Skip to main content
Log in

A simple strategy for signal enhancement in lateral flow assays using superabsorbent polymers

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

To enhance the sensitivity of lateral flow assays (LFAs), a simple strategy is proposed using a nitrocellulose membrane modified with a superabsorbent polymer (SAP). SAP was incorporated into a nitrocellulose membrane for the flow control of detection probes. When absorbing aqueous solutions, SAP promoted the formation of biomolecule complexes to achieve up to a tenfold sensitivity improvement for the detection of human IgG. The assay time was optimized experimentally and numerically to within 20 min using this strategy. Moreover, fluid saturation in LFAs modified with SAP was mathematically simulated to better understand the underlying process, and molecular dynamics simulations were carried out to determine the effect of SAP. The proposed design was also applied to samples spiked with human immunoglobulin-depleted serum to test its applicability. The strategy presented is unique in that it preserves the characteristics of conventional LFAs, as it minimizes user intervention and is simple to manufacture at scale.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jung W, Han J, Choi JW, Ahn CH (2015) Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies. Microelectron Eng 132:46–57. https://doi.org/10.1016/j.mee.2014.09.024

    Article  CAS  Google Scholar 

  2. Gong MM, Sinton D (2017) Turning the page: advancing paper-based microfluidics for broad diagnostic application. Chem Rev 117:8447–8480. https://doi.org/10.1021/acs.chemrev.7b00024

    Article  CAS  PubMed  Google Scholar 

  3. Wu G, Zaman MH (2012) Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings. Bull World Health Organ 90:914–920. https://doi.org/10.2471/BLT.12.102780

    Article  PubMed  PubMed Central  Google Scholar 

  4. Li F, You M, Li S et al (2019) Paper-based point-of-care immunoassays: Recent advances and emerging trends. Biotechnol Adv. https://doi.org/10.1016/j.biotechadv.2019.107442

    Article  PubMed  Google Scholar 

  5. Xiong X, Zhang J, Wang Z et al (2020) Simultaneous multiplexed detection of protein and metal ions by a colorimetric microfluidic paper-based analytical device. Biochip J 14:429–437. https://doi.org/10.1007/s13206-020-4407-9

    Article  CAS  Google Scholar 

  6. Hyung S, Karima G, Shin K et al (2021) A simple paper-based α-amylase separating system for potential application in biological sciences. Biochip J. https://doi.org/10.1007/s13206-021-00022-3

    Article  Google Scholar 

  7. Hidayat MA, Maharani DA, Purwanto DA et al (2020) Simple and sensitive paper-based colorimetric biosensor for determining total polyphenol content of the green tea beverages. Biotechnol Bioprocess Eng 25:255–263. https://doi.org/10.1007/s12257-019-0299-8

    Article  CAS  Google Scholar 

  8. Lim SH, Ryu YC, Hwang BH (2021) Aptamer-immobilized gold nanoparticles enable facile and on-site detection of staphylococcus aureus. Biotechnol Bioprocess Eng 26:107–113. https://doi.org/10.1007/s12257-020-0161-z

    Article  CAS  Google Scholar 

  9. Koczula KM, Gallotta A (2016) Lateral flow assays. Essays Biochem 60:111–120. https://doi.org/10.1042/EBC20150012

    Article  PubMed  PubMed Central  Google Scholar 

  10. Quesada-González D, Merkoçi A (2015) Nanoparticle-based lateral flow biosensors. Biosens Bioelectron 73:47–63. https://doi.org/10.1016/j.bios.2015.05.050

    Article  CAS  PubMed  Google Scholar 

  11. Carrilho E, Martinez AW, Whitesides GM (2009) Understanding wax printing: A simple micropatterning process for paper-based microfluidics. Anal Chem 81:7091–7095. https://doi.org/10.1021/ac901071p

