Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A portable device for nucleic acid quantification powered by sunlight, a flame or electricity

Nature Biomedical Engineering volume 2, pages 657–665 (2018)Cite this article

Subjects

Abstract

A decentralized approach to diagnostics can decrease the time to treatment of infectious diseases in resource-limited settings, yet most modern diagnostic tools require stable electricity and are not portable. Here, we describe a portable device for isothermal nucleic acid quantification that can operate with power from electricity, sunlight or a flame, and that can store heat from intermittent energy sources for operation when electrical power is not available or reliable. We deployed the device in two Ugandan health clinics, where it successfully operated through multiple power outages, with equivalent performance when powered via sunlight or electricity. A direct comparison between the portable device and commercial quantitative polymerase chain reaction machines for samples from 71 Ugandan patients (29 of which were tested in Uganda) for the presence of Kaposi’s sarcoma-associated herpesvirus DNA showed 94% agreement, with the four discordant samples having the lowest concentration of the herpesvirus DNA. The device’s flexibility in power supply provides a needed solution for on-field diagnostics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: TINY system overview.
Fig. 2: Construction and design of TINY.
Fig. 3: TINY heating characterization.
Fig. 4: LAMP assay performed using multiple heating methods.
Fig. 5: Standard curves for qPCR and LAMP.
Fig. 6: Analysis of 42 human skin samples for KSHV DNA.
Fig. 7: Analysis of human samples by TINY in Uganda.

Similar content being viewed by others

Data availability

All data supporting the findings in this study are available within the Article and its Supplementary Information. Additional data are available from the corresponding authors upon request.

References

  1. Global Health Observatory Data: Top 10 Causes of Death (World Health Organization, accessed 21 July 2017); http://www.who.int/gho/mortality_burden_disease/causes_death/top_10/en/

  2. Urdea, M. et al. Requirements for high impact diagnostics in the developing world. Nature 444, 73–79 (2006).

    Article  PubMed  Google Scholar 

  3. Jani, I. V. & Peter, T. F. How point-of-care testing could drive innovation in global health. N. Engl. J. Med. 368, 2319–2324 (2013).

    Article  PubMed  CAS  Google Scholar 

  4. Yager, P., Domingo, G. J. & Gerdes, J. Point-of-care diagnostics for global health. Annu. Rev. Biomed. Eng. 10, 107–144 (2008).

    Article  PubMed  CAS  Google Scholar 

  5. Creek, T. L. et al. Infant human immunodeficiency virus diagnosis in resource-limited settings: issues, technologies, and country experiences. Am. J. Obstet. Gynecol. 197, S64–S71 (2007).

    Article  PubMed  Google Scholar 

  6. 2015 Progress Report on the Global Plan Towards the Elimination of New HIV Infections Among Children and Keeping their Mothers Alive (Joint United Nations Programme on HIV and AIDS, 2015); http://www.unaids.org/en/resources/documents/2015/JC2774_2015ProgressReport_GlobalPlan

  7. Calmy, A. et al. HIV viral load monitoring in resource-limited regions: optional or necessary? Clin. Infect. Dis. 44, 128–134 (2007).

    Article  PubMed  Google Scholar 

  8. Lecher, S. et al. Scale-up of HIV viral load monitoring—seven sub-Saharan African countries. Morb. Mortal. Wkly Rep. 64, 1287–1290 (2015).

    Article  Google Scholar 

  9. Niemz, A., Ferguson, T. M. & Boyle, D. S. Point-of-care nucleic acid testing for infectious diseases. Trends Biotechnol. 29, 240–250 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Boehme, C. C. et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 377, 1495–1505 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Theron, G. et al. Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. Lancet 383, 424–435 (2014).

    Article  PubMed  CAS  Google Scholar 

  12. Plate, D. K. Evaluation and implementation of rapid HIV tests: the experience in 11 African countries. AIDS Res. Hum. Retroviruses 23, 1491–1498 (2007).

    Article  PubMed  Google Scholar 

  13. Cox, H. S. et al. Impact of decentralized care and the Xpert MTB/RIF test on rifampicin-resistant tuberculosis treatment initiation in Khayelitsha, South Africa. Open Forum Infect. Dis. 2, ofv014 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Garrett, N. J., Drain, P. K., Werner, L., Samsunder, N. & Abdool Karim, S. S. Diagnostic accuracy of the point-of-care Xpert HIV-1 viral load assay in a South African HIV clinic. J. Acquir. Immune Defic. Syndr. 72, 45–48 (2016).

    Article  Google Scholar 

  15. Nicol, M. P. et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect. Dis. 11, 819–824 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Piatek, A. S. et al. GeneXpert for TB diagnosis: planned and purposeful implementation. Glob. Health Sci. Pract. 1, 18–23 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Adair-Rohani, H. et al. Limited electricity access in health facilities of sub-Saharan Africa: a systematic review of data on electricity access, sources, and reliability. Glob. Health Sci. Pract. 1, 249–261 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Uganda National Household Survey Final Report (2016) (Uganda Bureau of Statistics, 2018); https://www.ubos.org/publications/statistical/23/

  19. Caliendo, A. M. et al. Better tests, better care: improved diagnostics for infectious diseases. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 57, S139–S170 (2013).

    Article  Google Scholar 

  20. Yan, L. et al. Isothermal amplified detection of DNA and RNA. Mol. Biosyst. 10, 970–1003 (2014).

    Article  PubMed  CAS  Google Scholar 

  21. Zhao, Y., Chen, F., Li, Q., Wang, L. & Fan, C. Isothermal amplification of nucleic acids. Chem. Rev. 115, 12491–12545 (2015).

    Article  PubMed  CAS  Google Scholar 

  22. Craw, P. & Balachandran, W. Isothermal nucleic acid amplification technologies for point-of-care diagnostics: a critical review. Lab. Chip. 12, 2469–2486 (2012).

