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NIST Home > Public Affairs Office > Tech Beat > NIST Tech Beat for October 13, 2010

Tech Beat - October 13, 2010

In This Issue...
  • JILA Unveils Improved 'Molecular Fingerprinting' for Trace Gas Detection
  • New Look at Multitalented Protein Sheds Light on Mysteries of HIV
  • Faster CARS, Less Damage: NIST Chemical Microscopy Shows Potential for Cell Diagnostics
  • NIST Mini-Sensor Traces Faint Magnetic Signature of Human Heartbeat
  • This Little Light of Mine: Changing the Color of Single Photons Emitted by Quantum Dots
  • Baldrige Program Name Change Emphasizes Performance Excellence
  • NIST, NTIA Seek Collaborators for Emergency Communications Demo Network
  • NIST Sponsors Second Cloud Computing Forum and Workshop Nov. 4-5
  • NIST’s Manufacturing Extension Partnership Awards $9.1 Million for Projects to Enhance U.S. Global Competitiveness
  • NIST Releases 2009 Department of Commerce Technology Transfer Report
  • NIST Identifies Five “Foundational” Smart Grid Standards
  • NIST Awards $50 Million in Grants for the Construction of Five Science Facilities
  • Popular Science Magazine Names Spielman One of Science’s ‘Brilliant Ten’
  • NIST Researcher Wins Presidential Award for Green Innovation
  • NIST's Arnold Receives Award for Smart Grid Leadership

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Editor: Michael Baum
Date created: October 13, 2010
Date Modified: October 13, 2010 
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JILA Unveils Improved 'Molecular Fingerprinting' for Trace Gas Detection

Scientists at JILA and collaborators have demonstrated an improved laser-based "molecular fingerprinting" technique that picks out traces of key hydrogen-containing and other molecules from a billion other particles in a gas in just 30 seconds or less—performance suitable for breathalyzers for diagnosing disease, measuring trace gases in the atmosphere, detecting security threats and other applications.

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Artist's rendering of JILA's molecular fingerprinting system. A gas mixture (left) is probed by a frequency comb, a laser-based tool for identifying different colors of light. By analyzing the amounts of specific colors absorbed, the system quickly identifies molecules and their concentrations. Applications may include diagnosing disease, detecting security threats, and measuring trace gases in the atmosphere.

Credit: Baxley/JILA
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JILA is jointly operated by the National Institute of Standards and Technology (NIST) and University of Colorado at Boulder (CU).

Described in Optics Express,* the research extends the range of an existing NIST/JILA invention** to cover the mid-infrared region of the electromagnetic spectrum. This is a critical range, because it includes the frequencies associated with strong molecular vibrations, including various hydrogen bonds. The technology thus can identify a much wider variety of molecules, including virtually any containing hydrogen—the most common element in the universe—and can measure lower concentration levels than before.

The heart of the JILA system is an optical frequency comb, a tool generated by ultrafast lasers that precisely identifies a wide range of different colors of light. Researchers identify specific molecules based on which colors of light, or comb "teeth," are absorbed by a gas, and in what amounts. The comb light usually passes through a gas mixture many times, significantly improving detection sensitivity. Concentrations are measured with the help of molecular "signatures" assembled from databases. The technique works quickly and reliably even when molecules have overlapping, continuous, or otherwise confusing absorption signatures. The rapid data collection, in particular, makes the technology suitable to replace or surpass conventional Fourier transform infrared (FTIR) spectrometers for many applications, according to the paper.

In the demonstration, scientists measured a dozen important molecules at partsperbillion precision, including the greenhouse gases methane, carbon dioxide, and nitrous oxide; and the pollutants isoprene and formaldehyde. In addition, the system detected molecules useful in human breath analysis: ethane (a sign of asthma) and methanol (a sign of kidney failure). The system is able to reach parts-per-trillion sensitivity for the first time in detecting carbon dioxide.

Collaborators from IMRA America, Inc. (Ann Arbor, Mich.), developed the fiber laser used to make the frequency comb. The comb itself is based on a non-linear optical process that shifts the light from the near-infrared to the mid infrared. The JILA researchers now plan to extend the system further into longer wavelengths to cover a second important molecular fingerprinting region, to identify a more diverse set of complex molecules containing carbon, and to modify the equipment to make it portable. Planning is also under way for clinical trials of the breathalyzer application.