    Article  CAS  PubMed  Google Scholar 

  12. Renault C, Koehne J, Ricco AJ, Crooks RM (2014) Three-dimensional wax patterning of paper fluidic devices. Langmuir 30:7030–7036. https://doi.org/10.1021/la501212b

    Article  CAS  PubMed  Google Scholar 

  13. Sena-Torralba A, Ngo DB, Parolo C et al (2020) Lateral flow assay modified with time-delay wax barriers as a sensitivity and signal enhancement strategy. Biosens Bioelectron 168:112559. https://doi.org/10.1016/j.bios.2020.112559

    Article  CAS  PubMed  Google Scholar 

  14. Preechakasedkit P, Siangproh W, Khongchareonporn N et al (2018) Development of an automated wax-printed paper-based lateral flow device for alpha-fetoprotein enzyme-linked immunosorbent assay. Biosens Bioelectron 102:27–32. https://doi.org/10.1016/j.bios.2017.10.051

    Article  CAS  PubMed  Google Scholar 

  15. He X, Liu Z, Yang Y et al (2019) Sensitivity enhancement of nucleic acid lateral flow assays through a physical-chemical coupling method: dissoluble saline barriers. ACS Sensors 4:1691–1700. https://doi.org/10.1021/acssensors.9b00594

    Article  CAS  PubMed  Google Scholar 

  16. Lutz B, Liang T, Fu E et al (2013) Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics. Lab Chip 13:2840–2847. https://doi.org/10.1039/c3lc50178g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zohuriaan-Mehr MJ, Kabiri K (2008) Superabsorbent polymer materials: A review. Iran Polym J English Ed 17:451–477

    CAS  Google Scholar 

  18. Zohuriaan-Mehr MJ, Omidian H, Doroudiani S, Kabiri K (2010) Advances in non-hygienic applications of superabsorbent hydrogel materials. J Mater Sci 45:5711–5735. https://doi.org/10.1007/s10853-010-4780-1

    Article  CAS  Google Scholar 

  19. Biswas GC, Rana MM, Kazuhiro T, Suzuki H (2019) A simple micropump based on a freeze-dried superabsorbent polymer for multiplex solution processing in disposable devices. R Soc Open Sci 6(3):182213. https://doi.org/10.1098/rsos.182213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Oyama Y, Osaki T, Kamiya K et al (2017) A sensitive point-of-care testing chip utilizing superabsorbent polymer for the early diagnosis of infectious disease. Sensors Actuators, B Chem 240:881–886. https://doi.org/10.1016/j.snb.2016.09.046

    Article  CAS  Google Scholar 

  21. Ambrosi A, Castañeda MT, Killard AJ et al (2007) Double-codified gold nanolabels for enhanced immunoanalysis. Anal Chem 79:5232–5240. https://doi.org/10.1021/ac070357m

    Article  CAS  PubMed  Google Scholar 

  22. Masoodi R, Pillai KM (2010) Darcy’s law-based model for wicking in paper-like swelling porous media. AIChE J 59:NA-NA. https://doi.org/10.1002/aic.12163

  23. Parolo C, Medina-Sánchez M, de la Escosura-Muñiz A, Merkoçi A (2013) Simple paper architecture modifications lead to enhanced sensitivity in nanoparticle based lateral flow immunoassays. Lab Chip 13:386–390. https://doi.org/10.1039/C2LC41144J

    Article  CAS  PubMed  Google Scholar 

  24. Liu M, Suo S, Wu J et al (2019) Tailoring porous media for controllable capillary flow. J Colloid Interface Sci 539:379–387. https://doi.org/10.1016/j.jcis.2018.12.068

    Article  PubMed  Google Scholar 

  25. Hess B, Kutzner C, Van Der Spoel D, Lindahl E (2008) GRGMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435–447. https://doi.org/10.1021/ct700301q

    Article  CAS  PubMed  Google Scholar 

  26. Lindahl E, Hess B, van der Spoel D (2001) GROMACS 3.0: A package for molecular simulation and trajectory analysis. J Mol Model 7:306–317. https://doi.org/10.1007/S008940100045

