CN112892619B - PDMS (polydimethylsiloxane) master mold with arc-shaped edge section, micro-fluidic valve and chip and preparation thereof - Google Patents
PDMS (polydimethylsiloxane) master mold with arc-shaped edge section, micro-fluidic valve and chip and preparation thereof Download PDFInfo
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Abstract
本发明公开了一种弧形边缘截面的PDMS母模、微流控阀和芯片及其制备。通过将印刷电路板各向同性蚀刻与PDMS表面改性相结合来制造具有弧形边缘截面结构的PDMS母模的方法,该方法简单、低成本、有效。带有弧形边缘截面通道的微流控芯片可以通过使用准备好的PDMS母模生成。本发明进一步证明,AC可以制造微流控气动阀,称为弧形边缘截面微流控阀,该阀可用于多路控制、兼容的大规模集成、液体控制、单细胞操作和检测。
The invention discloses a PDMS master mold with an arc-shaped edge section, a microfluidic valve, a chip and the preparation thereof. A simple, low-cost, and effective method for fabricating PDMS master molds with curved edge cross-sectional structures by combining isotropic etching of printed circuit boards with PDMS surface modification. Microfluidic chips with curved edge cross-section channels can be generated by using prepared PDMS master molds. The present invention further demonstrates that AC can fabricate microfluidic pneumatic valves, called arcuate edge section microfluidic valves, that can be used for multiplex control, compatible large-scale integration, liquid control, single-cell manipulation, and detection.
Description
技术领域technical field
本发明涉及微流控芯片技术领域,具体涉及一种弧形边缘截面的PDMS母模、微流控阀和芯片及其制备。The invention relates to the technical field of microfluidic chips, in particular to a PDMS master mold with an arc-shaped edge section, a microfluidic valve and a chip and preparations thereof.
背景技术Background technique
微流控技术的快速发展为化学、生物学、临床医学、生物工程等领域的发展做出了重要贡献。微流控装置的制备可以通过多种方法来实现,例如软光刻、微铣削、印刷电路板(PCB)蚀刻和3D打印。各种基材材料,如玻璃、硅聚合物、塑料,甚至是纸张都已被采纳用于微流控应用。不同的制造技术和基质材料的发展使得微流体技术具有多种功能,并在学术界和工业界都变得越来越容易获得。低成本和大批量生产的制造工艺对大规模生产非常重要。The rapid development of microfluidic technology has made important contributions to the development of chemistry, biology, clinical medicine, bioengineering and other fields. Fabrication of microfluidic devices can be achieved by various methods, such as soft lithography, micro-milling, printed circuit board (PCB) etching, and 3D printing. Various substrate materials such as glass, silicon polymers, plastics, and even paper have been adopted for microfluidic applications. The development of different fabrication techniques and matrix materials has made microfluidics versatile and increasingly accessible in both academia and industry. Low cost and high volume manufacturing processes are very important for mass production.
直接制造微流控芯片包括3D打印、激光微加工和立体光刻以及模塑,模塑无疑是大规模生产中最合适,最经济的方法。Direct fabrication of microfluidic chips includes 3D printing, laser micromachining and stereolithography, as well as molding, which is undoubtedly the most suitable and economical method for mass production.
在模具制造方法中,印刷电路板(PCB)技术具有以下几个优点:(1)精密加工过程高效、低成本和不需要洁净室设备即可容易达到;(2)铜主模具是耐用的,可以通过一步刻蚀制造高度从几百微米到一百微米的微流体结构;(3)PCB母模制备的PDMS微流控芯片已被证明具有生物相容性;(4)通常具有光刻胶预涂膜,并能通过商业服务来制备。Among the mold manufacturing methods, printed circuit board (PCB) technology has several advantages: (1) the precision machining process is efficient, low cost, and easily accessible without the need for clean room equipment; (2) the copper master mold is durable, Microfluidic structures with heights ranging from several hundred microns to one hundred microns can be fabricated by one-step etching; (3) PDMS microfluidic chips prepared from PCB master molds have been shown to be biocompatible; (4) Usually with photoresist Pre-coated films and can be prepared by commercial service.
微流控阀门作为微流控系统中的一个关键部件变得越来越不可或缺,因为它是用于进行连续样品处理,高平行分析,自动化流体和微粒操作的关键部件。因此,许多努力工作都集中在使用不同技术的新型材料制造微流体阀门,如单片PDMS阀门、阀瓣隔膜阀、蜡制微流体中的微阀,3D印刷的微流体阀等。有理由相信这些阀门可以使PDMS,阀瓣和纸芯片更强大。然而,除了多次软光刻之外,其他技术不能用于大规模生产,这取决于模塑方法。此外,单片PDMS阀门与其他类型阀门相比具有明显优势:(1)功能多样性:电磁阀,蠕动泵,混合器和捕集器(筛阀);(2)切实可行的大规模集成;(3)耐用和持久的驱动。因此,它们是微流体中最广泛采用和报告的微型阀。Microfluidic valves are becoming more and more indispensable as a key component in microfluidic systems as it is a key component for continuous sample processing, highly parallel analysis, automated fluidic and particle manipulation. Therefore, many efforts have been focused on the fabrication of microfluidic valves using novel materials of different technologies, such as monolithic PDMS valves, flapper-diaphragm valves, microvalves in wax-based microfluidics, 3D-printed microfluidic valves, etc. There is reason to believe that these valves could make PDMS, flaps and paper chips more powerful. However, other than multiple soft lithography, other techniques cannot be used for mass production, depending on the molding method. In addition, monolithic PDMS valves have obvious advantages over other types of valves: (1) functional diversity: solenoid valves, peristaltic pumps, mixers and traps (sieve valves); (2) feasible large-scale integration; (3) Durable and durable drive. Therefore, they are the most widely adopted and reported microvalves in microfluidics.
