TW201912244A - Method and apparatus of generating substantially monodisperse droplets - Google Patents

Method and apparatus of generating substantially monodisperse droplets Download PDF

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TW201912244A
TW201912244A TW106128670A TW106128670A TW201912244A TW 201912244 A TW201912244 A TW 201912244A TW 106128670 A TW106128670 A TW 106128670A TW 106128670 A TW106128670 A TW 106128670A TW 201912244 A TW201912244 A TW 201912244A
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phase fluid
length direction
microchannel
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dispersed phase
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TWI630956B (en
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陳暉
林鵬
黃柏翰
王俊凱
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台灣創新材料股份有限公司
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Abstract

The present invention relates to a method and apparatus for generating substantially monodisperse droplets. The invention involves flowing a continuous phase fluid in a microfluidic passageway which extends along a longitudinal length direction and has a substantially constant cross section along the length direction. Subsequently, a dispersed phase fluid is introduced into the microfluidic passageway along a traverse direction to the length direction through a plurality of inlet orifices to generate droplets of the dispersed phase fluid in the continuous phase fluid. The aforementioned inlet orifices have a substantially uniform diameter, and any adjacent two of the inlet orifices are arranged to be offset from each other in the length direction. The dispersed phase fluid is broken up by the shearing force generated by the continuous phase fluid to produce a large amount of monodisperse droplets. By the offsetting arrangement of the inlet orifices, droplets formed by two adjacent inlet orifices will not interfere with each other, thereby ensuring the uniformity of the droplets.

Description

產生實質上具有單分散性的微滴之方法及裝置Method and apparatus for producing droplets having substantially monodisperse

本發明係有關一種可產生大量單分散性微滴之方法及裝置。The present invention relates to a method and apparatus for producing a plurality of monodisperse droplets.

近20年來,生物和化學等領域越來越注重微型化,而微流控(Microfluidics)技術在這方面的發展尤為值得重視。“微流控”是一門在微電子、微製作、生物工程和納米技術等基礎上發展起來的全新的交叉學科,它利用微流控裝置(Microfluidic device)中的微通道(孔徑5∼500 μm)對微量液體或樣品在微觀尺度上進行操縱、處理與控制。微流控裝置通常是一種以微通道網路和各種功能單元集成化為特點的微流控晶片(Microfluidic chip),可以實現樣品的製備、反應、分離和檢測的集成,還可對這些過程進行調控。早期的研究工作主要集中在對微通道內連續流系統的操控,包括進樣、混合、反應、分離和檢測等。然而由於傳統連續流系統存在一定局限性,如樣品消耗量較大、微泵和微閥的結構與製造工藝複雜,易造成交叉污染以及在低雷諾係數下液流間難以快速混合等。In the past 20 years, the fields of biology and chemistry have become more and more focused on miniaturization, and the development of Microfluidics technology in this area is particularly worthy of attention. "Microfluidic" is a new interdisciplinary subject developed on the basis of microelectronics, micro-production, bioengineering and nanotechnology. It utilizes microchannels in a microfluidic device (aperture 5∼500 μm). Manipulate, process and control microscopic liquids or samples on a microscopic scale. The microfluidic device is usually a microfluidic chip featuring microchannel network and various functional unit integration, which can realize the integration of sample preparation, reaction, separation and detection, and can also perform these processes. Regulation. Early research efforts focused on the manipulation of continuous flow systems in microchannels, including injection, mixing, reaction, separation, and detection. However, due to the limitations of the traditional continuous flow system, such as large sample consumption, complex structure and manufacturing process of the micropump and microvalve, it is easy to cause cross-contamination and difficult to mix quickly between liquid flows under low Reynolds coefficient.

近年來,微流控領域出現了一個新的分支-非連續流微流控系統,亦被稱為微滴微流控系統。微滴微流控系統使用不相溶的兩相流體在微孔道界面處形成微滴。相對於連續流系統,微滴具有體積小、低擴散、無交叉污染、快速的反應動力學等特點,並且具有高通量分析的潛力。正是因為存在這些潛在優勢,從而使得微滴微流控技術受到越來越多研究工作者的關注。且經過幾年的發展,微滴的製備技術已日趨成熟,使其逐步應用於化學和生物化學分析等諸多領域。In recent years, a new branch-discontinuous flow microfluidic system has emerged in the field of microfluidics, also known as microfluidic microfluidic systems. The microfluidic microfluidic system uses incompatible two-phase fluid to form droplets at the microchannel interface. Compared to continuous flow systems, droplets have the characteristics of small volume, low diffusion, no cross-contamination, rapid reaction kinetics, and the potential for high-throughput analysis. It is precisely because of these potential advantages that microfluidic microfluidic technology is attracting more and more researchers' attention. And after several years of development, the preparation technology of droplets has become more and more mature, and it has been gradually applied to many fields such as chemical and biochemical analysis.

微滴微流控技術包括微滴生成和微滴驅動,依照生成方式可以將操控微滴的方法分為兩大類。一類是被動法,即通過對微通道結構的特別設計使流體的流動局部產生速度梯度來對微滴進行操控,主要為多相流法(multiphase flow)。該法的主要特點是可以快速批量生成微滴;而另一類是主動法,即通過電場力、熱能量等外力使液流局部產生能量梯度來對微滴進行操控,主要包括電潤濕法、介電電泳法、氣動法和熱毛細管法,該法的主要特點是可以對單個微滴的操控。Microfluidic microfluidic technology includes droplet generation and droplet driving. According to the generation method, the methods of controlling droplets can be divided into two categories. One type is the passive method, in which the droplets are manipulated locally by the special design of the microchannel structure to produce a velocity gradient, mainly multiphase flow. The main feature of the method is that it can rapidly generate droplets in batches; the other is the active method, which uses the external force such as electric field force and thermal energy to locally generate an energy gradient to control the droplets, mainly including electrowetting, Dielectrophoresis, pneumatics and thermal capillary methods, the main feature of this method is the manipulation of individual droplets.

其中,多相流法之原理是通過對流體微通道結構的獨特設計以及對流體流速的控制,藉由流體之間在剪切力、流體的黏度和表面張力的交互作用,使分散相流體在微通道局部產生速度梯度,從而被拆分生成微滴,產生的微滴均勻地分佈在互不相溶的連續相中,形成單分散系統。多相流法的優勢在於易對批量微滴進行整體操控。G. F. Christopher和S. L. Anna所著回顧性論文(G. F. Christopher and S. L. Anna, Microfluidic methods for generating continuous droplet streams,J. Phys. D: Appl. Phys . 40 (2007), R319–R336)述及多相流法製備微滴主要有三種方式:正交結構(T-junction)、流式聚焦(flow-focusing)和共軸流(co-axial flow)方式。該些方式中微流道的設計各有不同,其中影響製備微滴的因素包括有微通道材料性質、微通道的幾何尺寸和形狀、流體的性質(例如黏度、表面張力)和流速比等。Among them, the principle of multiphase flow method is to make the dispersed phase fluid in the interaction between the shear force, the viscosity of the fluid and the surface tension through the unique design of the fluid microchannel structure and the control of the fluid flow rate. The microchannel locally generates a velocity gradient that is split to generate droplets, and the resulting droplets are evenly distributed in the mutually incompatible continuous phase to form a monodisperse system. The advantage of the multiphase flow method is that it is easy to control the bulk droplets as a whole. A retrospective paper by GF Christopher and SL Anna (GF Christopher and SL Anna, Microfluidic methods for producing continuous droplet streams, J. Phys. D: Appl. Phys . 40 (2007), R319–R336) There are three main ways to prepare droplets: T-junction, flow-focusing, and co-axial flow. The design of the microchannels in these modes is different, and the factors affecting the preparation of the droplets include the properties of the microchannel material, the geometry and shape of the microchannel, the properties of the fluid (such as viscosity, surface tension), and the flow ratio.

