CN109647549A - Easily-replaced hydrophobic dielectric film and microfluidic chip - Google Patents
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Abstract
Description
技术领域technical field
本发明涉及微流控芯片领域，尤其是涉及一种易替换的疏水介电薄膜和一种微流控芯片。The invention relates to the field of microfluidic chips, in particular to an easily replaceable hydrophobic dielectric film and a microfluidic chip.
背景技术Background technique
基因组学和蛋白质组学是当今生物医学领域两大极为重要的研究领域。DNA/RNA测序是基因组学的重要组成部分，测序前文库构建工程浩大、费用昂贵，且非常耗时，一个训练有素的操作员需要执行近60个步骤才能准备好样品，一个样品需要工作超过12.5小时，也就是1.5个工作日(8小时/工作日)，准备4个样品则需要6天时间。如果4个样品平行进行，准备32个样品，需要12天时间，同时还需要规避污染或犯错的风险，文库构建的质量直接决定着测序实验的成败；而在以大规模检测蛋白质的结构和功能为主要目标的蛋白质组学研究中，要探明蛋白质的结构，首要任务就是开展大规模质谱检测和获取高质量的蛋白质结晶，因此涉及到大量样品预处理和最优结晶条件筛选。上述工作本质上都是一个样本处理问题,其中的目标样本稀缺，昂贵，体量极小，处理过程繁杂，有的还包含一定的化学反应。一段时间以来，学术界和产业界一直在寻求理想的基因组学和蛋白质组学通用的大规模，高效的样本处理技术。Genomics and proteomics are two extremely important research fields in today's biomedical field. DNA/RNA sequencing is an important part of genomics. Pre-sequencing library construction is a huge, expensive, and time-consuming process. A trained operator needs to perform nearly 60 steps to prepare a sample. A sample requires more than 12.5 hours, which is 1.5 working days (8 hours/working day), and it takes 6 days to prepare 4 samples. If 4 samples are performed in parallel, it will take 12 days to prepare 32 samples, and at the same time, the risk of contamination or mistakes needs to be avoided. The quality of library construction directly determines the success or failure of sequencing experiments; while large-scale detection of protein structure and function In proteomics research, which is the main goal, to determine the structure of proteins, the primary task is to carry out large-scale mass spectrometry detection and obtain high-quality protein crystallization. Therefore, it involves a large number of sample pretreatment and the screening of optimal crystallization conditions. The above work is essentially a sample processing problem, in which the target samples are scarce, expensive, extremely small in size, complicated in the processing process, and some contain certain chemical reactions. For some time now, academia and industry have been seeking large-scale, efficient sample processing techniques ideal for general use in genomics and proteomics.
微流控芯片技术被认为解决上述大量样本前处理的一个重要的潜在平台。微流控芯片的基本特征和最大优势是多种单元技术在微小可控平台上灵活组合和规模集成。液滴微流控技术是微流控芯片领域的一个重要分支，具有精准操控，形状可调，并行操作等优势。随着研究不断深入，数字液滴微流控技术逐渐显现出有别于现有其他技术的巨大潜力。Microfluidic chip technology is considered as an important potential platform to solve the above-mentioned large-scale sample pretreatment. The basic feature and greatest advantage of microfluidic chips is the flexible combination and scale integration of multiple unit technologies on tiny controllable platforms. Droplet microfluidic technology is an important branch in the field of microfluidic chips, which has the advantages of precise control, adjustable shape, and parallel operation. With the deepening of research, digital droplet microfluidics gradually shows great potential that is different from other existing technologies.
数字液滴微流控技术特点是灵活、易用和通用性强，对于从事生物医学研究的终端用户来说，将是一个革命性的工具。其潜在的应用包括但不限于：基因和蛋白质组学样品前处理、单细胞研究、临床诊断的即时检测、毒素和病菌的侦测和识别、环境监控、新药品筛选和精细化工合成等等。Digital droplet microfluidics is characterized by flexibility, ease of use, and versatility, and will be a revolutionary tool for end-users engaged in biomedical research. Its potential applications include, but are not limited to: genetic and proteomic sample preparation, single-cell research, point-of-care testing for clinical diagnosis, detection and identification of toxins and pathogens, environmental monitoring, new drug screening, and fine chemical synthesis, etc.
