CN108855255A - Measure micro-fluidic chip, preparation method and the application of dynamic light scattering - Google Patents
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Abstract
Description
技术领域technical field
本发明涉及微流控芯片检测技术和动态光散射测量领域，具体涉及一种用于动态光散射纳米颗粒检测的微流控芯片及其制备方法。The invention relates to the field of microfluidic chip detection technology and dynamic light scattering measurement, in particular to a microfluidic chip for dynamic light scattering nanoparticle detection and a preparation method thereof.
背景技术Background technique
动态光散射(DLS)也被称为准弹性光散射，通过测定由溶液中微粒的布朗运动而引起散射光的多普勒频移及其角度依赖性，确定溶液中分子或颗粒物的扩散系数、流体力学半径、并计算颗粒群粒径分布函数(也称粒径谱)。它无需对样品进行荧光标记，是唯一可能实现液体活检的粒径谱分析技术，具有响应速度快，信息量大，且测量下限可拓展到亚微米量级等优点。基于该原理的分析仪已在蛋白质结构表征、聚集过程解析及相互作用分析中发挥了重要作用。Dynamic light scattering (DLS), also known as quasi-elastic light scattering, determines the diffusion coefficient, Hydrodynamic radius, and calculate particle size distribution function (also known as particle size spectrum). It does not require fluorescent labeling of samples, and is the only particle size spectrometry analysis technology that can realize liquid biopsy. It has the advantages of fast response speed, large amount of information, and the lower limit of measurement can be extended to sub-micron levels. Analyzers based on this principle have played an important role in protein structure characterization, aggregation process resolution and interaction analysis.
但传统的用于测量动态光散射的装置，体积庞大，集成性差，测量前的准备工作较繁琐，同时测量结果的精确度不高，易受外界环境的影响。However, the traditional devices for measuring dynamic light scattering are bulky, poorly integrated, and the preparation work before measurement is cumbersome. At the same time, the accuracy of measurement results is not high, and they are easily affected by the external environment.
因此，需要开发一种新型的动态光散射测量方法或者装置，以能以较低的成本快速、简便地测量获得溶液中分子或者颗粒物的相关参数。Therefore, it is necessary to develop a new dynamic light scattering measurement method or device to quickly and easily measure and obtain relevant parameters of molecules or particles in solution at a lower cost.
发明内容Contents of the invention
针对现有技术的以上缺陷或改进需求，本发明提供了一种用于测量动态光散射的微流控芯片、其制备方法以及应用，本发明的其一目的在于在微流控技术的基础上，提供一种用于测量单角度或多角度动态光散射的集成了光纤的微流控芯片。在降低了外界干扰的同时，可以同时测量多个角度的散射光信号并提高测量的效率和准确度。本发明的其二目的在于提供一种制备上述微流控芯片的制备方法，此方法可有效实现微流控芯片的制备，简单直接。此外，本发明还提供了采用以上微流控芯片测量溶液中分子或者颗粒物的相关参数的方法。In view of the above defects or improvement needs of the prior art, the present invention provides a microfluidic chip for measuring dynamic light scattering, its preparation method and application. One purpose of the present invention is to , providing a microfluidic chip integrated with an optical fiber for measuring single-angle or multi-angle dynamic light scattering. While reducing external interference, it can simultaneously measure scattered light signals from multiple angles and improve measurement efficiency and accuracy. The second object of the present invention is to provide a method for preparing the above-mentioned microfluidic chip, which can effectively realize the preparation of the microfluidic chip, and is simple and direct. In addition, the present invention also provides a method for measuring relevant parameters of molecules or particles in a solution by using the above microfluidic chip.
