It is for good reason that you have been hearing about lab-on-a-chip technology recently. These devices can be used to mimic organs, perhaps replace animal models in biomedical research, but ultimately, they have the ability to carry out a range of complex tests that were previously restricted to the lab, now contained in a single, low cost, portable device. Malaria is endemic in some parts of the world, and 229 million new cases and 409,000 deaths were reported in 2019.
I have known about Malaria since I was a volunteer 25 years ago. I have gotten it at least two times and I have experienced the tremendous personal, clinical, and societal impact of this infection, which affects 3.5 billion people worldwide. Getting any infectious disease under control is dependent on rapid identification of individuals who have been exposed.
Malaria vaccines, antimalarial drugs, and strategies to block transmission are just some of the things that need to be developed. In parts of the world where the disease is rampant and resources are limited, point-of-care identification of malaria is still a challenge. Lab-on-chips allow the creation of automated smart devices that don't require experienced personnel to run them, because they can be integrated on a small chip with biochemical and electronic functions.
With excellent sensitivity and the ability to make results available to clinicians via the internet, this could enable a remote healthcare system with sizable reduction of costs and improvement of quality. The magnetic properties of red blood cells that had been exposed to the Malaria parasites were described in scientific publications. From a physics professor's point of view, this triggered an interest in Malaria.
The idea for a novel lab-on-chip diagnostic test based on this concept of magnetism came about after I thought to myself, 'If malaria infections are magnetic, then that's my job'. The parasites are able to survive by feeding off hemoglobin, which is found in red blood cells. The release of iron-containing heme, which is a substructure in hemoglobin, is one of the byproducts of this breakdown.
The hemozoin becomes paramagnetic when each heme has a single atom of iron. The local language of a small village in Africa called Mbalmayo is where a validation of the device was done. Professor Giorgio Ferrari, one of the study's authors, said that Tmek is based on a microchip that can be used to capture red blood cells and free hemozoin in a whole blood sample.
Red blood cells are captured on some micro-magnets fabricated on the chip while they are healthy. The red blood cells are trapped by the magnets built on top of the electrodes. As cells build up, the impedance increases.
A limit of detection of 10 parasites/l can be achieved with the use of the microchip, which is capable of capturing red blood cells and free pigment in a whole blood smear and quantifying their concentration using an electrical detection in just 10 minutes. Given the current landscape and limitations of rapid tests that are currently available for malaria, this achievement is significant. Professor Spinello Antinori, one of the study's authors, said that the WHO supports the use of rapid diagnostic tests based on the detection of parasites in a blood sample.
Rapid tests still have a high limit of detection, an operating time of 15-20 minutes, and do not provide any quantification of the level of parasites. There have been a lot of false positive and negative results from the rapid tests. More sensitive tests, such as PCR, can help bridge some of the limitations, however, they still require almost 60 minutes to run, are not quantitative, and are not compatible for widespread use in the field.
Tmek represents a step forward, as its limit of detection is one order of magnitude lower, according to Francersca Milesi, a PhD student in the physics department at Politecnico di Milano. To reconcile their passion for scientific discovery with its ability to make real societal impact, the team has filed their device under a social patent, which ensures that any generated revenue is re- invested into similar research projects with high societal impact. The enthusiasm and commitment of young researchers working with me on this cutting-edge technology with the clear scope of using it in Africa is extraordinary.
The potential of the collaboration with clinicians and laboratory technicians working at Mbalmayo is enormous. The device could be revolutionary, enhancing accuracy when tests such as a optical microscopy are unavailable. The test is an important tool to identify healthy carriers.
Tmek could be the lab-on-chip equivalent of microscopy, providing clinicians with an easy, fast, and automatic tool for the quantitative assessment of the parasitesmia, disease progression, and in assessing potential human-to-mosquito parasites. It is possible to use it beyond Malaria. According to Milesi, the concept of TMek could be used to target other diseases.
One example could be schistosomiasis, where worms produce the same molecule (hemozoin) that is responsible for the change of the magnetic properties of red blood cells. The test could be made available to patients in small medical centers in endemic zones, not equipped with relevant laboratory facilities and well experienced personnel, thus allowing reliable and fast diagnosis of Malaria in the field and remote areas. A Lab-On-chip tool for rapid, quantitative, and Stage-selective diagnosis of Malaria is a reference.
There is a DOI for 10.1002/advs.202004101."