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Massachusetts Institute of Technology - A new way to diagnose malaria

DCN Corp® - Red blood cells from a patient infected with Plasmodium falciparum.  Credit - image courtesy of Osaro Erhabor and MIT, USA

Employing magnetic fields an unique technique can detect parasite's waste products in infected blood cells

In the last few decades - malaria diagnosis, unfortunately, has not changed much.  Essentially after taking a blood sample from a patient, a specialist technician smears a blood sample on to a glass base substrate, subsequently stains with a special dye, and then looks under a microscope for the Plasmodium parasite, which is the root cause of the disease.  This method provides an accurate count of how many parasites are in the blood, which is an important measure of the disease severity, but it is not perfect because there is potential for human error.

Alternatively a research collaboration between Singapore-MIT Alliance for Research and Technology (SMART) has arrived on to a new method.  The researchers have managed to devise a way to employ Magnetic Resonance Relaxometry (MRR) - similar to Magnetic Resonance Imaging (MRI) - to efficiently detect a parasitic waste product in the blood of infected patients.  The methodology could offer a reliable way to detect malaria as claimed by Jongyoon Han - Professor of Electrical Engineering and Biological Engineering at MIT.

Han states - "there is real potential to make this into a field deployable system, especially since you don't need any kind of labels or dye. It's based on a naturally occurring bio-marker that does not require any biochemical processing of samples."

Please Note Han is a senior author in a paper describing the methodology in the 31st August issue of Nature Medicine.  In addition, Peter Rainer Preiser of SMART and Nanyang Technical University, Singapore, is also a senior author with the paper's lead author being Weng Kung Peng, another research scientist at SMART.

Hunting Malaria with magnets

With a traditional blood-smear technique, typically a technician stains the blood with a reagent that dyes the cell nuclei.  Normally red blood cells do not have nuclei, so any which do show up are presumed to be due to parasite cells.  Unfortunately, up-to-date technology and expertise required to identify the parasite is not always available in some of the regions of the world most affected by malaria.  As stated by Han - "the technicians don't always agree in their interpretations of the smears."

Unfortunately, as Han continues to state - "there's a lot of human-to-human variation regarding what counts as infected red blood cells versus some dust particles stuck on the plate. It really takes a lot of practice."

The new SMART system detects a parasitic waste product called hemozoin.  When the parasites infect red blood cells, they feed on to the nutrient rich hemoglobin carried by the cells.  As the hemoglobin breaks down, it releases iron, which can be toxic, so the parasite converts the iron into hemozoin - a weak paramagnetic crystallite.

The crystals interfere with the normal magnetic spins of hydrogen atoms.  Subsequently when exposed to a powerful magnetic field, the hydrogen atoms align their spins in the same direction.  And when a second smaller field perturbs the atoms, they should all change their spins in synchrony.  However, if another magnetic particle, such as hemozoin, is present, this synchrony is disrupted through a process known as relaxation.  The more magnetic particles which are present the more quickly the synchrony is disrupted.

Han states - "what we are trying to really measure is how the hydrogen's nuclear magentic resonance is affected by the proximity of other magnetic particles."

For their study, the researchers employed a 0.5 tesla magnet, which is less expensive and powerful then the 2- or 3- tesla magnets normally required for MRI diagnostic imaging, which can cost up to at least $2 million.  Excitingly the current device prototype is minute enough to sit on a table or laboratory bench, but the team is also working on a portable version, which is the size of a small electronic tablet. [1]

After taking a blood sample and spinning it down to concentrate the red blood cells, the sample analysis can take less then a minute.  Furthermore, only about 10 microliter of blood is required, which can be easily obtained with a finger prick, thus, making the procedure minimally invasive and much easier for current and future care workers trying to draw blood intravenously.

Peng states - "this system can be built at a very low cost, relative to the million-dollar MRI machines used in a hospital,"- and - "furthermore, since this technique does not rely on expensive labelling with chemical reagents, we are able to get each diagnostic test done at a cost of less than 10 cents."

Tracking Infection

Hemozoin crystals are produced in all four stages of a typical malaria infection, which includes the earliest stages, and are generated by all known species of the Plasmodium parasite.  Plus, the amount of hemozoin can reveal how severe the infection is, or whether it is responding to treatment.  Han states - "there are a lot of scenarios where you want to see the number, rather than a yes or no answer."

In their paper, the researchers showed that they could detect Plasmodium falciparum, the most dangerous form of the parasite, in the blood cells grown in the lab.  They managed to also detect the parasite in red blood cells from mice infected with Plasmodium berghei.

As supported by a Professor of Electrical engineering at Harvard University - "more sensitive, less error-prone, and requires less blood sample as compared to the standard blood-smear protocol," - and - "I think there is a strong potential here, and I look forward to its further development for reliable field deployment."

In the future, the researchers are planning to launch a spin-out company to make their technology available at an affordable price.  The team is also running field tests in South East Asia, and is exploring the powering of the device by solar energy, an important consideration for poor rural areas. Original article available here

The research, above, collaboratively highlights the potential of nanotechnology for the earlier diagnosis of fatal diseases and/or medical conditions.  As stated previously, DCN Corp strongly believes it can contribute, by surface enhancing several levels the early signs of fatal diseases and/or medical conditions. Going forward, if you and/or your colleagues are interested in making DCN Corp's alternative process reality - please ensure to contact the company as soon as practicably possible.

[1] Peng, W. K., Chen, L. and Han, J., Development of miniaturised, portable magnetic resonance relaxometry system for point-of-care medical diagnosis. Review of Scientific Instruments 83, 095115 (2012)