Skip to main content

Advertisement

SpringerLink
Log in

Exploiting NanoLuc luciferase for smartphone-based bioluminescence cell biosensor for (anti)-inflammatory activity and toxicity

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The availability of smartphones with high-performance digital image sensors and processing power has completely reshaped the landscape of point-of-need analysis. Thanks to the high maturity level of reporter gene technology and the availability of several bioluminescent proteins with improved features, we were able to develop a bioluminescence smartphone-based biosensing platform exploiting the highly sensitive NanoLuc luciferase as reporter. A 3D-printed smartphone-integrated cell biosensor based on genetically engineered Hek293T cells was developed. Quantitative assessment of (anti)-inflammatory activity and toxicity of liquid samples was performed with a simple and rapid add-and-measure procedure. White grape pomace extracts, known to contain several bioactive compounds, were analyzed, confirming the suitability of the smartphone biosensing platform for analysis of untreated complex biological matrices. Such approach could meet the needs of small medium enterprises lacking fully equipped laboratories for first-level safety tests and rapid screening of new bioactive products.

Smartphone-based bioluminescence cell biosensor

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. Spethmann S, Prescher S, Dreger H, Nettlau H, Baumann G, Knebel F, et al. Electrocardiographic monitoring during marathon running: a proof of feasibility for a new telemedical approach. Eur J Prev Cardiol. 2014;21:32–7.

    Article  Google Scholar 

  2. Garabedian LF, Ross-Degnan D, Wharam JF. Mobile phone and smartphone technologies for diabetes care and self-management. Curr Diab Rep. 2015;15:109.

    Article  Google Scholar 

  3. Roda A, Guardigli M, Calabria D, Calabretta MM, Cevenini L, Michelini E. A 3D-printed device for a smartphone-based chemiluminescence biosensor for lactate in oral fluid and sweat. Analyst. 2014;139:6494–501.

    Article  CAS  Google Scholar 

  4. Zhang D, Jiang J, Chen J, Zhang Q, Lu Y, Yao Y, et al. Smartphone-based portable biosensing system using impedance measurement with printed electrodes for 2,4,6-trinitrotoluene (TNT) detection. Biosens Bioelectron. 2015;70:81–8.

    Article  CAS  Google Scholar 

  5. Yin K, Zhang W, Chen L. Pyoverdine secreted by Pseudomonas aeruginosa as a biological recognition element for the fluorescent detection of furazolidone. Biosens Bioelectron. 2014;51:90–6.

    Article  CAS  Google Scholar 

  6. Li B, Longwen F, Zhang W, Feng W, Chen L. Portable paper-based device for quantitative colorimetric assays relying on light reflectance principle. Electrophoresis. 2014;35:1152–9.

    Article  CAS  Google Scholar 

  7. Turner AP. Biosensors: sense and sensibility. Chem Soc Rev. 2013;42:3184–96.

    Article  CAS  Google Scholar 

  8. Comina G, Suska A, Filippini D. Towards autonomous lab-on-a-chip devices for cell phone biosensing. Biosens Bioelectron. 2016;77:1153–67.

    Article  CAS  Google Scholar 

  9. Mirasoli M, Nascetti A, Caputo D, Zangheri M, Scipinotti R, Cevenini L, et al. Multiwell cartridge with integrated array of amorphous silicon photosensors for chemiluminescence detection: development, characterization and comparison with cooled-CCD luminograph. Anal Bioanal Chem. 2014;406:5645–56.

    Article  CAS  Google Scholar 

  10. Roda A, Cevenini L, Borg S, Michelini E, Calabretta MM, Schüler D. Bioengineered bioluminescent magnetotactic bacteria as a powerful tool for chip-based whole-cell biosensors. Lab Chip. 2013;13:4881–9.

    Article  CAS  Google Scholar 

  11. Roda A, Cevenini L, Michelini E, Branchini BR. A portable bioluminescence engineered cell-based biosensor for on-site applications. Biosens Bioelectron. 2011;26:3647–53.

    Article  CAS  Google Scholar 

  12. Zhang D, Liu Q. Biosensors and bioelectronics on smartphone for portable biochemical detection. Biosens Bioelectron. 2016;75:273–84.

    Article  CAS  Google Scholar 

  13. Roda A, Mirasoli M, Michelini E, Di Fusco M, Zangheri M, Cevenini L, et al. Progress in chemical luminescence-based biosensors: a critical review. Biosens Bioelectron. 2016;76:164–79.

    Article  CAS  Google Scholar 

  14. Liu X, Lin TY, Lillehoj PB. Smartphones for cell and biomolecular detection. Ann Biomed Eng. 2014;42:2205–17.

    Article  Google Scholar 

  15. Vashist SK, Mudanyali O, Schneider EM, Zengerle R, Ozcan A. Cellphone-based devices for bioanalytical sciences. Anal Bioanal Chem. 2014;406:3263–77.

