Article pubs.acs.org/jchemeduc
Low-Cost Rapid Prototyping of Whole-Glass Microfluidic Devices Po Ki Yuen* and Vasiliy N. Goral Science and Technology, Corning Incorporated, Corning, New York 14831, United States
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S Supporting Information *
ABSTRACT: A low-cost, straightforward, rapid prototyping of whole-glass microfluidic devices is presented using glass-etching cream that can be easily purchased in local stores. A self-adhered vinyl stencil cut out by a desktop digital craft cutter was used as an etching mask for patterning microstructures in glass using the glass-etching cream. A specific calcium-assisted glass-to-glass bonding at 115 °C in a standard laboratory oven for 2 h was used to complete the whole-glass microfluidic device fabrication process. Various functional microfluidic devices were demonstrated with this rapid prototyping method. The complete fabrication process from device-design concept to working device can be completed in approximately 3 to 4 h in a regular laboratory setting without the need of expensive equipment and the need to handle extremely hazardous hydrofluoric acid. This whole-glass rapid prototyping method will be of immediate benefit to the microfluidic and nano- or micro-fabrication community in potentially saving time and costs associated with prototyping of whole-glass microfluidic devices. Also, it lowers the barriers to new entrants to the field of microfluidics and could be useful at both undergraduate and graduate levels for hands-on microfabrication and microfluidic courses with limited resources for expensive and high tech equipment. KEYWORDS: General Public, Upper-Division Undergraduate, Analytical Chemistry, Interdisciplinary/Multidisciplinary, Laboratory Instruction, Hands-On Learning/Manipulatives, Biotechnology, Electrophoresis, Laboratory Equipment/Apparatus, Microscale Lab
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pattern microstructures in glass.10−13 Among them, the wellknown and well-established method for patterning microstructures in glass is to use hydrofluoric acid (HF), buffered HF (BHF), or reactive ion etch, and these processes are also commercially available. Typically, the glass microstructure patterning process involves masking a glass substrate with a metal layer followed by lithographic patterning of the metal mask. Then, the exposed glass substrate is etched with a HFbased solution or reactive ion etch to produce microstructures in the glass substrate. Finally, the mask is removed. On the other hand, glass etching with glass-etching cream, which can be easily purchased in local stores, is widely used in many craft projects at home or hobby stores for personalizing or decorating household glassware, glass windows, glass doors, glass mirrors, and so forth. Also, glass-etching cream is easy to use and is fairly inexpensive compared with HF or BHF. In addition, because of glass-etching cream’s high viscosity, the glass etching process only requires a customized self-adhered vinyl stencil instead of a patterned metal layer as an etching mask. In this article, we present a low-cost, straightforward, rapid prototyping method of whole-glass microfluidic devices using glass-etching cream and self-adhered vinyl mask. This low-cost rapid prototyping method eliminates the need of expensive equipment, clean-room facilities, and the need to handle extremely hazardous HF. New entrants to the field of microfluidics would be able to design, fabricate, and test their whole-glass microfluidic devices with ease in a regular laboratory setting. In the teaching laboratories such as
n the early development of microfluidic devices, glass and silicon were the materials of choice as these two materials can be processed with high precision and remarkable microstructures can be fabricated by the conventional micromachining techniques used in the semiconductor industry. Also, glass is optically transparent in a wide range of wavelengths, chemically inert, surface stable, and suitable for different metal depositions and silicon has good electrical properties and outstanding machinability. In addition, glass and silicon can be easily bonded by conventional anodic bonding. Thus, early microfluidic devices were made from these two materials.1−4 However, the use of glass and silicon to fabricate microfluidic devices requires well-trained operators and complicated and expensive equipment in a clean-room environment. These two materials were gradually replaced by plastics 5 and in particular, by poly(dimethylsiloxane) (PDMS).6,7 Albeit its shortcomings,8,9 PDMS became the material of choice for fabricating microfluidic devices for biological and chemical applications as the use of PDMS within microfluidic devices allows ease of fabrication, rapid prototyping, and reduced materials costs. Unfortunately, fundamental incompatibilities of PDMS with many solvents have limited its applications.8 Thus, there is still a need in glass-based microfluidic devices for applications where optical transparency, chemical inertness, surface stability, and good metal depositions are desired. Wet and dry etching, photolithography, electron-beam lithography, and other micromachining techniques used in the semiconductor industry, all of which require the use of clean-room facilities and equipment, are commonly used to © 2012 American Chemical Society and Division of Chemical Education, Inc.
