Alice on Trial, Redux

Pasadena, Calif.--When Alice revs her engine at the start of the Defense Advanced Research Projects Agency (DARPA) Urban Challenge qualifying rounds on October 27, multitudes of cameras will be pointing at her. But she'll only care about the eight cameras that will be facing away.

Alice is the tricked-out Ford E-350 van that has been revamped to autonomously navigate the vagaries of an urban setting. To do so, she sports eight cameras that feed information to computers at rates of hundreds of megabits per second. Six of those cameras face forward, one faces the rear, and one is mounted on a pan-tilt unit programmed to turn and look to the left and to the right.

Team Caltech leader Richard Murray, Everhart Professor of Control and Dynamical Systems, says there's good reason the team chose a setup in which several cameras and lasers feed visual information into decentralized computers. With multiple computers telling Alice about surrounding obstacles, "it's like having multiple parts of your brain telling you what to do," he says. The computers are arranged in a hierarchy, with "lower level" computers doing computations based on the information they receive and passing on results to higher levels, where the ultimate decision is made. This way, there's less chance of driving into an obstacle and more chance of staying on the path the cameras detect. Team Caltech also chose this setup because it could easily accommodate new sensors.

The Urban Challenge presents far greater complexities than the two previous Grand Challenges, which took place in the desert of Barstow, California. "In the desert challenge, you simply had to drive on flat spots," Murray says. The teams have road information from aerial photos and maps of this year's challenge site, a mock city at the George Air Force Base in Victorville, California. But, says Murray, "that's not the hard part. It's dealing with what's not on the map. We don't know where there will be obstacles or where other vehicles will be."

Team Caltech's attempts at winning the first two DARPA challenges were met with defeat. In 2004, Alice's predecessor Bob drove 1.3 miles before losing a fight with a barbed-wire fence. In communications theory, Alice and Bob stand for sender and receiver, so the next year, Bob gave way to Alice, who ended an eight-mile run at a concrete barrier. Now, Alice, redux, is one of 35 vehicles entering the qualifying round for this year's Urban Challenge. Murray is confident Team Caltech will advance to the final round, on November 3.

What makes the new challenge so difficult is not news to any driver--the rules come from the California driver's handbook. Any collision or damage wreaked gets the team automatically disqualified. Broken rules like turning without signaling or crossing a solid traffic line incur a time penalty. Each team will vie with up to 34 other vehicles that may qualify for the race, and DARPA may make things even trickier by including human-driven vehicles.

It would be impossible to imagine and prepare for every error that pops up, says Murray. Instead, he says, the team took the approach of following a sequence of actions to try to solve any dilemma. For example, if there were dirt on one sensor the computers might mistake it for a real obstacle. Then Alice might try backing up to check if the obstacle remained. The Jet Propulsion Laboratory (JPL) uses some of these approaches in building its autonomous rovers to explore other planets' surfaces. "Part of the approach we take is to build on what JPL has been doing for years," Murray says.

The Caltech team consists of almost 80 undergraduate and graduate students, postdocs, and faculty, many of whom participated in the previous Grand Challenge. Specialists from JPL and Northrop Grumman added their expertise. In the final event, the team whose vehicle reaches the finish line first in less than six hours wins $2 million, second place garners $1 million, and third, $500,000.

The public is invited to attend both the qualifying round and the finals, and admission is free for both events, with grandstand seating available. The qualifying round begins with an opening ceremony at 7 a.m. on October 26 and continues through October 31. The finalists will be announced on November 1, with the final round following on November 3. Spectator information is available at the DARPA Grand Challenge website: http://www.darpa.mil/grandchallenge/spectators.asp. For the latest information on Team Caltech, visit its website: http://gc.caltech.edu.

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Elisabeth Nadin
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Caltech Scientists Create Breakthrough Sensor Capable of Detecting Individual Molecules

PASADENA, Calif.- Applied physicists at the California Institute of Technology have figured out a way to detect single biological molecules with a microscopic optical device. The method has already proven effective for detecting the signaling proteins called cytokines that indicate the function of the immune system, and it could be used in numerous medical applications, such as the extremely early detection of cancer and other diseases, as well as in basic biological research.

