Skip to main content
SpringerLink
Log in

Development of a Paper-Based Luminescence Bioassay for Therapeutic Monitoring of Aminoglycosides: a Proof-of-Concept Study

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Aminoglycosides are widely used antibiotics that bind to the bacterial 30S ribosomal subunit to inhibit translation. Owing to their adverse side effects and narrow therapeutic index, monitoring blood levels of aminoglycosides is important to maximize their effectiveness and minimize their toxicity. Current monitoring techniques require a well-equipped diagnostic laboratory. The present study aimed to present a proof-of-concept for a simple, low-cost biochemical assay utilizing a paper platform for the detection of serum/whole blood aminoglycosides. A paper-based bioassay chip for the assay was developed by spotting and freeze-drying cell-free transcription/translation reaction machinery for a luminescent reporter protein (NanoLuc) within an array of wax circles printed on filter paper. The paper-based chip could be used to quantify serum/whole blood aminoglycosides within clinically relevant concentrations in 30–60 min by spotting minimal volumes of samples, followed by the NanoLuc substrate, in the wax circles and detecting the associated changes in luminescence signals, using a simple digital camera. Furthermore, a one-pot assay in which cell-free transcription/translation reaction machinery and NanoLuc substrate are mixed in advance and embedded in paper could be used to detect an aminoglycoside in serum. Overall, our paper-based bioassay can potentially provide a basic platform for the simple and low-cost therapeutic monitoring of aminoglycosides, especially in resource-limited regions.

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
Fig. 5

Similar content being viewed by others

References

  1. Avent, M. L., Rogers, B. A., Cheng, A. C., & Paterson, D. L. (2011). Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity. Internal Medicine Journal, 41(6), 441–449.

    Article  CAS  Google Scholar 

  2. Xie, J., Talaska, A. E., & Schacht, J. (2011). New developments in aminoglycoside therapy and ototoxicity. Hearing Research, 281(1-2), 28–37.

    Article  CAS  Google Scholar 

  3. McLawhon, R. W. (2012). Guidelines for the monitoring of vancomycin, aminoglycosides and certain antibiotics. In A. Dasgupta (Ed.), Therapeutic drug monitoring (pp. 197–218). San Diego: Academic Press.

    Chapter  Google Scholar 

  4. Bambeke, F. V., Mingeot-Leclercq, M. P., Glupczynski, Y., & Tulkens, P. M. (2017). Mechanisms of action. In J. Cohen, W. G. Powderly, & S. M. Opal (Eds.), Infectious diseases (pp. 1162–1180). Amsterdam: Elsevier.

    Chapter  Google Scholar 

  5. Roberts, J. A., Norris, R., Paterson, D. L., & Martin, J. H. (2012). Therapeutic drug monitoring of antimicrobials. British Journal of Clinical Pharmacology, 73(1), 27–36.

    Article  CAS  Google Scholar 

  6. Leggett, J. E. (2017). Aminoglycosides. In J. Cohen, W. G. Powderly, & S. M. Opal (Eds.), Infectious diseases (Vol. 2, pp. 1233–1238). Amsterdam: Elsevier.

    Chapter  Google Scholar 

  7. Roca, I., Akova, M., Baquero, F., Carlet, J., Cavaleri, M., Coenen, S., Cohen, J., Findlay, D., Gyssens, I., Heuer, O. E., Kahlmeter, G., Kruse, H., Laxminarayan, R., Liebana, E., Lopez-Cerero, L., MacGowan, A., Martins, M., Rodriguez-Bano, J., Rolain, J. M., Segovia, C., Sigauque, B., Tacconelli, E., Wellington, E., & Vila, J. (2015). The global threat of antimicrobial resistance: science for intervention. New Microbes and New Infections, 6, 22–29.

    Article  CAS  Google Scholar 

  8. Farouk, F., Azzazy, H. M., & Niessen, W. M. (2015). Challenges in the determination of aminoglycoside antibiotics, a review. Analytica Chimica Acta, 890, 21–43.

    Article  CAS  Google Scholar 

  9. Rowe, A. A., Miller, E. A., & Plaxco, K. W. (2010). Reagentless measurement of aminoglycoside antibiotics in blood serum via an electrochemical, ribonucleic acid aptamer-based biosensor. Analytical Chemistry, 82(17), 7090–7095.

    Article  CAS  Google Scholar 

  10. Nwobodo, N. (2014). Therapeutic drug monitoring in a developing nation: a clinical guide. JRSM Open, 5, 2054270414531121.

    Article  Google Scholar 

  11. Martinez, A. W., Phillips, S. T., Butte, M. J., & Whitesides, G. M. (2007). Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angewandte Chemie (International Ed. in English), 46(8), 1318–1320.

    Article  CAS  Google Scholar 

  12. Liana, D. D., Raguse, B., Gooding, J. J., & Chow, E. (2012). Recent advances in paper-based sensors. Sensors (Basel), 12(9), 11505–11526.

    Article  CAS  Google Scholar 

  13. Shah, P., Zhu, X., & Li, C. Z. (2013). Development of paper-based analytical kit for point-of-care testing. Expert Review of Molecular Diagnostics, 13(1), 83–91.

    Article  CAS  Google Scholar 

  14. Martinez, A. W., Phillips, S. T., Whitesides, G. M., & Carrilho, E. (2010). Diagnostics for the developing world: microfluidic paper-based analytical devices. Analytical Chemistry, 82(1), 3–10.