    Article  PubMed  CAS  Google Scholar 

  23. Mori, Y., Kitao, M., Tomita, N. & Notomi, T. Real-time turbidimetry of LAMP reaction for quantifying template DNA. J. Biochem. Biophys. Methods 59, 145–157 (2004).

    Article  PubMed  CAS  Google Scholar 

  24. LaBarre, P. et al. A simple, inexpensive device for nucleic acid amplification without electricity—toward instrument-free molecular diagnostics in low-resource settings. PLoS ONE 6, e19738 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Singleton, J. et al. Electricity-free amplification and detection for molecular point-of-care diagnosis of HIV-1. PLoS ONE 9, e113693 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Curtis, K. A. et al. Single-use, electricity-free amplification device for detection of HIV-1. J. Virol. Methods 237, 132–137 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Song, J. et al. Instrument-free point-of-care molecular detection of Zika virus. Anal. Chem. 88, 7289–7294 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Liao, S.-C. et al. Smart cup: a minimally-instrumented, smartphone-based point-of-care molecular diagnostic device. Sens. Actuat. B 229, 232–238 (2016).

    Article  CAS  Google Scholar 

  29. Craw, P. et al. A simple, low-cost platform for real-time isothermal nucleic acid amplification. Sensors 15, 23418–23430 (2015).

    Article  PubMed  CAS  Google Scholar 

  30. Stedtfeld, R. D. et al. Gene-Z: a device for point of care genetic testing using a smartphone. Lab. Chip. 12, 1454–1462 (2012).

    Article  PubMed  CAS  Google Scholar 

  31. Chang, Y., Cesarman, E., Pessin, M. S. & Lee, F. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266, 1865–1869 (1994).

    Article  PubMed  CAS  Google Scholar 

  32. Mesri, E. A., Cesarman, E. & Boshoff, C. Kaposi’s sarcoma and its associated herpesvirus. Nat. Rev. Cancer 10, 707–719 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Amerson, E. et al. Accuracy of clinical suspicion and pathologic diagnosis of Kaposi sarcoma in East Africa. J. Acquir. Immune Defic. Syndr. 71, 295–301 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jiang, L. et al. Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics. Sci. Rep. 4, 4137 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Snodgrass, R. et al. KS-Detect—validation of solar thermal PCR for the diagnosis of Kaposi’s sarcoma using pseudo-biopsy samples. PLoS ONE 11, e0147636 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Arvanitakis, L. et al. Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring kaposias sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein–Barr virus. Blood 88, 2648–2654 (1996).

    PubMed  CAS  Google Scholar 

  37. Kuhara, T. et al. Rapid detection of human herpesvirus 8 DNA using loop-mediated isothermal amplification. J. Virol. Methods 144, 79–85 (2007).

    Article  PubMed  CAS  Google Scholar 

  38. Nixon, G. et al. Comparative study of sensitivity, linearity, and resistance to inhibition of digital and nondigital polymerase chain reaction and loop mediated isothermal amplification assays for quantification of human cytomegalovirus. Anal. Chem. 86, 4387–4394 (2014).

    Article  PubMed  CAS  Google Scholar 

  39. Kong, J. E. Highly stable and sensitive nucleic acid amplification and cell-phone-based readout. ACS Nano 11, 2934–2943 (2017).

    Article  PubMed  CAS  Google Scholar 

  40. Notomi, T. et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 28, e63 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Nagamine, K., Hase, T. & Notomi, T. Accelerated reaction by loop-mediated isothermal amplification using loop primers. Mol. Cell. Probes 16, 223–229 (2002).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank P. Namaganda, M. Laker-Oketta, H. Byakwaga, P. Kyomuhangi, E. Mande and O. Mbabazi for their work at the Infectious Diseases Institute. We also thank O. Imsdahl, J. Gutierrez and J. Sullivan (Cornell University) for assistance in fabrication of the TINY prototypes. Special thanks to M. Kirya for assisting during visits of rural Ugandan health clinics in July 2016. This work was performed in part at the Cornell NanoScale Facility, a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (grant ECCS-1542081). The authors acknowledge support for this research from the US National Cancer Institute under grant UH2 CA202723. This study is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant no. 1144153.

Author information

Authors and Affiliations

  1. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA

    Ryan Snodgrass, Varun Lingaiah Kopparthy, Jens Duru & David Erickson

  2. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

    Andrea Gardner & Ethel Cesarman

  3. Infectious Diseases Institute, Kampala, Uganda

    Aggrey Semeere

  4. Department of Dermatology, University of California, San Francisco, CA, USA

    Toby Maurer

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Jeffrey Martin

Authors
  1. Ryan Snodgrass
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aggrey Semeere
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Varun Lingaiah Kopparthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jens Duru
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toby Maurer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeffrey Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ethel Cesarman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. David Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R.S. and A.G. wrote the manuscript with review from all other authors. R.S., V.K., J.D., E.C. and D.E. developed the TINY device. All authors were responsible for design of experiments. R.S., A.G. and J.D. conducted experiments. A.S. and J.M. coordinated collection of human samples. R.S. and A.G. analysed the data. R.S. generated the figures and tables.

Corresponding authors

Correspondence to Jeffrey Martin, Ethel Cesarman or David Erickson.

Ethics declarations

Competing interests

The authors have submitted a patent for the TINY system.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary methods, figures and tables

Reporting summary

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Snodgrass, R., Gardner, A., Semeere, A. et al. A portable device for nucleic acid quantification powered by sunlight, a flame or electricity. Nat Biomed Eng 2, 657–665 (2018). https://doi.org/10.1038/s41551-018-0286-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-018-0286-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing