Social Hormone Promotes Cooperation in Risky Situations

A hormone implicated in monogamy and aggression in animals also promotes trust and cooperation in humans in risky situations, Caltech researchers say.

The findings, published the week of February 8 in the online edition of the Proceedings of the National Academy of Sciences, could prove useful for helping groups cooperate beneficially.

Research in rodents shows the hormone arginine vasopressin (AVP) promotes monogamous pair bonding and parental behavior, but also aggression in males. "Part of the dark side of monogamy is that an AVP-pumped-up male is more likely to behave aggressively toward intruders," says study coauthor Colin Camerer, the Robert Kirby Professor of Behavioral Economics at Caltech.

In the new study, Camerer and his team tested the hypothesis that AVP might also play a role in social bonding in people and could help explain our species' cooperative tendencies. "One of the reasons humans rule the world rather than apes is that we do things that require a great deal of trust. We cooperate in large-scale groups," Camerer says. "Where does that come from? Is it something like pair bonding but just scaled up? And if it is, what role does AVP play?"

To investigate these questions, Camerer and his colleagues administered a nasal spray containing AVP or a hormone-free nasal spray (a placebo) to 59 male volunteers, aged 19 to 32 years old. Pairs of subjects then used computers to play a so-called assurance game in which they had to choose whether or not to cooperate with another player; "assurance" comes from the fact that subjects will take a risky action if they are sufficiently assured that others will, too. When they cooperated, both players received more points than they would have if they did not mutually cooperate. If one player chose not to cooperate but his partner made the opposite decision, the non-cooperative player received an intermediate payoff whereas the cooperative player received nothing.

"The game is designed to mimic situations in which people are willing to help, but only if everyone else helps too," Camerer says. "Think of pitching in on a team project, or of a group of soldiers rushing the enemy. If a critical mass cooperates, then everyone else should go along. Thus it is in your best interest to help only if enough others do."

To help ensure the players were engaged, the points they accumulated were converted into actual money at the end of the game (usually around $20).

The experiment showed that players who received AVP before the game were significantly more likely to cooperate than those who received the placebo. "By targeting a specific hormonal system in the human brain, we could manipulate people's willingness to cooperate and help them do better," says Gideon Nave, a graduate student in Camerer's lab and a coauthor on the study.

Using control experiments, the researchers were also able to rule out other explanations for why the subjects were cooperating. For example, one possibility is that AVP was increasing the subjects' appetite for risks. Alternatively, the administered hormone might be amplifying their altruistic tendencies, so that they just wanted to help other people regardless of the risk to themselves.

"We found that when we asked them, 'Do you want to just give some money to this stranger?' they don't do it," Camerer says. "So AVP seems to be quite specialized to this particular type of risky cooperation."

To better understand the neural mechanism underlying AVP's effect on risky cooperation, the researchers conducted the same experiment but this time had subjects—a separate group of 34 men—play the game while their brains were being imaged using a functional magnetic resonance imaging (fMRI) scanner. The scans indicated that after AVP administration, a part of the brain's reward system known as the ventral pallidum—a region that is known to have an abundance of AVP receptors—showed a change in neural activity when the players decided to cooperate.

"That was very encouraging, because it showed that the hormone is activating a part of the brain that is known to be rich in AVP receptors," Camerer says.

Could the discovery that AVP increases the likelihood of risky cooperation have practical applications and be used, for example, to engender trust and foster cooperation in groups? Perhaps.

"You could imagine a high-stakes situation, such as a military operation, in which people have to trust each other to all do something difficult and it fails if anyone chickens out," Camerer says. "In that case, you might want to administer AVP to help ensure that everyone is cooperative."

In addition to Camerer and Nave, other coauthors on the paper, "Vasopressin increases human risky cooperative behavior," include Claudia Brunnlieb, Stephan Schosser, and Bodo Vogt of the University of Magdeburg and Thomas Münte and Marcus Heldmann at the University of Lübeck in Germany. The research was funded by a special grant of the Center for Behavioral Brain Sciences and by the Gordon and Betty Moore Foundation. 

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Social Hormone Promotes Cooperation
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A hormone implicated in monogamy and aggression in animals also promotes trust and cooperation in humans in risky situations, Caltech researchers say.

Delivering Genes Across the Blood-Brain Barrier

Caltech biologists have modified a harmless virus in such a way that it can successfully enter the adult mouse brain through the bloodstream and deliver genes to cells of the nervous system. The virus could help researchers map the intricacies of the brain and holds promise for the delivery of novel therapeutics to address diseases such as Alzheimer's and Huntington's. In addition, the screening approach the researchers developed to identify the virus could be used to make additional vectors capable of targeting cells in other organs.

"By figuring out a way to get genes across the blood-brain barrier, we are able to deliver them throughout the adult brain with high efficiency," says Ben Deverman, a senior research scientist at Caltech and lead author of a paper describing the work in the February 1 online publication of the journal Nature Biotechnology.

The blood-brain barrier allows the body to keep pathogens and potentially harmful chemicals circulating in the blood from entering the brain and spinal cord. The semi-permeable blockade, composed of tightly packed cells, is crucial for maintaining a controlled environment to allow the central nervous system to function properly. However, the barrier also makes it nearly impossible for many drugs and other molecules to be delivered to the brain via the bloodstream.

To sneak genes past the blood-brain barrier, the Caltech researchers used a new variant of a small, harmless virus called an adeno-associated virus (AAV). Over the past two decades, researchers have used various AAVs as vehicles to transport specific genes into the nuclei of cells; once there, the genes can be expressed, or translated, from DNA into proteins. In some applications, the AAVs carry functional copies of genes to replace mutated forms present in individuals with genetic diseases. In other applications, they are used to deliver genes that provide instructions for generating molecules such as antibodies or fluorescent proteins that help researchers study, identify, and track certain cells.

Largely because of the blood-brain barrier problem, scientists have had only limited success delivering AAVs and their genetic cargo to the central nervous system. In general, they have relied on surgical injections, which deliver high concentrations of the virus at the injection site but little to the outlying areas. Such injections are also quite invasive. "One has to drill a hole through skull, then pierce tissue with a needle to the injection site," explains Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering at Caltech and senior author on the paper. "The deeper the injection, the higher the risk of hemorrhage. With systemic injection, using the bloodstream, none of that damage happens, and the delivery is more uniform."

