Wednesday, August 12, 2009

ALL-IN-ONE NANOPARTICLE: A SWISS ARMY KNIFE FOR NANOMEDICINE

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Nanoparticles are being developed to perform a wide range of medical uses -- imaging tumors, carrying drugs, delivering pulses of heat. Rather than settling for just one of these, researchers at the University of Washington have combined two nanoparticles in one tiny package.

The result is the first structure that creates a multipurpose nanotechnology tool for medical imaging and therapy. The structure is described in a paper published online this week in the journal Nature Nanotechnology.

"This is the first time that a semiconductor and metal nanoparticles have been combined in a way that preserves the function of each individual component," said lead author Xiaohu Gao, a UW assistant professor of bioengineering.

The current focus is on medical applications, but the researchers said multifunctional nanoparticles could also be used in energy research, for example in solar cells.

Quantum dots are fluorescent balls of semiconductor material just a few nanometers across, a small fraction of the wavelength of visible light (a nanometer is 1-millionth of a centimeter). At this tiny scale, quantum dots' unique optical properties cause them to emit light of different colors depending on their size. The dots are being developed for medical imaging, solar cells and light-emitting diodes.

Glowing gold nanoparticles have been used since ancient times in stained glass; more recently they are being developed for delivering drugs, for treating arthritis and for a type of medical imaging that uses infrared light. Gold also reradiates infrared heat and so could be used in medical therapies to cook nearby cells.

But combine a quantum dot and a gold nanoparticle, and the effects disappear. The electrical fields of the particles interfere with one another and so neither behaves as it would on its own. The two have been successfully combined on a surface, but never in a single particle.

The paper describes a manufacturing technique that uses proteins to surround a quantum dot core with a thin gold shell held at 3 nanometers distance, so the two components' optical and electrical fields do not interfere with one another. The quantum dot likely would be used for fluorescent imaging. The gold sphere could be used for scattering-based imaging, which works better than fluorescence in some situations, as well as for delivering heat therapy.

The manufacturing technique developed by Gao and co-author Yongdong Jin, a UW postdoctoral researcher, is general and could apply to other nanoparticle combinations, they said.

"We picked a tough case," Gao said. "It is widely known that gold or any other metal will quench quantum dot fluorescence, eliminating the quantum dot's purpose."

Gao and Jin avoided this problem by building a thin gold sphere that surrounds but never touches the quantum dot. They carefully controlled the separation between the gold shell and the nanoparticle core by using chains of polymer, polyethylene glycol. The distance between the quantum dot core and charged gold ion is determined by the length of the polymer chain and can be increased with nanometer precision by adding links to the chain. On the outside layer they added short amino acids called polyhistidines, which bind to charged gold atoms.

Gao compares the completed structure to a golden egg, where the quantum dot is the yolk, the gold is the shell, and polymers fill up the space of the egg white.

Using ions allowed the researchers to build a 2- to 3-nanometer gold shell that's thin enough to allow about half of the quantum dot's fluorescence to pass through.

"All the traditional techniques use premade gold nanoparticles instead of gold ions,"Gao said. "Gold nanoparticles are 3 to 5 nanometers in diameter, and with factoring in roughness the thinnest coating you can build is 5-6 nanometers. Gold ions are much, much smaller.”

The total diameter of the combined particle is roughly 15-20 nanometers, small enough to be able to slip into a cell.

Incorporating gold provides a well-established binding site to attach biological molecules that target particular cells, such as tumor cells. Gold could also potentially amplify the quantum dot's fluorescence by five to 10 times, as it has in other cases.
The gold sphere offers one further benefit. Gold is biocompatible, is medically approved and does not biodegrade. A gold shell could thus provide a durable non-toxic container for nanoparticles being used in the body, Gao said.

The research was supported by the National Institutes of Health, the National Science Foundation, the Seattle Foundation and the UW's Department of Bioengineering.

