Tag Archives: University of Oklahoma

Nanoscale measurements for osteoarthritis biomarker

There’s a new technique for measuring hyaluronic acid (HA), which appears to be associated with osteoarthritis. A March 12, 2018 news item on ScienceDaily makes the announcement,

For the first time, scientists at Wake Forest Baptist Medical Center have been able to measure a specific molecule indicative of osteoarthritis and a number of other inflammatory diseases using a newly developed technology.

This preclinical [emphasis mine] study used a solid-state nanopore sensor as a tool for the analysis of hyaluronic acid (HA).

I looked at the abstract for the paper (citation and link follow at end of this post) and found that it has been tested on ‘equine models’. Presumably they mean horses or, more accurately, members of the horse family. The next step is likely to be testing on humans, i.e., clinical trials.

A March 12, 2018 Wake Forest Baptist Medical Center news release (also on EurekAlert), which originated the news item, provides more details,

HA is a naturally occurring molecule that is involved in tissue hydration, inflammation and joint lubrication in the body. The abundance and size distribution of HA in biological fluids is recognized as an indicator of inflammation, leading to osteoarthritis and other chronic inflammatory diseases. It can also serve as an indicator of how far the disease has progressed.

“Our results established a new, quantitative method for the assessment of a significant molecular biomarker that bridges a gap in the conventional technology,” said lead author Adam R. Hall, Ph.D., assistant professor of biomedical engineering at Wake Forest School of Medicine, part of Wake Forest Baptist.

“The sensitivity, speed and small sample requirements of this approach make it attractive as the basis for a powerful analytic tool with distinct advantages over current assessment technologies.”

The most widely used method is gel electrophoresis, which is slow, messy, semi-quantitative, and requires a lot of starting material, Hall said. Other technologies include mass spectrometry and size-exclusion chromatography, which are expensive and limited in range, and multi-angle light scattering, which is non-quantitative and has limited precision.

The study, which is published in the current issue of Nature Communications, was led by Hall and Elaheh Rahbar, Ph.D., of Wake Forest Baptist, and conducted in collaboration with scientists at Cornell University and the University of Oklahoma.

In the study, Hall, Rahbar and their team first employed synthetic HA polymers to validate the measurement approach. They then used the platform to determine the size distribution of as little as 10 nanograms (one-billionth of a gram) of HA extracted from the synovial fluid of a horse model of osteoarthritis.

The measurement approach consists of a microchip with a single hole or pore in it that is a few nanometers wide – about 5,000 times smaller than a human hair. This is small enough that only individual molecules can pass through the opening, and as they do, each can be detected and analyzed. By applying the approach to HA molecules, the researchers were able to determine their size one-by-one. HA size distribution changes over time in osteoarthritis, so this technology could help better assess disease progression, Hall said.

“By using a minimally invasive procedure to extract a tiny amount of fluid – in this case synovial fluid from the knee – we may be able to identify the disease or determine how far it has progressed, which is valuable information for doctors in determining appropriate treatments,” he said.

Hall, Rahbar and their team hope to conduct their next study in humans, and then extend the technology with other diseases where HA and similar molecules play a role, including traumatic injuries and cancer.

Here’s a link to and a citation for the paper,

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor by Felipe Rivas, Osama K. Zahid, Heidi L. Reesink, Bridgette T. Peal, Alan J. Nixon, Paul L. DeAngelis, Aleksander Skardal, Elaheh Rahbar, & Adam R. Hall. Nature Communications volume 9, Article number: 1037 (2018) doi:10.1038/s41467-018-03439-x
Published online: 12 March 2018

This paper is open access.

Earthquakes, deep and shallow, and their nanocrystals

Those of us who live in this region are warned on a regular basis that a ‘big’ one is overdue somewhere along the West Coast of Canada and the US. It gives me an interest in the geological side of things  While the May 19, 2015 news items on Azonano featuring the research story as told by the University of Oklahoma and the University of California at Riverside doesn’t fall directly under my purview, it’s close enough.

Here’s the lead researcher, Harry W. Green II, from the University of California at Riverside explaining, the work,

The May 18, 2015 University of Oklahoma news release on EurekAlert offers a succinct summary,

A University of Oklahoma structural geologist and collaborators are studying earthquake instability and the mechanisms associated with fault weakening during slip. The mechanism of this weakening is central to understanding earthquake sliding.

Ze’ev Reches, professor in the OU School of Geology and Geophysics, is using electron microscopy to examine velocity and temperature in two key observations: (1) a high-speed friction experiment on carbonate at conditions of shallow earthquakes, and (2) a high-pressure/high-temperature faulting experiment at conditions of very deep earthquakes.

Reches and his collaborators have shown phase transformation and the formation of nano-size (millionth of a millimeter) grains are associated with profound weakening and that fluid is not necessary for such weakening. If this mechanism operates in major earthquakes, it resolves two major conflicts between laboratory results and natural faulting–lack of a thermal zone around major faults and the rarity of glassy rocks along faults.

