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Research Article

Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Ekaterina Y. Lukianova-Hleb, Kelly M. Campbell, Pamela E. Constantinou, Janet Braam, John S. Olson, Russell E. Ware, David J. Sullivan Jr., and Dmitri O. Lapotko
PNAS first published December 30, 2013; https://doi.org/10.1073/pnas.1316253111
Ekaterina Y. Lukianova-Hleb
aDepartment of Biochemistry and Cell Biology,
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Kelly M. Campbell
bRice University Animal Facility, and
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Pamela E. Constantinou
aDepartment of Biochemistry and Cell Biology,
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Janet Braam
aDepartment of Biochemistry and Cell Biology,
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John S. Olson
aDepartment of Biochemistry and Cell Biology,
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Russell E. Ware
aDepartment of Biochemistry and Cell Biology,
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David J. Sullivan Jr.
cW. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205
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Dmitri O. Lapotko
aDepartment of Biochemistry and Cell Biology,
dDepartment of Physics and Astronomy, Rice University, Houston, TX 77005-1892; and
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  • For correspondence: dl5@rice.edu
  1. Edited* by Robert F. Curl, Rice University, Houston, TX, and approved November 27, 2013 (received for review August 29, 2013)

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Significance

We report a noninvasive rapid transdermal detection of malaria infection without drawing blood or using any reagents. Our method uses harmless laser pulses to generate and detect through the skin tiny vapor nanobubbles specifically in malaria parasites in a patient’s body. This method is distinct from all previous diagnostic approaches, which all rely upon using a needle to obtain blood, require reagents to detect the infection, and are time- and labor-consuming. This nanobubble transdermal detection adds a new dimension to malaria diagnostics and can in the future support the rapid, high-throughput, and high-sensitive diagnosis and screening by nonmedical personnel under field conditions, including the detection of early and asymptomatic disease.

Abstract

Successful diagnosis, screening, and elimination of malaria critically depend on rapid and sensitive detection of this dangerous infection, preferably transdermally and without sophisticated reagents or blood drawing. Such diagnostic methods are not currently available. Here we show that the high optical absorbance and nanosize of endogenous heme nanoparticles called “hemozoin,” a unique component of all blood-stage malaria parasites, generates a transient vapor nanobubble around hemozoin in response to a short and safe near-infrared picosecond laser pulse. The acoustic signals of these malaria-specific nanobubbles provided transdermal noninvasive and rapid detection of a malaria infection as low as 0.00034% in animals without using any reagents or drawing blood. These on-demand transient events have no analogs among current malaria markers and probes, can detect and screen malaria in seconds, and can be realized as a compact, easy-to-use, inexpensive, and safe field technology.

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: dl5{at}rice.edu.
  • Author contributions: E.Y.L.-H. and D.O.L. designed research; E.Y.L.-H. and D.O.L. performed research; J.B., J.S.O., R.E.W., and D.J.S. contributed new reagents/analytic tools; E.Y.L.-H., K.M.C., P.E.C., and D.O.L. performed animal experiments; E.Y.L.-H., K.M.C., P.E.C., J.B., J.S.O., D.J.S., and D.O.L. analyzed data; and E.Y.L.-H., J.B., J.S.O., R.E.W., D.J.S., and D.O.L. wrote the paper.

  • ↵*This Direct Submission article had a prearranged editor.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1316253111/-/DCSupplemental.

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Transdermal malaria detection
Ekaterina Y. Lukianova-Hleb, Kelly M. Campbell, Pamela E. Constantinou, Janet Braam, John S. Olson, Russell E. Ware, David J. Sullivan, Dmitri O. Lapotko
Proceedings of the National Academy of Sciences Dec 2013, 201316253; DOI: 10.1073/pnas.1316253111

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Transdermal malaria detection
Ekaterina Y. Lukianova-Hleb, Kelly M. Campbell, Pamela E. Constantinou, Janet Braam, John S. Olson, Russell E. Ware, David J. Sullivan, Dmitri O. Lapotko
Proceedings of the National Academy of Sciences Dec 2013, 201316253; DOI: 10.1073/pnas.1316253111
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