How Are These Devices Manufactured?

  • Giorgio Gianini Morbioli
  • Thiago Mazzu-Nascimento
  • Amanda M. Stockton
  • Emanuel CarrilhoEmail author


Paper-based devices are a portable and low-cost technology alternative among conventional analytical tools for point-of-care testing that have been growing in popularity due to their versatility and ease of use. Since their introduction in 2007, different methods to fabricate such devices have been proposed in literature, including photolithography, plotting, inkjet printing, wax printing, and stamping, among other methods, each with its unique advantages and drawbacks. Here, we present the most common current fabrication methods of microfluidic paper-based analytical devices (μPADs) in two and three dimensions, comparing their processes of fabrication, resolution of the features, and costs associated with their manufacture presenting insights towards the most adequate choice of fabrication method.


Fabrication methods Photolithography Plotting Plasma treatment Wax printing Wax dipping Inkjet printing Inkjet etching Flexography printing Screen printing Laser treatment Stamping 



The authors would like to thank the funding agencies FAPESP (Grant No. 2011/13997-8), CNPq (Grant No. 205453/2014-7) by the scholarships and the financial support to the Instituto Nacional de Ciência e Tecnologia de Bioanalítica—INCTBio (FAPESP Grant Nr. 2008/57805-2/CNPq Grant Nr. 573672/2008-3), the Georgia Institute of Technology (Georgia Tech), and the State of Georgia, USA. The authors declare having no competing financial interests.


  1. 1.
    Yetisen AK, Akram MS, Lowe CR (2013) Paper-based microfluidic point-of-care diagnostic devices. Lab Chip 13:2210–2251CrossRefGoogle Scholar
  2. 2.
    Cate DM, Adkins JA, Mettakoonpitak J, Henry CS (2015) Recent developments in paper-based microfluidic devices. Anal Chem 87:19–41CrossRefGoogle Scholar
  3. 3.
    Xia Y, Si J, Li Z (2016) Fabrication techniques for microfluidic paper-based analytical devices and their applications for biological testing: a review. Biosens Bioelectron 77:774–789CrossRefGoogle Scholar
  4. 4.
    Carrilho E, Martinez AW, Whitesides GM (2009) Understanding wax printing: a simple micropatterning process for paper-based microfluidics. Anal Chem 81:7091–7095CrossRefGoogle Scholar
  5. 5.
    Morbioli GG, Mazzu-Nascimento T, Milan LA, Stockton AM, Carrilho E (2017) Improving sample distribution homogeneity in three-dimensional microfluidic paper-based analytical devices by rational device design. Anal Chem 89:4786–4792CrossRefGoogle Scholar
  6. 6.
    Peeling RW, Holmes KK, Mabey D, Ronald A (2006) Rapid tests for sexually transmitted infections (STIs): the way forward. Sex Transm Infect 82(Suppl 5):v1–v6CrossRefGoogle Scholar
  7. 7.
    Martinez AW, Phillips ST, Carrilho E, Thomas SW, Sindi H, Whitesides GM (2008) Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal Chem 80:3699–3707CrossRefGoogle Scholar
  8. 8.
    Evans E, Gabriel EFM, Coltro WKT, Garcia CD (2014) Rational selection of substrates to improve color intensity and uniformity on microfluidic paper-based analytical devices. Analyst 139:2127–2132CrossRefGoogle Scholar
  9. 9.
    Elizalde E, Urteaga R, Berli CLA (2015) Rational design of capillary-driven flows for paper-based microfluidics. Lab Chip 15:2173–2180CrossRefGoogle Scholar
  10. 10.
    Han SI, Hwang KS, Kwak R, Lee J (2016) Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization. Lab Chip 16:2219CrossRefGoogle Scholar
  11. 11.
    Wong SY, Cabodi M, Rolland J, Klapperich CM (2014) Evaporative concentration on a paper-based device to concentrate analytes in a biological fluid. Anal Chem 86:11981–11985CrossRefGoogle Scholar
  12. 12.
    Martinez AW, Phillips ST, Whitesides GM (2008) Three-dimensional microfluidic devices fabricated in layered paper and tape. Proc Natl Acad Sci U S A 105:19606–19611CrossRefGoogle Scholar
  13. 13.
    Osborn JL, Lutz B, Fu E, Kauffman P, Stevens DY, Yager P (2010) Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks. Lab Chip 10:2659CrossRefGoogle Scholar
  14. 14.
    Oh KW, Lee K, Ahn B, Furlani EP (2012) Design of pressure-driven microfluidic networks using electric circuit analogy. Lab Chip 12:515–545CrossRefGoogle Scholar
  15. 15.
