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[Sandia Lab News]

Vol. 55, No. 19           September 19, 2003
[Sandia National Laboratories]

Albuquerque, New Mexico 87185-0165    ||   Livermore, California 94550-0969
Tonopah, Nevada; Nevada Test Site; Amarillo, Texas

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Sandia nanolaser may help extend life-spans by rapidly analyzing possible neuroprotectant drugs Sandia, Los Alamos, NM Tech to team on 'energetic materials' research Sandia researchers seek ways to lower the cost of wind energy in less-than-optimal locations Jeff Brinker, Jim Gosler appointed Sandia Fellows

Sandia nanolaser may help extend life-spans by rapidly analyzing possible neuroprotectant drugs

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By Neal Singer

Anyone visiting a nursing home has seen the horror of humans living on beyond their brains' ability to make sense of their surroundings.

That loss of discrimination is caused by neurons killed by malfunctions in mitochondria -- the submicron-sized power packs found in every animal cell.

These malfunctions -- the 'dark side' of the otherwise 'white hat,' life-supporting organelle -- are the most immediate cause of afflictions like Parkinson's, Huntington's, and Alzheimer's diseases.

Malfunctioning mitochondria have also been linked to battlefield aftereffects caused by radiation or by nerve agents like sarin.

Because these malfunctions are caused in part by the actions of excess calcium ions in each cell, "'Waterproofing' the mitochondria with specific protectant drugs would increase the survival chances of the brain," says Marcus Keep, a neurosurgeon professor at the University of New Mexico School of Medicine.

But because mitochondria are so small, averaging a few hundred nanometers, scientists have been unable to study them in vitro with the necessary precision to determine the best possible neuroprotectants.

Now basic research at Sandia on a unique nanolaser has demonstrated the first-ever technique for rapidly studying the reactions of such ultrasmall biological organisms in their functioning state as they are subjected to neuroprotectant drugs.

"Our goal is make the brain less susceptible to diseases like Lou Gehrig's," says Sandia researcher Paul Gourley (1141), a physicist who grew up in a family of doctors. "But the subject is even bigger. If we can use this light probe to understand how mitochondria in nerve cells respond to various stimuli, we may be able to understand how all cells make life-or-death decisions -- a step on the road, perhaps, to longer lives."

How does the cell self-destruct?

To do that, he says, scientists must understand how a cell self-destructs, which means understanding how mitochondria send out signals that kill cells as well as energize them.

Mitochondria have long been known as the mechanism that produces ATP, the universal energy driver for animal life. ATP powers each cell like gas powers each automobile. But scientists have found that the tiny power plants have another function. When cells are signaled to die -- acceptably, as when biomaterial is shed from a uterus during its periodic menstrual cycle, or unacceptably, as the result of certain neurological diseases -- an excess of calcium ions and free radicals emerging from chemical reactions in the body open a large pore in the inner membrane in that cell's mitochondria. The pore enables release of a protein called cytochrome C that kills the cell. Meanwhile, the mitochondrion itself swells and explodes. One way to stop this suicidal process would be to find a chemical that would shield the mitochondria from these intruders.

The observation technique developed at Sandia to test for such effects came about almost by accident. In the innovative lab arrangement already developed by Paul's group, a micropump sends fluids containing suspect material through a submicron-sized lasing cavity. The cavity is formed between a light-emitting semiconductor and a reflective mirror.

The research group expected to push fluid containing mitochondria through the device and to see very weak signals emanating from the tiny organelles. Had this been true, signal-averaging techniques would have been necessary to generate a generalized, necessarily less crisp estimate of responses.

"We were pleasantly surprised but puzzled to see very large signals from each mitochondrion," Paul says. "A statistical average was unnecessary."

The researchers realized that each mitochondrion acted as a lens for light passing through it because the organelle had a higher index of refraction (1.42) than water (1.33). Light refracted into the mitochondria in effect emerged amplified. It was exactly analogous to a lens concentrating light passing through it.

"When a critical concentration of emitted photons is reached," says Paul, "stimulated emission of additional photons occurs in the semiconductor."

These photons, as well as those reflected from the mirror, retrace their paths back through the mitochondria. "Wildly wayward photons are lost," Paul says. "Only the photons that pass back through the tiny mitochondrion will arrive back at the semiconductor with the proper phase and location where the photon amplification (gain) can recur."

