Skip to main content
SpringerLink
Log in

Strip modification and alternative architectures for signal amplification in nanoparticle-based lateral flow assays

  • Trends
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Nanoparticle (NP)-based lateral flow assay (LFA) technology has outstanding characteristics that make it ideal for point-of-care bioanalytical applications. However, LFAs still have important limitations, especially related to sensitivity, which is in general worse than that of other well-established bioassays such as ELISA or PCR. Many efforts have been made for enhancing the sensitivity of LFAs, mainly actuating on the nanoparticle labels and on alternative optical detection modes. However, strip pads modification for such a purpose is an incipient vast field of research. This article gives a brief overview on the recent advances proposed for signal amplification actuating on different pads and the general architecture of the LFA strips. Such strategies offer universal tools that can be adapted to any LFA, independently of the kind of sample, analyte, and label. The principles of the different strategies developed to achieve novel signal amplification and sensitive detection are discussed, and some examples of relevant approaches are highlighted, together with future prospects and challenges.

Graphical abstract

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Kasetsirikul S, Shiddiky MJA, Nguyen NT. Challenges and perspectives in the development of paper-based lateral flow assays. Microfluid Nanofluid. 2020;24:17.

    Article  Google Scholar 

  2. Huang Y, Xu T, Wang W, Wen Y, Li K, Qian L, et al. Lateral flow biosensors based on the use of micro and nanomaterials: a review on recent developments. Microchim Acta. 2020;187:70.

    Article  CAS  Google Scholar 

  3. Tang RH, Liu LN, Zhang SF, He XC, Li XJ, Xu F, et al. A review on advances in methods for modification of paper supports for use in point-of-care testing. Microchim Acta. 2019;186:521.

    Article  Google Scholar 

  4. Li F, You M, Li S, Hu J, Liu C, Gong Y, et al. Paper-based point-of-care immunoassays: recent advances and emerging trends. Biotechnol Adv. 2020;39:107442.

    Article  CAS  Google Scholar 

  5. Soh JH, Chan HM, Ying JY. Strategies for developing sensitive and specific nanoparticle-based lateral flow assays as point-of-care diagnostic device. Nano Today. 2020;30:100831.

    Article  CAS  Google Scholar 

  6. Zhou Y, Ding L, Wu Y, Huang X, Lai W, Xiong Y. Emerging strategies to develop sensitive AuNP-based ICTS nanosensors. Trends Anal Chem. 2019;112:147–60.

    Article  CAS  Google Scholar 

  7. Huang X, Aguilar ZP, Xu H, Lai W, Xiong Y. Membrane-based lateral flow immunochromatographic strip with nanoparticles as reporters for detection: a review. Biosens Bioelectron. 2016;75:166–80.

    Article  CAS  Google Scholar 

  8. Liu L, Yang D, Liu G. Signal amplification strategies for paper-based analytical devices. Biosens Bioelectron. 2019;136:60–75.

    Article  CAS  Google Scholar 

  9. Hsieh HV, Dantzler JL, Weigl BH. Analytical tools to improve optimization procedures for lateral flow assays. Diagnostics. 2017;7:29.

    Article  CAS  Google Scholar 

  10. Liu Y, Zhan L, Qin Z, Sackrison J, Bischof JC. Ultrasensitive and highly specific lateral flow assays for point-of-care diagnosis. ACS Nano. 2021;15:3593–611.

    Article  CAS  Google Scholar 

  11. Ishii M, Preechakasedkit P, Yamada K, Chailapakul O, Suzuki K, Citterio D. Wax-assisted one-step enzyme-linked immunosorbent assay on lateral flow test devices. Anal Sci. 2018;34:51–6.

    Article  CAS  Google Scholar 

  12. Zhong Y, Chen Y, Yao L, Zhao D, Zheng L, Liu G, et al. Gold nanoparticles based lateral flow immunoassay with largely amplified sensitivity for rapid melamine screening. Microchim Acta. 2016;183:1989–94.

    Article  CAS  Google Scholar 

  13. Rivas L, de la Escosura-Muñiz A, Serrano L, Altet L, Francino O, Sánchez A, et al. Triple lines gold nanoparticle-based lateral flow assay for enhanced and simultaneous detection of Leishmania DNA and endogenous control. Nano Res. 2015;8:3704–14.

    Article  CAS  Google Scholar 

  14. Lu Z, Rey E, Vemulapati S, Srinivasan B, Mehta S, Erickson D. High-yield paper-based quantitative blood separation system. Lab Chip. 2018;18:3865–71.

    Article  CAS  Google Scholar 

  15. Shen Y, Shen G. Signal-enhanced lateral flow immunoassay with dual gold nanoparticle conjugates for the detection of hepatitis B surface antigen. ACS Omega. 2019;4:5083–7.

    Article  CAS  Google Scholar 

  16. Chen M, Yu Z, Liu D, Peng T, Liu K, Wang S, et al. Dual gold nanoparticle lateflow immunoassay for sensitive detection of Escherichia coli O157:H7. Anal Chim Acta. 2015;876:71–6.

    Article  CAS  Google Scholar 

  17. Rivas L, Medina-Sánchez M, de la Escosura-Muñiz A, Merkoçi A. Improving sensitivity of gold nanoparticle-based lateral flow assays by using wax-printed pillars as delay barriers of microfluidics. Lab Chip. 2014;14:4406–14.

    Article  CAS  Google Scholar 

  18. Zhang SF, Liu LN, Tang RH, Liu Z, He XC, Qu ZG, et al. Sensitivity enhancement of lateral flow assay by embedding cotton threads in paper. Cellulose. 2019;26:8087–99.

