degree of wetness, so if it is not treated in time, it may affect the subsequent interpretation results; in addition, the pores of the porous material are prone to residual reactants, which cannot be cleaned. It can be reused afterward; however, the drainage bottom plate 101 made of porous material can still be used in a disposable and instantly interpretable reaction procedure. In contrast, when the liquid discharge bottom plate 101 is made of non-porous material, as shown in FIGS. 5 to 7 , because the microfluidic channel 1011 uses capillary force and gradient height difference, the liquid of the reactant flows to the discharge After the liquid port 1012 is discharged, the liquid drain bottom plate 101 has no pores as a whole, so it will not quickly absorb the liquid containing the reactant on the wettable substrate M, so the wettability of the wettable substrate M will not be insufficient. That is, it is maintained in a state of containing liquid but the liquid does not disappear too quickly). In addition, the non-porous material of the drain bottom plate 101 can be cleaned and reused, which is more environmentally friendly. Therefore, the drain bottom plate 101 can also be made of suitable materials according to the needs of the user, or can be made into a disassembled module for convenient installation and replacement. In addition, as shown in FIG. 2 , a coating preparation area 1013 can be further set on the liquid discharge bottom plate 101 , and the coating head 2 can be moved horizontally to the wettable base after forming a stable liquid bridge in the coating preparation area 1013 . Coating is performed on the material M to maintain the set coating spacing and to prevent the coating head 2 from directly contacting the wettable substrate M and causing contamination. The coating preparation area 1013 may be formed integrally with the drain bottom plate 101 , or the coating preparation area 1013 may be additionally disposed on the drain bottom plate 101 .

本發明設備之進一步實施態樣為該設備更包含一震盪器102、一廢液儲存槽4;如圖1所示,該震盪器102係設置於該排液底板101下方;該廢液儲存槽4係設在該排液底板101與該吸力產生裝置3之間,並有管線P連接;該清洗液儲存槽5係連接該塗佈頭2,該滑軌6係設至於該清洗液儲存槽5的下方。本實施態樣之設備可清洗該可潤濕基材M,即當反應完成後,透過塗佈頭2將該清洗液儲存槽5中的清洗液塗佈至該可潤濕基材M,該排液底板101的該微流道1011可適當維持該可潤濕基材M濕潤並充滿清洗液,於此同時,該震盪器102即藉由震動以清洗該可潤濕基材M,去除多餘反應物。習知的實驗室清洗操作(例如西方墨點法)在清洗多餘反應物時,係將該可潤濕基材M移至於洗液盒內浸泡,以自然擴散輔以外加搖晃,並重複執行多次而達到清洗目的,過程耗費人力且冗長。相較下,本實施態樣之設備在清洗時無須移動該可潤濕基材M即可完成清洗,不僅避免該可潤濕基材M因移動而損害的風險,且震動清洗的清洗效果優於自然擴散及晃動。此外,當該排液底板101係使用非多孔性材質時,該微流道1011能使該可潤濕基材M上下兩端之壓力差在抽液時有較均勻地分布,以達到最少清洗液卻能最有效均勻的清洗效果,從而降低所需之操作時間。A further embodiment of the apparatus of the present invention is that the apparatus further includes an oscillator 102 and a waste liquid storage tank 4; as shown in FIG. 1 , the oscillator 102 is disposed under the drainage bottom plate 101; 4 is arranged between the drain bottom plate 101 and the suction generating device 3, and is connected with a pipeline P; the cleaning fluid storage tank 5 is connected to the coating head 2, and the slide rail 6 is arranged to the cleaning fluid storage tank 5 below. The apparatus of this embodiment can clean the wettable substrate M, that is, after the reaction is completed, the cleaning solution in the cleaning solution storage tank 5 is applied to the wettable substrate M through the coating head 2, and the The micro-channels 1011 of the drain bottom plate 101 can properly keep the wettable substrate M wet and filled with cleaning solution. At the same time, the oscillator 102 cleans the wettable substrate M by vibrating to remove excess Reactant. When cleaning excess reactants in conventional laboratory cleaning operations (eg, Western blotting method), the wettable substrate M is moved to a lotion box for immersion, with natural diffusion supplemented by shaking, and repeated for many times. In order to achieve the purpose of cleaning, the process is labor-intensive and lengthy. In contrast, the apparatus of this embodiment can complete the cleaning without moving the wettable substrate M during cleaning, which not only avoids the risk of damage to the wettable substrate M due to movement, but also has an excellent cleaning effect for vibration cleaning. Naturally spread and shake. In addition, when the drainage bottom plate 101 is made of non-porous material, the micro-channel 1011 can make the pressure difference between the upper and lower ends of the wettable substrate M more evenly distributed during pumping, so as to achieve minimal cleaning The liquid can provide the most effective and uniform cleaning effect, thereby reducing the required operating time.

