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Tech Beat - January 12, 2010

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Editor: Michael Baum
Date created: October 8, 2010
Date Modified: October 8, 2010 
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NIST Scientists Quantify Nanoparticle-Protein Interactions

A research team at the National Institute of Standards and Technology (NIST) has quantified the interaction of gold nanoparticles with important proteins found in human blood, an approach that should be useful in the development of nanoparticle-based medical therapies and for better understanding the physical origin of the toxicity of certain nanoparticles.

photo of fibrous masses

Insulin, one of the most common proteins in human blood, can accumulate into fibrous masses when it misfolds. Research by a team at NIST indicates that gold nanoparticles apparently increase insulin's tendency to form these fibers. (Color added for clarity.)

Credit: NIST
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Nanoparticles show promise as vehicles for drug delivery, as medical diagnostic tools, and as a cancer treatment agent in their own right. Gold nanoparticles, spheres that vary in size between 5 and 100 billionths of a meter in diameter, are especially useful because of the many ways their metal surfaces can be “functionalized” by attaching tailored molecules to perform different tasks in the body. However, treatments require a large number of particles to be injected into the bloodstream, and these could be hazardous if they interact with the body in unforeseen ways.

According to NIST materials scientist Jack Douglas, one of the principal problems confronting nanomedicine is the tendency of proteins to stick to the nanoparticles that float freely in the bloodstream. “Nanoparticles coated with proteins will generally alter their interaction with the body and the nanoparticles can be expected to induce a complementary change in protein chemical activity,” says Douglas. “The coating also can cause the nanoparticles to clump together in large aggregates, which can provoke a huge immune response. Of course, that’s something you want to avoid.”

Scientists have a poor understanding of these interactions, so the NIST team decided to explore what happens when nanoparticles of different sizes encounter five common blood proteins. With the aid of a bevy of microscopes and spectroscopy devices, the team found several general patterns of behavior. “Once the proteins stick to the nanoparticles, the optical properties of both the particles and the proteins change,” Douglas says. “Measuring these changes helps us quantify the stickiness of the nanoparticle for the proteins, the thickness of the adsorbed protein layer and the propensity of the particles to aggregate due to the presence of the protein layers.”

More specifically, the team learned that all five of the proteins stuck to the gold, causing the NPs to aggregate, and that increasing the spheres’ diameter increased their stickiness. They also found that this aggregation usually caused some change in the shape of the proteins—“which generally implies some change in their function as well,” Douglas says.

Aggregation does not always lead to a toxic response, Douglas says, but can affect whether the drugs on the nanoparticles ever reach their intended target. “The main thing is that interactions are largely set by the existence of the protein layer,” he says. “You want to know something about these protein layers if you want to know what nanoparticles are going to do in the body.”

Douglas says that the NIST study addresses metrology needs identified in a National Research Council report** published this past year calling for more quantitative testing for nanoparticle interactions with biological media and that much more work is needed along this and other lines. “For example, we do not yet understand how different-sized particles bind to the surface membranes of cells, which is where many drug interactions take place,” he says.

* S.H.D. Lacerda, J. Park, C. Meuse, D. Pristinski, M.L. Becker, A. Karim and J.F. Douglas. Interaction of gold nanoparticles with common human blood proteins. ACS Nano, December 18, 2009, DOI: 10.1021/nn9011187.

** NRC report, “Review of Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research,” available online at www.nap.edu/catalog.php?record_id=12559#toc.

Media Contact: Chad Boutin, boutin@nist.gov, 301-975-4261

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What Were They Drinking? Researchers Investigate Radioactive Crock Pots

Radioactive toothpaste, suppositories, makeup: Would-be inventors seeking to capitalize on the discovery of radioactivity in the late 19th century produced a plethora of questionable medical devices and treatments. Among the most famous of these was the Revigator, an earthenware vessel that, according to an advertisement, would infuse drinking water with “the lost element of original freshness—radioactivity.” With some technical assistance from the National Institute of Standards and Technology (NIST), researcher Michael Epstein and a group of students at Mount Saint Mary’s University in Emmitsburg, Md., discovered that the risk the Revigator posed flowed not so much from the radioactivity, but from the presence of toxic elements dissolved in the water.

the revigator water jar

The inventors of the Revigator claimed the device would restore the lost element of water "radio-activity," which "both creates cellular energy and removes cellular poisons." Despite the obvious risk associated with ingesting radioactive substances, researchers at Mount Saint Mary's University in Emmitsburg, Md., working with NIST, discovered that toxic elements dissolved in the water posed the greatest danger.