Published: July 13, 2012 1288
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performing capillary electrophoresis (CE) separation14,15 with a total laboratory time of 8 h, students either in the undergraduate or graduate level could take advantage of this low-cost, rapid prototyping method to gain hands-on laboratory experience on designing, fabricating, and testing their wholeglass microfluidic devices. Because of optical transparency, chemical inertness, surface stability, and good metal depositions of glass, students could use their whole-glass microfluidic devices to control and transfer tiny quantities of liquids to allow chemical reactions or biological assays that could not be accomplished with plastic or PDMS-based microfluidic devices and to study how fluid properties change at the microscale and how they can be exploited for new uses.8,9,14−18
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adhered to the glass surface without any bubbles by using a squeegee. Glass Microstructure Patterning
A thick layer of Armour Etch glass-etching cream (part #150150, Armour Products, Hawthorne, NJ; 3 ounce bottle for around U.S. $9.00) was applied to the openings of the selfadhered vinyl mask (Figure 1B,F). Other similar glass-etching creams such as etchall etching creme (B & B Product, Inc., Peoria, AZ; 1 ounce bottle for around U.S. $5.00) can also be used. To prevent the glass-etching cream from drying out during etching, the “creamed” glass substrate was covered with a 150 mm Pyrex Petri dish top (Corning Incorporated, Corning, NY) with a moist paper towel attaching to the inside bottom of the Pyrex Petri dish top. After the desired etching time, the glass-etching cream was washed away with a stream of running water and the self-adhered vinyl mask was removed. Care was taken to ensure that all traces of the glass-etching cream were completely removed from the glass surface. The glass substrate was dried with nitrogen gas (Figure 1C,G). Inlet and outlet holes were then mechanically drilled through an unetched glass substrate with a 1/20 in. diamond drill bit (DiamondBurs.Net LLC, Stone Mountain, GA). Alternatively, an electrochemical spark erosion method can be used to drill holes in the glass substrate or thermally bonded glass device.20 Finally, the two glass substrates, etched and unetched, were aligned and bonded together as described below (Figure 1D,H).
EXPERIMENTAL OVERVIEW
Self-Adhered Vinyl Mask Preparation
A customized microfluidic device design stencil or mask was cut from a vinyl self-adhesive sheet (item 699009, The Paper Studio, Oklahoma City, OK; 2 sheets of 12 in. × 36 in. for around U.S. $8.00) using a desktop digital craft cutter (cost between U.S. $150.00 and U.S. $300.00).19 The cut selfadhered vinyl mask was adhered to one side of a microscope glass slide (Corning 2947-75×25 micro slides, plain precleaned 75 mm × 25 mm, Corning Incorporated, Corning, NY) or a 100 mm Pyrex/Borofloat glass wafer (University Wafers, South Boston, MA) as an etching mask (Figure 1A,E). Borofloat glass is a replacement product of Pyrex glass as both glasses have similar properties. No precleaning was performed on the glass substrate before adhering the self-adhered vinyl mask. Also, care was taken to ensure that the self-adhered vinyl mask was fully
Glass-to-Glass Bonding
A specific calcium-assisted glass-to-glass bonding technique21 at 115 °C was chosen as the glass bonding process for the lowcost, rapid prototyping of whole-glass microfluidic devices. A glass-to-glass bonding process requiring temperatures between 500 and 620 °C is one of the well-researched areas for glass microfluidic device fabrication and is commercially available. Typically, glass-to-glass bonding is performed by thermal fusion boding in which two glass substrates are pressed together and heat is applied between 500 and 620 °C for few hours under controlled conditions.3 Bonding of glass microfluidic chips at room temperatures was also developed and demonstrated for capillary electrophoresis separations without the requirement of clean-room facilities, programmed high-temperature furnaces, pressurized water sources, adhesives, or pressurizing weights.22 However, three to four days are required to stabilize the bonding quality or high temperature treatment at 550 °C immediately after forced drying is required for same day usage. On the other hand, the calcium-assisted glass-to-glass bonding technique21 requires only washing of the glass surfaces with a calcium solution, clamping the processed glass substrates between two glass slides with binder clips, and 1−2 h of bonding at 115 °C in a standard laboratory oven (Isotemp Oven, Fisher Scientific, Pittsburgh, PA) without the need of high temperature oven.21
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HAZARDS The active ingredient of the glass-etching cream is ammonium bifluoride, which is hazardous in case of skin contact but it is less potent than HF, which should be handled with extreme care as it can penetrate the skin and cause destruction of deep tissue layers, including bone. Thus, anyone using the glassetching cream should be advised of the involved risks of accidental skin contact. In case of skin contact, the skin should be flushed with plenty of water for at least 15 min while
Figure 1. Fabrication of whole-glass microfluidic device with (A−D) 75 mm × 25 mm microscope glass slides and (E−H) 100 mm Pyrex/ Borofloat glass wafers. Self-adhered vinyl microfluidic device design masks were adhered onto (A) a 75 mm × 25 mm microscope glass slide and (E) a 100 mm Pyrex/Borofloat glass wafer. (B and F) Armour Etch glass-etching cream was applied on top of the selfadhered vinyl mask. (C and G) Patterned microfluidic device design after 15 min of etching. (D and H) Functional microfluidic device after inlet and outlet holes drilling and bonding. 1289
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removing contaminated clothing and shoes. The irritated skin should be covered with an emollient and medical attention sought immediately. As precaution, lab coats, gloves, and eye protections should be worn throughout the device fabrication process. Contaminated materials should be disposed appropriately as hazardous chemicals.
