The authors acknowledge the financial support from the programs of the Natural Science Foundation of the Jiangsu Higher Education (22KJB460033), and Jiangsu Science and Technology Programme - Young Scholar (BK20200251). This work is also partially supported by the XJTLU AI University Research Centre, Jiangsu Province Engineering Research Centre of Data Science and Cognitive Computation at XJTLU and SIP AI innovation platform (YZCXPT2022103). The support from State Key Laboratory for Manufacturing Systems Engineering via the open project (SKLMS2023019) and Key Laboratory of Bionic Engineering, Ministry of Education, are also acknowledged.

1. Microembossing process for microchannel patterning on nanopaper
<ol>
	<li>Mold preparation 
	NOTE: Refer to Yuan et al.12 for details on mold preparation.
	<ol>
		<li>Prepare a PTFE film as indicated in the Table of Materials.</li>
		<li>Laser-cut the prepared PTFE film to make a convex microchannel mold (Figure 1A-I). 
		NOTE: The dimensions of the PTFE mold determine the microchannel dimensions (<stro...

Micro-Embossed Fabrication of Nanocellulose Paper-Based Analytical Devices  

<ol>
	<li>Zhu, H., Fang, Z., Preston, C., Li, Y., Hu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transparent+paper:+fabrications,+properties,+and+device+applications.">Transparent paper: fabrications, properties, and device applications.</a> Energy &amp; Environmental Science. 7 (1), 269-287 (2013).</li><li>Nogi, M., Iwamoto, S., Nakagaito, A. N., Yano, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optically+transparent+nanofiber+paper.">Optically transparent nanofiber paper.</a> Advanced Materials. 21 (16), 1595-1598 (2009).</li><li>Li, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+sulfated+bacterial+cellulose/gelatin+composite+scaffolds+for+culturing+hepatocytes.">Three-dimensional sulfated bacterial cellulose/gelatin composite scaffolds for culturing hepatocytes.</a> Cyborg and Bionic Systems. 4, 0021 (2023).</li><li>Barhoum, A., Samyn, P., &#214;hlund, T., Dufresne, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+of+recent+research+on+flexible+multifunctional+nanopapers.">Review of recent research on flexible multifunctional nanopapers.</a> Nanoscale. 9 (40), 15181-15205 (2017).</li><li>Dufresne, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanocellulose:+a+new+ageless+bionanomaterial.">Nanocellulose: a new ageless bionanomaterial.</a> Materials Today. 16 (6), 220-227 (2013).</li><li>Martin-Martinez, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Designing+nanocellulose+materials+from+the+molecular+scale.">Designing nanocellulose materials from the molecular scale.</a> Proceedings of the National Academy of Sciences. 115 (28), 7174-7175 (2018).</li><li>Sehaqui, H., Liu, A., Zhou, Q., Berglund, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fast+preparation+procedure+for+large,+flat+cellulose+and+cellulose/inorganic+nanopaper+structures.">Fast preparation procedure for large, flat cellulose and cellulose/inorganic nanopaper structures.</a> Biomacromolecules. 11 (9), 2195-2198 (2010).</li><li>Fang, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+nanostructured+paper+with+ultrahigh+transparency+and+ultrahigh+haze+for+solar+cells.">Novel nanostructured paper with ultrahigh transparency and ultrahigh haze for solar cells.</a> Nano Letters. 14 (2), 765-773 (2014).</li><li>Zheng, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanostructured+paper+for+flexible+energy+and+electronic+devices.">Nanostructured paper for flexible energy and electronic devices.</a> MRS Bulletin. 38 (4), 320-325 (2013).</li><li>Chen, L., Ying, B., Song, P., Liu, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+nanocellulose-paper-based+sers+multiwell+plate+with+high+sensitivity+and+high+signal+homogeneity.">A nanocellulose-paper-based sers multiwell plate with high sensitivity and high signal homogeneity.</a> Advanced Materials Interfaces. 6 (24), 1901346 (2019).</li><li>Koga, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transparent,+conductive,+and+printable+composites+consisting+of+tempo-oxidized+nanocellulose+and+carbon+nanotube.">Transparent, conductive, and printable composites consisting of tempo-oxidized nanocellulose and carbon nanotube.</a> Biomacromolecules. 14 (4), 1160-1165 (2013).</li><li>Yuan, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facile+microembossing+process+for+microchannel+fabrication+for+nanocellulose-paper-based+microfluidics.">Facile microembossing process for microchannel fabrication for nanocellulose-paper-based microfluidics.</a> ACS Applied Materials &amp; Interfaces. 15 (5), 6420-6430 (2023).</li><li>Rolland, J. P., Mourey, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Paper+as+a+novel+material+platform+for+devices.">Paper as a novel material platform for devices.