Credit: M. Epstein
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The Radium Ore Revigator Company sold several hundred thousand of their glazed ceramic jugs between 1920 and the mid-1930s. The rough, porous inner surface of the Revigator was lined with clay containing carnotite ore, a potassium-uranium-vanadate mineral which released radon into the water as the radium in the ore decayed. According to the manufacturer, the radiation could treat or cure ailments ranging from arthritis and flatulence to senility and poisoning.

“The Revigator was an attempt to mimic spa, or spring water,” explains Epstein. “People figured that spring water was radioactive, and it seemed to be good for you, so why not make your own? Most of the literature on the Web has referenced the danger as coming from the radioactivity. My students and I wanted to see if that was true.”

Working with NIST scientist Lee Yu, the Mount St. Mary’s team set out to determine the extent of the hazards the Revigator might have posed. According to their recent paper,* the researchers measured the amount of radiation emanating from the vessel with a Geiger counter, the radon concentration in the air and water from a jar that had been sealed for one week, and the levels of toxic elements that may have dissolved into water sealed in the jars for one day and one week using a mass spectrometer, a highly sensitive instrument for detecting chemicals and elements.

The team found that radon concentrations in the air and water sampled from jars sealed for one week significantly exceeded the EPA-recommended maximum contaminant levels (MCL). Nevertheless, the team noted that the concentration of radon in the air, given the drafty conditions of an early 20th century home, would not have posed a significant health risk. Moreover, although the levels of radon in the water were high—between 50,000 and 200,000 picoCuries per liter—the study found that, compared to the myriad other disease-related causes of mortality at the time, the chances of dying as a result of drinking radon-infused water were relatively low.

Instead, they found the greatest risks associated with drinking the recommended six to eight daily glasses of “revigated” water was from toxic elements—arsenic, lead, vanadium and uranium—dissolved in the water. Although the concentrations varied with the containers and whether the samples were taken from the top of the containers or from the leaden spout, most of the containers exhibited levels of toxic elements in excess of EPA or OSHA recommendations. Especially striking were the samples of exposed water mixed with a mild acid to mimic wine or fruit juice. Ordinary water kept sealed in one of the jars contained two to twenty times the EPA MCL for arsenic, and some samples showed almost twice as much lead and uranium. The acidified water contained 300 times more arsenic and three times more uranium than the EPA MCL.

“For me, it was quite interesting that people at the time were drinking something that they didn’t understand given all that we now know about how harmful these things are to human health,” says Yu. “It’s amazing to me how eager companies were to commercialize new discoveries without a clear understanding of the risks involved.”

* M. Epstein, D.G. Miles Jr., and L.L. Yu. What were they drinking? A critical study of the radium ore revigator. Applied Spectroscopy. Volume 63, Issue 12, Pages 324A-354A and 1315-1442, (December 2009) , pp. 1406-1409(4). DOI: 10.1366/000370209790109003.

Media Contact: Mark Esser, mark.esser@nist.gov, 301-975-8735

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Theorists Close In on Improved Atomic Property Predictions

Scientists at the National Institute of Standards and Technology (NIST) and Indiana University (IU) have determined* the most accurate values ever for a fundamental property of the element lithium using a novel approach that may permit scientists to do the same for other atoms in the periodic table.

NIST’s James Sims and IU’s Stanley Hagstrom have calculated four excitation energies for the lithium atom approximately 100 times more accurately than any previous calculations or experimental measurements. Precise determination of excitation energy—the amount necessary to raise an atom from a base energy level to the next higher—has intrinsic value for fundamental research into atomic behavior, but the success of the method the team employed has implications that go beyond lithium alone.

