Monday 19 August 2013

Malaria could be tested early by cheap, portable device

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Malaria could be tested early by cheap, portable device
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A device that measures electrical properties of red blood cells is able to detect if they are infected with malaria in the early stages. The researchers hope their findings will lead to a portable and low-cost, yet highly sensitive device that can diagnose malaria on the spot using just a drop of blood.

Anantha Chandrakasan and colleagues from the Massachusetts Institute of Technology (MIT) write about how they developed and tested their experimental microfluidic device in the journal Lab Chip.

The device spreads the drop of blood on an electrode that can count individual cells as they stream past, and it can also take very accurate readings of their impedance or electrical resistance.

In previous studies, the team had already established that diseases like malaria alter the electrical properties of red blood cells.

Chandrakasan, who specializes in developing low-power electronic devices, told the press:

"Ultimately the goal would be to create a postage stamp-sized device with integrated electronics that can detect if a person has malaria and at what stage."

The researchers believe the same technology can be used to diagnose other diseases that change the electrical properties of red blood cells.

Malaria is caused by five strains of Plasmodium, a parasite that lives in the gut of the female Anopheles mosquito and passes to humans through her bite.

For this study, the researchers investigated the strain P. falciparum. When the parasite enters the human bloodstream, it invades red blood cells, making then more magnetic and more rigid.

These changes can be detected by various diagnostic devices, but they do not occur until the parasite has reached a more advanced stage, when the red blood cells have started sticking to small blood vessels, blocking circulation and causing severe symptoms.

The new device is sensitive to another property that is measurable in the earliest parasite stage, the ring stage. The property it measures is electrical resistance or impedance.

Chandrakasan, who is a principal investigator at MIT's Microsystems Technology Laboratories (MTL), and the Joseph F. and Nancy P. Keithley professor of electrical engineering, and colleagues managed to make the device so sensitive it can take very accurate measurements of the size and phase of electrical impedance of individual cells.

They also managed to find a way to stop the cells sticking to each other, and they eliminated interfering signals from the electrode substrate that the blood cells flow over.

In their study report, they describe how they tested the device on four types of cells: uninfected cells and cells containing the parasite in three different stages of development, known as ring, trophozoite and schizont.

Although the device was not sensitive enough to reliably differentiate the different stages of parasite development, the researchers were able to combine the measures mathematically so it could reliably differentiate between uninfected and infected cells, including those containing the ring stage of the parasite.

Matthias Marti, assistant professor of immunology and infectious diseases at the Harvard School of Public Health, did not take part in the study. But he describes the device as "really cool" because it can spot the difference between unifected red blood cells and blood cells infected with the parasite even when it is still very small and before it has had a chance to alter the cells very much.

The researchers hope their work will quickly lead to a portable and cheap testing kit that can rapidly diagnose malaria in places that have no labs and trained staff.

Although rapid diagnosis kits for malaria are starting to appear and are promising to overtake the traditional way of diagnosing malaria that requires a trained technician to examine blood smears under a microscope, these are not very sensitive.

"For a new device to be meaningful in the field, it would have to be more sensitive than these traditional approaches, as well as cheap and quick," says Marti.

The team is now working on converting the experimental device into something that can be realistically used in the field. For that, it will have to be portable, disposable and cheap.

They say it will also be interesting to see if they could use the device to detect malaria infection at the stage when the parasite is mature enough to pass to other humans, through mosquito bites.

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Written by Catharine Paddock PhD


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Electric impedance microflow cytometry for characterization of cell disease states; E. Du, Sungjae Ha, Monica Diez-Silva, Ming Dao, Subra Suresh, and Anantha P. Chandrakasan; Lab Chip 2013; DOI: 10.1039/C3LC50540E; Abstract/summary.

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