CN106219482A - The sealing-in device of a kind of micro-fluidic chip and method for sealing - Google Patents
The sealing-in device of a kind of micro-fluidic chip and method for sealing Download PDFInfo
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- 238000007789 sealing Methods 0.000 title claims abstract description 74
- 238000000034 method Methods 0.000 title claims abstract description 24
- 239000000758 substrate Substances 0.000 claims abstract description 27
- 238000009434 installation Methods 0.000 claims abstract description 11
- -1 polydimethylsiloxane Polymers 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims description 31
- 238000002474 experimental method Methods 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 4
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- 238000013461 design Methods 0.000 claims description 2
- 239000010408 film Substances 0.000 claims 7
- 239000007789 gas Substances 0.000 claims 4
- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 claims 4
- 239000010409 thin film Substances 0.000 claims 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims 1
- 239000011248 coating agent Substances 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- JZZIHCLFHIXETF-UHFFFAOYSA-N dimethylsilicon Chemical compound C[Si]C JZZIHCLFHIXETF-UHFFFAOYSA-N 0.000 claims 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims 1
- 230000005611 electricity Effects 0.000 claims 1
- 238000005194 fractionation Methods 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 210000001215 vagina Anatomy 0.000 claims 1
- 239000004205 dimethyl polysiloxane Substances 0.000 abstract description 26
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 abstract description 26
- 238000007906 compression Methods 0.000 abstract description 14
- 230000006835 compression Effects 0.000 abstract description 13
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 23
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 21
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 21
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- 238000004458 analytical method Methods 0.000 description 2
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- 239000003480 eluent Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00349—Creating layers of material on a substrate
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00222—Integrating an electronic processing unit with a micromechanical structure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C2201/00—Manufacture or treatment of microstructural devices or systems
- B81C2201/01—Manufacture or treatment of microstructural devices or systems in or on a substrate
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Abstract
本发明公开了一种微流控芯片的封接装置及其封接方法。精密导向结构件通过紧固件固定安装在基板上对应的定位构件中；所述基板上层叠有一层聚二甲基硅氧烷薄膜后放置微流控芯片；所述微流控芯片上层叠有第二层的所述聚二甲基硅氧烷薄膜；透明硬质盖板置于第二层的所述聚二甲基硅氧烷薄膜上，所述透明硬质盖板通过所述精密导向结构件来控制位置及运动方向；微动装置安装基座安装于所述精密导向结构件的末端，微动装置安装于所述微动装置安装基座上。组装好各装置后，设定微动装置压缩量，并进行动态调整，完成多维微流控芯片的高质量封接，且拆分便捷，各器件能够重复使用。
The invention discloses a microfluidic chip sealing device and a sealing method thereof. The precision guide structure is fixedly installed in the corresponding positioning member on the substrate through fasteners; a layer of polydimethylsiloxane film is laminated on the substrate and then a microfluidic chip is placed; the microfluidic chip is laminated with The polydimethylsiloxane film of the second layer; the transparent hard cover plate is placed on the polydimethylsiloxane film of the second layer, and the transparent hard cover plate passes through the precision guide The structure is used to control the position and direction of movement; the installation base of the micro-motion device is installed at the end of the precision guiding structure, and the micro-motion device is installed on the installation base of the micro-motion device. After assembling each device, set the compression amount of the micro-motion device and perform dynamic adjustment to complete the high-quality sealing of the multi-dimensional microfluidic chip, and it is convenient to disassemble, and each device can be reused.
Description
技术领域technical field
本发明涉及微流控芯片技术领域，具体涉及一种微流控芯片的封接装置与封接方法。The invention relates to the technical field of microfluidic chips, in particular to a sealing device and a sealing method for a microfluidic chip.
背景技术Background technique
在微通道系统中对流体进行操控的技术被称为微流控技术，以微流控技术为核心，通过加工不同流通关系的微通道，可用于生物、化学、生物医学等领域的分析研究工作，具有这样逻辑特征的、可进行信息传递的微通道芯片系统被称为微流控芯片。The technology of manipulating fluid in a microchannel system is called microfluidic technology. With microfluidic technology as the core, it can be used for analysis and research in the fields of biology, chemistry, and biomedicine by processing microchannels with different flow relationships. , A microchannel chip system with such logical features and capable of information transfer is called a microfluidic chip.