    Lewis GG, DiTucci MJ, Baker MS, Phillips ST (2012) High throughput method for prototyping three-dimensional, paper-based microfluidic devices. Lab Chip 12:2630–2633CrossRefGoogle Scholar
  16. 16.
    Zhu WJ, Feng DQ, Chen M, Chen ZD, Zhu R, Fang HL, Wang W (2014) Bienzyme colorimetric detection of glucose with self-calibration based on tree-shaped paper strip. Sensors Actuators B Chem 190:414–418CrossRefGoogle Scholar
  17. 17.
    Lutz B, Liang T, Fu E, Ramachandran S, Kauffman P, Yager P (2013) Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics. Lab Chip 13:2840–2847CrossRefGoogle Scholar
  18. 18.
    Houghtaling J, Liang T, Thiessen G, Fu E (2013) Dissolvable bridges for manipulating fluid volumes in paper networks. Anal Chem 85:11201–11204CrossRefGoogle Scholar
  19. 19.
    Li X, Tian J, Nguyen T, Shen W (2008) Paper-based microfluidic devices by plasma treatment. Anal Chem 80:9131–9134CrossRefGoogle Scholar
  20. 20.
    Schilling KM, Lepore AL, Kurian JA, Martinez AW (2012) Fully enclosed microfluidic paper-based analytical devices. Anal Chem 84:1579–1585CrossRefGoogle Scholar
  21. 21.
    Morbioli GG, Mazzu-Nascimento T, Stockton AM, Carrilho E (2017) Technical aspects and challenges of colorimetric detection with microfluidic paper-based analytical devices (μPADs)—a review. Anal Chim Acta 970:1–22CrossRefGoogle Scholar
  22. 22.
    Bhakta SA, Borba R, Taba M, Garcia CD, Carrilho E (2014) Determination of nitrite in saliva using microfluidic paper-based analytical devices. Anal Chim Acta 809:117–122CrossRefGoogle Scholar
  23. 23.
    Liu H, Crooks RM (2011) Three-dimensional paper microfluidic devices assembled using the principles of origami. J Am Chem Soc 133:17564–17566CrossRefGoogle Scholar
  24. 24.
    Connelly JT, Rolland JP, Whitesides GM (2015) Paper machine for molecular diagnostics. Anal Chem 87:7595–7601CrossRefGoogle Scholar
  25. 25.
    Schilling KM, Jauregui D, Martinez AW (2013) Paper and toner three-dimensional fluidic devices: programming fluid flow to improve point-of-care diagnostics. Lab Chip 13:628–631CrossRefGoogle Scholar
  26. 26.
    Martinez AW, Phillips ST, Butte MJ, Whitesides GM (2007) Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed 46:1318–1320CrossRefGoogle Scholar
  27. 27.
    Li X, Ballerini DR, Shen W (2012) A perspective on paper-based microfluidics: current status and future trends. Biomicrofluidics 6:11301–1130113CrossRefGoogle Scholar
  28. 28.
    Nie J, Zhang Y, Lin L, Zhou C, Li S, Zhang L, Li J (2012) Low-cost fabrication of paper-based microfluidic devices by one-step plotting. Anal Chem 84:6331–6335CrossRefGoogle Scholar
  29. 29.
    Lu R, Shi W, Jiang L, Qin J, Lin B (2009) Rapid prototyping of paper-based microfluidics with wax for low-cost, portable bioassay. Electrophoresis 30:1497–1500CrossRefGoogle Scholar
  30. 30.
    Songjaroen T, Dungchai W, Chailapakul O, Laiwattanapaisal W (2011) Novel, simple and low-cost alternative method for fabrication of paper-based microfluidics by wax dipping. Talanta 85:2587–2593CrossRefGoogle Scholar
  31. 31.
    Maejima K, Tomikawa S, Suzuki K, Citterio D (2013) Inkjet printing: an integrated and green chemical approach to microfluidic paper-based analytical devices. RSC Adv 3:9258CrossRefGoogle Scholar
  32. 32.
    Abe K, Suzuki K, Citterio D (2008) Inkjet-printed microfluidic multianalyte chemical sensing paper. Anal Chem 80:6928–6934CrossRefGoogle Scholar
  33. 33.
    Olkkonen J, Lehtinen K, Erho T (2010) Flexographically printed fluidic structures in paper. Anal Chem 82:10246–10250CrossRefGoogle Scholar
  34. 34.