按照本发明的一个方面，提供一种测量单角度或多角度动态光散射的微流控芯片，其包括溶液沟道、溶质注入通道、溶液注入通道、溶剂注入通道、输入自聚焦透镜、输出自聚焦透镜、增透膜、角度刻度盘、输入耦合光纤和输出耦合光纤，其中，According to one aspect of the present invention, there is provided a microfluidic chip for measuring single-angle or multi-angle dynamic light scattering, which includes a solution channel, a solute injection channel, a solution injection channel, a solvent injection channel, an input self-focusing lens, an output self- Focusing lens, anti-reflection coating, angle dial, input coupling fiber and output coupling fiber, wherein,
溶液沟通设置在微流控芯片上，溶液沟通用于溶质待测量的颗粒溶液，在溶液沟道一端处设置有溶液注入通道、溶质注入通道和溶剂注入通道，以分别用于通过对应的通道输入溶液、溶质或者溶剂，在溶液沟道的两侧分别设置有输入耦合光纤和输出耦合光纤，分别对应形成光源输入通道和散射光输出通道，在输入耦合光纤和输出耦合光纤各自靠近溶液沟道的一侧分别设置有输入自聚焦透镜和输出自聚焦透镜，在输出耦合光纤出射端设置有增透膜，增透膜同时位于微流控芯片上，The solution communication is set on the microfluidic chip, and the solution communication is used for the particle solution of the solute to be measured. A solution injection channel, a solute injection channel and a solvent injection channel are set at one end of the solution channel, which are respectively used for input through the corresponding channels. For solution, solute or solvent, an input coupling fiber and an output coupling fiber are respectively arranged on both sides of the solution channel to form a light source input channel and a scattered light output channel respectively, and the input coupling fiber and the output coupling fiber are respectively close to the solution channel. An input self-focusing lens and an output self-focusing lens are respectively provided on one side, and an anti-reflection film is provided at the exit end of the output coupling fiber, and the anti-reflection film is also located on the microfluidic chip.
在微流控芯片上还设置有角度刻度盘，角度刻度盘相对于微流控芯片可转动，输出耦合光纤能随角度刻度盘同步转动，以调节接受散射光的角度，同时所述角度刻度盘用于确定散射光接收的角度。An angle dial is also arranged on the microfluidic chip, and the angle dial is rotatable relative to the microfluidic chip. The output coupling optical fiber can rotate synchronously with the angle dial to adjust the angle of receiving scattered light. At the same time, the angle dial Used to determine the angle at which scattered light is received.
进一步的，所述散射光输出通道的数量及角度根据实际测量需求确定，能设置任意角度和任意数量的散射光输出通道，以用来检测特定散射角度的散射光信息。Further, the number and angle of the scattered light output channels are determined according to actual measurement requirements, and any angle and any number of scattered light output channels can be set to detect scattered light information at a specific scattering angle.
进一步的，光源输入通道上的输入自聚焦透镜用来聚焦、准直入射激光，使得激光以指定角度入射到溶液沟道中溶液的指定位置；Further, the input self-focusing lens on the light source input channel is used to focus and collimate the incident laser light, so that the laser light is incident on the specified position of the solution in the solution channel at a specified angle;
所述散射光输出通道上的输出自聚焦透镜将特定角度范围内的散射光聚焦，高效耦合进入输出耦合光纤。The output self-focusing lens on the scattered light output channel focuses the scattered light within a specific angle range and efficiently couples it into the output coupling fiber.
进一步的，所述溶液注入通道的数量可设置为多个，其能分别注入各种不同浓度溶液和溶剂，从而调控待测溶液的浓度或者成分。Further, the number of the solution injection channels can be set in multiples, which can respectively inject various concentrations of solutions and solvents, thereby regulating the concentration or composition of the solution to be tested.