極具發展前景的微流控技術已經引起了人們的廣泛關注,相關的研究已取得了一系列令人矚目的進展,但業界對於以簡單製程來精準控制可快速生產大量且尺寸均一的微滴,仍然有殷切的需求。The promising microfluidic technology has attracted wide attention, and related research has made a series of remarkable progress, but the industry can quickly produce a large number of uniform droplets with precise control by simple process. There is still an ardent demand.

有鑑於此,本發明提供一種可產生大量單分散性微滴之方法及裝置,為其主要目的者。In view of the above, the present invention provides a method and apparatus for producing a large number of monodisperse droplets, the main purpose of which.

本案產生實質上具有單分散性的微滴之方法,至少包含下列步驟: 使一連續相流體在一個沿著一縱長的長度方向延伸之微流道內流動,而該微流道沿著該長度方向具有實質恆定的截面;以及 順著相對於該長度方向之側向,將一分散相流體經由複數輸入孔引入該微流道內,以在該連續相流體內形成由該分散相流體所構成的單分散性微滴,其中複數輸入孔具有實質相同之孔徑,且相鄰任二個輸入孔被設置成在該長度方向上彼此錯開排列。The present invention produces a method of substantially monodisperse droplets comprising at least the steps of: flowing a continuous phase fluid in a microchannel extending along a lengthwise length along which the microchannel follows a substantially constant cross section in the length direction; and a dispersed phase fluid introduced into the microchannel along the lateral direction relative to the length direction to form a dispersed phase fluid in the continuous phase fluid A monodisperse droplet is constructed in which a plurality of input apertures have substantially the same aperture, and adjacent two input apertures are arranged to be staggered from each other in the length direction.

依據上述技術特徵,所述引入該分散相流體的步驟包含以相對於該長度方向成一約90度的角度引入該分散相流體。According to the above technical feature, the step of introducing the dispersed phase fluid comprises introducing the dispersed phase fluid at an angle of about 90 degrees with respect to the length direction.

本發明另提供一種產生實質上具有單分散性的微滴之裝置。該裝置包含一實質呈剛性的第一部件;以及一實質呈剛性的第二部件,係與該第一部件相對配置以在兩者之間界定出一微流道,可供一連續相流體流動,該微流道沿著一縱長的長度方向延伸,而且該微流道沿著該長度方向具有實質恆定的截面。該裝置形成有複數輸入孔,可供一分散相流體順著相對於該長度方向之側向被引入該微流道內,以在該連續相流體內形成由該分散相流體所構成的單分散性微滴,且其中該複數輸入孔具有實質相同之孔徑,且相鄰任二輸入孔係沿該微流道之長度方向彼此錯開排列。The invention further provides an apparatus for producing droplets having substantially monodisperse properties. The device includes a substantially rigid first member; and a substantially rigid second member disposed opposite the first member to define a micro flow passage therebetween for a continuous phase fluid flow The microchannel extends along a longitudinal length and the microchannel has a substantially constant cross section along the length. The apparatus is formed with a plurality of input apertures for introducing a dispersed phase fluid into the microchannel along a lateral direction relative to the length direction to form a monodisperse of the dispersed phase fluid in the continuous phase fluid And a plurality of input apertures having substantially the same aperture, and adjacent two input apertures are staggered from each other along a length direction of the microchannel.

依據本發明,分散相流體是透過複數輸入孔進入連續相流體內,利用該連續相流體被限於細窄環形間隔之微流道延長度方向高速流動,可藉由該流體內所形成之剪切力切斷分散相流體,以產生大量且尺寸實質上相等之單分散性微滴。藉由在長度方向上彼此錯開排列之複數輸入孔,且較佳為這些輸入孔之間具有實質上相等的間隔距離,讓相鄰任二輸入孔所形成之單分散性微滴不會相互干擾,以確保單分散性微滴之成形品質,並且藉由該微流道及輸入孔之特性以確保所產生之單分散性微滴具有均一品質。According to the present invention, the dispersed phase fluid enters the continuous phase fluid through the plurality of input holes, and the continuous phase fluid is restricted to flow at a high speed in the direction of the microchannel length of the narrow annular gap, and the shear formed by the fluid can be formed. The force cuts off the dispersed phase fluid to produce a large number of monodisperse droplets of substantially equal size. The monodisperse droplets formed by the adjacent two input holes do not interfere with each other by a plurality of input holes arranged in a staggered manner in the longitudinal direction, and preferably having substantially equal separation distances between the input holes To ensure the forming quality of the monodisperse droplets, and to ensure the uniform quality of the monodisperse droplets produced by the characteristics of the microchannels and the input pores.

依據上述技術特徵,所述第一部件被構形成為一沿著該長度方向延伸的棒體,該第二部件被構形成為一管狀外殼且以同心方式配置於該第一部件外,進而將該微流道界定成一環狀構形。第一部件以及第二部件可以選擇性地被構形成為具有圓形、方形、六角形或其他幾何形狀的截面。According to the above technical feature, the first member is configured as a rod extending along the length direction, the second member is configured as a tubular outer casing and is disposed concentrically outside the first member, and The microchannel is defined as an annular configuration. The first component and the second component can be selectively configured to have a circular, square, hexagonal, or other geometric cross section.

依據上述技術特徵,所述複數輸入孔係位於第一部件或第二部件。當輸入孔設置於該第一部件時,該第一部件被構形成一沿著該長度方向延伸的空心棒體。According to the above technical feature, the plurality of input holes are located in the first component or the second component. When the input aperture is disposed in the first component, the first component is configured to form a hollow rod extending along the lengthwise direction.

依據上述技術特徵,所述第一部件具有第一端,而該第一端處設置有一第一固定件,該第一固定件被固定於該第二部件的第一端,以防止該第一部件相對於該第二部件發生位移。According to the above technical feature, the first member has a first end, and the first end is provided with a first fixing member, the first fixing member is fixed to the first end of the second member to prevent the first end The component is displaced relative to the second component.

