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Online Seminar "Magnetism fights for health. A quantitative lab-on-chip rapid diagnostic test for Malaria" by Riccardo Bertacco (Mon, 20 April 2020)

The Seminars and Training Committee kindly invites you to the first ICMAB Online Periodical Lecture:

Magnetism fights for health. A quantitative lab-on-chip rapid diagnostic test for Malaria

by Riccardo Bertacco, Department of Physics, Politecnico di Milano, Milano (Italy); Istituto di Fotonica e Nanotecnologie (IFN) – CNR, Milano (Italy)

Monday, 20 April 2020 @ 12 pm
Online Periodical Lecture. Click here to register. 
(You will receive an email with the link to attend the meeting once registered)

Anna
Anna
31 March 2020

Abstract:

The search for new rapid diagnostic tests (RDT) for malaria is a priority to fight this endemic disease, according to WHO recommendations [1]. In fact, available RDT based on the detection of antigens, suffer from several limitations: they are not quantitative, display suboptimal performance for detecting non-falciparum species together with pfHRP2/3 gene deletions and delayed clearance dynamics for P. falciparum which are responsible for a sizable number of false positive and negative results. For these reasons WHO strongly recommend the development of novel RDTs with same sensitivity of the gold standard (optical microscopy examination) but a lower percentage of false positive and negative results. 

In this seminar I report on a new, easy to operate, lab-on-chip diagnostic test, TMek, for the quantification of the plasmodium parasitemia, which could improve malaria diagnostics. The method is based on the paramagnetic susceptibility of hemozoin crystals [2] (the malaria pigment produced by plasmodium as by-product of hemoglobin degradation) which are found within the infected red blood cells and free in the blood. A silicon microchip, with an array of Nickel posts underneath suitable electrodes, is put in contact with a smear of patient blood (7 microL) diluted with an anticoagulant and PBS, in the magnetic field produced by external magnets. Due to the competition between the magnetic and gravity force, only infected RBC and hemozoin crystals are attracted towards the concentrators, thus altering the impedance between electrodes. The entity of the impedance variation turns out to be proportional to the parasitemia and/or the hemozoin concentration, thus allowing for quantification. 

TMek has been first tested at Sacco Hospital (Milano) on control blood samples from healthy donors as well on some samples from patients affected by malaria, diagnosed by haemoscopy and LAMP (Malaria Illumigene – Meridian EU). The test turned out to have a limit of detection for parasitaemia around 0.0002%, 20 times better than currently used RDT, associated with an execution time of just 10 minutes, to be compared with the 20 min of commercial RDT. A pre-clinical validation in endemic zone has been carried out in Cameroon during April 2019. On 75 patients suspected of malaria, we checked our TMek test against the gold standard and conventional RDT. No false negative results are found, giving a 100% (92.3 – 100% C.I. 95%) sensitivity, while the test specificity is about 65% (45.7 – 82.1 C.I. 95%) due to some false positive results. However, specificity increases by reducing the delay between the blood sampling and the analysis, in the typical conditions foreseen for a lab-on-chip finger-prick test to be used on-field. 

These preliminary results indicate that TMek holds a great potential as novel rapid, quantitative and pan-malaria test for malaria suitable for on-field use in endemic zones. The technology is protected by two social patents [3] and has been developed within a project granted by the Polisocial Award program of Politecnico di Milano.

REFERENCES

[1] World Health Organization, “Malaria Rapid Diagnostic Test Performance,” 2017.
[2] M. Giacometti,  C. Rinaldi,  M. Monticelli, L. Callegari,  A. Collovini,  D. Petti, G. Ferrari,  and R. Bertacco, Electrical and magnetic properties of hemozoin nanocrystals, Appl. Phys. Lett., 113, 203703 (2018)[3] R.Bertacco et al., Italian Patent Applications 102017000082112 (2017) and 102019000000821 (2019). 

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