按照本发明的第二个方面，还提供一种如上微流控芯片在动态光散射测量中的应用，其包括如下步骤：According to the second aspect of the present invention, there is also provided an application of the above microfluidic chip in dynamic light scattering measurement, which includes the following steps:
将待测颗粒溶液输入溶液注入通道，流至溶液沟道，光源输入通道中的输入耦合光纤与激光器相连，激光器提供的激光耦合进入输入耦合光纤，激光通过输入耦合光纤到达输入自聚焦透镜，激光再经过输入自聚焦透镜准直后射入被测颗粒溶液，经被测颗粒溶液后发生散射，进入散射光输出通道，散射光输出通道中的输出耦合光纤与外界光学测量系统连接，被测溶液发出的散射光通过输出自聚焦透镜进入输出耦合光纤，并沿输出耦合光纤进入光学测量系统，从而实现对待测溶液的动态光散射的测量，最终根据动态散射光的信息获得待测颗粒溶液的对应参数。The particle solution to be measured is input into the solution injection channel and flows to the solution channel. The input coupling fiber in the light source input channel is connected to the laser. The laser light provided by the laser is coupled into the input coupling fiber, and the laser reaches the input self-focusing lens through the input coupling fiber. After being collimated by the input self-focusing lens, it is injected into the particle solution to be measured, and after being scattered by the particle solution to be measured, it enters the scattered light output channel, and the output coupling optical fiber in the scattered light output channel is connected to the external optical measurement system, and the measured solution The emitted scattered light enters the output coupling fiber through the output self-focusing lens, and enters the optical measurement system along the output coupling fiber, so as to realize the measurement of the dynamic light scattering of the solution to be measured, and finally obtain the corresponding particle solution of the solution to be measured according to the information of the dynamic scattered light. parameter.
按照本发明的第三个方面，还提供一种制备如上所述的微流控芯片的方法，其包括如下步骤：According to a third aspect of the present invention, there is also provided a method for preparing the above-mentioned microfluidic chip, which includes the following steps:
(1)根据微流控芯片的结构，制作掩膜版；(1) Make a mask plate according to the structure of the microfluidic chip;
(2)使用光刻曝光工艺，利用上述掩膜版，加工出制作微流控芯片所需的芯片基片模板；(2) Using the photolithography exposure process, using the above-mentioned mask plate, processing the chip substrate template required for making the microfluidic chip;
(3)将输入耦合光纤与输出耦合光纤根据设计放置在上述芯片基片模板上方的指定位置，进行倒模，将上述输入耦合光纤与输出耦合光纤集成到上述微流控芯片基片中，在芯片表面开孔，将输入和输出自聚焦透镜放置在输入耦合光纤通道口和输出耦合光纤通道口上；(3) Place the input coupling optical fiber and the output coupling optical fiber at the specified position above the above-mentioned chip substrate template according to the design, perform inversion, and integrate the above-mentioned input coupling optical fiber and output coupling optical fiber into the above-mentioned microfluidic chip substrate. Holes are opened on the surface of the chip, and the input and output self-focusing lenses are placed on the input coupling fiber channel port and the output coupling fiber channel port;
(4)在上述输入耦合光纤、输出耦合光纤以及输入自聚焦透镜、输出自聚焦透镜固定连接于上述微流控芯片基片后，加装与上述微流控芯片基片尺寸相当的微流控芯片盖片，完成微流控芯片制备。(4) After the above-mentioned input coupling optical fiber, output coupling optical fiber, input self-focusing lens, and output self-focusing lens are fixedly connected to the above-mentioned microfluidic chip substrate, install a microfluidic control device with a size equivalent to the above-mentioned microfluidic chip substrate. Cover the chip to complete the preparation of the microfluidic chip.
进一步的，步骤(1)中掩膜版采用基材为苏打玻璃(Sodalime)的苏打玻璃铬板。Further, the mask plate in step (1) uses a soda glass chrome plate whose substrate is soda glass (Sodalime).
进一步的，微流控芯片基片材质为聚二甲基硅氧烷。Further, the microfluidic chip substrate is made of polydimethylsiloxane.