According to Kerry Vahala, the Jenkins Professor of Information Science and Technology and professor of applied physics, this new detection technology revolves around a previous invention from his lab called an "ultra-high-Q microtoroid resonator." This is a donut-shaped glass device that is narrower than the width of a human hair and that is able to hold on to light very efficiently. Vahala explains that "the detector relies upon this feature to boost sensitivity to the single molecule level, albeit in a surprising way." He notes that the original idea was to detect an optical response elicited directly by molecules landing on the donut-shaped device. "As work proceeded, however, we were able to observe single molecule detection events with far greater ease than was originally expected." This pleasant surprise was traced to minute amounts of heat generated when molecules interact with the light stored within the microtoroid resonator. "This thermo-optic response boosts the sensitivity a millionfold," explains Vahala. Andrea Armani, who works in Vahala's laboratory and developed the detector as part of her thesis research, notes that besides being extremely sensitive, the device is also programmable by coating its surface with substances that react to a specific biological molecule. "The molecule which the device is targeting, whether it is a growth factor or a chemical like TNT, is determined by the surface treatment of the glass microtoroid. Fortunately, the biology and chemistry communities have developed very effective techniques for attaching proteins to glass surfaces, because most microscope slides are glass. All we had to do was adopt those techniques to fit our structure," explains Armani.

Vahala notes that "this combination of single-molecule sensitivity and programmable detection, that is, without labeling of the target molecule, has not been demonstrated before, and enables new kinds of tests and measurement."

Scott Fraser, the Rosen Professor of Biology, professor of bioengineering, and collaborator on the project, explains further that "this technology should lead to many applications for biological experiments, medical tests, and even medical treatments. The advantages are its ability to detect extremely small numbers of molecules, and the fact that there's no need to label target molecules. At this sensitivity level, it is possible even to study growth factors being emitted in real time from a single cell." Fraser adds, "This is the only sensor that currently has the requisite sensitivity and rapidity."

This type of experiment is important in monitoring how environmental changes, such as pH or temperature, can influence a cell's behavior. Currently, these types of experiments must be performed with populations of millions of cells, which often blurs results because it is like trying to pick out a single voice in a choir.

In the July 5 issue of the online journal Science Express, the team reports on its success in detecting a series of different molecules, including one immune response signaling protein, interleukin-2 (IL-2). For the latter, the targeting molecule the devices were coated with was a specific antibody that recognized IL-2. This surface preparation allowed the detector surface to bind the IL-2, while the thermo-optic mechanism provided the sensitivity required to detect the IL-2 at the single molecule level, even in serum (blood with the clotting factors and red blood cells removed).

"What is most exciting about this device is its ability to get single molecule results in real time without labeling. Because it can be programmed to detect almost any biological molecule, it is a universal detector, and as such opens the door to a whole field of new experiments," adds Armani.

The work was supported by the Defense Advanced Research Projects Agency-funded Center for Optofluidic Integration at Caltech.

The coauthors of the paper are Armani, a Clare Boothe Luce postdoctoral fellow; Vahala; Fraser; Richard Flagan, the McCollum-Corcoran Professor of Chemical Engineering and professor of environmental science and engineering; and Rajan Kulkarni, a recent Caltech biology doctoral graduate.

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Robert Tindol
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On-Chip Optics Makes Continuous Visible Light from Low-Power Infrared

PASADENA, Calif.--If you shine a red laser pointer through a glass window you wouldn't expect it to come out blue on the other side, but with a much brighter beam it just might. At high intensities light energy tends to combine and redistribute, so that red light really can produce blue.

It normally takes a lot of power to boost light into this high-intensity realm. Yet two scientists at the California Institute of Technology have found a way to do more with less, producing a continuous beam of visible light from an infrared source with less than a milliwatt of power.

"Usually this is accomplished using very brief, concentrated bursts of light," says Kerry Vahala, the Ted and Ginger Jenkins Professor of Information Science and Technology and professor of applied physics at Caltech. "To be able to do this continuously and at power levels below a milliwatt is remarkable."

Although infrared light is invisible to human eyes, it is essential to modern telecommunications, flowing through millions of miles of optical fiber. Technology to produce, amplify, and otherwise manipulate near-infrared light is well developed and readily available.