The research is funded by the Air Force Office for Scientific Research, Defense Advanced Research Projects Agency, the Agilent Foundation, NIST, and the National Science Foundation.

* F. Adler, P. Masłowski, A. Foltynowicz, K.C. Cossel, T.C. Briles, I. Hartl and J. Ye. Mid-Infrared frequency comb Fourier transform spectroscopy with a broadband frequency comb. Optics Express, Vol. 18, No. 21. Oct. 11, 2010.

** J. Ye, M.J. Thorpe, K. Moll and J.R. Jones. U.S. Patent number 7,538,881, "Sensitive, Massively Parallel, Broad-Bandwidth, Real-Time Spectroscopy," issued in May 2009, NIST docket number 06-004, CU Technology Transfer case number CU1541B. Licensing rights have been consolidated in CU. See more in "Optical 'Frequency Comb' Can Detect the Breath of Disease ," in NIST Tech Beat for Feb. 19, 2008, at www.nist.gov/public_affairs/techbeat/tb2008_0219.htm#comb.

Media Contact: Laura Ost, laura.ost@nist.gov, 303-497-4880

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New Look at Multitalented Protein Sheds Light on Mysteries of HIV

New insights into the human immunodeficiency virus (HIV) infection process, which leads to acquired immunodeficiency syndrome (AIDS), may now be possible through a research method recently developed in part at the National Institute of Standards and Technology (NIST), where scientists have glimpsed an important protein molecule's behavior with unprecedented clarity.

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The Gag protein is central to the assembly of new HIV virus particles. (a) Folded Gag molecules (multicolored) arise in the cellular cytoplasm. (b) Gag binds the viral RNA (black wavy lines) and drags it into the forming particle. (c) Gag molecules also may create assembly sites, where (d) Gag must stretch out to pack into the growing virus. (e) Virus particles eventually bud off from the host cell.

Credit: NIST
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The HIV protein, known as Gag, plays several critical roles in the assembly of the human immunodeficiency virus in a host cell, but persistent difficulties with imaging Gag in a lab setting have stymied researchers' efforts to study how it functions.

"A better understanding of Gag's behavior might allow researchers to develop antiviral drugs that target the HIV assembly process, which remains unassailed by medical science," says Hirsh Nanda, a postdoctoral researcher at the NIST Center for Neutron Research (NCNR) and a member of the multi-institutional research team. "Our method might reveal how to inhibit new viruses as they grow."

The Gag molecule is a microscopic gymnast. At different stages during HIV assembly, the protein twists itself into several different shapes inside a host cell. One shape, or conformation, helps it to drag a piece of HIV genetic material toward the cell membrane, where the viral particles grow. Gag's opposite end becomes anchored there, stretching the protein into a rod-like conformation that eventually helps form a barrier surrounding the infectious genes in the finished virus. But while scientists have been aware for years that Gag appears to play several roles in HIV assembly, the specifics have remained mysterious.

The research team potentially solved this problem by creating an artificial cell membrane where Gag can show off its gymnastic prowess for the neutron probes at the NCNR. The center includes a variety of instruments specifically designed to observe large organic molecules like proteins.

"We were able to mimic the different stages of the virus's development, and look at what Gag's conformation was at these various stages," Nanda says. "We saw conformations that had never been seen before."

Nanda describes the team's first paper* on the subject as an important first step in describing their observational method, which was a joint effort between NIST, the National Cancer Institute and Carnegie-Mellon University. They plan another paper detailing what the method has revealed about HIV.

"Our efforts have not yet shown us how many steps are involved in Gag's work assembling an HIV particle, but at least we can see what it looks like in each major interaction that likely occurs in the cell during assembly," Nanda says. "It may allow us to characterize them for the first time."

Nanda says that their technique will also allow scientists to examine large classes of membrane proteins, which like Gag are notoriously hard to examine.

