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Roughly 0.6 million people die each year from malaria due to lack of early diagnosis and well-timed treatment. Our previous study demonstrated great potential of in vivo photoacoustic (PA) flow cytometry (PAFC) for early diagnosis of deadly diseases with focus on cancer and thromboembolic complications. Here we demonstrate potential of advanced PAFC platforms using new laser, ultrasound transducer array and recording system to detect infected red blood cells (iRBCs) with malaria-associated pigment hemozoin which has a higher PA contrast than blood background. Mature parasites of human infecting species such as P. falciparum characteristically sequester mature iRBCs in the capillary bed and display synchrony in their reproductive cycle. To address this issue prior to clinical application, new PAFC platform was verified in a pre-clinical study using new animal models. Specifically, we used P. chabaudi (a rodent malaria species that mimics the characteristics of the most virulent human counterpart) to estimate the detection sensitivity with immature ring-stage parasites in peripheral blood, compared PA signals from the differing species, and examined the relationship between PA signal amplitudes and level of blood oxygenation. Based on previous successful trials on melanoma patients with melanin as an intrinsic PA marker, which has similar absorption as hemozoin, we believe that after additional malaria–related clinical trials, PAFC with a small 1064 nm laser and wearable a cost-effective, easy-to-use, watch-like, safe PA probe will provide malaria diagnosis in humans at parasitemia levels 10e4 -times lower than the current gold standard of diagnosis, the Giemsa-stained blood smear. It can reduce malaria-related mortality by well-timed treatment, especially in children in malaria-endemic countries.
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