The theorists have overcome major computational and conceptual hurdles that for decades have prevented scientists from using quantum mechanics to predict electron excitation energies from first principles. Sims first proposed in the late 1960s that such a quantum approach could be possible, but its application to anything more than two electrons required a fiendishly difficult set of calculations that, until recently, was beyond the capacity of even the world’s fastest computers. In 2006 the team used a novel combination of algorithms, extended precision computing and the increase in power brought about by parallel computing to calculate the most accurate values ever for a simple, two-electron hydrogen molecule.**

By making improvements to those algorithms, Sims and Hagstrom now have been able to apply their approach to the significantly more difficult problem of lithium, which has three electrons. Much of the original difficulty with their method stems from the fact that in atoms with more than one electron the mutually repulsive forces among these tiny elementary particles introduces complications that make calculations extremely time-consuming, if not practically impossible.

Sims says that while the lithium calculation is valuable in itself, the deeper import of refining their method is that it should enable the calculation of excitation energies for beryllium, which has four electrons. In turn, this next achievement should enable theorists to predict with greater accuracy values for all of the remaining elements in the second row of the periodic table, from beryllium to neon, and potentially the rest of the periodic table as well. “The mathematical troubles we have with multiple electrons can all be reduced to problems with four electrons,” says Sims, a quantum chemist in the mathematics and computational sciences division. “Once we’ve tackled that, the mathematics for other elements is not any more difficult inherently—there’s just more number-crunching involved.”

To obtain their results, the researchers used 32 parallel processors in a NIST computer cluster, where they are currently working on the calculations for beryllium.

High precision determinations of excitation energies are of interest to scientists and engineers who characterize and model all types of gaseous systems, including plasmas and planetary atmospheres. Other application areas include astrophysics and health physics.

* J.S. Sims and S.A. Hagstrom. Hylleraas-configuration-interaction study of the 2 2S ground state of neutral lithium and the first five excited 2S states. Physical Review A, Nov. 19 2009, 10.1103/PhysRevA.80.052507.

** See “Algorithm Advance Produces Quantum Calculation Record,” NIST Tech Beat, March 16, 2006.

Media Contact: Chad Boutin, boutin@nist.gov, 301-975-4261

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$123 Million in Grants Will Fund New Research Facilities

The National Institute of Standards and Technology (NIST) last week announced grants totaling more than $123 million to 11 universities and a non-profit research organization to provide cost-shared support for the construction of new scientific research facilities.

With ultimate research targets ranging from off-shore wind power and coral reef ecology to quantum physics and nanotechnology, the 12 cost-shared projects will launch more than $250 million in new laboratory construction projects beginning early this year.

The 12 construction project awards, the result of a competition announced by NIST last May, include:

  • $15 million to the University of Pittsburgh (Pittsburgh, Pa.) for new laboratories for nanoscience and experimental physics,
  • $15 million to Nova Southeastern University Inc. (Fort Lauderdale-Davis, Fla.) for a Center of Excellence for Coral Reef Ecosystem Science research facility,
  • $12.4 million to the University of Maine (Orono, Me.) for an Advanced Nanocomposites in Renewable Energy Laboratory,
  • $12.3 million to the University of Kansas Center for Research (Lawrence, Kan.) for the new Measurement, Materials and Sustainable Environment Center (M2SEC),
  • $11.8 million to the University of Kentucky (Lexington, Ky.) for an expansion of the Center for Applied Energy Research Laboratory,
  • $11.8 million to Purdue University (West Lafayette, Ind.) for a Center for High Performance Buildings at the Ray W. Herrick Laboratories,
  • $11.6 million to the Georgia Tech Research Corporation (Atlanta, Ga.) for a pilot-scale laboratory for carbon-neutral energy solutions,
  • $10.3 million to the University of Maryland (College Park, Md.) for a  laboratory for advanced quantum science in the school’s new Physical Sciences Complex,
  • $8.1 million to the Woods Hole Oceanographic Institution (Barnstable, Mass.) for the Laboratory for Ocean Sensors and Observing Systems (LOSOS),
  • $6.9 million to the University of Nebraska – Lincoln (Lincoln, Neb.) for a nanoscience metrology facility,
  • $6.9 million to Georgetown University (Washington, D.C.) for The Institute for Soft Matter Synthesis and Metrology, and
  • $1.4 million to Columbia University (New York, N.Y.) for an ultraclean geochemistry laboratory at Lamont-Doherty Earth Observatory.


