Turning biological cells to stone improves cancer and stem cell research

Sandia researchers Bryan Kaehr (1815) and Kristin Meyer (1815) analyze a silicized surface using optical microscopy and multiphoton fluorescence. (Photo by Randy Montoya)

by Neal Singer

Changing flesh to stone sounds like the work of a witch in a fairy tale.

But a new technique to transmute living cells into more permanent materials that defy rot and can endure high-powered probes is widening research opportunities for biologists who are developing cancer treatments, tracking stem cell evolution, or even trying to understand how spiders vary the quality of the silk they spin.

The simple, silica-based method also offers materials scientists the ability to “fix” small biological entities like red blood cells into more commercially useful shapes. And, at least in theory, the method can transmute naturally grown objects like livers and spleens into non-organic, “zombie” replicas that function simultaneously at a variety of length scales in more sophisticated ways than the most advanced machinery can produce.

 “Why go to the trouble of making objects, if nature will do it for you?” asks Sandia lead investigator Bryan Kaehr (1815).

The unusual method has been the subject of papers in Proceedings of the National Academy of Sciences, the Journal of the American Chemical Society (JACS), and most recently, Nature Communications.

Perfectly replicated cells

The initial insight came when Bryan and then-University of New Mexico postdoctoral student Jason Townson discovered that the silica slurry they were using had an unexpected property: At a reasonably low pH level, the silica molecules, instead of clotting with each other, bound only to surfaces against which they rested, forming the thinnest of coatings.

Bryan wondered if a similar coating on biological cells would strengthen cell structures so they could be examined for longer periods with more powerful tools. So the researchers put cultured tissue cells in a silica solution and let the mix harden overnight. Then they raised the temperature to burn off the biomaterial. What remained, astonishingly, were perfectly replicated cells, like little row houses of glass.

The replicated cells were so sturdy that Bryan surmised that the slurry must have coated the cells inside as well as out. Breaking a row of cells as one would a tiny pane of glass, the team examined their interiors with an electron microscope. They found they had indeed replicated the nanoscopic organelles of the cell as well as its exterior. They had discovered a way to create a near-perfect silica counterfeit of a biological organism, from its overall shape down to its nanostructures.

This initial result is already being used by biologists in Finland to create three-dimensional models that preserve the different stages of stem cells as they evolve to their final form, says Sandia Fellow and paper co-author Jeff Brinker (1000), who is also a UNM professor. 

Townson, now on the faculty at UNM, uses the method to research the movements of cancer-fighting nanoparticles inserted into chicken cells prior to their conversion to silica. “With optical microscopy, it is difficult to form an image of the interactions of nanoparticles with cells while preserving a three-dimensional context,” he said. Bioreplication, where the sample can be mechanically dissected and investigated with electron microscopes, offers better three-dimensional resolution at the nanoscale.

The method is also being used in England’s Oxford University to study the internal biological changes by which spiders create different types of silk, adjusting their mechanisms on the fly (so to speak) to create thicker or stickier strands, says Jeff.

Permanent alterations

In the JACS article, Bryan’s group showed they could use the silica technique to make permanent alterations in natural objects. They introduced chemicals that transformed red blood cells from life-saver-like objects to spikey spheres. By then introducing the silica slurry to the dish containing the altered red blood cells and letting the mixture harden, Bryan and colleagues made the change permanent. Burning off the protoplasmic original, the team was left with microparticles that might be useful in rubber composites created by tire companies that routinely insert silica spheres in their tire mix for additional strength. Manufacturers would no longer need an energy-consuming factory to make the inserted material which, by bioreplication, would form cheaply and easily. 

“I have a proposal with a major tire manufacturer to use this method to create tire additives,” says Bryan. “Our method has good potential over traditional silica additives, and its raw material — blood — is considered a waste product in the meat industry. I’ve done a back-of-the-envelope calculation as to its potential yield from bovines per year; it would work.”

In addition to food industry waste products, he says, “there’s a huge amount of harmless bacteria out there we could co-opt to create still other shapes.” Bacteria are harder to harvest, he says, because they are protected by a double sheath against silica invasion, but it could be done.

In the Nature Communications paper, Bryan and colleagues took the same technique a step further.  They took a liver, submerged it in a silica solution, and then heated it anaerobically to come up with a hardened, carbonized, exact duplicate of the liver, from centimeter to nanometer scales.

“We let nature do the work,” he says, “because we don’t yet know how to build an object accurately across six length scales from centimeter to nanometers.

“Think about electrodes in batteries,” he says. “That’s a three-dimensional question.  Now in livers and spleens, for example, evolution has already optimized absorption and diffusion in a three-dimensional organization. The liver is a marvelously effective organ with tremendous surface area for absorption and an unparalleled ability to release materials in channels ranging from large arteries to capillaries a few micrometers wide.

 “If we transfer the hierarchical structure of a liver to an electrode, rather than having just a passive piece of solid material, the zombie result would have greater surface area per volume, greater energy storage, and have a creation that is already optimized to output fluids and small particles to much larger highways like large veins and arteries.”