</a> MRS Bulletin. 38 (4), 299-305 (2013).</li><li>Martinez, A. W., Phillips, S. T., Butte, M. J., Whitesides, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patterned+paper+as+a+platform+for+inexpensive,+low-volume,+portable+bioassays.">Patterned paper as a platform for inexpensive, low-volume, portable bioassays.</a> Angewandte Chemie International Edition. 46 (8), 1318-1320 (2007).</li><li>Chin, C. D., Linder, V., Sia, S. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lab-on-a-chip+devices+for+global+health:+past+studies+and+future+opportunities.">Lab-on-a-chip devices for global health: past studies and future opportunities.</a> Lab on a Chip. 7 (1), 41-57 (2006).</li><li>Chin, C. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidics-based+diagnostics+of+infectious+diseases+in+the+developing+world.">Microfluidics-based diagnostics of infectious diseases in the developing world.</a> Nature Medicine. 17 (8), 1015-1019 (2011).</li><li>Martinez, A. W., Phillips, S. T., Whitesides, G. M., Carrilho, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostics+for+the+developing+world:+microfluidic+paper-based+analytical+devices.">Diagnostics for the developing world: microfluidic paper-based analytical devices.</a> Analytical Chemistry. 82 (1), 3-10 (2010).</li><li>Carrilho, E., Martinez, A. W., Whitesides, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+wax+printing:+a+simple+micropatterning+process+for+paper-based+microfluidics.">Understanding wax printing: a simple micropatterning process for paper-based microfluidics.</a> Analytical Chemistry. 81 (16), 7091-7095 (2009).</li><li>Lu, Y., Shi, W., Qin, J., Lin, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+and+characterization+of+paper-based+microfluidics+prepared+in+nitrocellulose+membrane+by+wax+printing.">Fabrication and characterization of paper-based microfluidics prepared in nitrocellulose membrane by wax printing.</a> Analytical Chemistry. 82 (1), 329-335 (2010).</li><li>Li, X., Zhao, C., Liu, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+paper-based+microfluidic+biosensor+integrating+zinc+oxide+nanowires+for+electrochemical+glucose+detection.">A paper-based microfluidic biosensor integrating zinc oxide nanowires for electrochemical glucose detection.</a> Microsystems &amp; Nanoengineering. 1 (1), 1-7 (2015).</li><li>Nie, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrochemical+sensing+in+paper-based+microfluidic+devices.">Electrochemical sensing in paper-based microfluidic devices.</a> Lab on a Chip. 10 (4), 477-483 (2010).</li><li>Cai, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+paper-based+microfluidic+analytical+device+with+a+highly+integrated+on-chip+valve+for+autonomous+ELISA.">A paper-based microfluidic analytical device with a highly integrated on-chip valve for autonomous ELISA.</a> 2022 IEEE 35th International Conference on Micro Electro Mechanical Systems Conference (MEMS). , 271-274 (2022).</li><li>Murdock, R. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimization+of+a+paper-based+ELISA+for+a+human+performance+biomarker).">Optimization of a paper-based ELISA for a human performance biomarker).</a> Analytical Chemistry. 85 (23), 11634-11642 (2013).</li><li>Cheng, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Paper-based+ELISA.">Paper-based ELISA.</a> Angewandte Chemie. 122 (28), 4881-4884 (2010).</li><li>Holstein, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immobilizing+affinity+proteins+to+nitrocellulose:+a+toolbox+for+paper-based+assay+developers.">Immobilizing affinity proteins to nitrocellulose: a toolbox for paper-based assay developers.</a> Analytical and Bioanalytical Chemistry. 408 (5), 1335-1346 (2016).</li><li>Tenda, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Paper-based+antibody+detection+devices+using+bioluminescent+bret-switching+sensor+proteins.">Paper-based antibody detection devices using bioluminescent bret-switching sensor proteins.</a> Angewandte Chemie International Edition. 57 (47), 15369-15373 (2018).</li><li>Gong, M. M., Nosrati, R., San Gabriel, M. C., Zini, A., Sinton, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+DNA+Analysis+with+paper-based+ion+concentration+polarization.">Direct DNA Analysis with paper-based ion concentration polarization.</a> Journal of the American Chemical Society. 137 (43), 13913-13919 (2015).</li><li>Gan, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+filter+paper-based+microdevice+for+low-cost,+rapid,+and+automated+DNA+extraction+and+amplification+from+diverse+sample+types.">A filter paper-based microdevice for low-cost, rapid, and automated DNA extraction and amplification from diverse sample types.