在此,本发明提出了一种基于PCB各向同性蚀刻和PDMS表面改性相结合,以简单、低成本、有效且容易获得的方法来制备包含弧形截面结构的PDMS母模。使用PDMS母模,可以生成含有弧形截面通道(ACs)的微流控芯片。本发明还进一步证明ACs可以制造单片气动阀,称为弧形截面单片阀(AMVs)。AMVs芯片可用于多路复用控制,兼容大规模集成,并用于液体控制,单细胞操作和检测。这种制造PDMS模具的方法有6个优点:(1)低成本(PCB比SU8便宜得多);(2)可达性(紫外光,甚至阳光均可用于曝光);(3)效率(通过一步蚀刻,微通道的高度范围从几微米到一百微米);(4)简单(PCB蚀刻非常容易学习);(5)扩大生产(PDMS模具可以通过PCB母模进一步扩大生产);6)功能(可以使用一步PCB蚀刻方法制造用于液体和微粒操作的AMVs芯片)。Herein, the present invention proposes a simple, low-cost, effective and easy-to-obtain method based on the combination of PCB isotropic etching and PDMS surface modification to prepare a PDMS master mold containing an arc-shaped cross-section structure. Using PDMS master molds, microfluidic chips containing arcuate cross-section channels (ACs) can be generated. The present invention further demonstrates that ACs can fabricate monolithic pneumatic valves, termed arcuate section monolithic valves (AMVs). AMVs chips can be used for multiplexed control, compatible with large-scale integration, and used for liquid control, single-cell manipulation and detection. This method of making PDMS molds has 6 advantages: (1) low cost (PCB is much cheaper than SU8); (2) accessibility (UV light, even sunlight can be used for exposure); (3) efficiency (via One-step etching, the height of microchannels ranges from a few microns to a hundred microns); (4) Simple (PCB etching is very easy to learn); (5) Scale-up (PDMS molds can be further scaled up by PCB master); 6) Functional (AMVs chips for liquid and particle manipulation can be fabricated using a one-step PCB etching method).
发明内容SUMMARY OF THE INVENTION
本发明的第一个目的在于提供一种通过将印刷电路板(printed circuit board,PCB)各向同性蚀刻与PDMS(聚二甲基硅氧烷)表面改性相结合来制造具有弧形边缘截面的PDMS母模的方法,该方法简单、低成本、有效。A first object of the present invention is to provide a method for fabricating a cross-section with curved edges by combining isotropic etching of printed circuit board (PCB) with PDMS (polydimethylsiloxane) surface modification The method of the PDMS master mold is simple, low-cost and effective.
本发明的第二个目的在于提供一种由以上第一个目的中的制备方法得到的具有弧形边缘截面的PDMS母模。The second object of the present invention is to provide a PDMS master mold with an arc-shaped edge section obtained by the preparation method in the first object above.
本发明的第三个目的在于提供一种弧形边缘截面微流控阀的制备方法;该制备方法使用以上第二个目的中的PDMS母模生成具有弧形边缘截面通道的流体层,然后与控制层对齐制备弧形边缘截面微流控阀(arc section microfluidic valve,AMV)。The third object of the present invention is to provide a preparation method of a microfluidic valve with an arc-shaped edge section; the preparation method uses the PDMS master mold in the above second object to generate a fluid layer with an arc-shaped edge section channel, and then combines with The arc section microfluidic valve (AMV) was prepared by the alignment of the control layer.
本发明的第四个目的在于提供一种由以上第三个目的中的制备方法得到的弧形边缘截面微流控阀;该阀可用于多路控制、兼容的大规模集成、液体控制、单细胞操作和检测。The fourth object of the present invention is to provide a microfluidic valve with an arc-shaped edge section obtained by the preparation method in the third object above; the valve can be used for multiplex control, compatible large-scale integration, liquid control, single Cell manipulation and detection.
本发明的第五个目的在于提供一种包含以上弧形边缘截面微流控阀的微流控芯片。The fifth object of the present invention is to provide a microfluidic chip including the above arc-shaped edge section microfluidic valve.
为了实现以上第一个目的,本发明采用以下技术方案:In order to realize above first purpose, the present invention adopts following technical scheme:
本发明第一个方面提供一种具有弧形边缘截面的PDMS母模的制备方法,包括以下步骤:A first aspect of the present invention provides a method for preparing a PDMS master mold with an arc-shaped edge section, comprising the following steps:
S100、在带有光刻胶的印刷电路板(PCB)上通过图案化形成弧形边缘截面的凹槽,得到PCB母模;S100, forming a groove with an arc-shaped edge cross-section by patterning on a printed circuit board (PCB) with photoresist to obtain a PCB master mold;
S200、将PDMS预聚物倒在PCB母模上并聚合,得到具有弧形边缘截面的PDMS母模。S200, pouring the PDMS prepolymer on the PCB master mold and polymerizing to obtain a PDMS master mold with an arc-shaped edge section.
该制备方法将印刷电路板(printed circuit board,PCB)各向同性蚀刻与PDMS(聚二甲基硅氧烷)表面改性相结合,在PCB上铸造和固化PDMS预聚物,这些PDMS复制品即作为PDMS母模。The preparation method combines isotropic etching of printed circuit board (PCB) with PDMS (polydimethylsiloxane) surface modification, casting and curing PDMS prepolymer on PCB, these PDMS replicas That is, as a PDMS master.
该制备方法中的印刷电路板PCB可直接商业购买,通常具有光刻胶预涂膜。The printed circuit board PCB in this preparation method can be directly purchased commercially, and usually has a photoresist pre-coating film.
在该具有弧形边缘截面的PDMS母模的制备方法中,所述PDMS预聚物中的基料和固化剂的选择以及比例根据需要进行调节,可直接购买,也可购买后进行配置;优选地,所述PDMS预聚物中的基料和固化剂的质量比为5:1。In the preparation method of the PDMS master mold with the arc-shaped edge section, the selection and proportion of the base material and the curing agent in the PDMS prepolymer are adjusted as required, which can be purchased directly or configured after purchase; preferably Specifically, the mass ratio of the binder and the curing agent in the PDMS prepolymer is 5:1.