This discovery suggested the laser cavity be set up sensitively -- like a gun on a hair-trigger -- by carefully setting the power of an external pump laser that beams energy into the cavity. When a mitochondria cell is present, the light in the cavity reaches critical concentration to trigger the avalanche of photons necessary for laser action.

Thus the tiny organelle becomes the center of a lasing process that yields light signals as bright as that emitted by an entire cell several orders of magnitude larger, offering possibilities for analysis that light scattering -- the current method of choice for rapid mitochondrial analysis -- lacks.

'Waterproofing' the mitochondria

Because the light has to squeeze through such a tiny object, a process Paul calls "nano-squeezing," the lasing spectra are dramatically altered, which makes cell identification and detection easier.

Keep, who is also chief executive officer of the Albuquerque-based Swedish-American company Maas BiolAB, has contributed the neuroprotective agent Cyclosporin A, for which his company holds a patent. According to Keep, Cyclosporin A does "waterproof" the mitochondria, but not well enough. The idea here is to use the Sandia biolaser to establish a benchmark for performance against which to measure other, potentially even more effective drugs.

"Cyclosporin protects mitochondria better than anything else known, but it is not a perfect drug," says Keep. "It has side effects, like immunosuppression. Unrelated drugs may have a similar protective effect on mitochondria. Paul's device will lead to a rapid screening device for hundreds of cyclosporin derivatives or even of chemical compounds never tested before."

While testing with conventional methods would take many people and many batches of mitochondria, says Keep, the nanolaser requires only tiny amounts of mitochondria and drug to test.

"With one tube on the left flowing in a number of mitochondria per second, and microliters of different drugs in different packets flowing in to join them on the right, we could rapidly run through hundreds of different compounds. Each mitochondrion scanned through the analyzer would show if there were a change in its lasing characteristics. That would determine the effectiveness of chemical compounds and identify new and even better neuroprotectants," says Keep.

Currently, he says, only a few materials can be tested each day.

Mitochondria with and without neuroprotectant would have calcium ions added to the mix to see the effect of each potential drug.

Helping Gulf War victims

Keep has applied for a grant from the US Congress to develop treatments based on Cyclosporin A to help Gulf War victims who develop the neuron disease amyotrophic lateral sclerosis (ALS). ALS or Lou Gehrig's disease is a neurodegenerative disorder affecting both Gulf War veterans and civilians that kills motor neurons causing paralysis and death in three years. The mitochondria are believed to be the final common pathway leading to the loss of motor neurons. The portion that would go to his work with Paul on the nanolaser screening for next-generation cyclosporin neuroprotectants would be $225,000. Their goal is to find a better mitochondrial waterproofing drug to treat ALS, and potentially the other diseases that rob a person of their mental function such as Alzheimer's and Parkinson's diseases.

Paul's biolaser, using the same techniques to analyze anthrax spores, recently won first place in the DOE's annual Basic Energy Sciences' competition; this is expected to lead to an enhancement to his current program funding from BES. Other funding has come from DOE's Office of Biological and Environmental Research and Sandia's Laboratory Directed Research and Development. Work thus far has measured the mitochondrial size and the swelling effect caused by the addition of calcium ions. The researchers expect to introduce neuroprotectant drugs into experiments this month.< - - Neal Singer

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Sandia, Los Alamos, NM Tech to team on 'energetic materials' research

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By Bill Murphy

Researchers in the technical security community often call them "energetic materials and devices." The public calls them explosives and bombs. By any name, as the nation remains under the threat of terrorist attack, there is a growing urgency to develop advanced capabilities to identify, evaluate, test, and disarm such devices. At the same time, there has been a decline in recent years in research into the science of energetic materials, and a corresponding decrease in development of new energetic devices for both peaceful and military applications.

To address the immediate terrorist threat as well as the longer-term need to revitalize the nation's energetic R&D activities, Sandia, Los Alamos National Laboratory, and the New Mexico Institute of Mining and Technology are establishing the Center for Energetic Materials and Energetic Devices (CEMED). Officials from the three organizations this week were to sign a memorandum of understanding spelling out the scope of the new research center.

