CN114950584B - A three-dimensional microfluidic channel chip structure and manufacturing method for droplet generation - Google Patents
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Abstract
本发明公开了一种用于液滴生成的三维立体微流道芯片结构和制作方法,包括上下设置的五个微通道层,第一微通道层和第二微通道层用于第一相和第二相的引入和分流,第三微通道层设有矩阵式排列的混合单元,用于第一相和第二相的混合,第四微通道流程设有与混合单元一一对应的液滴释放单元,用于第一相和第二相混合后形成液滴,第五微流道用于液滴的汇集和引出。本发明解决了平面液滴生成芯片可产液滴较少的问题,应用三维立体的微流道缩小单个液滴生成模块的占地面积,通过矩阵式的排列可实现每小时几升的液滴产量,有望实现年产吨级。
The invention discloses a three-dimensional microchannel chip structure and manufacturing method for droplet generation, including five microchannel layers arranged up and down, the first microchannel layer and the second microchannel layer are used for the first phase and the second microchannel layer. The introduction and diversion of the second phase, the third microchannel layer is provided with matrix-arranged mixing units for the mixing of the first phase and the second phase, and the fourth microchannel process is provided with liquid droplets corresponding to the mixing units one-to-one The releasing unit is used for forming droplets after the first phase and the second phase are mixed, and the fifth microchannel is used for collecting and leading out the droplets. The invention solves the problem that the planar droplet generation chip can produce fewer droplets, and uses three-dimensional micro-channels to reduce the footprint of a single droplet generation module, and can realize several liters of droplets per hour through the matrix arrangement It is expected to achieve an annual output of tons.
Description
技术领域technical field
本发明属于微加工技术领域,具体涉及一种用于液滴生成的三维立体微流道芯片结构及制造方法。The invention belongs to the technical field of micromachining, and in particular relates to a three-dimensional microfluidic channel chip structure and a manufacturing method for liquid drop generation.
背景技术Background technique
传统液滴采用振荡法、搅拌法、超声波乳化等方法生成,应用在食品、化妆品及药物的定点运输等领域。随着生物检测技术及微纳米材料的快速发展,微纳米级尺寸的液滴开始应用于微分子的生物检测、微型胶囊的制备以及微纳米颗粒的制备等工作。Traditional droplets are generated by methods such as oscillation, stirring, and ultrasonic emulsification, and are used in the fields of fixed-point transportation of food, cosmetics, and drugs. With the rapid development of biological detection technology and micro-nano materials, micro-nano-sized droplets have begun to be used in the biological detection of micromolecules, the preparation of microcapsules, and the preparation of micro-nano particles.
针对微型胶囊以及微纳米颗粒的制备,如何实现高通量的液滴生成是液滴生成芯片商业化的关键。现有的平面微流体液滴生成芯片以并行阵列化方式增加并行液滴生成模块数量,已实现采用玻璃-硅-玻璃材料,其中单个平面液滴生成模块长1.4mm,宽80um,生成液滴的尺寸21-28um,每小时产量最高达到升量级,液滴的产量有待进一步提高。For the preparation of microcapsules and micro-nanoparticles, how to achieve high-throughput droplet generation is the key to the commercialization of droplet generation chips. The existing planar microfluidic droplet generation chip uses parallel arrays to increase the number of parallel droplet generation modules. Glass-silicon-glass materials have been used. A single planar droplet generation module is 1.4mm long and 80um wide to generate droplets. The size of the droplet is 21-28um, and the output per hour can reach the liter level, and the output of the droplet needs to be further improved.
发明内容Contents of the invention
针对现有技术方案存在的问题与不足,本发明公开了一种应用于液滴生成的三维阵列式立体微流道芯片结构及制造方法。Aiming at the problems and deficiencies in the existing technical solutions, the present invention discloses a structure and a manufacturing method of a three-dimensional array three-dimensional micro-channel chip applied to droplet generation.
为了实现以上目的,本发明的技术方案为:In order to achieve the above object, the technical solution of the present invention is:
一种用于液滴生成的三维立体微流道芯片结构,A three-dimensional microfluidic chip structure for droplet generation,
本发明的有益效果为:The beneficial effects of the present invention are:
1)提出了微流体液滴生成的芯片三维立体阵列式微流道结构及其制造方法,解决了平面微流体液滴生成芯片可产液滴较少的问题,应用三维立体的微流道缩小单个液滴生成流道的占地面积,其中流体剪切处尺寸最小可至1-2um;1) The three-dimensional array microchannel structure and manufacturing method of the microfluidic droplet generation chip are proposed, which solves the problem that the planar microfluidic droplet generation chip can produce fewer droplets, and the three-dimensional microfluidic channel is used to reduce the size of a single chip. The footprint of the droplet generation channel, where the size of the fluid shear can be as small as 1-2um;
2)通过阵列式的三维立体微流道,液滴尺寸在5um至几百um的范围,并可达到每小时几升的液滴的较高产量,有望实现每年吨级的生产。2) Through the arrayed three-dimensional micro-channels, the droplet size ranges from 5um to hundreds of um, and can achieve a high output of several liters of droplets per hour, which is expected to achieve the production of tons per year.