在本发明的一个优选方案中,以上具有弧形边缘截面的PDMS母模的制备方法中,所述图案化过程包括以下步骤:In a preferred solution of the present invention, in the above method for preparing a PDMS master mold with an arc-shaped edge section, the patterning process includes the following steps:
S110、带有光刻胶的印刷电路板上覆盖光掩模,并进行曝光;S110, covering a photomask on a printed circuit board with photoresist, and exposing it;
S120、进行显影,图案转移至光刻胶上;S120, developing, and transferring the pattern to the photoresist;
S130、用三氯化铁溶液蚀刻,在印刷电路板中的铜板上形成凹槽;其中的凹槽由于是通过蚀刻形成的,其边缘为弧形,凹槽的横截面为弧形边缘截面;S130, etch with ferric chloride solution to form a groove on the copper plate in the printed circuit board; the groove is formed by etching, and its edge is arc-shaped, and the cross-section of the groove is an arc-shaped edge section;
S140、用丙酮除去光刻胶,得到PCB母模。S140, removing the photoresist with acetone to obtain a PCB master mold.
在该优选方案中,所述曝光可以使用UV光,也可以使用其他光源,如阳光;优选地,所述曝光采用UV光。In this preferred solution, the exposure can use UV light, or other light sources, such as sunlight; preferably, the exposure uses UV light.
本领域技术人员容易理解的,以上图案化过程为本领域常规的技术手段,采用正性光刻胶或反性光刻胶均可实现以上图案化形成凹槽的目的,本发明在此不再一一列举。Those skilled in the art can easily understand that the above patterning process is a conventional technical means in the field, and both positive photoresist or reverse photoresist can be used to achieve the purpose of forming grooves by patterning above, and the present invention will no longer be used here. List them one by one.
在本发明的一个优选方案中,以上具有弧形边缘截面的PDMS母模的制备方法中,S200的步骤具体包括:In a preferred solution of the present invention, in the above preparation method of the PDMS master mold with arc-shaped edge section, the step of S200 specifically includes:
S210、将PDMS预聚物倒在PCB母模上,S210, pour the PDMS prepolymer on the PCB master mold,
S220、PCB母模上的PDMS预聚物进行聚合;S220, the PDMS prepolymer on the PCB master mold is polymerized;
S230、将聚合后的PDMS进行剥离,使用泊洛沙姆407处理后,得到具有弧形边缘截面的PDMS母模。S230 , peeling off the polymerized PDMS and treating with poloxamer 407 to obtain a PDMS master mold with an arc-shaped edge section.
在S230中,关于使用泊洛沙姆407对聚合后的PDMS进行处理的过程,在本发明的一个具体实施例中,直接使用泊洛沙姆407(即PF127)浸泡3小时即可。In S230, regarding the process of using poloxamer 407 to treat the polymerized PDMS, in a specific embodiment of the present invention, poloxamer 407 (ie, PF127) can be directly soaked for 3 hours.
为了实现以上第二个目的,本发明采用以下技术方案:In order to realize the above second purpose, the present invention adopts the following technical solutions:
本发明第二个方面提供一种具有弧形边缘截面的PDMS母模,通过以上第一个方面提供的具有弧形边缘截面的PDMS母模的制备方法制备得到。A second aspect of the present invention provides a PDMS master mold with an arc-shaped edge section, which is prepared by the method for preparing a PDMS master mold with an arc-shaped edge section provided in the first aspect.
本发明中所提及的具有弧形边缘截面的PDMS母模,具有与PCB母模上的凹槽对应的凸起,凸起的横截面具有弧形边缘。使用该PDMS母模可制备具有弧形边缘截面通道的流体层,进而与控制层一起用于制备弧形边缘截面微流控阀(AMV)和包含此弧形边缘截面微流控阀的微流控芯片。The PDMS master mold with arc-shaped edge section mentioned in the present invention has protrusions corresponding to the grooves on the PCB master mold, and the cross-section of the protrusions has arc-shaped edges. Using this PDMS master mold, a fluidic layer with curved edge cross-section channels can be prepared, which in turn, together with a control layer, can be used to prepare an arcuate edge cross-section microfluidic valve (AMV) and a microfluidic containing the curved edge cross-section microfluidic valve. control chip.
该具有弧形边缘截面的PDMS母模中的凸起的尺寸可通过调节光掩模中图案的尺寸以及刻蚀时间进行控制。所述凸起的尺寸对应于使用该PDMS母模制备的具有弧形边缘截面通道的尺寸,可具体根据对于通道的尺寸需求调整光掩模中图案的尺寸以及刻蚀时间,本发明对此不做限定。The size of the protrusions in the PDMS master with curved edge section can be controlled by adjusting the size of the pattern in the photomask and the etching time. The size of the protrusion corresponds to the size of the channel with an arc-shaped edge cross-section prepared by using the PDMS master mold. The size of the pattern in the photomask and the etching time can be adjusted according to the size requirements of the channel, which is not the present invention. Do limit.
为了实现以上第三个目的,本发明采用以下技术方案:In order to realize the above third purpose, the present invention adopts the following technical solutions:
本发明第三个方面提供一种弧形边缘截面微流控阀的制备方法,该制备方法包括以下步骤:A third aspect of the present invention provides a preparation method of an arc-shaped edge section microfluidic valve, the preparation method comprising the following steps:
S300、在带有光刻胶的印刷电路板(PCB)上通过图案化形成弧形边缘截面的凸起,得到PCB控制层母模;S300, forming a convex edge cross-section on a printed circuit board (PCB) with photoresist by patterning to obtain a PCB control layer master mold;
S400、在PCB控制层母模上旋涂PDMS预聚物,聚合后得到具有控制通道的控制层;S400, spin coating PDMS prepolymer on the master mold of the PCB control layer, and obtain a control layer with control channels after polymerization;
S500、使用以上第二方面的具有弧形边缘截面的PDMS母模制备具有弧形边缘截面通道的流体层;S500, using the PDMS master mold with the arc-shaped edge section of the second aspect above to prepare a fluid layer with an arc-shaped edge section channel;
S600、将所述控制层和流体层对准,并使用平的PDMS层进行密封,得到所述弧形边缘截面微流控阀。S600. Align the control layer and the fluid layer, and use a flat PDMS layer for sealing to obtain the arc-shaped edge section microfluidic valve.
