CN114917754B - Microfluidic colloidal particle separation device and separation method - Google Patents
Microfluidic colloidal particle separation device and separation method Download PDFInfo
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Abstract
Description
技术领域technical field
本发明涉及一种胶体颗粒分离装置及分离方法,具体涉及的是在微流控领域的一种胶体颗粒分离装置和分离方法。The invention relates to a colloid particle separation device and a separation method, in particular to a colloid particle separation device and a separation method in the field of microfluidics.
背景技术Background technique
胶体颗粒的分离在药物筛选、食品安全、航空航天、环境监测和军事装备等领域具有很好的应用前景。目前,胶体颗粒的分离技术有很多种:如微孔膜分离法、惯性分离法、磁泳分离法、电泳/介电泳分离法和热泳分离法等。The separation of colloidal particles has good application prospects in the fields of drug screening, food safety, aerospace, environmental monitoring and military equipment. At present, there are many separation techniques for colloidal particles: such as microporous membrane separation, inertial separation, magnetophoretic separation, electrophoretic/dielectrophoretic separation, and thermophoretic separation.
微孔膜分离技术出现较早,该技术采用过滤方法,但存在膜制作成本高、通用性差和膜孔易堵塞等缺点。Microporous membrane separation technology appeared earlier. This technology adopts filtration method, but there are disadvantages such as high cost of membrane production, poor versatility and easy clogging of membrane pores.
惯性分离技术利用微通道的几何结构来实现不同尺寸的颗粒的分离。惯性分离器具有通量高、成本低,不伤害活性颗粒、可连续流动等优点。对于尺寸从几微米到几十微米的颗粒来说,惯性分离是非常有效的;但是,当高通量分离目标颗粒时,惯性分离器分离纯度相对较低,很难将直径相近的颗粒有效分离。Inertial separation technology utilizes the geometry of microchannels to achieve separation of particles of different sizes. Inertial separators have the advantages of high throughput, low cost, no harm to active particles, and continuous flow. For particles ranging in size from several microns to tens of microns, inertial separation is very effective; however, when high-throughput separation of target particles occurs, the separation purity of inertial separators is relatively low, and it is difficult to effectively separate particles with similar diameters .
磁泳分离技术是指磁性颗粒在磁场力的驱动下定向移动从而实现颗粒分离。然而,大部分颗粒为非磁性颗粒,非磁性颗粒无法直接利用磁场力进行分离,所以大多采用颗粒先与磁珠结合后再用磁场力进行分离的方法,这样就必须预先对被分离颗粒进行磁珠标记。Magnetophoretic separation technology refers to the directional movement of magnetic particles driven by magnetic field force to achieve particle separation. However, most of the particles are non-magnetic particles, and non-magnetic particles cannot be separated directly by magnetic field force. Therefore, most of the particles are combined with magnetic beads and then separated by magnetic force. In this way, the separated particles must be magnetically separated in advance. Bead tag.
电泳分离技术是带电颗粒在电场下的运动(即为“电泳”)。介电泳分离技术是电场对中性粒子偶极矩的作用(即为“介电泳”)。电泳/介电泳分离技术的通量相对较高,颗粒的分离效果取决于颗粒的带电量/介电常数、尺寸和结构等,还取决于电解质流体的电学特性等。然而,一些活性颗粒在交流电场很有可能被极化,产生极化电荷导致死亡。Electrophoretic separation technology is the movement of charged particles under an electric field (ie "electrophoresis"). Dielectrophoretic separation technology is the effect of an electric field on the dipole moment of neutral particles (that is, "dielectrophoresis"). The flux of electrophoretic/dielectrophoretic separation technology is relatively high, and the separation effect of particles depends on the charge/dielectric constant, size and structure of the particles, as well as the electrical characteristics of the electrolyte fluid. However, some active particles are likely to be polarized in the AC electric field, resulting in polarized charges and death.
热泳分离技术是利用温度梯度场中冷热区对颗粒的热泳力大小不同,实现颗粒的分离。但同时热泳分离技术存在加热缓慢,温度场比较难精确控制等缺点。Thermophoretic separation technology uses the different thermophoretic forces of particles in the cold and hot areas in the temperature gradient field to achieve particle separation. But at the same time, the thermophoretic separation technology has the disadvantages of slow heating and difficult precise control of the temperature field.
