Early infection detection

MIT team unveils work on microfluidic device for early-stage malaria detection

Kelsey Kaustinen
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CAMBRIDGE, Mass.—Malaria, a mosquito-transmitted diseasethat results in high fevers, chills and anemia, is still an endemic issue inmany parts of the world. Prevention efforts are helping to slow the spread, anddevelopment of vaccine candidates is underway, but there is still room forimprovement in detecting malaria in its early stages.
That is the goal of scientists from the laboratories ofAnantha Chandrakasan and Subra Suresh at the Massachusetts Institute ofTechnology (MIT). This team has created an experimental microfluidic devicethat can detect early-stage malarial infection by streaming a single drop ofblood across an electrode that measures a signal distinguishing infected cellsfrom uninfected cells. The research was published Aug. 8 in Lab on a Chip.
The basis of this detection approach focuses on theelectrical signatures of infected cells. As noted by the World HealthOrganization (WHO) on its website, malaria is caused by the parasite Plasmodiumfalciparum, which is transmitted to humansby mosquitoes. After being infected, the parasites multiply in the liver, theninfect red blood cells. When the malaria parasite infects a red blood cell, itbecomes more magnetic and rigid. These changes are hard to detect, however,before the parasite matures past the ring stage, which is the earliest stage,and the only one found in circulating blood. Later in the infection, theinfected cells stick to small capillaries.
Given those properties, the researchers decided toinvestigate the possibility of using electrical impedance, a measure ofelectrical resistance across the cell membrane, as a diagnostic signal. Whilestudies had already examined electrical changes in infected cells in laterstages of the disease, it wasn't known if cells in the early, ring stage ofinfection would demonstrate the same charges. 
Sungjae Ha, a graduate student in the Chandrakasan lab, andSarah Du, a postdoc in the Suresh lab, decided to test this by building amicrofluidic device that could measure the magnitude and phase of theelectrical impedance of individual cells. Ha and Du are first authors of thestudy.
The team tested four cell types while optimizing the device:uninfected cells, and infected cells at the ring, trophozoite and schizontstages. Small differences were detected between each, but nothing significantenough to distinguish between stages. They then mathematically combined themeasures into an index known as delta, at which point the differences betweenuninfected cells and infected cells at all three stages became clear.
The current standard for detecting malarial infection is theobservation of blood smears under a microscope, and recently there have beensome diagnostic tests that detect an antigen to the parasite in the blood.Unfortunately, neither approach has the desired sensitivity. WHO notes on itswebsite that "microscopy remains the mainstay of malaria diagnosis in mostlarge health clinics and hospitals, but the quality of microscopy-baseddiagnosis is frequently inadequate."
"What's really cool about this device is that it canactually differentiate between uninfected red blood cells and circulating ringinfected red blood cells, even though the parasite is still very small at thisstage and the host cells have hardly been modified," Matthias Marti, anassistant professor of immunology and infectious diseases at the Harvard Schoolof Public Health, said in a press release. Marti did not participate in thestudy, but noted this device might also be capable of picking out cellsinfected with Plasmodium falciparumduring its transmission stage.
As development continues, the MIT team is working tointegrate the technology into a small, low-cost package. They also plan toinvestigate whether it could be used to examine the electrical properties ofother types of diseased cells to determine if this approach could be usedbroadly for diagnostics.
"Our hope is that such technologies as those described inthis work will ultimately help meet the need for a new generation of portable,disposable and inexpensive diagnostics for a variety of human diseases," saidSuresh.
According to WHO, some 3.3 billion people are at risk ofmalaria. Roughly 219 million cases of malaria were reported in 2010 (with anuncertainty range of 154 million to 289 million), with an estimated 660,000deaths (with an uncertainty range of 490,000 to 836,000). Fortunately, diseaseprevention and control measures have reduced malaria death rates by more than25 percent since 2000.

Kelsey Kaustinen

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