Emerging Techniques in the Fabrication of Microfluidic Devices

Devin Keck, Jordon Gilmore, Monsur Islam, and Rodrigo Martinez-Duarte
Multiscale Manufacturing Laboratory
Department of Mechanical Engineering
Clemson University

Although a number of techniques are established to manufacture microfluidic networks, there is always a push to innovate new ones that would allow for increased fabrication throughput, decrease the cost per device, feature smaller dimensions and enable higher levels of geometric complexity. Here we present three emerging techniques that deserve special mention: 3D Printing, Ion Milling and Print-Cut-Lamination (PCL).

3-Dimensional (3D) Printing

Additive manufacturing processes, the fabrication of pieces layer-by-layer, was introduced in the 1980’s, with 3D Systems Inc’s creation of the stereolithography 3D printer [1]–[4]. A number of additive manufacturing techniques have been developed since and their application in different fields is an active area of research.

The competitive marketplace for state of the art 3-D printers in industrial, consumer, and research settings has resulted in relatively low costs for high quality 3-D printers, which makes 3-D printers desirable for fabrication of microfluidic devices. These devices are classified into three different categories governed by the type of pre-processed material: liquid based, powder based, and solid based[3]. Powder based 3-D printing technologies require an extensive cleaning process to remove the excess material, making them unsuitable for the fabrication of microfluidic devices with internal channels [5]. Furthermore, solid based 3-D printing technologies are also not suitable for the creation of microfluidic devices due to the fact that even the higher precision selective deposition lamination (SDL) printers can only produce a layer thickness as low as 100 µm.

The 3-D printing technologies that are the most promising for the creation of microfluidic devices are the liquid-based printing technologies, however even most of these printers are currently not capable of achieving resolutions as small as those that are obtained using traditional microfluidic manufacturing techniques.

Figure 1: Comparison of 3D Printed and Clean room fabricated trigger valves for autonomous microfluidic capillary circuits. Reprinted with permission from Royal Society of Chemistry. (Olanrewaju et al., 2016)

The Fused Deposition Modeling (FDM) printer is limited by the resolution of the z-stepper motor, the nozzle size, and the rheology of the softened material. The higher quality FDM printers ($10,000-$15,000) advertise resolutions as low as 100 µm. The resolution of the stereolithography (SLA) printer depends on the laser spot size. The SLA printer provides better resolutions than the FDM (25-75 µm) for lower coet ($3,000-5,000), but still does not match the resolution of traditional manufacturing techniques. The high demand and competitive marketplace for 3D printers has led to prices and resolutions that continue to improve each year for both the FDM and SLA printers. If these trends continue the use of 3D printers for microfluidic devices will become standard manufacturing technique within the next decade. Old World Laboratories currently advertises a SLA printer achieving resolutions as low as 0.1 µm at a price of $4,900. If these resolutions hold true, this printer could readily fabricate microfluidic devices and would be an affordable machine in microfluidic laboratories. Resolutions down to 0.1 µm, and the capability to fabricate several devices with repeatable dimensions, can be obtained with more sophisticated equipment, i.e. the two photon technology 3D printer, but currently comes at a price of over $500,000.

As the price and resolutions of 3D printers continue to drop they will become extremely useful tools in microfluidics. The fact that they are small in size and require no additional infrastructure (with the exception of ventilation for some 3-D printers) makes them extremely easy to implement in all settings. Current fabrication techniques using 3D printers to manufacture microfluidic devices include a FDM printer able to create scaffolds of various geometries. The scaffolds are suspended in liquid PDMS and used to make microfluidic channels with a diameter as low as 200 µm by curing the PDMS and removing the scaffolds via an acetone bath [6]. Additionally, Shallan et al. uses a stereolithography printer to fabricate transparent microfluidic devices achieving a minimum channel cross sectional area of 250 µm [7]. These examples illustrate how the layer by layer additive manufacturing process used in 3-D printers allows for the design and fabrication of complex microchannels that were previously not possible using the traditional bulk and surface subtractive manufacturing techniques. Although the machines capable of mass production of reproducible parts still carry an expensive tag, it is expected that this price will drop significantly given continuous support for additive manufacturing techniques and demand from the field.

Ion Milling

Ion milling or micromilling are the general terms for a group of fabrication methods that utilize the purely physical phenomenon of sputtering to create highly precise anisotropic structures. Focused ion beam (FIB) technology is one of these methods, and has been praised for the ability to create high-quality, high-precision microfluidic devices. Using FIB, researchers have been able to achieve submicron structures [8]. Enabled by the potential nanoscale channel dimensions, researchers such as Campbell and coworkers, have employed ion milling techniques for electrophoretic manipulation of single DNA molecules [9]. Similarly, Cannon Jr. et al. demonstrated the multiplexing of FIB-milled nanofluidic channels for single molecule gates in molecular detection assays [10]. Ion milling also allows for the vertical etching of sidewalls in order that specific features can be designed in both the x and y directions. For example, Harnett and colleagues patterned metal onto silicon-on-insulator (SOI) walls vertically-etched by ion milling so that AC current could be passed through fluid flowing through the microchannels [11]. While ion milling does provide the ability to precisely fabricate nanoscale, one major drawback (Figure 2), damage to the substrate surface is often caused by ions that do not precisely hit the targeted pattern. This damage can lead to surface imperfections and inconsistencies [10].

Figure 2: A Single cylindrical FIB-fabricated nanopore (shaded region, scale bar – 2 µm). Inset – Damage to SOI surface caused by ion milling process. Reprinted with permission from AIP Publishing LLC.[10]
Print-Cut-Lamination (PCL)

An emerging technique for fabricating microfluidic chips is the print-cut-lamination (PCL) method, where a stack of patterned transparency-films is bonded using a laser printer to fabricate the microfluidic chip [12]. In this method, patterns are designed by a computer-aided design (CAD) software and printed on a transparency film using a laser printer. Once printed, microfluidic architectures i.e. reservoirs, holes and channels are cut on the film using laser ablation. The printed and ablated transparency films are then aligned manually, followed by roll pressing with a heated roll laminator. During hot roll pressing the toner on the transparency films melts and the films are bonded. Figure 3 shows the different layers containing the holes, reservoirs and channels and final microfluidic device on a CD. A resolution of 100 µm can be achieved with this PCL method, and depends on the resolution of the printer. Compared to soft lithography, the PCL method is fast, relatively inexpensive, and straightforward since it doesn’t require any master. The disadvantage of this process is that the depth of channels and other features cannot be completely tailored but instead depends on the thickness of the films. Partial ablation of the polymer films is theoretically possible but may be challenging to do so reproducibly.

Figure 3: Schematic of different layers of films with printer toner and the assembled CD device with a 3D view of a single chamber, fabricated with PCL method. Reprinted with permission from the Royal Society of Chemistry [13]
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