</a> Lab on a Chip. 14 (19), 3719-3728 (2014).</li><li>Liu, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluorescent+paper-based+analytical+devices+for+ultra-sensitive+dual-type+RNA+detections+and+accurate+gastric+cancer+screening.">Fluorescent paper-based analytical devices for ultra-sensitive dual-type RNA detections and accurate gastric cancer screening.</a> Biosensors and Bioelectronics. 197, 113781 (2022).</li><li>Yuan, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microfluidic-assisted+Caenorhabditis+elegans+sorting:+current+status+and+future+prospects.">Microfluidic-assisted Caenorhabditis elegans sorting: current status and future prospects.</a> Cyborg and Bionic Systems. 4, 0011 (2023).</li><li>Kim, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Origami-paper-based+device+for+microvesicle/exosome+preconcentration+and+isolation.">Origami-paper-based device for microvesicle/exosome preconcentration and isolation.</a> Lab on a Chip. 19 (23), 3917-3921 (2019).</li><li>Ying, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NanoPADs+and+nanoFACEs:+an+optically+transparent+nanopaper-based+device+for+biomedical+applications.">NanoPADs and nanoFACEs: an optically transparent nanopaper-based device for biomedical applications.</a> Lab on a Chip. 20 (18), 3322-3333 (2020).</li><li>Shin, S., Hyun, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Matrix-assisted+three-dimensional+printing+of+cellulose+nanofibers+for+paper+microfluidics.">Matrix-assisted three-dimensional printing of cellulose nanofibers for paper microfluidics.</a> ACS Applied Materials &amp; Interfaces. 9 (31), 26438-26446 (2017).</li><li>Browne, C., Garnier, G., Batchelor, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moulding+of+micropatterned+nanocellulose+films+and+their+application+in+fluid+handling.">Moulding of micropatterned nanocellulose films and their application in fluid handling.</a> Journal of Colloid and Interface Science. 587, 162-172 (2021).</li><li>Paul, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shear+stress+related+blood+damage+in+laminar+couette+flow.">Shear stress related blood damage in laminar couette flow.</a> Artificial Organs. 27 (6), 517-529 (2003).</li><li>Thuo, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+of+low-cost+paper-based+microfluidic+devices+by+embossing+or+cut-and-stack+methods.">Fabrication of low-cost paper-based microfluidic devices by embossing or cut-and-stack methods.</a> Chemistry of Materials. 26 (14), 4230-4237 (2014).</li><li>Garstecki, P., Fuerstman, M. J., Stone, H. A., Whitesides, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formation+of+droplets+and+bubbles+in+a+microfluidic+T-junction-scaling+and+mechanism+of+break-up.">Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up.</a> Lab on a Chip. 6 (3), 437-446 (2006).</li><li>Nisisako, T., Torii, T., Higuchi, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Droplet+formation+in+a+microchannel+network.">Droplet formation in a microchannel network.</a> Lab on a Chip. 2 (1), 24-26 (2002).</li><li>Wang, Y., Zhang, X., Wen, G., Liang, A., Jiang, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facile+synthesis+of+a+highly+SERS+active+nanosilver+sol+using+microwaves+and+its+application+in+the+detection+of+E.+coli+using+Victoria+blue+B+as+a+molecular+probe.">Facile synthesis of a highly SERS active nanosilver sol using microwaves and its application in the detection of E. coli using Victoria blue B as a molecular probe.</a> Analytical Methods. 8 (24), 4881-4887 (2016).</li><li>Pham, T. T. H., Dien, N. D., Vu, X. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facile+synthesis+of+silver/gold+alloy+nanoparticles+for+ultra-sensitive+rhodamine+B+detection.">Facile synthesis of silver/gold alloy nanoparticles for ultra-sensitive rhodamine B detection.</a> RSC Advances. 11 (35), 21475-21488 (2021).</li><li>Li, D., Li, D. W., Li, Y., Fossey, J. S., Long, Y. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cyclic+electroplating+and+stripping+of+silver+on+Au@SiO2+core/shell+nanoparticles+for+sensitive+and+recyclable+substrate+of+surface-enhanced+Raman+scattering.">Cyclic electroplating and stripping of silver on Au@SiO2 core/shell nanoparticles for sensitive and recyclable substrate of surface-enhanced Raman scattering.</a> Journal of Materials Chemistry. 20 (18), 3688-3693 (2010).</li><li>Sun, C. H., Wang, M. L., Feng, Q., Liu, W., Xu, C. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surface-enhanced+Raman+scattering+(SERS)+study+on+Rhodamine+B+adsorbed+on+different+substrates.">Surface-enhanced Raman scattering (SERS) study on Rhodamine B adsorbed on different substrates.</a> Russian Journal of Physical Chemistry A. 89 (2), 291-296 (2015).</li></ol>

