Microfluidic Devices Made of Glass

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Microfluidic Devices Made of Glass A. Freitag, D. Vogel, R. Scholz and T. R. Dietrich Journal of Laboratory Automation 2001 6: 45 DOI: 10.1016/S1535-5535(04)00143-1 The online version of this article can be found at: http://jla.sagepub.com/content/6/4/45

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Microfluidic Devices Made of Glass A. Freitag, D. Vogel, R. Scholz, T. R. Dietrich mgt mikroglas technik AG, Mainz, Germany

ABSTRACT

M

ikroglas is a young, innovative and highly-specialized enterprise, which has special know-how in the development of microstructured glass components. Due to its unique properties, glass plays an important role in the field of microtechnology. Most important for many of these new applications are: · its optical transparency and good fluorescence properties, allowing the user to carry out in-situ-measurements, e.g., to detect products after a chemical reaction directly in the device · its stability at high temperatures so that reactions can be influenced by heating different zones of the device · its chemical resistivity, e.g., to handle aggressive substances · its high electrical resistivity, e.g., to transport liquids by electrophoresis or to carry out electrical measurements · its good biological compatibility which is necessary for medical and biological applications The process of structuring FOTURAN will be described. With this technology different microfluidic devices have been manufactured. The channels have a width and depth of 50 µm up to 1 mm and a length of 20 mm up to 280 mm. Various parameters have been measured, e. g., the heat exchange and transfer coefficient for pure water as a function of the temperature. Also optical and thermal analysis techniques have been used to characterize the fluidic components. The results combined with advanced computational fluidic simulations lead to new solutions for different tasks. MATERIAL PROPERTIES

Glass is an amorphous material. Mechanical drilling, milling, sandblasting or isotropic wet etching processes are different ways of structuring it. During the latter process the glass is etched nearly equally fast in all directions. Therefore it is not possible to generate very fine and deep structures with a high aspect ratio. FOTURAN is a photosensitive glass, which means that the material itself is sensitive to UV light of a wavelength of around 310 nm. The material is exposed through a quartz mask with a structured chromium layer. The chromium layer shows the structures needed. After exposure a heat treatment step follows. The substrate is heated up to 600°C so that the exposed parts of the material crystallize while the non-exposed parts retain their glass structure. The crystallization causes warpage of the material surface. The substrate has to be polished subsequently. The crystallized parts can then be etched away in a solution of hydrofluoric acid.

Figure 1. Structurization of Glass

Figure 2. Structurization of FOTURAN

The etching rate of the ceramic is 20 times higher than that of the glass. An aspect ratio of 20:1 (exposed : unexposed) can be achieved. A thus structured substrate can be bonded to another structured or unstructured substrate by diffusion bonding. It is also possible to form chambers or channel systems in which liquids or gases can be handled 1. BIOTE CHNOLOGICA L APPLICATIONS

Microtiterplates were one of the first products which were developed for biotechnological applications. The hole plate is made of FOTURAN ®, either in transparent glass or in an opaque black ceramic version. Standard microscopy glass sheets or UV transparent quartz plates can be used as bottom plates. Because of the different heat expansion coefficient, quartz has to be glued to the hole plate. The microtiterplates are available with 96, 384 or 1536 wells, or in a customized design. Due to the FOTURAN technique, the plates are limited to 2.5 mm in thickness. In order to handle the plates with automized standard lab equipment, an adapter had to be developed according to the

Figure 3. Standard mikroglas® titerplates and adapters.

Figure 5. Single hole, width approx. 30 µm.

SBS standards. The hole diameters can vary from 40 µm to 7 mm. For special applications it is possible to combine several plates with different hole sizes. In Figure 4 a two-layered structure is shown which contains in the first layer holes with a diameter in the range of approximately 1.5 mm and in the second layer of approximately 40 µm. This plate can be used for the integrated synthesis on beads and biological testing in small volumes. The condensed format enables the efficient use of scarce chemical and biological resources2.