Now, Vahala and Tal Carmon, a postdoctoral scholar in applied physics at Caltech, have linked that mature technology right into the center of the visible spectrum. Their work is basic research that could leverage an established technology for new uses. "When we developed this, we knew there were a number of potential applications," Vahala says.

Yet generating continuous visible light from infrared came as a pleasant surprise. Usually researchers in infrared optics can't directly see their results. This time, Carmon says, "I just turned off the lights and you could see the effect immediately."

At high intensities, light enters the regime of nonlinear optics. We usually notice nonlinearity when there gets to be enough of something to change its environment and rewrite the rules. For example, when a freeway is nearly empty and vehicles effectively have the road to themselves, traffic will behave the same way even with twice as many cars. The only difference is that the flow will double, which is a proportional, or linear, response. But once traffic nears peak capacity, the vehicles no longer act independently, and the flow becomes miserably nonlinear.

Similarly, light beams pass right through each other at the low intensities we typically encounter, because the photons that make up the beams can usually ignore the cross traffic. At high intensities, however, photons become much more likely to collide and reassemble into other photons. Picture three Mini Coopers in dense traffic coalescing into an SUV. The big vehicles of the photon world lie at the higher-energy or blue end of the spectrum, with lower-energy photons appearing as red or even infrared light.

Nonlinear optics usually requires brief megawatt intensities, analogous to flooding the freeway with a sudden burst of traffic, but the Caltech researchers employ a different strategy. They achieve their optical congestion from a much smaller flow, by diverting traffic into a tiny no-exit roundabout.

Their traffic circle is a miniscule glass donut, a microresonator smaller across than a human hair. It accumulates power so that a mere milliwatt of infrared light flowing outside the device can sustain an internal flow of 300 watts, an amplification of 300,000. Although infrared light is essentially trapped inside, energy can still escape as visible light, when three infrared photons combine into a single photon of tripled frequency: the third harmonic.

The two researchers describe this work in the Nature Physics article: "Visible Continuous Emission from a Silica Microphotonic Device by Third-Harmonic Generation."

"Our device has several important features," Vahala says. "First it triples the light frequency, and second, it works in a wide range of frequencies. This means full access to the entire visible spectrum, and likely ultraviolet. Right now there isn't a way of doing UV generation on a chip. Tunable ultraviolet-that's exciting." Coherent UV sources have applications in sensing and also data storage where, for example, wavelength determines the physical size of the information bit on a compact disk.

The microresonator is part of a promising approach for on-chip optical devices using the silica-on-silicon platform, which is compatible with the electronics of ordinary computer chips. Integrating optics and electronics on the same chip makes the device useful for lab-on-a-chip designs, and the ability to use established fabrication techniques makes large-scale, low-cost production possible.

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JA
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Early Rocketeer Homer Stewart Dies

PASADENA, Calif.—Homer Stewart, an early pioneer of rocket research who helped develop Explorer I, America's first satellite, died Saturday, May 26, at his home in Altadena, California. He was 91.

A native of Dubuque, Iowa, Stewart came to the California Institute of Technology for graduate study in 1936 and became interested in the early pioneering rocket research that was being carried out at the time by a small group of Caltech engineers and scientists, chief among them Theodore von Kármán. Stewart, von Kármán, and others began testing rockets in a rugged foothill area of the San Gabriel Mountains about five miles northeast of the Pasadena campus, thereby forming the nucleus of the research group that would evolve into the Jet Propulsion Laboratory.

In 1938, Stewart joined the Caltech faculty from 1938, teaching both aeronautics and meteorology; but for many years he divided his time between his faculty duties and research at JPL. As chief of the research analysis section, he participated in many rocket projects, including the WAC Corporal, the Corporal, the Sergeant, and the Jupiter C. He was chief of JPL's liquid propulsion systems division when JPL and the Army Ballistic Missile Agency (now the Marshall Space Flight Center) developed and launched Explorer I.

His research interests included rocket exhaust velocity requirements for maintaining the exact trajectories of spacecraft. He also conducted research in wind-driven energy, using his knowledge of fluid flow to construct with von Kármán a turbine in the mountains of Vermont in the late 1930s. The the machine generated up to a megawatt of power and operated through World War II in cooperation with a local electrical company. The project was abandoned after the war, in part because of the easy availability of cheap fossil-fuel energy.