该弧形边缘截面微流控阀包括有流体层和控制层,相对应的包括有弧形边缘截面通道和控制通道。The arc-shaped edge section microfluidic valve includes a fluid layer and a control layer, and correspondingly includes an arc-shaped edge section channel and a control channel.
该制备方法中的印刷电路板PCB与本发明第一方面的制备方法中的印刷电路板PCB一样,可直接商业购买,通常具有光刻胶预涂膜。The printed circuit board PCB in the preparation method is the same as the printed circuit board PCB in the preparation method of the first aspect of the present invention, which can be directly purchased commercially, and usually has a photoresist pre-coating film.
在该具有弧形边缘截面的PDMS母模的制备方法中,所述PDMS预聚物中的基料和固化剂的比例根据需要进行调节,可直接购买,也可购买后进行配置;优选地,所述PDMS预聚物中的基料和固化剂的质量比为20:1。In the preparation method of the PDMS master mold with the arc-shaped edge section, the ratio of the base material and the curing agent in the PDMS prepolymer is adjusted as required, and can be purchased directly or configured after purchase; preferably, The mass ratio of the binder and the curing agent in the PDMS prepolymer is 20:1.
在本发明的一个优选方案中,以上弧形边缘截面微流控阀的制备方法中,S300中所述图案化过程包括以下步骤:In a preferred solution of the present invention, in the above method for preparing a microfluidic valve with an arc-shaped edge section, the patterning process described in S300 includes the following steps:
S310、带有光刻胶的印刷电路板上覆盖光掩模,并进行曝光;S310, covering a photomask on a printed circuit board with photoresist, and exposing it;
S320、进行显影,图案转移至光刻胶上;S320, developing, and transferring the pattern to the photoresist;
S330、用三氯化铁溶液蚀刻,在印刷电路板中的铜板上形成凸起;其中的凸起由于是通过蚀刻形成的,其边缘为向内凹陷的弧形,凸起的横截面为向内凹陷的弧形边缘截面;S330, etching with ferric chloride solution to form bumps on the copper plate in the printed circuit board; because the bumps are formed by etching, the edges of the bumps are inwardly concave arcs, and the cross-sections of the bumps are Inwardly concave arc edge section;
S340、用丙酮除去光刻胶,得到PCB控制层母模。S340, removing the photoresist with acetone to obtain a master mold of the PCB control layer.
在该优选方案中,所述曝光可以使用UV光,也可以使用其他光源,如阳光;优选地,所述曝光采用UV光。In this preferred solution, the exposure can use UV light, or other light sources, such as sunlight; preferably, the exposure uses UV light.
本领域技术人员容易理解的,以上图案化过程为本领域常规的技术手段,采用正性光刻胶或反性光刻胶均可实现以上图案化形成凸起的目的,本发明在此不再一一列举。Those skilled in the art can easily understand that the above patterning process is a conventional technical means in the field, and both positive photoresist or reverse photoresist can be used to achieve the purpose of forming protrusions by the above patterning, and the present invention will no longer be used here. List them one by one.
在以上弧形边缘截面微流控阀的制备方法中,S500中所述流体层的制备过程具体包括:将PDMS预聚物倒入本发明第二方面所提供的PDMS母模上,固化后剥离得到所述流体层。In the above method for preparing a microfluidic valve with curved edge section, the preparation process of the fluid layer in S500 specifically includes: pouring the PDMS prepolymer onto the PDMS master mold provided in the second aspect of the present invention, and peeling off after curing The fluid layer is obtained.
在该流体层的制备过程中,所述PDMS预聚物中的基料和固化剂的比例根据需要进行调节,可直接购买,也可购买后进行配置;优选地,所述PDMS预聚物中的基料和固化剂的质量比为5:1。在本发明的一个具体实施例中,流体层与PDMS母模所采用的PDMS预聚物一致。During the preparation of the fluid layer, the ratio of the base material and the curing agent in the PDMS prepolymer can be adjusted as needed, which can be purchased directly or configured after purchase; preferably, in the PDMS prepolymer The mass ratio of binder and curing agent is 5:1. In a specific embodiment of the present invention, the fluid layer is consistent with the PDMS prepolymer used in the PDMS master mold.
在以上弧形边缘截面微流控阀的制备方法中,S600中所述平的PDMS层为部分固化,密封后进行固化。In the above preparation method of the arc-shaped edge section microfluidic valve, the flat PDMS layer described in S600 is partially cured, and cured after being sealed.
以上,本发明的制备方法中所提及的聚合、固化、部分固化等的具体条件,本领域技术人员均可根据具体的预聚物中基料和固化剂的具体种类及比例进行优化选择;本发明在此不做限定。Above, the specific conditions of polymerization, curing, partial curing, etc. mentioned in the preparation method of the present invention can be optimized and selected by those skilled in the art according to the specific types and proportions of the binder and the curing agent in the specific prepolymer; The present invention is not limited herein.
为了实现以上第四个目的,本发明采用以下技术方案:In order to realize the above fourth purpose, the present invention adopts the following technical solutions:
本发明第四个方面提供一种弧形边缘截面微流控阀,通过以上第三个方面提供的弧形边缘截面微流控阀的制备方法制备得到。A fourth aspect of the present invention provides an arc-shaped edge section microfluidic valve, which is prepared by the preparation method of the arc-shaped edge section microfluidic valve provided in the third aspect above.