附图说明Description of drawings
图1为三维立体阵列式微流道结构;Fig. 1 is a three-dimensional array microfluidic channel structure;
图2为三维立体阵列式微流道结构拆解图;Fig. 2 is a dismantling diagram of a three-dimensional array microfluidic structure;
图3为三维立体阵列式微流道结构截面图;3 is a cross-sectional view of a three-dimensional array microfluidic structure;
图4为三维立体阵列式微流道液滴生成示意图(三维图);Fig. 4 is a schematic diagram (three-dimensional diagram) of three-dimensional array microfluidic droplet generation;
图5为三维立体阵列式微流道液滴生成示意图(截面图);Fig. 5 is a schematic diagram (sectional view) of three-dimensional array microchannel droplet generation;
图6-12为三维立体阵列式微流道制造工艺流程图。Figure 6-12 is a flow chart of the manufacturing process of the three-dimensional array microfluidic channel.
具体实施方式Detailed ways
以下结合附图和具体实施例对本发明做进一步解释。本发明的各附图仅为示意以更容易了解本发明,其具体比例可依照设计需求进行调整。The present invention will be further explained below in conjunction with the accompanying drawings and specific embodiments. The drawings of the present invention are only schematic diagrams for easier understanding of the present invention, and their specific proportions can be adjusted according to design requirements.
本实例公开了一种用于液滴生成的三维立体阵列式微流道芯片结构,可参考图1-图3,包括五层微流道层,由下至上分别为第一微流道层100、第二微流道层200、第三微流道层300、第四微流道层400及第五微流道层500。This example discloses a three-dimensional array microchannel chip structure for droplet generation, which can refer to Figures 1-3, including five microchannel layers, from bottom to top are the
第一微流道层100具有第一垂直微流道101和第一半开放式平面微流道102;The
第二微流道层200具有第二垂直微流道201;The
第三微流道层300具有第二半开放式平面微流道301、第三垂直微流道302以及第三半开放式平面微流道303;The
第四微流道层400具有第四垂直微流道401和第五垂直微流道402;The
第五微流道层500具有第四半开放式平面微流道501和第六垂直微流道502。The
若该微流道芯片结构用于水包油液滴的生成,则微通道壁需具备亲水性;若生成油包水液滴,则微通道壁面需疏水。微流道的亲疏水性可通过材料选择或对通道壁进行表面改性来实现。If the microchannel chip structure is used to generate oil-in-water droplets, the microchannel wall must be hydrophilic; if water-in-oil droplets are to be generated, the microchannel wall must be hydrophobic. The hydrophilicity and hydrophobicity of microchannels can be achieved by material selection or surface modification of channel walls.
五个微流道层通过叠合导通形成多个流体的通入、分流和汇集的通道,例如,用于连续相流体和离散相流体生成液滴时:The five microfluidic layers are superposed and connected to form channels for the introduction, diversion and collection of multiple fluids, for example, when the continuous phase fluid and the discrete phase fluid generate droplets:
第一半开放式平面微流道102分为叉指设计的连续相分散流道105和离散相分散流道106,第一垂直微流道101分为与连续相分散流道105和离散相分散流道106一一对应连通的连续相入口103和离散相入口104;第一微流道层100用于多相流体的独立进入和传输;The first semi-open
第二垂直微流道201分为分别与连续相分散流道105和离散相分散流道106对应连通的多个连续相流道202和离散相流道203;第二微流道层200用于流体的分流;The second
第三微流道层300形成若干阵列式排布的混合单元,各混合单元由由下至上的第二半开放式平面微流道301、第三垂直微流道302和第三半开放式平面微流道303组合而成,分为连续相流道304和离散相流道305,并分别与连续相流道202和离散相流道203对应连通,使连续相和离散相分别进入混合单元;本实施例中,每个混合单元连通1个离散相流道203和2个连续相流道202,且离散相流道203位于两个连续相流道202中间;第二半开放式平面微流道301具有蜿蜒的流道结构,以作为流体流阻通道保证进入混合单元的连续相、离散相动压一致;第三半开放式平面微流道303形成使连续相流道304和离散相流道305连通的流体汇聚。The
第四垂直微流道401和第五垂直微流道402一一上下连接形成液滴释放单元,并与前述混合单元一一对应导通,第四垂直微流道401形成流体剪切,第五垂直微流道402用于液滴释放,各混合单元的流体两相混合后在第四微流道层400形成液滴;即,第三微流道层300和第四微流道层400组合形成单个液滴生成模块,多个模块阵列式排布。The fourth vertical micro-channel 401 and the fifth vertical micro-channel 402 are connected up and down to form a droplet discharge unit, and are connected with the aforementioned mixing unit one by one. The fourth vertical micro-channel 401 forms a fluid shear, and the fifth The
第五垂直微流道402与第四半开放式平面微流道501和第六垂直微流道502,第四半开放式平面微流道501用于液滴汇集,第六垂直微流道502设有液滴出口,用于液滴引出。The fifth vertical micro-channel 402 and the fourth semi-open planar micro-channel 501 and the sixth vertical micro-channel 502, the fourth semi-open planar micro-channel 501 is used for droplet collection, the sixth vertical micro-channel 502 A droplet outlet is provided for droplet extraction.
