Pushing the Limits of Spatial Assay Resolution for Paper-Based Microfluidics Using Low-Cost and High-Throughput Pen Plotter Approach

Abstract

To transform from reactive to proactive healthcare, there is an increasing need for low-cost and portable assays to continuously perform health measurements. The paper-based analytical devices could be a potential fit for this need. To miniaturize the multiplex paper-based microfluidic analytical devices and minimize reagent use, a fabrication method with high resolution along with low fabrication cost should be developed. Here, we present an approach that uses a desktop pen plotter and a high-resolution technical pen for plotting high-resolution patterns to fabricate miniaturized paper-based microfluidic devices with hundreds of detection zones to conduct different assays. In order to create a functional multiplex paper-based analytical device, the hydrophobic solution is patterned on the cellulose paper and the reagents are deposited in the patterned detection zones using the technical pens. We demonstrated the effect of paper substrate thickness on the resolution of patterns by investigating the resolution of patterns on a chromatography paper with altered effective thickness. As the characteristics of the cellulose paper substrate such as thickness, resolution, and homogeneity of pore structure affect the obtained patterning resolution, we used regenerated cellulose paper to fabricate detection zones with a diameter as small as 0.8 mm. Moreover, in order to fabricate a miniaturized multiplex paper-based device, we optimized packing of the detection zones. We also showed the capability of the presented method for fabrication of 3D paper-based microfluidic devices with hundreds of detection zones for conducting colorimetric assays.

Hemp-Based Microfluidics

“…The result proves that hemp paper has a significant capacity, as capable as WG1 paper, regarding the hydrophobic feature of the paper. [88]. Images of a water droplet (i) on hemp paper, and (j) WG1 paper; substrates were coated by Comix ink.…”

“…AxiDraw is a desktop pen plotter with an XY resolution of 80 steps per mm, a ±0.1 mm reproducibility, and a maximum plotting speed of 177 mm/s [ 88 ]. The speed is adjustable, directly affecting the amount of ink diffused through the paper and the feature size of the plotted patterns.…”

“…( e ) SEM image of surface and cross-section of WG1 paper with 250× magnification and ( f ) 750× magnification. ( g ) SEM image of the surface of WG1 paper with 250× magnification and ( h ) 750× magnification [ 88 ]. Images of a water droplet ( i ) on hemp paper, and ( j ) WG1 paper; substrates were coated by Comix ink.…”

Microfluidics for microalgal biotechnology

“…Numerous applications from diagnosis to environmental monitoring by chemical and biological detection have been demonstrated (Juang & Chang, 2016; S. M. Knowlton, Sencan, et al, 2015; S. Knowlton, Yu, et al, 2015; Luo et al, 2015; Solanki et al, 2020; Yenilmez et al, 2016). As microfluidic technologies offer many advantages like fast and low‐cost accessibility (Amin, Ghaderinezhad, et al, 2017; Amin et al, 2020; Ghaderinezhad et al, 2017; Ghaderinezhad et al, 2020; Lepowsky et al, 2017) and sensitivity, several biological samples such as plant, human and animal cells, pathogens, yeasts, and other microorganisms have been studied by microfluidics (Knowlton et al, 2017; Tasoglu et al, 2013; Tasoglu et al, 2015; Yenilmez et al, 2016). In contrast to microfluidics, most of the traditional technologies or applications cannot provide both cost‐effective and high‐quality features simultaneously (Solanki et al, 2020).…”

Recent Advances in Microfluidic Devices for Contamination Detection and Quality Inspection of Milk

“…Microfluidic technology has advanced rapidly over the past decade and has resulted in the development of many lab-on-a-chip [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ] and lab-on-paper [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ] platforms for total analysis systems in fields such as medicine and healthcare, environmental monitoring, cell biology, food safety inspection, and so on. Both platforms offer the advantages of cost-effectiveness, a simple operation, high reliability, high sensitivity, low sample/reagent consumption, and a near-instant on-site detection capability.…”