*H. Nanda, S.A.K. Datta, F. Heinrich, M. Lösche, A. Rein, S. Krueger, J.E. Curtis. Electrostatic interactions and binding orientation of HIV-1 matrix, studied by neutron reflectivity. Biophysical Journal, Vol. 99 (8), Oct. 20, 2010.

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

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Faster CARS, Less Damage: NIST Chemical Microscopy Shows Potential for Cell Diagnostics

A paper by researchers at the National Institute of Standards and Technology (NIST) may breathe new life into the use of a powerful—but tricky—diagnostic technique for cell biology. The paper,* appearing this week in the Biophysical Journal, demonstrates that with improved hardware and better signal processing, a powerful form of molecular vibration spectroscopy can quickly deliver detailed molecular maps of the contents of cells without damaging them. Earlier studies have suggested that to be useful, the technique would need power levels too high for cells.

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B-CARS chemical imaging: Test cells from a mouse as seen in an optical microscope image (l.), and using B-CARS (r.). The CARS image detects specific molecules to highlight the cell nucleus (green) and intracellular fluid (blue). Images show an area approximately 40 micrometers across. B-CARS image represents approx. 17,000 individual spectra.

Credit: NIST
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The technique, "B-CARS,"** is one of several variations on Raman spectroscopy, which measures the frequencies associated with different modes of vibration of atoms and their bonds in a molecule. The exact mix of these frequencies is an extremely discriminating "fingerprint" for any particular molecule, so Raman spectroscopy has been used as a chemical microscope, able to detail the structure of complex objects by mapping the chemical composition at each point in a three-dimensional space.

In the biosciences, according to NIST chemist Marcus Cicerone, Raman spectroscopy has been used to detect microscopic cellular components such as mitochondria, detect how stem cells differentiate into new forms and distinguish between subtly different cell and tissue types. It can, for example, detect minor differences between various precancerous and cancerous cells, potentially providing valuable medical diagnostic information. Even better, it does this without the need to add fluorescent dyes or other chemical tags to identify specific proteins.

The catch, says Cicerone, is speed. The usual method, spontaneous Raman scattering takes a long time to gather enough data to generate a single spectrum—as much as seven minutes for fine detail—and that's for each point in the image. "Seven minutes or even five seconds per spectrum is not feasible when we need a million spectra for an image," he observes. CARS, which uses a pair of lasers to pump up the vibrational states and increase signal, is part of the answer. The current breakthroughs for a broadband CARS instrument developed at NIST since 2004, says Cicerone, gets the same information in 50 milliseconds per pixel.

The new catch is power. Recent papers have argued that to get the necessary data, the lasers used in CARS must run at power levels above the damage threshold for living cells, making the technique nearly useless for clinical purposes. Not quite, according to the NIST team. Their paper describes a combination of improved hardware to gather spectra over a very broad range of wavelengths, and a clever mathematical technique that effectively amplifies the useable signal by examining a portion of signal normally ignored as background interference. The result, says Cicerone, pushes their minimum power level below the damage threshold while retaining the speed of CARS. "We have all the information that you have in a Raman spectrum but we get it 5 to 100 times faster," he says, adding that some obvious modifications should push that higher, opening the door to more widespread use of vibrational spectroscopy in both biology and clinical diagnosis.

* S.H. Parekh, Y.J. Lee, K.A. Aamer and M.T. Cicerone. Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy. Biophysical Journal. V. 99, Oct. 13, 2010.

** For "broadband coherent anti-Stokes Raman scattering"

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

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NIST Mini-Sensor Traces Faint Magnetic Signature of Human Heartbeat

Researchers from the National Institute of Standards and Technology (NIST) and the German national metrology institute have used NIST's miniature atom-based magnetic sensor to successfully track a human heartbeat, confirming the device's potential for biomedical applications.

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NIST's miniature magnetic sensor is about the size of a sugar cube. The lid has been removed to show the inner square cell, which contains a gas of rubidium atoms. The diagonal bar is an electrical connection to the cell's heaters, which are powered by the red, black and white electrical wires. The clear optical fiber extending from the middle bottom of the sensor connects to a control box.

