In This Issue...
Scaffold Gradients: Finding the Right Environment for Developing Cells
People often have strong opinions on the "right" firmness of mattresses for themselves, and, as it turns out, some cell types have similar preferences for their support structures. Now a research team from the National Institute of Standards and Technology (NIST) and the National Institutes of Health (NIH) has developed a way to offer cells a three-dimensional scaffold that varies over a broad range of degrees of stiffness to determine where they develop best. Their recently published technique* is a way to rapidly optimize 3D cell growth media to meet the developmental needs of specific cell types for a wide variety of potential tissue-replacement therapies.
Tissue engineering is a relatively new field that is developing methods to grow or regenerate bodily tissues—skin, bone, cartilage, blood vessels, perhaps one day even whole organs—to replace those damaged by injury or disease. One of the key challenges in the field is developing appropriate three-dimensional "scaffolds," artificial materials that can hold tissue progenitor cells and allow them to be nurtured and supported while they multiply and develop into desired tissues. Research has shown that cells often need to develop in a 3D environment if they are to mature and differentiate properly.
Hydrogels—most familiar for their use in soft contact lenses—are a promising material for tissue scaffolds. They consist of a loose network of polymer chains that is swollen with water; in fact, like the majority of the body’s tissues, they are mostly water.
But, says NIST materials scientist Kaushik Chatterjee, deciding on a hydrogel is just the beginning. "Now you’ve got these gels, what sort of properties do you want? What gets you the best kind of whatever tissue you’re after—in our case, bone? We focused on stiffness because cells are known to sense and respond to changes in the stiffness of their environment."
To test this, the research team developed a method to create samples of a typical hydrogel used in biomedical research, PEGDM**, where the stiffness of the gel increases smoothly from one end of the sample to the other. This approach, using smoothly varying gradients of compounds to test many possible combinations simultaneously, is called combinatorial screening. NIST has pioneered such techniques for a variety of materials problems***, but this research is one of the first applications of combinatorial screening to 3D scaffolds for tissue engineering. The team tested the technique on mouse osteoblasts—cells responsible for building bone—mixed in with the PEGDM gel. Interestingly, although cell survival rates were higher at the softer end of the test strips and got progressively worse towards the stiffer ends, cell differentiation and mineralization, which are measures of how well the cells actually develop into bone tissue, did the reverse. Fewer cells survive in a stiff gel, but those that do are much more active in building bone. That result, of course, is specific to osteoblasts, says Chatterjee, "These are bone cells and they seem to like the stiffer environment more than softer ones, but you could apply something similar to, say, nerve cells, and they might like the softer ones more."
In addition, the researchers note, the gel stiffness gradient induced a matching gradient in the tissue mineralization. This is potentially important, they say, because tissue gradients often occur naturally at the interfaces of, for example, teeth or ligaments, so 3D scaffold gradients could be a valuable tool for engineering graded tissues for regenerative medicine.
The research was supported by NIST and NIH.
* K. Chatterjee, S. Lin-Gibson, W.E. Wallace, S.H. Parekh, Y.J. Lee, M.T. Cicerone, M.F. Young and C.G. Simon Jr. The effect of 3D hydrogel scaffold modulus on osteoblast differentiation and mineralization revealed by combinatorial screening. Biomaterials 31 (2010), doi:10.1016/j.biomaterials.2010.03.024.
** poly(ethylene glycol) dimethacrylate
*** See, for example, "NIST Study Finds a Decade of High-Payoff, High-Throughput Research," NIST Tech Beat, May 20, 2009 at http://www.nist.gov/msel/polymers/throughput_052009.cfm.
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NIST Scientists Gain New 'Core' Understanding of Nanoparticles
While attempting to solve one mystery about iron oxide-based nanoparticles, a research team working at the National Institute of Standards and Technology (NIST) stumbled upon another one. But once its implications are understood, their discovery* may give nanotechnologists a new and useful tool.
The nanoparticles in question are spheres of magnetite so tiny that a few thousand of them lined up would stretch a hair’s width, and they have potential uses both as the basis of better data storage systems and in biological applications such as hyperthermia treatment for cancer. A key to all these applications is a full understanding of how large numbers of the particles interact magnetically with one another across relatively large distances so that scientists can manipulate them with magnetism.
“It’s been known for a long time that a big chunk of magnetite has greater magnetic ‘moment’—think of it as magnetic strength—than an equivalent mass of nanoparticles,” says Kathryn Krycka, a researcher at the NIST Center for Neutron Research. “No one really knows why, though. We decided to probe the particles with beams of low-energy neutrons, which can tell you a great deal about a material’s internal structure.”