发明内容Contents of the invention
本发明所要解决的技术问题是针对上述现有技术的不足,而提供了一种用于胶体颗粒分离的装置及方法,该装置具有结构简单、操作简便、成本低廉、分离效果好的特点,并能够根据所需分离颗粒尺寸的不同,设计相应分离通道的尺寸、分离级数,达到良好的分离效果。The technical problem to be solved by the present invention is to provide a device and method for the separation of colloidal particles in view of the deficiencies of the above-mentioned prior art. The device has the characteristics of simple structure, easy operation, low cost and good separation effect, and The size and number of separation stages of the corresponding separation channel can be designed according to the different particle sizes required for separation, so as to achieve a good separation effect.
为解决上述技术问题,本发明所采用的技术方案是:In order to solve the problems of the technologies described above, the technical solution adopted in the present invention is:
一种微流控胶体颗粒分离装置,其特征在于:包括微流体主通道、分离通道及侧通道;所述分离通道包括一级分离通道和二级分离通道;所述一级分离通道和二级分离通道沿所述微流体主通道的流动方向呈前后布置;在所述一级分离通道和二级分离通道出口分别设置一个所述侧通道;在所述微流体主通道中通入含有所需分离胶体颗粒的电解质溶液;在所述一级分离通道出口的侧通道和所述二级分离通道出口的侧通道通入不同浓度的具有与微流体主通道内电解质溶液相同电解质的溶液,使得一级分离通道和二级分离通道内产生溶液浓度梯度。A microfluidic colloidal particle separation device, characterized in that: it includes a microfluidic main channel, a separation channel and a side channel; the separation channel includes a primary separation channel and a secondary separation channel; the primary separation channel and the secondary The separation channel is arranged forward and backward along the flow direction of the microfluidic main channel; one side channel is respectively provided at the outlet of the primary separation channel and the secondary separation channel; Electrolyte solution for separating colloidal particles; the side channel at the outlet of the primary separation channel and the side channel at the outlet of the secondary separation channel are passed into different concentrations of solutions with the same electrolyte as the electrolyte solution in the microfluidic main channel, so that a The solution concentration gradient is generated in the primary separation channel and the secondary separation channel.
本发明涉及微流控胶体颗粒分离装置及分离方法,基本原理是通过对装置的设计及通道中通入的微流体的控制,在分离通道内部形成溶液浓度差,由于在溶液浓度梯度下带有不同电荷阴阳离子的扩散速度不同将产生自生电场,从而驱动胶体颗粒运动。The invention relates to a microfluidic colloid particle separation device and a separation method. The basic principle is to form a solution concentration difference inside the separation channel through the design of the device and the control of the microfluid introduced in the channel. The different diffusion speeds of anions and cations with different charges will generate a self-generated electric field, thereby driving the movement of colloidal particles.
对于需要分离的胶体颗粒,使之悬浮在一定的电解质溶液中,细微胶体颗粒在电解质溶液呈现带电特性,由于装置的分离通道内存在溶液的浓度梯度,电解质溶液中自由移动的离子由于具有不同扩散率,在离子浓度梯度作用下产生了局部电场,带电粒子在该电场下发生电泳迁移,产生定向运动。对于需要分离的胶体颗粒,还可使之悬浮在一定的离子型表面活化剂溶液中。表面活化剂中在水中电离后产生的离子会强烈吸附在胶体颗粒表面,使表面电荷高度带电,并在离子浓度梯度作用下产生了局部电场中发生电泳迁移。表面活化剂可以诱导对胶体颗粒大小或表面电荷不敏感的胶体颗粒产生扩散电泳。For the colloidal particles that need to be separated, suspend them in a certain electrolyte solution. The fine colloidal particles exhibit charging characteristics in the electrolyte solution. Due to the concentration gradient of the solution in the separation channel of the device, the freely moving ions in the electrolyte solution have different diffusion characteristics. Under the action of the ion concentration gradient, a local electric field is generated, and the charged particles undergo electrophoretic migration under the electric field, resulting in directional motion. For the colloidal particles that need to be separated, they can also be suspended in a certain ionic surfactant solution. The ions generated after ionization in water in the surfactant will be strongly adsorbed on the surface of the colloidal particles, making the surface charge highly charged, and electrophoretic migration occurs in the local electric field generated by the ion concentration gradient. Surfactants can induce diffusion electrophoresis of colloidal particles that are not sensitive to colloidal particle size or surface charge.
为了使装置胶体颗粒分离效果最优,应使粒子的扩散速度足够大,根据电解质溶液梯度中扩散电泳理论可知粒子的扩散速度表达式为:In order to optimize the separation effect of colloidal particles in the device, the diffusion velocity of the particles should be large enough. According to the theory of diffusion electrophoresis in the electrolyte solution gradient, the expression of the diffusion velocity of the particles is:
其中,∈为流体的介电常数,kB为玻尔兹曼定律常数,T为绝对温度,η为流体粘度,z为电解质离子价,e为元素电荷,ζ为粒子的zeta电位,C为电解质溶液浓度。Among them, ∈ is the dielectric constant of the fluid, k B is the Boltzmann's law constant, T is the absolute temperature, η is the fluid viscosity, z is the electrolyte ion valence, e is the element charge, ζ is the zeta potential of the particle, and C is electrolyte solution concentration.