该弧形边缘截面微流控阀中的控制通道的尺寸对应于PCB控制层母模中的凸起的尺寸,可通过调节光掩模中图案的尺寸以及刻蚀时间进行控制;本领域技术人员可具体根据对于控制通道的尺寸需求调整光掩模中图案的尺寸以及刻蚀时间,本发明对此不做限定。The size of the control channel in the arc-shaped edge section microfluidic valve corresponds to the size of the protrusion in the master mold of the PCB control layer, which can be controlled by adjusting the size of the pattern in the photomask and the etching time; those skilled in the art The size of the pattern in the photomask and the etching time may be adjusted according to the size requirements of the control channel, which are not limited in the present invention.
为了实现以上第五个目的,本发明采用以下技术方案:In order to realize the above fifth purpose, the present invention adopts the following technical solutions:
本发明第五个方面提供一种包含以上第四个方面提供的弧形边缘截面微流控阀的微流控芯片。A fifth aspect of the present invention provides a microfluidic chip including the arc-shaped edge section microfluidic valve provided in the fourth aspect.
进一步的,所述微流控芯片包括自制控制器,所述自制控制器包括8个电磁阀,用于驱动所述控制通道。Further, the microfluidic chip includes a self-made controller, and the self-made controller includes 8 solenoid valves for driving the control channel.
本发明提供了一种通过将印刷电路板(printed circuit boards,PCB)各向同性蚀刻与PDMS(聚二甲基硅氧烷)表面改性相结合来制造具有弧形边缘截面结构的PDMS母模的方法,该方法简单、低成本、有效。带有弧形边缘截面通道(arc section microchannel,AC)的微流控芯片可以通过使用准备好的PDMS母模生成。本发明进一步证明,AC可以制造微流控气动阀,称为弧形边缘截面微流控阀(AMV),该阀可用于多路控制、兼容的大规模集成、液体控制、单细胞操作和检测。The present invention provides a PDMS master mold with a curved edge cross-sectional structure by combining isotropic etching of printed circuit boards (PCB) with PDMS (polydimethylsiloxane) surface modification The method is simple, low-cost and effective. Microfluidic chips with arc section microchannels (AC) can be generated by using prepared PDMS master molds. The present invention further demonstrates that AC can fabricate microfluidic pneumatic valves, termed arcuate edge section microfluidic valves (AMVs), which can be used for multiplex control, compatible large-scale integration, liquid control, single-cell manipulation, and detection .
本发明具有以下有益效果:The present invention has the following beneficial effects:
1)低成本:PCB比SU8便宜得多;1) Low cost: PCB is much cheaper than SU8;
2)易用性:紫外线,甚至阳光也可用于曝光;2) Ease of use: UV light, even sunlight can be used for exposure;
3)效率:一步蚀刻,微通道的高度范围从几微米到100微米;3) Efficiency: one-step etching, the height of the microchannel ranges from a few microns to 100 microns;
4)简单:PCB蚀刻非常容易学习;4) Simple: PCB etching is very easy to learn;
5)扩大生产:PDMS模具可通过PCB母模进一步制造;5) Expand production: PDMS molds can be further manufactured by PCB master molds;
6)功能:用于液体和颗粒操作的AMV芯片可通过一步式PCB蚀刻方法制造。6) Function: AMV chips for liquid and particle manipulation can be fabricated by a one-step PCB etching method.
附图说明Description of drawings
图1为实施例1中PDMS母模的制备方法中S110的示意图。1 is a schematic diagram of S110 in the preparation method of the PDMS master mold in Example 1.
图2为实施例1中PDMS母模的制备方法中S120的示意图。FIG. 2 is a schematic diagram of S120 in the preparation method of the PDMS master mold in Example 1. FIG.
图3为实施例1中PDMS母模的制备方法中S130的示意图。3 is a schematic diagram of S130 in the preparation method of the PDMS master mold in Example 1.
图4为实施例1中PDMS母模的制备方法中S140的示意图。4 is a schematic diagram of S140 in the preparation method of the PDMS master mold in Example 1.
图5为实施例1中PDMS母模的制备方法中S210的示意图。5 is a schematic diagram of S210 in the preparation method of the PDMS master mold in Example 1.
图6为实施例1中PDMS母模的制备方法中S220的示意图。6 is a schematic diagram of S220 in the preparation method of the PDMS master mold in Example 1.
图7为实施例1中PDMS母模的制备方法中S230的示意图。7 is a schematic diagram of S230 in the preparation method of the PDMS master mold in Example 1.
图8为实施例1中PDMS母模的制备方法中S240的示意图。8 is a schematic diagram of S240 in the preparation method of the PDMS master mold in Example 1.
图9a为实施例2中使用具有35μm宽图案的光掩模,蚀刻25分钟后,制得PDMS母模。FIG. 9a shows the PDMS master mold obtained after etching for 25 minutes using a photomask with a 35 μm wide pattern in Example 2. FIG.
图9b为实施例2中使用具有70μm宽图案的光掩模,蚀刻25分钟后,制得PDMS母模。FIG. 9b shows the PDMS master mold obtained after etching for 25 minutes using a photomask with a 70 μm wide pattern in Example 2. FIG.
图9c为实施例2中使用具有140μm宽图案的光掩模,蚀刻25分钟后,制得PDMS母模。FIG. 9c shows the PDMS master mold obtained after etching for 25 minutes using a photomask with a pattern of 140 μm wide in Example 2. FIG.
图9d为使用图9a中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 9d is a curved edge cross-sectional channel (AC) fabricated using the PDMS master of Figure 9a.
图9e为使用图9b中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 9e is a curved edge cross-sectional channel (AC) fabricated using the PDMS master in Figure 9b.
图9f为使用图9c中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 9f is a curved edge cross-sectional channel (AC) fabricated using the PDMS master of Figure 9c.
图10a为实施例3中使用35μm宽图案的光掩模蚀刻10min后的PDMS母模。FIG. 10a shows the PDMS master after etching for 10 min using a photomask with a 35 μm wide pattern in Example 3. FIG.
