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Sensitive Detection of Malaria Infection by Third Harmonic Generation Imaging

Jonathan M. Bélisle ^*, Santiago Costantino ^*, Mara L. Leimanis , Marie-Josée Bellemare , D. Scott Bohle , Elias Georges  and Paul W. Wiseman ^* 

^* Department of Physics, McGill University, Montreal, Quebec, Canada; Institute of Parasitology, McGill University, Macdonald Campus, Ste-Anne de Bellevue, Quebec, Canada; and Department of Chemistry, McGill University, Montreal, Quebec, Canada

Correspondence: Address reprint requests and inquiries to P. W. Wiseman, Tel.: 514-398-6524; E-mail: paul.wiseman{at}mcgill.ca.

Malaria remains a major health concern worldwide, with 350–500 million cases reported annually in endemic countries. In this study, we report a novel and highly sensitive optical-based detection of malaria-infected blood cells by third harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited by the parasite during its lifecycle. The THG signal from the hemozoin was greater than we have observed in any cell type with signal/noise ratios that reach 1000:1. This method allows a rapid and robust detection of early stage infections of blood cells. The immense nonlinear response of the intrinsic parasitic by-product pigments suggests that automated optical detection by THG could be used for sensitive and rapid screening of parasite infection in blood samples.