The carbonized method also can be used to better examine cancers and other growths without the often tedious and expensive processes normally necessary to “fix,” process and stabilize the organic material for examination and prevent it from falling apart under electron-beam analysis. Carbon, because it conducts electricity instead of absorbing it, is not weakened and destroyed like protoplasm.

This creative consideration of the possibilities of the natural world in new and dizzying ways is in line with Bryan’s research sponsor — DOE’s Office of Science, which is interested, he says in “the exploration, discovery and design of biomimetic materials.”

Portions of this work were performed at the Center for Integrated Nanotechnologies and DOE Office of Science user facility, jointly led by Los Alamos and Sandia National Laboratories. 

Sandia and UNM have applied for a joint patent on the set of methods.


-- Neal Singer

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Storing hydrogen underground could boost transportation, energy security

Salt caverns such as the one depicted here could provide a low-cost solution for the geologic storage of hydrogen. The colors in the illustration represent depth, with blue as the deepest part of the cavern and red the most shallow.

by Mike Janes

Large-scale storage of low-pressure, gaseous hydrogen in salt caverns and other underground sites for transportation fuel and grid-scale energy applications offers several advantages over above-ground storage, says a recent Sandia study sponsored by the Department of Energy’s Fuel Cell Technologies Office.

Geologic storage of hydrogen gas could make it possible to produce and distribute large quantities of hydrogen fuel for the growing fuel cell electric vehicle market, the researchers concluded.

Geologic storage solutions can service a number of key hydrogen markets since “costs are more influenced by the geology available rather than the size of the hydrogen market demand,” says Anna Snider Lord (6912), the study’s principal investigator.

The work, Anna says, could provide a roadmap for further research and demonstration activities, such as an examination of environmental issues and geologic formations in major metropolitan areas that can hold gas. Researchers could then determine whether hydrogen gas mixes with residual gas or oil, reacts with minerals in the surrounding rock, or poses any environmental concerns.

Storage seen as key to realizing hydrogen’s market growth

Should the market demands for hydrogen fuel increase with the introduction of fuel cell electric vehicles, the US will need to produce and store large amounts of cost-effective hydrogen from domestic energy sources, such as natural gas, solar, and wind, says Daniel Dedrick (8367), Sandia hydrogen program manager.

As Toyota, General Motors, Hyundai, and others move ahead with plans to develop and sell or lease hydrogen fuel cell electric vehicles, practical storage of hydrogen fuel at large scale is necessary to enable widespread hydrogen-powered transportation infrastructure. Such storage options, Daniel says, are needed to realize the full potential of hydrogen for transportation.

Additionally, installation of electrolyzer systems on electrical grids for power-to-gas applications, which integrate renewable energy, grid services, and energy storage, will require large-capacity, cost-effective hydrogen storage.

Storage above ground requires tanks, which cost three to five times more than geologic storage, Anna says. In addition to cost savings, underground storage of hydrogen gas offers advantages in volume. “Above-ground tanks can’t even begin to match the amount of hydrogen gas that can be stored underground,” she says.

The massive quantities of hydrogen stored in geologic features can subsequently be distributed as a high-pressure gas or liquid to supply hydrogen fuel markets.

Model helps identify the most favorable storage locations

While geologic storage may prove to be a viable option, several issues need to be explored, says Anna, including permeability of various geologic formations.

A geologist in Sandia’s geotechnology and engineering group, Anna for years has been involved in the geologic storage of the US Strategic Petroleum Reserve, the world’s largest emergency supply of crude oil.

For her study on geologic storage, Anna and her colleagues analyzed and reworked the geologic storage module of Argonne National Laboratory’s Hydrogen Delivery Scenario Analysis Model. To help refine the model, Anna studied storing hydrogen in salt caverns to meet peak summer driving demand for four cities: Los Angeles, Houston, Pittsburgh, and Detroit.

She determined that 10 percent above the average daily demand for 120 days should be stored. She then modeled how much hydrogen each city would need if hydrogen met 10, 25, and 100 percent of its driving fuel needs.

Los Angeles has three times the population of Detroit and more than six and a half times the population of Pittsburgh, but the nearest salt formations are in Arizona, so Anna included the cost of getting the stored hydrogen from Arizona to Los Angeles.

Even so, Los Angeles’ modeled costs are significantly less than those for Detroit and Pittsburgh. Salt formations in Arizona are thicker than those for Detroit and Pittsburgh, with larger and fewer caverns. Houston has the best conditions of the four cities because the Gulf Coast offers large, deep salt formations.

To examine the cost of geologic hydrogen storage, Anna started by selecting geologic formations that currently store natural gas. Working with Sandia economist Peter Kobos (6926), Anna analyzed costs to store hydrogen gas in depleted oil and gas reservoirs, aquifers, salt caverns, and hard rock caverns.

Their paper, “Geologic storage of hydrogen: Scaling up to meet city transportation demands,” was published in the International Journal of Hydrogen Energy.

A geologic solution for peak period storage

Other fuels are already stored geologically. Oil from the Strategic Petroleum Reserve, for example, is held in large man-made caverns along the Gulf Coast. Natural gas is stored in more than 400 geologic sites to meet winter heating demands.