較佳地,該震盪器102為超音波震盪器,可於清洗該可潤濕基材M之過程中自動啟動,以每秒幾萬次的快速橫向相對運動,達到提升清洗效果及大幅縮減清洗時間之功用。藉由該排液底板101及該震盪器102之組合,利於該可潤濕基材M在短時間內有效完成清洗,且抑制檢測結果信號中的背景雜訊而提高系統功能,使信號更清晰。較佳地,本發明此一實施態樣之設備係利用排液底板1011及超音波震盪器102之組合,可以在短時間內有效完成清洗,在信號呈現方面背景的雜訊能夠有效地抑制,因此能提高系統功能使信號更清晰。Preferably, the oscillator 102 is an ultrasonic oscillator, which can be automatically activated in the process of cleaning the wettable substrate M, and can perform relatively fast lateral movements of tens of thousands of times per second, so as to improve the cleaning effect and greatly reduce the amount of cleaning. function of time. By the combination of the draining bottom plate 101 and the oscillator 102, the wettable substrate M can be cleaned effectively in a short time, and the background noise in the detection result signal is suppressed to improve the system function and make the signal clearer . Preferably, the apparatus of this embodiment of the present invention utilizes the combination of the drain bottom plate 1011 and the ultrasonic oscillator 102, which can effectively complete the cleaning in a short period of time, and can effectively suppress the background noise in terms of signal presentation. Therefore, the system function can be improved to make the signal clearer.

使用本發明之設備進行西方墨點法可獲得強的偵測信號;如圖8所示,當反應物分別為嚴重急性呼吸道症候群新冠狀病毒核衣殼蛋白 (SARS-CoV-2 NP)、嚴重急性呼吸道症候群冠狀病毒核衣殼蛋白 (SARS-CoV NP)、中東呼吸症候群冠狀病毒核衣殼蛋白(MERS-CoV NP)及人類冠狀病毒NL63核衣殼蛋白(HCoV-NL63),左圖係使用習知西方墨點法的實驗結果,偵測信號有雜訊及不清晰;相較之下,右圖係使用本發明之設備的實驗結果,偵測信號無雜訊及清晰。Using the equipment of the present invention to perform western blotting method can obtain a strong detection signal; as shown in Figure 8, when the reactants are severe acute respiratory syndrome new coronavirus nucleocapsid protein (SARS-CoV-2 NP), severe acute respiratory syndrome Acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV NP), Middle East respiratory syndrome coronavirus nucleocapsid protein (MERS-CoV NP) and human coronavirus NL63 nucleocapsid protein (HCoV-NL63), the left picture is used The experimental results of the conventional western ink dot method show that the detected signals are noisy and unclear. In contrast, the right picture shows the experimental results using the device of the present invention, and the detected signals are noise-free and clear.

本發明另一方面係提供一種快速標定一被反應物之系統,係包含本發明之設備及一光學影像擷取分析模組。該光學影像擷取分析模組包含一攝像機,可用以擷取及呈像本發明之設備所完成的檢測(如西方墨點法)實驗結果;該光學影像擷取分析模組亦可包含一激發光源、一濾鏡,其擷取的影像信號可包含冷光、UV光、螢光及可見光,本發明並不予以限定。本發明之系統利於一站式快速完成篩檢及呈像,能作為具有高精準度及高效的生醫檢測系統,不同於習知的西方墨點法進行時需要多站式、長時間且耗人力。Another aspect of the present invention is to provide a system for rapidly calibrating a reactant, which includes the apparatus of the present invention and an optical image capture and analysis module. The optical image capture and analysis module includes a camera, which can be used to capture and display the experimental results of the detection (such as Western ink dot method) completed by the apparatus of the present invention; the optical image capture and analysis module may also include an excitation The light source and a filter, the captured image signal can include cold light, UV light, fluorescent light and visible light, which is not limited in the present invention. The system of the present invention facilitates one-stop rapid screening and imaging, and can be used as a biomedical detection system with high accuracy and efficiency, which is different from the conventional western ink dot method, which requires multi-station, long time and time-consuming. manpower.