The primary focus of this study is to develop a simple method for fabricating microchannels on nanopaper. An efficient embossing technique was devised using PTFE as the mold to address this challenge12. By optimizing the temperature and embossing pressure, a series of experiments were conducted to establish a reliable fabrication process for NanoPADs. Additionally, the use of a quick-reference table to adjust the applications of NanoPADs in different fields was demonstrated. Although this method i...

Recently, nanofibrillated cellulose (NFC) paper (nanopaper) has emerged as a highly promising substrate material for various applications such as flexible electronics, energy devices, and biomedicals1,2,3,4. Derived from natural plants, nanopaper is cost-effective, biocompatible, and biodegradable, making it an appealing alternative to traditional cellulose paper5,6. Its exceptional properties include an ultra-smooth surface with a surface roughness of less than 25 nm and a dense cellulose matrix structure, allowing for the creation of highly structured nanostructures7. Abundant hydroxyl groups of nanopaper contribute to its compact and tightly packed nanocellulose structure8. Nanopaper exhibits excellent optical transparency and minimal optical haze, making it well-suited for optical sensors. Additionally, its inherent hydrophilicity enables pump-free flow, even with its thick structure, providing autonomous fluid motion9,10. Nanocellulose has diverse applications in biological sensors, conductive electronic devices, cell culture platforms, supercapacitors, batteries, and more, showcasing its versatility and potential11,12. Particularly, nanocellulose is promising for paper-based analytical microfluidic devices (&#181;PADs), offering unique advantages over conventional chromatography paper.
In the past decade, &#181;PADs have achieved significant attention due to their affordability, biocompatibility, pump-free operation, and ease of production13,14. These devices have emerged as effective point-of-care diagnostic tools, particularly in resource-limited settings15,16,17. A significant advancement in this field was the development of wax printing, pioneered by George Whitesides18 and the Bingcheng Lin group19, enabling the creation of functional &#181;PADs by incorporating microchannels on chromatography paper. Subsequently, &#181;PADs rapidly evolved, and various biosensing techniques, including electrochemical methods20, chemiluminescence21, and enzyme-linked immunosorbent assay (ELISA)22,23,24, were successfully implemented for the detection of diverse biomarkers such as proteins25,26, DNAs27,28, RNAs29,30, and exosomes31. Despite these achievements, &#181;PADs still face challenges, including slow flow speeds and solvent evaporation.
Several methods have been proposed for creating microchannels on nanopaper32,33,34. One approach involves 3D printing sacrificial ingredients into the material, but it requires a hydrophobic coating that limits pump-free operation33. Another technique involves manually stacking channel layers between nanopaper sheets using glue, which is labor-intensive32. Alternatively, spray-coating nanocellulose fibers onto pre-patterned molds can create microchannels, but it involves time-consuming and expensive mold preparation34. Notably, these methods are limited to millimeter-scale microchannels, compromising the advantages of microfluidic devices regarding reagent volume consumption and integration. Developing a simple nanopaper microchannel patterning process with micrometer-scale resolution remains a challenge.
This study presents a unique nanopaper microchannel patterning method based on practical microembossing. The approach offers several advantages over existing methods, as it requires no expensive or specialized equipment, is simple, cost-effective, and highly accurate. A convex microchannel mold is fabricated by laser cutting a polytetrafluoroethylene (PTFE) film, known for its chemical inertness and nonstick properties. This mold is then used to emboss microchannels onto a nanopaper gel membrane. A second layer of nanopaper gel is applied on top to create closed hollow channels. Using this patterning technique, fundamental microfluidic devices on nanopaper are developed, including a laminar mixer and droplet generator. Additionally, the fabrication of surface-enhanced Raman microscopy (SERS) NanoPADs is demonstrated. In-situ creation of a silver nanoparticle-based SERS substrate is achieved by introducing two chemical reagents (AgNO3 and NaBH4) into the channels, resulting in a remarkable performance with low limits of detection (LODs).