Each CEMED partner brings unique capabilities to the table. Sandia for more than 50 years has had as one of its core missions the design and production of advanced energetic devices and subsystems. CEMED projects will offer Sandia and its Regional Alliance for Manufacturing Program (RAMP) partners a chanced to stretch their manufacturing capabilities on high-consequence/low-volume systems and assemblies. Los Alamos brings to the new partnership a long history of developing and characterizing new energetic materials under normal and extreme conditions using sophisticated experimental diagnostics and accurate materials and test fabrication facilities. New Mexico Tech is the only US university to offer degrees in explosives engineering; it conducts research and testing related to energetic materials and explosives for industry and government agencies.

Customers for CEMED will include DOE, the departments of Defense, Justice, Homeland Security, and Agriculture, and other federal and state agencies with an interest in energetic materials and devices. In addition, the center will be a resource for US companies that develop, use, and manufacture energetic materials and devices. They include companies from various industry sectors including transportation, mining, oil and gas, automotive, and munitions manufacturers.

Initial projects CEMED is pursuing include developing energetic devices to help fight wild fires for the forest service and experimental tests to determine blast pressure and validate simulation models of building demolitions.

Key participants in the development of CEMED include, from Sandia, Bob Bickes (2523), Greg Scharrer (2553), Cesar Lombana (14011), Clint Atwood (1314), and Bill Alzheimer (Sandia emeritus). Also involved were, from Los Alamos, John Sanchez, and from New Mexico Tech, Jim Forster and Christa Hockensmith. Bill Alzheimer, former Sandia Director of Energy Components and Metrology, will be the Executive Director of CEMED.

Signatories to the MOU include Sandia VP for Manufacturing Systems, Science, and Technology Lenny Martinez, LANL Associate Laboratory Director for Weapons Physics Raymond Juzaitis, New Mexico Tech Director of Energetic Materials Research and Testing Center John Meason, and New Mexico Tech Acting VP for Administration and Finance Lonnie Marquez. -- Bill Murphy

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Sandia researchers seek ways to lower the cost of wind energy in less-than-optimal locations

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By Chris Burroughs

As the popularity of wind energy rapidly grows worldwide, Sandia researchers are developing ways to lower the cost of this alternative energy and enable turbines to produce more power.

Current wind turbines are cost effective in very windy sites. The goal of the DOE wind program is to extend that cost effectiveness to convenient sites that are not as windy. This can be done by making the rotor sweep area larger and slowing the rotation rate down.

"We are looking at methods of building larger, stronger blades for turbines using a hybrid of carbon graphite fibers and fiberglass that sweep a greater area without greater cost," says Paul Veers, Manager of Wind Energy Technology Dept. 6214. "By next summer we expect to have experimental blades ready for testing that we believe will be lighter and stiffer than blades currently used in the industry."

Sandia has been researching wind energy since the 1970s, but it's only now that the alternative energy source has become economical enough to find widespread use. Over the past ten years the cost of wind energy has fallen dramatically -- to 2.5-5 cents a kilowatt-hour in the most windy sites, says Paul. However, further cost reductions are necessary in critical subcomponents in design, manufacturing, and system integration, Paul says, to make turbine cost effective in sites with modest winds.

Wind farms -- fields of wind turbines -- can be found in California, Southwest Texas, Minnesota, the Washington-Oregon border, Iowa, West Virginia, Pennsylvania, and several other states. A newly developed wind farm recently began operations at a Public Service Company of New Mexico Wind Energy Center near Fort Sumner in New Mexico.

Paul says that in Europe, where wind energy has become particularly popular, turbine manufacturers are starting to produce very large machines. They are frequently used for offshore applications where winds are steady and strong.

"However, as machines have grown larger, issues of scaling and loads have made detailed engineering even more important," Paul says.

That's where Sandia comes in -- researching how to overcome some of these issues.

Today, the most popular commercial wind turbines have 35-meter blades on towers that are 65 to 80 meters tall. They produce about 1.5 megawatts each, and the blades are primarily made of fiberglass, although at least one European manufacturer uses wood.