所述的攝像機可包含CCD或CMOS等,本發明並不予以限制。The camera may include CCD or CMOS, etc., which is not limited in the present invention.

進一步地,本發明之系統可包含與一預先固定一或多種目標被反應物之試片搭配使用,該試片即係可用於本發明之設備的可潤濕基材M,由於該試片已預先固定一或多種目標被反應物,當欲檢測含有未知反應物的樣本時,即可快速完成快篩檢測。較佳地,該試片係預先固定有多種目標被反應物,因具有多種被反應物的試片,所呈現出的檢測圖譜(例如西方墨點法的實驗結果),可取代習知僅係檢測某單一被反應物而判斷是否有感染的快篩。Further, the system of the present invention can be used in conjunction with a test piece pre-fixed with one or more target reactants, which is the wettable substrate M that can be used in the apparatus of the present invention, since the test piece has been One or more target reactants are pre-fixed, and quick screening can be completed quickly when samples containing unknown reactants are to be detected. Preferably, the test strip is pre-fixed with a variety of target reactants, because the test strip with a variety of reactants presents a detection pattern (for example, the experimental results of the Western blotting method), which can replace the conventional system only. A rapid screening for detecting a single reactant to determine whether there is an infection.

進一步地,本發明之系統可包含一非暫態機器可讀媒體,其儲存一程式用以判讀該試片經反應後之結果,該非暫態機器可讀媒體係選自任一項或二種以上由以下模組所組成之群組:一影像判讀、一定量模組、一參照資料庫模組及一比對模組。該影像判讀及定量模組係用以判讀該試片經反應後之影像。定量模組係用以定量該試片之目標被反應物之含量。該參照資料庫係儲存該試片之該目標被反應物之檢測圖譜及相關臨床症狀。該比對模組係用以將該影像與檢測圖譜進行比對,以確定該試片反應後之結果。具體而言,透過分子生物學與血清學的設計與選擇,可設計出具有不同檢測反應物圖譜之試片;當該試片使用本發明之設備完成反應後,可經由該非暫態機器可讀媒體的該程式進行判讀。藉由該影像判讀及定量模組判讀該試片之該影像後,該比對模組會將該影像與儲存在該參照資料庫的該檢測圖譜進行比對,得到檢測結果。此外,參照資料庫中因存有檢測圖譜對應的相關臨床症狀,若經比對後發現該影像及該檢測圖譜中有相同的結果,亦可對照相關臨床症狀,取代目前僅有單項被反應物單純判斷是否有感染的快篩。因此,藉由本發明之系統能利於在各種情況下,能夠即時與客觀的提供有用的病況檢測資訊即受測者的病況發展與相對應臨床統計資訊,以協助醫事人員作出正確的診斷及處置。Further, the system of the present invention may include a non-transitory machine-readable medium, which stores a program for interpreting the result of the test strip after the reaction, the non-transitory machine-readable medium is selected from any one or two kinds The above is a group consisting of the following modules: an image interpretation, a certain amount of modules, a reference database module and a comparison module. The image interpretation and quantification module is used for interpreting the image of the test piece after reaction. The quantitative module is used to quantify the content of the target reactant of the test piece. The reference database stores the detection pattern and related clinical symptoms of the target reactant of the test piece. The comparison module is used to compare the image with the detection map to determine the result after the test piece reacts. Specifically, through the design and selection of molecular biology and serology, test strips with different detection reactant profiles can be designed; when the test strips are reacted with the device of the present invention, they can be read by the non-transitory machine. The program of the media is interpreted. After the image of the test piece is interpreted by the image interpretation and quantification module, the comparison module compares the image with the detection map stored in the reference database to obtain detection results. In addition, since there are relevant clinical symptoms corresponding to the test pattern in the reference database, if the image and the test pattern have the same results after comparison, the relevant clinical symptoms can also be compared to replace the current only single reactant. A quick screening for simply judging whether there is an infection. Therefore, the system of the present invention can provide useful disease detection information, ie, the development of the subject's disease and corresponding clinical statistical information, in a real-time and objective manner in various situations, so as to assist medical personnel to make correct diagnosis and treatment.

