X-Rays Shine Light on Enzyme Secrets

Imagine solving a 30,000-piece three-dimensional puzzle when you don’t know what it’s supposed to look like and when many of the pieces are identical. That’s essentially what scientists at NIST and the Center for Advanced Research in Biotechnology (jointly operated by NIST and the University of Maryland) did recently when they solved the three-dimensional structure of an enzyme called threonine deaminase.

The enzyme controls production of vital amino acids in E. coli, a ubiquitous bacteria used as a research model. The enzyme structure long has intrigued scientists because it has a switch on one end for turning itself on or off. Pharmaceutical researchers now can use knowledge of its structure to develop new antibiotic drugs.

The colorized computer model above (first reported in the journal Structure) shows the symmetry of the four-part molecule. The NIST/CARB researchers produced the model by coaxing the enzyme’s molecules to assemble into crystals and then shining X-rays through the crystals. A map derived from the scattering data then was painstakingly compared with known patterns for specific amino acids to determine the enzyme’s detailed 30,000-atom structure.

The newly revealed structure also may be useful for developing better weed control chemicals and for improving production of biodegradable plastics.

Contact: Travis Gallagher, (301) 975-5726.

Genetic Bar Coding Speeds DNA Testing

Just as bar codes have helped speed up trips to the supermarket, a new technology developed with co-funding from the NIST Advanced Technology Program is helping scientists speed up identification of genetic variations.

Developed by Third Wave Technologies Inc. of Madison, Wis., the novel genetic screening technique provides a fast, inexpensive way to turn DNA samples into individualized bar code patterns that can be scanned quickly for specific mutations. The technique costs up to 79 percent less per sample than other methods, including automated DNA sequencing.

DNA sequencing laboriously identifies the precise order in which four chemical bases appear in a gene fragment. In contrast, Third Wave’s CFLP method uses patented processing methods and enzymes to create and identify tell-tale folds in single-stranded DNA that indicate specific chemical sequences. If DNA sequencing is equivalent to reading every word of an organism’s assembly instructions, then CFLP is a speed reading method that concentrates on critical junctures to infer the rest of the book.

CFLP (cleavage fragment length polymorphism) generates a distinct bar code for every unique DNA sequence. Thus mutations can be detected by comparing a sample to a normal coding pattern. The method should have a broad range of applications for research, diagnosing and treating infections and hereditary diseases, and accelerating drug development. For example, CFLP can distinguish between different strands of the bacterium that causes tuberculosis. This means doctors will be able to treat specific patients with tailored drug treatments that minimize drug resistance problems.

Third Wave recently received a second ATP award to develop generic, enzyme-based technologies suitable for health-care applications, such as large-scale treatment monitoring and point-of-care testing.

Contact: Lance Fors, (608) 663-7000.

Versatile Crystals Find Markets

What’s harder than nails, pretty as diamond, and hotter than red hot chili peppers? Silicon carbide.

If you haven’t heard about it yet, don’t feel badly. Silicon carbide crystals and semiconductor wafers are an emerging technology developed by Cree Research, a small Durham, N.C., company. Back in 1991, Cree received almost $2 million in co-funding from NIST’s Advanced Technology Program for a two-year project to develop a better way to process silicon carbide into large, high-quality single crystals. Today, the company has growing revenues for a wide range of silicon-carbide-based products and for the sale of raw silicon carbide wafers to the electronics industry.

Silicon carbide long has been known for its useful properties. It’s almost as hard as diamond, tolerates high temperatures, and responds to electrical currents by emitting blue light. The problem with the material has been in trying to grow enough high-quality silicon carbide crystals at large enough sizes to make the material economically viable.

Cree’s ATP funding helped the company double wafer sizes from 1 to 2 inches, reduce defects from 400 to 180 per cm2, and reduce costs for blue LEDs (light-emitting diodes, see photo above) from 48 cents to 18 cents. Cree’s lightweight blue LEDs now are used in a wide range of products from auto dashboards to giant stadium “instant replay” displays. Other applications under development by Cree, its customers, and research partners include:
n power semiconductors, which could enhance by up to 20 percent the efficiency of electrical vehicles and electric power switching systems;

• blue lasers, which could enable four- to eight-fold increases in the storage capacity of digital video disks now using longer wavelength red lasers;
• microwave devices that could increase the power and reduce the complexity of cellular base stations;
• powerful, low-cost, high-definition television systems, and
• diamond-like jewelry made of silicon carbide crystals.

Contact: Calvin Carter, (919) 361-5709.

79 R&D Projects Get ATP Award

New technologies to provide stand-alone sources of clean, reliable electric power; a possible method to restore nerve function to victims of spinal-cord injuries; advanced materials and manufacturing technologies for future generations of integrated circuits; and a truly three-dimensional computer display technology are among the diverse goals set by 79 new industrial research projects selected for co-funding with industry by NIST’s Advanced Technology Program.

The majority of the awards, 54, went to small businesses, either for single-company projects or as the lead company in an industry joint venture. Eleven universities and more than 150 companies are involved in the projects as formal participants.

