Multilayer thin-film optical filters for reflectance-based malaria diagnostics

Malaria diagnosis relies on optical microscopy and/or rapid diagnostic tests based on detecting specific malaria antigens. The clinical sensitivity of these methods is highly dependent on parasite density, with low levels of detection at low parasite density, challenging the worldwide malaria elimination efforts. Therefore, there is a need for diagnostic methods with higher sensitivity, demanding innovative diagnostics devices able to detect malaria at low parasite density and at early stages of the disease. We propose an innovative optical device for malaria diagnosis, based on optical reflectance spectrophotometry, for the detection of parasites through the quantification of haemozoin. For this purpose, a set of eight thin-film optical filters, based on multilayer stacks of MgO/TiO2 and SiO2/TiO2 thin-films, with high transmittance and low full width at half maximum (FWHM) at specific wavelengths, was designed and fully characterized (both numerically and experimentally). A preliminary assessment of its potential to reconstruct the original spectra of red blood cells was performed, both in uninfected and Plasmodium falciparum-infected samples. The obtained results show that, although the experimental filters have a non-ideal performance characteristic, they allow us to distinguish, based on only 8 discrete points in the optical spectrum, between healthy and malaria infected samples, up to a detection limit of 12 parasites/μL of red blood cells. Those results enhance the potential of using such a device for malaria diagnostics, aiming for non-invasiveness.Project NORTE-01-0145-FEDER-028178 funded by NORTE 2020 Portugal Regional Operational Program under PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund and the Fundação para a Ciência e Tecnologia (FCT), IP. This work was also supported by national funds, through the Portuguese FCT, under the reference projects UIDB/04436/2020, UIDP/04436/2020, UIDB/50026/2020 and UIDP/50026/2020, and by the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBIPortuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122). V. Baptista thanks FCT for the SFRH/BD/145427/2019 grant. Maria Isabel Veiga thanks FCT for her contract funding provided through 2020.03113.CEECIND. Susana Catarino thanks FCT for her contract funding provided through 2020.00215.CEECIN