Fabrication of Microfluidic Chips using Soft Lithography

Monsur Islam and Rodrigo Martinez-Duarte
Multiscale Manufacturing Laboratory
Department of Mechanical Engineering
Clemson University

Soft lithography is by far the most well documented process to fabricate a microfluidic system. First introduced by G.M. Whitesides et al. in the 1990s (Xia & Whitesides, 1998) soft lithography relies on casting of polydimethylsiloxane (PDMS), a soft polymer, to fabricate a microfluidics network. Although a number of commercial PDMS formulations exist, Sylgard 184 has been one of the most popular ones. A master mold is required in soft lithography and is often fabricated using SU-8 photolithography (Martinez-duarte & Madou, 2011), silicon bulk microfabrication (i.e. deep reactive ion etching, or DRIE) (Kuo-Shen Chen, Ayon, Xin Zhang, & Spearing, 2002) or computerized numerically controlled (CNC) machining (Huang et al., 2013). Other techniques include xurography (Islam, Natu, & Martinez-Duarte, 2015; Pinto et al., 2014), 3D printing (Hwang, Paydar, & Candler, 2015) and wax printing (Kaigala et al., 2007). The choice of technique will depend on the equilibrium between cost and robustness of the mold and the desired resolution and surface roughness of the walls. In general, photolithography and DRIE processes are expensive and require complex set ups and a clean room environment; but will yield molds with very high resolution (usually few microns but hundreds of nanometers is possible) and excellent surface roughness. CNC machining is a relatively inexpensive alternative, but the surface roughness and feature resolution may be compromised in this case. In any case, an advantage of a master mold is that it can be used for relatively fast mass production of microfluidic chips. PDMS films are also commercially available or can be made in house using spin coating or alternative fabrication techniques (http://blogs.rsc.org/chipsandtips/2012/04/18/easy-and-inexpensive-fabrication-of-pdms-films-of-different-thicknesses/).

Once the master mold is fabricated, the casting process is implemented without the absolute need for a cleanroom as follows. 1) Mix PDMS in a ratio of 10:1 polymer: crosslinking agent, 2) degas the mixture, 3) cast it over the mold, and 4) heat on a hotplate or convection oven to finalize crosslinking. Changing the ratio of PDMS: cross linker allows for the tailoring of the hardness of the microfluidic piece, i.e. a 20:1 yields a squishy material, like decorative window clings. Some researchers also choose to use a silane molecule to coat the master mold to facilitate de-molding. This is useful but not always necessary. Degassing can be done either of the bulk mixture or after the polymer has been cast. The latter is recommended because the casting process may introduce air bubbles, and also because the thickness of the cast parts is often thinner than the distance an air bubble would travel to the surface in a bulk mixture. After the PDMS piece is crosslinked, it can be manually de-molded and then plasma treated (for example in an O2 plasma or using a plasma wand) to activate the surface for bonding. Plasma treatment is recommended to facilitate a robust bond between PDMS and its substrate, glass or polymer (Kim et al., 2011) specifically if a flow-through device is required. A PDMS mixing ratio of >10:1 is enough to provide some bonding when fabricating devices meant for experiments with stationary samples. Importantly, the cross-linked PDMS piece is gas permeable.

Owing to its simplicity and low cost (excluding the cost of making the master mold), PDMS microfluidics are used by the immense majority of researchers. The flexible nature of the polymer enabled the so-called “Quake” valves that have facilitated microfluidics at very large scale to study reaction and single-cell dynamics. A large number of electrokinetics-based devices use PDMS, but in a few it has been an enabling feature. For example, in contactless dielectrophoresis, PDMS is used as the insulating capacitive barrier (Shafiee, Caldwell, Sano, & Davalos, 2009). Here the PDMS separates the sample channel from the other two side-microchannels which are filled with conductive solution. AC signal is applied to the side microchannels and through the capacitive effect of the PDMS layer, an electric filed is generated to the sample microchannel. Also in case of liquid metal electrode-microfluidic devices, PDMS layers are fabricated by soft lithography to define the channel for liquid metal flow (So & Dickey, 2011). It also separates the liquid metal from the sample channel. PDMS can also be doped by mixing the dopant in the initial mixture. Lepiriyawong et al. used silver doped PDMS as electrodes for dielectrophoretic separation of particles (Lewpiriyawong, Yang, & Lam, 2010). More details on these techniques can be found in an article in this same website (http://www.aesociety.org/areas/micromanufacturing.php).

Disadvantages of PDMS include low elastic modulus (E ~ 1 MPa) and high Poisson’s ration (ʋ ~ 0.5), which makes the PDMS microchannel highly flexible and compliant. Although this compliance is exploited in the implementation of microfluidic valves, i.e. “Quake” valves, it also makes it difficult to fabricate high aspect ratio PDMS structures, i.e. tall pillars tend to bend and buckle (Hui, Jagota, Lin, & Kramer, 2002). Microchannels made of PDMS can also deform significantly when pressurized above 105 Pa (Dangla et al., 2010). Non-compatibility with some solvents is also an issue.. Due to the porous nature of PDMS, some solvents (e.g. hydrocarbons and toluene) diffuse and get adsorbed into the PDMS matrix, which causes swelling of the PDMS (Lee, Park, & Whitesides, 2003).

Figure 1: Schematic of a soft lithography process to fabricate a microfluidics chip. Although the mold shown here is fabricated out of a photoresist, the mold can be fabricated by different means. Adapted with the permission from Nature (Mazutis et al., 2013)
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