4.8 Article

Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

Journal

ACS NANO
Volume 6, Issue 12, Pages 10676-10683

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/nn3038594

Keywords

droplet microfluidics; malaria; diagnosis; enzyme activity detection; rolling-circle amplification; lab-on-a-chip

Funding

  1. NIH [HL89764]
  2. NSF [EEC-0425626]
  3. Danish Research Councils [11-116325/FTP, 11-105736/FSS]
  4. Karen Elise Jensen's Foundation
  5. Dagmar Marshall's Foundation
  6. Dir. Einar Hansen og Vera Hansen's Foundation
  7. Harboe Foundation
  8. Augustinus Foundation
  9. Louis Hansen's Foundation
  10. Horslev Foundation
  11. Fabrikant Einar Willumsen's Foundation
  12. Kobmand Sven Hansen & hustru Ina Hansen's Foundation
  13. Dir. Emil Hertz & hustru Inger Hertz' Foundation
  14. Civilingenior Frode Nygaard's Foundation
  15. Kong Christian den Tiende's Foundation
  16. Gangsted Foundation
  17. KU's Foundation for Cancer Research
  18. Ludvig og Franciska Andersen's Foundation
  19. Arvid Nilsson's Foundation
  20. Frimodt-Heineke's Foundation
  21. Aase and Ejnar Danielsens Foundation
  22. Minister Erna Hamiltons Foundation for Science and Art
  23. Apolodoro Plausonius Foundation
  24. Italian Association for Cancer Research (AIRC)

Ask authors/readers for more resources

We present an attractive new system for the specific and sensitive detection of the malaria-causing Plasmodium parasites. The system relies on isothermal conversion of single DNA cleavage ligation events catalyzed specifically by the Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite/mu L. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly to meet this demand. Moreover, potential future adaptation of the presented setup for the detection of other microorganisms may form the basis for the development of a more generic platform for diagnosis, fresh water or food quality control, or other purposes within applied or basic science.

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