微流控芯片的键合封接过程一般可以分为两种：不可逆键合封接和可逆键合封接。不可逆键合封接可靠性高、封接均匀性好、成本高、实验参数不可变，而可逆键合封接成本低、可循环使用、可进行多参数实验、可靠性低、均匀性差。在现有所有的键合封接方案中对PDMS(Polydimethylsiloxane，聚二甲基硅氧烷)材料键合封接的强度和压力均不可控，过小的键合封接强度会导致泄漏的发生，过大的键合封接强度则对前端流体驱动力提出更大的要求，而更大的驱动压力又导致后端键合封接和管路密封的可靠性降低。综上所述，微流控芯片现有的键合封接方法，无法保障有高可靠性和均匀键合封接效果的同时实现低成本、循环使用和同时进行多项参数实验，无法满足科学研究的需要。The bonding and sealing process of microfluidic chips can generally be divided into two types: irreversible bonding and sealing and reversible bonding and sealing. Irreversible bonding and sealing have high reliability, good sealing uniformity, high cost, and unchangeable experimental parameters, while reversible bonding and sealing are low in cost, recyclable, multi-parameter experiments can be performed, low in reliability, and poor in uniformity. In all existing bonding and sealing schemes, the strength and pressure of PDMS (Polydimethylsiloxane, polydimethylsiloxane) material bonding and sealing are uncontrollable, and too small bonding and sealing strength will lead to leakage , Excessive bonding and sealing strength puts forward greater requirements on the driving force of the front-end fluid, and greater driving pressure leads to a decrease in the reliability of the rear-end bonding and sealing of the pipeline. In summary, the existing bonding and sealing methods for microfluidic chips cannot guarantee high reliability and uniform bonding and sealing effects while achieving low cost, recycling, and simultaneous multi-parameter experiments, which cannot meet scientific requirements. research needs.
随着科学研究的进一步深入，一维微流控芯片已经不能满足要求，多维逻辑关系的流通通道势必成为微流控芯片的发展方向。使用多维通道的多维分离微流控芯片是一种新型芯片，可将不同分离方法加以集成，构建多维分离系统，用于对复杂样品的分离分析。在多维分离系统中，不同维度分离之间的接口设计是分离系统的关键技术，具体地，在多维分离系统中，不同维度分离的控制和转接需要通过气动微阀来实现。气动微阀是有源阀中的一种，利用外接压缩气体(或负压)作为驱动力驱动微阀对微流体进行控制，而且气动微阀是微流控芯片上应用最多的微阀，对键合与封接的可靠性、均匀性提出了更高的要求，而传统键合封接方法已经不能满科学研究的需求，需要一套专门用于复杂微流控芯片的高键合封接成功率、封接压力均匀可控、低成本、可重复使用的封接装置与封接方法。With the further deepening of scientific research, one-dimensional microfluidic chips can no longer meet the requirements, and the circulation channel of multi-dimensional logical relationship is bound to become the development direction of microfluidic chips. The multidimensional separation microfluidic chip using multidimensional channels is a new type of chip that can integrate different separation methods to build a multidimensional separation system for the separation and analysis of complex samples. In the multi-dimensional separation system, the interface design between different dimensional separations is the key technology of the separation system. Specifically, in the multi-dimensional separation system, the control and switching of different dimensional separations need to be realized through pneumatic microvalves. Pneumatic microvalve is a kind of active valve, which uses external compressed gas (or negative pressure) as the driving force to drive the microvalve to control the microfluidics, and the pneumatic microvalve is the most widely used microvalve on the microfluidic chip. The reliability and uniformity of bonding and sealing put forward higher requirements, and the traditional bonding and sealing methods can no longer meet the needs of scientific research, and a set of high bonding and sealing success rates specially used for complex microfluidic chips is required , uniform and controllable sealing pressure, low cost, reusable sealing device and sealing method.
发明内容Contents of the invention
有鉴于此，本发明的目的在于提供一种微流控芯片的封接装置与封接方法，能够对多维复杂微流控芯片进行封接，在保证高封接质量和成功率，且封接压力均匀可调，可适用于不同规格的微流控芯片的封接的同时，可以循环重复使用。In view of this, the object of the present invention is to provide a microfluidic chip sealing device and sealing method, which can seal multi-dimensional and complex microfluidic chips, while ensuring high sealing quality and success rate, and sealing The pressure is uniform and adjustable, and it is applicable to the sealing of microfluidic chips of different specifications, and can be used repeatedly.