上列詳細說明係針對本發明之一可行實施例之具體說明,惟該實施例並非用以限制本發明之專利範圍,凡未脫離本發明技藝精神所為之等效實施或變更,均應包含於本發明之專利範圍中。The above detailed description is a specific description of a feasible embodiment of the present invention, but this embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the technical spirit of the present invention shall be included in the within the scope of the patent of the present invention.

1:機台本體 101:排液底板 102:震盪器 1011:微流道 1012:排液口 1013:塗佈準備區 2:塗佈頭 201:狹縫 202:注入開口 203:液體排出口 3:吸力產生裝置 4:廢液儲存槽 5:清洗液儲存槽 6:滑軌 M:可潤濕基材 P:管線 1: Machine body 101: Drain bottom plate 102: Oscillator 1011: Microfluidics 1012: Drain port 1013: Coating Preparation Area 2: Coating head 201: Slit 202: Injection opening 203: Liquid discharge port 3: Suction generating device 4: Waste liquid storage tank 5: Cleaning fluid storage tank 6: Slide rail M: Wettable substrate P: Pipeline

圖1是本發明之一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之設備(一)的外觀示意圖。FIG. 1 is a schematic appearance diagram of an apparatus (1) of the present invention for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate.

圖2係本發明之設備的塗佈頭及排液底板的外觀示意圖。FIG. 2 is a schematic view of the appearance of the coating head and the liquid discharge bottom plate of the apparatus of the present invention.

圖3係本發明之設備的塗佈頭的斜側視圖。Figure 3 is an oblique side view of the coating head of the apparatus of the present invention.

圖4係本發明之一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之塗佈設備(二)外觀示意圖。4 is a schematic diagram of the appearance of a coating apparatus (2) of the present invention for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate.

圖5係本發明之非多孔性材質的排液底板(一)的外觀示意圖。FIG. 5 is a schematic view of the appearance of the non-porous material drainage bottom plate (1) of the present invention.

圖6係本發明之非多孔性材質的排液底板(二)的外觀示意圖。FIG. 6 is a schematic appearance diagram of the non-porous material drainage bottom plate (2) of the present invention.

圖7係本發明之非多孔性材質的排液底板(三)的外觀示意圖。FIG. 7 is a schematic view of the appearance of the non-porous material drainage bottom plate (3) of the present invention.

圖8係西方墨點法的實驗結果圖:右圖係使用本發明之設備完成;左圖係使用習知西方墨點法完成。Figure 8 is a graph of the experimental results of the western ink dot method: the right picture is completed by the equipment of the present invention; the left picture is completed by the conventional western ink dot method.

1:機台本體 1: Machine body

101:排液底板 101: Drain bottom plate

102:震盪器 102: Oscillator

2:塗佈頭 2: Coating head

3:吸力產生裝置 3: Suction generating device

4:廢液儲存槽 4: Waste liquid storage tank

5:清洗液儲存槽 5: Cleaning fluid storage tank

6:滑軌 6: Slide rail

P:管線 P: Pipeline

Claims (15)

