NIST Tech Beat - December 9, 2008

In a pioneering effort, researchers at the National Institute of Standards and Technology (NIST) and the University of Queensland in Australia have successfully demonstrated* that they can count, size and gauge the quality of virus-like particle-based (VLP) vaccines much more quickly and accurately than previously possible. Their findings could reduce the time it takes to produce a vaccine from months to weeks, allowing a much more agile and effective response to potential outbreaks.

Viruses are small, simple bodies consisting of DNA or RNA wrapped in a protein shell studded with short strands of protein. Viruses use these short strands of protein like a skeleton key to unlock and invade healthy cells, replace their DNA, hijack the cells’ replication machinery and turn them into virus-producing factories. As with smallpox and influenza, the only way to combat the virus is through vaccination, in which dead or weakened viruses are injected into the body. Unable to cause any real harm, the dead or weakened viruses allow the body to develop antigens that can fight off the infection in the future.

“The problem with this approach is that it takes a long time to develop vaccines because viruses have to be grown in chicken eggs or cell culture, which can take months,” said Leonard Pease, a NIST researcher working on the project. “In the case of new diseases, such as bird flu, which spread very rapidly, thousands or even millions of people could become infected and die in the time it takes to produce an effective vaccine.”

In order to speed the creation and delivery of these life-saving treatments, scientists at NIST and the University of Queensland in Australia are working to develop a new class of vaccines with virus-like particles (VLP). First used in the cervical cancer vaccine, VLP-based vaccines consist of an artificial protein shell that has been coated with proteins specific to whatever disease the vaccine is intended to control. Although the VLP is dressed up to look like the real thing to the body’s immune system, it contains no DNA or RNA and is incapable of causing infection. Because VLPs do not have to be grown, vaccines based on these particles can be deployed much faster than traditional vaccines.

Whether or not a VLP-based vaccine will be effective depends on whether the VLPs are well-formed and properly coated. Electrospray differential mobility analysis (ES-DMA) is a particle sizing technique able to count millions of particles an hour with subnanometer resolution. NIST researcher Leonard Pease and his team were able to determine that well-formed VLPs that have been coated with bird flu proteins are 2 nanometers larger than those without, a critical step towards the creation of future bird flu vaccines. The team verified their results using a number of other highly accurate, but much slower, particle sizing methods. This experiment marked the first time that ES-DMA has been used to characterize VLPs, though researchers at NIST have also shown the technique to be useful for other biological applications (See “NIST Trumps the Clumps: Making Biologic Drugs Safer”.)

NIST scientists plan to adapt the technique as a means of creating virus filter testing solutions in collaboration with virus filter manufacturers to ensure vaccines given to the public meet Food and Drug Administration safety standards.

* L.F. Pease III, D.I. Lipin, D-H. Tsai, M.R. Zachariah, L.H.L. Lua, M.J. Tarlov and A.P.J. Middelberg. Quantitative characterization of virus-like particles by asymmetrical flow field flow Fractionation, electrospray differential mobility analysis, and transmission electron microscopy (http://dx.doi.org/10.1002/bit.22085). Biotechnology and Bioengineering. Published Online: Aug. 18, 2008.

Scientists at the National Institute of Standards and Technology (NIST) have developed software that improves the accuracy of the tracking devices in its immersive, or virtual, research environment by at least 700 percent. The software can be used by scientists in other immersive environments with slight modifications for their individual laboratories. This advance is a step forward in transforming immersive technology that has traditionally been a qualitative tool into a scientific instrument with which precision measurements can be made.

Immersive environments such as NIST’s are typically made up of two or more 8 foot by 8 foot walls onto which images ranging from larger-than-life bodies or actual-size buildings can be displayed on the walls and the floors. The images are three-dimensional. Researchers wear 3-D glasses and hold a wand, each of whose location is tracked. Using these devices the researcher can walk around and interact with the virtual world with the help of the underlying graphics system.

While these small virtual reality laboratories have been around for more than a decade, they have mainly been used for a scientist to get inside a project and develop a feel of the object of study, explained NIST mathematician John Hagedorn. Researchers can walk inside hallways of newly designed buildings before they are constructed to ensure the proportions are correct, or inspect microscopic structures, for example.

The visuals in immersive environments are sometimes not quite accurate because of an inherent problem with the electromagnetic transmitters and receivers used to track where the user is in the space. Ferrous metals such as rebar in the walls, other metal in the room or metal walls, throw off the communications between the stationary and the small receivers attached to the tracked devices. These distortions are especially obvious when an image with lines or edges meets the virtual environment’s 90 degree angles where the walls and the floor meet. These distortions interfere with the “reality” aspect and limit the immersive environment’s value as a measurement tool.

To improve the image’s accuracy, Hagedorn and colleagues concentrated on the inaccuracy of the tracking devices. They knew there was a difference between where the tracking device said it was and where it really was. The researchers mapped two sets of data points—where they knew the sensors actually were and where the computer said they were. Using this data, they developed software that transforms the reported positions of the sensors into the actual position. “Our program,” Hagedorn said, “provides corrections of both the location and the orientation in the 3-D space.” Average location errors were reduced by a factor of 22; average orientation errors by a factor of 7.5.