Stewart earned his bachelor's degree at the University of Minnesota in 1936 and his doctorate in aeronautics at Caltech in 1940. He served continuously on the Caltech faculty from 1938 until his retirement in 1980.

He is survived by two daughters, Barbara Mogel of Chesapeake Beach, Maryland, and Kay Stewart of San Diego; a son, Dr. Robert J. Stewart of Burien, Washington; and two grandchildren.

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Robert Tindol
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Twisted Flux Tubes Expel "Wrong-Way" Ions

PASADENA, Calif.—Physicists seeking to tame plasma have figured out yet another of its wily ways. Knowing how plasma escapes the grip of magnetic fields may help researchers design better magnetic bottles to contain it. Magnetic confinement could be a crucial technology for electric power plants that harness nuclear fusion, the powerful process fueling the sun.

Metaphorically, it is hard to stop leaks when you haven't yet found them all, and three applied physicists at the California Institute of Technology identify a new leakage mechanism in the current issue of Physical Review Letters. Their model explains certain types of magnetic confinement degradation observed in the laboratory, and it may well be relevant to similar situations in the solar corona.

Nuclear fusion requires great energy to start, and it can release even more. At high energies, electrons are torn from atoms to make plasma, a gaseous mixture of electrons and ions. Although fusion-grade plasma is far too hot for solid walls to hold, a suitably arranged magnetic field can confine it, because electrons and ions are each subject to magnetic forces.

The solar corona provides a compelling example of plasma confinement by magnetic fields. Above the solar surface, magnetic fields sculpt plasma into vast glowing loops, which can last for weeks, only to burst in a violent spray of high-energy particles. Such sudden failures of magnetic confinement are not fully understood, but the Caltech physicists have modeled a process by which the magnetic fields presumed to confine plasmas may instead expel certain ions, under conditions they label "radially unstable motion" (RUM).

"My intuition wouldn't have predicted this effect," says Professor of Applied Physics Paul Bellan. "It's always been assumed that electrons and ions stay close to their magnetic field lines. The model wasn't easy because we had to change our thinking. You have to follow the mathematics and let that change your intuition."

The RUM model provides an explanation for mysterious phenomena previously observed in tokamaks. The tokamak is the configuration most likely to provide magnetic plasma confinement for industrial-scale fusion power generation. Like a twisted rope with ends spliced together, a tokamak is a plasma-filled, twisted magnetic flux tube that acts as a donut-shaped magnetic bottle. Through the plasma a very large electric current circles the donut hole, so that magnetohydrodynamic (MHD) forces confine the plasma within the flux tube.

One method for fueling tokamaks is to inject the plasma with energetic beams of neutral atoms, which quickly lose electrons to become energetic ions. Such ions escape much more quickly when they move against the direction of electric current than when they move along it. Because MHD does not distinguish between countermoving and comoving ions, MHD does not predict this behavior.

The RUM model shows that when an electric current flows along a flux tube, the associated magnetic field interacts with ion motion so that rapidly countermoving ions experience a significantly different energy landscape than other ions. Like flowing water, particles tend "downhill" toward regions of lower potential energy, remaining confined in energy valleys and flowing away from energy hills.

In a flux tube with a corkscrew-shaped magnetic field, the tube's center is an energy valley for comoving and slow countermoving ions, but seems uphill to fast countermoving ions, which accelerate outward and may be visible as an intense jet of plasma away from the tube. Such jets were observed experimentally before they were understood.

"We'd seen some hints of this right from the beginning," says Bellan. The effect is proportional to mass, so it is not as evident in hydrogen plasmas. "It was blatantly obvious in the argon experiment."

The researchers investigated this phenomenon in an experiment that simulated plasma-filled magnetic flux tubes looping through the solar corona. They applied high voltage between electrodes at opposite ends of a semicircular magnetic flux tube. This high voltage ionized argon gas to form plasma, which MHD forces concentrated into a bright arch about 20 centimeters long, like a solar coronal loop but a billion times smaller.