In addition, Gradinaru notes, "many disorders are not tightly localized. Neurodegenerative disorders like Huntington's disease affect very large brain areas. Also, many complex behaviors are mediated by distributed interacting networks. Our ability to target those networks is key in terms of our efforts to understand what those pathways are doing and how to improve them when they are not working well."

In 2009, a group led by Brian Kaspar of Ohio State University published a paper, also in Nature Biotechnology, showing that an AAV strain called AAV9 injected into the bloodstream could make its way into the brain—but it was only efficient when used in neonatal, or infant, mice.

"The big challenge was how do we achieve the same efficiency in an adult," says Gradinaru.

Although one might like to design an AAV that is up to the task, the number of variables that dictate the behavior of any given virus, as well as the intricacies of the brain and its barrier, make that extremely challenging. Instead, the researchers developed a high-throughput selection assay, CREATE (Cre REcombinase-based AAV Targeted Evolution), that allowed them to test millions of viruses in vivo simultaneously and to identify those that were best at entering the brain and delivering genes to a specific class of brain cells known as astrocytes.

They started with the AAV9 virus and modified a gene fragment that codes for a small loop on the surface of the capsid—the protein shell of the virus that envelops all of the virus' genetic material. Using a common amplification technique, known as polymerase chain reaction (PCR), they created millions of viral variants. Each variant carried within it the genetic instructions to produce more capsids like itself.

Then they used their novel selection process to determine which variants most effectively delivered genes to astrocytes in the brain. Importantly, the new process relies on strategically positioning the gene encoding the capsid variants on the DNA strand between two short sequences of DNA, known as lox sites. These sites are recognized by an enzyme called Cre recombinase, which binds to them and inverts the genetic sequence between them. By injecting the modified viruses into transgenic mice that only express Cre recombinase in astrocytes, the researchers knew that any sequences flagged by the lox site inversion had successfully transferred their genetic cargo to the target cell type—here, astrocytes.

After one week, the researchers isolated DNA from brain and spinal cord tissue, and amplified the flagged sequences, thereby recovering only the variants that had entered astrocytes.

Next, they took those sequences and inserted them back into the modified viral genome to create a new library that could be injected into the same type of transgenic mice. After only two such rounds of injection and amplification, a handful of variants emerged as those that were best at crossing the blood-brain barrier and entering astrocytes.

"We went from millions of viruses to a handful of testable, potentially useful hits that we could go through systematically and see which ones emerged with desirable properties," says Gradinaru.

Through this selection process, the researchers identified a variant dubbed AAV-PHP.B as a top performer. They gave the virus its acronym in honor of the late Caltech biologist Paul H. Patterson because Deverman began this work in Patterson's group. "Paul had a commitment to understanding brain disorders, and he saw the value in pushing tool development," says Gradinaru, who also worked in Patterson's lab as an undergraduate student.

To test AAV-PHP.B, the researchers used it to deliver a gene that codes for a protein that glows green, making it easy to visualize which cells were expressing it. They injected the AAV-PHP.B or AAV9 (as a control) into different adult mice and after three weeks used the amount of green fluorescence to assess the efficacy with which the viruses entered the brain, the spinal cord, and the retina.

"We could see that AAV-PHP.B was expressed throughout the adult central nervous system with high efficiency in most cell types," says Gradinaru. Indeed, compared to AAV9, AAV-PHP.B delivers genes to the brain and spinal cord at least 40 times more efficiently.  

"What provides most of AAV-PHP.B's benefit is its increased ability to get through the vasculature into the brain," says Deverman. "Once there, many AAVs, including AAV9 are quite good at delivering genes to neurons and glia."

Gradinaru notes that since AAV-PHP.B is delivered through the bloodstream, it reaches other parts of the body. "Although in this study we were focused on the brain, we were also able to use whole-body tissue clearing to look at its biodistribution throughout the body," she says.

Whole-body tissue clearing by PARS CLARITY, a technique developed previously in the Gradinaru lab to make normally opaque mammalian tissues transparent, allows organs to be examined without the laborious task of making thin slide-mounted sections. Thus, tissue clearing allows researchers to more quickly screen the viral vectors for those that best target the cells and organs of interest.

"In this case, the priority was to express the gene in the brain, but we can see by using whole-body clearing that you can actually have expression in many other organs and even in the peripheral nerves," explains Gradinaru. "By making tissues transparent and looking through them, we can obtain more information about these viruses and identify targets that we might overlook otherwise."

The biologists conducted follow-up studies up to a year after the initial injections and found that the protein continued to be expressed efficiently. Such long-term expression is important for gene therapy studies in humans. 

In collaboration with colleagues from Stanford University, Deverman and Gradinaru also showed that AAV-PHP.B is better than AAV9 at delivering genes to human neurons and glia.

The researchers hope to begin testing AAV-PHP.B's ability to deliver potentially therapeutic genes in disease models. They are also working to further evolve the virus to make even better performing variants and to produce variants that target certain cell types with more specificity.

Deverman says that the CREATE system could indeed be applied to develop AAVs capable of delivering genes specifically to many different cell types. "There are hundreds of different Cre transgenic lines available," he says. "Researchers have put Cre recombinase under the control of gene regulatory elements so that it is only made in certain cell types. That means that regardless of whether your objective is to target liver cells or a particular type of neuron, you can almost always find a mouse that has Cre recombinase expressed in those cells."

"The CREATE system gave us a good hit early on, but we are excited about the future potential of using this approach to generate viruses that have very good cell-type specificity in different organisms, especially the less genetically tractable ones," says Gradinaru. "This is just the first step. We can take these tools and concepts in many exciting directions to further enhance this work, and we—with the Beckman Institute and collaborators—are ready to pursue those possibilities." 

The Beckman Institute at Caltech recently opened a resource center called CLOVER (CLARITY, Optogenetics, and Vector Engineering Research Center) to support such research efforts involving tissue clearing and imaging, optogenetic studies, and custom gene-delivery vehicle development. Deverman is the center's director, and Gradinaru is the principal investigator.

Additional Caltech authors on the paper, "Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain," are Sripriya Ravindra Kumar, Ken Y. Chan, Abhik Banerjee, Wei-Li Wu, and Bin Yang, as well as former Caltech students Piers L. Pravdo and Bryan P. Simpson. Nina Huber and Sergiu P. Pasca of Stanford University School of Medicine are also coauthors. The work was supported by funding from the Hereditary Disease Foundation and the Caltech-City of Hope Biomedical Initiative, a National Institutes of Health (NIH) Director's New Innovator Award, the NIH's National Institute of Aging and National Institute of Mental Health, the Beckman Institute, and the Gordon and Betty Moore Foundation.