为实现上述目的，本发明实施例提供一种微流控芯片的封接装置，包含基板、PDMS薄膜、精密导向结构件、透明硬质盖板、紧固件、微动装置安装基座和微动装置；所述精密导向结构件通过所述紧固件固定安装在所述基板上对应的定位构件中；所述基板上层叠有一层所述PDMS薄膜后放置所述微流控芯片；所述微流控芯片上层叠有第二层的所述PDMS薄膜；所述透明硬质盖板置于第二层的所述PDMS薄膜上，所述透明硬质盖板通过所述精密导向结构件来控制位置及运动方向；所述微动装置安装基座安装于所述精密导向结构件的末端，所述微动装置安装于所述微动装置安装基座上。In order to achieve the above purpose, an embodiment of the present invention provides a sealing device for a microfluidic chip, which includes a substrate, a PDMS film, a precision guide structure, a transparent hard cover, fasteners, a micro-motion device mounting base, and a micro-fluidic device. The moving device; the precision guide structure is fixedly installed in the corresponding positioning member on the substrate through the fastener; the microfluidic chip is placed after a layer of the PDMS film is stacked on the substrate; the The second layer of the PDMS film is stacked on the microfluidic chip; the transparent hard cover is placed on the second layer of the PDMS film, and the transparent hard cover is passed through the precision guide structure. Control the position and direction of movement; the installation base of the micro-motion device is installed at the end of the precision guide structure, and the micro-motion device is installed on the installation base of the micro-motion device.
具体地，所述微动装置为极细螺纹致动杆或压电陶瓷促动器。Specifically, the micro-motion device is an actuating rod with extremely fine threads or a piezoelectric ceramic actuator.
可选地，所述精密导向结构为燕尾副、螺纹副、滚珠丝杠、多杆组合机构、精密加工的导轨之一Optionally, the precision guide structure is one of dovetail pair, thread pair, ball screw, multi-rod combination mechanism, and precision-machined guide rail
具体地，所述基板有平面度、平行度和垂直度要求，与所述精密导向结构件配合的定位构件有公差尺寸要求。Specifically, the base plate has requirements for flatness, parallelism and perpendicularity, and the positioning components that cooperate with the precision guide structure have requirements for tolerance dimensions.
具体地，所述透明硬质盖板由透明硬质材料制成，有平面度、平行度和垂直度要求，与所述精密导向结构件的配合的定位构件有公差尺寸要求。Specifically, the transparent hard cover plate is made of transparent hard material, which requires flatness, parallelism, and perpendicularity, and the positioning member that cooperates with the precision guiding structure has tolerance size requirements.
具体地，所述透明硬质盖板和所述基板上均设置有微流控芯片气体接口、液体接口以及电接口，不同规格的所述透明硬质盖板和所述基板上的微流控芯片气体接口、液体接口以及电接口的规格、数量和布局有所不同，能够根据不同微流控芯片的通道布局和/或实验需要进行更换，或根据特定微流控芯片的需求和/或实验需要进行定制。Specifically, the transparent hard cover and the substrate are provided with a microfluidic chip gas interface, a liquid interface, and an electrical interface, and the transparent hard cover and the microfluidic interface on the substrate have different specifications. The specifications, quantity and layout of the chip gas interface, liquid interface and electrical interface are different, and can be replaced according to the channel layout and/or experimental needs of different microfluidic chips, or according to the needs and/or experimental needs of specific microfluidic chips Customization is required.
具体地，所述透明硬质盖板的表面经过镀膜处理。Specifically, the surface of the transparent hard cover is coated.