    Article  CAS  Google Scholar 

  27. Van Der Spoel D, Lindahl E, Hess B et al (2005) GROMACS: Fast, flexible, and free. J Comput Chem 26:1701–1718. https://doi.org/10.1002/jcc.20291

    Article  CAS  Google Scholar 

  28. Brooks BR, Brooks CL, Mackerell AD et al (2009) CHARMM: The biomolecular simulation program. J Comput Chem 30:1545–1614. https://doi.org/10.1002/jcc.21287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) Charmm - a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4:187–217

    Article  CAS  Google Scholar 

  30. Sunhwan JO, Taehoon KIM, Vidyashankara G, Iyer WI (2008) CHARMM-GUI: A Web-Based Graphical User Interface for CHARMM. J Comput Chem 29:1859–1865. https://doi.org/10.1002/jcc

    Article  Google Scholar 

  31. Jorgensen WL, Chandrasekhar J, Madura JD et al (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935. https://doi.org/10.1063/1.445869

    Article  CAS  Google Scholar 

  32. Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014101. https://doi.org/10.1063/1.2408420

    Article  CAS  PubMed  Google Scholar 

  33. Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys 52:7182–7190

    Article  CAS  Google Scholar 

  34. Essmann U, Perera L, Berkowitz ML et al (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593. https://doi.org/10.1063/1.470117

    Article  CAS  Google Scholar 

  35. Hess B (2008) P-LINCS: A parallel linear constraint solver for molecular simulation. J Chem Theory Comput 4:116–122. https://doi.org/10.1021/ct700200b

    Article  CAS  PubMed  Google Scholar 

  36. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: A Linear Constraint Solver for molecular simulations. J Comput Chem 18:1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12%3c1463::AID-JCC4%3e3.0.CO;2-H

    Article  CAS  Google Scholar 

  37. Omidian H, Hashemi SA, Sammes PG, Meldrum I (1999) Modified acrylic-based superabsorbent polymers (dependence on particle size and salinity). Polymer (Guildf) 40:1753–1761. https://doi.org/10.1016/S0032-3861(98)00394-2

    Article  CAS  Google Scholar 

  38. Sawut A, Yimit M, Sun W, Nurulla I (2014) Photopolymerisation and characterization of maleylatedcellulose-g- poly(acrylic acid) superabsorbent polymer. Carbohydr Polym 101:231–239. https://doi.org/10.1016/j.carbpol.2013.09.054

    Article  CAS  PubMed  Google Scholar 

  39. Fredrickson GH (1996) The theory of polymer dynamics. Curr Opin Solid State Mater Sci 1:812–816. https://doi.org/10.1016/S1359-0286(96)80106-9

    Article  CAS  Google Scholar 

  40. Cheeveewattanagul N, Morales-Narváez E, Hassan ARHA et al (2017) Straightforward immunosensing platform based on graphene oxide-decorated nanopaper: a highly sensitive and fast biosensing approach. Adv Funct Mater 27:1–8. https://doi.org/10.1002/adfm.201702741

    Article  CAS  Google Scholar 

  41. Gao Y, Zhu Z, Xi X et al (2019) An aptamer-based hook-effect-recognizable three-line lateral flow biosensor for rapid detection of thrombin. Biosens Bioelectron 133:177–182. https://doi.org/10.1016/j.bios.2019.03.036

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was carried out with the support of the ‘‘Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ014238042021)” Rural Development Administration, Republic of Korea, as well as the Inha University Research Grant.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yun Suk Huh, Sun Min Kim or Tae-Joon Jeon.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2594 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

You, T., Jeong, W., Lee, H. et al. A simple strategy for signal enhancement in lateral flow assays using superabsorbent polymers. Microchim Acta 188, 364 (2021). https://doi.org/10.1007/s00604-021-05026-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-021-05026-2

Keywords

Navigation