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In vivo photoacoustic flow cytometry for early malaria diagnosis
Author(s) -
Cai Chengzhong,
Carey Kai A.,
Nedosekin Dmitry A.,
Menyaev Yulian A.,
Sarimollaoglu Mustafa,
Galanzha Ekaterina I.,
Stumhofer Jason S.,
Zharov Vladimir P.
Publication year - 2016
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22854
Subject(s) - parasitemia , flow cytometry , cytometry , hemozoin , malaria , photoacoustic imaging in biomedicine , in vivo , biology , biomedical engineering , materials science , plasmodium falciparum , immunology , medicine , optics , physics , microbiology and biotechnology
In vivo photoacoustic (PA) flow cytometry (PAFC) has already demonstrated a great potential for the diagnosis of deadly diseases through ultrasensitive detection of rare disease‐associated circulating markers in whole blood volume. Here, we demonstrate the first application of this powerful technique for early diagnosis of malaria through label‐free detection of malaria parasite‐produced hemozoin in infected red blood cells (iRBCs) as high‐contrast PA agent. The existing malaria tests using blood smears can detect the disease at 0.001–0.1% of parasitemia. On the contrary, linear PAFC showed a potential for noninvasive malaria diagnosis at an extremely low level of parasitemia of 0.1%, which is ∼10 3 times better than the existing tests. Multicolor time‐of‐flight PAFC with high‐pulse repetition rate lasers at wavelengths of 532, 671, and 820 nm demonstrated rapid spectral and spatial identification and quantitative enumeration of individual iRBCs. Integration of PAFC with fluorescence flow cytometry (FFC) provided real‐time simultaneous detection of single iRBCs and parasites expressing green fluorescence proteins, respectively. A combination of linear and nonlinear nanobubble‐based multicolor PAFC showed capability to real‐time control therapy efficiency by counting of iRBCs before, during, and after treatment. Our results suggest that high‐sensitivity, high‐resolution ultrafast PAFC–FFC platform represents a powerful research tool to provide the insight on malaria progression through dynamic study of parasite–cell interactions directly in bloodstream, whereas portable hand‐worn PAFC device could be broadly used in humans for early malaria diagnosis. © 2016 International Society for Advancement of Cytometry