Doppler velocity measurements confirmed the existence of rapidly countermoving ions. The researchers varied the current, plasma density, and magnetic field to test the association between RUM and these fast "wrong-way" ions. They found their RUM onset prediction to be an excellent indicator for the loss of such ions from the magnetic flux loop through the resulting emission of plasma jets.

The authors of the paper, "Observation of Kinetic Plasma Jets in a Coronal-Loop Simulation Experiment," are Caltech postdoctoral fellow Shreekrishna Tripathi, who is now at UCLA, Paul Bellan, and Caltech graduate student in applied physics Gunsu Yun.

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John Avery
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Mechanical Engineering at Caltech Celebrates Centennial

PASADENA, Calif.- Typical universities have mechanical engineering faculty who teach and conduct occasional consulting projects on the side, but the California Institute of Technology is not like most universities and its ME department is anything but typical.

The department, which is celebrating its 100th anniversary on March 30 and 31, has played a key role in the aerospace industry and has contributed to projects including with the Grand Coulee Dam, the Space Shuttle, and the California Aqueduct, among many others.

"It's all about ME," as the celebration is called, will briefly look back at the department's history, but the majority of the agenda is devoted to addressing the problems faculty are currently working to solve, and projects that Caltech students and alumni are undertaking.

Students will demonstrate Alice, their entry in the DARPA Urban Challenge, a November 3 competition in which autonomous ground vehicles will be required to navigate themselves through 60 miles of city streets, using Global Positioning Systems and other technology.

The program on Friday, March 30, will include a reprise of a mechanical engineering design competition and a poster session featuring undergraduate and graduate research achievements. Graduate students will discuss their work in materials with memory, medical applications such as simulating shocks to break up kidney stones, and trying to better understand why some sand dunes create a booming or humming sound when perturbed. Faculty speakers will describe current research projects in medical robotics and modeling earthquake processes. This will be followed by a banquet.

Saturday is devoted to talks by alumni on such topics as "The Future of Oil and Gas Exploration and Recovery," "The Electric Car," "Nanomechanics of Biological Structures--DNA, Membranes, and Viruses," "Manned Space Exploration," and "The 2003 Mars Exploration Rover Project: A Major Engineering Challenge."

The mechanical engineering department consists of 17 professorial faculty members who teach and conduct research in a wide range of areas including thermal sciences, fluid and solid mechanics, mechanical systems, robotics, control systems, and engineering design.

The department is ranked third among graduate programs by US News & World Report and fourth by the Institute for Scientific Information for the strength of its impact on research worldwide (as measured by the number of citations of papers published by its faculty), despite being much smaller than its competition.

Caltech's close association with the Jet Propulsion Laboratory gives students and faculty ready access to projects and facilities related to advanced spacecraft, microelectronics and micromechanical system fabrication, and interplanetary navigation test beds.

Students are encouraged to take a wide range of courses in mechanical engineering and related disciplines at Caltech. The department has an outstanding record of placement for graduates at all degree levels. A large number of undergraduates continue for advanced degrees, and many of the graduate-program alumni have become professors at top research universities. Others have gone on to influential positions in industry and government.

For more information on the centennial events, see http://www.me.caltech.edu/centennial/ or call Christine Silva at (626) 395-4107.

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Contact: Jill Perry (626) 395-3226 jperry@caltech.edu

Visit the Caltech Media Relations website at http://pr.caltech.edu/media.

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JP
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Negative Refraction of Visible Light Demonstrated; Could Lead to Cloaking Devices

PASADENA, Calif.—For the first time, physicists have devised a way to make visible light travel in the opposite direction that it normally bends when passing from one material to another, like from air through water or glass. The phenomenon is known as negative refraction and could in principle be used to construct optical microscopes for imaging things as small as molecules, and even to create cloaking devices for rendering objects invisible.

In the March 22 in the online publication Science Express, California Institute of Technology applied physics researchers Henri Lezec, Jennifer Dionne, and Professor Harry Atwater, will report their success in constructing a nanofabricated photonic material that creates a negative index of refraction in the blue-green region of the visible spectrum. Lezec is a visiting associate in Atwater's Caltech lab, and Dionne is a graduate student in applied physics.