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RESULTS AND DISCUSSION
Glass Microstructure Patterning
It is instructive to note that the etched glass surface texture of the microscope glass slide and the Pyrex/Borofloat glass wafer was completely different with the glass-etching cream. The etched microscope glass slide surface had a rough surface texture and a frosted appearance whereas the etched Pyrex/ Borofloat glass wafer surface remained smooth and transparent (compare Figure 1C with Figure 1G, and see Figures 2 and 3).
Figure 3. Microscopic images of patterned microstructures in a 100 mm Pyrex/Borofloat glass wafer using a self-adhered vinyl mask and Armour Etch glass-etching cream after different etching times. Arrows indicate random etched structures due to poor adhesion of selfadhered vinyl mask: (A) 5 min, (B) 15 min, (C) 30 min, and (D) 60 min.
applications, the glass-etching cream would be a perfect alternative for fabricating glass-based microfluidic devices. However, roughened surface may be used to enhance mixing in microfluidic applications and students are encouraged to explore this further when designing their own microfluidic devices. The etch rate of Pyrex/Borofloat glass at room temperature in Armour Etch glass-etching cream, which contains ammonium/sodium bifluorides, and in etchall etching creme, which contains 20% ammonium bifluoride, is similar (Figure 4). Figure 2. Microscopic images of patterned microstructures (A and C) in a 75 mm × 25 mm microscope glass slide, and (B and D) in a 100 mm Pyrex/Borofloat glass wafer using self-adhered vinyl mask and Armour Etch glass-etching cream after 15 min of etching. (C and D) Magnified views of box in panels A and B, respectively. Dashed line in panel D indicates boundary of self-adhered vinyl mask and arrows indicate random etched structures due to poor adhesion of selfadhered vinyl mask.
The active ingredient of the glass-etching cream is ammonium bifluoride, which is designed for soda-lime glasses (for example, microscope glass slides). Soda-lime glass is commonly made with a combination of various oxides or oxygen-based compounds, such that the etched surface with the glass-etching cream will be roughened and will appear frosted due to insoluble compounds. On the other hand, Pyrex/Borofloat glass has no alkaline earth metals or other constituents that would form an insoluble fluoride. In addition, the boron on Pyrex/Borofloat glass would serve to limit the formation of insoluble compounds. Thus, the etched surface of the Pyrex/ Borofloat glass with the glass-etching cream will remain smooth and transparent, and in the hobby and craft projects, glassetching cream is not recommended for Pyrex/Borofloat glass. Because Pyrex/Borofloat glass is typically the glass of choice in the field of microfluidics, and a smooth surface and transparent appearance are typically required for most of the microfluidic
Figure 4. Etch rate of Pyrex/Borofloat glass at room temperature as a function of time.