本发明实施例还提供一种微流控芯片的封接方法，该方法包含如下步骤：The embodiment of the present invention also provides a method for sealing a microfluidic chip, the method comprising the following steps:
步骤1.组装封接装置：精密导向结构件通过紧固件固定安装在基板上对应的定位构件中，将微流控芯片置于层叠有一层PDMS薄膜的所述基板上，所述微流控芯片上层叠第二层所述PDMS薄膜，所述第二层PDMS薄膜上加盖透明硬质盖板，所述透明硬质盖板通过所述精密导向结构件来控制位置及运动方向，微动装置安装基座安装在所述精密导向结构的末端，微动装置安装在所述微动装置安装基座上，自此，整个封接装置处于基本组装完毕的状态；Step 1. Assembling the sealing device: the precision guiding structure is fixedly installed in the corresponding positioning member on the substrate through fasteners, and the microfluidic chip is placed on the substrate laminated with a layer of PDMS film. The microfluidic The second layer of the PDMS film is stacked on the chip, and the second layer of PDMS film is covered with a transparent hard cover, and the transparent hard cover controls the position and the direction of movement through the precision guiding structure, and the micro-movement The installation base of the device is installed at the end of the precision guide structure, and the micro-motion device is installed on the installation base of the micro-motion device. Since then, the entire sealing device is in a basically assembled state;
步骤2.参数设定和初始调节：根据所选用或设计的所述微动装置特性，对所述微动装置进行调零/调同步，并根据所选用的微流控芯片中通道深浅、前端流体驱动压强大小等因素设置所述微动装置的压缩量，并进行压缩；Step 2. Parameter setting and initial adjustment: According to the selected or designed characteristics of the micro-motion device, perform zero adjustment/synchronization of the micro-motion device, and according to the depth of the channel in the selected microfluidic chip, the front end Factors such as fluid driving pressure set the compression amount of the micro-motion device and perform compression;
步骤3.动态调试：将所需的气体外部连接件、液体外部连接件以及电外部连接件通过对应的气体接口、液体接口以及电接口接入所述微流控芯片，打开液路系统，在液体入口处供给实验用液、标准液(如：缓冲溶液、洗脱液)等，根据预封接后的所述微流控芯片是否泄漏、所述微流控芯片出口液体流速是否正常等反馈状态实时调整所述微动装置的压缩量，若所述微流控芯片中液体流速变化小，所述微流控芯片无泄漏，则达到最佳工作状态；之后，打开气路系统，调节所述微动装置，使得气动微阀能够正常开闭，即工作在最佳状态，调整完毕后，所述微动装置自锁。Step 3. Dynamic debugging: Connect the required gas external connectors, liquid external connectors and electrical external connectors to the microfluidic chip through the corresponding gas interface, liquid interface and electrical interface, open the liquid circuit system, and The liquid inlet is supplied with experimental liquid, standard liquid (such as buffer solution, eluent), etc., according to whether the pre-sealed microfluidic chip is leaking, whether the flow rate of the liquid at the outlet of the microfluidic chip is normal, etc. adjust the compression amount of the micro-motion device in real time, if the change of the liquid flow rate in the microfluidic chip is small and the microfluidic chip has no leakage, then the best working state is reached; after that, open the gas circuit system and adjust the The above-mentioned micro-motion device enables the pneumatic micro-valve to open and close normally, that is, it works in the best state. After the adjustment, the micro-motion device is self-locking.
通过上述三个步骤，完成对所述微流控芯片的封接，从而进行后续实验工作。Through the above three steps, the sealing of the microfluidic chip is completed, so that subsequent experimental work can be performed.
具体地，通过反向调整所述微动装置的压缩量的方式，能够快速拆分已封接的微流控芯片，且所述拆分后的微流控芯片及所述封接装置均能够重复使用。Specifically, the sealed microfluidic chip can be disassembled quickly by reversely adjusting the compression amount of the micro-motion device, and both the disassembled microfluidic chip and the sealing device can reuse.
从上面所述可以看出，本发明实施例提供的微流控芯片的封接装置及封接方法操作简便，封接方法步骤简单，可以重复使用，封接压力均匀可调，封接质量高，同时封接装置中的微动装置的压缩量可调，可适用于不同规格的的微流控芯片的封接。另外，封接装置中的透明硬质盖板和基板均能够根据需求进行更换，也能够根据特定微流控芯片的需要或实验需求进行定制，以满足多维分离微流控芯片的封接需求。It can be seen from the above that the sealing device and sealing method of the microfluidic chip provided by the embodiment of the present invention are easy to operate, the steps of the sealing method are simple, can be used repeatedly, the sealing pressure is uniform and adjustable, and the sealing quality is high , and at the same time, the compression amount of the micro-motion device in the sealing device is adjustable, which is applicable to the sealing of microfluidic chips of different specifications. In addition, the transparent hard cover and substrate in the sealing device can be replaced according to requirements, and can also be customized according to the needs of specific microfluidic chips or experimental requirements, so as to meet the sealing requirements of multi-dimensional separation microfluidic chips.
附图说明Description of drawings
图1(a)为本发明实施例微流控芯片的封接装置的主视图，图1(b)为本发明实施例微流控芯片的封接装置的俯视图；Fig. 1(a) is a front view of a sealing device for a microfluidic chip according to an embodiment of the present invention, and Fig. 1(b) is a top view of a sealing device for a microfluidic chip according to an embodiment of the present invention;
图2为本发明实施例的微流控芯片的封接方法的流程图。FIG. 2 is a flowchart of a sealing method for a microfluidic chip according to an embodiment of the present invention.
