Transdermal Diagnosis of Malaria Using Vapor Nanobubbles - Volume 21, Number 7—July 2015 - Emerging Infectious Disease journal - CDC

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Transdermal Diagnosis of Malaria Using Vapor Nanobubbles - Volume 21, Number 7—July 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 7—July 2015

Research

Transdermal Diagnosis of Malaria Using Vapor Nanobubbles

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• Materials and Methods
• Results and Discussion
• Suggested Citation

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Ekaterina Lukianova-Hleb, Sarah Bezek, Reka Szigeti, Alexander Khodarev, Thomas Kelley, Andrew Hurrell, Michail Berba, Nirbhay Kumar, Umberto D’Alessandro, and Dmitri Lapotko 

Author affiliations: Rice University, Houston, Texas, USA (E. Lukianova-Hleb, D. Lapotko); Baylor College of Medicine, Houston (S. Bezek, R. Szigeti); Ben Taub General Hospital, Houston (S. Bezek, R. Szigeti); X Instruments LLC, Fremont, California, USA (A. Khodarev); Precision Acoustics Ltd, Dorset, UK (T. Kelley, A. Hurrell); Standa UAB, Vilnius, Lithuania (M. Berba); Tulane University, New Orleans, Louisiana, USA (N. Kumar); Medical Research Council, Banjul, The Gambia (U. D’Alessandro); London School of Hygiene and Tropical Medicine, London, UK (U. D’Alessandro)

Suggested citation for this article

Abstract

A fast, precise, noninvasive, high-throughput, and simple approach for detecting malaria in humans and mosquitoes is not possible with current techniques that depend on blood sampling, reagents, facilities, tedious procedures, and trained personnel. We designed a device for rapid (20-second) noninvasive diagnosis of Plasmodium falciparum infection in a malaria patient without drawing blood or using any reagent. This method uses transdermal optical excitation and acoustic detection of vapor nanobubbles around intraparasite hemozoin. The same device also identified individual malaria parasite–infectedAnopheles mosquitoes in a few seconds and can be realized as a low-cost universal tool for clinical and field diagnoses.

Malaria control and elimination would benefit greatly from an efficient and universal diagnostic tool that is fast (provides results in seconds), noninvasive and safe (uses no blood sampling or reagents), simple to use (can be operated by nonmedical personnel), sensitive and specific (detects low-level asymptomatic infections), and inexpensive and that detects malarial infection in humans and in mosquitoes (1–21). We recently proposed a transdermal blood- and reagent-free approach based on hemozoin-generated vapor nanobubbles (H-VNBs) (22) in which malaria parasite–specific endogenous nanocrystals of hemozoin are optically excited in vivo with a safe and short laser pulse (delivered to blood vessels through the skin). The light is converted into nonstationary localized heat that evaporates the adjacent nanovolume of liquid and thus generates an expanding and collapsing vapor nanobubble inside the parasite. The nanosize and high optical absorbance of hemozoin provide higher malaria infection specificity of these H-VNBs than does any normal blood and tissue components (23–26). Their transient expansion and collapse result in a noninvasive pressure pulse that is easily detected through the skin with an ultrasound sensor. In our preliminary studies (22), H-VNBs detected parasitemia as low as 0.0001% in vitro (human blood), and 0.00034% in vivo (transdermal detection in animals), with no false-positive signals. Therefore, H-VNB might be able to detect extremely low parasite densities provided the method can be applied to humans or mosquitoes simply and inexpensively.

To determine the technical and medical feasibility of H-VNBs for malaria diagnosis and screening, we prototyped a diagnostic device and evaluated it in a patient with confirmed malaria and in noninfected persons as controls. We also evaluated the device in Plasmodium falciparum–infected mosquitoes.

Dr. Lukianova-Hleb is a research scientist at Rice University. Her research interests include nanophotonics and nanomedicine with the focus on cancer and infectious diseases.

Acknowledgments

We thank K. Keene, A. Garbino, P. Hotez, S. Hoxhaj, K. Mattox, J. Braam, and J. Olson for their support and assistance with the study.

Studies in the laboratory of N.K. are supported by National Institutes of Health grants (AI47089 and AI101427). The patent application for the method described has been filed by Rice University.

The authors have the following competing financial interests: M.B. for Standa UAB; A.K. for X Instruments LLC; T.K. and A.H. for Precision Acoustics Ltd.

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Figures

• Figure 1. A) Experimental laboratory prototype of a malaria diagnostic device with the pulsed laser and the integrated probe shown being scanned across a human wrist. B) Functional diagram of the...
• Figure 2. A) Acoustic traces obtained in vitro in response to a single laser pulse exposure (532 nm, 36 mJ/cm2 delivered at 0 time point) from the sample of whole human...

Suggested citation for this article: Lukianova-Hleb E, Bezek S, Szigeti R, Khodarev A, Kelley T, Hurrell A, et al. Transdermal diagnosis of malaria using vapor nanobubbles. Emerg Infect Dis. 2015 Jul [date cited]. http://dx.doi.org/10.3201/eid2107.150089

DOI: 10.3201/eid2107.150089