以上发明构思中的用于测量动态光散射的微流控芯片，其内部同时设置了光纤和透镜，将传统动态光散射装置的光路集成在微流控芯片中，使动态光散射测量装置的体积小型化。在芯片输出光这一侧沿着横截面刻出一个扇形凹槽，凹槽的厚度略大于光纤包层的直径，使得光纤可以插入凹槽中，又可以在其中的位置固定下来，不会轻易发生移动。同时可以在凹槽内刻上角度，这样就方便依照实验需要调节输出光纤所插入的位置，以上就构成了一个角度刻度盘的形式。The microfluidic chip used to measure dynamic light scattering in the above inventive concept is equipped with optical fiber and lens at the same time, and the optical path of the traditional dynamic light scattering device is integrated in the microfluidic chip, so that the volume of the dynamic light scattering measurement device miniaturization. A fan-shaped groove is engraved along the cross-section on the side of the chip output light. The thickness of the groove is slightly larger than the diameter of the fiber cladding, so that the fiber can be inserted into the groove and can be fixed in its position. Movement occurs. At the same time, the angle can be engraved in the groove, so that it is convenient to adjust the position where the output optical fiber is inserted according to the experimental needs, and the above constitutes a form of an angle dial.
总体而言，通过本发明所构思的以上技术方案与现有技术相比，能够取得下列有益效果：Generally speaking, compared with the prior art, the above technical solutions conceived by the present invention can achieve the following beneficial effects:
(1)通过使用微流道和角度刻度盘的形式，将角度旋转台集成在芯片上，克服了传统动态光散射实验装置体积大，集成性差的缺点。(1) By using the form of microchannel and angle dial, the angle rotation stage is integrated on the chip, which overcomes the shortcomings of large volume and poor integration of traditional dynamic light scattering experimental devices.
(2)可以通过设计不同角度和不同数量的散射光通道，用来测量特定散射角度的散射光信息，获取更多的测量信息，进而获取更准确的颗粒粒度分布。(2) By designing scattered light channels with different angles and different numbers, it can be used to measure the scattered light information of a specific scattering angle, obtain more measurement information, and then obtain more accurate particle size distribution.
(3)通过在输出面镀增透膜，降低激光在出射面的反射率，减少二次散射，可以大大提高了动态光散射测量的效率。(3) By coating the output surface with an anti-reflective coating, the reflectivity of the laser light on the exit surface is reduced, and secondary scattering is reduced, which can greatly improve the efficiency of dynamic light scattering measurement.
(4)设计与输入激光光斑尺寸相匹配的沟道，使得输入光束能完全进入溶液，从而避免散射光中含有入射光束的成分，提高实验精度。(4) Design a channel that matches the size of the input laser spot, so that the input beam can completely enter the solution, thereby avoiding the component of the incident beam in the scattered light and improving the accuracy of the experiment.
(5)将溶液注入通道设置为三个，中间一个通道用于注入溶液，另外两个通道分别用于注入溶质和溶剂，利用泵或滴管的形式，精确控制进入沟道的量，从而实现在实验过程中随时改变溶液的浓度。(5) The solution injection channel is set to three, the middle channel is used to inject the solution, and the other two channels are used to inject the solute and the solvent respectively, and the amount entering the channel is precisely controlled by using a pump or a dropper, so as to realize Change the concentration of the solution at any time during the experiment.
(6)本发明还提出一种制备上述微流控芯片的制备方法，此方法可高效实现用于动态光散射测量的集成了光纤的微流控芯片的制备。(6) The present invention also proposes a method for preparing the above-mentioned microfluidic chip, which can efficiently realize the preparation of a microfluidic chip integrated with an optical fiber for dynamic light scattering measurement.
附图说明Description of drawings
图1是本发明实施例中微流控芯片的剖面图；Fig. 1 is a cross-sectional view of a microfluidic chip in an embodiment of the present invention;
图2是本发明实施例中微流控芯片局部俯视图。Fig. 2 is a partial top view of the microfluidic chip in the embodiment of the present invention.
