Hemozoin as a Diagnostic Biomarker: A Scoping Review of Next-Generation Malaria Detection Technologies.

Abstract

Accurate malaria diagnosis is essential for effective case management and transmission control; however, the sensitivity, operational requirements, and field applicability of current conventional methods are limited. Hemozoin, an optically and magnetically active crystalline biomarker produced by <i>Plasmodium</i> species, offers a reagent-free target for next-generation diagnostics. This scoping review, following PRISMA-ScR and Joanna Briggs Institute guidance, synthesizes recent advances in hemozoin-based detection technologies and maps the current landscape. Twenty-four studies were reviewed, spanning eight major technology classes: magneto-optical platforms, magnetophoretic microdevices, photoacoustic detection, Raman/SERS spectroscopy, optical and hyperspectral imaging, NMR relaxometry, smartphone-based microscopy, and flow cytometry. Magneto-optical systems-including Hz-MOD, Gazelle™, and RMOD-demonstrated the highest operational readiness, with robust specificity but reduced sensitivity at low parasitemia. Photoacoustic Cytophone studies demonstrated promising sensitivity and noninvasive in vivo detection. Raman/SERS platforms achieved sub-100 infected cell/mL analytical sensitivity but remain laboratory-bound. Microfluidic and smartphone-based tools offer emerging, potentially low-cost alternatives. Across modalities, performance varied by parasite stage, with reduced detection of early ring forms. In conclusion, hemozoin-targeted diagnostics represent a rapidly evolving field with multiple viable translational pathways. While magneto-optical devices are closest to field deployment, further clinical validation, improved low-density detection, and standardized comparison across platforms are needed to support future adoption in malaria-endemic settings.