The Armour Etch glass-etching cream has a slower etch rate (approximately 0.13 μm/min) compared with the etchall etching creme (approximately 0.15 μm/min) whereas the etch rate of Pyrex glass in commonly used BHF (5% HF) is about 3 times slower (approximately 0.04 μm/min at room temperature) than both etching creams.23 However, it is wellknown that by adding hydrochloric acid (HCl) or by increasing the concentration of HF, glass etch rate can be increased dramatically, for example, the etch rate of Pyrex glass at room 1290
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than the etching mask could be more severe with the selfadhered vinyl mask due to its poor adhesion to glass. However, one of the advantages of using the self-adhered vinyl mask and the glass-etching cream is that curved glass surfaces can easily be patterned and etched which may be very difficult to achieve with the conventional photolithography metal masking and HF etching techniques. The calcium-assisted glass-to-glass bonding technique was used to assemble functional whole-glass microfluidic devices (Figures 1 and 6). The most important aspect of the calcium-
temperature can be increased to approximately 0.23 and 3.4 μm/min by adding 5−10% HCl to BHF (5% HF) and in 40% HF, respectively.23 Thus, it is possible to add HCl to the glassetching cream to increase the etching rate. Because the etch rate in glass-etching cream is relatively low, etching times are fairly long for deep features. Also, as expected, due to insoluble products, the etch rate will decrease as the etching time increases, for example, after 60 min of etching, the etch depth was approximately 5.1 μm for Armour Etch glassetching cream and 4.8 μm for etchall etching creme. In addition, due to its poor adhesion to glass, it is expected that the limitation in using self-adhered vinyl stencil as an etching mask is that it will gradually lift off during etching and hence allow the glass-etching cream to etch the glass substrate indiscriminately (Figures 2D and 3). For example, after 15 min of etching in the glass-etching cream, visible random etched structures were observed around the patterned structures (Figure 3). Also, because the desktop digital craft cutter has a cutting resolution of approximately 200 μm19 and the resulting cut mask patterns will always have rough edges, the cut selfadhered vinyl mask and hence the etched structures in glass will always be limited by these cutting limitations. As a result, there may be limitations for microfluidic applications that require a sharp, well-defined interface between the unetched and etched surfaces. Fortunately, there is a solution. To prevent etching mask lift-off problems and to improve etching mask patterning, a metal mask patterned by conventional photolithography process with good quality of adhesion layer can be used together with the glass-etching cream for patterning good quality of microstructures in glass. For example, Tay et al.24 reported the use of a low stress chromium-gold with assistance of photoresist as masking layer for deep wet etch of annealed Pyrex glass in highly concentrated HF. Glass is an amorphous material. Thus, as expected, glass etching with the glass-etching cream is also isotropic. As a result, sharp corners and high aspect ratios cannot be achieved by the glass-etching cream even with an etching mask that has excellent adhesion layer to glass. Also, inherent to isotropic etching, underetching and etched pattern wider than the etching mask are expected (Figure 5). In addition, it is expected that with longer etching time, the effect of etched pattern wider
Figure 6. (A) Patterned microfluidic chamber in a 75 mm × 25 mm microscope glass slide using self-adhered vinyl mask after 15 min of etching in Armour Etch glass-etching cream. (B) Assembled wholeglass microfluidic chamber filled with blue-colored food dye.
assisted glass-to-glass bonding technique is cleaning the glass substrates and making sure that there are no defects (Newton rings) in the seal after the initial drying at 60 °C in a standard laboratory oven for 1 h. Also, this bonding technique is easier to master for small glass substrates. For example, for the 100 mm Pyrex/Borofloat glass wafers, a temperature-controlled press was used instead of glass slides, binder clips, and a standard laboratory oven. Nonetheless, the calcium-assisted glass-to-glass bonding technique is a simple and easy way to bond glass substrates at low temperature in a regular laboratory setting.
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CONCLUSION The self-adhered vinyl mask and glass-etching cream together with the calcium-assisted glass-to-glass bonding technique provides low-cost, straightforward, rapid prototyping of whole-glass microfluidic devices that can be easily fabricated in a regular laboratory without any conventional photolithography metal masking and the need to handle extremely hazardous HF. This whole-glass rapid prototyping method will be of immediate benefit to the microfluidic and nano- or microfabrication community in potentially saving them time and costs associated with prototyping of whole-glass microfluidic devices. Also, it lowers the barriers to new entrants to the field of microfluidics and could be useful in teaching laboratories with limited resources for expensive and high tech equipment.
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ASSOCIATED CONTENT
S Supporting Information *
The procedure for designing and cutting the self-adhered vinyl mask with the digital craft cutter. This material is available via the Internet at http://pubs.acs.org.
Figure 5. Cross-sectional views generated by confocal images of etched microchannel in Pyrex/Borofloat glass wafer using etchall etching creme with a self-adhered vinyl mask that had an approximately 500 μm wide × 5 mm long opening. Z is the etch depth of the microchannel: (A) 10 min of etching; (B) 15 min of etching, and (C) 60 min of etching.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. 1291
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Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We would like to thank Daniel A. Sternquist, Ruchirej Yongsunthon, and Todd L. Heck for their help on this work. REFERENCES
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