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>AgNO3&#160;</td>
			<td>Hushi (Shanghai, China)</td>
			<td>7761-88-8</td>
			<td>&#62;99%</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Hushi (Shanghai, China)</td>
			<td>64-17-5</td>
			<td>&#62;99%</td>
		</tr>
		<tr>
			<td>Hexadecane</td>
			<td>Macklin (Shanghai, China)</td>
			<td>544-76-3</td>
			<td>&#62;99%</td>
		</tr>
		<tr>
			<td>LabSpec software</td>
			<td>Horiba (Japan)</td>
			<td>LabSpec5</td>
			<td></td>
		</tr>
		<tr>
			<td>Melamine</td>
			<td>Macklin (Shanghai, China)</td>
			<td>108-78-1</td>
			<td>&#62;99%</td>
		</tr>
		<tr>
			<td>NaBH4</td>
			<td>Aladdin (Shanghai, China)</td>
			<td>16940-66-2</td>
			<td>&#62;99%</td>
		</tr>
		<tr>
			<td>Origin lab software</td>
			<td>OriginLab (USA)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Polyethylene terephthalate (PET)&#160;</td>
			<td>Myers Industries (Akron, USA)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Polytetrafluoroethylene films</td>
			<td>Shenzhen Huashenglong plastic material Co., Ltd. (Shenzhen, China)</td>
			<td></td>
			<td>Teflon film</td>
		</tr>
		<tr>
			<td>PVDF filter membrane</td>
			<td>EMD Millipore Corporation (USA)</td>
			<td>VVLP04700</td>
			<td>pore size: 0.1 &#956;m</td>
		</tr>
		<tr>
			<td>Raman spectrometer</td>
			<td>Horiba (Japan)</td>
			<td>Xplo RA</td>
			<td></td>
		</tr>
		<tr>
			<td>Rhodamine B</td>
			<td>Macklin (Shanghai, China)</td>
			<td>81-88-9</td>
			<td>&#62;95%</td>
		</tr>
		<tr>
			<td>Scanning electron microscopy (SEM)</td>
			<td>FEI(USA)</td>
			<td>Scios 2 HiVac</td>
			<td></td>
		</tr>
		<tr>
			<td>Silicon wafer</td>
			<td>Horiba (Japan)</td>
			<td></td>
			<td>diameter: 5 mm</td>
		</tr>
		<tr>
			<td>TEMPO-oxidized NFC slurry</td>
			<td>Tianjin University of Science and Technology</td>
			<td></td>
			<td>1.0 wt% solid, carboxylate level 2.0 mmol/g solid, average nanofiber diameter: 10 nm</td>
		</tr>
	</tbody>
</table>

microembossing: a convenient process for fabricating microchannels on nanocellulose paper-based microfluidics