Figure 6. Isotropically etched channels, Width: approx. 30 µm, Depth: approx. 13 µm.

Figure 4. Two-layered structure of FOTURAN plates (150µm thick) bonded together.

The technique of structuring FOTURAN can also be combined with conventional isotropic etching. This creates the possibility to manufacture so called Lab-on-a-chip systems in a fairly easy way. The plates are manufactured by using a combination of the FOTURAN process (for the access holes with depths of 0.5 to 1 mm and diameters of up to 3 or 4 mm) and a standard photolithography process (for the 13 x 30 µm channels). Microfluidic devices for application in the field of pharmaceutical research can also be built with this technique. Channels with a

Figure 7. Nozzel system consisting of three layers of FOTURAN

width of 300 µm have been etched into a plate with a thickness of also 300 µm. This channel system has been sealed with an unstructured top and bottom plate.

immediately draw off the heat from the highly exothermal reaction in order to reduce side products. The liquids are chemically very aggressive and the reactor material had to withstand these chemicals. Another necessary property was its optical transparency so that methods for optical analysis could be integrated. All these requirements made FOTURAN the most appropriate material for the reactor device because of its chemical and thermal stability and its optical transparency.

Figure 8. Microreactor

Figure 9. Sketch of one Reaction Chamber of the Microreactor.

This system consists of four structured layers: · The bottom plate is unstructured · The second plate contains the cooling channels, the supply channels for the two educts and the resulting product. This plate is 700 µm in thickness · The third plate is only 200 µm in thickness and separates the cooling liquid from the educt and product flow · The fourth plate is the core of the reactor: It contains the inlet channels of the two liquids which are to be mixed. These channels lead into the mixing chamber where the two liquids react heavily exothermal. The expected process heat of DHR = 500 - 1000 kJ/mol has to be drawn off within 1 s in the adjoining cooling channels to avoid side products · The system is covered with a plate that also provides the holes for connecting the tubes All channels have a length of 18 mm. The width of the product and cooling channels is 700 µm. The surface of the wall for the heat exchange is 12.6 mm2 for one channel. In this system 20 channels run parallel and the total area is 252 mm2. A flow rate for the total system of 36 ml/min is expected. In the experiments performed by the ICT, different nitrating agents were used. Other materials than glass were tested too, but they did not withstand corrosion processes inside the microstructures. The mixing performance of the reactor was characterized and the experiments clearly showed a laminar flow behavior of the educt streams and thus a diffusion controlled mixing of the reactants. Depending on the flow rates complete mixing was achieved at the end of the reaction channel or much earlier. These experimental data could be confirmed by CFD simulations 3. HEAT EXCHANGER

Figure 10. mikroglas® heat exchanger

MICROFLUIDIC DEVICES FOR CHE MICAL APPLICATIONS

The above described technology was used for designing a new microreaction system together with the Fraunhofer Institute for Chemical Technology (ICT) in Pfinztal, Germany. This system was designed to mix two liquids and to almost

The system consists of seven structured layers, into which the channels and other structures have been etched. The design is based on a tube-in-tube heat exchanger. There are five channels which run in parallel. They have a width of 1 mm and a depth of 400 µm. The channel length is 280 mm. The resulting surface of the separating layer between the channels is 1400 mm2. Due to this design the layer between the channels is responsible for the heat exchange and therefore has to be as thin as possible. A compromise between the effectiveness of the heat exchange and the mechanical stability of the thin layer had to be found. A thickness of the separating layer of around 200 µm was the solution. In order to connect the tubes a metal housing was designed. The tubes will be pressed to the glass surface. This is a leakage free connection which was tested up to 9 bar drop in pressure. After the realization of the heat exchanger it has been analysed by the use of thermal photography. The liquid used for these tests was pure water, heated up externally. Gear pumps were used to push the water through the heat exchanger.