具体实施方式detailed description
为使本发明的目的、技术方案和优点更加清楚明白，以下结合具体实施例，并参照附图，对本发明进一步详细说明。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with specific embodiments and with reference to the accompanying drawings.
需要说明的是，本发明实施例中所有使用“第一”和“第二”的表述均是为了区分两个相同名称非相同的实体或者非相同的参量，可见“第一”“第二”仅为了表述的方便，不应理解为对本发明实施例的限定，后续实施例对此不再一一说明。It should be noted that all expressions using "first" and "second" in the embodiments of the present invention are to distinguish two entities with the same name but different parameters or parameters that are not the same, see "first" and "second" It is only for the convenience of expression, and should not be construed as a limitation on the embodiments of the present invention, which will not be described one by one in the subsequent embodiments.
如图1(a)所示，为本发明实施例微流控芯片的封接装置的主视图，如图1(b)所示，为本发明实施例微流控芯片的封接装置的俯视图。所述微流控芯片的封接装置包含微流控芯片1、透明硬质盖板2、基板3、微动装置4、精密导向结构件5、紧固件7、微动装置安装基座8、PDMS薄膜9。具体地，精密导向结构件5通过紧固件7固定安装在基板3上的定位构件中，基板3上层叠有一层PDMS薄膜9，微流控芯片1放置在PDMS薄膜9上，微流控芯片1上层叠有第二层PDMS薄膜9，透明硬质盖板2置于所述第二层PDMS薄膜9上，透明硬质盖板2通过所述精密导向结构件5来控制位置及运动方向，微动装置安装基座8安装于精密导向结构件5末端，微动装置4安装于该微动装置安装基座8上。As shown in Figure 1(a), it is a front view of the sealing device of the microfluidic chip according to the embodiment of the present invention, and as shown in Figure 1(b), it is a top view of the sealing device of the microfluidic chip according to the embodiment of the present invention . The sealing device of the microfluidic chip includes a microfluidic chip 1, a transparent hard cover plate 2, a substrate 3, a micro-motion device 4, a precision guiding structure 5, a fastener 7, and a micro-motion device mounting base 8 , PDMS film 9. Specifically, the precision guiding structure 5 is fixedly installed in the positioning member on the substrate 3 through the fastener 7, and a layer of PDMS film 9 is stacked on the substrate 3, and the microfluidic chip 1 is placed on the PDMS film 9, and the microfluidic chip 1 is laminated with a second layer of PDMS film 9, and a transparent hard cover plate 2 is placed on the second layer of PDMS film 9, and the position and direction of movement of the transparent hard cover plate 2 are controlled by the precision guide structure 5, The micro-motion device installation base 8 is installed on the end of the precision guide structure 5 , and the micro-motion device 4 is mounted on the micro-motion device installation base 8 .
本发明实施例的透明硬质盖板2用于执行施压过程，将压力均匀施加在与透明硬质盖板2接触的PDMS薄膜9上，并传递给微流控芯片1；同时，透明硬质盖板2还起到观察窗口作用，用于观察所述微流控芯片1的工作情况，以及观察所述微流控芯片1中产生的荧光及反应结果等；另外，透明硬质盖板2还具有微流控芯片的气体接口、液体接口以及电接口功能，用于安装对应的气体外部连接件、液体外部连接件以及电外部连接件。综上，透明硬质盖板2应选择透明硬质材料制成，且有平面度、平行度和垂直度要求，其上有与精密导向结构件5配合的定位构件，为保障配合的精确度，所述定位构件有公差尺寸要求；本发明实施例中，优选地，透明硬质盖板2表面经过镀膜处理，用于选择透过实验中需要的特定光线，滤去不需要的杂光，这样有利于外部系统对微弱信号的检测；透明硬质盖板2上设置有用于连接对应的气体外部连接件、液体外部连接件以及电外部连接件的气体接口、液体接口以及电接口；不同规格的透明硬质盖板2上的气体接口、液体接口以及电接口布局、数量和规格有所不同，同时不同规格的透明硬质盖板2表面镀膜不同，与精密导向结构件5相配合的定位构件的位置和大小也不同，透明硬质盖板2的规格能够根据实验需要进行更换，也能够根据特定微流控芯片的需要或实验需求进行定制。The transparent hard cover plate 2 of the embodiment of the present invention is used to perform the pressure application process, and the pressure is evenly applied on the PDMS film 9 in contact with the transparent hard cover plate 2, and transmitted to the microfluidic chip 1; at the same time, the transparent hard cover plate 2 The hard cover plate 2 also acts as an observation window for observing the working conditions of the microfluidic chip 1, and observing the fluorescence and reaction results generated in the microfluidic chip 1; in addition, the transparent hard cover plate 2 also has the gas interface, liquid interface and electrical interface functions of the microfluidic chip, and is used to install corresponding gas external connectors, liquid external connectors and electrical external connectors. To sum up, the transparent hard cover plate 2 should be made of transparent hard materials, and has requirements for flatness, parallelism and verticality. , the positioning member has a tolerance size requirement; in the embodiment of the present invention, preferably, the surface of the transparent hard cover plate 2 is coated to select the specific light required in the experiment and