依據上述技術特徵,所述第一部件具有相對於該第一端之第二端,而該第二端處設置有一第二固定件,該第二固定件徑向地抵靠於該第二部件相對於其第一端之第二端,以防止該第一部件相對於該第二部件發生徑向偏移。According to the above technical feature, the first member has a second end opposite to the first end, and the second end is provided with a second fixing member, the second fixing member radially abuts against the second member Relative to the second end of the first end thereof to prevent radial displacement of the first component relative to the second component.

依據上述技術特徵,所述第一固定件形成有一供該連續相流體進入的入口,以及其中該第一部件的第一端在該長度方向上朝向該入口呈尺寸漸縮,藉此與第二部件之第一端共同界定出一第一連通道,而該第一連通道以流體連通方式連接該入口和該微流道。According to the above technical feature, the first fixing member is formed with an inlet for the continuous phase fluid to enter, and wherein the first end of the first member is tapered in size in the length direction toward the inlet, thereby being second The first ends of the components collectively define a first connecting passage, and the first connecting passage connects the inlet and the micro flow passage in fluid communication.

依據上述技術特徵,所述第二固定件形成有一出口,以及其中該第一部件的第二端在該長度方向上朝向該出口呈尺寸漸縮,藉此與第二部件之第二端共同界定出一第二連通道,而該第二連通道以流體連通方式連接該出口和該微流道。According to the above technical feature, the second fixing member is formed with an outlet, and wherein the second end of the first member is dimensioned toward the outlet in the length direction, thereby being defined together with the second end of the second member A second connecting passage is provided, and the second connecting passage connects the outlet and the micro flow passage in fluid communication.

依據上述技術特徵,所述輸入孔被設置成可使得該分散相流體能夠以相對於該長度方向成一約90度的角度被引入該微流道。According to the above technical feature, the input aperture is configured to enable the dispersed phase fluid to be introduced into the microchannel at an angle of about 90 degrees with respect to the length direction.

除非另外說明,否則本申請說明書和申請專利範圍中所使用的下列用語具有下文給予的定義。請注意,本申請說明書和申請專利範圍中所使用的單數形用語「一」意欲涵蓋在一個以及一個以上的所載事項,例如至少一個、至少二個或至少三個,而非意味著僅僅具有單一個所載事項。此外,申請專利範圍中使用的「包含」、「具有」等開放式連接詞是表示請求項中所記載的元件或成分的組合中,不排除請求項未載明的其他組件或成分。亦應注意到用語「或」在意義上一般也包括「及/或」,除非內容另有清楚表明。本申請說明書和申請專利範圍中所使用的用語「約(about)」或「實質上(substantially)」,是用以修飾任何可些微變化的誤差,但這種些微變化並不會改變其本質。Unless otherwise stated, the following terms used in the specification and claims of the present application have the definitions given below. It is to be understood that the singular <RTI ID=0.0>&quot;&quot;&quot;&quot;&quot; A single item. In addition, the open-ended conjunctions such as "including" and "having" used in the claims are intended to mean that the components or components described in the claims are not excluded. It should also be noted that the term "or" generally includes "and/or" in the sense, unless the content clearly indicates otherwise. The terms "about" or "substantially" as used in the specification and claims of the present application are intended to modify any error that may vary slightly, but such minor variations do not alter the nature.

本發明中產生單分散性微滴之方法大致上涉及利用前文提及之G. F. Christopher和S. L. Anna所著回顧性論文中述及的正交結構(T-junction)微流道來製造微滴,該件論文被完整地納入於本文,以作為參考。在微流控這個技術領域中,所謂「正交結構」乃是一般性地指涉將一分散相流體成一角度匯入於一連續相流體中。所述角度通常位於60至90度的範圍內,較佳為位於80至90度的範圍內,尤以接近90度為佳。本發明所稱「連續相」是指由同一物質構成相互連接的一相,在該連續相中可容納一些相互隔離的異相物質。而「分散相」是由散布於前述連續相中的許多相互隔離的微量物質共同構成的一相,分散相中的每一隔離單位都被連續相包圍。由一個連續相和一個分散相組成的兩相系統,通稱為分散系統(disperse systems)。所述「分散相流體」和「連續相流體」通常是兩種不相混溶的流體(immiscible fluids),它們可以在正交結構的匯流處(joint)形成由分散相流體分散於連續相流體內的微滴。如相關技術領域中具有通常知識者所熟悉,微滴的尺寸及其生成的頻率通常由流道的構形、流體的流速和流體的性質來決定。The method of producing monodisperse droplets in the present invention generally involves the use of orthogonal structures (T-junction) microchannels as described in the retrospective papers previously mentioned by GF Christopher and SL Anna, which are used to make droplets. A paper is fully incorporated herein by reference. In the art of microfluidics, the term "orthogonal structure" generally refers to the incorporation of a dispersed phase fluid into a continuous phase fluid at an angle. The angle is typically in the range of 60 to 90 degrees, preferably in the range of 80 to 90 degrees, especially near 90 degrees. The term "continuous phase" as used in the present invention means a phase in which the same substance is interconnected, and in the continuous phase, a plurality of mutually separated heterogeneous substances can be accommodated. The "dispersed phase" is a phase composed of a plurality of mutually isolated trace substances dispersed in the aforementioned continuous phase, each of which is surrounded by a continuous phase. A two-phase system consisting of one continuous phase and one dispersed phase is known as a disperse system. The "dispersed phase fluid" and the "continuous phase fluid" are generally two immiscible fluids which can be formed at the confluence of the orthogonal structure by the dispersed phase fluid dispersed in the continuous phase flow. Microdroplets in the body. As is well known to those of ordinary skill in the relevant art, the size of the droplets and the frequency of their generation are typically determined by the configuration of the flow channels, the flow rate of the fluid, and the nature of the fluid.

首先,本案方法涉及使一連續相流體在微流道3內流動。請參閱第1圖所示為本發明中裝置之第一結構示意圖,微流道3是由第一、第二部件2、3所界定出來的一個區域。如圖所示之實施例中,第一部件1與第二部件2相對配置,較佳為第二部件2係實質平行地配置於第一部件1一側,藉此,第一、第二部件1、2間隔配置而界定出微流道3。微流道3沿著一縱長的長度方向T1延伸,供連續相流體沿著長度方向T1流動。微流道3沿著長度方向T1上具有實質恆定的截面,使得通過微流道3的流體不會實質改變其流速。第一、第二部件1、2可以獨立地由相同或不同的剛性材料所製成。本案所使用之用語「剛性(rigid)」意指在實施本發明時不會發生實質形變。適用於本發明之剛性材料的實例包括但不限於金屬(例如不鏽鋼)、玻璃、石英、陶瓷、非撓性塑膠(例如丙烯酸塑膠)等。基於第一部件1與第二部件2的剛性特質,由此二者所界定出來的微流道3在尺寸上可維持恆定。First, the method of the present invention involves flowing a continuous phase fluid within the microchannel 3. Referring to Figure 1, there is shown a first schematic view of the apparatus of the present invention. The microchannel 3 is an area defined by the first and second members 2, 3. In the embodiment shown, the first member 1 is disposed opposite to the second member 2, and preferably the second member 2 is disposed substantially parallel to the first member 1 side, whereby the first and second members are 1, 2 interval configuration to define the micro flow channel 3. The microchannel 3 extends along a longitudinal length direction T1 for the continuous phase fluid to flow along the length direction T1. The microchannel 3 has a substantially constant cross section along the length direction T1 such that the fluid passing through the microchannel 3 does not substantially change its flow rate. The first and second members 1, 2 can be independently made of the same or different rigid materials. The term "rigid" as used in this context means that substantial deformation does not occur in the practice of the present invention. Examples of rigid materials suitable for use in the present invention include, but are not limited to, metals (e.g., stainless steel), glass, quartz, ceramics, non-flexible plastics (e.g., acrylic plastic), and the like. Based on the rigid nature of the first component 1 and the second component 2, the microchannels 3 defined by the two can be kept constant in size.