If carried through to completion, the 79 projects will be funded at approximately $224 million from private industry, matched by approximately $236 million from the ATP. Details about the projects are available at www.atp.nist.gov or by calling (301) 975-2758.

Smaller Chips Need Ever Smaller Rulers

U.S. industry increasingly has called for more accurate methods with which to measure the widths of circuit features inside those ever shrinking microchips. The problem is that semiconductor manufacturers now are able to produce circuits with features that are actually too small to be measured reliably with existing metrology systems.

NIST and Sandia National Laboratories—with support and funding from International SEMATECH and the Department of Energy—are hoping to solve this dilemma by creating a reference material for microscopes designed to allow accurate measurement of circuit features as small as one-tenth of a micrometer (or 500 times thinner than a human hair).

The NIST prototype reference material contains silicon lines etched with extremely flat tops and vertical, flat walls. This makes them inherently easier to measure consistently than current artifacts that have less perfect boxy shapes.

Crystalline silicon atoms form repeating patterns that have been well studied in the past. Like the metal bars of a cubic jungle gym, the centers of atoms in a “perfect” silicon crystal lattice are each the same distance away from their nearest neighbors. This means scientists can use the known atom spacings as a ruler for measuring circuit line widths.

The prototype artifact includes a window that has been cut out of the silicon substrate below the specially made lines. (See micrograph below.) The window cut in the substrate provides an unobstructed view of the lines, allowing an electron beam to be shined on the line from below and the transmitted electrons collected on the other side. The pattern of electron transmission reveals the number of silicon lattice spacings across each silicon line. This, in turn, should allow the researchers to determine linewidths more precisely than with other methods, short of counting individual atoms. So far they have demonstrated the prototype with a 0.35 micrometer line and are working to apply the concept to narrower linewidths.

The electronics industry is expected to use the reference materials to calibrate machines that monitor linewidth as microchips are being manufactured. The research team is forming an industrial consortium to evaluate the performance of the latest prototype chips.

Contact: Michael Cresswell, (301) 975-2072.

Better Detectors With Microgravity

If you hear hoof beats think horses, not zebras. Good advice, except the simple answer isn’t always the right one. When a high-tech company wanted to increase the sensitivity of its specialty crystals for detecting high-energy radiation, it joined a project with NIST and the National Aeronautics and Space Administration to grow the crystals on the space shuttle. All crystals are expected to grow better without the strain of gravity tugging in one direction. Experiments on two space shuttle flights proved that the crystals of mercuric iodide grown in space did indeed perform better as gamma-ray detectors.

But a recent series of X-ray diffraction experiments conducted by the NIST research team at the Brookhaven National Synchrotron Light Source produced a surprising reason for the improvement. The crystal planes of the space-grown crystals were actually less uniform than the Earth-grown variety, but the lack of gravity caused fewer chemical composition flaws in the materials. Constellation Technology Corp. of Largo, Fla., now is using results of this research to improve processing of the crystals on Earth. Because mercuric iodide crystals work at room temperature, they may be able to replace more costly radiation detection materials that require cooling to liquid nitrogen temperatures.

The difference between the Earth-grown and space-grown crystals is seen easily in these colorized, multiple-exposure diffraction images. A beam of highly parallel X-rays was reflected off crystals grown both on Earth and on the space shuttle. A perfectly made crystal would diffract all the X-rays evenly, creating a uniformly light image.

The space crystal on the left diffracted much more of the X-ray energy than the crystal on the right made on Earth. The researchers found that the Earth-grown crystals contained more chemical flaws. The individual cells of the Earth crystals, which are shaped like elongated boxes, also were more likely to be pointing in slightly different directions, which blocked diffraction of more X-rays, producing a darker image.

Contact: Bruce Steiner, (301) 975-5977 or
Lodewijk van den Berg, (727) 547-0600, ext. 6175.

Smoke Alarms with 'Brains'

A new generation of “smart” smoke alarms soon may end the many false alarms caused by hypervigilant detectors. Some current detectors are activated by steam from the shower or by a small amount of smoke from cooking. False alarms in the cargo holds of commercial aircraft can force unnecessary emergency landings. NIST fire researchers have developed a flow tunnel—similar to a wind tunnel—specially designed to test smart smoke detectors. The smart detectors can use as many as three different detection technologies and microprocessor technology to help the detector “decide” when to signal an alarm. For example, a detector might be programmed to ignore vapor that is not accompanied by rising temperatures. The NIST facility will allow smoke detector manufacturers to see how their products react to vapor, varying humidity levels, smoke produced by different kinds of fires, and even invisible gases such as carbon monoxide.

Contact: Thomas Cleary, (301) 975-6858.

Bullet 'Fingerprints' Meet Their Match

They’re not your typical used bullets. In fact, they are fired bullet look-alikes—painstakingly designed replicas that NIST aims to develop into standard tools to help solve gun-related crimes. For the National Institute of Justice, NIST plans to manufacture batches of “standard bullets,” each bearing almost identical sets of ultrafine surface marks produced with a computer-controlled cutting tool. The marks are reproductions of scratch-like grooves that a bullet acquires as it exits through the barrel. Unique to each firearm, patterns of these striations can be used to match a bullet recovered at a crime scene to the gun that fired it. Detailed optical measurements of these signature patterns yield images that can be compared to images from other bullets stored in databases. However, the highest levels of consistency between instruments are required to make definitive matches. NIST’s standard bullets will help forensics experts check the consistency of their instruments. If the instruments correctly match the standard bullet to its computerized image file, then those same instruments are likely to correctly match bullets collected as evidence to images on file. The project is part of a planned integrated ballistics information network for forensics labs.