在电解质浓度梯度下,不同迁移率的离子发生扩散产生的电场强度表达式为:Under the electrolyte concentration gradient, the expression of the electric field strength generated by the diffusion of ions with different mobility is:
其中,β为溶液中阳离子(D+)和阴离子(D-)的扩散系数的相对比值,表达式为:Among them, β is the relative ratio of the diffusion coefficients of cations (D + ) and anions (D - ) in solution, and the expression is:
由β的表达式可知,-1≤β≤1,其值取决于阳离子和阴离子的扩散系数。It can be seen from the expression of β that -1≤β≤1, its value depends on the diffusion coefficient of cations and anions.
为达到更好的分离效果,应增大粒子的扩散速度,一方面,溶液中阳离子和阴离子的扩散系数差异越大,|β|值越大,产生的电场强度就越大,粒子扩散速度也增大。另一方面,由表达式(1)可知,粒子的zeta电位ζ越大,扩散速度也越大。因此对于不同的溶液,胶体颗粒分离的效果也不同。In order to achieve a better separation effect, the diffusion velocity of the particles should be increased. On the one hand, the greater the difference in the diffusion coefficients of cations and anions in the solution, the greater the value of |β|, the greater the electric field intensity generated, and the greater the particle diffusion velocity. increase. On the other hand, it can be known from the expression (1) that the greater the zeta potential ζ of the particle, the greater the diffusion rate. Therefore, for different solutions, the effect of colloidal particle separation is also different.
本发明涉及的微流控技术是在微米尺度下对以层流或低雷诺数为主要特征的微流体进行操控的技术。胶体颗粒的尺寸为微米尺度,而微流控分离技术的操控范围也正好在微米尺度。微流控技术在胶体颗粒分离领域具有非常广阔的应用前景。The microfluidic technology involved in the present invention is a technology for manipulating microfluids whose main characteristics are laminar flow or low Reynolds number at the micron scale. The size of colloidal particles is on the micrometer scale, and the control range of microfluidic separation technology is exactly on the micrometer scale. Microfluidic technology has a very broad application prospect in the field of colloidal particle separation.
本发明涉及的建立溶液浓度梯度,对于离子型表面活化剂溶液,由于其电离出的离子在能够强烈吸附在胶体颗粒表面上,且其阳离子和阴离子的扩散系数差异较大,具有较大的β值,增强了扩散电泳作用,因此分离效果较一般电解质溶液更好。The establishment of the concentration gradient of the solution involved in the present invention, for the ionic surfactant solution, because the ionized ions can be strongly adsorbed on the surface of the colloidal particles, and the difference in the diffusion coefficients of the cations and anions is large, it has a large β Value, enhanced diffusion electrophoresis, so the separation effect is better than the general electrolyte solution.
本发明涉及的建立溶液浓度梯度,由于对于不同的溶液,其β值可正可负,故其产生的自身电场方向并不唯一,则需针对不同的微流体,需对其进行不同的控制:The establishment of the concentration gradient of the solution involved in the present invention, because the β value can be positive or negative for different solutions, so the direction of its own electric field generated by it is not unique, and it needs to be controlled differently for different microfluids:
以氯化钠溶液为例,由于其β<0,带负电荷的聚苯乙烯胶体颗粒(ζ<0)向有较高溶质浓度的区域移动,因此在对通入的微流体控制时,应使侧通道中通入相比于主通道中更高浓度的氯化钠溶液。同理,对于β>0的溶液,带负电荷的聚苯乙烯胶体颗粒(ζ<0)向有较低溶质浓度的区域移动,应使侧通道中通入相比于主通道中更低浓度的溶液。Taking sodium chloride solution as an example, because of its β<0, the negatively charged polystyrene colloidal particles (ζ<0) move to areas with higher solute concentrations, so when controlling the incoming microfluidics, it should be A higher concentration of sodium chloride solution is passed through the side channel than in the main channel. Similarly, for a solution with β>0, the negatively charged polystyrene colloidal particles (ζ<0) move to the region with a lower solute concentration, and the side channel should be filled with a lower concentration than that in the main channel. The solution.
