Multilayer Paperfluidics - Lucas Rozanski
Introduction and Motivation
Multilayer paperfluidics describes the expansion of a monolayer paper microfluidic device into a complex 3D structure. Monolayer devices have a considerable drawback from their simplicity, typically being used in lateral flow assays. A multilayered paperfluidic device allows for both vertical and lateral flow without mixing,[1] thus increasing detection capabilities. These devices are typically used as analytical and diagnostic systems where there is a desire for low cost, a degree of simplicity, and robustness.[1]
Manufacturing Methods
The first multilayer paperfluidic device was fabricated by adhering each layer to the next with double-sided tape, shown in Figure 1.[1] The double-sided tape used is water impermeable, allowing for the separation of channels between each layer of paper. To allow for vertical flow in such a device, holes can be cut into the tape to connect the channels of each layer. To complete the connection between the two layers, cellulose powder can be filled in before adhering the top layer. This method proved to some to be too imprecise, as the assembly of the device requires both precision cutting and layering.
In response, research has been conducted into alternative layering methods. Some devices take advantage of the multiple layers by employing a folding technique, wherein adherence is achieved via magnetic sheets in the device.[2] The magnetic sheets are made of plastic, and also have holes cut out of them to allow for vertical flow. This hole can be similarly backfilled with cellulose powder or another desired flow medium. This provides the further advantage of allowing for each individual layer to be opened for analysis.
Another alternative method is to use wax patterning, wherein wax is strategically melted into paper to create channels.[3] This has the advantage of decreasing the risk of contamination, and also takes advantages of the properties of wax. Wax is hydrophobic, and thus, this patterning method can be used to create specific hydrophilic channels of unwaxed paper.[3] The wax is melted into the paper in this method, and channel dimensions can be manipulated by strategically choosing the quantity and location of molten wax, as shown in Figure 2.
Folding sees use in newly developed devices due to its simplicity, although many examples forego the magnetic sheets. For more complicated devices, wax patterning is used commonly.
Applications
Multilayered paper microfluidic devices have applications where a simple, low-cost device is desired. This is due in part to their ease of fabrication and relatively cheap material cost. They are generally used in biochemical applications, such as bioassays. When used in this capacity, the devices are subject to the fluid, which is then run through a varying degree of channels. The four primary detection techniques are colorimetric, electrochemical, chemiluminescence, and electrochemiluminescence detection.[4] Colorimetric is the most frequent method, where color is correlated to the concentration of the component of interest, and can then be used to determine the concentration in the original fluidic sample.[5]
Expanding to a 3D structure allows for more complex device designs, which allow their capabilities to be expanded. Detection of multiple compounds requires more space on the device itself. The addition of vertical flow is able to reduce the size of such devices, and thus improve their accessibility.[4] Paper microfluidic devices also have a relatively low flow rate, as they depend upon capillary action for fluid flow. A device made with wax patterning found that by introducing gaps between paper channels in a 3D device, flow rates were able to drastically increase, as shown in Figure 3. The 3D geometry allows for the flow of the liquid in the gap between two paperfluidic layers to dominate the driving force of flow through the paper, as opposed to the lesser capillary driving force.[6]
References
[1] Martinez, A. W., Phillips, S. T., & Whitesides, G. M. Three-dimensional microfluidic devices fabricated in layered paper and tape. Proceedings of the National Academy of Sciences 2008. https://doi.org/10.1073/pnas.0810903105.
[2] Deng, H.; Zhou, X.; Liu, Q.; Li, B.; Liu, H.; Huang, R.; Xing, D. Paperfluidic Chip Device for Small RNA Extraction, Amplification, and Multiplexed Analysis. ACS Appl. Mater. Interfaces 2017, 9 (47), 41151–41158. https://doi.org/10.1021/acsami.7b12637.
[3] Renault, C.; Koehne, J.; Ricco, A. J.; Crooks, R. M. Three-Dimensional Wax Patterning of Paper Fluidic Devices. Langmuir 2014, 30 (23), 7030–7036. https://doi.org/10.1021/la501212b.
[4] Li, X.; Ballerini, D. R.; Shen, W. A Perspective on Paper-Based Microfluidics: Current Status and Future Trends. Biomicrofluidics 2012, 6 (1), 011301-011301–011313. https://doi.org/10.1063/1.3687398.
[5] Neris, N. M.; Guevara, R. D.; Gonzalez, A.; Gomez, F. A. 3D Multilayered Paper- and Thread/Paper-Based Microfluidic Devices for Bioassays. Electrophoresis 2019, 40 (2), 296–303. https://doi.org/10.1002/elps.201800383.
[6] Channon, R. B.; Nguyen, M. P.; Henry, C. S.; Dandy, D. S. Multilayered Microfluidic Paper-Based Devices: Characterization, Modeling, and Perspectives. Anal. Chem. 2019, 91 (14), 8966–8972. https://doi.org/10.1021/acs.analchem.9b01112.
