A breath-takingly simple test for human exposure to potentially toxic substances

 

The search for a rapid, non-invasive way to determine whether people have been exposed to potentially toxic substances in their workplaces, homes and elsewhere in the environment has led scientists to a technology that literally takes a person's breath away. Their report identifying exhaled breath as an ideal indicator of such exposure appears in ACS' Environmental Science & Technology.

Andrea M. Dietrich, Masoud Agah, and their students Heather Vereb and Bassam Alfeeli explain that scientists have known since the late 1970s that exhaled breath contains traces of any potentially toxic substances that people may have inhaled. Research has shown that those amounts are an accurate reflection of the levels that exist in a person's blood. Those advances have positioned exhaled breath as the ideal substance to use in rapid, non-invasive, simple testing for human exposure to potentially harmful substances in the air. Sampling breath is less invasive than drawing blood, more convenient than taking urine samples and "shows promise as an inexpensive method with a fast turnaround time," they state.

The article describes how advances in microelectronics have helped position breath analysis for more extensive use in the 21st century. Equipment for analyzing substances in human breath that once had to be housed in laboratories, for instance, have shrunk to hand-held size. The technology can detect minute amounts of substances in the breath and do so quickly — offering the promise of helping limit human exposure and improve health.

More information: The Possibilities Will Take Your Breath Away: Breath Analysis for Assessing Environmental Exposure, Environ. Sci. Technol., Article ASAP. DOI: 10.1021/es202041j

Abstract
Human breath is the gaseous exchange with the blood and thus contains trace organic contaminants and metabolites representative of environmental doses. Sampling and analysis of gaseous components in human breath offers a noninvasive and quick means of qualitatively and quantitatively assessing internalized doses of environmental contaminants. Although the humid and complex nature of breath is a challenge for detection of part-per-trillion to part-per-billion concentrations of environmental contaminants, recent advances in chemical analysis and instrumentation are allowing determination of environmental exposure and disease detection.

Provided by American Chemical Society (news : web)

New way to store sun's heat: Modified carbon nanotubes can store solar energy indefinitely, then be recharged by exposure to the sun

 A novel application of carbon nanotubes, developed by MIT researchers, shows promise as an innovative approach to storing solar energy for use whenever it's needed.

Storing the sun's heat in chemical form -- rather than converting it to electricity or storing the heat itself in a heavily insulated container -- has significant advantages, since in principle the chemical material can be stored for long periods of time without losing any of its stored energy. The problem with that approach has been that until now the chemicals needed to perform this conversion and storage either degraded within a few cycles, or included the element ruthenium, which is rare and expensive.

Last year, MIT associate professor Jeffrey Grossman and four co-authors figured out exactly how fulvalene diruthenium -- known to scientists as the best chemical for reversibly storing solar energy, since it did not degrade -- was able to accomplish this feat. Grossman said at the time that better understanding this process could make it easier to search for other compounds, made of abundant and inexpensive materials, which could be used in the same way.

Now, he and postdoc Alexie Kolpak have succeeded n doing just that. A paper describing their new findings has just been published online in the journal Nano Letters, and will appear in print in a forthcoming issue.

The new material found by Grossman and Kolpak is made using carbon nanotubes, tiny tubular structures of pure carbon, in combination with a compound called azobenzene. The resulting molecules, produced using nanoscale templates to shape and constrain their physical structure, gain "new properties that aren't available" in the separate materials, says Grossman, the Carl Richard Soderberg Associate Professor of Power Engineering.

Not only is this new chemical system less expensive than the earlier ruthenium-containing compound, but it also is vastly more efficient at storing energy in a given amount of space -- about 10,000 times higher in volumetric energy density, Kolpak says -- making its energy density comparable to lithium-ion batteries. By using nanofabrication methods, "you can control [the molecules'] interactions, increasing the amount of energy they can store and the length of time for which they can store it -- and most importantly, you can control both independently," she says.

