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.
Highlights
IntroductionThe increasing costs of healthcare services and health insurance premiums drive the need to transition from reactive and hospital-centered care to proactive healthcare management and wellness
The increasing costs of healthcare services and health insurance premiums drive the need to transition from reactive and hospital-centered care to proactive healthcare management and wellness.This shift from a reactive to a more proactive approach, encompassing preventive, evidence-based, and person-centered care, improves the quality of care and decreases the costs of healthcare [1]
To be able to decrease the size of the paper-based assays and miniaturize them, an appropriate high-resolution fabrication method should be found to meet all other needs of high-throughput fabrication such as being low-cost, simple, and easy
Summary
The increasing costs of healthcare services and health insurance premiums drive the need to transition from reactive and hospital-centered care to proactive healthcare management and wellness. For low-cost, point-of-care diagnostic devices, a method that could dynamically alter the fabrication pattern and reagent deposition through digital means has a significant advantage We have compared both analog and digital fabrication methods based on several comparison metrics including resolution, throughput, required equipment, and cost as well as the limitations and advantages (Tables S1 and S2). Among those approaches, the methods that are appropriate for mass-scale fabrication are wax printing [19,26,27], inkjet printing [5,8,21], screen printing [18], flexographic printing [12], and pen plotting [29,30] with the reported channel resolution of 228 ± 30 μm [10], 272 ± 19 μm [12], 671 ± 50 μm [2], 500 ± 30 μm [3], and 391 ± 68 μm [30], respectively. Figure 1F.igHuriegh1-.rHesioglhu-rteiosonluftaibonricfaabtiroicnatoiofnmouf ltmipulletixplpexappearp-ebra-bseasdedmmicircorflofuluididiicc ddeevviicceess uussiinnggaa ppeenn plotter plotter machine and high-resolution technical pens. (a) Desktop pen plotter with a high-resolution machinteecahnndicahligphe-nr.es(bo)luHtiiognh-rteescohluntiicoanl pteecnhns.ic(aal)pDeneskwtiothp 0p.e1nmpmlotptelarstwicitthipauhsiegdh-froersopaluttteironnintgechnical pen. (b)hHydigrohp-hreosboiclusotliuotniotnectohcnriecaatlepdeentecwtiiotnhz0o.n1ems. m(c)pTleacshtnicictailppeunsendibfworitpha0t.1temrnminpglahstyicdtrioppuhseodbfiocrsolution to createpadtetetrencitnigonhyzdornopesh.ob(cic) sToelcuhtinonicoanl paepnenr sibubwstirtahte0. (.1d,me) mCropslsa-seticctiotinpouf csherdomfoartopgartatpehrnyipnagpehry(d)r,ophobic solutionchornompaatpogerraspuhbysptraapteer. a(dfte,er)bCeirnogssc-osaetcedtiownitohfhcyhdrroomphaotboigcrsaopluhtyionpaupseinrg(dth)e, cwhirdoemmaatorkgerra(peh),y paper after berienggenecroaatetdedpawpeirth(f),haynddrcooprrheospboincdsinoglucitricounlarupsainttgernth(2emwmiddieammeaterrk) eorn t(heo)s,erpeagpeenr esurabtsetrdateps.aper (f), and corTrehsepyoenlldowingfocoidrcduylearispaaptptleirend t(o2 tmhemhyddiraompheitleicr)siodne tohf opsaepepratpoedrisstuinbgsutirsahteits.frTohmehyyedlrloopwhofboiocd dye is appliedstidoet.he hydrophilic side of paper to distinguish it from hydrophobic side
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