在所有附图中，相同的附图标记用来表示相同的元件或结构，其中：Throughout the drawings, the same reference numerals are used to designate the same elements or structures, wherein:
1、输入光纤2、输出光纤3、增透膜4、溶液沟道5-1、输入自聚焦透镜5-2、输出自聚焦透镜6、微流控芯片7、溶质注入通道8、溶液注入通道9、溶剂注入通道10、角度刻度盘1. Input optical fiber 2, output optical fiber 3, anti-reflection coating 4, solution channel 5-1, input self-focusing lens 5-2, output self-focusing lens 6, microfluidic chip 7, solute injection channel 8, solution injection channel 9. Solvent injection channel 10. Angle dial
具体实施方式Detailed ways
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。此外，下面所描述的本发明各个实施方式中所涉及到的技术特征只要彼此之间未构成冲突就可以相互组合。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not constitute a conflict with each other.
微流控技术是随着微纳制造工艺发展起来的生化分析技术，液体可在微流沟道中进行反应和检测，已经广泛用于蛋白质、DNA等物质分析监测。微流通道与光纤所激发的光斑直径相当，易于实现光路耦合。基于以上基础，做出了本发明申请。Microfluidic technology is a biochemical analysis technology developed along with the micro-nano manufacturing process. Liquids can be reacted and detected in microfluidic channels, and have been widely used in the analysis and monitoring of proteins, DNA and other substances. The diameter of the spot excited by the microfluidic channel is equivalent to that of the optical fiber, and it is easy to realize optical path coupling. Based on the above basis, the present invention application has been made.
图1是本发明实施例中微流控芯片的剖面图；图2是本发明实施例中微流控芯片局部俯视图，由以上两图可知，该微流控芯片包括溶液沟道、输入自聚焦透镜、输出自聚焦透镜、溶质注入通道、溶剂注入通道、溶液注入通道、输入耦合光纤、输出耦合光纤、增透膜以及角度刻度盘。Figure 1 is a cross-sectional view of the microfluidic chip in the embodiment of the present invention; Figure 2 is a partial top view of the microfluidic chip in the embodiment of the present invention, as can be seen from the above two figures, the microfluidic chip includes a solution channel, an input self-focusing Lens, output self-focusing lens, solute injection channel, solvent injection channel, solution injection channel, input coupling fiber, output coupling fiber, anti-reflection coating and angle dial.
其中，所述微流控芯片其内部设置有溶液沟道4，在溶液沟道上方设置有溶液注入通道8、溶质注入通道7和溶剂注入通道9；溶液沟道4的两侧分别设置有输入耦合光纤1和输出耦合光纤2，在光纤靠近沟道这一侧，分别设置有输入自聚焦透镜5-1和输出自聚焦透镜5-2。所述散射光输出通道的数量及角度根据实际测量需求确定，理论上可以设置任意角度和多个数量的散射光输出通道，用来检测特定散射角度的散射光信息。所述光源输入通道口的自聚焦透镜5-1用来聚焦、准直入射激光，使得激光以指定角度入射到直沟道中溶液的指定位置；所述散射光输出通道口的输出自聚焦透镜5-2将特定角度范围内的散射光聚焦，高效耦合进入光纤。Wherein, the microfluidic chip is provided with a solution channel 4 inside, and a solution injection channel 8, a solute injection channel 7 and a solvent injection channel 9 are arranged above the solution channel; both sides of the solution channel 4 are respectively provided with input The coupling fiber 1 and the output coupling fiber 2 are respectively provided with an input self-focusing lens 5-1 and an output self-focusing lens 5-2 on the side of the fiber close to the channel. The number and angle of the scattered light output channels are determined according to the actual measurement requirements. In theory, any angle and multiple numbers of scattered light output channels can be set to detect scattered light information at a specific scattering angle. The self-focusing lens 5-1 of the input channel port of the light source is used to focus and collimate the incident laser light, so that the laser light is incident on the specified position of the solution in the straight channel at a specified angle; the output self-focusing lens 5-1 of the scattered light output channel port -2 Focus the scattered light in a specific angle range and couple it into the optical fiber efficiently.