Thermo-chemical storage of solar energy uses a molecule whose structure changes when exposed to sunlight, and can remain stable in that form indefinitely. Then, when nudged by a stimulus -- a catalyst, a small temperature change, a flash of light -- it can quickly snap back to its other form, releasing its stored energy in a burst of heat. Grossman describes it as creating a rechargeable heat battery with a long shelf life, like a conventional battery.

One of the great advantages of the new approach to harnessing solar energy, Grossman says, is that it simplifies the process by combining energy harvesting and storage into a single step. "You've got a material that both converts and stores energy," he says. "It's robust, it doesn't degrade, and it's cheap." One limitation, however, is that while this process is useful for heating applications, to produce electricity would require another conversion step, using thermoelectric devices or producing steam to run a generator.

While the new work shows the energy-storage capability of a specific type of molecule -- azobenzene-functionalized carbon nanotubes -- Grossman says the way the material was designed involves "a general concept that can be applied to many new materials." Many of these have already been synthesized by other researchers for different applications, and would simply need to have their properties fine-tuned for solar thermal storage.

The key to controlling solar thermal storage is an energy barrier separating the two stable states the molecule can adopt; the detailed understanding of that barrier was central to Grossman's earlier research on fulvalene dirunthenium, accounting for its long-term stability. Too low a barrier, and the molecule would return too easily to its "uncharged" state, failing to store energy for long periods; if the barrier were too high, it would not be able to easily release its energy when needed. "The barrier has to be optimized," Grossman says.

Already, the team is "very actively looking at a range of new materials," he says. While they have already identified the one very promising material described in this paper, he says, "I see this as the tip of the iceberg. We're pretty jazzed up about it."

Yosuke Kanai, assistant professor of chemistry at the University of North Carolina at Chapel Hill, says "the idea of reversibly storing solar energy in chemical bonds is gaining a lot of attention these days. The novelty of this work is how these authors have shown that the energy density can be significantly increased by using carbon nanotubes as nanoscale templates. This innovative idea also opens up an interesting avenue for tailoring already-known photoactive molecules for solar thermal fuels and storage in general."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Massachusetts Institute of Technology. The original article was written by David L. Chandler, MIT News Office.

Journal Reference:

Alexie M. Kolpak, Jeffrey C. Grossman. Azobenzene-Functionalized Carbon Nanotubes As High-Energy Density Solar Thermal Fuels. Nano Letters, 2011; : 110705085331088 DOI: 10.1021/nl201357n

Understanding methods of assessing botulinum neurotoxin exposure

Popular in cosmetic medicine for making tiny frown wrinkles go away, botulinum neurotoxin (BoNT) is, perhaps, more notorious for historic outbreaks of respiratory paralysis and death. Traditionally, medical responders have relied on the highly sensitive, but slow, mouse assay to confirm the presence of BoNT and determine its serotype. But today, research emphasis has turned to developing in vitro immunoassay techniques with high sensitivity and rapid sample results -- both important for potential exposure.

"Each immunoassay approach has its own advantages and disadvantages," said Dr. Jay Grate, a Laboratory Fellow at the Pacific Northwest National Laboratory. "Some techniques are slow and some are fast; some are extremely sensitive and some are less so, but they are all useful."

To gain a better understanding of the breadth and depth of immunoassay techniques for BoNT, Grate and his research team reviewed current scientific literature to focus on the most promising approaches. The team's review is described as an invited cover article in the journal Trends in Analytical Chemistry. (TrAC, November 2010.)

Natural cases of BoNT intoxication can occur through consumption of contaminated food, infection of an open wound, and intestinal infection in infants. Intoxication can also occur through inhalation, raising concerns about use of this potent neurotoxin as a tool of warfare or terrorism. In fact, the U.S. Centers for Disease Control has listed BoNT as one of the six highest-risk threat agents for bioterrorism. According to Grate, a better understanding of immunoassay techniques for BoNT is important for public safety and national security.