“This improvement in motion tracking has furthered our goal of turning the immersive environment from a qualitative tool into a quantitative one—a sort of virtual laboratory,” Hagedorn explained. The first test with the new software was measuring a lattice structure with elements of about 2 to 3 millimeters in size designed to grow artificial skin replacements or bone. A 3-D image of the structure was constructed (see photo) using data obtained from a high-resolution microscope. NIST scientists interactively measured the diameters of the fibers and the spacing between the layers of fiber using the virtual lab. These precision measurements enabled the researchers to determine that the manufactured material substantially deviated from the design specification. On the other hand, additional measurements in the immersive environment showed that the angles between fibers in the manufactured material closely matched the design.

Carbon, the active ingredient in charcoal, is normally not considered a fire retardant, but researchers at the National Institute of Standards and Technology (NIST) have determined that adding a small amount of carbon nanofibers to the polyurethane foams used in some upholstered furniture can reduce flammability by about 35 percent when compared to foam infused with conventional fire retardants.

Laws require mattresses and upholstered furniture sold in California and used in public spaces such as hotels and offices be treated with fire retardants or barrier fabrics to minimize fire fatalities and injuries and to cut damage costs. According to the National Fire Protection Association, the total burden of fire in the United States was about $270 billion in 2005.

Ten years ago, NIST scientists found that nanoclays could be used as an effective fire retardant additive, but researchers have been seeking alternatives because nanoclay flame retardants do not prevent the melting and dripping of polyurethane foam when exposed to a fire. This molten foam accelerates the burning rate by as much as 300 percent. “It also creates so much smoke that it is a life-safety hazard,” said Jeff Gilman, leader of the Materials Flammability Group in the Building and Fire Research Laboratory.

Researchers added carbon nanofibers to the foam because they knew that adding nanoparticles to a polymer normally increases the viscosity, so it doesn’t flow as easily. “The carbon nanofibers help prevent the foam from dripping in a pool under the furniture and increasing the fire intensity,” Gilman said. Studies of the foam after the experiments showed that carbon nanofibers seemed to create a thermally stable, entangled network that kept the foam from dripping.

NIST fire researchers have traditionally used upholstered furniture to study its flammability, but in this study, they developed a small-scale technique for evaluating the effect of dripping and pooling on foam flammability. About the size of a slice of toast, the foam samples were treated with one of six combinations of carbon nanofibers or conventional clay flame retardants. The foam “toast” was suspended vertically over a pan, ignited, and the amount of drip was measured. The foam with carbon nanofibers did not drip.

“These small-scale experiments correlate well with the fire behavior of larger foam samples and are easier and less expensive to conduct,” said Gilman. “The small-scale tests will allow us to cost-effectively perform more experiments and help us find an optimal fire retardant faster.”

“Carbon nanofibers are still more expensive than conventional flame retardant materials, but because the price is decreasing and so little needs to be used, they could soon be an affordable and effective option,” Gilman explained.

NIST fire scientists will continue to study the mechanisms that reduce flammability and dripping and work with chemical companies, nano-additive suppliers, flame retardant suppliers and foam manufacturers to test new blends of foam and carbon nanofibers to improve flame retardant material. Additionally, new work is planned to develop sustainable, environmentally friendly fire retardants using cellulosic nanofibers and testing other innovative fire retardant approaches.

The National Institute of Standards and Technology (NIST) has announced the first conference on an open cryptographic competition to select a new “hash” algorithm for securing digital signatures and other information security applications. The First SHA-3 Candidate Conference will be held Feb. 25-28, 2009, at the Katholieke Universiteit Leuven, a university in Belgium, immediately following the 16th International Workshop on Fast Software Encryption.

The ultimate purpose of the NIST-sponsored competition, which has inspired dozens of entries from around the world, will be to select a new algorithm—SHA-3—that is more secure and efficient than its predecessors. A hash algorithm is a widely-used mathematical tool that converts a file, message or block of data to a short “fingerprint” for use in digital signatures, message authentication and other computer security applications.

NIST has been determining which of the 64 entries it has received are “complete and proper” and therefore can be accepted as first-round candidates. At the February conference, the first-round candidates will be presented by their submitters, and NIST will discuss the next steps for the competition. By 2012, NIST plans to hold two more conferences to narrow down the candidates and decide upon the finalist, which will then be incorporated into government cryptographic standards.

Because of the large response to the competition, it appears that the number of accepted submissions will considerably exceed the number that NIST and the community can analyze thoroughly in a reasonable time. NIST is considering ways to involve the cryptographic community in quickly reducing the number of submissions to a more manageable number. The process and criteria for this selection will be a major topic of this conference.

Nine staff members of the National Institute of Standards and Technology (NIST) have been elected new fellows of the American Physical Society, the largest professional organization of physicists based in North America with approximately 46,000 members. APS fellowships are a recognition of professional achievement as judged by peers and go to no more than one half of one percent of APS members each year.

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Editor: Michael Baum

Date created: December 9, 2008
Date updated: December 9, 2008
Contact: inquiries@nist.gov