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Optimization of malaria detection based on third harmonic generation imaging of hemozoin

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Abstract

The pigment hemozoin is a natural by-product of the metabolism of hemoglobin by the parasites which cause malaria. Previously, hemozoin was demonstrated to have a very high nonlinear optical response enabling third harmonic generation (THG) imaging. In this study, we present a complete characterization of the nonlinear THG response of natural hemozoin in malaria-infected red blood cells, as well as in pure isostructural synthesized hematin anhydride, in order to determine optimal imaging parameters for detection. Our study demonstrates the wavelength range for optimal pulsed femtosecond laser excitation of THG from hemozoin crystals. In addition, we show the hemozoin crystal detection as a function of crystal size, incident laser power, and the emission response of the hemozoin crystals to different incident laser polarization states. Our systematic measurements of the nonlinear optical response from hemozoin establish detection limits, which are essential for the optimal design of malaria detection technologies that exploit the THG response of hemozoin.

Combined overlay image of THG (bright crystals in blue, one scan per frame) and TP autofluorescence (oval cells in red, average of 15 sequential frame scans) of natural hemozoin crystals and red blood cells (infected with FCR-3 Plasmodium falciparum), respectively, collected at the laser excitation wavelength of 1170 nm with 100 mW average incident power and pixel dwell time of 5 μs

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Acknowledgments

We thank the Natural Science Education Research Canada (NSERC) for an NSERC I2I grant and a Discovery grant to carry out these studies (PWW and EG). PWW also acknowledges funding from the Fessenden Chair in Science Innovation and the Canadian Foundation for Innovation. DSB acknowledges support from NSERC, the CRC, and the FQRNT.

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Authors and Affiliations

  1. Department of Physics, McGill University, 3600 University St., Montreal, QC, H3A 2T8, Canada

    Umakanta Tripathy, Mohammad Hussain Sangji & Paul W. Wiseman

  2. Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC, H3A 2K6, Canada

    Maxime Giguère-Bisson, Marie-Josée Bellemare, D. Scott Bohle & Paul W. Wiseman

  3. Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, QC, H9X 3V9, Canada

    Elias Georges

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  1. Umakanta Tripathy
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  2. Maxime Giguère-Bisson
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  3. Mohammad Hussain Sangji
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  4. Marie-Josée Bellemare
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  5. D. Scott Bohle
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  6. Elias Georges
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  7. Paul W. Wiseman
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Correspondence to Paul W. Wiseman.

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Tripathy, U., Giguère-Bisson, M., Sangji, M.H. et al. Optimization of malaria detection based on third harmonic generation imaging of hemozoin. Anal Bioanal Chem 405, 5431–5440 (2013). https://doi.org/10.1007/s00216-013-6985-z

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  • DOI: https://doi.org/10.1007/s00216-013-6985-z

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