"In the event of an outbreak of BoNT intoxication—whether natural, accidental, or through intentional release—it will be critical to have rapid, sensitive assays to assess a large number of samples," said Grate.

The team was invited to author an article for the TrAC article after publishing four primary research papers about BoNT detection from 2004 to 2009. In review, the team documented the progress that scientists around the world have made to develop more sensitive and rapid assays. This, says Grate, involves tremendous effort in capturing the toxin from the sample and concentrating it to a small volume to generate a strong signal.

The team's review concludes that longer assay times continue to yield the lowest achievable limits of detection. However, as research continues to replace the sluggish mouse assay, rapid new techniques are much more sensitive than in the past. For example, luminescence-detection methods have largely replaced colorimetric enzyme-amplified methods, and microfluidic formats have emerged for very sensitive assays. Plate-based formats continue to be important, as they are suitable for robotic automation. And one of the key trends that emerged from the review was a growing focus on solid phases, such as beads, for heterogeneous immunoassays.

"This technique, which helps separate the components of the assay, is not a trend that's unique to this field, but people have applied it in this area of research to achieve very low detection limits," explained Grate. "The use of solid phases has been an integral part of our approach for as long as we've been developing biodetection systems. So this review confirmed that this is a strong approach."

Grate and his research team will continue to research immunoassay techniques to rapidly screen for BoNT and other toxins.

"This is a dynamic and evolving field where researchers are all working toward better public health and safety," said Grate. "I don't think anybody—yet—has the final answer."

More information: Grate JW, et al. 2010. "Advances in Assays and Analytical Approaches for Botulinum Toxin Detection." Trends in Analytical Chemistry. TrAC 29(10):1137-1156. DOI:10.1016/j.trac.2010.07.005

Provided by Pacific Northwest National Laboratory (news : web)

OSU chemist developing solution to nerve agent exposure

Scientists are working to develop a new drug that will regenerate a critical enzyme in the human body that "ages" after a person is exposed to deadly chemical warfare agents.

Christopher Hadad, Ph.D., professor of chemistry at The Ohio State University (OSU), is leveraging Ohio Supercomputer Center (OSC) resources to help develop a more effective antidote to lethal chemicals called organophosphorus (OP) nerve agents.

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," said Hadad.

OP nerve agents inhibit the ability of an enzyme called acetylcholinesterase (AChE) to turn off the messages being delivered by acetylcholine (ACh), a neurotransmitter, to activate various muscles, glands and organs throughout the body. After exposure to OP agents, AChE undergoes a series of reactions, culminating in an "aging" process that inhibits AChE from performing its critical biological function. Without the application of an effective antidote, neurosynaptic communication continues unabated, resulting in uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms, which, if untreated, result in death.

Conventional antidotes to OP nerve agents block the activity of the nerve agent by introducing oxime compounds, which have been the focus of a number of studies. These compounds attach to the phosphorus atom of the nerve agent, after the OP is bound to AChE, and then split it away from the AChE enzyme, allowing the AChE to engage with receptors and finally relax the tissues.

However, in some cases, the combined nerve agent/AChE molecule undergo a process called aging, in which groups of single-bonded carbon and hydrogen atoms called alkyl groups are removed from the molecule and a phosphonate residue is left behind in the AChE active site. Relatively unstudied in nerve agents, this process, called dealkylation, makes the nerve agent/AChE molecule unreceptive to oximes – an unfortunate situation, considering that certain nerve agents (e.g., soman) can undergo aging within minutes of exposure to AChE.

A docking simulation constructed at the Ohio Supercomputer Center by Ohio State Professor Christopher Hadad, Ph.D., illustrates binding in the active site of tabun-inhibited AChE. Credit: Hadad/OSU

Hadad's study is focused on the identification of compounds that would return an appropriate alkyl group to the aged nerve agent/AChE molecule, thus allowing treatment with oximes to provide for complete recovery. The project is investigating common OP nerve agents Tabun, VX, VR, Sarin, Soman, Cyclosarin and Paraoxon, all of which take on a similar molecular structure upon aging.

