MIT scientists say they have found a way to detect early-stage malarial infection of blood cells by measuring changes in the infected cells’ electrical properties.

The research team, from the laboratories of MIT’s Anantha Chandrakasan, Ph.D., and Subra Suresh, Sc.D., who is now president of Carnegie Mellon University, built an experimental microfluidic device that takes a drop of blood and streams it across an electrode that measures a signal differentiating infected cells from uninfected cells.

“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,” says Dr. Chandrakasan, the Joseph F. and Nancy P. Keithley professor of electrical engineering and a principal investigator at MIT’s Microsystems Technology Laboratories.

When the malaria parasite Plasmodium falciparum infects a red blood cell, the cell becomes more magnetic and more rigid, properties that can be detected in a rapid-diagnostic device. But these changes are hard to detect before the parasite matures beyond the ring stage, its earliest stage, and the only stage found in circulating blood. At later stages of infection, the infected red blood cells adhere to small capillaries, blocking circulation and causing various symptoms, and even death in severe cases.

The researchers decided to look into using electrical impedance as a diagnostic signal. Several types of infection, including malaria, alter a cell’s impedance, a measure of electrical resistance across the cell membrane. Studies had already measured electrical changes in later-stage infected cells, but it wasn’t clear that cells that had reached only the ring stage of infection would exhibit electrical changes.

To find out, first authors Sungjae Ha, a graduate student in the Chandrakasan lab, and Sarah Du, Ph.D., a postdoc in the Suresh lab, built a microfluidic device capable of measuring the magnitude and phase of the electrical impedance of individual cells. The device is essentially a cell-counting device, similar in approach to other low-cost, portable devices being developed to diagnose illnesses such as HIV.

In tests of cells of four cell types—uninfected cells and infected cells at the ring, trophozoite, and schizont stages—the device detected small differences in measures of magnitude and seemingly random differences in phase, but not quite enough to definitively differentiate among stages.

However, a mathematical combination of the measures into an index called delta allowed the differences between uninfected cells and all three stages to become clear.

Traditionally, technicians detect malarial infection visually, by observing blood smears through a microscope. More recently, the World Health Organization has supported the use of rapid diagnostic tests that detect an antigen to the parasite in the blood. These tests provide results in about 15 minutes and do not require skilled technicians, so sick people can be diagnosed and treated on the spot.

The next steps for further development involve integrating this new technology into a small, low-cost package.

“Our hope is that such technologies as those described in this work will ultimately help meet the need for a new generation of portable, disposable, and inexpensive diagnostics for a variety of human diseases,” says Dr. Suresh.

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