第一部件1和第二部件2的製作工序為相關技術領域中具有通常知識者所熟悉,而且可以依據材質不同而進行調整。舉例而言,當第一部件1和第二部件2是由金屬材料製成時,可以藉由沖壓、輾軋、車削加工、壓模成型、鍛造等習用金屬加工製程來製作。The manufacturing process of the first member 1 and the second member 2 is familiar to those of ordinary skill in the related art, and can be adjusted depending on the material. For example, when the first member 1 and the second member 2 are made of a metal material, they can be produced by a conventional metal working process such as stamping, rolling, turning, press molding, forging, and the like.

本申請的裝置形成有複數輸入孔。如圖所示之實施例中,第二部件2形成有複數輸入孔21,可供分散相流體順著相對於長度方向T1之側向被引入微流道3。如圖所示之實施例中,各輸入孔21被設置成可使得分散相流體能夠以相對於長度方向T1成一位於60至90度的範圍內的角度被引入微流道3內,較佳為所述角度位於80至90度的範圍內,更佳為所述角度約90度。輸入孔21具有實質相同之尺寸。請同時參閱第2圖所示,相鄰任二輸入孔21係沿著長度方向T1彼此錯開排列,且較佳為這些輸入孔之間具有實質上相等的間隔距離。當然,這些輸入孔21亦可位於第一部件1上。The device of the present application is formed with a plurality of input holes. In the illustrated embodiment, the second member 2 is formed with a plurality of input apertures 21 for introducing the dispersed phase fluid into the microchannels 3 along the lateral direction with respect to the length direction T1. In the illustrated embodiment, each of the input apertures 21 is configured to enable the dispersed phase fluid to be introduced into the microchannel 3 at an angle in the range of 60 to 90 degrees with respect to the length direction T1, preferably The angle is in the range of 80 to 90 degrees, more preferably the angle is about 90 degrees. The input holes 21 have substantially the same size. Referring to FIG. 2 at the same time, the adjacent two input holes 21 are arranged offset from each other along the longitudinal direction T1, and it is preferable that the input holes have substantially equal separation distances between the input holes. Of course, these input holes 21 can also be located on the first component 1.

如第3圖所示,分散相流體經由輸入孔21被引入微流道3時,藉由連續相流體於微流道內流動所形成之剪切力F1而切斷分散相流體,而於微流道3內形成由分散相流體被分散於連續相流體內的複數微滴4。由於微流道3沿著長度方向T1之截面為實質恆定,且單分散性微滴與連續相的體積比很低時,使得流經微流道3之連續相流體的流速趨近恆定,且複數輸入孔21之尺寸實質上相等,所以可產生大量單分散性微滴4。本案所稱「單分散性」意指所生成的複數微滴4具有狹窄的尺寸分佈,較佳為具有一低於8%的多分散性指數(polydispersity index)。藉由彼此錯開排列之複數輸入孔21,讓相鄰任二輸入孔21所形成之單分散性微滴4相互錯開,不會沿長度方向T1流動時相互干擾而相互接觸發生沾黏或破裂,可維持單分散性微滴的完整性,以確保單分散性微滴4之成形品質。As shown in FIG. 3, when the dispersed phase fluid is introduced into the microchannel 3 via the input hole 21, the dispersed phase fluid is cut by the shear force F1 formed by the flow of the continuous phase fluid in the microchannel, and A plurality of droplets 4 dispersed in the continuous phase fluid by the dispersed phase fluid are formed in the flow channel 3. Since the cross section of the microchannel 3 along the longitudinal direction T1 is substantially constant, and the volume ratio of the monodisperse droplet to the continuous phase is low, the flow velocity of the continuous phase fluid flowing through the microchannel 3 is made constant, and The plurality of input apertures 21 are substantially equal in size, so that a large number of monodisperse droplets 4 can be produced. As used herein, "monodisperse" means that the resulting plurality of droplets 4 have a narrow size distribution, preferably having a polydispersity index of less than 8%. The monodisperse droplets 4 formed by the adjacent two input holes 21 are staggered from each other by the plurality of input holes 21 arranged in a staggered manner, and do not interfere with each other when flowing in the longitudinal direction T1, and are in contact with each other to cause sticking or cracking. The integrity of the monodisperse droplets can be maintained to ensure the forming quality of the monodisperse droplets 4.

在較佳的具體例中,第一部件1與第二部件2相隔一位於150微米至1毫米之範圍內的距離,使得微流道3具有一位於150微米至1毫米之範圍內的寬度。但是上述寬度範圍並不表示為該距離的下限或上限。一般而言,個別輸入孔21的孔徑被設置成實質上小於微流道3的寬度。In a preferred embodiment, the first component 1 is spaced from the second component 2 by a distance in the range of 150 microns to 1 millimeter such that the microchannel 3 has a width in the range of 150 microns to 1 mm. However, the above width range is not represented as the lower limit or upper limit of the distance. In general, the aperture of the individual input apertures 21 is set to be substantially smaller than the width of the microchannels 3.

如第2圖所示,輸入孔21可以沿著長度方向T1成鋸齒狀排列,使得相鄰任二輸入孔21在長度方向T1上相互錯開。如第4圖所示,輸入孔21之排列方向可以與長度方向T1垂直。如第5圖所示,輸入孔21可以排列成數列,分別與長度方向T1垂直,且相鄰二列中的輸入孔21在長度方向T1上相互錯開,使得相鄰任二輸入孔21在長度方向T1上相互錯開。As shown in Fig. 2, the input holes 21 may be arranged in a zigzag shape along the longitudinal direction T1 such that the adjacent two input holes 21 are shifted from each other in the longitudinal direction T1. As shown in Fig. 4, the arrangement direction of the input holes 21 may be perpendicular to the longitudinal direction T1. As shown in FIG. 5, the input holes 21 may be arranged in a plurality of columns, respectively perpendicular to the longitudinal direction T1, and the input holes 21 in the adjacent two columns are shifted from each other in the longitudinal direction T1 such that the adjacent two input holes 21 are in the length. The directions T1 are staggered from each other.