使用时，颗粒悬浮液通过溶液注入通道8，进入溶液沟道4。激光经过输入光纤1，经过输入自聚焦透镜5-1耦合后，照射溶液沟道4中的样品。通过样品后的散射光经输出自聚焦透镜5-2耦合后，可以从输出光纤2输出，经过增透膜3减少二次散射光后，得到精确的测量结果。In use, the particle suspension passes through the solution injection channel 8 and enters the solution channel 4 . The laser light passes through the input optical fiber 1 and is coupled by the input self-focusing lens 5-1 to irradiate the sample in the solution channel 4. After passing through the sample, the scattered light can be output from the output optical fiber 2 after being coupled by the output self-focusing lens 5-2, and after passing through the anti-reflection coating 3 to reduce the secondary scattered light, an accurate measurement result can be obtained.
具体的，一种测量单角度或多角度动态光散射的微流控芯片的应用，其包括如下步骤：Specifically, an application of a microfluidic chip for measuring single-angle or multi-angle dynamic light scattering, which includes the following steps:
待测溶液从溶液注入通道8进入，流至溶液沟道4。光源输入通道中的输入耦合光纤1与激光器相连，激光器提供的激光耦合进入发射光纤，激光通过发射光纤到达发射自聚焦透镜5-1，激光再经过发射自聚焦透镜准直后射入被测溶液；散射光通道中的输出耦合光纤2与光学测量系统连接，被测溶液发出的散射光通过接收自聚焦透镜5-2进入接收光纤，并沿接收光纤进入光学测量系统，从而实现对待测溶液的动态光散射的测量。The solution to be tested enters from the solution injection channel 8 and flows to the solution channel 4 . The input coupling fiber 1 in the input channel of the light source is connected to the laser, and the laser provided by the laser is coupled into the emitting fiber, and the laser passes through the emitting fiber to the emitting self-focusing lens 5-1, and then the laser is collimated by the emitting self-focusing lens and injected into the solution to be measured The output coupling optical fiber 2 in the scattered light channel is connected with the optical measurement system, and the scattered light sent by the measured solution enters the receiving optical fiber through the receiving self-focusing lens 5-2, and enters the optical measuring system along the receiving optical fiber, thereby realizing the measurement of the solution to be measured Measurement of dynamic light scattering.
同时,在微流控芯片中，还可以加入了角度刻度盘10这一模块。输出散射光经过自聚焦透镜5-2耦合后，进入到输出光纤2中，由于实验的需要，经常会测量多个不同角度的散射光，如30度，45度，60度等。角度刻度盘10的设计，很好的解决了这一问题。可以根据测量的需要，将输出光纤插入凹槽中，使输出光纤卡合至对应的角度，从而就可以得到某一特定角度的散射光。At the same time, in the microfluidic chip, the module of angle dial 10 can also be added. The output scattered light enters the output optical fiber 2 after being coupled by the self-focusing lens 5-2. Due to the needs of the experiment, scattered light at multiple different angles is often measured, such as 30 degrees, 45 degrees, 60 degrees, etc. The design of the angle dial 10 solves this problem well. According to the needs of measurement, the output optical fiber can be inserted into the groove, so that the output optical fiber can be snapped to the corresponding angle, so that the scattered light at a specific angle can be obtained.