According to Lezec, the key to understanding the technology is first in understanding how light normally bends when it passes from one medium to another. If a pencil is placed in a glass of water at an angle, for example, it appears to bend upward and outward if we look into the water from a vantage point above the surface. This effect is due to the wave nature of light and the normal tendency of different materials to disperse light in different ways-in this case, the materials being the air outside the glass and the water inside it.

However, physicists have thought that, if new optical materials could be constructed at the nanoscale level in a certain way, it might be possible to make the light bend at the same angle, but in the opposite direction. In other words, the pencil angled into the water would appear to bend backward as we looked at it.

The details are complicated, but have to do with the speed of light through the material itself. Researchers in recent years have created materials with negative diffraction for microwave and infrared frequencies. These achievements have exploited the relatively long wavelengths at those frequencies--the wavelength of microwaves being a few centimeters, and that of infrared frequencies about the width of a human hair. Visible light, because its wavelength is at microscopic dimensions--about one-hundredth the width of a hair—has defeated this conventional approach.

Dionne, one of the lead authors, says that the breakthrough is made possible by the Atwater lab's work on plasmonics, an emerging field that "squeezes" light with specially designed materials to create a wave known as a plasmon. In this case, the plasmons act in a manner somewhat similar to a wave carrying ripples across the surface of a lake, carrying light along the silver-coated surface of a silicon-nitride material, and then across a nanoscale gold prism so that the light reenters the silicon-nitride layer with negative refraction.

Thus, the process is not the same as the one used for negative refraction of microwaves and infrared radiation, but it still works, says Dionne. And this discovery is particularly exciting because visible light, as its name suggests, is the wavelength associated with the world of objects we see, provided they are not too small.

"Maybe you could create a superlens that can beat the diffraction limit," says Dionne. "You might be able to see DNA and protein molecules clearly just by looking at them, without having to use a more complicated method like X-ray crystallography."

Atwater, who is the Howard Hughes Professor and professor of applied physics and materials science at Caltech, says the plasmonic technique indeed has potential for a compact "perfect lens" that could have a huge number of biomedical and other technological applications. "Once the light coming from a nearby object passes through the negative-refraction material, it would be possible to recover all the spatial information," he says, adding that the loss of this information is why there is ordinarily a limit to the size of an object that can be seen in a microscope.

Even more tantalizing is the possibility of an optical "invisibility cloak" device that would surround an object and bend light in such a way that it would be perfectly refocused on the opposite side. This would provide perfect invisibility for the object inside the cloak, in a manner similar to the cloaks used by Harry Potter or the Klingons in the old Star Trek television series.

"Of course, anyone inside the cloak would not be able to see out," Atwater says.

"But maybe you could have some small windows," Dionne adds.

The title of the paper is "Negative Refraction at Visible Frequencies." It will be available on the Science Express website at http://www.sciencexpress.org when the embargo lifts and will be published in the journal Science at a later date. To obtain advanced copies of the paper, contact the American Association for the Advancement of Science news office at (202) 326-6440 or scipak@aaas.org.

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Robert Tindol
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Researchers Create DNA Logic Circuit That Work in Test Tubes

PASADENA, Calif.—Computers and liquids are not very compatible, as many a careless coffee-drinking laptop owner has discovered. But a new breakthrough by researchers at the California Institute of Technology could result in future logic circuits that literally work in a test tube—or even in the human body.

In the current issue of the journal Science, a Caltech group led by computer scientist Erik Winfree reports that they have created DNA logic circuits that work in salt water, similar to an intracellular environment. Such circuits could lead to a biochemical microcontroller, of sorts, for biological cells and other complex chemical systems. The lead author of the paper is Georg Seelig, a postdoctoral scholar in Winfree's lab.

"Digital logic and water usually don't mix, but these circuits work in water because they are based on chemistry, not electronics," explains Winfree, an associate professor of computer science and computation and neural systems who is also a recipient of a MacArthur genius grant.

Rather than encoding signals in high and low voltages, the circuits encode signals in high and low concentrations of short DNA molecules. The chemical logic gates that perform the information processing are also DNA molecules, with each gate a carefully folded complex of multiple short DNA strands.

When a gate encounters the right input molecules, it releases its output molecule. This output molecule in turn can help trigger a downstream gate—so the circuit operates like a cascade of dominoes in which each falling domino topples the next one.