一種使一可潤濕基材上所含之一被反應物與一反應物加速並均勻反應之設備 ,其包含: 一機台本體,具有供該可潤濕基材置放於上之一排液底板;及 一塗佈頭,係設於該機台本體上方,並可維持一預設高度沿著該可潤濕基材以水平方向移動,該塗佈頭具有一或多個狹縫,該狹縫一端具有一注入開口,該狹縫的另一端具有一液體排出口。 A device for accelerating and uniformly reacting a reactant and a reactant contained on a wettable substrate, comprising: a machine body having a drain bottom plate on which the wettable substrate is placed; and A coating head is installed above the machine body and can maintain a predetermined height and move in a horizontal direction along the wettable substrate. The coating head has one or more slits, one end of the slits There is an injection opening, and the other end of the slit has a liquid discharge port. 如請求項1之設備,其中該設備更包含一吸力產生裝置,該吸力產生裝置係連接於該排液底板,提供該可潤濕基材一吸力。The apparatus of claim 1, wherein the apparatus further comprises a suction force generating device, the suction force generating device is connected to the drainage bottom plate to provide a suction force to the wettable substrate. 如請求項1之設備,其中該排液底板係一多孔性材質或一非多孔性材質,且當該排液底板為該非多孔性材質,該排液底板於其表面設有微流道。The device of claim 1, wherein the drain bottom plate is made of a porous material or a non-porous material, and when the liquid drain bottom plate is made of the non-porous material, the drain bottom plate is provided with micro-channels on its surface. 如請求項3之設備,其中該微流道之溝槽深度具一梯度(gradient)。The apparatus of claim 3, wherein the groove depth of the microfluidic channel has a gradient. 如請求項4之設備,其中該排液底板與該吸力產生裝置之間進一步設有一廢液儲存槽。The apparatus of claim 4, wherein a waste liquid storage tank is further provided between the liquid discharge bottom plate and the suction generating device. 如請求項5之設備,其中該排液底板下方進一步設有一震盪器。The device of claim 5, wherein a vibrator is further provided below the draining bottom plate. 如請求項6之設備,其中該塗佈頭進一步與一清洗液儲存槽連接。The apparatus of claim 6, wherein the coating head is further connected to a cleaning fluid storage tank. 如請求項1之設備,其中該排液底板的至少一側邊具有一塗佈準備區。The apparatus of claim 1 , wherein at least one side of the drain bottom plate has a coating preparation area. 如請求項1之設備,其中該狹縫之兩側係非平行。The apparatus of claim 1, wherein the two sides of the slit are non-parallel. 一種快速標定一被反應物之系統,其包含如請求項1至9任一項之設備及一光學影像擷取分析模組。A system for quickly calibrating a reactant, which comprises the device according to any one of claims 1 to 9 and an optical image capture analysis module. 如請求項10之系統,其中該光學影像擷取分析模組包含一攝像機。The system of claim 10, wherein the optical image capture analysis module includes a camera. 如請求項11之系統,其進一步包含與一預先固定一或多種目標被反應物之試片搭配使用。The system of claim 11, further comprising cooperating with a test strip pre-fixed with one or more target reactants. 如請求項12之系統,其進一步包含一非暫態機器可讀媒體,其儲存一程式用以判讀該試片經反應後之結果,該非暫態機器可讀媒體係選自任一項或二種以上由以下模組所組成之群組: 一影像判讀,用以判讀該試片經反應後之影像; 一定量模組,用以定量該試片之目標被反應物之含量; 一參照資料庫模組,係儲存該試片之該目標被反應物之檢測圖譜及相關臨床症狀;及 一比對模組,用以將該影像與檢測圖譜進行比對,以確定該試片反應後之結果。 The system of claim 12, further comprising a non-transitory machine-readable medium storing a program for interpreting the result of the reaction of the test strip, the non-transitory machine-readable medium being selected from any one or two more than one group consisting of the following modules: An image interpretation, used to interpret the image of the test piece after the reaction; A certain amount of module is used to quantify the content of the target reactant of the test piece; a reference database module, storing the detection pattern and related clinical symptoms of the target reactant of the test piece; and A comparison module is used to compare the image with the detection map to determine the result after the test piece reacts. 一塗佈頭,其具有一或多個狹縫,該狹縫一端具有一無需限制置於幾何對稱中心的注入開口,該狹縫的另一端具有一液體排出口。A coating head has one or more slits, one end of the slit has an injection opening which is not limited to be placed at the center of geometric symmetry, and the other end of the slit has a liquid discharge port. 如請求項14之塗佈頭,其中該狹縫之兩側係非平行。The coating head of claim 14, wherein both sides of the slit are non-parallel.
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