    Article  CAS  Google Scholar 

  16. Liao SC, Peng J, Mauk MG, Awasthi S, Song J, Friedman H, et al. Smart cup: a minimally-instrumented, smartphone-based point-of-care molecular diagnostic device. Sens Actuators B Chem. 2016;229:232–38.

    Article  CAS  Google Scholar 

  17. Petryayeva E, Algar WR. Multiplexed homogeneous assays of proteolytic activity using a smartphone and quantum dots. Anal Chem. 2014;86:3195–202.

    Article  CAS  Google Scholar 

  18. Nicolini AM, Fronczek CF, Yoon JY. Droplet-based immunoassay on a ‘sticky’ nanofibrous surface for multiplexed and dual detection of bacteria using smartphones. Biosens Bioelectron. 2015;67:560–9.

    Article  CAS  Google Scholar 

  19. Cevenini L, Calabretta MM, Tarantino G, Michelini E, Roda A. Smartphone-interfaced 3D printed toxicity biosensor integrating bioluminescent “sentinel cells”. Sens Actuators B: Chem. 2016;225:249–57.

    Article  CAS  Google Scholar 

  20. Charrier T, Durand MJ, Jouanneau S, Dion M, Pernetti M, Poncelet D, et al. A multi-channel bioluminescent bacterial biosensor for the on-line detection of metals and toxicity. Part I: design and optimization of bioluminescent bacterial strains. Anal Bioanal Chem. 2011;400:1051–60.

    Article  CAS  Google Scholar 

  21. Bazin I, Seo HB, Suehs CM, Ramuz M, De Waard M, Gu MB. Profiling the biological effects of wastewater samples via bioluminescent bacterial biosensors combined with estrogenic assays. Environ Sci Pollut Res Int. 2016. doi:10.1007/s11356-016-6050-5.

    Google Scholar 

  22. Elad T, Seo HB, Belkin S, Gu MB. High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array. Biosens Bioelectron. 2015;68:699–704.

    Article  CAS  Google Scholar 

  23. Michelini E, Cevenini L, Calabretta MM, Calabria D, Roda A. Exploiting in vitro and in vivo bioluminescence for the implementation of the three Rs principle (replacement, reduction, and refinement) in drug discovery. Anal Bioanal Chem. 2014;406:5531–9.

    Article  CAS  Google Scholar 

  24. Class B, Thorne N, Aguisanda F, Southall N, McKew JC, Zheng W. High-throughput viability assay using an autonomously bioluminescent cell line with a bacterial Lux reporter. J Lab Autom. 2015;20:164–74.

    Article  CAS  Google Scholar 

  25. Raut N, O’Connor G, Pasini P, Daunert S. Engineered cells as biosensing systems in biomedical analysis. Anal Bioanal Chem. 2012;402:3147–59.

    Article  CAS  Google Scholar 

  26. Michelini E, Cevenini L, Mezzanotte L, Leskinen P, Virta M, Karp M, et al. A sensitive recombinant cell-based bioluminescent assay for detection of androgen-like compounds. Nat Protoc. 2008;3:1895–902.

    Article  CAS  Google Scholar 

  27. Branchini BR, Southworth TL, Fontaine DM, Kohrt D, Talukder M, Michelini E, et al. An enhanced chimeric firefly luciferase-inspired enzyme for ATP detection and bioluminescence reporter and imaging applications. Anal Biochem. 2015;484:148–53.

    Article  CAS  Google Scholar 

  28. Branchini BR, Southworth TL, Fontaine DM, Davis AL, Behney CE, Murtiashaw MHA. Photinus pyralis and Luciola italica chimeric firefly luciferase produces enhanced bioluminescence. Biochemistry. 2014;53:6287–9.

    Article  CAS  Google Scholar 

  29. Yasunaga M, Murotomi K, Abe H, Yamazaki T, Nishii S, Ohbayashi T, et al. Highly sensitive luciferase reporter assay using a potent destabilization sequence of calpain 3. J Biotechnol. 2015;194:115–23.

    Article  CAS  Google Scholar 

  30. Ohmiya Y. Simultaneous multicolor luciferase reporter assays for monitoring of multiple genes expressions. Comb Chem High Throughput Screen. 2015;18:937–45.

    Article  CAS  Google Scholar 

  31. Hall MP, Unch J, Binkowski BF, Valley MP, Butler BL, Wood MG, et al. Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chem Biol. 2012;7:1848–57.

    Article  CAS  Google Scholar 

  32. Masser AE, Kandasamy G, Kaimal JM, Andréasson C. Luciferase NanoLuc as a reporter for gene expression and protein levels in Saccharomyces cerevisiae. Yeast. 2016;33:191–200.

    Article  CAS  Google Scholar 

  33. De Niz M, Stanway RR, Wacker R, Keller D, Heussler VT. An ultrasensitive NanoLuc-based luminescence system for monitoring Plasmodium berghei throughout its life cycle. Malar J. 2016;15:232.

