微流控气动笼：在芯片水晶捕获，处理的新方法和控制化学处理
Summary
Herein, we describe the fabrication and operation of a double-layer microfluidic system made of polydimethylsiloxane (PDMS). We demonstrate the potential of this device for trapping, directing the coordination pathway of a crystalline molecular material and controlling chemical reactions onto on-chip trapped structures.
Abstract
The precise localization and controlled chemical treatment of structures on a surface are significant challenges for common laboratory technologies. Herein, we introduce a microfluidic-based technology, employing a double-layer microfluidic device, which can trap and localize in situ and ex situ synthesized structures on microfluidic channel surfaces. Crucially, we show how such a device can be used to conduct controlled chemical reactions onto on-chip trapped structures and we demonstrate how the synthetic pathway of a crystalline molecular material and its positioning inside a microfluidic channel can be precisely modified with this technology. This approach provides new opportunities for the controlled assembly of structures on surface and for their subsequent treatment.
Introduction
分子材料长期被研究在科学界，因为在诸如分子电子学，光学和传感器1-4他们的应用广泛的数目。在这些有机导体是一个特别令人兴奋的类，因为它们在柔性显示器和集成功能元件5,6的中心作用的分子的材料。然而，用于使能在基于分子的材料的电子电荷传输方法被限制的电荷输送配合物（的CTC）和电荷输送的盐（CTS消息）7-10的形成。频繁，的CTC和CTS消息是通过电化学方法或通过直接化学氧化还原反应产生的;妨碍供体或受体部分的受控转换到更复杂的结构，其中多功能可以设想流程。因此，为可控生成和分子基的操纵新系统的方法的澄清拆建物料仍保留在材料科学和分子工程领域的一个显著的挑战，如果成功，无疑将导致新的功能和新技术应用。
在这种情况下，微流体技术最近已用于合成基于分子的材料，由于其在合成过程11,12，以控制热与质量传递以及试剂的反应扩散体积的能力。简单地说，在连续的流动和在低雷诺数两个或更多个试剂流之间的稳定的接口，可以实现，其中，得到流路，其中，混合仅通过扩散13-16发生内部良好控制的反应区的形成。事实上，我们先前采用层流来本地化结晶分子材料，例如微流体通道17内的配位聚合物（CPS）的合成途径。虽然这种方法已经显示摹原位 18来实现在实现新颖的CP的纳米结构，所述直接集成这样的结构在表面上，以及控制化学处理它们的形成还没有经过REAT承诺。为了克服这一限制，最近我们表明，在两层微流体装置引入微流体气动笼（或阀门）的致动可以有利在这方面可以使用。由于地震的研究小组19的创举，微流控气动阀经常被用于单细胞捕获和隔离20，酶活性调查21，小的流体体积22俘获，在表面23和蛋白质结晶24功能材料的国产化。然而，我们已经表明，双层的微流体装置可用于捕获，本地化和原位整合形成的结构，以读出的组件和表面上的18。此外，我们还证明，这种技术可以用来在捕获结构进行控制的化学处理，使这两个“微流体辅助配体交换”18和控制的化学有机晶体18,25的掺杂。在这两种情况下，的CTC可以控制微流体的条件下进行合成，并在最近的研究中，多功能可以在相同的材料片进行说明。这里，我们证明采用染料载货流动这些双层的微流体装置的性能，产生和控制一个CP的协调通路以及其微流体通道的表面上的定位和最后评估控制的化学处理到芯片上被困结构。
Protocol
Representative Results
Discussion
The reported approach can be easily modified to fabricate different valve shapes to afford other applications such as fluid confinement. Indeed, the flexibility of this protocol also allows for modification of the thickness of the bottom layer, and thereby of the PDMS membrane, from a couple of tens to a few hundreds of microns to fulfill any application of interest. Moreover, dimensions of structures in each layer of the device can be optimized for the desired application and various heights of structures on the master molds can be simply achieved by spinning the photoresist at different velocities. Spinning the photoresist at a higher speed results in thinner structures.
To better implement the protocol, a clean room environment for the fabrication of the master molds is substantially essential; otherwise, the fabrication procedure will lead to defective master molds and thereby to unusable microfluidic devices. Two critical aspects should be emphasized in this protocol: i) the constant temperature of the oven that needs to be adjusted to 80 °C and ii) the programmed time period between processes that has to be complied accurately. Any modification of temperature and time frame in the protocol might lead to non-bonded chips, and thus, to non-functional devices.
The “turbulent free” conditions typically encountered in microfluidic systems have recently been employed for the generation of microstructures or molecular materials inside30 and outside single layer microfluidic chips31. In double-layer microfluidic chips, the laminar flow regime, and hence, the interface generated between continuous co-flows can be manipulated using pneumatic cages18,28. These devices also provide for effective control over the synthetic pathway, which in turn leads to precise localization and trapping on surfaces18.