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Kimm Fesenmaier
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Delivering Genes Across the Blood-Brain Barrier
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Caltech biologists have developed a vector capable of noninvasive delivery of genetic cargo throughout the adult central nervous system.

Novel Calibration Tool Will Help Astronomers Look for Habitable Exoplanets

Promising new calibration tools, called laser frequency combs, could allow astronomers to take a major step in discovering and characterizing earthlike planets around other stars. These devices generate evenly spaced lines of light, much like the teeth on a comb for styling hair or the tick marks on a ruler—hence their nickname of "optical rulers." The tick marks serve as stable reference points when making precision measurements such as those of the small shifts in starlight caused by planets pulling gravitationally on their parent stars.

Yet today's commercially available combs have a significant drawback. Because their tick marks are so finely spaced, the light output of these combs must be filtered to produce useful reference lines. This extra step adds complexity to the system and requires costly additional equipment.

To resolve these kinds of issues, Caltech researchers looked to a kind of comb not previously deployed for astronomy. The novel comb produces easily resolvable lines, without any need for filtering. Furthermore, the Caltech comb is built from off-the-shelf components developed by the telecommunications industry.

"We have demonstrated an alternative approach that is simple, reliable, and relatively inexpensive," says paper coauthor Kerry Vahala, the Ted and Ginger Jenkins Professor of Information Science and Technology and Applied Physics as well as the executive officer for Applied Physics and Materials Science in Caltech's Division of Engineering and Applied Science. The kind of frequency comb used by the researchers previously has been studied in the Vahala group in a different application, the generation of high-stability microwaves.

"We believe members of the astronomical community could greatly benefit in their exoplanet hunting and characterization studies with this new laser frequency comb instrument," says Xu Yi, a graduate student in Vahala's lab and the lead author of a paper describing the work published in the January 27, 2016, issue of the journal Nature Communications.

Scientists first began widely using laser frequency combs as precision rulers in the late 1990s in fields like metrology and spectroscopy; for their work, the technology's developers (John L. Hall of JILA and the National Institute of Standards and Technology (NIST) and Theodor Hänsch of the Max Planck Institute of Quantum Optics and Ludwig Maximilians University Munich) were awarded half of the Nobel Prize in Physics in 2005. In astronomy, the combs are starting to be utilized in the radial velocity, or "wobble" method, the earliest and among the most successful methods for identifying exoplanets.

The "wobble" refers to the periodic changes in a star's motion, accompanied by starlight shifts owing to the Doppler effect, that are induced by the gravitational pull of an exoplanet orbiting around the star. The magnitude of the shift in the starlight's wavelength—on the order of quadrillionths of a meter—together with the period of the wobble can be used to determine an exoplanet's mass and orbital distance from its star. These details are critical for assessing habitability parameters such as surface temperature and the eccentricity of the exoplanet's orbit. With exoplanets that pass directly in front of (or "transit") their host star, allowing their radius to be determined directly, it is even possible to determine the bulk composition—for example, if the planet is built up primarily of gas, ice, or rock. 

In recent years, so-called mode-locked laser combs have proven useful in this task. These lasers generate a periodic stream of ultrashort light pulses to create the comb. With such combs, however, approximately 49 out of every 50 tick marks must be blocked out. This requires temperature- and vibration-insensitive filtering equipment.

The new electro-optical comb that Vahala and his team studied relies on microwave modulation of a continuous laser source, rather than a pulsed laser. It produces comb lines spaced by tens of gigahertz. These lines have from 10 to 100 times wider spacing than the tick marks of pulsed laser combs.

To see how well a prototype would work in the field, the researchers took their comb to Mauna Kea in Hawaii. In September 2014, the instrument was tested at the NASA Infrared Telescope Facility (IRTF); in March 2015, it was tested with the Near Infrared Spectrometer on the W. M. Keck Observatory's Keck II telescope with the assistance of UCLA astronomer Mike Fitzgerald (BS '00) and UCLA graduate student Emily Martin, coauthors on the paper. The researchers found that their simplified comb (the entire electro-optical comb apparatus requires only half of the space available on a standard 19-inch instrumentation rack) provided steady calibration at room temperature for more than five days at IRTF. The comb also operated flawlessly during the second test—despite having been disassembled, stored for six months, and reassembled.

"From a technological maturity point of view, the frequency comb we have developed is already basically ready to go and could be installed at many telescopes," says paper coauthor Scott Diddams of NIST.

The Caltech comb produces spectral lines in the infrared, making it ideal for studying red dwarf stars, the most common stars in the Milky Way. Red dwarf stars are brightest in infrared wavelengths. Because red dwarfs are small, cool, and dim, planets orbiting these types of stars are easier to detect and analyze than those orbiting hotter sun-like stars. NASA's Kepler space observatory has shown that almost all red dwarf stars host planets in the range of one to four times the size of Earth, with up to 25 percent of these planets located in the temperate, or "habitable," zone around their host stars. Thus, many astronomers predict that red dwarfs provide the best chance for the first discovery of a world capable of supporting life.

"Our goal is to make these laser frequency combs simple and sturdy enough that you can slap them onto every telescope, and you don't have to think about them anymore," says paper coauthor Charles Beichman, senior faculty associate in astronomy and the executive director of the NASA ExoPlanet Science Institute at Caltech. "Having these combs routinely available as a modest add-on to current and future instrumentation really will expand our ability to find potentially habitable planets, particularly around very cool red dwarf stars," he says.

The research team is planning to double the frequency of the prototype comb's light output—now centered around 1,550 nanometers, in the infrared—to reach into the visible light range. Doing so would allow the comb also to calibrate spectra from sun-like stars, whose light output is at shorter, visible wavelengths, and thus seek out planets that are Earth's "twins."

Other authors of the paper are Jiang Li, a visitor in applied physics and materials science, graduate students Peter Gao and Michael Bottom, and scientific research assistant Elise Furlan, all from Caltech; Stephanie Leifer, Jagmit Sandhu, Gautam Vasisht, and Pin Chen of JPL; Peter Plavchan (BS '01), formerly at Caltech and now a professor at Missouri State University; G. Ycas of NIST; Jonathan Gagne of the University of Montréal; and Greg Doppmann of the Keck Observatory.