    Dungchai W, Chailapakul O, Henry CS (2011) A low-cost, simple, and rapid fabrication method for paper-based microfluidics using wax screen-printing. Analyst 136:77–82CrossRefGoogle Scholar
  35. 35.
    Chitnis G, Ding Z, Chang C-L, Savran CA, Ziaie B (2011) Laser-treated hydrophobic paper: an inexpensive microfluidic platform. Lab Chip 11:1161–1165CrossRefGoogle Scholar
  36. 36.
    Curto VF, Lopez-Ruiz N, Capitan-Vallvey LF, Palma AJ, Benito-Lopez F, Diamond D (2013) Fast prototyping of paper-based microfluidic devices by contact stamping using indelible ink. RSC Adv 3:18811CrossRefGoogle Scholar
  37. 37.
    Garcia PDT, Cardoso TMG, Garcia CD, Carrilho E, Coltro WKT (2014) A handheld stamping process to fabricate microfluidic paper-based analytical devices with chemically modified surface for clinical assays. RSC Adv 4:37637–37644CrossRefGoogle Scholar
  38. 38.
    Carrilho E, Phillips ST, Vella SJ, Martinez AW, Whitesides GM (2009) Paper microzone plates. Anal Chem 81:5990–5998CrossRefGoogle Scholar
  39. 39.
    Martinez AW, Phillips ST, Wiley BJ, Gupta M, Whitesides GM (2008) FLASH: a rapid method for prototyping paper-based microfluidic devices. Lab Chip 8:2146–2150CrossRefGoogle Scholar
  40. 40.
    He Y, Wu Y, Fu JZ, Wu WB (2015) Fabrication of paper-based microfluidic analysis devices: a review. RSC Adv 5:78109–78127CrossRefGoogle Scholar
  41. 41.
    OuYang L, Wang C, Du F, Zheng T, Liang H (2014) Electrochromatographic separations of multi-component metal complexes on a microfluidic paper-based device with a simplified photolithography. RSC Adv 4:1093CrossRefGoogle Scholar
  42. 42.
    He Y, Wu W, Fu J (2015) Rapid fabrication of paper-based microfluidic analytical devices with desktop stereolithography 3D printer. RSC Adv 5:2694–2701CrossRefGoogle Scholar
  43. 43.
    He PJW, Katis IN, Eason RW, Sones CL (2015) Laser-based patterning for fluidic devices in nitrocellulose. Biomicrofluidics 9Google Scholar
  44. 44.
    Wang X (2008) US Patent 8,741,039.
  45. 45.
    Kumar S, Chauhan VS, Chakrabarti SK (2012) Separation and analysis techniques for bound and unbound alkyl ketene dimer (AKD) in paper: a review. Arab J Chem 9:S1636–S1642CrossRefGoogle Scholar
  46. 46.
    Jaeger CW (2000) How does a solid ink printer work? Accessed 3 Oct 2015
  47. 47.
    Jacob JAM (2013) Desenvolvimento de placas de microtitulação em papel. Universidade Nova de Lisboa, LisboaGoogle Scholar
  48. 48.
    Morbioli GG (2015) Funcionalização de celulose para ensaios bioanalíticos em dispositivos microfluídicos baseados em papel (μPADs). Universidade de São Paulo, São PauloCrossRefGoogle Scholar
  49. 49.
    Yamada K, Henares TG, Suzuki K, Citterio D (2015) Paper-based inkjet-printed microfluidic analytical devices. Angew Chem Int Ed 54:5294–5310CrossRefGoogle Scholar
  50. 50.
    Sameenoi Y, Nongkai PN, Nouanthavong S, Henry CS, Nacapricha D (2014) One-step polymer screen-printing for microfluidic paper-based analytical device (μPAD) fabrication. Analyst 139:6580–6588CrossRefGoogle Scholar
  51. 51.
    Mazzu-Nascimento T, Morbioli GG, Milan LA, Donofrio FC, Mestriner CA, Carrilho E (2017) Development and statistical assessment of a paper-based immunoassay for detection of tumor markers. Anal Chim Acta 950:156–161CrossRefGoogle Scholar
  52. 52.
    Mazzu-Nascimento T, Morbioli GG, Milan LA, Silva DF, Donofrio FC, Mestriner CA, Carrilho E (2017) Improved assessment of accuracy and performance indicators in paper-based ELISA. Anal Methods 9:2644–2653CrossRefGoogle Scholar
  53. 53.
    Zhang Y, Zhou C, Nie J, Le S, Qin Q, Liu F, Li Y, Li J (2014) Equipment-free quantitative measurement for micro fluidic paper-based analytical devices fabricated using the principles of movable-type printing. Anal Chem 86:2005–2012CrossRefGoogle Scholar
  54. 54.