As mentioned earlier, pneumatic actuation in double-layer microfluidic chips has been previously employed for various applications such as cell trapping20, enzymatic activity studies21 and protein crystallization24. However, the main objective of the reported approach is to propose a platform to be used for trapping and directing the coordination pathway of a crystalline molecular material and controlling chemical reactions onto on-chip trapped structures18,25.
The described method does not only allow trapping of anisotropic structures but can be used to localize particles onto surfaces. Future studies can be effectively directed towards the design of new valve shapes for additional application in biology, materials science and sensor technologies. The combination of different valve shapes as well as altered channel heights and membrane thicknesses can be employed to fulfill specific applications, such as chemical studies based on diffusional mixing and the localization of material growth.
A further application of the described microfluidic platforms is in the controlled chemical doping of crystals, which can lead to a rationalized formation of interfaces in crystalline structures19. This approach also provides for a wide range of post-treatments of on-chip trapped structures; a methodology that will undoubtedly open new horizons in materials engineering.
It is important to underline that the number of technologies enabling controlled chemical reactions under dynamic conditions and onto crystalline matter are very limited at present, hence making this approach very attractive in materials-related fields. However, a major limitation of this technology is the use of PDMS. PDMS elastomer is incompatible with many organic solvents, which limits the number of reactions that can be conducted inside these microfluidic chips. In future, the development of other elastomers that can tolerate and be stable against a broader number of organic solvents will be highly required in order to expand this field of research to other materials and chemistries.
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
Authors would like to thank the financial support from Swiss National Science Foundation (SNF) through the project no. 200021_160174.
Materials
| High resolution film masks | Microlitho, UK | – | Features down to 5um |
| SU8 photoresist | MicroChem Corp., USA | SU8-3050 | – |
| Silicon wafers | Silicon Materials Inc., Germany | 4" Silicon Wafers | Front surface: polished, Back surface: etched |
| Silicone Elastomer KIT (PDMS) | Dow Corning, USA | Sylgard® 184 | – |
| Spinner | Suiss MicroTech, Germany | Delta 80 spinner | – |
| UV-Optometer | Gigahertz-Optik Inc., USA | X1-1 | – |
| Mask Aligner | Suiss MicroTech, Germany | Karl Suss MA/BA6 | – |
| SU8 developer | Micro resist technology GmbH, Germany | mr-Dev 600 | – |
| Trimethylsilyl chloride | Sigma-Aldrich, Switzerland | 386529 | ≥97%, CAUTION: Handle it only under fume hood. |
| Biopsy puncher | Miltex GmBH, Germany | 33-31AA-P/25 | 1 mm |
| Biopsy puncher | Miltex GmBH, Germany | 33-31A-P/25 | 1.5 mm |
| Glass coverslip | Menzel-Glaser, Germany | BB024040SC | 24 mm × 60 mm, #5 |
| Laboratory Corona Treater | Electro-Technic Products, USA | BD-20ACV | – |
| PTFE tubing | PKM SA, Switzerland | AWG-TFS-XXX | AWG 20TFS, roll of 100 m |
| Silicone rubber tubing | Hi-Tek Products, UK | – | 1 mm I.D. |
| neMESYS Syringe Pumps | Cetoni GmbH, Germany | Low Pressure (290N) | – |
| High resolution camera | Zeiss, Germany | Axiocam MRc 5 | – |
| Fluorescent inverted microscope | Zeiss, Germany | Axio Observer A1 | Operable at two wavelengths i.e. 350 nm and 488 nm |
| Green polystyrene fluorescent particles | Fisher Scientific, Switzerland | 11523363 | Size: 5.0 um, solid content: 1% |
| Silver nitrate (AgNO3) | Sigma-Aldrich, Switzerland | 209139 | ≥99.0%, |
| L-Cysteine (Cys) | Sigma-Aldrich, Switzerland | W326305 | ≥97.0%, |
| Disposable weighing dish | Sigma-Aldrich, Switzerland | Z154881 | L × W × H : 86 mm × 86 mm × 25 mm |
| Disposable weighing dish | Sigma-Aldrich, Switzerland | Z708593 | Hexagonal, Size XL |
| Plastic spatula | Semadeni, Switzerland | 3340 | L × W : 135 mm x 14 mm |
| Dye, Bemacron ROT E-G | Bezema, Switzerland | BZ 911.231 | Red |
| Stereomicroscope | Wild Heerbrugg, Switzerland | Wild M8 | 500x magnification |
| Disposable scalpels | B. Braun, Switzerland | 233-5320 | Nr. 20 |
| L-Ascorbic acid | Sigma-Aldrich, Switzerland | A4403 | – |
