Quantitative imaging of intraerythrocytic hemozoin by transient absorption microscopy.

Published on Dec 1, 2019in Journal of Biomedical Optics3.17
· DOI :10.1117/1.JBO.25.1.014507
Andy J. Chen4
Estimated H-index: 4
(Purdue University)
Sources
Abstract
Hemozoin, the heme detoxification end product in malaria parasites during their growth in the red blood cells (RBCs), serves as an important marker for diagnosis and treatment target of malaria disease. However, the current method for hemozoin-targeted drug screening mainly relies on in-vitro β-hematin inhibition assays, which may lead to false-positive events due to under-representation of the real hemozoin crystal. Quantitative in-situ imaging of hemozoin is highly desired for high-throughput screening of antimalarial drugs and for elucidating the mechanisms of antimalarial drugs. We present transient absorption (TA) imaging as a high-speed single-cell analysis platform with chemical selectivity to hemozoin. We first demonstrated that TA microscopy is able to identify β-hematin, the artificial form of hemozoin, from the RBCs. We further utilized time-resolved TA imaging to in situ discern hemozoin from malaria-infected RBCs with optimized imaging conditions. Finally, we quantitatively analyzed the hemozoin amount in RBCs at different infection stages by single-shot TA imaging. These results highlight the potential of TA imaging for efficient antimalarial drug screening and drug mechanism investigation.
References36
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Source
Heme, a hydrophobic and cytotoxic macrocycle, is an essential cofactor in a large number of proteins and is important for cell signaling. This must mean that heme is mobilized from its place of synthesis or entry into the cell to other parts of the cell where hemoproteins reside. However, the cellular dynamics of heme movement is not well understood, in large part due to the inability to image heme noninvasively in live biological systems. Here, using high-resolution transient absorption microsc...
Source
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Malaria is a parasitic disease with high prevalence in regions with inefficient healthcare conditions. Currently, the most used diagnostic methods in endemic regions are microscopy and rapid diagnostic tests by immunochromatographic assays. This work proposes an alternative miniaturized optical diagnostic method by spectrophotometry, for hemozoin (Hz) and hemoglobin (Hb) quantification and classification. Hz is a subproduct of the malaria parasite, produced by degradation of Hb, inside the red b...
Source
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Background The haem-haemozoin biocrystallization pathway is an attractive target where several efficacious and safe anti-malarial drugs act. Consequently, in vitro haemozoin (Hz) inhibition assays have been developed to identify novel compounds. However, results may differ between assays and often require complex methods or sophisticated infrastructure. The recently reported growth of haemozoin-like crystals (HLC) appears to be a simple alternative although the endproduct is structurally differe...
Source
#1Lu Wei (Columbia University)H-Index: 19
#2Fanghao Hu (Columbia University)H-Index: 23
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