以阴离子表面活性剂十二烷基硫酸钠(SDS)溶液为例,其β>0,带负电荷的聚苯乙烯胶体颗粒(ζ<0)向有较低溶质浓度的区域移动,因此在对通入的微流体控制时,应使侧通道中通入相比于主通道中更低浓度的十二烷基硫酸钠(SDS)溶液。Taking the anionic surfactant sodium dodecyl sulfate (SDS) solution as an example, its β>0, and the negatively charged polystyrene colloidal particles (ζ<0) move to the area with a lower solute concentration, so in the opposite When the microfluidic control is passed through, the side channel should be passed through a sodium dodecyl sulfate (SDS) solution with a lower concentration than that in the main channel.
以阳离子表面活性剂十二烷基三甲基溴化铵(DTAB)溶液为例,其β<0,带正电荷的表面活性剂离子(DTA+)吸附到聚苯乙烯胶体颗粒表面,从而改变其电荷,使之带正电(ζ>0)。因此在对通入的微流体控制时,应使侧通道中通入相比于主通道中更低浓度的十二烷基三甲基溴化铵(DTAB)溶液。Taking cationic surfactant dodecyltrimethylammonium bromide (DTAB) solution as an example, its β<0, the positively charged surfactant ion (DTA + ) is adsorbed on the surface of polystyrene colloidal particles, thereby changing Its charge makes it positively charged (ζ>0). Therefore, when controlling the incoming microfluid, the side channel should be fed with a lower concentration of dodecyltrimethylammonium bromide (DTAB) solution than that in the main channel.
本发明涉及的胶体颗粒分离通道,分离通道的尺寸及分离级数可根据所需分离胶体颗粒的特性设计,达到最优化分离效果,且分离级数不局限于一级或二级。The size and number of separation stages of the colloidal particle separation channel involved in the present invention can be designed according to the characteristics of the colloidal particles to be separated to achieve the optimal separation effect, and the number of separation stages is not limited to one or two stages.
有益效果:Beneficial effect:
本发明涉及一种微流控胶体颗粒分离装置,由于胶体颗粒分离所受的驱动力由溶液浓度梯度产生,故只需建立起溶液浓度差,无需外界条件,也无需外加场力。与以往胶体颗粒分离装置相比,大大简化了装置结构,降低成本,且该装置涉及的方法对胶体颗粒无其他物性要求,无需对胶体颗粒预处理,因此其应用范围更广,具有很高的应用价值。The invention relates to a microfluidic colloidal particle separation device. Since the driving force for the colloidal particle separation is generated by the concentration gradient of the solution, it only needs to establish the concentration difference of the solution without external conditions or external field force. Compared with the previous colloidal particle separation device, the structure of the device is greatly simplified and the cost is reduced, and the method involved in the device has no other requirements on the physical properties of the colloidal particles and does not require pretreatment of the colloidal particles, so its application range is wider and it has high Value.
附图说明Description of drawings
图1为微流控胶体颗粒分离装置的整体结构示意图;1 is a schematic diagram of the overall structure of a microfluidic colloidal particle separation device;
图2为微流控胶体颗粒分离装置的原理示意图;2 is a schematic diagram of the principle of a microfluidic colloidal particle separation device;
图中1.微流体主通道;2.分离通道;3.侧通道。In the figure 1. microfluidic main channel; 2. separation channel; 3. side channel.
具体实施方式Detailed ways
为了加深本发明的理解,下面我们将结合附图对本发明作进一步详述,该实施例仅用于解释本发明,并不构成对本发明保护范围的限定。In order to deepen the understanding of the present invention, the present invention will be further described below in conjunction with the accompanying drawings. This embodiment is only used to explain the present invention, and does not constitute a limitation to the protection scope of the present invention.
图1示出了本发明一种微流控胶体颗粒分离装置的基本结构示意图。Fig. 1 shows a schematic diagram of the basic structure of a microfluidic colloidal particle separation device of the present invention.
图2示出了本发明一种微流控胶体颗粒分离装置的原理示意图。Fig. 2 shows a schematic diagram of the principle of a microfluidic colloidal particle separation device of the present invention.
本发明一种微流控胶体颗粒分离装置,包括微流体主通道1、分离通道2及侧通道3。分离通道2包括一级分离通道和二级分离通道;一级分离通道和二级分离通道沿微流体主通道1的流动方向呈前后布置;在一级分离通道和二级分离通道出口分别设置一个侧通道3。A microfluidic colloid particle separation device of the present invention comprises a microfluidic main channel 1 , a separation channel 2 and a side channel 3 . The separation channel 2 includes a primary separation channel and a secondary separation channel; the primary separation channel and the secondary separation channel are arranged forward and backward along the flow direction of the microfluidic main channel 1; Side channel 3.