Credit: S. Knappe/NIST
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Described in Applied Physics Letters,* the study is the first to be performed under conditions resembling a clinical setting with the NIST mini-sensors, which until now have been operated mostly in physics laboratories. The new experiments were carried out at the Physikalisch Technische Bundesanstalt (PTB) in Berlin, Germany, in a building described as having the world's best magnetic shielding—necessary to block the Earth's magnetic field and other external sources from interfering with the high-precision measurements. PTB has an ongoing program in biomagnetic imaging using human subjects.

The NIST sensor—a tiny container of about 100 billion rubidium atoms in gas form, a low-power infrared laser, and optics—measured the heart's magnetic signature in picoteslas (trillionths of a tesla). The tesla is the unit that defines magnetic field strength. For comparison, the Earth's magnetic field is a million times stronger (measured in millionths of a tesla) than a heartbeat, and an MRI machine uses fields several million times stronger still (operating at several tesla).

In the experiments at PTB, the NIST sensor was placed 5 millimeters above the left chest of a person lying face up on a bed. The sensor successfully detected the weak but regular magnetic pattern of the heartbeat. The same signals were recorded using the "gold standard" for magnetic measurements, a SQUID (superconducting quantum interference device). A comparison of the signals confirmed that the NIST mini-sensor correctly measured the heartbeat and identified many typical signal features. The NIST mini-sensor generates more "noise" (interference) in the signal but has the advantage of operating at room temperature, whereas SQUIDs work best at minus 269 degrees Celsius and require more complicated and expensive supporting apparatus.

A spin-off of NIST's miniature atomic clocks, NIST's magnetic mini-sensors were first developed in 2004. Recently, they were packaged with fiber optics for detecting the light signals that register magnetic field strength. (See the 2007 NIST news release "New NIST Mini-Sensor May Have Biomedical and Security Applications" at www.nist.gov/public_affairs/releases/magnetometer.cfm.) In addition, the control system has been reduced in size, so the entire apparatus can be transported easily to other laboratories.

The new results suggest that NIST mini-sensors could be used to make magnetocardiograms, a supplement or alternative to electrocardiograms. The study also demonstrated for the first time that atomic magnetometers can offer sensing stability lasting tens of seconds, as needed for an emerging technique called magnetorelaxometry (MRX), which measures the magnetization decay of magnetic nanoparticles. MRX is used to localize, quantify and image magnetic nanoparticles inserted into biological tissue for medical applications such as targeted drug treatments. Further tests of the NIST sensors at PTB are planned.

* S. Knappe, T.H. Sander, O. Kosch, F. Wiekhorst, J. Kitching and L. Trahms. Cross-validation of microfabricated atomic magnetometers with SQUIDs for biomagnetic applications. Applied Physics Letters. 97, 133703 (2010); doi:10.1063/1.3491548. Online publication: Sept. 28, 2010.

Media Contact: Laura Ost, laura.ost@nist.gov, 303-497-4880

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This Little Light of Mine: Changing the Color of Single Photons Emitted by Quantum Dots

Researchers at the National Institute of Standards and Technology (NIST) have demonstrated* for the first time the conversion of near-infrared 1,300 nm wavelength single photons emitted from a true quantum source, a semiconductor quantum dot, to a near-visible wavelength of 710 nm. The ability to change the color of single photons may aid in the development of hybrid quantum systems for applications in quantum communication, computation and metrology.

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In new NIST experiments, the “color” (wavelength) of photons from a quantum dot single photon source (QD SPS) is changed to a more convenient shade using an up-conversion crystal and pump laser. To test that the process truly acts on single photons without degrading the signal (by creating additional photons), the output is split in two and sent to parallel detectors—true single photons should not be detected simultaneously in both paths.

Credit: NIST
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Two important resources for quantum information processing are the transmission of data encoded in the quantum state of a photon and its storage in long-lived internal states of systems like trapped atoms, ions or solid-state ensembles. Ideally, one envisions devices that are good at both generating and storing photons. However, this is challenging in practice because while typical quantum memories are suited to absorbing and storing near-visible photons, transmission is best accomplished at near-infrared wavelengths where information loss in telecommunications optical fibers is low.