第一、第二部件可以是任何能夠界定出沿著長度方向T1上具有實質恆定截面之微流道3的結構元件。在較佳的具體例中,如第6圖以及第7圖所示,第一部件1被構形成為一空心或實心棒體,例如空心或實心的圓柱形棒體,沿著長度方向T1延伸,而第二部件2被構形成為管狀外殼,且第二部件2係以同心方式配置於第一部件1外,藉此使得第一、第二部件1、2將微流道3界定成一環狀構形。相較於其他構形,具有環狀構形的微流道更適合於經由精密加工而成型。由於微流道3的寬度很小而且均一,流體運行其間幾近於在兩個平板間移動,使得靠近第一,第二部件的表面附近有很大的流變量以及剪切力。第一部件1具有第一端101和相對於第一端101之第二端102,而第二部件2具有第一端201和相對於第一端201之第二端202。為了使第一、第二部件1、2間之相對位置固定,第一部件1與第二部件2間設有至少一固定件。如圖所示之實施例中,於第一端101設有第一固定件11,供固定於第二部件2。在一具體例中,第一固定件11被構形成為一突出於第二部件2外的膨大部分(enlarged portion),用於扣持第二部件2的外緣。第一固定件11可用於防止第一部件1相對於第二部件2在長度方向T1以及徑向上相對於第二部件2產生位移,使得第一、第二部件1、2間不會因為連續相流體或分散相流體之流動拖拉而相對位移。在一具體例中,第二端102進一步設有第二固定件12,供固定於第二部件2,以防止第一部件1相對於第二部件2形成徑向偏移,便於與第二部件2維持同心對位。較佳為第一固定件11被構形成為一位於第二部件2內的膨大部分,用於徑向地抵靠於第二部件2之第二端202。The first and second components may be any structural element capable of defining a microchannel 3 having a substantially constant cross section along the length direction T1. In a preferred embodiment, as shown in Figures 6 and 7, the first component 1 is configured as a hollow or solid rod, such as a hollow or solid cylindrical rod extending along the length direction T1. And the second component 2 is configured as a tubular outer casing, and the second component 2 is disposed concentrically outside the first component 1 , whereby the first and second components 1 , 2 define the micro flow channel 3 as a ring Shape configuration. Compared to other configurations, microchannels having a ring configuration are more suitable for molding through precision machining. Since the width of the microchannel 3 is small and uniform, the fluid moves nearly twice between the plates, so that near the first, there is a large flow variable and shear force near the surface of the second member. The first component 1 has a first end 101 and a second end 102 opposite the first end 101, while the second component 2 has a first end 201 and a second end 202 opposite the first end 201. In order to fix the relative positions between the first and second members 1, 2, at least one fixing member is disposed between the first member 1 and the second member 2. In the embodiment shown, a first fixing member 11 is provided at the first end 101 for fixing to the second member 2. In a specific example, the first fixing member 11 is configured as an enlarged portion protruding from the outside of the second member 2 for holding the outer edge of the second member 2. The first fixing member 11 can be used to prevent the first member 1 from being displaced relative to the second member 2 in the longitudinal direction T1 and in the radial direction relative to the second member 2, so that the first and second members 1, 2 are not separated by the continuous phase. The flow of the fluid or dispersed phase fluid is dragged and displaced. In a specific example, the second end 102 is further provided with a second fixing member 12 for fixing to the second member 2 to prevent the first member 1 from being radially offset from the second member 2, facilitating the second member. 2 Maintain a concentric alignment. Preferably, the first fixing member 11 is configured as a bulging portion located in the second member 2 for radially abutting against the second end 202 of the second member 2.

如第6和7圖所示,第一固定件11形成有一入口111,供連續相流體進入。第一部件1的第一端101在長度方向T1上朝向入口111逐漸縮小尺寸,藉此與第二部件2之第一端201共同界定出一個第一連通道301。第一連通道301則以流體連通方式連接入口111和微流道3。第一連通道301由入口111朝向微流道3逐漸變窄,使得通過入口111的連續相流體能夠在第一連通道301內穩定地加速,再抵達微流道3。類似地,第二固定件12形成有一出口121,供連續相流體流出。第一部件1的第二端102在長度方向T1上朝向出口121逐漸縮小尺寸,藉此與第二部件2之第二端202共同界定出一第二連通道302。第二連通道302則以流體連通方式連接出口121和微流道3。第二連通道302由微流道3朝向出口121逐漸變寬,使得通過微流道3的連續相流體能夠在第二連通道302內穩定地減速,再經由出口121流出。As shown in Figures 6 and 7, the first fixture 11 is formed with an inlet 111 for continuous phase fluid entry. The first end 101 of the first component 1 is gradually reduced in size in the length direction T1 toward the inlet 111, whereby a first connecting passage 301 is defined together with the first end 201 of the second component 2. The first connecting passage 301 connects the inlet 111 and the micro flow passage 3 in fluid communication. The first connecting passage 301 is gradually narrowed toward the micro flow passage 3 by the inlet 111, so that the continuous phase fluid passing through the inlet 111 can be stably accelerated in the first connecting passage 301 and then reaches the micro flow passage 3. Similarly, the second fixture 12 is formed with an outlet 121 for the continuous phase fluid to flow out. The second end 102 of the first component 1 is gradually reduced in size in the length direction T1 toward the outlet 121, thereby cooperating with the second end 202 of the second component 2 to define a second connecting passage 302. The second connecting passage 302 connects the outlet 121 and the micro flow passage 3 in fluid communication. The second connecting passage 302 is gradually widened by the micro flow passage 3 toward the outlet 121, so that the continuous phase fluid passing through the micro flow passage 3 can be stably decelerated in the second connecting passage 302 and then discharged through the outlet 121.

另外,進一步設有一第一饋送單元51,如第6圖所示,其係扣接於第一固定件11處,並且與入口111呈流體連通,藉此經由入口111供應連續相流體。第一饋送單元51可為任何能夠補充連續相流體並將連續相流體流通至微流道者,其可包括但不限於具儲液功能的槽,且結構或形狀上都無特別的限制,第一饋送單元51較佳是可保持內部連續相流體最低污染機率且具有可調整連續相流體的輸出壓力、流動速度及/或單位時間輸出量等功能。另外,也可以進一步設有一第二饋送單元52,其係與複數輸入孔21呈流體連通,用於供應分散相流體。在一個優選具體實施方案中,所述第二饋送單元52可為任何能簡易填充分散相流體為氣體的形式,並將氣體以氣流的形式流通至輸入孔21者,其可例如但不限於具儲氣功能的槽,結構或形狀上亦無特別的限制。第二饋送單元52較佳是可保持內部氣體最低污染機率且具有可調整氣流的噴出壓力、流動速度及/或氣體單位時間內輸出量等功能。Further, a first feeding unit 51 is further provided, as shown in Fig. 6, which is fastened to the first fixing member 11 and is in fluid communication with the inlet 111, whereby the continuous phase fluid is supplied via the inlet 111. The first feeding unit 51 may be any one capable of replenishing the continuous phase fluid and circulating the continuous phase fluid to the micro flow channel, which may include, but is not limited to, a tank having a liquid storage function, and has no particular limitation in structure or shape. A feed unit 51 preferably maintains a minimum contamination probability of the internal continuous phase fluid and has the function of adjusting the output pressure, flow rate, and/or unit time output of the continuous phase fluid. Additionally, a second feed unit 52 may be further provided in fluid communication with the plurality of input apertures 21 for supplying the dispersed phase fluid. In a preferred embodiment, the second feeding unit 52 can be any form that can easily fill the dispersed phase fluid as a gas, and circulates the gas in the form of a gas stream to the input hole 21, which can be, for example but not limited to, There are no particular restrictions on the tank, structure or shape of the gas storage function. The second feeding unit 52 preferably has a function of maintaining a minimum internal contamination rate of the internal gas and having an adjustable discharge pressure, a flow velocity, and/or a gas output per unit time.