针对前述用于液滴生成的三维立体阵列式微流道芯片结构,相应液滴生成的方法,可参考图4-图5,连续相和离散相流体分别经第一微流道层、第二微流道层、第三微流道层、第四微流道层后形成液滴,并利用第五微流道层汇集并引出液滴。For the above-mentioned three-dimensional array microchannel chip structure for droplet generation, the corresponding droplet generation method can refer to Figure 4-Figure 5, the continuous phase and the discrete phase fluid pass through the first microchannel layer and the second microchannel layer respectively. After the channel layer, the third micro channel layer and the fourth micro channel layer, droplets are formed, and the fifth micro channel layer is used to collect and draw out the droplets.
首先,连续相流体602经连续相入口103,离散相流体601经离散相入口104引入微流道后,经连续相分散流道105和离散相分散流道106到达单个液滴生成模块。进一步地,流经连续相流道202(离散相流道203)、第二半开放式平面微流道301、连续相流道304(离散相流道305)至第三半开放式平面微流道303实现流体汇聚后,于第四垂直微流道401交汇并经第五垂直微流道402形成液滴603。最后,阵列中的与第四垂直微流道401及第五垂直微流道402同样的位置均生成液滴并连通第四半开放式平面微流道501,并经第六垂直微流道502引出大量的液滴。通过分别控制连续相和离散相流体进入芯片的流量(ul/min)以及微流道流体剪切处的尺寸达几微米/几十微米尺度,可实现5um至几百um级别的液滴生成。First, the
第三微流道层300中设计的流体流阻通道,保证阵列中进入每一个液滴生成模块的连续相、分散相的动压一致。通过阵列式排布数以万计的单个三维立体微流道阵列液滴生成模块,即生成每小时数升的液滴。The fluid flow resistance channels designed in the
进一步参考图6-12,本实例还公开一种用于水包油液滴生成的三维立体阵列式微流道芯片制造方法,包括如下步骤:With further reference to Figures 6-12, this example also discloses a method for manufacturing a three-dimensional array microfluidic channel chip for generating oil-in-water droplets, including the following steps:
步骤1,如图6(a)所示,第一微流道层100采用聚二甲基硅氧烷作基底,通过聚合物复制成形技术在下表面110加工第一垂直微流道101,如图6(b)所示上表面120加工出第一半开放式平面微流道102,且第一垂直微流道101与第一半开放式平面微流道102连通,并在微流道上形成亲水涂层;Step 1, as shown in Figure 6(a), the
步骤2,如图7所示,第二微流道层200采用玻璃作基底,通过激光加工技术可形成连通下表面210和上表面220的第二垂直微流道层201;Step 2, as shown in FIG. 7 , the
步骤3,如图8(a)所示,第三微流道层300采用硅作基底,通过深反应离子刻蚀技术在下表面310上蚀刻出第二半开放式平面微流道301,如图8(b)所示并在上表面320蚀刻出第三半开放式平面微流道303,如图8(c)所示,在第二半开放式平面微流道303往下加工出第三垂直微流道302;Step 3, as shown in Figure 8(a), the
步骤4,如图9(a)所示,第四流道层400采用玻璃作衬底,通过激光加工技术在上表面420上加工出第五垂直微流道402后,如图9(b)所示,在下表面410上加工出第四垂直微流道401;Step 4, as shown in Figure 9(a), the fourth
步骤5,如图10(a)所示,第五微流道层500采用聚二甲基硅氧烷作基底,通过聚合物复制成形技术在下表面510加工第四半开放式平面微流道501,如图10(b)所示,上表面120加工出第六垂直微流道502,且第四半开放式平面微流道501与第六垂直微流道502连通,并在微流道上形成亲水涂层;Step 5, as shown in Figure 10(a), the
步骤6,如图11所示,采用硅玻璃阳极键合工艺,在第三微流道层300两侧分别键合上第二流道层200和第四微流道层400,以连通第二垂直微流道层201、第二半开放式平面微流道301、第三垂直微流道302、第三半开放式平面微流道303、第四垂直微流道401和第五垂直微流道402;Step 6, as shown in FIG. 11 , uses a silicon glass anodic bonding process to bond the
步骤7,如图12所示,在步骤7的基础上采用等离子体键合的方法,在第二微流道层200的下表面键合上第一微流道层100,在第四微流道层400的上表面键合上第五微流道层100,实现了第一垂直微流道101至第六垂直微流道的连通。Step 7, as shown in Figure 12, adopts the plasma bonding method on the basis of step 7 to bond the first
微流道特征尺寸最小可达1-2um,也可控制为几十或几百微米尺度;单个液滴生成模块的占地面积小于1mm*50um。The minimum characteristic size of the microchannel can reach 1-2um, and it can also be controlled to a scale of tens or hundreds of microns; the footprint of a single droplet generation module is less than 1mm*50um.