在微流体主通道1中通入含有所需分离胶体颗粒的电解质溶液;在一级分离通道出口的侧通道和二级分离通道出口的侧通道通入不同浓度的具有与微流体主通道内电解质溶液相同电解质的溶液,使得一级分离通道和二级分离通道内产生溶液浓度梯度。Pass into the electrolytic solution that contains required separation colloidal particle in microfluidic main channel 1; In the side channel of one-level separation channel outlet and the side channel of secondary separation channel outlet, pass into the electrolyte solution that has the electrolyte in the microfluidic main channel of different concentrations The solution is a solution of the same electrolyte, so that a solution concentration gradient is generated in the primary separation channel and the secondary separation channel.
一级分离通道包括等间距设置的至少两条一级通道;二级分离通道包括等间距设置的至少两条二级通道;一级通道的宽度小于第二通道的宽度。The primary separation channel includes at least two primary channels arranged at equal intervals; the secondary separation channel includes at least two secondary channels arranged at equal intervals; the width of the primary channel is smaller than that of the second channel.
一级通道的宽度是第二通道的宽度的一半。The width of the primary channel is half the width of the second channel.
分离通道宽度大于胶体颗粒且小于100μm;The width of the separation channel is larger than that of colloidal particles and less than 100 μm;
胶体颗粒在电解质溶液中呈现带电特性,包括带正电的胶体粒子和带负电的胶体粒子。带正电的胶体粒子包括金属的氧化物、金属的氢氧化物胶体粒子。带负电的胶体粒子包括金属的硫化物、非金属氧化物、土壤胶体粒子、硅酸胶体粒子科和银铂金胶体粒子。Colloidal particles present charged characteristics in electrolyte solution, including positively charged colloidal particles and negatively charged colloidal particles. The positively charged colloidal particles include metal oxide and metal hydroxide colloidal particles. Negatively charged colloidal particles include metal sulfides, non-metallic oxides, soil colloidal particles, silicic acid colloidal particles and silver platinum colloidal particles.
如图2所示,假设所需分离的胶体颗粒直径为0.5μm和1μm的聚苯乙烯胶体颗粒,通入的流体为十二烷基硫酸钠(SDS)溶液。设计主通道宽5μm,一级通道宽1μm,长5μm,间距2μm,二级通道宽2μm,长5μm,间距2μm。并在主通道通入浓度为10×10-3mol/L含有聚苯乙烯胶体颗粒的十二烷基硫酸钠(SDS)溶液,在两级侧通道都通入浓度为0.1×10-3mol/L的十二烷基硫酸钠(SDS)溶液。本装置工作时,十二烷基硫酸钠(SDS)溶液电离出的阴离子(十二烷基硫酸根离子,DS—)会吸附在胶体颗粒表面上,使聚苯乙烯胶体颗粒带负电。并且装置分离通道内会形成的离子浓度差,在离子浓度梯度下,由于阳离子(Na+)扩散速度大于阴离子(十二烷基硫酸根离子,DS—)扩散速度,阳离子以更快的速度往分离通道迁移,则带负电的聚苯乙烯胶体颗粒在阳离子的吸引下同样往分离通道迁移,达到分离的目的。小胶体颗粒则在一级通道得以分离,大胶体颗粒在二级通道得以分离。As shown in Figure 2, assuming that the colloidal particles to be separated have diameters of 0.5 μm and 1 μm polystyrene colloidal particles, the fluid passed through is sodium dodecyl sulfate (SDS) solution. The main channel is designed with a width of 5 μm, a primary channel with a width of 1 μm, a length of 5 μm, and a spacing of 2 μm, and a secondary channel with a width of 2 μm, a length of 5 μm, and a spacing of 2 μm. A sodium dodecyl sulfate (SDS) solution with a concentration of 10×10 -3 mol/L containing polystyrene colloidal particles is passed into the main channel, and a concentration of 0.1×10 -3 mol is passed into the two-stage side channels. /L of sodium dodecyl sulfate (SDS) solution. When the device is working, the anions (dodecylsulfate ion, DS - ) ionized from the sodium dodecyl sulfate (SDS) solution will be adsorbed on the surface of the colloidal particles, making the polystyrene colloidal particles negatively charged. And the ion concentration difference will be formed in the separation channel of the device. Under the ion concentration gradient, because the diffusion speed of cations (Na + ) is faster than the diffusion speed of anions (dodecyl sulfate ion, DS — ), the cations go to the When the separation channel migrates, the negatively charged polystyrene colloidal particles also migrate to the separation channel under the attraction of cations to achieve the purpose of separation. Small colloidal particles are separated in the primary channel, and large colloidal particles are separated in the secondary channel.
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