在上述第一、第二實施例中,第一部件較佳為被構形成為一空心或實心的圓柱形棒體,第二部件較佳為被構形成為圓形管狀外殼,該些輸入孔係位於第二部件。該第一、第二部件亦可被構形成具有方形、六角形或其他幾何形狀的截面。如第8圖之第三實施例所示,第一及第二部件1、2被構形為二個相互套合且具有方形截面的管體,藉此,兩者之間所界定出之微流道3具有一方形環狀構形的截面,而該些輸入孔13係位於第一部件1。在第三實施例中,第一部件1被構形成為一空心圓柱形棒體,使得輸入孔13可以與第二饋送單元52(圖未示)呈流體連通,以供應分散相流體。In the first and second embodiments described above, the first member is preferably configured as a hollow or solid cylindrical rod, and the second member is preferably configured as a circular tubular housing, the input holes It is located in the second part. The first and second components may also be configured to have a cross-section having a square, hexagonal or other geometric shape. As shown in the third embodiment of Fig. 8, the first and second members 1, 2 are configured as two tubular bodies which are mutually nested and have a square cross section, whereby the two are defined The flow passage 3 has a cross section of a square annular configuration, and the input holes 13 are located in the first member 1. In a third embodiment, the first component 1 is configured as a hollow cylindrical rod such that the input aperture 13 can be in fluid communication with a second feed unit 52 (not shown) to supply the dispersed phase fluid.

根據前文述及之G. F. Christopher和S. L. Anna所著論文,微滴的尺寸通常可藉由等參數依據下式決定:d係為微滴的直徑,σ係為連續相流體和分散相流體間的表面張力(surface tension),η係為連續相流體的黏度(viscosity),˙ε 係為連續相流體在輸入孔附近的流變率(shear rate) ,τ係為連續相流體在輸入孔附近的剪切力(shear stress)。因此,本發明可以藉由調整輸入孔21的孔徑、微流道3的寬度、連續相流體的饋送壓力、分散相流體的流速、分散相流體的黏度、連續相流體和分散相流體間的表面張力等參數,來控制微滴4的尺寸。藉由本案所揭方法和裝置可製造出大量尺寸均一的微滴。經由調整上述幾種參數,微滴直徑可對應調整至一特定尺寸,其大小可以位於50微米至1毫米之範圍內,並且具有低於8%的多分散性指數。According to the papers mentioned by GF Christopher and SL Anna, the size of the droplets can usually be determined by the following parameters: d is the diameter of the droplet, σ is the surface tension between the continuous phase fluid and the dispersed phase fluid, η is the viscosity of the continuous phase fluid, and ̇ ε is the continuous phase fluid near the input hole The shear rate, τ is the shear stress of the continuous phase fluid near the input hole. Therefore, the present invention can adjust the diameter of the input hole 21, the width of the microchannel 3, the feed pressure of the continuous phase fluid, the flow rate of the dispersed phase fluid, the viscosity of the dispersed phase fluid, the surface between the continuous phase fluid and the dispersed phase fluid. Parameters such as tension to control the size of the droplet 4. A large number of droplets of uniform size can be produced by the method and apparatus disclosed in the present invention. By adjusting several of the above parameters, the droplet diameter can be correspondingly adjusted to a specific size, which can range from 50 microns to 1 mm and have a polydispersity index of less than 8%.

在一個優選具體實施方案中,連續相流體的黏度介於50 CP 至200 CP,連續相流體的流量介於100毫升/分鐘至500毫升/分鐘,分散相流體的壓力介於0.1 bar至0.5 bar,可產生直徑介於100µm至500µm之間的單分散性微滴。In a preferred embodiment, the viscosity of the continuous phase fluid ranges from 50 CP to 200 CP, the flow rate of the continuous phase fluid ranges from 100 ml/min to 500 ml/min, and the pressure of the dispersed phase fluid ranges from 0.1 bar to 0.5 bar. Monodisperse droplets having a diameter between 100 μm and 500 μm can be produced.

所述單分散性微滴可依連續相流體以及分散相流體之不同類型而形成不同的結構組成,例如連續相流體係為液體,該分散相流體係為氣體,而形成之單分散性微滴係為氣泡;在一個優選具體實施方案中,所述連續相流體為水溶液或有機溶液,所述分散相流體為空氣、氮氣或混合氣體。在另一個優選具體實施方案中,該連續相流體以及分散相流體係為不互溶的液體,而形成之單分散性微滴係呈乳液形式。在另一個優選具體實施方案中,該連續相流體以及分散相流體係可相互發生物理或化學反應,而形成之單分散性微滴具有核殼結構,可應用於醫藥或催化劑領域。The monodisperse droplets may form different structural compositions according to different types of continuous phase fluids and dispersed phase fluids, for example, a continuous phase flow system is a liquid, and the dispersed phase flow system is a gas, and the monodisperse droplets are formed. It is a bubble; in a preferred embodiment, the continuous phase fluid is an aqueous solution or an organic solution, and the dispersed phase fluid is air, nitrogen or a mixed gas. In another preferred embodiment, the continuous phase fluid and the dispersed phase flow system are immiscible liquids, and the monodisperse droplets formed are in the form of an emulsion. In another preferred embodiment, the continuous phase fluid and the dispersed phase flow system may physically or chemically react with each other, and the monodisperse droplets formed have a core-shell structure and are applicable to the field of medicine or catalyst.