The paper is titled "Demonstration of a near-IR line-referenced electro-optical laser frequency comb for precision radial velocity measurements in astronomy." The research performed at Caltech and JPL was funded through the President's and Director's Fund Program, and the work at NIST was funded by the National Science Foundation. 

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Novel Tool Aids Exoplanet Hunt
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Researchers have developed a laser frequency comb that expands the ability to find habitable worlds.

Where Is Solar Energy Headed?

In a new paper in ScienceNate Lewis, the George L. Argyros Professor of Chemistry at Caltech, reviews recent developments in solar-energy utilization and looks at some of the challenges and opportunities that lie ahead in the research and development of solar-electricity, solar-thermal, and solar-fuels technologies. Read the full paper.

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Caltech Researchers Find Evidence of a Real Ninth Planet

Caltech researchers have found evidence of a giant planet tracing a bizarre, highly elongated orbit in the outer solar system. The object, which the researchers have nicknamed Planet Nine, has a mass about 10 times that of Earth and orbits about 20 times farther from the sun on average than does Neptune (which orbits the sun at an average distance of 2.8 billion miles). In fact, it would take this new planet between 10,000 and 20,000 years to make just one full orbit around the sun.

The researchers, Konstantin Batygin and Mike Brown, discovered the planet's existence through mathematical modeling and computer simulations but have not yet observed the object directly.

"This would be a real ninth planet," says Brown, the Richard and Barbara Rosenberg Professor of Planetary Astronomy. "There have only been two true planets discovered since ancient times, and this would be a third. It's a pretty substantial chunk of our solar system that's still out there to be found, which is pretty exciting."

Brown notes that the putative ninth planet—at 5,000 times the mass of Pluto—is sufficiently large that there should be no debate about whether it is a true planet. Unlike the class of smaller objects now known as dwarf planets, Planet Nine gravitationally dominates its neighborhood of the solar system. In fact, it dominates a region larger than any of the other known planets—a fact that Brown says makes it "the most planet-y of the planets in the whole solar system."

Batygin and Brown describe their work in the current issue of the Astronomical Journal and show how Planet Nine helps explain a number of mysterious features of the field of icy objects and debris beyond Neptune known as the Kuiper Belt.

"Although we were initially quite skeptical that this planet could exist, as we continued to investigate its orbit and what it would mean for the outer solar system, we become increasingly convinced that it is out there," says Batygin, an assistant professor of planetary science. "For the first time in over 150 years, there is solid evidence that the solar system's planetary census is incomplete."

The road to the theoretical discovery was not straightforward. In 2014, a former postdoc of Brown's, Chad Trujillo, and his colleague Scott Sheppard published a paper noting that 13 of the most distant objects in the Kuiper Belt are similar with respect to an obscure orbital feature. To explain that similarity, they suggested the possible presence of a small planet. Brown thought the planet solution was unlikely, but his interest was piqued.

He took the problem down the hall to Batygin, and the two started what became a year-and-a-half-long collaboration to investigate the distant objects. As an observer and a theorist, respectively, the researchers approached the work from very different perspectives—Brown as someone who looks at the sky and tries to anchor everything in the context of what can be seen, and Batygin as someone who puts himself within the context of dynamics, considering how things might work from a physics standpoint. Those differences allowed the researchers to challenge each other's ideas and to consider new possibilities. "I would bring in some of these observational aspects; he would come back with arguments from theory, and we would push each other. I don't think the discovery would have happened without that back and forth," says Brown. " It was perhaps the most fun year of working on a problem in the solar system that I've ever had."

Fairly quickly Batygin and Brown realized that the six most distant objects from Trujillo and Sheppard's original collection all follow elliptical orbits that point in the same direction in physical space. That is particularly surprising because the outermost points of their orbits move around the solar system, and they travel at different rates.

"It's almost like having six hands on a clock all moving at different rates, and when you happen to look up, they're all in exactly the same place," says Brown. The odds of having that happen are something like 1 in 100, he says. But on top of that, the orbits of the six objects are also all tilted in the same way—pointing about 30 degrees downward in the same direction relative to the plane of the eight known planets. The probability of that happening is about 0.007 percent. "Basically it shouldn't happen randomly," Brown says. "So we thought something else must be shaping these orbits."

The first possibility they investigated was that perhaps there are enough distant Kuiper Belt objects—some of which have not yet been discovered—to exert the gravity needed to keep that subpopulation clustered together. The researchers quickly ruled this out when it turned out that such a scenario would require the Kuiper Belt to have about 100 times the mass it has today.

That left them with the idea of a planet. Their first instinct was to run simulations involving a planet in a distant orbit that encircled the orbits of the six Kuiper Belt objects, acting like a giant lasso to wrangle them into their alignment. Batygin says that almost works but does not provide the observed eccentricities precisely. "Close, but no cigar," he says.

Then, effectively by accident, Batygin and Brown noticed that if they ran their simulations with a massive planet in an anti-aligned orbit—an orbit in which the planet's closest approach to the sun, or perihelion, is 180 degrees across from the perihelion of all the other objects and known planets—the distant Kuiper Belt objects in the simulation assumed the alignment that is actually observed.

"Your natural response is 'This orbital geometry can't be right. This can't be stable over the long term because, after all, this would cause the planet and these objects to meet and eventually collide,'" says Batygin. But through a mechanism known as mean-motion resonance, the anti-aligned orbit of the ninth planet actually prevents the Kuiper Belt objects from colliding with it and keeps them aligned. As orbiting objects approach each other they exchange energy. So, for example, for every four orbits Planet Nine makes, a distant Kuiper Belt object might complete nine orbits. They never collide. Instead, like a parent maintaining the arc of a child on a swing with periodic pushes, Planet Nine nudges the orbits of distant Kuiper Belt objects such that their configuration with relation to the planet is preserved.

"Still, I was very skeptical," says Batygin. "I had never seen anything like this in celestial mechanics."

But little by little, as the researchers investigated additional features and consequences of the model, they became persuaded. "A good theory should not only explain things that you set out to explain. It should hopefully explain things that you didn't set out to explain and make predictions that are testable," says Batygin.

And indeed Planet Nine's existence helps explain more than just the alignment of the distant Kuiper Belt objects. It also provides an explanation for the mysterious orbits that two of them trace. The first of those objects, dubbed Sedna, was discovered by Brown in 2003. Unlike standard-variety Kuiper Belt objects, which get gravitationally "kicked out" by Neptune and then return back to it, Sedna never gets very close to Neptune. A second object like Sedna, known as 2012 VP113, was announced by Trujillo and Sheppard in 2014. Batygin and Brown found that the presence of Planet Nine in its proposed orbit naturally produces Sedna-like objects by taking a standard Kuiper Belt object and slowly pulling it away into an orbit less connected to Neptune.