    Article  CAS  Google Scholar 

  15. Wu, G., & Zaman, M. H. (2012). Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings. Bulletin of the World Health Organization, 90(12), 914–920.

    Article  Google Scholar 

  16. Pardee, K., Green, A. A., Takahashi, M. K., Braff, D., Lambert, G., Lee, J. W., Ferrante, T., Ma, D., Donghia, N., Fan, M., Daringer, N. M., Bosch, I., Dudley, D. M., O'Connor, D. H., Gehrke, L., & Collins, J. J. (2016). Rapid, low-cost detection of Zika virus using programmable biomolecular components. Cell, 165(5), 1255–1266.

    Article  CAS  Google Scholar 

  17. Pardee, K., Green, A. A., Ferrante, T., Cameron, D. E., DaleyKeyser, A., Yin, P., & Collins, J. J. (2014). Paper-based synthetic gene networks. Cell, 159(4), 940–954.

    Article  CAS  Google Scholar 

  18. Duyen, T. T. M., Matsuura, H., Ujiie, K., Muraoka, M., Harada, K., & Hirata, K. (2017). Paper-based colorimetric biosensor for antibiotics inhibiting bacterial protein synthesis. Journal of Bioscience and Bioengineering, 123(1), 96–100.

    Article  CAS  Google Scholar 

  19. Hosoda, K., Sunami, T., Kazuta, Y., Matsuura, T., Suzuki, H., & Yomo, T. (2008). Quantitative study of the structure of multilamellar giant liposomes as a container of protein synthesis reaction. Langmuir, 24(23), 13540–13548.

    Article  CAS  Google Scholar 

  20. Carrilho, E., Martinez, A. W., & Whitesides, G. M. (2009). Understanding wax printing: a simple micropatterning process for paper-based microfluidics. Analytical Chemistry, 81(16), 7091–7095.

    Article  CAS  Google Scholar 

  21. Griss, R., Schena, A., Reymond, L., Patiny, L., Werner, D., Tinberg, C. E., Baker, D., & Johnsson, K. (2014). Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring. Nature Chemical Biology, 10(7), 598–603.

    Article  CAS  Google Scholar 

  22. Shimizu, Y., Inoue, A., Tomari, Y., Suzuki, T., Yokogawa, T., Nishikawa, K., & Ueda, T. (2001). Cell-free translation reconstituted with purified components. Nature Biotechnology, 19(8), 751–755.

    Article  CAS  Google Scholar 

  23. Hall, M. P., Unch, J., Binkowski, B. F., Valley, M. P., Butler, B. L., Wood, M. G., Otto, P., Zimmerman, K., Vidugiris, G., Machleidt, T., Robers, M. B., Benink, H. A., Eggers, C. T., Slater, M. R., Meisenheimer, P. L., Klaubert, D. H., Fan, F., Encell, L. P., & Wood, K. V. (2012). Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chemical Biology, 7(11), 1848–1857.

    Article  CAS  Google Scholar 

  24. McCoy, L. S., Xie, Y., & Tor, Y. (2011). Antibiotics that target protein synthesis. Wiley Interdisciplinary Reviews. RNA, 2(2), 209–232.

    Article  CAS  Google Scholar 

  25. Zhang, D., & Liu, Q. (2016). Biosensors and bioelectronics on smartphone for portable biochemical detection. Biosensors & Bioelectronics, 75, 273–284.

    Article  CAS  Google Scholar 

  26. Quesada-Gonzalez, D., & Merkoci, A. (2017). Mobile phone-based biosensing: an emerging "diagnostic and communication" technology. Biosensors & Bioelectronics, 92, 549–562.

    Article  CAS  Google Scholar 

  27. Karig, D. K., Bessling, S., Thielen, P., Zhang, S., & Wolfe, J. (2017). Preservation of protein expression systems at elevated temperatures for portable therapeutic production. Journal of the Royal Society, Interface, 14(129), 20161039.

    Article  Google Scholar 

Download references

Acknowledgments

We thank the Biological Resource Center in the National Institute of Technology and Evaluation (NBRC, Japan) for providing E. coli phage T3. The study was supported by a grant from Long-range Research Initiative (LRI) by the Japan Chemical Industry Association (JCIA) (13_PT05-01) and in part by Kurita Water and Environment Foundation, Japan.

Author information

Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hideyuki Matsuura, Kazuki Ujiie, Tran Thi My Duyen, Koki Izutsu, Shinichiro Maeda, Kazuo Harada & Kazumasa Hirata

  2. College of Aquaculture and Fisheries, Can Tho University, Campus II, 3/2 Street, Can Tho City, Vietnam

    Tran Thi My Duyen

  3. International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kazuhito Fujiyama

Authors
  1. Hideyuki Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuki Ujiie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tran Thi My Duyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koki Izutsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuhito Fujiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shinichiro Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazuo Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazumasa Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideyuki Matsuura.

Ethics declarations

Conflict of Interest

There are no conflicts of interest to declare.

Additional information

Publisher’s Note

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

Electronic Supplementary Material

ESM 1

(DOCX 110 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsuura, H., Ujiie, K., Duyen, T.T.M. et al. Development of a Paper-Based Luminescence Bioassay for Therapeutic Monitoring of Aminoglycosides: a Proof-of-Concept Study. Appl Biochem Biotechnol 189, 798–809 (2019). https://doi.org/10.1007/s12010-019-03048-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-019-03048-4

Keywords

Search

Navigation