    Article  CAS  Google Scholar 

  19. Tsai TT, Huang TH, Chen CA, Ho NYJ, Chou YJ, Chen CF. Development a stacking pad design for enhancing the sensitivity of lateral flow immunoassay. Sci Rep. 2018;8:17319.

    Article  Google Scholar 

  20. Kim K, Joung HA, Han GR, Kim MG. An immunochromatographic biosensor combined with a water-swellable polymer for automatic signal generation or amplification. Biosens Bioelectron. 2016;85:422–8.

    Article  CAS  Google Scholar 

  21. Panraksa Y, Apilux A, Jampasa, Puthong S, Henry CS, Rengpipatf S, et al. A facile one-step gold nanoparticles enhancement based on sequential patterned lateral flow immunoassay device for C-reactive protein detection. Sensors Actuators B Chem. 2021;329:129241.

    Article  CAS  Google Scholar 

  22. Preechakasedkit P, Siangproh W, Khongchareonporn N, Ngamrojanavanich N, Chailapakul O. Development of an automated wax-printed paper-based lateral flow device for alpha-fetoprotein enzyme-linked immunosorbent assay. Biosens Bioelectron. 2018;102:27–32.

    Article  CAS  Google Scholar 

  23. He X, Liu Z, Yang Y, Li L, Wang L, Li A, et al. Sensitivity enhancement of nucleic acid lateral flow assays through a physical−chemical coupling method: dissoluble saline barriers. ACS Sensors. 2019;4:1691–700.

    Article  CAS  Google Scholar 

  24. Bikkarolla SK, McNamee SE, McGregor S, Vance P, McGhee H, Marlow EL, et al. A lateral flow immunoassay with self-sufficient microfluidic system for enhanced detection of thyroid-stimulating hormone. AIP Adv. 2020;10:125316.

    Article  CAS  Google Scholar 

  25. Credou J, Volland H, Danob J, Berthelot T. A one-step and biocompatible cellulose functionalization for covalent antibody immobilization on immunoassay membranes. J Mater Chem B. 2013;1:3277–86.

    Article  CAS  Google Scholar 

  26. Yew CHT, Azari P, Choi JR, Muhamad F, Pingguan-Murphy B. Electrospun polycaprolactone nanofibers as a reaction membrane for lateral flow assay. Polymers. 2018;10:1387.

    Article  Google Scholar 

  27. Zhang LX, Jiang L, Willett DR, Marcus RK. Parallel, open-channel lateral flow (immuno) assay substrate based on capillary-channeled polymer films. Analyst. 2016;141:807–14.

    Article  CAS  Google Scholar 

  28. Quesada-González D, Stefani C, González I, de la Escosura-Muñiz A, Domingo N, Mutjé P, et al. Signal enhancement on gold nanoparticle-based lateral flow tests using cellulose nanofibers. Biosens Bioelectron. 2019;141:111407.

    Article  Google Scholar 

  29. Zhang Y, Liu X, Wang L, Yang H, Zhang X, Zhu C, et al. Improvement in detection limit for lateral flow assay of biomacromolecules by test-zone pre-enrichment. Sci Rep. 2020;10:9604.

    Article  Google Scholar 

  30. Parolo C, Medina-Sánchez M, de la Escosura-Muñiz A, Merkoçi A. Simple paper architecture modifications lead to enhanced sensitivity in nanoparticle based lateral flow immunoassay. Lab Chip. 2013;13:386–90.

    Article  CAS  Google Scholar 

  31. Nunes-Pauli GE, de la Escosura-Muñiz A, Parolo C, Helmuth-Bechtold I, Merkoçi A. Lab-in-a-syringe using gold nanoparticles for rapid immunosensing of protein biomarkers. Lab Chip. 2015;15:399–405.

    Article  CAS  Google Scholar 

  32. Zadehkafi A, Siavashi M, Asiaei S, Bidgoli MR. Simple geometrical modifications for substantial color intensity and detection limit enhancements in lateral-flow immunochromatographic assays. J Chromatogr B 2019;1110–1111:1–8.

  33. Eltzov E, Marks RA. Colorimetric stack pad immunoassay for bacterial identification. Biosens Bioelectron. 2017;87:572–8.

    Article  CAS  Google Scholar 

  34. Afriat R, Chalupowicz D, Eltzov E. Development of a point-of-care technology for bacterial identification in milk. Talanta. 2020;219:121223.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The financial support of the FC-GRUPIN-ID/2018/000166 project from the Asturias Regional Government and the CTQ2017-86994-R project from the Spanish Ministry of Economy and Competitiveness (MINECO) is gratefully acknowledged. A. de la Escosura-Muñiz also acknowledges the Spanish Ministry of Science and Innovation (MICINN) for the “Ramón y Cajal” Research Fellow (RyC-2016-20299).

Author information

Authors and Affiliations

  1. NanoBioAnalysis Group-Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, 33006, Oviedo, Spain

    María Díaz-González & Alfredo de la Escosura-Muñiz

  2. Biotechnology Institute of Asturias, University of Oviedo, Santiago Gascon Building, 33006, Oviedo, Spain

    Alfredo de la Escosura-Muñiz

Authors
  1. María Díaz-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alfredo de la Escosura-Muñiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo de la Escosura-Muñiz.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Díaz-González, M., de la Escosura-Muñiz, A. Strip modification and alternative architectures for signal amplification in nanoparticle-based lateral flow assays. Anal Bioanal Chem 413, 4111–4117 (2021). https://doi.org/10.1007/s00216-021-03421-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03421-5

Keywords

Search

Navigation