现有技术通常是采用在电极上直接镀疏水介电薄膜方式，存在如下问题：1.疏水介电薄膜与驱动电极板直接相连，容易被击穿；2.由于驱动电极板表面凹凸不平容易造成上方的疏水介电薄膜表面平整度不够；3.当疏水介电薄膜破损或者需要更换疏水介电薄膜时，只能将连接的驱动电极一起丢弃，造成驱动电极板不必要的浪费。本申请欲开发一种疏水介电薄膜，用于数字微流控芯片，目的是改善现有芯片表面问题。The prior art usually adopts the method of directly plating a hydrophobic dielectric film on the electrode, which has the following problems: 1. The hydrophobic dielectric film is directly connected to the driving electrode plate, which is easy to be broken down; 2. The uneven surface of the driving electrode plate is easy to cause The surface flatness of the upper hydrophobic dielectric film is not enough; 3. When the hydrophobic dielectric film is damaged or the hydrophobic dielectric film needs to be replaced, only the connected driving electrodes can be discarded together, resulting in unnecessary waste of the driving electrode plate. The present application intends to develop a hydrophobic dielectric film for use in digital microfluidic chips, in order to improve the surface problems of existing chips.
发明内容SUMMARY OF THE INVENTION
针对现有技术的不足，本发明所要解决的技术问题是提供一种易替换的疏水介电薄膜和一种微流控芯片。In view of the deficiencies of the prior art, the technical problem to be solved by the present invention is to provide an easily replaceable hydrophobic dielectric film and a microfluidic chip.
本发明所采取的技术方案是：The technical scheme adopted by the present invention is:
本发明提供一种易替换的疏水介电薄膜，包括疏水介电薄膜和贴在所述疏水介电薄膜上的框架。The present invention provides an easily replaceable hydrophobic dielectric film, comprising the hydrophobic dielectric film and a frame attached to the hydrophobic dielectric film.
优选地，所述框架的材料选自铝、亚克力中的任一种。为了起到支撑疏水介电薄膜和节约成本的目的，框架材料一般选用不易变形且易加工的材料。Preferably, the material of the frame is selected from any one of aluminum and acrylic. For the purpose of supporting the hydrophobic dielectric film and saving costs, the frame material is generally selected from a material that is not easily deformed and easy to process.
优选地，所述疏水介电薄膜包括介电层和疏水层。本发明的疏水介电薄膜可以是传统的介电层和疏水层组成的两层结构如在介电层聚对二甲苯(Parylene-C)上面涂覆疏水性材料特氟龙(teflon)，也可以是能够替代传统两层结构的同时具有疏水性和介电性的一层结构如CYTOP(perfluoro(1-butenyl vinyl ether)polymer)。本发明适用于所有的疏水材料包括CYTOP、PDMS以及各种商业超疏水涂料，如neverwet(R)，Fluoropel(Cytonix)，Ultra-Ever Dry等。Preferably, the hydrophobic dielectric film includes a dielectric layer and a hydrophobic layer. The hydrophobic dielectric film of the present invention can be a two-layer structure composed of a traditional dielectric layer and a hydrophobic layer, such as coating the hydrophobic material Teflon (teflon) on the dielectric layer Parylene-C, or It may be a one-layer structure such as CYTOP (perfluoro(1-butenyl vinyl ether) polymer) which can replace the traditional two-layer structure with both hydrophobicity and dielectricity. The present invention is applicable to all hydrophobic materials including CYTOP, PDMS and various commercial superhydrophobic coatings, such as neverwet(R), Fluoropel(Cytonix), Ultra-Ever Dry and the like.
本发明还提供一种微流控芯片，包括驱动电极、涂覆在所述驱动电极上的绝缘液体层和设置在所述绝缘液体层上的上述的疏水介电薄膜。The present invention also provides a microfluidic chip, comprising a driving electrode, an insulating liquid layer coated on the driving electrode, and the above-mentioned hydrophobic dielectric film disposed on the insulating liquid layer.
优选地，所述微流控芯片为单面驱动结构或双面驱动结构。Preferably, the microfluidic chip is a single-sided driving structure or a double-sided driving structure.
优选地，所述绝缘液体层的材料的介电常数>1.1。Preferably, the dielectric constant of the material of the insulating liquid layer is >1.1.
优选地，所述绝缘液体层的材料为天然绝缘油或人工合成绝缘油。Preferably, the material of the insulating liquid layer is natural insulating oil or synthetic insulating oil.
进一步优选地，所述天然绝缘油选自植物油和矿物油。Further preferably, the natural insulating oil is selected from vegetable oils and mineral oils.
进一步优选地，所述人工合成绝缘油选自芳香烃类绝缘油、醚类绝缘油、酯类绝缘油和硅油。Further preferably, the synthetic insulating oil is selected from aromatic hydrocarbon insulating oil, ether insulating oil, ester insulating oil and silicone oil.