The team applied a magnetic field to nanocrystals composed of 9 nm-wide particles, made by collaborators at Carnegie Mellon University. The field caused the particles to line up like iron filings on a piece of paper held above a bar magnet. But when the team looked closer using the neutron beam, what they saw revealed a level of complexity never seen before.
“When the field is applied, the inner 7 nm-wide ‘core’ orients itself along the field’s north and south poles, just like large iron filings would,” Krycka says. “But the outer 1 nm ‘shell’ of each nanoparticle behaves differently. It also develops a moment, but pointed at right angles to that of the core.”
In a word, bizarre. But potentially useful.
The shells are not physically different than the interiors; without the magnetic field, the distinction vanishes. But once formed, the shells of nearby particles seem to heed one another: A local group of them will have their shells’ moments all lined up one way, but then another group’s shells will point elsewhere. This finding leads Krycka and her team to believe that there is more to be learned about the role that particle interaction has on determining internal, magnetic nanoparticle structure—perhaps something nanotechnologists can harness.
“The effect fundamentally changes how the particles would talk to each other in a data storage setting,” Krycka says. “If we can control it—by varying their temperature, for example, as our findings suggest we can—we might be able to turn the effect on and off, which could be useful in real-world applications.”
The research team, which also included scientists from Oberlin College and Los Alamos National Laboratory, used neutron instrumentation supported in part by the National Science Foundation (NSF). Research at Carnegie Mellon and Oberlin also received support from NSF.
* K.L. Krycka, R.A. Booth, C. Hogg, Y. Ijiri, J.A. Borchers, W.C. Chen, S.M. Watson, M. Laver, T.R. Gentile, L.R. Dedon, S. Harris, J.J. Rhyne and S.A. Majetich. Core-shell magnetic morphology of structurally uniform magnetite nanoparticles. Physical Review Letters, 104, 207203 (2010), DOI 10.1103/PhysRevLett.104.207203
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NDE Methods for Evaluating Ancient Coins Could be Worth Their Weight in Gold
Demonstrating that chemistry sometimes can inform history, researchers from the National Institute of Standards and Technology (NIST), Colorado College and Mount Saint Mary's University in Emmitsburg, Md., have shown that sensitive nondestructive evaluation (NDE) techniques can be used to determine the elemental composition of ancient coins, even coins that generally have been considered too corroded for such methods*. Along the way, the researchers’ analysis of coins minted in ancient Judea has raised new questions about who ruled the area while giving insight into trading patterns and industry in the region.
Elemental and isotope analysis of the metals in ancient artifacts sometimes can pinpoint the places where the metal was mined, because ores in a given region often have a unique composition. This can be combined with historical records of when mines in the area were operating to determine when the coin was likely struck. The results not only help date the coin, but also offer insight into trade and power relationships in the region.
To compare the effectiveness of various nondestructive analytical methods with destructive methods often used to determine the age and origin of ancient coins, the group studied coins minted by Kings Herod Agrippa I and Agrippa II in what is modern day Palestine and Israel, a biblically and historically significant period.
The vast numbers of a particular coin, a prutah, found in the archaeological record has led scholars to disagree about when they were struck and by whom. The provenance of the coin is important because it is used to establish dates for places and events in the early years of Christianity and the onset of the Jewish War (66-70 CE) against the Romans and the Diaspora that followed.
To better establish whether the coins were minted by Agrippa I (41-45 CE) or Agrippa II (after 61 CE), the team performed X-ray fluorescence and lead isotope analysis to fingerprint the ores used in the production of the coins. These NDE methods are not commonly used on corroded coins because the corrosion can affect the results—in some cases making it difficult to get a result at all. The team showed that these problems could be overcome using polarizing optics and powerful new software for X-ray fluorescence analysis, combined with careful calibration of the mass spectrometer using Standard Reference Materials from NIST**.
The lead isotope analysis, performed at NIST, showed that the coins that had been attributed to Agrippa I were indeed from that era. More interestingly, however, the group found that the copper from which the coins were made most likely came from mines that scholars thought hadn’t been opened until a century later.
“All the archaeological evidence has thus far suggested that the Romans had moved into Arabia in the 2nd century CE,” says Nathan Bower of Colorado College. “What this analysis shows is that the Romans may have reached the region earlier or found that these mines had already been opened. Either way, our findings suggest that the Romans had a much closer relationship with this particular region than scholars had previously thought.”