To satisfy these two conflicting requirements, the NIST team combined a fiber-coupled single photon source with a frequency up-conversion single photon detector. Both developed at NIST, the frequency up-conversion detector uses a strong pump laser and a special non-linear crystal to convert long wavelength (low frequency) photons into short wavelength (high frequency) photons with high efficiency and sensitivity (www.nist.gov/itl/antd/nir_082509.cfm).

According to Matthew Rakher and Kartik Srinivasan, two authors of the paper, previous up-conversion experiments looked at the color conversion of highly attenuated laser beams that contained less than one photon on average. However, these light sources still exhibited "classical" photon statistics exactly like that of an unattenuated laser, meaning that the photons are organized in such as way that at most times there are no photons while at other times there are more than one. Secure quantum communications relies upon the use of single photons.

"The quantum dot can act as a true single photon source," says Srinivasan. "Each time we excite the dot, it subsequently releases that energy as a single photon. In the past, we had little control over the wavelength of that photon, but now we can generate a single photon of one color on demand, transmit it over long distances with fiber optics, and convert it to another color."

Converting the photon's wavelength also makes it easier to detect, say co-authors Lijun Ma and Xiao Tang. While commercially available single photon detectors in the near-infrared suffer noise problems, detectors in the near-visible are a comparatively mature and high-performance technology. The paper describes how the wavelength conversion of the photons improved their detection sensitivity by a factor of 25 with respect to what was achieved prior to conversion.

*M. T. Rakher, L. Ma, O. Slattery, X. Tang, and K. Srinivasan. Quantum transduction of telecommunications band single photons from a quantum dot by frequency upconversion. Nature Photonics. Published online Oct. 3, 2010, doi:10.1038/nphoton.2010.221

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

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Baldrige Program Name Change Emphasizes Performance Excellence

After 23 years as the "Baldrige National Quality Program," the nation's public-private partnership dedicated to performance excellence has decided to highlight that mission with a new name—the Baldrige Performance Excellence Program.

"Performance excellence" describes a focus on overall organizational quality, and for years, followers of the Baldrige Criteria for Performance Excellence have indicated that this term best reflects what makes Baldrige work. This opinion was confirmed by a study in 2007 that recommended changing the name of the Baldrige Program. The recent realignment of the Baldrige Program's parent agency, the National Institute of Standards and Technology (NIST), provided a logical time to make this happen.

Baldrige Program Director Harry Hertz said, "We are pleased to now make performance excellence a central part of our name. In the more than two decades since the inception of the Malcolm Baldrige National Quality Award, the field of quality has evolved from a focus on product, service and customer quality to a broader, strategic focus on overall organizational quality—which we have called performance excellence. In line with this concept of overall organizational excellence, which some people refer to as "biq Q" quality, the Baldrige Criteria have evolved to stay on the leading edge of validated management practice and needs, so it is fitting that our new name emphasizes the concept of excellence."

For more information on the Baldrige Performance Excellence Program and the Baldrige Award, go to www.nist.gov/baldrige.

Media Contact: Michael E. Newman, michael.newman@nist.gov, 301-975-3025

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NIST, NTIA Seek Collaborators for Emergency Communications Demo Network

The National Institute of Standards and Technology (NIST) and the National Telecommunications and Information Administration (NTIA) are seeking partners in the telecommunications industry to help create a demonstration broadband communications network for the nation’s emergency services agencies.

The demonstration network, currently being developed by the joint NIST-NTIA Public Safety Communications Research (PSCR) program, will provide a common site for manufacturers, carriers, and public safety agencies to test and evaluate advanced broadband communications equipment and software tailored specifically to the needs of emergency first responders. The network will use a portion of the 700 megahertz (MHz) radio frequency spectrum freed up by last year’s transition of U.S. broadcast television from analog to digital technologies (see NIST Tech Beat, Dec. 15, 2009, at www.nist.gov/oles/network_121509.cfm).

Alcatel-Lucent is the first vendor of public safety broadband equipment to formally join the PSCR demonstration network project, signing a Cooperative Research and Development Agreement (CRADA) with NIST and NTIA in September, 2010. The two agencies hope that other companies will follow suit, creating a truly multi-vendor environment for testing and evaluating the demonstration network, as well as the e

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