步骤1、5中衬底,除聚二甲基硅氧烷以外还可选择硅或玻璃或特氟龙或亚克力或其他的高分子材料;步骤1、5中,除采用聚合物复制成形技术还可选择深反应离子刻蚀技术或激光诱导蚀刻快速成型技术或湿法刻蚀或热压印技术或激光烧蚀或喷砂或超声微加工或CNC机械加工等方法;In steps 1 and 5, in addition to polydimethylsiloxane, silicon or glass or Teflon or acrylic or other polymer materials can also be selected for the substrate; in steps 1 and 5, in addition to using polymer replication molding technology, You can choose deep reactive ion etching technology or laser-induced etching rapid prototyping technology or wet etching or hot embossing technology or laser ablation or sandblasting or ultrasonic micromachining or CNC machining and other methods;
步骤2、4中衬底,除采用玻璃作基底外还可选择硅或特氟龙或亚克力或聚二甲基硅氧烷或其他的高分子材料;步骤2、4中除采用激光加工技术还可选择深反应离子刻蚀技术或激光诱导蚀刻快速成型技术或湿法刻蚀或热压印技术或激光烧蚀或喷砂或超声微加工或或CNC机械加工等方法;Substrate in steps 2 and 4, in addition to using glass as the substrate, silicon or Teflon or acrylic or polydimethylsiloxane or other polymer materials can also be selected; in steps 2 and 4, in addition to using laser processing technology You can choose deep reactive ion etching technology or laser-induced etching rapid prototyping technology or wet etching or hot embossing technology or laser ablation or sandblasting or ultrasonic micromachining or CNC machining and other methods;
步骤3中衬底,除采用硅作基底外还可选择玻璃或特氟龙或亚克力或聚二甲基硅氧烷或其他的高分子材料;步骤3中除采用深反应离子刻蚀技术还可选择激光诱导蚀刻快速成型技术或湿法刻蚀或热压印技术或激光烧蚀或喷砂或超声微加工或或CNC机械加工等方法;In step 3, the substrate can be selected from glass or Teflon or acrylic or polydimethylsiloxane or other polymer materials except that silicon is used as the substrate; in step 3, in addition to using deep reactive ion etching technology, Choose laser-induced etching rapid prototyping technology or wet etching or hot embossing technology or laser ablation or sandblasting or ultrasonic micromachining or CNC machining;
步骤6中除采用硅玻璃阳极键合工艺,还可采用热键合或胶键合或金属中间层键合或低温键合技术等方法。In step 6, in addition to the silicon glass anodic bonding process, thermal bonding or glue bonding or metal interlayer bonding or low temperature bonding technology can also be used.
步骤7中除采用等离子体键合的方法,还可采用热键合或胶键合或金属中间层键合或低温键合技术等方法。In step 7, in addition to the plasma bonding method, thermal bonding, glue bonding, metal interlayer bonding, or low-temperature bonding technology can also be used.
上述实施例仅用来进一步说明本发明的一种用于液滴生成的三维立体阵列式微流道芯片结构及制造方法,但本发明并不局限于实施例,凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均落入本发明技术方案的保护范围内。The above-mentioned embodiments are only used to further illustrate a three-dimensional array microfluidic channel chip structure and manufacturing method for droplet generation of the present invention, but the present invention is not limited to the embodiments. Any simple modifications, equivalent changes and modifications made in the embodiments all fall within the protection scope of the technical solution of the present invention.
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