本案所形成之單分散性微滴經由收集後,可應用於上述所提及之化學和生物化學分析等諸多領域外;其中,因為收集單分散性微滴的過程中,單分散性微滴會自發性地呈球形構形而自行組裝堆疊成緊密排列。當單分散性微滴為氣泡時,氣泡與氣泡之間的氣泡壁所含的溶液可透過化學反應進而發生膠化,以固定相鄰兩氣泡間彼此的相對位置,而形成一有彈性之三維支架。相鄰兩氣泡間的氣泡壁可經由低壓膨脹過程產生小孔,可使該二氣泡形成貫通之連續空間。 此單分散性氣泡集合體是具有似海綿狀或蜂巢狀的結構,而內部具有大量適於附著或接種細胞的連續貫通之圓形孔洞。上述之三維支架具有特殊的物理性質,如重量輕、熱傳導性低、多孔性等等,因此常應用於諸多工程、醫學領域上,其中最受矚目的是作為培養細胞的組織支架,其功用為模仿細胞外基質(extracellular matrix),使細胞可在支架中生長,係將選用的細胞附著、或灌注或接種至此支架上,或三維支架本身即為細胞的培養基,讓細胞於支架中生長。之後,給予細胞合適的生長訊號及化學刺激,使細胞在模擬的環境下增殖、生長與分化,進而組成擬似治療標的再生組織或器官,當移植入病患體內後,即可取代原有之受損、或具功能障礙或壞死的組織器官以達成醫療的目的。最常被作為組織支架的天然材料為動物身上所取得的膠原蛋白或含水膠質的植物,例如明膠(gelatin)、膠原蛋白(collagen)、甲殼素(chitosan)或海藻酸鈉(sodium alginate)等等,而人造材料則包含聚乳酸(polylactate, PLLA)、聚甘醇酸(polyglycolate, PGA)、聚乳酸-羥基乙酸共聚物(poly- lactic co-glycolic acid, PLGA)等等。組織支架除了供應細胞生長環境之外,還可以調節細胞之間的連結並防止擠壓,使細胞得到最好的生長空間。The monodisperse droplets formed in this case can be applied to many fields such as the above-mentioned chemical and biochemical analysis after collection; among them, monodisperse droplets will be collected during the process of collecting monodisperse droplets. Spontaneously in a spherical configuration and self-assembled and stacked in a tight arrangement. When the monodisperse droplet is a bubble, the solution contained in the bubble wall between the bubble and the bubble can be gelled by a chemical reaction to fix the relative positions of the adjacent two bubbles to form a flexible three-dimensional shape. support. The bubble wall between the adjacent two bubbles can generate small holes through the low pressure expansion process, and the two bubbles can be formed into a continuous space. The monodisperse bubble assembly has a sponge-like or honeycomb-like structure, and has a large number of continuous through-holes suitable for attaching or seeding cells. The above-mentioned three-dimensional scaffold has special physical properties, such as light weight, low thermal conductivity, porosity, etc., and thus is often used in many engineering and medical fields, and the most noticeable one is as a tissue scaffold for culturing cells, and its function is Imitate the extracellular matrix so that the cells can grow in the scaffold, attach or inoculate or inoculate the selected cells onto the scaffold, or the three-dimensional scaffold itself is the medium of the cells, allowing the cells to grow in the scaffold. After that, the cells are given appropriate growth signals and chemical stimulation, so that the cells can proliferate, grow and differentiate under the simulated environment, and then form a regenerative tissue or organ that is intended to be treated as a therapeutic target. When transplanted into the patient, it can replace the original one. Damage, or dysfunctional or necrotic tissue and organs for medical purposes. The most commonly used natural material for tissue scaffolds is collagen or hydrocolloids obtained from animals, such as gelatin, collagen, chitosan or sodium alginate. The man-made material comprises polylactate (PLLA), polyglycolate (PGA), poly-lactic-co-glycolic acid (PLGA), and the like. In addition to supplying the cell growth environment, tissue scaffolds can also regulate the connections between cells and prevent extrusion, allowing cells to get the best growth space.

值得特別注意的是,依據本發明中產生單分散性微滴之方法及其裝置,僅需一微流道所具有之複數輸入孔將流過的連續相流體與分散相流體形成大量的單分散性微滴,是為一種簡易且快速的製備方式。此外,本發明產生單分散性微滴之方法及其裝置中所使用的連續相流體可依據使用者所需而輕易地置換,因而可產生不同尺寸的單分散性微滴,亦可客製化不同組成的單分散性微滴(例如氣泡、乳液或核殼結構)。在本發明之部分實施例中,利用適當的條件控制,依據本發明之方法所製成的單分散性微滴其尺寸實質上相等。再者,利用本發明之製備方法所製成的單分散性微滴,可進一步應用於細胞培養或組織工程可利用之三維支架,不僅操作簡單大量生產,可以減少在製作過程中的成本支出。It is worth noting that, according to the method and apparatus for producing monodisperse droplets in the present invention, only a plurality of input channels having a microchannel have a large number of monodisperse flow of the continuous phase fluid and the dispersed phase fluid flowing therethrough. Sexual droplets are an easy and fast way to prepare. In addition, the method for producing monodisperse droplets of the present invention and the continuous phase fluid used in the device can be easily replaced according to the needs of the user, thereby producing monodisperse droplets of different sizes, and can also be customized. Monodisperse droplets of different composition (such as bubbles, emulsions or core-shell structures). In some embodiments of the invention, monodisperse droplets made in accordance with the methods of the present invention are substantially equal in size, using appropriate conditional control. Furthermore, the monodisperse droplets prepared by the preparation method of the present invention can be further applied to a three-dimensional scaffold which can be utilized for cell culture or tissue engineering, and is not only easy to operate and mass-produced, but also can reduce the cost in the manufacturing process.

綜上所述,本發明提供產生單分散性微滴一較佳可行之方法及其裝置,爰依法提呈發明專利之申請;本發明之技術內容及技術特點巳揭示如上,然而熟悉本項技術之人士仍可能基於本發明之揭示而作各種不背離本案發明精神之替換及修飾。因此,本發明之保護範圍應不限於實施例所揭示者,而應包括各種不背離本發明之替換及修飾,並為以下之申請專利範圍所涵蓋。In summary, the present invention provides a method and apparatus for producing a monodisperse droplet, and an apparatus for presenting an invention patent according to the law; the technical content and technical features of the present invention are disclosed above, but are familiar with the technology. The person skilled in the art may still make various substitutions and modifications without departing from the spirit of the invention. Therefore, the scope of the present invention should be construed as being limited by the scope of the appended claims