A predicted consequence of Planet Nine is that a second set of confined objects should also exist. These objects are forced into positions at right angles to Planet Nine and into orbits that are perpendicular to the plane of the solar system. Five known objects (blue) fit this prediction precisely.
Credit: Caltech/R. Hurt (IPAC) [Diagram was created using WorldWide Telescope.]

But the real kicker for the researchers was the fact that their simulations also predicted that there would be objects in the Kuiper Belt on orbits inclined perpendicularly to the plane of the planets. Batygin kept finding evidence for these in his simulations and took them to Brown. "Suddenly I realized there are objects like that," recalls Brown. In the last three years, observers have identified four objects tracing orbits roughly along one perpendicular line from Neptune and one object along another. "We plotted up the positions of those objects and their orbits, and they matched the simulations exactly," says Brown. "When we found that, my jaw sort of hit the floor."

"When the simulation aligned the distant Kuiper Belt objects and created objects like Sedna, we thought this is kind of awesome—you kill two birds with one stone," says Batygin. "But with the existence of the planet also explaining these perpendicular orbits, not only do you kill two birds, you also take down a bird that you didn't realize was sitting in a nearby tree."

Where did Planet Nine come from and how did it end up in the outer solar system? Scientists have long believed that the early solar system began with four planetary cores that went on to grab all of the gas around them, forming the four gas planets—Jupiter, Saturn, Uranus, and Neptune. Over time, collisions and ejections shaped them and moved them out to their present locations. "But there is no reason that there could not have been five cores, rather than four," says Brown. Planet Nine could represent that fifth core, and if it got too close to Jupiter or Saturn, it could have been ejected into its distant, eccentric orbit.

Batygin and Brown continue to refine their simulations and learn more about the planet's orbit and its influence on the distant solar system. Meanwhile, Brown and other colleagues have begun searching the skies for Planet Nine. Only the planet's rough orbit is known, not the precise location of the planet on that elliptical path. If the planet happens to be close to its perihelion, Brown says, astronomers should be able to spot it in images captured by previous surveys. If it is in the most distant part of its orbit, the world's largest telescopes—such as the twin 10-meter telescopes at the W. M. Keck Observatory and the Subaru Telescope, all on Mauna Kea in Hawaii—will be needed to see it. If, however, Planet Nine is now located anywhere in between, many telescopes have a shot at finding it.

"I would love to find it," says Brown. "But I'd also be perfectly happy if someone else found it. That is why we're publishing this paper. We hope that other people are going to get inspired and start searching."

In terms of understanding more about the solar system's context in the rest of the universe, Batygin says that in a couple of ways, this ninth planet that seems like such an oddball to us would actually make our solar system more similar to the other planetary systems that astronomers are finding around other stars. First, most of the planets around other sunlike stars have no single orbital range—that is, some orbit extremely close to their host stars while others follow exceptionally distant orbits. Second, the most common planets around other stars range between 1 and 10 Earth-masses.

"One of the most startling discoveries about other planetary systems has been that the most common type of planet out there has a mass between that of Earth and that of Neptune," says Batygin. "Until now, we've thought that the solar system was lacking in this most common type of planet. Maybe we're more normal after all."

Brown, well known for the significant role he played in the demotion of Pluto from a planet to a dwarf planet adds, "All those people who are mad that Pluto is no longer a planet can be thrilled to know that there is a real planet out there still to be found," he says. "Now we can go and find this planet and make the solar system have nine planets once again."

The paper is titled "Evidence for a Distant Giant Planet in the Solar System."

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Kimm Fesenmaier
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Evidence of a Real Ninth Planet
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The giant planet, nicknamed Planet Nine, traces a bizarre, highly elongated orbit in the outer solar system.

Toward Liquid Fuels from Carbon Dioxide

In the quest for sustainable alternative energy and fuel sources, one viable solution may be the conversion of the greenhouse gas carbon dioxide (CO2) into liquid fuels.

Through photosynthesis, plants convert sunlight, water, and CO2 into sugars, multicarbon molecules that fuel cellular processes. CO2 is thus both the precursor to the fossil fuels that are central to modern life as well as the by-product of burning those fuels. The ability to generate synthetic liquid fuels from stable, oxygenated carbon precursors such as CO2 and carbon monoxide (CO) is reminiscent of photosynthesis in nature and is a transformation that is desirable in artificial systems. For about a century, a chemical method known as the Fischer-Tropsch process has been utilized to convert hydrogen gas (H2) and CO to liquid fuels. However, its mechanism is not well understood and, in contrast to photosynthesis, the process requires high pressures (from 1 to 100 times atmospheric pressure) and temperatures (100–300 degrees Celsius).

More recently, alternative conversion chemistries for the generation of liquid fuels from oxygenated carbon precursors have been reported. Using copper electrocatalysts, CO and CO2 can be converted to multicarbon products. The process proceeds under mild conditions, but how it takes place remains a mystery.

Now, Caltech chemistry professor Theo Agapie and his graduate student Joshua Buss have developed a model system to demonstrate what the initial steps of a process for the conversion of CO to hydrocarbons might look like.

The findings, published as an advanced online publication for the journal Nature on December 21, 2015 (and appearing in print on January 7, 2016), provide a foundation for the development of technologies that may one day help neutralize the negative effects of atmospheric accumulation of the greenhouse gas CO2 by converting it back into fuel. Although methods exist to transform CO2 into CO, a crucial next step, the deoxygenation of CO molecules and their coupling to form C–C bonds, is more difficult.

In their study, Agapie and Buss synthesized a new transition metal complex—a metal atom, in this case molybdenum, bound by one or more supporting molecules known as ligands—that can facilitate the activation and cleavage of a CO molecule. Incremental reduction of the molecule leads to substantial weakening of the C–O bonds of CO. Once weakened, the bond is broken entirely by introducing silyl electrophiles, a class of silicon-containing reagents that can be used as surrogates for protons.