To follow up on their research, the group is planning to perform more tests to determine if the mines in question may have been operating even earlier than their recent findings suggest.
* M. Epstein, D. Hendin, L. Yu, and N. Bower. Chemical attribution of corroded coins using X-ray fluorescence and lead isotope ratios: A case study from first century Judaea. Applied Spectroscopy, Vol. 64, Issue 4, pp. 384-390 (2010).
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Robots Big and Small Showcase Their Skills at NIST Alaskan Events
Make room, Bender, Rosie and R2D2! Your newest mechanical colleagues are a few steps closer to reality, thanks to lessons learned during two robotics events hosted by the National Institute of Standards and Technology (NIST) at the recent IEEE International Conference on Robotics and Automation (ICRA) in Anchorage, Alaska. The events—the Virtual Manufacturing Automation Competition (VMAC) and the Mobile Microrobotics Challenge (MMC)—were designed to prove the viability of advanced technologies for robotic automation of manufacturing and microrobotics.
In the first of two VMAC matches, contestants used off-the-shelf computer gaming engines to run simulations of a robot picking up boxes of various sizes and weights from a conveyor belt and arranging them on a pallet for shipping. The two teams in the competition—both from the Georgia Institute of Technology—showed that their systems were capable of solving mixed palletizing challenges. To do this, the system had to receive a previously unseen order list, create a logical plan for stacking and arranging boxes on a pallet to fulfill that order, and then computer simulate the process to show that the plan worked. Getting all of the boxes onto the pallet is relatively straightforward; however, creating a stable, dense pallet is a difficult challenge for a robot.
The second manufacturing contest “road tested” a robot’s mobility in a one-third scale factory environment. The lone participating team, the University of Zagreb (Croatia), demonstrated that it could successfully deliver packages simultaneously to different locations in the mock factory by controlling three robotic Automated Guided Vehicles (AGVs) at once.
In the microrobotics match-up, six teams from Canada, Europe and the United States pitted their miniature mechanisms—whose dimensions are measured in micrometers (millionths of a meter)—against each other in three tests: a two-millimeter dash in which microbots sprinted across a distance equal to the diameter of a pin head; a microassembly task inserting pegs into designated holes; and a freestyle competition showcasing a robot’s ability to perform a specialized activity emphasizing one or more of the following: system reliability, level of autonomy, power management and task complexity.
In the two-millimeter dash, the microbot from Carnegie Mellon University broke the world record held by Switzerland’s ETH Zurich (the event also was part of earlier NIST-hosted “nanosoccer” competitions) with an average time of 78 milliseconds. However, the achievement was short-lived. Less than an hour later, the French team (representing two French research agencies: the FEMTO-ST Institute and the Institut des Systèmes Intelligents et de Robotique, or ISIR) shattered the mark with an average time of 32 milliseconds.
ETH Zurich was the champion in the microassembly event with a perfect 12 for 12 score steering pegs approximately 500 micrometers long (about the size of a dust particle) into holes at the edge of a microchip. Runner-up was Carnegie Mellon whose microbot successfully placed 4 of 9 pegs.
ETH Zurich’s robot also captured the freestyle event, amazing spectators with its unprecedented ability to maneuver in three dimensions within a water medium. In fact, in one demonstration, the Swiss device “flew” over the edge of the microassembly field, reversed direction and pushed out the pegs it had inserted earlier. Taking second place in the freestyle event was the team from Carnegie Mellon that demonstrated how three microbots could be combined into a single system and then disassembled again into separate units. Third place in the event went to the microbot from the Stevens Institute of Technology.
NIST conducted the VMAC in cooperation with IEEE and Georgia Tech, and collaborated on the MMC with the IEEE Robotics and Automation Society. More events of this kind with evolving challenges are planned for the future, as robotics technologies mature. NIST will work with university and industry partners on these events with the goal of advancing skills that future robots—both full-size and micro-size—will need to carry out their functions.
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Time Is Money: SIM Time Network Has Far-Reaching Benefits
Clocks in the Americas and the Caribbean Islands are now ticking in unison thanks to the work of the Sistema Interamericano de Metrologia (SIM), a regional metrology organization that works to promote accurate measurements throughout the Americas. Since 2005, SIM has been building a time network, designed by the U.S. National Institute of Standards and Technology (NIST), that now extends to 16 nations.
The SIM Time Network allows each of these nations to continuously compare their clocks, with the time differences between the nations displayed on a SIM Web site. These time differences generally are very small, often less than 100 nanoseconds (100 billionths of a second).