Nanopaper, derived from nanofibrillated cellulose, has generated considerable interest as a promising material for microfluidic applications. Its appeal lies in a range of excellent&#160;qualities, including an exceptionally smooth surface, outstanding optical transparency, a uniform nanofiber matrix with nanoscale porosity, and customizable chemical properties. Despite the rapid growth of nanopaper-based microfluidics, the current techniques used to create microchannels on nanopaper, such as 3D printing, spray coating, or manual cutting and assembly, which are crucial for practical applications, still possess certain limitations, notably susceptibility to contamination. Furthermore, these methods are restricted to the production of millimeter-sized channels. This study introduces a straightforward process that utilizes convenient plastic micro-molds for simple microembossing operations to fabricate microchannels on nanopaper, achieving a minimum width of 200 &#181;m. The developed microchannel outperforms existing approaches, achieving a fourfold improvement, and can be fabricated within 45 min. Furthermore, fabrication parameters have been optimized, and a convenient quick-reference table is provided for application developers. The proof-of-concept for a laminar mixer, droplet generator, and functional nanopaper-based analytical devices (NanoPADs) designed for Rhodamine B sensing using surface-enhanced Raman spectroscopy was demonstrated. Notably, the NanoPADs exhibited exceptional performance with improved limits of detection. These outstanding results can be attributed to the superior optical properties of nanopaper and the recently developed accurate microembossing method, enabling the integration and fine-tuning of the NanoPADs.

Author Spotlight: Revolutionizing Microfluidics Through Microchannel Fabrication on Nanopaper 

Microembossing: A Convenient Process for Fabricating Microchannels on Nanocellulose Paper-Based Microfluidics

Our research introduces nanopaper as an innovative substrate, in contrast to conventional paper. Nanopaper offers optical transparency, exceptional smoothness, and chemical adaptability. Now the substrate currently lacks an efficient microchannel fabrication method, limiting its broader adoption in microfluidics.The progression of manufacturing technologies, including laser cutting and micro-or nano-3D printing has significantly improved motor precision. Consequently, it has simplified and enhanced the precision of microfluidic fabrication. Additionally, the images of innovative substrate materials like nanocellulose paper, have further activated the performance of paper-based analytical microfluidic devices.Currently, one of the experimental challenges we face is laser-cutting processing, which limited most wide to 200 micrometers and impacts microchannel accuracy. To overcome this, future research will explore nano-3D printing for MoS, aiming to achieve a higher precision level in nanopaper-based analytic microfluidic devices. In contrast, to establish the techniques for microchannel fabrication on nanocellulose paper, such as 3D printing, spray coating, or manual cutting and assembly, our method offers a distinct advantage.It combines simplicity with superior accuracy, ensuring user friendliness, cost effectiveness, time efficiency, and the attunement of micrometer-level macro channels. Our findings provide a new, accurate and simple method to fabricate microchannels on nanopaper and eventually for making nanopaper-based microfluidic devices. In the big picture, with this method, the existing paper substrate nanopaper can be easily used in the field of microfluidics.

A unique method for creating microchannel patterns on nanopaper has been devised utilizing the practical plastic micro-molds through the convenient microembossing technique. Notably, this method accomplishes microchannel patterning at a scale as small as 200 &#181;m, which represents a fourfold improvement compared to existing methods32,33,34. After fine-tuning the patterning parameters, the provided guidelines exhibit excellent...

Watch this Scientific Journal Video about Revolutionizing Microfluidics Through Microchannel Fabrication on Nanopaper at JoVE.com

This protocol describes a straightforward process that utilizes convenient plastic micro-molds for simple microembossing operations to fabricate microchannels on nanofibrillated cellulose paper, achieving a minimum width of 200 &#181;m.

Nanopaper, derived from nanofibrillated cellulose, has generated considerable interest as a promising material for microfluidic applications. Its appeal ...