Microfluidica Gabbie pneumatici: un nuovo approccio per In-chip di cristallo Trapping, manipolazione e trattamento chimico Controlled
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
Materiali molecolari sono stati a lungo studiati nella comunità scientifica a causa del loro ampio numero di applicazioni in campi quali l'elettronica molecolare, ottica e sensori 1-4. Tra questi, i conduttori organici sono una classe particolarmente emozionante di materiali molecolari a causa del loro ruolo centrale nel display flessibili e dispositivi funzionali integrati 5,6. Tuttavia, metodologie utilizzate per consentire il trasporto di carica elettronica in materiali molecolari basati sono limitate alla formazione di complessi di trasporto di carica (CTC) e sali di trasporto di carica (CTSS) 7-10. Frequentemente, CTC e CTS sono generati mediante metodi elettrochimici o da reazioni redox chimiche dirette; processi che ostacolano una trasformazione controllata di porzioni donatori o accettori ad architetture più complesse in cui la multifunzionalità può essere concepito. Pertanto, la spiegazione di nuovi metodi sistematici per la generazione controllabile e manipolazione di molecolare-based materiali rimane una sfida significativa nel campo della scienza dei materiali e ingegneria molecolare, e in caso di successo sarà senza dubbio portare a nuove funzioni e nuove applicazioni tecnologiche.
In questo contesto, le tecnologie microfluidica sono state recentemente utilizzate per sintetizzare materiali molecolari basati grazie alla loro capacità di controllare il calore e di massa e il volume di reazione-diffusione dei reagenti durante un processo sintetico 11,12. In poche parole, flussi continui e a bassi numeri di Reynolds un'interfaccia stabile tra due o più flussi di reagenti può essere realizzato, che permette la formazione di una zona di reazione ben controllato all'interno del percorso di flusso, in cui la miscelazione avviene solo per diffusione 13-16. In effetti, abbiamo precedentemente impiegato flussi laminari di localizzare il percorso di sintesi di materiali molecolari cristallini quali polimeri di coordinazione (CP) all'interno di canali microfluidica 17. Sebbene questa metodologia ha dimostrato gpromessa reat nel realizzare nanostrutture romanzo CP, l'integrazione diretta di tali strutture su superfici, nonché trattamento chimico controllato dopo la loro formazione deve ancora essere realizzato in situ 18. Per superare questa limitazione, abbiamo recentemente dimostrato che l'azionamento di gabbie microfluidica pneumatici (o valvole) incorporate nei dispositivi microfluidici due strati può essere vantaggiosamente utilizzata a questo riguardo. Dal momento che il lavoro pionieristico del gruppo di Quake 19, valvole pneumatiche microfluidica sono spesso stati utilizzati per la cattura a cella singola e isolamento 20, indagini di attività enzimatica 21, cattura di piccoli volumi di fluidi 22, la localizzazione di materiali funzionali sulle superfici 23 e cristallizzazione delle proteine 24. Tuttavia, abbiamo dimostrato che i dispositivi microfluidici doppio strato possono essere usati per intercettare, localizzare e integrare in situ strutture leggere fuori componenti formata e sulle superfici 18. Inoltre, abbiamo anche dimostrato che tale tecnologia può essere utilizzata per eseguire trattamenti chimici controllati su strutture intrappolati, permettendo sia, "microfluidica assistita scambio ligando" 18 e il doping chimica controllata di cristalli organici 18,25. In entrambi i casi, CTC possono essere sintetizzate in condizioni controllate microfluidica, e nella più recente studio, multifunzionalità potrebbero essere descritte nello stesso pezzo di materiale. Qui, dimostriamo le prestazioni di questi doppio strato dispositivi microfluidici impiegano flussi colorante carichi, generare e controllare il percorso coordinamento di CP e la sua localizzazione sulla superficie di un canale microfluidico e infine valutare controllato trattamenti chimici su on-chip strutture in trappola.
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.
Divulgations
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 | – |