本发明的有益效果是：The beneficial effects of the present invention are:
本发明提供一种疏水介电薄膜，并平铺到驱动电极表面形成微流控芯片，具有以下技术优势：1、降低成本，只需要更换液滴下面的疏水介电薄膜即可，不需要将下面驱动电极一起丢弃，电极芯片可重复使用，成本低廉、对环境友好；2、制造时间缩短，不需要重新制作驱动电极板；3、耐击穿，在相同电压下，本发明不容易发生击穿，克服了传统芯片最大障碍易击穿的缺陷；4、采用铺膜方式，薄膜表面非常平整，不会受到粗糙电极表面的影响，平整度增加，降低了液滴移动阻力。本发明提供的疏水介电薄膜表面平整，将其铺设在涂覆有绝缘液体的驱动电极上制备得到的微流控芯片能够解决现有技术中直接采用在驱动电极上镀疏水介电薄膜的方式存在的缺陷，容易更换并且降低了成本，在需要时只要更换液滴下面的疏水介电薄膜即可，不需要将下面驱动电极一起丢弃，在微流控芯片领域具有较好的应用前景。The present invention provides a hydrophobic dielectric film, which is flattened on the surface of the driving electrode to form a microfluidic chip, and has the following technical advantages: 1. Cost reduction, only the hydrophobic dielectric film under the droplet needs to be replaced, and no The following driving electrodes are discarded together, the electrode chip can be reused, the cost is low, and it is environmentally friendly; 2. The manufacturing time is shortened, and there is no need to re-make the driving electrode plate; 3. Breakdown resistance, under the same voltage, the invention is not easy to break 4. Using the film laying method, the surface of the film is very flat and will not be affected by the rough electrode surface, the flatness is increased, and the resistance of droplet movement is reduced. The surface of the hydrophobic dielectric film provided by the invention is flat, and the microfluidic chip prepared by laying it on the driving electrode coated with insulating liquid can solve the problem of directly using the method of plating the hydrophobic dielectric film on the driving electrode in the prior art. The existing defects are easy to replace and reduce the cost. When necessary, only the hydrophobic dielectric film under the droplet can be replaced, and the lower driving electrodes do not need to be discarded together, which has a good application prospect in the field of microfluidic chips.
附图说明Description of drawings
图1为实施例1中的疏水介电薄膜的结构示意图；1 is a schematic structural diagram of a hydrophobic dielectric film in Example 1;
图2为实施例2中微流控芯片的结构示意图；2 is a schematic structural diagram of a microfluidic chip in Example 2;
图3为现有的微流控芯片在施加电压下的击穿示意图；3 is a schematic diagram of the breakdown of an existing microfluidic chip under an applied voltage;
图4为实施例2组装的微流控芯片在施加电压下的使用示意图。FIG. 4 is a schematic diagram of the use of the microfluidic chip assembled in Example 2 under applied voltage.
具体实施方式Detailed ways
以下将结合实施例对本发明的构思及产生的技术效果进行清楚、完整地描述，以充分地理解本发明的目的、特征和效果。显然，所描述的实施例只是本发明的一部分实施例，而不是全部实施例，基于本发明的实施例，本领域的技术人员在不付出创造性劳动的前提下所获得的其他实施例，均属于本发明保护的范围。The concept of the present invention and the technical effects produced will be clearly and completely described below with reference to the embodiments, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts are all within the scope of The scope of protection of the present invention.
实施例1Example 1
参见图1，本实施例提供一种易替换的疏水介电薄膜3，包括疏水介电薄膜1和贴在所述疏水介电薄膜上的框架2，所述疏水介电薄膜1包括介电层11和疏水层12。Referring to FIG. 1 , this embodiment provides an easily replaceable hydrophobic dielectric film 3 , including a hydrophobic dielectric film 1 and a frame 2 attached to the hydrophobic dielectric film, and the hydrophobic dielectric film 1 includes a dielectric layer 11 and the hydrophobic layer 12.
上述易替换的疏水介电薄膜1的制备过程如下：用RCA标准制程清洗硅片，去离子水冲洗三次，氮气吹干，涂覆约1u牺牲层光刻胶烘干后，再涂10um PDMS介电层，随后蒸镀30nm的cytop疏水层，最后贴亚克力架，揭膜后收入收纳盒中备用。The preparation process of the above-mentioned easily replaceable hydrophobic dielectric film 1 is as follows: use the RCA standard process to clean the silicon wafer, rinse with deionized water three times, blow dry with nitrogen, apply about 1u of sacrificial layer photoresist and dry, and then apply 10um of PDMS dielectric. The electric layer was then evaporated to a 30nm cytop hydrophobic layer, and finally an acrylic frame was attached.
