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Rapid test would help clinics detect Ebola early, prevent epidemics.
August 1, 2017

Tony Hu aims to make new test as simple and accessible as possible, using equipment already found in most hospitals and labs

To catch a serial killer, homicide detectives must quickly and accurately find clues. Trace evidence left at a crime scene may eventually reveal the killer’s presence and identity, but the detectives first have to know what to look for.

Like a criminal hiding in plain sight, contagious pathogens spread by capitalizing on the delay between initial infection and telltale symptoms in their hosts. That reality was painfully clear during the 2014 Ebola outbreak when clinics struggled to prevent transmission from patients to caregivers overwhelmed by the disease. The deadly virus traveled across continents before its symptoms were detected and the infected patients were quarantined.

The 2014 epidemic subsided, but recent cases in the Congo indicate the virus is still an active threat. In preparation for future outbreaks, researchers are racing to equip field clinicians with diagnostic tools that will detect virus-infected individuals early to prevent new epidemics.

One of those tools is a nanotechnology platform developed by Arizona State University engineer Tony Hu  that detects disease molecules in blood samples. In this assay, diluted patient blood samples are mixed with porous silicon nanodisks (pSiNDs). A machine called a mass spectrometer (MS) measures the mass of all the molecules bound by these pSiNDs. The method, known as pSiND-MS, is very sensitive and can identify specific amino acid sequences of peptides belonging to viruses like Ebola.

“Ebola is a disease, but it is also a family. For each strain, the treatment can be different. We want to develop a method that only uses one step, one method [to identify these strains],” said Hu (pictured above).

Hu, a researcher at the Virginia Piper Center for Personal Diagnostics at ASU’s Biodesign Institute and associate professor at the Ira A. Fulton Schools of Engineering, previously applied the pSiND-MS method to Tuberculosis testing and succeeded in reducing the diagnosis time from days to mere hours. He plans to apply a similar approach to Ebola by using the pSiND-MS method to improve detection of three telltale biomarkers in Ebola patient blood samples.

These three biomarkers are peptide sequences. The virus produces one of these peptides, Ebola antigen VP40, soon after infection. The other two peptides, Serum Amyloid A and alpha-1-antichymotrypsin, are produced by the patient’s immune system in response to the infection.

“Once you enrich the antigen directly from the blood, then we have some special way to digest this antigen and profile their fragment picture landscape on the mass spec,” Hu said.

All three peptides are detectable in blood samples even before viral particles themselves are detectable. They are a trio of clues that reveal in just two hours whether a person has contracted Ebola.

Thanks to a new grant from the National Institutes of Health, Hu’s lab will partner with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) to improve and expand the rapid Ebola test even further. Hu’s lab is located at ASU’s Biodesign Institute, but USAMRIID’s Biosafety Level-4 facility in Fort Detrick, Maryland, will conduct all the Ebola experiments.

The two primary goals of partnering with USAMRIID are to refine the pSiND-MS method for detecting and counting the three Ebola biomarkers. The researchers also want to determine how different patterns of these biomarkers correlate with different strains of Ebola.

Hu aims to make the new test as simple and accessible as possible, which is why it relies on mass spectrometers commonly found in most hospitals and laboratories.

Sharing diagnostic data quickly between rural clinics, hospitals and laboratories significantly improves management of contagious epidemics. Equipping caregivers with simple, sensitive and rapid tools is a pivotal weapon in the struggle to detect and contain viral outbreaks before they claim more victims.

 

Top photo: ASU bioengineer Tony Hu discusses his partnership with the U.S. Army to develop faster diagnostic tests for Ebola. Photo by Jason Drees/Biodesign Institute

Grace Clark

Student Assistant Science Writer , Biodesign Institute

480-727-8140

 
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ASU geoscientists explain puzzling pockets of rock deep in Earth's mantle

Isolated pockets of rock in Earth's mantle have puzzled scientists — until now.
August 2, 2017

A team led by geoscientists from Arizona State University and Michigan State University has used computer modeling to explain how pockets of mushy rock accumulate at the boundary between Earth's core and mantle.

These pockets, lying roughly 2,900 kilometers (1,800 miles) below the surface, have been known for many years but previously lacked an explanation of how they formed.

The relatively small rock bodies are termed "ultra-low velocity zones" because seismic waves greatly slow down as they pass through them. Geoscientists have thought the zones are partially molten, yet the pockets are puzzling because many are observed in cooler regions of the deep mantle.

"These small regions have been assumed to be a partially molten version of the rock that surrounds them," said Mingming Li, lead author of the study, which was published today in the journal Nature Communications. "But their global distribution and large variations of density, shape and size suggest that they have a composition different from the mantle."