Additional information on each project may be read in the NIST news release “NIST Awards $123 Million in Recovery Act Grants To Construct New Research Facilities” (www.nist.gov/public_affairs/releases/20100108_cgp_awards.htm.)

Media Contact: Michael Baum, baum@nist.gov, 301-975-2763

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NIST Awards Over $34 Million for Research in Measurement Science

The National Institute of Standards and Technology (NIST) last week awarded $34.12 million in grants for 27 research projects in measurement science and engineering. The one-time grants, ranging from $408,996 to $1.5 million, will fund projects lasting up to three years projects at higher-education, commercial, and nonprofit organizations in 18 states.

The NIST Measurement Science and Engineering Research Grants Program, funded under the American Recovery and Reinvestment Act, supports research to advance measurement science in six areas of critical national importance, including energy, environment and climate change, information technology and cyber security, bioscience and health care, manufacturing and physical infrastructure.

“With these grants, we are leveraging our nation’s brightest minds in measurement science to address important national needs,” said NIST Director Patrick Gallagher. “These projects will bolster U.S. scientific and technological infrastructure, increasing our nation’s ability to innovate, compete, and solve scientific and technological problems.”

Full details of the NIST measurement science grants are available in the NIST news announcement, “Commerce Department’s National Institute of Standards and Technology Awards Over $34 Million in Recovery Act Grants to Increase Innovation and Improve American Competitiveness,” (www.nist.gov/public_affairs/releases/measurementgrants2010.html.)

Media Contact: Ben Stein, bstein@nist.gov, 301-975-3097

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Agilent CTO Joins NIST Advisory Group

Darlene J.S. Solomon, chief technology officer for Agilent Technologies, has been chosen to serve on the Visiting Committee on Advanced Technology (VCAT), the primary policy advisory board of the National Institute of Standards and Technology (NIST). Solomon’s three-year term runs through Jan. 2, 2013.

Solomon joined Agilent Technologies when the company was first formed in 1999 and has also served as vice president and director of Agilent Laboratories. Prior to her time at Agilent, Solomon worked at Hewlett Packard as a member of the technical staff. With numerous patents and publications to her name, Solomon was inducted into the Women in Technology International’s Hall of Fame in 2001 and named to Corporate Board Member’s 50 Top Women in Technology in 2008.

Solomon serves on numerous other academic and government advisory and review boards, including the National Research Council Review Committee for NIST, California’s Blue Ribbon Task Force on Nanotechnology (as the chair of R&D), and an external advisory board for the National Science Foundation Nanobiotechnology Center.

The VCAT was established by Congress in 1988 to review and make recommendations on NIST’s policies, organization, budget and programs, and was recently updated by the 2007 America COMPETES Act. The next VCAT meeting will take place Feb. 2-3, 2010 in Gaithersburg, Md.

For a list of all members and more information, see the VCAT Web page at www.nist.gov/director/vcat/.

Media Contact: Michael Baum, baum@nist.gov, 301-975-2763

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Sriram, Williams Honored as AAAS Fellows

Two scientists at the National Institute of Standards and Technology (NIST) were recently elected as 2009 fellows of the American Association for the Advancement of Science (AAAS), an honor bestowed upon association members by their peers.

Ram D. Sriram and Carl J. Williams are among 531 AAAS members cited “for meritorious efforts to advance science or its applications.” The association is the world’s largest general scientific society and publisher of the journal Science.

Sriram conducts research on standards for interoperability of computer-aided design systems. An engineer in NIST’s Manufacturing Engineering Laboratory, he was chosen “for outstanding contributions and technical leadership in developing tools and techniques for engineering design automation.”

Williams, a member of the NIST Physics Laboratory and the chief of NIST’s Atomic Physics Division, was recognized “for distinguished contributions to the theory of cold atom collisions and small molecule spectroscopy, in particular to ultracold photoassociation spectroscopy and dynamics of ultracold gases.”