Anna envisions that excess hydrogen produced throughout the year could be brought to geologic storage sites and then piped to cities during the summer, when the demand for driving fuels peaks.

Depleted oil and gas reservoirs and aquifers initially seem the most economically attractive options, she says. “Just looking at numbers, because they can hold such a larger volume relative to any cavern you create, they look cheaper,” she says.

But hydrogen gas is a challenging substance to store. “Because it’s a smaller molecule than methane, for example, it has the potential to leak easier and move faster through the rock,” Anna says.

Depleted oil and gas reservoirs and aquifers could leak hydrogen, and cycling — filling a storage site, pulling hydrogen out for use and refilling the site — can’t be done more than once or twice a year to preserve the integrity of the rock formation, Anna says.

With a salt cavern or hard rock cavern, “there are no permeability issues, there’s really no way anything can leak,” she says. “You can bring more product in and out, and that will, in the long run, decrease your costs.”

Hard rock caverns are relatively unproven; only one site holds natural gas. But salt caverns, which are created 1,000 to 6,000 feet below ground by drilling wells in salt formations, pumping in undersaturated water to dissolve the salt, then pumping out the resulting brine, are used more extensively and already store hydrogen on a limited scale, Anna says.

Future challenges

Anna says her work could lead to demonstration projects to further cement the viability of underground hydrogen storage. Salt caverns are the logical choice for a pilot project due to their proven ability to hold hydrogen, she says. Environmental concerns such as contamination could also be further analyzed.

However, salt formations are limited. None exist in the Pacific Northwest, much of the East Coast and much of the South, except for the Gulf Coast area. Other options are needed for development of a nationwide hydrogen storage system.

Anna’s work adds to Sandia’s capabilities and decades of experience in hydrogen and fuel cells systems. Sandia leads a number of other hydrogen research efforts, including the Hydrogen Fueling Infrastructure Research and Station Technology (H2FIRST) project co-led by the National Renewable Energy Laboratory (NREL), a maritime fuel cell demonstration, a development project focused on hydrogen-powered forklifts, and a recent study of how many California gas stations can safely store and dispense hydrogen.


-- Mike Janes

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Sandia turns on Sky Bridge supercomputer

COOL GUY — Dave Martinez (9324) shows off the new Sky Bridge installation. Dave is the Facilities project lead and is responsible for making sure the supercomputer gets power and cooling. He has been a key innovator for Sandia’s corporate data centers and has enabled us the Labs to deploy new technologies in power and cooling in machines such as Sky Bridge.

by Neal Singer

A ribbon-cutting ceremony for the 600-teraflop Sky Bridge supercomputer, the most powerful institutional machine ever acquired by Sandia, will be held on Dec. 18.

Sky Bridge’s new home at one time housed ASCI Red, the world’s first teraflop computer. Technical advances have enabled Sky Bridge, with nearly 600 times the computational muscle, to draw only two-thirds the electrical power and require about half the space of its illustrious predecessor.

The efficiently water-cooled machine also should cost about 50 percent less to operate than comparable air-cooled machines, and will execute the newest computer programs well enough to “enable new solutions to difficult national security-related problems,” says John Noe, manager of Scientific Computing Systems (9328).

Sky Bridge will increase Sandia’s mission-computing capacity by nearly 40 percent, providing 259 million processor hours per year across its 1,848 nodes.

Sky Bridge was funded with $10 million through the newly launched Institutional Computing program, which itself was created by an executive leadership decision to support large-scale computing as an ongoing Laboratories capability. 

The machine is considered a capacity cluster, which means it can handle a broad range of small- to medium-size workloads while running multiple problems at the same time, says Steve Monk (9328).

“In dedicated access mode, it can be used to solve problems that require lots of compute capability, but that is not its normal operations model,” Steve says.

One factor in the acquisition decision was the cost savings associated with the liquid-cooled system, says John. “The facilities cost for a hybrid liquid/air-cooled system was 50 percent of the cost of a completely air-cooled system, because the latter would have required many computer-room air conditioners. And it should be cheaper to run.” 

The liquid-cooling option also reduces noise to less-than-hazardous levels, meaning that operations personnel do not require hearing protection to service Sky Bridge.

Lest anyone think that Sandians would jubilate over unproven cost savings, “We have a unique opportunity to measure identical systems, one air-cooled in another computer and one hybrid liquid/air cooled (Sky Bridge) to determine the exact operating cost differences,” says John.

Built by Cray Inc., Sky Bridge relies on the same generation of hardware found on the successful (though air-cooled) Tri-Lab Linux capacity cluster supercomputers installed at Sandia, Los Alamos, and Lawrence Livermore national laboratories.

Sandia’s new Institutional Computing program also provides funds to augment traditional scientific computing platforms with specialized systems that perform well on informatics, graph analysis, big data searches, “emulytics,” and other burgeoning problem areas.  Emulytics is a Sandia-coined term indicating “the practice of using a powerful computer or network of computers to emulate a highly complex but unmanageable system in an attempt to gain knowledge about the behavior of the larger system,” says John. 

Sky Bridge should be available to Sandia HPC users in January.





-- Neal Singer

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