(Photo: University of Washington)

University of Washington

ANTS MORE RATIONAL THAN HUMANS

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In a study released online on July 22 in the journal Proceedings of the Royal Society: Biological Sciences, researchers at Arizona State University and Princeton University show that ants can accomplish a task more rationally than our – multimodal, egg-headed, tool-using, bipedal, opposing-thumbed – selves.

This is not the case of humans being “stupider” than ants. Humans and animals simply often make irrational choices when faced with very challenging decisions, note the study’s architects Stephen Pratt and Susan Edwards.

“This paradoxical outcome is based on apparent constraint: most individual ants know of only a single option, and the colony’s collective choice self-organizes from interactions among many poorly-informed ants,” says Pratt, an assistant professor in the School of Life Sciences in ASU’s College of Liberal Arts and Sciences.

The authors’ insights arose from an examination of the process of nest selection in the ant, Temnothorax curvispinosus. These ant colonies live in small cavities, as small as an acorn, and are skillful in finding new places to roost. The challenge before the colony was to “choose” a nest, when offered two options with very similar advantages.

What the authors found is that in collective decision-making in ants, the lack of individual options translated into more accurate outcomes by minimizing the chances for individuals to make mistakes. A “wisdom of crowds” approach emerges, Pratt believes.

“Rationality in this case should be thought of as meaning that a decision-maker, who is trying to maximize something, should simply be consistent in its preferences.” Pratt says. “For animals trying to maximize their fitness, for example, they should always rank options, whether these are food sources, mates, or nest sites, according to their fitness contribution.”

“Which means that it would be irrational to prefer choice ‘A’ to ‘B’ on Tuesday and then to prefer ‘B’ to ‘A’ on Wednesday, if the fitness returns of the two options have not changed.”

“Typically we think having many individual options, strategies and approaches are beneficial,” Pratt adds, “but irrational errors are more likely to arise when individuals make direct comparisons among options.”

Studies of how or why irrationality arises can give insight into cognitive mechanisms and constraints, as well as how collective decision making occurs. Insights such as Pratt’s and Edward’s could also translate into new approaches in the development of artificial intelligence.

“A key idea in collective robotics is that the individual robots can be relatively simple and unsophisticated, but you can still get a complex, intelligent result out of the whole group,” says Pratt. “The ability to function without complex central control is really desirable in an artificial system and the idea that limitations at the individual level can actually help at the group level is potentially very useful.” Pratt is a member of Heterogeneous Unmanned Networked Team (HUNT), a project funded by the Office of Naval Research (ONR) to enable to development of bio-inspired solutions to engineering problems.

What do these findings potentially say about understanding human social systems?

“It is hard to say. But it’s at least worth entertaining the possibility that some strategic limitation on individual knowledge could improve the performance of a large and complex group that is trying to accomplish something collectively,” Pratt says.

(Photo: Arizona SU)

Arizona State University

CALTECH RESEARCHERS LINK TINY SEA CREATURES TO LARGE-SCALE OCEAN MIXING

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Using a combination of theoretical modeling, energy calculations, and field observations, researchers from the California Institute of Technology (Caltech) have for the first time described a mechanism that explains how some of the ocean's tiniest swimming animals can have a huge impact on large-scale ocean mixing.

Their findings are being published in the July 30 issue of the journal Nature.

"We've been studying swimming animals for quite some time," says John Dabiri, a Caltech assistant professor of aeronautics and bioengineering who, along with Caltech graduate student Kakani Katija, discovered the new mechanism. "The perspective we usually take is that of how the ocean—by its currents, temperature, and chemistry—is affecting the animals. But there have been increasing suggestions that the inverse is also important-how the animals themselves, via swimming, might impact the ocean environment."

Specifically, Dabiri says, scientists have increasingly been thinking about how and whether the animals in the ocean might play a role in larger-scale ocean mixing, the process by which various layers of water interact with one another to distribute heat, nutrients, and gasses throughout the oceans.

Dabiri notes that oceanographers have previously dismissed the idea that animals might have a significant effect on ocean mixing, saying that the viscosity of water would damp out any turbulence created, especially by small planktonic animals. "They said that there was no mechanism by which these animals could impact large-scale ocean mixing," he notes.