    Wang W, Wu W-Y, Zhu J-J (2010) Tree-shaped paper strip for semiquantitative colorimetric detection of protein with self-calibration. J Chromatogr A 1217:3896–3899CrossRefGoogle Scholar
  55. 55.
    Jiang Y, Hao Z, He Q, Chen H (2016) A simple method for fabrication of microfluidic paper-based analytical devices and on-device fluid control with a portable corona generator. RSC Adv 6:2888–2894CrossRefGoogle Scholar
  56. 56.
    Demirel G, Babur E (2014) Vapor-phase deposition of polymers as a simple and versatile technique to generate paper-based microfluidic platforms for bioassay applications. Analyst 139:2326–2331CrossRefGoogle Scholar
  57. 57.
    Bruzewicz DA, Reches M, Whitesides GM (2008) Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in paper. Anal Chem 80:3387–3392CrossRefGoogle Scholar
  58. 58.
    He Q, Ma C, Hu X, Chen H (2013) Method for fabrication of paper-based microfluidic devices by alkylsilane self-assembling and UV/O3-patterning. Anal Chem 85:1327–1331CrossRefGoogle Scholar
  59. 59.
    Wang J, Monton RN, Zhang X, Filipe CDM, Pelton R, Monton MRN, Zhang X, Filipe CDM, Pelton R, Brennan JD (2014) Hydrophobic sol-gel channel patterning strategies for paper-based microfluidics. Lab Chip 14:691–695CrossRefGoogle Scholar
  60. 60.
    Rajendra V, Sicard C, Brennan JD, Brook MA (2014) Printing silicone-based hydrophobic barriers on paper for microfluidic assays using low-cost ink jet printers. Analyst 139:6361–6365CrossRefGoogle Scholar
  61. 61.
    Li X, Tian J, Garnier G, Shen W (2010) Fabrication of paper-based microfluidic sensors by printing. Colloids Surf B Biointerfaces 76:564–570CrossRefGoogle Scholar
  62. 62.
    Liana DD, Raguse B, Justin Gooding J, Chow E (2012) Recent advances in paper-based sensors. Sensors 12:11505–11526CrossRefGoogle Scholar
  63. 63.
    Fridley GE, Holstein CA, Oza SB, Yager P (2013) The evolution of nitrocellulose as a material for bioassays. MRS Bull 38:326–330CrossRefGoogle Scholar
  64. 64.
    Lu Y, Shi W, Qin J, Lin B (2010) Fabrication and characterization of paper-based microfluidics prepared in nitrocellulose membrane by wax printing. Anal Chem 82:329–335CrossRefGoogle Scholar
  65. 65.
    Byrnes S, Thiessen G, Fu E (2013) Progress in the development of paper-based diagnostics for low-resource point-of-care settings. Bioanalysis 5:2821–2836CrossRefGoogle Scholar
  66. 66.
    de Araujo WR, Paixão TRLC (2014) Fabrication of disposable electrochemical devices using silver ink and office paper. Analyst 139:2742–2747CrossRefGoogle Scholar
  67. 67.
    Arena A, Donato N, Saitta G, Bonavita A, Rizzo G, Neri G (2010) Flexible ethanol sensors on glossy paper substrates operating at room temperature. Sensors Actuators B Chem 145:488–494CrossRefGoogle Scholar
  68. 68.
    Murphy A, Gorey B, de Guzman K, Kelly N, Nesterenko EP, Morrin A (2015) Microfluidic paper analytical device for the chromatographic separation of ascorbic acid and dopamine. RSC Adv 5:93162–93169CrossRefGoogle Scholar
  69. 69.
    Yoshihiro K, Hodges S, Cook BS, Zhang C, Abowd GD (2013) Instant inkjet circuits: lab-based inkjet printing to support rapid prototyping of ubicomp devices. Proceedings of the 2013 ACM International Joint Conference on Pervasive Ubiquitous Computing—UbiComp ’13, p 363–372Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Giorgio Gianini Morbioli
    • 1
  • Thiago Mazzu-Nascimento
    • 2
    • 3
  • Amanda M. Stockton
    • 1
  • Emanuel Carrilho
    • 2
    • 3
    Email author
  1. 1.School of Chemistry and BiochemistryGeorgia Institute of TechnologyAtlantaUSA
  2. 2.Instituto de Química de São CarlosUniversidade de São PauloSão CarlosBrazil
  3. 3.Instituto Nacional de Ciência e Tecnologia de BioanalíticaCampinasBrazil

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