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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

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

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 (121). 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 (2326). 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.

References

  1. Sturrock HJHsiang MSCohen JMSmith DLGreenhouse BBousema TTargeting asymptomatic malaria infection: active surveillance in control and elimination. PLoS Med2013;10:e1001467DOIPubMed
  2. The malERA Consultative Group on Diagnoses and Diagnostics. A research agenda for malaria eradication: diagnoses and diagnostics. PLoS Med.2011;8:e1000396DOIPubMed
  3. World Health Organization. World malaria report 2014 [cited 2014 Dec 19].http://www.who.int/malaria/publications/world_malaria_report_2014/report/en/
  4. McMorrow MLAidoo MKachur SPMalaria rapid diagnostic tests in elimination settings—can they find the last parasite? Clin Microbiol Infect.2011;17:162431DOIPubMed
  5. Oriero ECJacobs JVan Geertruyden JNwakanma DD’Alessandro UMolecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination. J Antimicrob Chemother2015;70:213DOIPubMed
  6. Wongsrichanalai CBarcus MMuth SSutamihardja AWernsdorfer WA review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg2007;77:11927 .PubMed
  7. Ochola LBVounatsou PSmith TMabaso MLNewton CRThe reliability of diagnostic techniques in the diagnosis and management of malaria in the absence of a gold standard. Lancet Infect Dis2006;6:5828DOIPubMed
  8. Horning MPDelahunt CBSingh SRGaring SHNichols KPA paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window. Lab Chip2014;14:20406DOIPubMed
  9. Newman DMHeptinstall JMatelon RJSavage LWears MLBeddow JA magneto-optic route toward the in vivo diagnosis of malaria: preliminary results and preclinical trial data. Biophys J2008;95:9941000DOIPubMed
  10. Demirev PAFeldman ABKongkasuriyachai DScholl PSullivan D JrKumar NDetection of malaria parasites in blood by laser desorption mass spectrometry. Anal Chem2002;74:32626DOIPubMed
  11. Wood BRHermelink ALasch PBambery KRWebster GTKhiavi MAResonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics. Analyst (Lond)2009;134:111925DOIPubMed
  12. Wilson BKBehrend MRHorning MPHegg MCDetection of malarial byproduct hemozoin utilizing its unique scattering properties. Opt Express.2011;19:121906DOIPubMed
  13. Webster GTde Villiers KAEgan TJDeed STilley LTobin MJDiscriminating the intraerythrocytic lifecycle stages of the malaria parasite using synchrotron FT-IR microspectroscopy and an artificial neural network. Anal Chem2009;81:251624DOIPubMed
  14. Butykai AOrbán AKocsis VSzaller DBordács STátrai-Szekeres EMalaria pigment crystals as magnetic micro-rotors: key for high-sensitivity diagnosis. Sci Rep. 2013;3:1431.
  15. Orbán AButykai ÁMolnár APröhle ZFülöp GZelles TEvaluation of a novel magneto-optical method for the detection of malaria parasites. PLoS ONE2014;9:e96981DOIPubMed
  16. Peng WKKong TFNg CSChen LHuang YBhagat AAMicromagnetic resonance relaxometry for rapid label-free malaria diagnosis. Nat Med.2014;20:106973DOIPubMed
  17. Delahunt CHorning MWilson BProctor JHegg MLimitations of haemozoin-based diagnosis of Plasmodium falciparum using dark-field microscopy. Malar J2014;13:147DOIPubMed
  18. Balasubramanian DMohan Rao CPanijpan BThe malaria parasite monitored by photoacoustic spectroscopy. Science1984;223:82830.DOIPubMed
  19. Custer JKariuki MBeerntsen BViator JPhotoacoustic detection of hemozoin in human mononuclear cells as an early indicator of malaria infection. Proc SPIE2010;7564:75641FDOI
  20. Samson EBGoldschmidt BSWhiteside PJSudduth ASCuster JRBeerntsen BPhotoacoustic sepctroscopy of β-hematin. J Opt2012;14:065302.DOIPubMed
  21. Beier JCPerkins PVKoros JKOnyango FKGargan TPWirtz RAMalaria sporozoite detection by dissection and ELISA to assess infectivity of afrotropical Anopheles (Diptera: Culicidae). J Med Entomol1990;27:37784DOIPubMed
  22. Lukianova-Hleb EYCampbell KMConstantinou PEBraam JOlson JSWare REHemozoin-generated vapor nanobubbles for transdermal reagent and needle-free detection of malaria. Proc Natl Acad Sci U S A2014;111:9005DOIPubMed
  23. Lee JClarke MLTokumasu FLesoine JFAllen DWChang RAbsorption-based hyperspectral imaging and analysis of single erythrocytes. IEEE J Sel Top Quantum Electron2012;18:11309DOI
  24. Zonios GBykowski JKollias NSkin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy. J Invest Dermatol2001;117:14527DOIPubMed
  25. Sullivan DJ JrGluzman IYGoldberg DEPlasmodium hemozoin formation mediated by histidine-rich proteins. Science1996;271:21922.DOIPubMed
  26. Egan TJRecent advances in understanding the mechanism of hemozoin (malaria pigment) formation. J Inorg Biochem2008;102:128899.DOIPubMed
  27. Lukianova-Hleb EYLapotko DOExperimental techniques for imaging and measuring transient vapor nanobubbles. Appl Phys Lett.2012;101:264102DOIPubMed
  28. Lapotko DOptical excitation and detection of vapor bubbles around plasmonic nanoparticles. Opt Express2009;17:253856 and. DOIPubMed
  29. Anderson RRParrish JASelective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science1983;220:5247.DOIPubMed
  30. Wang LVHu SPhotoacoustic tomography: in vivo imaging from organelles to organs. Science2012;335:145862 and. DOIPubMed
  31. Laser Institute of America. American national standard for safe use of lasers (ANSI Z136.1–2007) (approved March 16, 2007). Orlando (FL): American Standards Institute, Inc.; 2007.
  32. Sullivan D. Hemozoin: a biocrystal synthesized during the degradation of heloglobin. Biopolym Online. 2005;9 [cited 2014 Dec 19].
  33. Nagaraj VASundaram BVaradarajan NMSubramani PAKalappa DMGhosh SKMalaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection. PLoS Pathog2013;9:e1003522DOIPubMed

Figures

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

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