A magneto-optic route toward the in vivo diagnosis of malaria: preliminary results and preclinical trial data - PubMed (original) (raw)

A magneto-optic route toward the in vivo diagnosis of malaria: preliminary results and preclinical trial data

Dave M Newman et al. Biophys J. 2008 Jul.

Abstract

We report the development of magneto-optic technology for the rapid quantitative diagnosis of malaria that may also be realizable in a noninvasive format. Hemozoin, the waste product of malarial parasitic action on hemoglobin, is produced in a form that under the action of an applied magnetic field gives rise to an induced optical dichroism characteristic of the hemozoin concentration. Here we show that precise measurement of this induced dichroism may be used to determine the level of malarial infection because this correlates, albeit in a complex manner throughout the infection cycle, with the concentration of hemozoin in the blood and tissues of infected patients. Under conservative assumptions for the production of hemozoin as a function of parasitemia, initial results indicate that the technique can match or exceed other current diagnostic techniques. The validity of the approach is confirmed by a small preliminary clinical trial on 13 patients, and measurements on live parasitized cells obtained from in vitro culture verify the possibility of producing in vivo diagnostic instrumentation.

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Figures

FIGURE 1

FIGURE 1

(a) Difference in transmission (normalized to value at 1 T) for orthogonal polarized beams as a result of magnetically induced dichroism in a _β_-hematin (BH) suspension (20 _μ_g/ml). (b) Magnetic orientation of crystals suspended in fluid modeled following formalism described in text. (c) Experimental configuration. (d) Magnetically aligned 20 _μ_g/ml concentration of BH set in 10% w/v gelatin gel behaving as a dichroic polarizer. (e) Dynamic response of dispersion of BH to alternating magnetic field.

FIGURE 2

FIGURE 2

Fractional change in transmittance Δ_I_/I associated with magnetically induced dichroism. (a) Differing concentrations of _β_-hematin dispersed in whole fresh blood, and (b) differing concentrations of hemozoin in the form of parasitized red blood cells (PRBCs) grown in culture and lysed by freezing before dilution with whole fresh blood. (Insets) Electron micrographs of synthesized _β_-hematin (BH) and hemozoin (HZ) extracted from cultured cells. Legends 1, 2, and 3 refer to samples mixed and measured on different occasions. Correlation between the hemozoin concentration and parasitemia scales on both the upper and lower graphs is made as described in the text.

FIGURE 3

FIGURE 3

Fractional change in transmittance Δ_I_/I associated with magnetically induced dichroism arising from rotation of hemozoin crystals within the cell vacuoles of live parasitized cells grown and sampled from nonsynchronous culture.

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