filter out unnecessary stray light. This is conducive to the detection of weak signals by the external system; the transparent hard cover plate 2 is provided with gas interfaces, liquid interfaces and electrical interfaces for connecting corresponding gas external connectors, liquid external connectors and electrical external connectors; different specifications The gas interface, liquid interface, and electrical interface layout, quantity and specification on the transparent hard cover plate 2 are different. At the same time, the surface coatings of the transparent hard cover plate 2 of different specifications are different. The positions and sizes of the components are also different, and the specifications of the transparent hard cover plate 2 can be replaced according to the experimental needs, and can also be customized according to the needs of specific microfluidic chips or experimental requirements.
本发明实施例的基板3用于承载微流控芯片1和PDMS薄膜9，该基板3有平面度、平行度和垂直度要求，该基板3上设置有与所述精密导向结构件5相适应的定位构件；另外，所述基板3上还设有用于连接对应的气体外部连接件、液体外部连接件以及电外部连接件的气体接口、液体接口以及电接口；不同规格的基板3上与所述精密导向结构件5相适应的定位构件的位置和大小不同，用于连接对应的气体外部连接件、液体外部连接件以及电外部连接件的气体接口、液体接口以及电接口的规格、数量和布局也不同，可根据实验需要进行更换，也可根据特定微流控芯片的需要或实验需求进行定制。The substrate 3 of the embodiment of the present invention is used to carry the microfluidic chip 1 and the PDMS film 9. The substrate 3 has requirements for flatness, parallelism and verticality. In addition, the substrate 3 is also provided with a gas interface, a liquid interface and an electrical interface for connecting the corresponding gas external connectors, liquid external connectors and electrical external connectors; the substrate 3 of different specifications is connected to the The positions and sizes of the positioning members adapted to the precision guide structure 5 are different, and the specifications, quantities and specifications of the gas interfaces, liquid interfaces and electrical interfaces used to connect the corresponding gas external connectors, liquid external connectors and electrical external connectors are different. The layout is also different, and can be replaced according to experimental needs, or customized according to the needs of specific microfluidic chips or experimental requirements.
优选地，本发明实施例的微动装置4选用带有自锁功能的微动装置作为压缩驱动装置，通过提供微小运动量向透明硬质盖板2施加压力，并可根据实际需要精确调节压缩量，从而保证透明硬质盖板2受力均匀且精准可控；在完成压缩过程后，通过自锁功能自锁，保证封接质量。可选地，微动装置4可以采用极细螺纹致动杆或压电陶瓷促动器等。Preferably, the micro-motion device 4 of the embodiment of the present invention selects a micro-motion device with self-locking function as the compression drive device, which applies pressure to the transparent hard cover plate 2 by providing a small amount of movement, and can precisely adjust the amount of compression according to actual needs , so as to ensure that the force on the transparent hard cover plate 2 is uniform and precisely controllable; after the compression process is completed, the self-locking function is used to self-lock to ensure the sealing quality. Optionally, the micro-movement device 4 may use an actuating rod with extremely fine threads or a piezoelectric ceramic actuator or the like.
本发明实施例的精密导向结构件5用于确定透明硬质盖板2的位置并限定透明硬质盖板2的运动方向，从而保证封接压力的均匀分布。图1所示的实施例中提供了采用精密加工的导轨作为精密导向结构件5的例子，但本发明并不限定于此。本发明的精密导向结构件5还可以采用燕尾副、螺纹副、滚珠丝杠和多杆组合机构等。譬如，当采用燕尾副作为精密导向结构件时，图1中的四根精密加工的导轨可用一个燕尾副替代，同时其它结构应做相应的调整。The precision guide structure 5 of the embodiment of the present invention is used to determine the position of the transparent hard cover 2 and limit the movement direction of the transparent hard cover 2, so as to ensure uniform distribution of sealing pressure. The embodiment shown in FIG. 1 provides an example of using a precision-machined guide rail as the precision guide structure 5 , but the present invention is not limited thereto. The precision guiding structure 5 of the present invention can also adopt dovetail pair, screw thread pair, ball screw and multi-rod combination mechanism and the like. For example, when a dovetail pair is used as a precision guide structure, the four precision-machined guide rails in Figure 1 can be replaced by a dovetail pair, and other structures should be adjusted accordingly.
