Laser-Driven Nanobubbles Noninvasively Detect Malaria

A noninvasive, laser scanner “vapor nanobubble” technology using no dyes or diagnostic chemicals can detect even a single malaria-infected cell among a million normal cells, with zero false-positive readings.

The transdermal diagnostic method, which recently completed its first preclinical tests at Rice University, takes advantage of the optical properties and nanosize of hemozoin, a nanoparticle produced by a malaria parasite inside infected red blood cells. The technology uses a low-power laser to create tiny vapor nanobubbles inside malaria-infected cells. The bursting bubbles have a unique acoustic signature that allows for an extremely sensitive diagnosis.

This graphic shows how a laser pulse creates a vapor nanobubble in a malaria-infected cell and is used to noninvasively diagnose malaria rapidly and with high sensitivity. Courtesy of E. Lukianova-Hleb/Rice University.

“Ours is the first through-the-skin method that’s been shown to rapidly and accurately detect malaria in seconds without the use of blood sampling or reagents,” said lead investigator Dmitri Lapotko, a Rice scientist who invented the vapor nanobubble technology.

Malaria is one of the world’s deadliest diseases, affecting more than 300 million people and killing more than 600,000 each year, most of them young children. Despite widespread global efforts, malaria parasites have become more resistant to drugs, and efficient epidemiological screening and early diagnosis are largely unavailable in the countries most affected by the disease.

Inexpensive rapid diagnostic tests exist, but they lack sensitivity and reliability. The gold standard for diagnosing malaria is a “blood smear” test, which requires a sample of the patient’s blood, a trained laboratory technician, chemical reagents and a high-quality microscope. These are often unavailable in low-resource hospitals and clinics in the developing world.

“The vapor nanobubble technology for malaria detection is distinct from all previous diagnostic approaches,” said co-author Dr. David Sullivan, a malaria clinician and researcher at the Malaria Research Institute at Johns Hopkins University. “The vapor nanobubble transdermal detection method adds a new dimension to malaria diagnostics, and it has the potential to support rapid, high-throughput and highly sensitive diagnosis and screening by nonmedical personnel under field conditions.”

One battery-powered device should be able to screen up to 200,000 people per year, with the cost of diagnosis estimated to be below 50 cents, Lapotko said.

Lapotko, a faculty fellow in biochemistry and cell biology and in physics and astronomy, and lead co-author Ekaterina Lukianova-Hleb found that hemozoin absorbs the energy from a short laser pulse and creates a transient vapor nanobubble. This short-lived vapor nanobubble emerges around the hemozoin nanoparticle and is detected both acoustically and optically with extraordinary sensitivity.

“The nanobubbles are generated on demand and only by hemozoin,” said Lukianova-Hleb, a research scientist in biochemistry and cell biology. “For this reason, we found that our tests never returned a false-positive result, one in which malaria was mistakenly detected in a normal uninfected cell.”

The first trials in humans are expected to begin in Houston in early 2014, Lapotko said.

The abstract of the preclinical study published this week in PNAS, “Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria,” is available here.

For more information, visit: www.rice.edu