Tom Ashwill (6214), who leads the blade development team, says that the research blades will be built at subscale sizes of nine to ten meters in order for the researchers to cost-effectively grapple with issues such as fiber material form (i.e., stitched or woven), degree of carbon/glass hybridization, manufacturability -- vacuum-assisted resin transfer molding -- and other traditional issues like aerodynamics, structural strength, and reliability. It is expected that qualities of successfully tested subscale blades can be scaled up to carbon/glass blades 50 meters long that would reside on turbines with 100-meter towers and that produce 2 to 5 megawatts each.

Sandia is concurrently working with industry, both manufacturers and designers, to bring the findings of these subscale blade studies up to full-scale application in commercial prototypes. Public-private partnerships are being funded through the DOE Low Wind Speed Turbine program.

By next summer the researchers hope to have six to 12 different blades to test at the National Wind Technology Center near Boulder, Colo., using its large blade test facilities, and at the Department of Agriculture's research station in Bushland, Texas, using three experimental turbines.

"We expect over the next few months to make some real inroads to developing better blades for turbines," Tom says. "It's a project we are all looking forward to." -- Chris Burroughs

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Jeff Brinker, Jim Gosler appointed Sandia Fellows

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By Neal Singer

Jim Gosler (5901) and Jeff Brinker (1846) have been appointed Sandia Fellows by Laboratory Director C. Paul Robinson.

They are the fifth and sixth Sandians so honored since the Laboratories were founded 57 years ago, and they already have plans to use their new positions -- which correspond to director of a line organization -- and distinctive capabilities to perform work that wouldn't have occurred to them before their appointments.

Says Jeff, "Maybe Gordon [Osbourn (1001), the only other active Fellow], Jim, and I will come up with a common denominator to find and work critical problems that would be of importance to the Laboratories. Maybe we can do something interesting instead of being disconnected entities."

Ordinarily, he said, "My world doesn't intersect with Jim's at all. But he has major issues he's identified. Maybe Gordon can provide modeling, I do the materials work, and Jim identifies the threats."

Jim is a widely recognized expert in areas of information security that are generally classified as "dark" areas. Jeff is an internationally recognized expert in materials science, particularly in the area of sol-gel processing of ceramics and self-assembling nanostructures.

Says Jim, "One of the loves of my life is what has historically been known as blackhatting. In the past, I've pulled together a collection of diverse technical people looking for vulnerabilities in weapons components that bad guys might attempt to exploit, with the idea of getting there before they do. Over the last 15 years, I've been deeply involved with the operational world and finding novel applications of technology to support that world. I suppose that broadens the definition of Sandia Fellow in the Labs; I don't fit the Brinker-Osbourn scientist mold. So we agreed that the three of us get together on problems of national interest where the blend of our expertise could be useful in finding solutions to these problems and perhaps provide seed material for others within the lab."

Gordon, Jim says, was one of the first to e-mail him congratulations and suggest further talks upon learning of his appointment.

Says Pace VanDevender, VP 1000, who supported Jeff's nomination and saw it through the intensive scrutiny required, "Jeff, who has been a Senior Scientist in Materials & Process Sciences Center 1800, is an internationally recognized materials scientist, and is best known as one of the founding fathers of the field of sol-gel processing. Jeff's work in the new field of nano-engineering has substantially contributed to establishing Sandia's credibility as a leader in the National Nanotechnology Initiative."

Open research vs. classified world

Sandia VP for Nonproliferation and Assessments Al Romig (5000) proposed both Jeff's and Jim's nomination.

"This award is given to honor Sandia researchers who have had a significant impact on the nation and their community," says Al. "While Jeff and Gordon have had a visible impact on the scientific community, Jim has done the same -- less visibly, obviously -- on national security for the intelligence community. Frankly, it's easier to measure papers, awards, and citations for scientists. Measuring impact in the classified world is based on our evaluation of the large impact that Jim's information technology applications have in the nation's intelligence community. That impact was highlighted in George Tenet's [Director of Central Intelligence] presentation of a major award to Jim in a private ceremony a few years ago. That was only one of many praises from senior intelligence people. These endorsements were used in supporting Jim's selection as a Sandia Fellow."

Jim, an expert in vulnerability assessment, "is mysterious for what he's done, and boy, has he done it well," quipped Al, who hired into Sandia on almost the same day as Jim and shared the same uncleared office in 1979.