F1‧‧‧剪切力 F1‧‧‧ shear force

T1‧‧‧長度方向 T1‧‧‧ length direction

1‧‧‧第一部件 1‧‧‧ first part

101‧‧‧第一端 101‧‧‧ first end

102‧‧‧第二端 102‧‧‧ second end

11‧‧‧第一固定件 11‧‧‧First fixture

111‧‧‧入口 111‧‧‧ Entrance

12‧‧‧第二固定件 12‧‧‧Second fixture

121‧‧‧出口 121‧‧‧Export

13‧‧‧輸入孔 13‧‧‧Input hole

2‧‧‧第二部件 2‧‧‧ second part

201‧‧‧第一端 201‧‧‧ first end

202‧‧‧第二端 202‧‧‧ second end

21‧‧‧輸入孔 21‧‧‧Input hole

3‧‧‧微流道 3‧‧‧microchannel

301‧‧‧第一連通道 301‧‧‧The first link

302‧‧‧第二連通道 302‧‧‧Second link

4‧‧‧微滴 4‧‧‧microdroplets

52‧‧‧第一饋送單元 52‧‧‧First feeding unit

53‧‧‧第二饋送單元 53‧‧‧second feed unit

第1圖為本發明中裝置第一實施例之結構示意圖。 第2圖為本發明中複數輸入孔第一實施例之結構示意圖。 第3圖為本發明中單分散性微滴形成之示意圖。 第4圖為本發明中複數輸入孔第二實施例之結構示意圖。 第5圖為本發明中複數輸入孔第三實施例之結構示意圖。 第6圖為本發明中裝置第二實施例之結構示意圖。 第7圖為本發明中裝置第二實施例之結構立體圖。 第8圖為本發明中裝置第三實施例之結構示意圖。Figure 1 is a schematic view showing the structure of a first embodiment of the apparatus of the present invention. Figure 2 is a schematic view showing the structure of the first embodiment of the plurality of input holes in the present invention. Figure 3 is a schematic illustration of the formation of monodisperse droplets in the present invention. Figure 4 is a schematic view showing the structure of the second embodiment of the plurality of input holes in the present invention. Figure 5 is a schematic view showing the structure of a third embodiment of a plurality of input holes in the present invention. Figure 6 is a schematic view showing the structure of the second embodiment of the apparatus of the present invention. Figure 7 is a perspective view showing the structure of the second embodiment of the apparatus of the present invention. Figure 8 is a schematic view showing the structure of a third embodiment of the apparatus of the present invention.

Claims (11)

一種產生實質上具有單分散性的微滴之方法,至少包含下列步驟: 使一連續相流體在一個沿著一縱長的長度方向延伸之微流道內流動,而該微流道沿著該長度方向具有實質恆定的截面;以及 順著相對於該長度方向之側向,將一分散相流體經由複數輸入孔引入該微流道內,以在該連續相流體內形成由該分散相流體所構成的單分散性微滴,其中複數輸入孔具有實質相同之孔徑,且相鄰任二個輸入孔被設置成在該長度方向上彼此錯開排列。A method of producing droplets having substantially monodispersity, comprising at least the steps of: flowing a continuous phase fluid in a microchannel extending along a lengthwise length along which the microchannel follows a substantially constant cross section in the length direction; and a dispersed phase fluid introduced into the microchannel along the lateral direction relative to the length direction to form a dispersed phase fluid in the continuous phase fluid A monodisperse droplet is constructed in which a plurality of input apertures have substantially the same aperture, and adjacent two input apertures are arranged to be staggered from each other in the length direction. 如請求項1所述之方法,其中,該引入該分散相流體的步驟包含以相對於該長度方向成一約90度的角度引入該分散相流體。The method of claim 1 wherein the step of introducing the dispersed phase fluid comprises introducing the dispersed phase fluid at an angle of about 90 degrees relative to the length direction. 一種產生實質上具有單分散性的微滴之裝置,其包含: 一實質呈剛性的第一部件;以及 一實質呈剛性的第二部件,係與該第一部件相對配置以在兩者之間界定出一微流道,可供一連續相流體流動,該微流道沿著一縱長的長度方向延伸,而且該微流道沿著該長度方向具有實質恆定的截面; 其中該裝置形成有複數輸入孔,可供一分散相流體順著相對於該長度方向之側向被引入該微流道內,以在該連續相流體內形成由該分散相流體所構成的單分散性微滴,且其中該複數輸入孔具有實質相同之孔徑,且相鄰任二輸入孔係沿該微流道之長度方向彼此錯開排列。A device for producing substantially monodisperse droplets, comprising: a substantially rigid first component; and a substantially rigid second component disposed opposite the first component to intervene therebetween Defining a microchannel for flowing a continuous phase fluid, the microchannel extending along a lengthwise direction, and the microchannel having a substantially constant cross section along the length; wherein the device is formed a plurality of input apertures for introducing a dispersed phase fluid into the microchannel along a lateral direction relative to the length direction to form a monodisperse droplet of the dispersed phase fluid in the continuous phase fluid, And wherein the plurality of input holes have substantially the same aperture, and the adjacent two input holes are staggered from each other along the length direction of the micro flow channel. 如請求項3所述之裝置,其中,該第一部件被構形成為一沿著該長度方向延伸的棒體,該第二部件被構形成為一管狀外殼且以同心方式配置於該第一部件外,進而將該微流道界定成一環狀構形。The device of claim 3, wherein the first member is configured as a rod extending along the length direction, the second member is configured as a tubular outer casing and is disposed concentrically in the first Outside the component, the microchannel is defined as an annular configuration. 如請求項4所述之裝置,其中,該等輸入孔係位於該第二部件。The device of claim 4, wherein the input apertures are located in the second component. 如請求項4所述之裝置,其中,該等輸入孔係位於該第一部件,且該第一部件被構形成一空心棒體。The device of claim 4, wherein the input apertures are located in the first component and the first component is configured as a hollow rod. 如請求項4所述之裝置,其中,該第一部件具有第一端,而該第一端處設置有一第一固定件,該第一固定件被固定於該第二部件的第一端,以防止該第一部件相對於該第二部件發生位移。The device of claim 4, wherein the first member has a first end, and the first end is provided with a first fixing member, the first fixing member being fixed to the first end of the second member, To prevent displacement of the first component relative to the second component. 如請求項7所述之裝置,其中,該第一部件具有相對於該第一端之第二端,而該第二端處設置有一第二固定件,該第二固定件徑向地抵靠於該第二部件相對於其第一端之第二端,以防止該第一部件相對於該第二部件發生徑向偏移。The device of claim 7, wherein the first member has a second end opposite the first end, and the second end is provided with a second fixing member, the second fixing member abuts radially The second member is opposite the second end of the first end thereof to prevent radial displacement of the first member relative to the second member. 如請求項8所述之裝置,其中,該第一固定件形成有一供該連續相流體進入的入口,以及其中該第一部件的第一端在該長度方向上朝向該入口呈尺寸漸縮,藉此與第二部件之第一端共同界定出一第一連通道,而該第一連通道以流體連通方式連接該入口和該微流道。The device of claim 8, wherein the first fixing member is formed with an inlet for the continuous phase fluid to enter, and wherein the first end of the first member is tapered in size toward the inlet in the length direction, Thereby, a first connecting passage is defined together with the first end of the second member, and the first connecting passage connects the inlet and the micro flow passage in fluid communication. 如請求項9所述之裝置,其中,該第二固定件形成有一出口,以及其中該第一部件的第二端在該長度方向上朝向該出口呈尺寸漸縮,藉此與第二部件之第二端共同界定出一第二連通道,而該第二連通道以流體連通方式連接該出口和該微流道。The device of claim 9, wherein the second fixing member is formed with an outlet, and wherein the second end of the first member is dimensioned toward the outlet in the length direction, thereby being combined with the second member The second end collectively defines a second connecting passage, and the second connecting passage connects the outlet and the micro flow passage in fluid communication. 如請求項10所述產生單分散性微滴之裝置,其中,該等輸入孔被設置成可使得該分散相流體能夠以相對於該長度方向成一約90度的角度被引入該微流道。The apparatus for producing a monodisperse droplet according to claim 10, wherein the input holes are arranged to enable the dispersed phase fluid to be introduced into the microchannel at an angle of about 90 degrees with respect to the length direction.
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