图10b为实施例3中使用35μm宽图案的光掩模蚀刻25min后的PDMS母模。FIG. 10b shows the PDMS master after etching for 25 min using a photomask with a 35 μm wide pattern in Example 3. FIG.
图10c为实施例3中使用35μm宽图案的光掩模蚀刻50min后的PDMS母模。FIG. 10c shows the PDMS master after etching for 50 min using a photomask with a 35 μm wide pattern in Example 3. FIG.
图10d为实施例3中使用35μm宽图案的光掩模蚀刻75min后的PDMS母模。FIG. 10d shows the PDMS master after etching for 75 min using a photomask with a 35 μm wide pattern in Example 3. FIG.
图10e为使用图10a中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 10e is a curved edge cross-sectional channel (AC) fabricated using the PDMS master of Figure 10a.
图10f为使用图10b中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 10f is a curved edge cross-sectional channel (AC) prepared using the PDMS master of Figure 10b.
图10g为使用图10c中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 10g is a curved edge cross-sectional channel (AC) prepared using the PDMS master of Figure 10c.
图10h为使用图10d中的PDMS母模制备的弧形边缘截面通道(AC)。Figure 10h is a curved edge cross-sectional channel (AC) prepared using the PDMS master of Figure 10d.
图11为实施例4中使用PDMS母模制得40μm深的凹槽,比例尺:20μm。FIG. 11 shows grooves with a depth of 40 μm obtained by using the PDMS master mold in Example 4, scale bar: 20 μm.
图12为实施例4中使用PDMS母模制得100μm深的凹槽,比例尺:20μm。FIG. 12 shows grooves with a depth of 100 μm obtained by using a PDMS master mold in Example 4, scale bar: 20 μm.
图13为实施例5中弧形边缘截面微流控阀的制备方法中S310的示意图。13 is a schematic diagram of S310 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5. FIG.
图14为实施例5中弧形边缘截面微流控阀的制备方法中S320的示意图。14 is a schematic diagram of S320 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5. FIG.
图15为实施例5中弧形边缘截面微流控阀的制备方法中S330的示意图。15 is a schematic diagram of S330 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5. FIG.
图16为实施例5中弧形边缘截面微流控阀的制备方法中S340和S400的示意图。16 is a schematic diagram of S340 and S400 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5.
图17为实施例5中弧形边缘截面微流控阀的制备方法中S600的示意图之一。17 is one of the schematic diagrams of S600 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5. FIG.
图18为实施例5中弧形边缘截面微流控阀的制备方法中S600的示意图之二。FIG. 18 is the second schematic diagram of S600 in the preparation method of the arc-shaped edge section microfluidic valve in Example 5. FIG.
图19a为实施例6中制造的控制层的弧形边缘横截面微流控阀(AMV),比例尺:50μm。Figure 19a is an arcuate edge cross-sectional microfluidic valve (AMV) of the control layer fabricated in Example 6, scale bar: 50 μm.
图19b为弧形边缘横截面单片阀(AMV)未关闭时的液体流通情况。Figure 19b shows the flow of liquid when the arcuate edge cross-section monolithic valve (AMV) is not closed.
图19c为实施例6中使用2000rpm转速旋涂PDMS预聚物到控制层主模具上,所制得的弧形边缘横截面单片阀(AMV)未完全关闭。Figure 19c shows that in Example 6, the PDMS prepolymer was spin-coated onto the control layer master mold at 2000 rpm, and the resulting arcuate edge cross-sectional monolithic valve (AMV) was not fully closed.
图19d为实施例6中使用3000rpm转速旋涂PDMS预聚物到控制层主模具上,所制得的弧形边缘横截面单片阀(AMV)完全关闭。Fig. 19d shows that in Example 6, the PDMS prepolymer was spin-coated onto the control layer master mold at 3000 rpm, and the resulting curved edge cross-section monolithic valve (AMV) was completely closed.
图20a为实施例7中使用25min蚀刻产生的弧形边缘横截面通道(AC)。FIG. 20a is a curved edge cross-sectional channel (AC) produced in Example 7 using a 25 min etch.
图20b为实施例7中使用50min蚀刻产生的弧形边缘横截面通道(AC)。Figure 20b shows the curved edge cross-sectional channel (AC) produced in Example 7 using a 50 min etch.
图20c为实施例7中3000rpm(20μm厚)旋涂产生的110μm宽的控制通道的荧光图像。20c is a fluorescence image of the 110 μm wide control channel produced by spin coating at 3000 rpm (20 μm thick) in Example 7. FIG.
图20d为实施例7中4000rpm(20μm厚)旋涂产生的110μm宽的控制通道的荧光图像。FIG. 20d is a fluorescence image of the 110 μm wide control channel produced by spin coating at 4000 rpm (20 μm thick) in Example 7. FIG.
附图标记说明:Description of reference numbers:
10-印刷电路板,11-基板,12-铜板,13-光刻胶,20-光掩模,30-UV光照,40-图案,50-凹槽,51-凹槽边缘,60-PDMS母模,61-Pluronic F-127,62-聚合后的PDMS,70-弧形边缘截面通道(AC);10-Printed Circuit Board, 11-Substrate, 12-Copper Board, 13-Photoresist, 20-Photomask, 30-UV Lighting, 40-Pattern, 50-Groove, 51-Groove Edge, 60-PDMS Master Mold, 61-Pluronic F-127, 62-PDMS after polymerization, 70-Arc edge section channel (AC);
100-流体层,200-控制层,300-部分固化的平面PDMS。100 - fluid layer, 200 - control layer, 300 - partially cured planar PDMS.
具体实施方式Detailed ways
为了更清楚地说明本发明,下面结合优选实施例对本发明做进一步的说明。本领域技术人员应当理解,下面所具体描述的内容是说明性的而非限制性的,不应以此限制本发明的保护范围。In order to illustrate the present invention more clearly, the present invention will be further described below with reference to the preferred embodiments. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not limit the protection scope of the present invention.