Re Jeff, Al said, "One of the things Paul [Robinson, Labs President] likes to say is that Jeff almost owns Science and Nature magazines. It's true that Jeff has been a very prolific author there. In professional journals, he's one of the most highly cited authors we have at Sandia. He's almost without peer. He's also the only Sandian with the rights of a Sandia Fellow and at the University of New Mexico of a full professor. In addition to his extraordinary accomplishments, he is also more than ready, willing, and able to apply his expertise to solve problems that are critical to Sandia. There have been a number of issues critical to the national security enterprise when DOE looked across its labs and Jeff was the only one who could do it, and he did it."

Exhilarated, honored

Says Jim, "One thing I want to do with the remaining parts of my career is to take all that I have learned technically, programmatically, and operationally and apply that as best I can helping the people back East solve problems relating to the war on terrorism, and help Sandians apply their wonderful technical capabilities in supporting those efforts. The three of us are pretty different in our background, so we may get a lot done.

"I'm really exhilarated and honored to have this opportunity; I had an opportunity to work with Gus Simmons [a retired Sandia Fellow] in my early years. He had a significant impact on me at the Lab. He took the time to provide input and guidance. He helped me along the way. So it's particularly delightful for me to now hold the same position."

Says Jeff, more the cautious researcher, "I knew it was in the works, but I wasn't sure when. I'm not sure yet what it all means, but . . . I'm hoping it means I don't have to spend as much time digging for money [to support my research]. Then I'll have huge amounts of time to do more science." Jeff says it takes probably 30 percent of his time to obtain, maintain, and administer the funding needed to support himself and his research group of 25 undergraduates, graduate students, and postdocs.

Both men seem to embody the inverse of Parkinson's whimsical law that work expands to fill the time available. In their case, the work must obligingly contract, since they do so much of it.

Creativity at the nanoscale

Jeff is a researcher, teacher, editor, patent holder, and prolific article writer. He serves on the editorial board of five technical publications. This year, he has been awarded the 2003 Materials Research Society Medal "for pioneering the application of principles of sol-gel chemistry to the self-assembly of functional nanoscale materials" (Lab News, Sept. 5). In 2002, he won DOE's E.O. Lawrence Award -- the highest, if only the latest, in a string of his DOE awards for advances in materials science (Lab News, Oct. 4, 2002). In the same year, he was elected a member of the National Academy of Engineering. In his capacity as professor at UNM, he has advised 25 graduate students, one of whom -- Dhaval Doshi -- won the 2001 "Collegiate Inventors Competition" from the National Inventors Hall of Fame. The award was accompanied by a $30,000 check to (mainly) student and (also) professor. Mostly, though, Jeff is known for his work in sol-gel processing, which has produced a series of innovations in nanotechnology over the last decade that emerged with the logic and excitement and, nearly, the structure of a popular novel. The papers of the Brinker group, appearing regularly in publications like Nature and Science, have been well-chronicled in Lab News as the team went from flat surface coatings to multiple layers to nanospheres and beyond. These stories are available in the online Lab News on the Sandia web site, search "nano."

Clandestine information technology

While Jim's work is harder to itemize (imagine a series of blackouts here), it can be said that Jim was Sandia's first loaned employee to the National Security Agency, beginning a partnership between Labs and Agency that continues to this day. He solved problems there that many considered unsolvable, emerging as perhaps the preeminent expert in vulnerability assessment. In 1995, he was named Sandia Manager of the Year and also received Sandia's first NOVA award from Lockheed Martin for leadership. In 1996, then-CIA director John Deutsch requested Jim's support in establishing Information Operations as a core element of the CIA's clandestine technical collection arsenal. Jim was named Founding Director of the CIA's Clandestine Information Technology Office. After six months of analysis, Jim reengineered his office to take advantage of available synergies, which enabled CITO to achieve extraordinary impact on US national security. Among his awards are the Director of Central Intelligence Director's Award, the Intelligence Medal of Merit, the National Intelligence Medal of Achievement, and the Clandestine Service Medallion.

"There were a lot of talented people already there working in these areas and I just brought coherence," he says, a description that itself speaks for his ability to work with others.

A significant difference between current appointees Jim, Jeff, and Gordon and preceding Sandia Fellows is that recent appointees are active researchers in the middle of their careers. Predecessors Gus Simmons, Walt Herrmann, and Wendell Weart were nearing the end of their tenures before receiving the honor. -- Neal Singer

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