This cleavage results in the formation of a terminal carbide—a single carbon atom bound to a metal center—that subsequently makes a bond with the second CO molecule coordinated to the metal. Although a carbide is commonly proposed as an intermediate in CO reductive coupling, this is the first direct demonstration of its role in this type of chemistry, the researchers say. Upon C–C bond formation, the metal center releases the C2 product. Overall, this process converts the two CO units to an ethynol derivative and proceeds easily even at temperatures lower than room temperature.

"To our knowledge, this is the first example of a well-defined reaction that can take two carbon monoxide molecules and convert them into a metal-free ethynol derivative, a molecule related to ethanol; the fact that we can release the C2 product from the metal is important," Agapie says.

While the generated ethynol derivative is not useful as a fuel, it represents a step toward being able to generate synthetic multicarbon fuels from carbon dioxide. The researchers are now applying the knowledge gained in this initial study to improve the process. "Ideally, our insight will facilitate the development of practical catalytic systems," Buss says.

The scientists are also working on a way to cleave the C–O bond using protons instead of silyl electrophiles. "Ultimately, we'd like to use protons from water and electron equivalents derived from sunlight," Agapie says. "But protons are very reactive, and right now we can't control that chemistry."

The research in the paper, "Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site," was funded by Caltech and the National Science Foundation.

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Toward Liquid Fuels from Carbon Dioxide
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Caltech researchers gain insight into carbon monoxide coupling, one carbon atom at a time

15 for 2015: The Year in Research News at Caltech

The year 2015 proved to be another groundbreaking year for research at Caltech. From seeing quantum motion, to reconfiguring jellyfish limbs, to measuring stellar magnetic fields, researchers continued to ask and answer the deepest scientific questions.

In case you missed any of them, here are 15 stories highlighting a few of the discoveries, methods, and technologies that came to life at Caltech in 2015.

 

 

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Here are 15 stories highlighting a few of the discoveries, methods, and technologies that came to life at Caltech in 2015.

Developing a Picture of the Earth's Mantle

Deep inside the earth, seismic observations reveal that three distinct structures make up the boundary between the earth's metallic core and overlying silicate mantle at a depth of about 2,900 kilometers—an area whose composition is key to understanding the evolution and dynamics of our planet. These structures include remnants of subducted plates that originated near the earth's surface, ultralow-velocity zones believed to be enriched in iron, and large dense provinces of unknown composition and mineralogy. A team led by Caltech's Jennifer Jackson, professor of mineral physics has new evidence for the origin of these features that occur at the core-mantle boundary.

"We have discovered that bridgmanite, the most abundant mineral on our planet, is a reasonable candidate for the material that makes up these dense provinces that occupy about 20 percent of the core-mantle boundary surface, and rise up to a depth of about 1,500 kilometers. Integrated by volume that's about the size of our moon!" says Jackson, coauthor of a study that outlines these findings and appears online in the Journal of Geophysical Research: Solid Earth. "This finding represents a breakthrough because although bridgmanite is the earth's most abundant mineral, we only recently have had the ability to precisely measure samples of it in an environment similar to what we think the materials are experiencing inside the earth."

Previously, says Jackson, it was not clear whether bridgmanite, a perovskite structured form of (Mg,Fe)SiO3, could explain seismic observations and geodynamic modeling efforts of these large dense provinces. She and her team show that indeed they do, but these structures need to be propped up by external forces, such as the pinching action provided by cold and dense subducted slabs at the base of the mantle.

Jackson, along with then Caltech graduate student Aaron Wolf (PhD '13), now a research scientist at the University of Michigan at Ann Arbor, and researchers from Argonne National Laboratory, came to these conclusions by taking precise X-ray measurements of synthetic bridgmanite samples compressed by diamond anvil cells to over 1 million times the earth's atmospheric pressure and heated to thousands of degrees Celsius.

The measurements were done utilizing two different beamlines at the Advanced Photon Source of Argonne National Laboratory in Illinois, where the team used powerful X-rays to measure the state of bridgmanite under the physical conditions of the earth's lower mantle to learn more about its stiffness and density under such conditions. The density controls the buoyancy—whether or not these bridgmanite provinces will lie flat on the core-mantle boundary or rise up. This information allowed the researchers to compare the results to seismic observations of the core-mantle boundary region.

"With these new measurements of bridgmanite at deep-mantle conditions, we show that these provinces are very likely to be dense and iron-rich, helping them to remain stable over geologic time," says Wolf.

Using a technique known as synchrotron Mössbauer spectroscopy, the team also measured the behavior of iron in the crystal structure of bridgmanite, and found that iron-bearing bridgmanite remained stable at extreme temperatures (more than 2,000 degrees Celsius) and pressure (up to 130 gigapascals). There had been some reports that iron-bearing bridgmanite breaks down under extreme conditions, but the team found no evidence for any breakdown or reactions.

"This is the first study to combine high-accuracy density and stiffness measurements with Mössbauer spectroscopy, allowing us to pinpoint iron's behavior within bridgmanite," says Wolf. "Our results also show that these provinces cannot possibly contain a large complement of radiogenic elements, placing strong constraints on their origin. If present, these radiogenic elements would have rapidly heated and destabilized the piles, contradicting many previous simulations that indicate that they are likely hundreds of millions of years old."

In addition, the experiments suggest that the rest of the lower mantle is not 100 percent bridgmanite as had been previously suggested. "We've shown that other phases, or minerals, must be present in the mantle to satisfy average geophysical observations," says Jackson. "Until we made these measurements, the thermal properties were not known with enough precision and accuracy to uniquely constrain the mineralogy."

"There is still a lot of work to be done, such as identifying the dynamics of subducting slabs, which we believe plays a role in providing an external force to shape these large bridgmanite provinces," she says. "We know that the earth did not start out this way. The provinces had to evolve within the global system, and we think these findings may help large-scale geodynamic modeling that involves tectonic plate reconstructions."

The results of the study were published in a paper titled "The thermal equation of state of (Mg,Fe)SiO3bridgmanite (perovskite) and implications for lower mantle structures." In addition to Jackson and Wolf, other authors on the study are Przemeslaw Dera and Vitali B. Prakapenka from the Center for Advanced Radiation Sources at Argonne National Laboratory. Support for this research was provided by the National Science Foundation, the Turner Postdoctoral Fellowship at the University of Michigan, and the California Institute of Technology.

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A team led by Caltech's Jennifer Jackson, professor of mineral physics has new evidence for the origin of features that occur at the core-mantle boundary.