New fellows will be honored at a Feb. 20 ceremony during the 2009 AAAS Annual Meeting in San Diego, Calif. For more information and the full list of the 2009 AAAS Fellows, visit www.aaas.org/news/releases/2009/1218fellows.shtml.

Media Contact: Michael Baum, baum@nist.gov, 301-975-2763

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Six NIST Researchers Selected as IEEE Fellows

Six researchers at the National Institute of Standards and Technology (NIST) have been named fellows of IEEE, as association for professionals involved in areas ranging from aerospace systems, computers and telecommunications to biomedical engineering, electric power and consumer electronics. The IEEE grade of Fellow is conferred by the board of directors upon a person with an extraordinary record of accomplishments in any of the IEEE fields of interest. IEEE Fellow is the highest grade of membership and is recognized by the technical community as a prestigious honor and an important career achievement.

The new IEEE fellows from NIST are:

  • James Baker-Jarvis of the Electronics and Electrical Engineering Laboratory for contributions to dielectric measurement and analysis of microwave measurement structures
  • Samuel Paul Benz of the Electronics and Electrical Engineering Laboratory for contributions to quantum-based Josephson junction array waveform synthesizer
  • Christopher L. Holloway of the Electronics and Electrical Engineering Laboratory for application of new material in the field of electromagnetic compatibility
  • Nicholas G. Paulter of the Electronics and Electrical Engineering Laboratory for contributions to ultra-high speed waveform measurements
  • P. Jonathon Phillips of the Information Technology Laboratory for contributions to the evolution of face recognition techniques
  • Jeffrey Mark Voas of the Information Technology Laboratory for leadership in the development of trustworthy software, including improved metrics and process optimization.


For more information on IEEE fellows, see www.ieee.org/web/aboutus/news/2009/3december.html

Media Contact: Michael Baum, baum@nist.gov, 301-975-2763

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NIST Quantum Computing Research Among Top Stories of 2009

Three science magazines have selected quantum computing research by the National Institute of Standards and Technology (NIST) as top stories of 2009. All the research was performed by physicist David Wineland’s group at NIST’s campus in Boulder, Colo. The group, which previously demonstrated many components needed for quantum computing with electrically charged atoms (ions), combined them to make new experimental advances described in three major papers published in 2009.

Physics World, the news magazine of the Institute of Physics in the United Kingdom, selected one of these papers as the most significant breakthrough of 2009. The cited NIST work demonstrated sustained, reliable information-processing operations with ions (see “NIST Demonstrates Sustained Quantum Processing in Step Toward Building Quantum Computers”). The achievement raises prospects for scaling up ion trapping technology to build a practical quantum computer, which could harness the unusual rules of the submicroscopic world of quantum physics to solve some problems that are intractable with today’s technology. Physics World’s top breakthroughs of 2009 are described at “Physics World’s 2009 wrap-up” (www.iop.org/News/news_38580.html) and “The first complete ’quantum computer’” (http://physicsworld.com/cws/article/news/41270).

Science News selected NIST’s demonstration of a universal, programmable quantum processor (“NIST Demonstrates ‘Universal’ Programmable Quantum Processor for Quantum Computers”) as the leading story of 2009 in the matter and energy category. The experimental processor used two ions to perform 160 randomly chosen programs. The magazine also selected the Wineland group’s third paper as another top story in the same category. This work linked the vibrations of two separated ion pairs to demonstrate the curious quantum property of “entanglement” in a mechanical system similar to those in the large-scale everyday world (“NIST Physicists Demonstrate Quantum Entanglement in Mechanical System”). The magazine’s summary of the top news of 2009 can be found at “ 2009 Science News of the Year: Matter & Energy” (www.sciencenews.org/view/feature/id/50947/title/2009_Science_News_of_the_Year_Matter_%2B_Energy) and www.sciencenews.org/view/feature/id/50907/title/2009_Science_News_of_the_Year.

Discover magazine named the NIST demonstration of entanglement in a mechanical system as number 40 of the 100 top stories of 2009. “The experiment will help scientists explore why small objects follow the weird rules of quantum mechanics but large ones do not—one of the greatest enigmas in physics,” the magazine noted.

Media Contact: Michael Baum, baum@nist.gov, 301-975-2763

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