But Dabiri and Katija thought there might be a mechanism that had been overlooked—a mechanism they call Darwinian mixing, because it was first discovered and described by Charles Darwin. (No, not that Darwin; his grandson.)

"Darwin's grandson discovered a mechanism for mixing similar in principle to the idea of drafting in aerodynamics," Dabiri explains. "In this mechanism, an individual organism literally drags the surrounding water with it as it goes."

Using this idea as their basis, Dabiri and Katija did some mathematical simulations of what might happen if you had many small animals all moving at more or less the same time, in the same direction. After all, each day, billions of tiny krill and copepods migrate hundreds of meters from the depths of the ocean toward the surface. Darwin's mechanism would suggest that they drag some of the colder, heavier bottom water up with them toward the warmer, lighter water at the top. This would create instability, and eventually, the water would flip, mixing itself as it went.

What the Caltech researchers also found was that the water's viscosity enhances Darwin's mechanism and that the effects are magnified when you're dealing with such minuscule creatures as krill and copepods. "It's like a human swimming through honey," Dabiri explains. "What happens is that even more fluid ends up being carried up with a copepod, relatively speaking, than would be carried up by a whale."

"This research is truly reflective of the type of exciting, without-boundaries research at which Caltech engineering professors excel—in this case a deep analysis of the movement of fluid surrounding tiny ocean creatures leading to completely revelatory insights on possible mechanisms of global ocean mixing," says Ares Rosakis, chair of the Division of Engineering and Applied Science at Caltech.

To verify the findings from their simulations, Katija and collaborators Monty Graham (from the Dauphin Island Sea Laboratory), Jack Costello (from Providence College), and Mike Dawson (from the University of California, Merced) traveled to the island of Palau, where they studied this animal-led transport of water—otherwise known as induced drift—among jellyfish, which are the focus of much of Dabiri's work.

"From a fluid mechanics perspective, this study had less to do with the fact that they're jellyfish, and more to do with the fact that they're solid objects moving through water," Dabiri explains.

Katija's jellyfish experiments involved putting fluorescent dye in the water in front of the sea creatures, and then watching what happened to that dye—or, to be more specific, to the water that took up the dye—as the jellyfish swam. And, indeed, rather than being left behind the jellyfish—or being dissipated in turbulent eddies—the dye travelled right along with the swimming creatures, following them for long distances.

These findings verified that, yes, swimming animals are capable of carrying bottom water with them as they migrate upward, and that movement indeed creates an inversion that results in ocean mixing. But what the findings didn't address was just how much of an impact this type of ocean mixing—performed by impossibly tiny sea creatures—could have on a large scale.

After a series of calculations, Dabiri and Katija were able to estimate the impact of this so-called biogenic ocean mixing. And, Dabiri says, it's quite a significant impact.

"There are enough of these animals in the ocean," he notes, "that, on the whole, the global power input from this process is as much as a trillion watts of energy—comparable to that of wind forcing and tidal forcing."

In other words, the amount of power that copepods and krill put into ocean mixing is on the same scale as that of winds and tides, and thus their impact is expected to be on a similar scale as well.

And while these numbers are just estimates, Dabiri says, they are likely to be conservative estimates, having been "based on the fluid transport induced by individual animals swimming in isolation." In the ocean, these individual contributions to fluid transport may actually interact with one another, and amplify how far the ocean waters can be pulled upward.

In addition, says Dabiri, they have yet to consider the effects of such things as fecal pellets and marine snow (falling organic debris), which no doubt pull surface water with them as they drift downward. "This may have an impact on carbon sequestration on the ocean floor," says Dabiri. "It's something we need to look at in the future."

Dabiri says the next major question to answer is how these effects can be incorporated into computer models of the global ocean circulation. Such models are important for simulations of global climate-change scenarios.


(Photo: Monty Graham and Kakani Katija)

California Institute of Technology

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