Li joined ASU's School of Earth and Space Exploration this month as an assistant professor. He was a graduate student of former ASU Associate Professor Allen McNamara, also a co-author on the paper; McNamara is now at Michigan State's Department of Earth and Environmental Sciences. The additional co-authors are ASU Professor Edward Garnero and his doctoral student Shule Yu.

“We don’t know what ultra-low velocity zones are,” said McNamara. “They are either hot, partially molten portions of otherwise normal mantle, or they are something else entirely, some other composition."

Because seismic evidence allows both possibilities, he said, "We decided to model mantle convection by computer to investigate whether their shapes and positions can answer the question.”

Do pockets relate to blobs?

About year ago, Garnero, McNamara and School of Earth and Space Exploration Associate Professor Dan Shim reported that two gigantic structures of rock deep in the Earth are likely made of something different from the rest of the mantle. They called the large structures "thermochemical piles," or more simply, blobs.

"While the origin and composition of these blobs are unknown," Garnero said at the time, "we suspect they hold important clues as to how the Earth was formed and how it works today."

What the big blobs are made of and how they formed still remain unknown, said Garnero. "But the new computer modeling explains how these ultra-low velocity zones are associated with the much bigger blobs."

Li said, "The ultra-low velocity zones are generally around tens of kilometers tall, and hundreds of kilometers wide or less. They are mostly located near the edges of the much larger blobs, but some of them are detected both inside the blobs and well away from them."

Tiny regions of compositionally distinct rock (red material, known as ultra-low velocity zones), collect at Earth’s core-mantle boundary (tan surface), nearly halfway to the center of our planet. Small accumulations of this distinct rock collect near the margins of large thermochemical piles (green) that reside at the base of Earth’s mantle. Image by Edward Garnero/ASU

The outcome of the computer modeling showed that most of these ultra-low velocity zones are different in composition from the surrounding mantle, Li said. What's more, the modeling showed that pockets of rock with different compositions will migrate from anywhere on the core-mantle boundary toward the margins of the large blobs.

"The margins of the thermochemical piles are where mantle flow patterns converge," McNamara said, "and therefore these areas provide a 'collection depot' for denser types of rock."

Gathered by heat

The force driving this movement is heat, which powers convection in the mantle.

Earth's mantle is made of hot rock, but it behaves more like fudge simmering slowly on a stove. In the mantle, heat comes both from radioactivity within the mantle rock and from the planet's core, the center of which is about as hot as the sun's surface. Mantle rock responds to this heat with a slow churning — convective — motion.

"The details are not completely clear," Li said. But the modeling shows that rocks of different composition respond to the convection in a way that gathers compositionally similar materials together. This moves the small pockets of chemically distinct rocks to the edges of the hotter blobs above the core-mantle boundary.

"We ran 3-D high-resolution computer modeling, and we developed a method to track the movement of both the small pockets of ultra-low velocity zones and the much larger thermochemical piles." Li explained. "This allowed us to study how the small pockets move around and how their locations can be related to their origin."

McNamara said, "What was new about our approach — and also computationally challenging — was that the modeling simultaneously took into account vastly different scales of motion." These ranged from global mantle-scale convection patterns, to the large thermochemical piles in the lower mantle, and down to the very small-scale pockets of ultra-low velocity zone at the bottom.

"What we ultimately found," he said, "is that if ultra-low velocity zones are caused by melting of otherwise normal mantle, they should be located well inside of the thermochemical piles, where mantle temperatures are the hottest."

But he added, "If the ultra-low velocity pockets of rock have a composition different from the ordinary mantle rock, then mantle convection would continually carry them to the edges of piles where they collect.

"This is consistent with what we see in the seismic observations.”

Rocks diving deep?

Where do the different materials in the deep mantle come from in the first place?

"There are several possibilities," Garnero said. "Some material might be associated with former basaltic oceanic crust that got subducted deeply. Or it might be associated with chemical reactions between the outer core's iron-rich fluid and the crystalline silicate mantle."

Garnero said that where the rock in ultra-low velocity zones originally came from is currently unsolved. But the process of collecting this material into small pockets of rock is clear.

"You can have various mechanisms, such as plate tectonics, that push rock of differing chemistries into the deepest mantle anywhere on Earth," he said.

"But once these different rocks have gone down deep, convection wins and sweeps them to the hot regions, namely, where the continental-sized thermochemical piles reside."

Robert Burnham

Science writer , School of Earth and Space Exploration

480-458-8207