The heat exchanger was tested up to a flow rate of 3.0 ml/s flow rate. The temperatures applied were in a range of 20° C up to 80° C. The calculated heat exchange coefficient based on the data measured starts at 500 W/m2K and goes up to 4500 W/m2K. The pertinent literature gives heat exchange coefficients from 500 W/m2K up to 1500 W/m2K for typical heat exchangers with dimensions found in lab or mini-plant applications 4. Compared to these the heat exchange coefficient of the micro heat exchanger discussed here is three times better. Even higher heat exchange coefficients are possible at higher volume flows5. MICROMIXER

There are many different designs for static mixing systems. One of the ideas is to split two streams into many small streams and to let them flow parallel into a mixing chamber. The mixing takes

place by diffusion. Together with the Institute of Microtechnology Mainz GmbH (IMM) a static mixing system has been realized based on this idea. Two liquids are split into 30 small streams. These streams flow alternatingly into the mixing chamber. The mixing chamber therefore may have different designs to fulfill different tasks.6 The system consists of structured layers which have different functions. They contain channels for the supply of the two educts, that are to be mixed. The channels lead into the mixing chamber where the two liquids react. The system is covered with a plate that also provides the holes for connecting the tubes. The total length of the mixer is 76 mm and the total width is 26 mm. The small channels for the inlet have a width of 70 µm and a depth of 150 µm. The walls between these channels have a thickness of only 30 µm but the bonding of the plates was sufficient to secure

Figure 12. Micromixing Unit. Figure 11. Thermal photography.

Figure 13. SEM Picture of the Mixing Chamber.

Figure 14. Flow Profile for a Volume Flow of 1000 ml/h. Figure 15. Computational Fluid Simulation.

a leakage-free separation of the streams. The channel behind the mixing chamber has a length of 30 mm. This system was tested with flow rates of up to 1000 ml/h for each liquid. The picture was made by pumping pure and blue coloured water through the micromixer. It shows the thin lamellae which run parallel. This picture will not change even for different flow rates. That means that the mixing quality only depends on the diffusion coefficient of the two media. For encouraging the mixing it is helpful to decrease the thickness of the lamellae by focussing. This was the reason why a triangular mixing chamber was designed. At the end of the chamber when it runs into the reaction channel the lamellae only have a thickness of several µm. SUMM ARY

All the examples described in this paper show the potential of FOTURAN as an excellent material for microfluidic devices. Its high chemical resistance allows it to be used where aggressive and hazardous chemicals need to be handled. Its optical transparency makes it easy to look directly into the flow conditions. With this information it is easy to design new and better devices. ACKNOWLEDGEMENT

The authors thank Dr. Löbbecke, Mr. Türcke and Mr. Marioth from the ICT for their support in the development of the microreactor. Furthermore we thank Dr. Löwe and Dr. Hessel from the IMM for their very efficient cooperation in the development of the micromixing unit.

REFERENCES

1. T. R. Dietrich, W. Ehrfeld, M. Lacher, M. Krämer, and B. Speit, “Fabrication technologies for microsystems utilizing photoetch able glass”, Microelectronic Engineering 30 (1996) 497-504 2. “Pharmaceutical Research at Merck”, CHEManager Screening 2 (2001) 10-12 3. S. Löbbecke, J. Antes, T. Türcke, E. Marioth, K. Schmid, H. Krause, “The Potential of Microreactors for the Synthesis of Energetic Materials”, 31st Int. Annu. Conf. ICT Energetic Materials - Analysis, Diagnostics and Testing, 33, 27 - 30 June 2000, Karlsruhe 4. VDI-Wärmeatlas, Berechnungsblätter für den Wärmeübergang, 6. Erweiterte Auflage”, VDI-Verlag GmbH, Düsseldorf 1991 5. R. Scholz, „Herstellung und Vermessung von Mikrowärmeübertragern aus photostrukturierbarem Glas”, Diploma thesis, University of Applied Science, Frankfurt am Main 1999 6. H. Löwe, W. Ehrfeld, V. Hessel, Th. Richter, J. Schiewe, “Micromixing Technology”, Proceedings IMRET 4 (2000) 31-47