一种用于测量单角度或多角度动态光散射的集成了光纤的微流控芯片的制备方法：A preparation method of a microfluidic chip integrated with an optical fiber for measuring single-angle or multi-angle dynamic light scattering:
(1)根据上述微流控芯片的结构，制作掩膜版；掩膜版设计使用辅助软件AutoCAD绘制平面掩模图形，由于负光刻胶显影时溶解未曝光部分，因此流道结构部分设置为透光，周围背景设置为不透光；光通道部分同周围背景一样设置为不透光；为了具体制备掩膜版，优选地，掩膜版用基材为苏打玻璃(Sodalime)的苏打玻璃铬板；(1) According to the structure of the above-mentioned microfluidic chip, make a mask plate; the mask plate design uses the auxiliary software AutoCAD to draw a plane mask pattern, and the unexposed part is dissolved when the negative photoresist is developed, so the flow channel structure is set as Translucent, the surrounding background is set to be opaque; the light channel part is set to be opaque like the surrounding background; in order to specifically prepare the mask plate, preferably, the mask plate is soda glass (Sodalime) with a base material of soda glass chrome plate;
(2)使用光刻曝光工艺，加工出制作上述微流控芯片所需的芯片模板；为了具体实现芯片模板的制备，优选地，使用4英寸直径的单面抛光单晶硅片制作芯片模板；将匀胶，软烤后的硅片与上述光刻掩膜版放入光刻机中曝光，将曝光后的硅片经过后烤、显影之后，成为芯片基片模板；(2) Using a photolithography exposure process to process the chip template required for making the above-mentioned microfluidic chip; in order to specifically realize the preparation of the chip template, preferably, a single-sided polished single-crystal silicon wafer with a diameter of 4 inches is used to make the chip template; Put the silicon wafer after uniform glue and soft baking and the above-mentioned photolithography mask into a photolithography machine for exposure, and after the exposed silicon wafer is post-baked and developed, it becomes a chip substrate template;
(3)将上述入射光纤与出射光纤根据设计放置在上述芯片基片模板上方的指定位置，进行芯片倒模；为了具体制作出微流控芯片，优选地，采用具有良好光学特性的聚合物材料PDMS制作微流控芯片，即聚二甲基硅氧烷(Polydimethylsiloxane)；为了具体实现输入耦合光纤和输出偶尔会光纤的功能，优选地，采用SMA905光谱仪光纤，纤芯直径为100μm，数值孔径为0.20-0.37；将未凝固的PDMS混合液倒入装有上述芯片基片模具与光纤的培养皿中，并用负压环境将培养皿中气泡抽出，加速固化后将PDMS混合液固化后的培养皿取出，用手术刀将模板与固化PDMS部分剥离，并按照芯片边框裁剪成一定大小，完成芯片基片的倒模；在制作完成的PDMS芯片基片表面精确开孔，将直径为0.3mm的输入、输出自聚焦透镜放置在光通道口；(3) The above-mentioned incident optical fiber and outgoing optical fiber are placed on the specified position above the above-mentioned chip substrate template according to the design, and the chip is inverted; in order to specifically make a microfluidic chip, preferably, a polymer material with good optical properties is used PDMS makes a microfluidic chip, that is, polydimethylsiloxane (Polydimethylsiloxane); in order to specifically realize the function of input coupling optical fiber and output occasionally optical fiber, preferably, adopt SMA905 spectrometer optical fiber, the core diameter is 100 μ m, and the numerical aperture is 0.20-0.37; Pour the unsolidified PDMS mixture into the petri dish equipped with the above-mentioned chip substrate mold and optical fiber, and use a negative pressure environment to pump out the air bubbles in the petri dish, accelerate the curing and cure the petri dish after the PDMS mixture is cured Take it out, peel off the template and the cured PDMS part with a scalpel, and cut it into a certain size according to the chip frame to complete the inversion of the chip substrate; precisely open holes on the surface of the completed PDMS chip substrate, and input a 0.3mm diameter , The output self-focusing lens is placed at the optical channel port;
(4)以上述芯片基片为基准，在固化PDMS上裁剪出相同大小的芯片盖片；选取对应口径的打孔器，在上述芯片基片中的液室部分沿垂直于芯片平面方向打孔，构建输入、输出通道；将上述芯片基片与芯片盖片经过表面处理后贴合压紧并加热，将两片芯片组件牢固键合。(4) Based on the above-mentioned chip substrate, cut out a chip cover sheet of the same size on the cured PDMS; select a puncher with a corresponding caliber, and punch holes in the liquid chamber part of the above-mentioned chip substrate along the direction perpendicular to the plane of the chip , to build input and output channels; after surface treatment, the above-mentioned chip substrate and chip cover are bonded, pressed and heated, and the two chip components are firmly bonded.
本领域的技术人员容易理解，以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。It is easy for those skilled in the art to understand that the above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention, All should be included within the protection scope of the present invention.
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