However, unlike dominoes and electronic circuits, components of these DNA circuits have no fixed position and cannot be simply connected by a wire. Instead, the chemistry takes place in a well-mixed solution of molecules that bump into each other at random, relying on the specificity of the designed interactions to ensure that only the right signals trigger the right gates.

"We were able to construct gates to perform all the fundamental binary logic operations—AND, OR, and NOT," explains Seelig. "These are the building blocks for constructing arbitrarily complex logic circuits."

As a demonstration, the researchers created a series of circuits, the largest one taking six inputs processed by 12 gates in a cascade five layers deep. While this is not large by the standards of Silicon Valley, Winfree says that it demonstrates several design principles that could be important for scaling up biochemical circuits.

"Biochemical circuits have been built previously, both in test tubes and in cells," Winfree says. "But the novel thing about these circuits is that their function relies solely on the properties of DNA base-pairing. No biological enzymes are necessary for their operation.

"This allows us to use a systematic and modular approach to design their logic circuits, incorporating many of the features of digital electronics," Winfree says.

Other advantages of the approach are signal restoration for the production of correct output even when noise is introduced, and standardization of the chemical-circuit signals by the use of translator gates that can use naturally occurring biological molecules, such as microRNA, as inputs. This suggests that the DNA logic circuits could be used for detecting specific cellular abnormalities, such as a certain type of cancer in a tissue sample, or even in vivo.

"The idea is not to replace electronic computers for solving math problems," Winfree says. "Compared to modern electronic circuits, these are painstakingly slow and exceedingly simple. But they could be useful for the fast-growing discipline of synthetic biology, and could help enable a new generation of technologies for embedding 'intelligence' in chemical systems for biomedical applications and bionanotechnology."

The other authors of the paper are David Soloveichik and Dave Zhang, both Caltech grad students in computation and neural systems.

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Robert Tindol
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Microfuidic Device Used for Multigene Analysis of Individual Environmental Bacteria

PASADENA, Calif.—When it comes to digestive ability, termites have few rivals due to the gut activities that allow them to literally digest a two-by-four. But they do not digest wood by themselves—they are dependent on the 200 or so diverse microbial species that call termite guts home and are found nowhere else in nature.

Despite several successful attempts, the majority of these beneficial organisms have never been cultivated in the laboratory. This has made it difficult to determine precisely which species perform the numerous, varied functions relevant to converting woody plant biomass into a material that can be directly used as food and energy by their insect hosts.

Now, scientists using state-of-the-art microfluidic devices have come up with a new way of investigating microbial ecology. In the December 1 issue of the journal Science, California Institute of Technology associate professor of environmental microbiology Jared Leadbetter, biology graduate student Elizabeth Ottesen, and their colleagues announce a new and efficient way of revealing guild-species relationships in complex microbial communities. The approach allows them to discover connections between bacterial cells from natural samples, and the activities encoded by genes.

The results also reveal important insights into the relationship between termites and key gut microbes called spirochetes, which aid them in the process of digesting wood.

"I think these results involve two pinnacles of novelty," says Leadbetter, "What we're showing are key results relevant to the symbiosis that occurs between termites and the bacteria involved in the conversion of wood fiber into a form of energy that can be used by the insect. But we're also revealing an approach that can lead to a better understanding of the many microbial processes that underlie the environments in which we all live."

According to Leadbetter, the techniques of gene amplification, cloning, and sequencing developed over the past two decades have already revolutionized microbial ecology. As a result, we now have a much greater appreciation of the vast diversity of microbial species occurring in nature, as well as the diversity of genes involved with processes that we know are mediated by as-yet unstudied microbes in the environment.

However, researchers have had difficulty in determining which subset of the species that have been inventoried actually encode these various key genes. The biggest problem has been the practice of extracting as one mass the composite genetic information of an entire, complex sample. This destroys the individual cells that are the source of the information, thus mixing together that which is encoded by hundreds if not thousands of unique species. As a result, the procedure inevitably dissolves the natural order underlying the organization of genetic information in the environment.