实施例1Example 1
本实施例提供一种典型的PDMS母模的制备方法:This embodiment provides a preparation method of a typical PDMS master mold:
S110、如图1所示,带有光刻胶13的印刷电路板10上覆盖光掩模20,并通过UV光照30曝光。其中的印刷电路板10为商业购买,包括基板11、铜板12和光刻胶13。S110 , as shown in FIG. 1 , the printed
S120、进行显影,图案40转移至光刻胶13上;如图2所示。S120, developing, and transferring the
S130、用FeCl3溶液蚀刻,在印刷电路板中的铜板12上形成凹槽50;其中的凹槽50由于是通过蚀刻形成的,其边缘51为弧形,凹槽的横截面为弧形边缘截面;如图3所示。S130, etching with FeCl 3 solution to form a
S140、用丙酮除去光刻胶13,得到PCB母模,如图4所示。S140 , removing the
S210、将PDMS预聚物(基料:固化剂=5:1,w.t.;Sylgard 184,Dow Corning,Midland,MI)倒在PCB母模上,如图5所示。S210. Pour the PDMS prepolymer (binder:curing agent=5:1, w.t.; Sylgard 184, Dow Corning, Midland, MI) on the PCB master mold, as shown in FIG. 5 .
S220、PCB母模上的PDMS预聚物进行聚合;如图6所示。示例性的,65℃下固化30分钟。S220, the PDMS prepolymer on the PCB master mold is polymerized; as shown in FIG. 6 . Exemplarily, cure at 65°C for 30 minutes.
S230、将聚合后的PDMS 62进行剥离得到,使用2%Pluronic F-127(PF127)61进行表面处理3小时。将表面干燥(约30分钟)后,这些PDMS复制品作为PDMS母模60;如图7所示。S230, the polymerized
S240、将PDMS预聚物(基料:固化剂=5:1,w.t.)倒入PDMS母模60上,固化后剥离得到弧形边缘截面通道(AC)70;如图8所示。具有AC特征的聚合PDMS复制品容易从PDMS母模上剥离。S240. Pour the PDMS prepolymer (base material: curing agent=5:1, w.t.) onto the
实施例2Example 2
采用实施例1中的典型制备过程,分别使用35μm、70μm和140μm宽度图案的光掩模,蚀刻25分钟后,制得PDMS母模。得到的PDMS母模如图9a-图9c所示。Using the typical preparation process in Example 1, using photomasks patterned with widths of 35 μm, 70 μm, and 140 μm, respectively, after etching for 25 minutes, PDMS master molds were prepared. The resulting PDMS master molds are shown in Figures 9a-9c.
相应地,使用所得到的PDMS母模制备的弧形边缘截面通道(AC)如图9d-图9f所示。Correspondingly, the curved edge cross-section channels (AC) fabricated using the resulting PDMS master are shown in Figures 9d-9f.
该具有弧形边缘截面的PDMS母模中的凸起的宽度在蚀刻时间一定的情况下,可通过调节光掩模中图案的宽度进行控制。所述凸起的宽度对应于使用该PDMS母模制备的具有弧形边缘截面通道AC的宽度,可具体根据对于通道的宽度需求调整光掩模中图案的宽度。The width of the protrusions in the PDMS master mold with the arc-shaped edge section can be controlled by adjusting the width of the pattern in the photomask under the condition of a certain etching time. The width of the protrusion corresponds to the width of the channel AC with the arc-shaped edge section prepared by using the PDMS master mold, and the width of the pattern in the photomask can be adjusted according to the width requirement of the channel.
实施例3Example 3
采用实施例1中的典型制备过程,使用35μm宽度图案的光掩模,分别蚀刻10min,25min,50min和75min后,制得PDMS母模。得到的PDMS母模如图10a-图10d所示。The PDMS master mold was prepared after etching for 10 min, 25 min, 50 min and 75 min respectively using the typical preparation process in Example 1, using a photomask with a pattern width of 35 μm. The resulting PDMS master molds are shown in Figures 10a-10d.
相应地,使用所得到的PDMS母模制备的弧形边缘截面通道(AC)如图10e-图10h所示。Correspondingly, arcuate edge cross-section channels (AC) fabricated using the resulting PDMS master are shown in Figures 10e-10h.
该具有弧形边缘截面的PDMS母模中的凸起的尺寸在图案宽度一定的情况下,可通过调节蚀刻时间对宽度进行控制。所述凸起的尺寸对应于使用该PDMS母模制备的具有弧形边缘截面通道AC的尺寸,可具体根据对于通道的尺寸需求调整蚀刻时间。The size of the protrusions in the PDMS master mold with the arc-shaped edge section can be controlled by adjusting the etching time under the condition that the pattern width is constant. The size of the protrusion corresponds to the size of the channel AC with arc-shaped edge cross-section prepared by using the PDMS master mold, and the etching time can be adjusted according to the size requirements of the channel.
实施例4Example 4
采用实施例1中的典型制备过程,使用不同的PCB制备PDMS母模;并且该PDMS母模中的凸起为并列排布的多个。其中不同的PCB中的铜板厚度不同,分别为40μm和100μm。Using the typical preparation process in Example 1, different PCBs were used to prepare a PDMS master mold; and the bumps in the PDMS master mold were arranged in parallel. Among them, the thickness of the copper plate in different PCBs is different, which are 40 μm and 100 μm respectively.
然后使用制备的PDMS母模分别制备具有多个凹槽的PDMS复制品。分别如图11和图12所示。PDMS replicas with multiple grooves were then prepared separately using the prepared PDMS master. As shown in Figure 11 and Figure 12, respectively.
由图中可知,凹槽的深度取决于铜层的厚度。As can be seen from the figure, the depth of the groove depends on the thickness of the copper layer.