The May 18, 2015 University of California at Riverside (UCR) news release provides more detail about earthquakes,

Earthquakes are labeled “shallow” if they occur at less than 50 kilometers depth.  They are labeled “deep” if they occur at 300-700 kilometers depth.  When slippage occurs during these earthquakes, the faults weaken.  How this fault weakening takes place is central to understanding earthquake sliding.

A new study published online in Nature Geoscience today by a research team led by University of California, Riverside geologists now reports that a universal sliding mechanism operates for earthquakes of all depths – from the deep ones all the way up to the crustal ones.

“Although shallow earthquakes – the kind that threaten California – must initiate differently from the very deep ones, our new work shows that, once started, they both slide by the same physics,” said deep-earthquake expert Harry W. Green II, a distinguished professor of the Graduate Division in UC Riverside’s Department of Earth Sciences, who led the research project. “Our research paper presents a new, unifying model of how earthquakes work. Our results provide a more accurate understanding of what happens during earthquake sliding that can lead to better computer models and could lead to better predictions of seismic shaking danger.”

The UCR news release goes on to describe the physics of sliding and a controversy concerning shallow and deep earthquakes,

The physics of the sliding is the self-lubrication of the earthquake fault by flow of a new material consisting of tiny new crystals, the study reports. Both shallow earthquakes and deep ones involve phase transformations of rocks that produce tiny crystals of new phases on which sliding occurs.

“Other researchers have suggested that fluids are present in the fault zones or generated there,” Green said. “Our study shows fluids are not necessary for fault weakening. As earthquakes get started, local extreme heating takes place in the fault zone. The result of that heating in shallow earthquakes is to initiate reactions like the ones that take place in deep earthquakes so they both end up lubricated in the same way.”

Green explained that at 300-700 kilometers depth, the pressure and temperature are so high that rocks in this deep interior of the planet cannot break by the brittle processes seen on Earth’s surface. In the case of shallow earthquakes, stresses on the fault increase slowly in response to slow movement of tectonic plates, with sliding beginning when these stresses exceed static friction. While deep earthquakes also get started in response to increasing stresses, the rocks there flow rather than break, except under special conditions.

“Those special conditions of temperature and pressure induce minerals in the rock to break down to other minerals, and in the process of this phase transformation a fault can form and suddenly move, radiating the shaking – just like at shallow depths,” Green said.

The research explains why large faults like the San Andreas Fault in California do not have a heat-flow anomaly around them. Were shallow earthquakes to slide by the grinding and crunching of rock, as geologists once imagined, the process would generate enough heat so that major faults like the San Andreas would be a little warmer along their length than they would be otherwise.

“But such a predicted warm region along such faults has never been found,” Green said.  “The logical conclusion is that the fault must move more easily than we thought.  Extreme heating in a very thin zone along the fault produces the very weak lubricant.  The volume of material that is heated is very small and survives for a very short time – seconds, perhaps – followed by very little heat generation during sliding because the lubricant is very weak.”

The new research also explains why faults with glass on them (reflecting the fact that during the earthquake the fault zone melted) are rare. As shallow earthquakes start, the temperature rises locally until it is hot enough to start a chemical reaction – usually the breakdown of clays or carbonates or other hydrous phases in the fault zone.  The reactions that break down the clays or carbonates stop the temperature from climbing higher, with heat being used up in the reactions that produce the nanocrystalline lubricant.

If the fault zone does not have hydrous phases or carbonates, the sudden heating that begins when sliding starts raises the local temperature on the fault all the way to the melting temperature of the rock.  In such cases, the melt behaves like a lubricant and the sliding surface ends up covered with melt (that would quench to a glass) instead of the nanocrystalline lubricant.

“The reason this does not happen often, that is, the reason we do not see lots of faults with glass on them, is that the Earth’s crust is made up to a large degree of hydrous and carbonate phases, and even the rocks that don’t have such phases usually have feldspars that get crushed up in the fault zone,” Green explained. “The feldspars will ‘rot’ to clays during the hundred years or so between earthquakes as water moves along the fault zone. In that case, when the next earthquake comes, the fault zone is ready with clays and other phases that can break down, and the process repeats itself.”

The research involved the study of laboratory earthquakes – high-pressure earthquakes as well as high-speed ones – using electron microscopy in friction and faulting experiments. It was Green’s laboratory that first conducted a serendipitous series of experiments, in 1989, on the right kind of mantle rocks that give geologists insight into how deep earthquakes work. In the new work, Green and his team also investigated the Punchbowl Fault, an ancestral branch of the San Andreas Fault that has been exhumed by erosion from several kilometers depth, and found nanometric materials within the fault – as predicted by their model.

Here’s a link to and a citation for the paper,

Phase transformation and nanometric flow cause extreme weakening during fault slip by H. W. Green II, F. Shi, K. Bozhilov, G. Xia, & Z. Reches. Nature Geoscience (2015) doi:10.1038/ngeo2436 Published online 18 May 2015

This paper is behind a paywall.