15 for 2015: The Year in Research News at Caltech

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15 for 2015: The Year in Research News at Caltech
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Credit: K.Batygin/Caltech

New Research Suggests Solar System May Have Once Harbored Super-Earths

Thanks to recent surveys of exoplanets—planets in solar systems other than our own—we know that most planetary systems typically have one or more super-Earths (planets that are substantially more massive than Earth but less massive than Neptune) orbiting closer to their suns than Mercury does. In March, researchers showed that our own solar system may have once had these super-Earths, but they were destroyed by Jupiter's inward and outward migration through the solar system. This migration would have gravitationally flung small planetesimals through the solar system, setting off chains of collisions that would push any interior planets into the sun.
Credit: Lance Hayashida/Caltech and the Hoelz Laboratory/Caltech

Caltech Biochemists Shed Light on Cellular Mystery

The nuclear pore complex (NPC) is an intricate portal linking the cytoplasm of a cell to its nucleus. It is made up of many copies of about 34 different proteins. Around 2,000 NPCs are embedded in the nuclear envelope of a single human cell and each NPC shuttles hundreds of macromolecules of different shapes and sizes between the cytoplasm and nucleus. In February, Caltech biochemists determined the structure of a significant portion of the NPC called the outer rings; in August, the same group solved the structure of the pore's inner ring. Understanding the structure of the NPC could lead to new classes of cancer drugs as well as antiviral medicines.
Credit: iStockphoto

Research Suggests Brain's Melatonin May Trigger Sleep

For decades, supplemental melatonin has been sold over the counter as a sleep aid despite the absence of scientific evidence proving its effectiveness. Few studies have investigated melatonin produced naturally in the human body. This March, Caltech researchers studying zebrafish—animals that, like humans, are awake during the day and asleep at night—determined that the melatonin hormone does help the body fall asleep and stay asleep. Specifically, they found that zebrafish larvae that could not produce melatonin slept for only half as long as normal larvae.
Credit: Gregg Hallinan/Caltech

Advances in Radio Astronomy

In May, a new radio telescope array called the Owens Valley Long Wavelength Array (OV-LWA) saw its first light. Developed by a consortium led by Caltech, the OV-LWA has the ability to image simultaneously the entire sky at radio wavelengths with unmatched speed, helping astronomers to search for objects and phenomena that pulse, flicker, flare, or explode.

In July, Caltech researchers used both radio and optical telescopes to observe a brown dwarf located 20 light-years away and found that these so-called failed stars host powerful auroras near their magnetic poles.
Credit: Michael Abrams and Ty Basinger

Injured Jellyfish Seek to Regain Symmetry

Some kinds of animals can regrow lost limbs and body parts, but moon jellyfish have a different strategy. In June, Caltech researchers reported that the star-shaped eight-armed moon jellyfish rearranges itself when injured to maintain symmetry. It is hypothesized that the rearrangement helps to preserve the jellyfish's propulsion mechanism.
Credit: NASA/JPL-Caltech

Geologists Characterize Nepal Earthquake

In April, a magnitude 7.8 earthquake rocked Nepal. While the damage was extensive, it was not as severe as many geologists predicted. This year, a Caltech team of geologists used satellite radar imaging data and measurements from seismic instruments in Nepal to create models of fault rupture and ground movement. They found that the quake ruptured only a small fraction of the "locked" tectonic plate and that there is still the potential for the locked portion to produce a large earthquake.
Credit: Caltech/JPL

New Polymer Creates Safer Fuels

Plane crashes cause devastating damage, but this damage is often exacerbated by the highly explosive nature of jet fuel. This October, researchers at Caltech and JPL discovered a polymeric fuel additive that can reduce the intensity of postimpact explosions that occur during accidents and crashes. Preliminary results show that the additive can provide this benefit without adversely affecting fuel performance. The polymer works by inhibiting "misting"—the process that causes fuel to rapidly disperse and easily catch fire—under crash conditions.
Credit: Spencer Kellis/Caltech

Controlling a Robotic Arm with a Patient's Intentions

When you reach for a glass of water, you do not consciously think about moving your arm muscles or grasping with your fingers—you think about the goal of the movement. This May, by implanting neural prosthetic devices into the posterior parietal cortex (PCC)—the region of the brain that governs intentions for movement—rather than the motor cortex, which controls movement, Caltech researchers enabled a paralyzed patient to more smoothly and naturally control a prosthetic limb. In November, the researchers showed that there are individual neurons in the PPC that encode for entire hand shapes, such as those used for grasping or gesturing.

 

Caltech Scientists Develop Cool Process to Make Better Graphene

Graphene is an ultrastrong and conductive material made of a single layer of carbon atoms. While it is a promising material for scientific and engineering advances, manufacturing it on an industrially relevant scale has proven to be impractical, requiring temperatures of around 1,800 degrees Fahrenheit and long periods of time. A new technique invented at Caltech allows the speedy production of graphene—in just a few minutes—at room temperatures. The technique also produces graphene that is stronger, smoother, and more electrically conductive than normally produced synthetic graphene.
Credit: Rafael A. García (SAp CEA), Kyle Augustson (HAO), Jim Fuller (Caltech) & Gabriel Pérez (SMM, IAC), Photograph from AIA/SDO

Astronomers Peer Inside Stars, Finding Giant Magnets

Before this October, astronomers have only been able to study the magnetic fields of stars on the stellar surfaces. Now, using a technique called asteroseismology, scientists were able to probe the fusion-powered hearts of dozens of red giants (stars that are evolved versions of our sun) to calculate the magnetic field strengths inside those stars. They found that the internal magnetic fields of the red giants were as much as 10 million times stronger than Earth's magnetic field. Magnetic fields play a key role in the interior rotation rate of stars, which has a dramatic effect on how the stars evolve.
Credit: Chan Lei and Keith Schwab/Caltech

Seeing Quantum Motion

To the casual observer, an object at rest is just that—at rest, motionless. But on the subatomic scale, the object is most certainly in motion—quantum mechanical motion. Quantum motion, or noise, is ever-present in nature, and in August, Caltech researchers discovered how to observe and manipulate that motion in a small device. By creating what they called a "quantum squeezed state," they were able to periodically reduce the quantum fluctuations of the device. The ability to control quantum noise could one day be used to improve the precision of very sensitive measurements.
Credit: Ali Hajimiri/Caltech

New Camera Chip Provides Superfine 3-D Resolution

3-D printing can produce a wide array of objects in relatively little time, but first the printer needs to have a blueprint of what to print. The blueprints are provided by 3-D cameras, which scan objects and create models for the printer. Caltech researchers have now developed a 3-D camera that produces the highest depth-measurement accuracy of any similar device, allowing it to deliver replicas of an object to be 3-D printed within microns of similarity to the original object. In addition, the camera, known as a nanophotonic coherent imager, is inexpensive and small.
Credit: Image provided courtesy of Joint Center for Artificial Photosynthesis; artwork by Darius Siwek.