It has been said that the world’s most commonly asked question is “What time is it?” Nations that maintain accurate time standards benefit all of their residents. Accurate time and synchronization are crucial for much or our modern technology, enabling the efficient operation of telecommunications, computer networks, electric power distribution, and many other parts of the technology infrastructure that we use every day.
The SIM Time Network began in 2005 by adopting technology developed at NIST to more easily distribute accurate time and frequency information to remote locations. NIST developed a self-contained, user-friendly system about the size of a microwave oven that can be quickly installed in any laboratory. One or more atomic clocks then are connected to the automated system, which uses the Internet and the Global Positioning System (GPS) to compare the clocks’ time with clocks at other laboratories on the network and report the results to the central servers of the SIM Time Network.
The SIM Time Network initially compared the national time standards among Canada, Mexico and the United States. The network has been rapidly expanding, and now includes time standards in Argentina, Brazil, Chile, Colombia, Costa Rica, Jamaica, Panama, Paraguay, Peru, St. Lucia, Uruguay, Guatemala, and Trinidad and Tobago as well. The time from each nation is measured every second, and the measurements are transferred across the network every 10 minutes and displayed on the Internet. The results are publicly available so that anyone can see in near real-time comparisons between the time standards for all the participating countries.
Michael Lombardi, the NIST scientist who designed the network, says that it has helped several laboratories gain status as the official timekeepers for their respective countries, and several of the SIM Time Network participants also have begun participating for the first time in the generation of official international time—Coordinated Universal Time (UTC)—a sort of weighted average of time kept by official clocks maintained by the International Bureau of Weights and Measures in France (French acronym BIPM).
The SIM Time Network has led to increased cooperation and scientific collaboration among its members. Mauricio Lopez of the Centro Nacional de Metrología (CENAM) of Mexico, who chairs the SIM Time and Frequency Working group, and his staff at CENAM led the development of a project that combines the time kept by all of the clocks in the network and produces an average timescale, called SIM Time (SIMT). The laboratories in the network can then compare their clocks to each other and to SIMT.
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NIST to Sponsor Greenhouse Gas Emissions Workshop
The National Institute of Standards and Technology (NIST) is sponsoring a workshop on June 2 and 3 to discuss technical barriers to our ability to accurately measure, report and verify greenhouse gas emissions, a critical issue in addressing a major factor in climate change.
The Greenhouse Gas Emissions Quantification and Verification Strategies Workshop, to be held at Scripps Seaside Forum in La Jolla, Calif., aims to create a dialog among scientific and industrial experts concerning the best ways to measure, report and verify greenhouse gas emissions from varied sources both in local areas and globally. These insights will form the basis for a consensus document, which will outline the key recommendations for quantifying emissions and verification strategies for the future.
Among the main questions for consideration at the workshop will be:
To register and for more information, visit http://events.energetics.com/NISTScripps2010/. Registration costs $195; fee includes two continental breakfasts and two lunches.
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July Workshop Devoted to Improving Usability of Health Care IT
Improving the ease of use of information systems for the health care industry could significantly facilitate the adoption of technology that has great potential to improve the quality of health care while reducing costs. The goal is to allow medical professionals interact with health care information technology quickly and easily to support their primary tasks rather than complicate them. Along the way, steps must be taken to ensure that health IT systems are accessible to people with disabilities.
Toward these ends, the National Institute of Standards and Technology (NIST) will be hosting a one-day workshop on improving the usability—ease of use—of health IT. Co-sponsored by the Department of Health and Human Services Office of the National Coordinator and the Agency for Healthcare Research and Quality, the workshop will take place on July, 13, 2010, at the NIST Gaithersburg campus.
The goal of the workshop is to promote collaboration in health IT usability among federal agencies, industry, academia and others. Attendees will discuss ways to prioritize, align and coordinate short-, medium-, and long-term strategies and tactics to improve the usability of electronic health records (EHRs). Specific objectives of the workshop will be to establish an immediate-term set of actions to inform the national initiative to drive the adoption and meaningful use of EHRs; develop a strategic approach to measure and assess the use of EHRs and the impact of usability on their adoption and innovation; develop strategies to drive best practices and innovation in health care IT; and inspire follow-on activities in health care IT usability.
Information and registration for the conference can be found at www.nist.gov/itl/usability_hit.cfm. On-line registration will end at 5 p.m. Eastern time on July 6, 2010.
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