本发明实施例的微流控芯片中的流道6横截面为长方形，但本发明并不应限定于此，由于微流控芯片的微通道布局多种多样，故所述微流控芯片中的流道6的横截面可以为菱形、圆形或其它形状。The cross-section of the flow channel 6 in the microfluidic chip of the embodiment of the present invention is rectangular, but the present invention should not be limited thereto. Since the microchannel layout of the microfluidic chip is varied, the microfluidic chip in the microfluidic chip The cross-section of the flow channel 6 can be rhombus, circle or other shapes.
本发明实施例中紧固件7用于实现部件间的紧固联接，紧固件7与其它部件的连接方式可以为螺纹连接、粘接和焊接等。In the embodiment of the present invention, the fastener 7 is used to realize the fast connection between the components, and the connection method between the fastener 7 and other components can be threaded connection, bonding, welding and the like.
本发明实施例中微动装置安装基座8用于实现微动装置4的正确安装，使微动装置4提供的压缩驱动力正确地传递至透明硬质盖板2上。In the embodiment of the present invention, the installation base 8 of the micro-motion device is used to realize the correct installation of the micro-motion device 4 , so that the compression driving force provided by the micro-motion device 4 can be correctly transmitted to the transparent hard cover plate 2 .
本发明实施例中PDMS薄膜9用于对微流控芯片1进行辅助封接，提高微流控芯片与封接装置接触界面的封接可靠性，并对插入的气体外部连接件、液体外部连接件以及电外部连接件起密封作用；本发明中PDMS薄膜厚度为50微米至1毫米，优选地，该PDMS薄膜厚度为50微米。In the embodiment of the present invention, the PDMS film 9 is used for auxiliary sealing of the microfluidic chip 1, improving the sealing reliability of the contact interface between the microfluidic chip and the sealing device, and sealing the inserted gas external connectors and liquid external connectors. Parts and electrical external connectors play a sealing role; the thickness of the PDMS film in the present invention is 50 microns to 1 mm, preferably, the thickness of the PDMS film is 50 microns.
如上所述，基于本发明的微流控芯片的封接装置结构简单，操作简便，可以重复使用，封接压力均匀可调，封接质量高。As mentioned above, the sealing device based on the microfluidic chip of the present invention is simple in structure, easy to operate, reusable, uniform and adjustable in sealing pressure, and high in sealing quality.
另外，本发明实施例还提供一种微流控芯片的封接方法。如图2所示，该封接方法主要包括：In addition, an embodiment of the present invention also provides a sealing method for a microfluidic chip. As shown in Figure 2, the sealing method mainly includes:
步骤11，组装封接装置：精密导向结构件5通过紧固件7固定安装在基板3上对应的定位构件中，将微流控芯片1置于层叠有一层PDMS薄膜9的基板3上，在微流控芯片1上层叠第二层PDMS薄膜9，在所述第二层PDMS薄膜9上加盖透明硬质盖板2，透明硬质盖板2通过精密导向结构件5来控制位置及运动方向，微动装置安装基座8安装在精密导向结构5的末端，微动装置4安装在所述微动装置安装基座8上，自此，整个封接装置处于基本组装完毕的状态；Step 11, assembling the sealing device: the precision guiding structure 5 is fixedly installed in the corresponding positioning member on the substrate 3 through the fastener 7, and the microfluidic chip 1 is placed on the substrate 3 with a layer of PDMS film 9 stacked on it. A second layer of PDMS film 9 is stacked on the microfluidic chip 1, and a transparent hard cover plate 2 is added on the second layer of PDMS film 9, and the position and movement of the transparent hard cover plate 2 are controlled by a precision guiding structure 5 direction, the micro-motion device mounting base 8 is installed on the end of the precision guide structure 5, and the micro-motion device 4 is mounted on the micro-motion device mounting base 8, and since then, the entire sealing device is in a basically assembled state;
步骤12，参数设定和初始调节：根据所选用或设计的微动装置特性，对微动装置4进行调零/调同步，并根据所选用的微流控芯片1中通道深浅、前端流体驱动压强大小等因素设置微动装置4的压缩量，并进行压缩；Step 12, parameter setting and initial adjustment: According to the characteristics of the selected or designed micro-motion device, perform zero adjustment/synchronization of the micro-motion device 4, and according to the channel depth and front-end fluid drive of the selected microfluidic chip 1 Factors such as the size of the pressure set the compression amount of the micro-motion device 4, and perform compression;