实施例5Example 5
本实施例提供一种典型的PDMS母模的制备方法:This embodiment provides a preparation method of a typical PDMS master mold:
S310、带有光刻胶的印刷电路板上覆盖光掩模20,并通过UV曝光;如图13所示。S310 , the
S320、进行显影,图案转移至光刻胶上;如图14所示。S320 , developing, and transferring the pattern to the photoresist; as shown in FIG. 14 .
S330、用FeCl3溶液蚀刻,在印刷电路板中的铜板上形成凸起;其中的凸起由于是通过蚀刻形成的,其边缘为向内凹陷的弧形,凸起的横截面为向内凹陷的弧形边缘截面;如图15所示。S330, etching with FeCl 3 solution to form bumps on the copper plate in the printed circuit board; because the bumps are formed by etching, the edges of the bumps are inwardly concave arcs, and the cross-sections of the bumps are inwardly concave The curved edge section of ; as shown in Figure 15.
S340、用丙酮除去光刻胶,得到PCB控制层母模。S340, removing the photoresist with acetone to obtain a master mold of the PCB control layer.
S400、在得到的PCB控制层母模上,使用匀胶机(KW-4A,中国科学院微电子研究所,北京,中国)旋涂PDMS预聚物(基质:固化剂=20:1,w.t.),聚合后得到具有控制通道的控制层200;如图16所示。示例性的,此处的聚合固化条件为在65℃下部分固化40分钟。S400. On the obtained master mold of the PCB control layer, spin coat PDMS prepolymer (matrix: curing agent=20:1, w.t.) using a glue spinner (KW-4A, Institute of Microelectronics, Chinese Academy of Sciences, Beijing, China). , and a
S600、将所述控制层200和流体层100对准,如图17所示,将流体层和控制层在65℃烘箱中再固化50分钟。该组件在玻璃上用部分固化的平面PDMS 300密封,如图18所示。最后,微流控装置在65℃孵育过夜;得到所述弧形边缘截面微流控阀。S600 , align the
实施例6Example 6
采用实施例5中的典型制备过程,采用不同蚀刻时间以及不同转速(3000rpm和2000rpm)进行旋涂得到的控制层,对其进行密封,进行荧光照射以检验其密封性。Using the typical preparation process in Example 5, the control layer obtained by spin coating with different etching times and different rotational speeds (3000 rpm and 2000 rpm) was sealed, and subjected to fluorescent irradiation to test its tightness.
图19a为实施例6中制造的控制层的弧形边缘横截面微流控阀(AMV),比例尺:50μm。Figure 19a is an arcuate edge cross-sectional microfluidic valve (AMV) of the control layer fabricated in Example 6, scale bar: 50 μm.
图19b为弧形边缘横截面单片阀(AMV)未关闭时的液体流通情况。Figure 19b shows the flow of liquid when the arcuate edge cross-section monolithic valve (AMV) is not closed.
图19c为实施例6中使用2000rpm转速旋涂PDMS预聚物到控制层主模具上,所制得的弧形边缘横截面单片阀(AMV)未完全关闭。Figure 19c shows that in Example 6, the PDMS prepolymer was spin-coated onto the control layer master mold at 2000 rpm, and the resulting arcuate edge cross-sectional monolithic valve (AMV) was not fully closed.
图19d为实施例6中使用3000rpm转速旋涂PDMS预聚物到控制层主模具上,所制得的弧形边缘横截面单片阀(AMV)完全关闭。Figure 19d shows that in Example 6, the PDMS prepolymer was spin-coated onto the control layer master mold at 3000 rpm, and the resulting curved edge cross-section monolithic valve (AMV) was completely closed.
如图20a所示,为使用25min蚀刻产生的弧形边缘横截面通道(AC)。比例尺:50μm。As shown in Figure 20a, the curved edge cross-sectional channel (AC) was produced using a 25 min etch. Scale bar: 50 μm.
如图20b所示,为使用50min蚀刻产生的弧形边缘横截面通道(AC)。比例尺:50μm。As shown in Figure 20b, the curved edge cross-sectional channel (AC) was produced using a 50 min etch. Scale bar: 50 μm.
如图20c所示,为3000rpm(20μm厚)旋涂产生的110μm宽的控制通道的荧光图像。由图像看出,有少量液体渗入通道。比例尺:50μm。As shown in Figure 20c, a fluorescence image of a 110 μm wide control channel produced by spin coating at 3000 rpm (20 μm thick). As can be seen from the image, a small amount of liquid seeps into the channel. Scale bar: 50 μm.
如图20d所示,为4000rpm(20μm厚)旋涂产生的110μm宽的控制通道的荧光图像。由图像看出,完全没有液体流入通道。比例尺:50μm。Fluorescence image of a 110 μm wide control channel generated for spin coating at 4000 rpm (20 μm thick) as shown in Figure 20d. As can be seen from the image, there is no liquid flowing into the channel at all. Scale bar: 50 μm.
本发明以上实施例中所使用的PCB中的光刻胶均为正性光刻胶,本领域技术人员容易理解的,采用负性光刻胶同样可以实现目的,相应的调整光掩模即可。且以上PCB图案化过程均为本领域的常规技术手段,本发明中只列举出了一种较为通用的,在此不再一一列举。The photoresists in the PCB used in the above embodiments of the present invention are all positive photoresists, and those skilled in the art can easily understand that the use of negative photoresists can also achieve the purpose, and the photomask can be adjusted accordingly. . In addition, the above PCB patterning processes are all conventional technical means in the art, and only one more general one is listed in the present invention, which will not be listed one by one here.
显然,本发明的上述实施例仅仅是为清楚地说明本发明所作的举例,而并非是对本发明的实施方式的限定,对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动,这里无法对所有的实施方式予以穷举,凡是属于本发明的技术方案所引伸出的显而易见的变化或变动仍处于本发明的保护范围之列。Obviously, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the embodiments of the present invention. Changes or changes in other different forms cannot be exhausted here, and all obvious changes or changes derived from the technical solutions of the present invention are still within the protection scope of the present invention.
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