Monsur Islam and Rodrigo Martinez-Duarte
Multiscale Manufacturing Laboratory
Department of Mechanical Engineering
Paper microfluidics is a simple and low-cost microfluidics technique for fluid manipulation and molecular diagnostics. Whitesides and his group at Harvard University are to be credited for the invention of this technique (Martinez, Phillips, Wiley, Gupta, & Whitesides, 2008). The fundamental principle of the technique is the patterning of paper with hydrophobic substances to create channels. The channels remain un-treated and the fluid can be driven through them thanks to wicking. There are three main processes to paper patterning: (1) physically blocking the pores of the cellulose fibril network of paper; (2) deposition of hydrophobic material on the cellulose fibres; and (3) chemical modification of the cellulose fibres by reacting with the hydroxyl groups. Photolithography of SU-8 photoresist (Klasner et al., 2010) and plotting of PDMS (Bruzewicz, Reches, & Whitesides, 2008) have been employed for physically blocking of the pores of the cellulose fibril network. For material deposition, paraffin wax was chosen as inexpensive hydrophobic material and the availability of techniques to pattern it such as direct printing (Lu, Shi, Jiang, Qin, & Lin, 2009) and screen printing (Dungchai, Chailapakul, & Henry, 2011). Aside from wax, polystyrene has been used by patterning using ink jet etching (Abe, Suzuki, & Citterio, 2008) and flexography printing techniques (Olkkonen, Lehtinen, & Erho, 2010). Regarding chemical modification, alkyl ketene dimer (AKD) was used as the reactive agent and patterned using ink jet printing (Delaney, Hogan, Tian, & Shen, 2011) and plasma treatment (Li, Tian, & Shen, 2010).
Among the techniques mentioned above, SU-8 photolithography and wax printing are the most popular methods for paper microfluidics. For SU-8 photolithography, the paper is soaked in un-crosslinked SU-8 and patterned using photolithography. After developing the unexposed regions, the whole paper is treated with oxygen plasma eliminate any residues of un-crosslinked SU-8. A minimum resolution of 200 µm was achieved using this method (Li, Ballerini, & Shen, 2012). In the case of wax printing, the printer head can dispense melted wax on the paper in form of liquid droplets of 50-60 µm diameter. Since the printed wax solidifies rapidly upon contact with the paper, the printed paper must be heated to 150 °C so the wax melts and spreads through the thickness of the paper to further define the microchannel walls. A minimum resolution of 550 µm can be achieved for the microchannel width using this method (Carrilho, Martinez, & Whitesides, 2009). In other noteworthy works, Whitesides and colleagues demonstrated a method to fabricate 3D microfluidic device by stacking 2D patterned papers featuring double sided adhesives (Martinez, Phillips, & Whitesides, 2008). They first patterned different layers on 2D papers using photolithography. The patterned papers were then aligned and bonded together using a double sided adhesive to create the 3D microfluidic device. A number of researchers have also used the art of origami to fabricate 3D paper microfluidic devices. All the layers were first patterned on single paper and folded. Different pieces were then clamped together to complete the device (Ge, Wang, Song, Ge, & Yu, 2012; Liu & Crooks, 2011).
The advantages of using paper microfluidics are extremely low costs, user-friendliness and portability. These position the technology as an important platform for disease diagnostics and environmental monitoring. Paper microfluidics has been successfully used for quantitative analysis of several analytes from biological samples such as glucose, lactate and uric acid from urine (Dungchai, Chailapakul, & Henry, 2010). Disadvantages include that the amount of sample that reaches to the detection chamber is less than 50% of the total amount of sample loaded into the device. Hence when the sample quantity is small or the concentration of targeted molecules is low, the detection becomes challenging. Also, it is not well suited for analysis where particles or cells are present since the microfluidics channels are full of paper fibers.
|FIGURE 1: A. Schematic of the fabrication of paper based microfluidics device using photolithography method (left) and wax printing method (right). Adapted with the permission from ACS Publications (Martinez, Phillips, Whitesides, & Carrilho, 2010); B. Example of a paper microfluidic device fabricated by photolithography of SU8 photoresist. Adapted with the permission from ACS Publications (Martinez, Phillips, Carrilho, et al., 2008); C. An example of 3D paper based microfluidic device. Adapted with the permission from PNAS (Martinez, Phillips, & Whitesides, 2008).|