    Article  Google Scholar 

  34. Dixon AS, Schwinn MK, Hall MP, Zimmerman K, Otto P, Lubben TH, et al. NanoLuc complementation reporter optimized for accurate measurement of protein interactions in cells. ACS Chem Biol. 2016;11:400–8.

    Article  CAS  Google Scholar 

  35. Boute N, Lowe P, Berger S, Malissard M, Robert A, Tesar M. NanoLuc luciferase—a multifunctional tool for high throughput antibody screening. Front Pharmacol. 2016;7:27.

    Article  Google Scholar 

  36. England CG, Ehlerding EB, Cai W. NanoLuc: a small luciferase is brightening up the field of bioluminescence. Bioconjug Chem. 2016;27:1175–87.

    Article  CAS  Google Scholar 

  37. Arts R, den Hartog I, Zijlema SE, Thijssen V, van der Beelen SH, Merkx M. Detection of antibodies in blood plasma using bioluminescent sensor proteins and a smartphone. Anal Chem. 2016;88:4525–32.

    Article  CAS  Google Scholar 

  38. Fahrmann JF, Ballester OF, Ballester G, Witte TR, Salazar AJ, Kordusky B, et al. Inhibition of nuclear factor kappa B activation in early-stage chronic lymphocytic leukemia by omega-3 fatty acids. Cancer Invest. 2013;31:24–38.

    Article  Google Scholar 

  39. Bak YK, Lampe JW, Sung MK. Effects of dietary supplementation of glucosamine sulfate on intestinal inflammation in a mouse model of experimental colitis. J Gastroenterol Hepatol. 2014;29:957–63.

    Article  CAS  Google Scholar 

  40. Sánchez-Fidalgo S, Villegas I, Rosillo MÁ, Aparicio-Soto M, de la Lastra CA. Dietary squalene supplementation improves DSS-induced acute colitis by downregulating p38 MAPK and NFkB signaling pathways. Mol Nutr Food Res. 2015;59:284–92.

    Article  Google Scholar 

  41. Ferri M, Bin S, Vallini V, Fava F, Michelini E, Roda A, et al. Recovery of polyphenols from red grape pomace and assessment of their antioxidant and anti-cholesterol activities. N Biotechnol. 2016;33:338–44.

    Article  CAS  Google Scholar 

  42. Cevenini L, Calabretta MM, Calabria D, Roda A, Michelini E. Luciferase genes as reporter reactions: how to use them in molecular biology? Adv Biochem Eng Biotechnol. 2016;154:3–17.

    CAS  Google Scholar 

  43. Jara-Palacios MJ, Hernanz D, Cifuentes-Gomez T, Escudero-Gilete ML, Heredia FJ, Spencer JP. Assessment of white grape pomace from winemaking as source of bioactive compounds, and its antiproliferative activity. Food Chem. 2015;183:78–82.

    Article  CAS  Google Scholar 

  44. Nunes C, Ferreira E, Freitas V, Almeida L, Barbosa RM, Laranjinha. Intestinal anti-inflammatory activity of red wine extract: unveiling the mechanisms in colonic epithelial cells. J.Food Funct. 2013;4:373-383

Download references

Acknowledgements

The grape pomace samples were obtained in the frame of a project supported by the Sadam Engineering (Sadam Eridania Spa group, Bologna, Italy) to Annalisa Tassoni. This research was sponsored in part by the NATO Science for Peace and Security Programme under Grant No. 985042.

Author information

Authors and Affiliations

  1. Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126, Bologna, Italy

    Luca Cevenini, Maria Maddalena Calabretta, Antonia Lopreside, Giuseppe Tarantino, Aldo Roda & Elisa Michelini

  2. Centro Interdipartimentale di Ricerche sul Cancro “Giorgio Prodi” (CIRC), Bologna, Italy

    Giuseppe Tarantino

  3. Department of Biological, Geological, and Environmental Sciences, University of Bologna, via Irnerio 42, 40126, Bologna, Italy

    Annalisa Tassoni & Maura Ferri

  4. INBB, Istituto Nazionale di Biostrutture e Biosistemi, Viale delle Medaglie d’Oro 305, 00136, Rome, Italy

    Aldo Roda & Elisa Michelini

Authors
  1. Luca Cevenini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Maddalena Calabretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonia Lopreside
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Tarantino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annalisa Tassoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maura Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aldo Roda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elisa Michelini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Aldo Roda or Elisa Michelini.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Published in the topical collection Highlights of Analytical Chemical Luminescence with guest editors Aldo Roda, Hua Cui, and Chao Lu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 853 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cevenini, L., Calabretta, M.M., Lopreside, A. et al. Exploiting NanoLuc luciferase for smartphone-based bioluminescence cell biosensor for (anti)-inflammatory activity and toxicity. Anal Bioanal Chem 408, 8859–8868 (2016). https://doi.org/10.1007/s00216-016-0062-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-0062-3

Keywords

Search

Navigation