步骤13，动态调试：将所需的气体外部连接件、液体外部连接件以及电外部连接件通过对应的气体接口、液体接口以及电接口接入到微流控芯片1，打开液路系统，在液体入口处供给实验用液、标准液(如：缓冲溶液、洗脱液)等，根据预封接后的微流控芯片是否泄漏、微流控芯片出口液体流速是否正常等反馈状态实时调整微动装置4的压缩量，若微流控芯片1中液体流速变化小，微流控芯片1无泄漏，则达到最佳工作状态；之后，打开气路系统，调节微动装置4，使得气动微阀能够正常开闭，即工作在最佳状态，调整完毕后，微动装置4自锁。Step 13, dynamic debugging: Connect the required gas external connectors, liquid external connectors and electrical external connectors to the microfluidic chip 1 through the corresponding gas interface, liquid interface and electrical interface, open the liquid circuit system, and The liquid inlet is supplied with experimental liquid, standard liquid (such as buffer solution, eluent), etc., and the microfluidic chip is adjusted in real time according to the feedback status such as whether the pre-sealed microfluidic chip leaks and whether the flow rate of the liquid at the outlet of the microfluidic chip is normal. The compression amount of the moving device 4, if the change of the liquid flow rate in the microfluidic chip 1 is small, and the microfluidic chip 1 has no leakage, then the best working condition is reached; after that, open the air circuit system and adjust the micromoving device 4 so that the pneumatic microfluidic chip The valve can be opened and closed normally, that is, it works in the best state. After the adjustment is completed, the micro-motion device 4 is self-locking.
通过上述步骤11、步骤12、步骤13三个步骤，完成对微流控芯片1的封接，从而能够正常进行微流控芯片1的后续实验。Through the above three steps of step 11, step 12, and step 13, the sealing of the microfluidic chip 1 is completed, so that subsequent experiments on the microfluidic chip 1 can be carried out normally.
试验完成后，通过反向调节微动装置4的压缩量，撤去微动装置4的压力，可以快速方便的完成已封接的微流控芯片1的拆分。After the test is completed, by reversely adjusting the compression amount of the micro-motion device 4 and removing the pressure from the micro-motion device 4 , the disassembly of the sealed microfluidic chip 1 can be completed quickly and conveniently.
本发明实施例提供的微流控芯片的封接方法步骤简单，操作简便，通过上述三个步骤可简单快速地完成对微流控芯片的封接，且封接过程可逆，所有部件均可重复使用，能够满足多维微流控芯片的封接需求。The sealing method of the microfluidic chip provided by the embodiment of the present invention has simple steps and is easy to operate. The sealing of the microfluidic chip can be completed simply and quickly through the above three steps, and the sealing process is reversible, and all parts can be repeated. It can meet the sealing requirements of multi-dimensional microfluidic chips.
所属领域的普通技术人员应当理解：以上任何实施例的讨论仅为示例性的，并非旨在暗示本公开的范围(包括权利要求)被限于这些例子；在本发明的思路下，以上实施例或者不同实施例中的技术特征之间也可以进行组合，步骤可以以任意顺序实现，并存在如上所述的本发明的不同方面的许多其它变化，为了简明它们没有在细节中提供。Those of ordinary skill in the art should understand that: the discussion of any of the above embodiments is exemplary only, and is not intended to imply that the scope of the present disclosure (including claims) is limited to these examples; under the idea of the present invention, the above embodiments or Combinations between technical features in different embodiments are also possible, steps may be carried out in any order, and there are many other variations of the different aspects of the invention as described above, which are not presented in detail for the sake of brevity.
本发明的实施例旨在涵盖落入所附权利要求的宽泛范围之内的所有这样的替换、修改和变型。因此，凡在本发明的精神和原则之内，所做的任何省略、修改、等同替换、改进等，均应包含在本发明的保护范围之内。Embodiments of the present invention are intended to embrace all such alterations, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent replacements, improvements, etc. within the spirit and principles of the present invention shall be included within the protection scope of the present invention.
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