The approach of Leadbetter and his collaborators is to use microfluidic devices, in which thousands of individual cells harvested from the environment can be distributed into separate chambers prior to any gene-based analysis, so that each can be studied as an individual. If the cell reveals that it has a certain key gene of interest, then the researchers are also able to determine the species identity of the cell, or whether it contains other key genes of interest.

The traditional approach involves removing the gut contents of individual termites, smashing the microbial cells, than extracting and pooling their DNA as one mass, with subsequent analysis of the genes found in the randomized mash. The genes are there, but assigning relationships between any two genes or to the organisms from which they are derived is complicated at best, and often just not possible.

"We're trying to move beyond investigating the jumbled information," says Leadbetter. "In the past, trying to study a microbial environment using gene-based techniques was often like studying the contents of several hundred books in a library after first having torn off their covers, ripped up all the pages into small pieces, and jumbled them together into a big pile. We would find sentences and paragraphs that we found extremely interesting and important, but then we were left frustrated. It was very difficult to determine what was in the rest of the book.

"But with this technique, we are suddenly able to read portions of the books without having first torn off their covers. We are still reading with a narrow penlight, but certainly, when we identify a sentence of interest, we can rapidly ascertain the title and author of the book that we are reading, and even move on to examine the other pages."

In the paper, the researchers describe an analysis of a complex, species-rich microbial community that allowed two genes of interest to be colocalized to the same environmental genome. An early result analyzing thousands of individual cells harvested straight from the gut environment reveals the species identity of a group of microbes resident in the California dampwood termite (Zootermopsis) that perform a key act in the nutritional symbiosis involved in wood decay.

The good news for nonscientists is that this provides a new path to reaching a better understanding of many diverse ecosystems. It also leads to a refined appreciation of certain details underlying the activities of a destructive pest, while shedding light on a key step involved in the conversion of plant biomass into useful products. Understanding that conversion in detail is critical to achieving a current societal need-the conversion of low-value lignocellulose materials into biofuels and other commodities of greater value.

Termites are extremely abundant and active in many tropical ecosystems, so the current work could also lead to a better understanding of several processes of global environmental relevance, Leadbetter adds.

"There are 2,600 different species of termites, and it is estimated that there are at least a million billion individual termites on Earth. It is thought that they emit two and four percent of the global carbon dioxide and methane budget, respectively-both mediated directly or indirectly by their microbes," he says. "Also, by extrapolation of what we understand from numerous studies of a few dozen termites species, we think that there could be millions of unique and novel microbial species found only in the hindguts of termites."

The other authors of the paper are Stephen Quake, professor of bioengineering at Stanford, and Jong Wook Hong, an assistant professor of materials engineering at Auburn University.

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Robert Tindol
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Watson Lecture: Amazing Bubbles

PASADENA, Calif.--There is more to bubbles than just froth. The same phenomenon that puts foam in your latte can also reduce kidney stones or chew holes in propellers. Understanding how bubbles form and collapse has led to a variety of applications, from faster torpedoes to cleaner teeth.

"Bubbles have some amazing properties that can be both harmful and beneficial," says Christopher E. Brennen, the Richard L. and Dorothy M. Hayman Professor of Mechanical Engineering at the California Institute of Technology. "In particular, they are used in a startling number of modern medical applications, for example the remote removal of kidney stones by lithotripsy [pulverizing stones with ultrasound]."

On Wednesday, November 8, Brennen will cover the history of these phenomena (including Caltech's special role in their discovery) and will end with a vision of new horizons for the bubble. His talk, "The Amazing World of Bubbles," is the second program of the fall/winter 2006-07 Earnest C. Watson Lecture Series.

The talk will be presented at 8 p.m. in Beckman Auditorium, 332 S. Michigan Avenue, south of Del Mar Boulevard, on the Caltech campus in Pasadena. Seating is available on a free, no-ticket-required, first-come, first-served basis.

Caltech has offered the Watson Lecture Series since 1922, when it was conceived by the late Caltech physicist Earnest Watson as a way to explain science to the local community.

For more information, call (626) 395-4652. Outside the greater Pasadena area, call toll-free, 1(888) 2CALTECH (1-888-222-5832).

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Contact: Kathy Svitil (626) 395-8022 ksvitil@caltech.edu

Visit the Caltech Media Relations website at: http://pr.caltech.edu/media

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KS
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