本实施例制备得到一种带有框架的疏水介电薄膜，在疏水介电薄膜上贴有铝框，薄膜无形变，厚度仅10um。该薄膜是数字微流控芯片中的唯一耗材，可以极大降低数字微流控芯片成本。将水滴在上述疏水介电薄膜上，水滴在薄膜表面形成的接触角为120°。In this example, a hydrophobic dielectric film with a frame is prepared, an aluminum frame is attached to the hydrophobic dielectric film, the film has no deformation, and the thickness is only 10um. The film is the only consumable in the digital microfluidic chip, which can greatly reduce the cost of the digital microfluidic chip. Water droplets are placed on the above hydrophobic dielectric film, and the contact angle formed by the water droplets on the surface of the film is 120°.
实施例2Example 2
参见图2，本实施例提供一种微流控芯片，包括驱动电极4、涂覆在所述驱动电极上的绝缘液体层5和设置在所述绝缘液体层上的实施例1中的疏水介电薄膜3。本实施例的微流控芯片以完全不用上极板的单面驱动结构为例，实际本发明适用的微流控芯片包含但不限于上述结构，还可以适用于需要上极板作为接地板的单面驱动结构以及双面驱动结构，并且使用的驱动电极适用于所有的电极结构。Referring to FIG. 2 , this embodiment provides a microfluidic chip, including a driving electrode 4 , an insulating liquid layer 5 coated on the driving electrode, and the hydrophobic dielectric in Embodiment 1 disposed on the insulating liquid layer. Electric film 3. The microfluidic chip in this embodiment takes the single-sided driving structure without the upper plate as an example. In practice, the microfluidic chip to which the present invention is applicable includes but is not limited to the above-mentioned structure, and can also be applied to a device that requires the upper plate as a ground plate. Single-sided driving structure as well as double-sided driving structure, and the driving electrodes used are suitable for all electrode structures.
上述微流控芯片的组装方法，具体如下：在驱动电极表面涂一层食用油，将实施例1中的疏水介电薄膜放置在驱动电极正上方，然后贴在驱动电极表面，该疏水介电薄膜能够极大降低驱动电极表面的粗糙度，明显降低液滴移动的阻力，液滴在电驱动下快速移动至目标电极，不产生任何拖尾的现象。The assembling method of the above-mentioned microfluidic chip is as follows: coating a layer of edible oil on the surface of the driving electrode, placing the hydrophobic dielectric film in Example 1 directly above the driving electrode, and then sticking it on the surface of the driving electrode. The thin film can greatly reduce the roughness of the driving electrode surface and significantly reduce the resistance of droplet movement. The droplet moves quickly to the target electrode under electric drive without any trailing phenomenon.
耐击穿实验：Breakdown resistance test:
取按传统工艺自制的以硅片或玻璃片为基板的数字微流控芯片，通过蒸镀和匀胶等工艺直接在基板上涂覆介电层和疏水层，持续施加200v驱动电压，实验结果显示去离子水液滴在移动若干次循环后(不超过100次)，微流控芯片表面出现鼓泡、烧黑等明显的击穿现象，如图3所示。Take a digital microfluidic chip with a silicon wafer or glass wafer as the substrate, which is self-made according to the traditional process, and directly coat the dielectric layer and the hydrophobic layer on the substrate through the processes of evaporation and uniform glue, and continuously apply a driving voltage of 200v. The experimental results It is shown that after the deionized water droplets move for several cycles (not more than 100 times), the surface of the microfluidic chip has obvious breakdown phenomena such as bubbling and black burning, as shown in Figure 3.
取本实施例组装的微流控芯片，同等条件下施加200v驱动电压，实验结果显示去离子水液滴往复移动数千次(＞1000次)，微流控芯片表面未发生任何击穿痕迹如图4所示，后经持续施加电压，测试本发明的微流控芯片寿命在5h以上。Take the microfluidic chip assembled in this example and apply a driving voltage of 200v under the same conditions. The experimental results show that the deionized water droplets move back and forth thousands of times (> 1000 times), and there is no breakdown mark on the surface of the microfluidic chip, such as As shown in FIG. 4 , after continuous application of voltage, the lifespan of the microfluidic chip of the present invention is tested to be more than 5h.
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