"Computational studies of the interaction of the alkylating compounds with AChE were used to provide insight for the design of selective reagents," Hadad explained. "Ligand-receptor docking, followed by molecular dynamics simulations of the interactions of alkylating compounds with aged OP-AChE, was carried out in conjunction with experimental studies to investigate the binding of alkylating compounds to AChE. These results were then used to suggest interactions that aided in the orientation of alkylating compounds for maximal efficacy."

Throughout the project, Hadad employed computational studies to guide the progress of each objective, as well as to rationalize the observed experimental results.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," said Ashok Krishnamurthy, interim co-executive director of OSC. "It was by design that OSC's flagship system, the Glenn IBM 1350 Opteron cluster, was developed to meet the needs of the bioscience research investigators, such as Dr. Hadad."

Provided by Ohio Supercomputer Center

Toward a solution to nerve agent exposure: Chemist uses supercomputers to test reagents for new treatments

Scientists are working to develop a new drug that will regenerate a critical enzyme in the human body that "ages" after a person is exposed to deadly chemical warfare agents.

Christopher Hadad, Ph.D., professor of chemistry at The Ohio State University (OSU), is leveraging Ohio Supercomputer Center (OSC) resources to help develop a more effective antidote to lethal chemicals called organophosphorus (OP) nerve agents.

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," said Hadad.

OP nerve agents inhibit the ability of an enzyme called acetylcholinesterase (AChE) to turn off the messages being delivered by acetylcholine (ACh), a neurotransmitter, to activate various muscles, glands and organs throughout the body. After exposure to OP agents, AChE undergoes a series of reactions, culminating in an "aging" process that inactivates AChE from performing its critical biological function. Without the application of an effective antidote, neurosynaptic communication continues unabated, resulting in uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms, which, if untreated, result in death.

Conventional antidotes to OP nerve agents block the activity of the nerve agent by introducing oxime compounds, which have been the focus of a number of studies. These compounds attach to the phosphorus atom of the nerve agent, after the OP is bound to AChE, and then split it away from the AChE enzyme, allowing the AChE to engage with receptors and finally relax the tissues.

However, in some cases, the combined nerve agent/AChE molecule undergo a process called aging, in which groups of single-bonded carbon and hydrogen atoms called alkyl groups are removed from the molecule and a phosphonate residue is left behind in the AChE active site. Relatively unstudied in nerve agents, this process, called dealkylation, makes the nerve agent/AChE molecule unreceptive to oximes -- an unfortunate situation, considering that certain nerve agents (e.g., soman) can undergo aging within minutes of exposure to AChE.

Hadad's study is focused on the identification of compounds that would return an appropriate alkyl group to the aged nerve agent/AChE molecule, thus allowing treatment with oximes to provide for complete recovery. The project is investigating common OP nerve agents Tabun, VX, VR, Sarin, Soman, Cyclosarin and Paraoxon, all of which take on a similar molecular structure upon aging.

"Computational studies of the interaction of the alkylating compounds with AChE were used to provide insight for the design of selective reagents," Hadad explained. "Ligand-receptor docking, followed by molecular dynamics simulations of the interactions of alkylating compounds with aged OP-AChE, was carried out in conjunction with experimental studies to investigate the binding of alkylating compounds to AChE. These results were then used to suggest interactions that aided in the orientation of alkylating compounds for maximal efficacy."

Throughout the project, Hadad employed computational studies to guide the progress of each objective, as well as to rationalize the observed experimental results.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," said Ashok Krishnamurthy, interim co-executive director of OSC. "It was by design that OSC's flagship system, the Glenn IBM 1350 Opteron cluster, was developed to meet the needs of the bioscience research investigators, such as Dr. Hadad."

Hadad's investigations of nerve agent antidotes are funded by the Defense Threat Reduction Agency (W81XWH-10-2-0044) and supported by the award of an OSC Discovery Account.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ohio Supercomputer Center.