Contact: Junfeng Song, (301) 975-3799.

NIST Sponsors Historic Data Scrambling Battle

When Alexander the Great stormed across three continents, he sent his army commanders encoded messages. Today, encoded messages are essential for everything from million-dollar bank transfers, to electronic mail, to the use of credit cards on the Internet. To help ensure that computer encryption systems are tough enough for the 21st century, NIST invited cryptographers from around the world to compete in the Advanced Encryption Standard contest. Researchers from 12 different countries submitted 15 candidate algorithms for the AES. These sophisticated mathematical formulas are at the heart of computerized encryption systems, which scramble and decode information so that it can be understood only by the intended recipient. NIST is evaluating the algorithms, and cryptographers have been asked to “attack” each of the formulas to try to crack the codes. The American candidates include algorithms developed by IBM Corp., RSA Laboratories of San Mateo, Calif., Cylink Corp. of Sunnyvale, Calif., Counterpane Systems of Minneapolis, and a computer scientist from the University of Arizona.

Contact: James Foti, (301) 975-5237.

Testing Cameras Get an Eyeful

It’s hard to beat the human eye for detecting fine shades of black to white—few cameras can come close. As a result, measurements of contrast ratios—an essential yardstick used by industry to rate electronic displays—have not been as discriminating between displays of different qualities as researchers would like. Now, NIST researchers have borrowed a feature from the human eye to improve these measurements. Because the eye is filled with liquid, it does not suffer as much from extraneous light reflections that typically cause glare in artificial lens systems. NIST researchers built a prototype system containing oil between the lens and the camera’s charge-coupled device, or CCD, sensor. Initial results showed a dramatic improvement in the camera’s ability to discern contrast ratios; the liquid system was nearly 70 times better than the same system without liquid. Such an innovation one day might enable U.S. manufacturers to better test displays that they plan on purchasing. The liquid-filled camera concept also might be useful for digital cameras, which typically use CCD sensors.

Contact: Edward Kelley, (301) 975-3842.

Microscope Doctor -- A collaborative effort by NIST, Hewlett Packard, and SPECTEL Co. of Mountain View, Calif., was recently honored with a R&D 100 award from Research and Development magazine. The team’s SEM Monitor is the first technology to qualitatively and quantitatively measure a scanning electron microscope’s performance, astigmatism, and image quality. SEM Monitor makes measurements in less than a fifth of a second, enabling users to adjust and align a microscope in real time and optimize performance. This in-line performance check and improvement system greatly benefits the semiconductor industry, which depends on SEMs to inspect silicon wafers. Contact: Michael Postek, (301) 975-2299.

Optical Lab --The W.M. Keck Foundation of Los Angeles has awarded a $962,000 grant to establish an optical measurement laboratory at JILA, a joint institute of NIST and the University of Colorado. Scheduled to open in the summer of 1999, the facility will provide a world-class resource for optical metrology. Major activity areas will include optical materials preparation, laser characterization, fiber nanofabrication, and electronic signal analysis. Contact: James Faller, (303) 492-8509

Manufacturing Help -- Excalibur USA of Oxnard, Calif., recently got some welcome help from the California Manufacturing Technology Center, an affiliate of NIST’s Manufacturing Extension Partnership. Excalibur asked the center to help it improve the quality of its window covering systems, while increasing process flow and management of inventory. After implementing changes recommended by CMTC, productivity increased by 63 percent, wait-time for shipping orders decreased by 10 percent, and employee turnover has been cut by 10 percent because of improved morale. Smaller manufacturers can call 1-800-MEP-4MFG to reach the MEP center that serves them. For information on CMTC or Excalibur, contact Bob Bishop at (310) 263-3082.

Standards Summit -- The U.S. economy will suffer unless American companies, standards-developing organizations, and government agencies join together to realize a more coherent and effective standards strategy, participants at a U.S. “standards summit” agreed in September. Attended by more than 300 industry, association, and federal representatives, the meeting took steps toward achieving that strategy. Held in Washington, D.C., the conference was co-sponsored by NIST and the American National Standards Institute. To receive a summary report on the summit now in preparation, call (301) 975-4000.

About Technology at a Glance:

NIST is an agency of the U.S. Department of Commerce's Technology Administration. NIST promotes U.S. economic growth by working with industry to develop and apply technology, measurements, and standards. Technology at a Glance is produced by Public and Business Affairs, A903 Administration Bldg., NIST, Gaithersburg, Md. 20899-0001. Any mention of commercial products is for information only; it does not imply recommendation or endorsement by NIST. Technology at a Glance Editor: Gail Porter, (301) 975-3392, email: gail.porter@nist.gov. For patent information, call (301) 975-3084.

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