One Step Closer to Artificial Photosynthesis and 'Solar Fuels'

Plants are masters of photosynthesis—the process of turning carbon dioxide, sunlight, and water into oxygen and sugar. Inspired by this natural and energy-efficient process, Caltech researchers have created an "artificial leaf" that takes in CO2, sunlight, and water to produce hydrogen fuels. This solar-powered system, one researcher says, shatters all of the combined safety, performance, and stability records for artificial leaf technology by factors of 5 to 10 or more.
Credit: Santiago Lombeyda and Robin Betz

Potassium Salt Outperforms Precious Metals As a Catalyst

Rare precious metals have been the standard catalyst for the formation of carbon-silicon bonds, a process crucial to the synthesis of a host of products from new medicines to advanced materials. However, they are expensive, inefficient, and produce toxic waste byproducts. This February, Caltech researchers discovered a much more sustainable catalyst in the form of a simple potassium salt that is one of the most abundant metals on Earth and thousands of times less expensive than other commonly used catalysts. In addition, the potassium salt is much more effective at running challenging chemical reactions than state-of-the-art precious metal complexes.
Credit: Qi Zhao/National University of Singapore

Probing the Mysterious Perceptual World of Autism

The way in which people with autism spectrum disorder (ASD) perceive the world is unique. It has been a long-standing belief that people with ASD often miss facial cues, contributing to impaired social interaction. In a study published in October, Caltech researchers showed 700 images to 39 subjects and found that people with ASD pay closer attention to simple edges and patterns in images than to the faces of people. The study also found that subjects were strongly attracted to the center of images—regardless of what was placed there—and to differences in color and contrast rather than facial features. These findings may help doctors diagnose and more effectively treat the different forms of autism.
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The year 2015 proved to be another groundbreaking year for research at Caltech. From seeing quantum motion, to reconfiguring jellyfish limbs, to measuring stellar magnetic fields, researchers continued to ask and answer the deepest scientific questions.

In case you missed any of them, here are 15 stories highlighting a few of the discoveries, methods, and technologies that came to life at Caltech in 2015.

Written by Lori Dajose

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Popping Microbubbles Help Focus Light Inside the Body

A new technique developed at Caltech that uses gas-filled microbubbles for focusing light inside tissue could one day provide doctors with a minimally invasive way of destroying tumors with lasers, and lead to improved diagnostic medical imaging.

The primary challenge with focusing light inside the body is that biological tissue is optically opaque. Unlike transparent glass, the cells and proteins that make up tissue scatter and absorb light. "Our tissues behave very much like dense fog as far as light is concerned," says Changhuei Yang, professor of electrical engineering, bioengineering, and medical engineering. "Just like we cannot focus a car's headlight through fog, scientists have always had difficulty focusing light through tissues."

To get around this problem, Yang and his team turned to microbubbles, commonly used in medicine to enhance contrast in ultrasound imaging.

The gas-filled microbubbles are encapsulated by thin protein shells and have an acoustic refractive index—a property that affects how sound waves propagate through a medium—different from that of living tissue. As a result, they respond differently to sound waves. "You can use ultrasound to make microbubbles rapidly contract and expand, and this vibration helps distinguish them from surrounding tissue because it causes them to reflect sound waves more effectively than biological tissue," says Haowen Ruan, a postdoctoral scholar in Yang's lab.

In addition, the optical refractive index of microbubbles is not the same as that of biological tissue. The optical refractive index is a measure of how much light rays bend when transitioning from one medium (a liquid, for example) to another (a gas).

Yang, Ruan, and graduate student Mooseok Jang developed a novel technique called time-reversed ultrasound microbubble encoded (TRUME) optical focusing that utilizes the mismatch between the acoustic and optical refractive indexes of microbubbles and tissue to focus light inside the body. First, microbubbles injected into tissue are ruptured with ultrasound waves. By measuring the difference in light transmission before and after such an event, the Caltech researchers can modify the wavefront of a laser beam so that it is focuses on the original locations of the microbubbles. The result, Yang explains, "is as if you're searching for someone in a dark field, and suddenly the person lets off a flare. For a brief moment, the person is illuminated and you can home in on their location."

In a new study, published online November 24, 2015, in the journal Nature Communications, the team showed that their TRUME technique could be used as an effective "guidestar" to focus laser beams on specific locations in a biological tissue. A single, well-placed microbubble was enough to successfully focus the laser; multiple popping bubbles located within the general vicinity of a target functioned as a map for the light.

"Each popping event serves as a road map for the twisting light trajectories through the tissue," Yang says. "We can use that road map to shape light in such a way that it will converge where the bubbles burst."

If TRUME is shown to work effectively inside living tissue—without, for example, any negative effects from the bursting microbubbles—it could enable a range of research and medical applications. For example, by combining the microbubbles with an antibody probe engineered to seek out biomarkers associated with cancer, doctors could target and then destroy tumors deep inside the body or detect malignant growths much sooner.

"Ultrasound and X-ray techniques can only detect cancer after it forms a mass," Yang says. "But with optical focusing, you could catch cancerous cells while they are undergoing biochemical changes but before they undergo morphological changes."

The technique could take the place of other of diagnostic screening methods. For instance, it could be used to measure the concentrations of a protein called bilirubin in infants to determine their risk for jaundice. "Currently, this procedure requires a blood draw, but with TRUME, we could shine a light into an infant's body and look for the unique absorption signature of the bilirubin molecule," Ruan says.

In combination with existing techniques that allow scientists to activate individual neurons in lab animals using light, TRUME could help neuroscientists better understand how the brain works. "Currently, neuroscientists are confined to superficial layers of the brain," Yang says. "But our method of optical focusing could allow for a minimally invasive way of probing deeper regions of the brain."

The paper is entitled "Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded (TRUME) light." Support for the research was provided by the National Institutes of Health, the National Institutes of Health BRAIN Initiative, and a GIST-Caltech Collaborative Research Proposal.

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A new technique could one day provide doctors with a minimally invasive way of destroying tumors with lasers, and lead to improved diagnostic medical imaging.

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