Caltech Team Uses Laser Light to Cool Object to Quantum Ground State

PASADENA, Calif.—For the first time, researchers at the California Institute of Technology (Caltech), in collaboration with a team from the University of Vienna, have managed to cool a miniature mechanical object to its lowest possible energy state using laser light. The achievement paves the way for the development of exquisitely sensitive detectors as well as for quantum experiments that scientists have long dreamed of conducting.

"We've taken a solid mechanical system—one made up of billions of atoms—and used optical light to put it into a state in which it behaves according to the laws of quantum mechanics. In the past, this has only been achieved with trapped single atoms or ions," says Oskar Painter, professor of applied physics and executive officer for applied physics and materials science at Caltech and the principal investigator on a paper describing the work that appears in the October 6 issue of the journal Nature

As described in the paper, Painter and his colleagues have engineered a nanoscale object—a tiny mechanical silicon beam—such that laser light of a carefully selected frequency can enter the system and, once reflected, can carry thermal energy away, cooling the system.

By carefully designing each element of the beam as well as a patterned silicon shield that isolates it from the environment, Painter and colleagues were able to use the laser cooling technique to bring the system down to the quantum ground state, where mechanical vibrations are at an absolute minimum. Such a cold mechanical object could help detect very small forces or masses, whose presence would normally be masked by the noisy thermal vibrations of the sensor.

"In many ways, the experiment we've done provides a starting point for the really interesting quantum-mechanical experiments one wants to do," Painter says. For example, scientists would like to show that a mechanical system could be coaxed into a quantum superposition—a bizarre quantum state in which a physical system can exist in more than one position at once. But they need a system at the quantum ground state to begin such experiments.

To reach the ground state, Painter's group had to cool its mechanical beam to a temperature below 100 millikelvin (-273.15°C). That's because the beam is designed to vibrate at gigahertz frequencies (corresponding to a billion cycles per second)—a range where a large number of phonons are present at room temperature. Phonons are the most basic units of vibration just as the most basic units or packets of light are called photons. All of the phonons in a system have to be removed to cool it to the ground state. 

Conventional means of cryogenically cooling to such temperatures exist but require expensive and, in some cases, impractical equipment. There's also the problem of figuring out how to measure such a cold mechanical system. To solve both problems, the Caltech team used a different cooling strategy. 

"What we've done is used the photons—the light field—to extract phonons from the system," says Jasper Chan, lead author of the new paper and a graduate student in Painter's group. To do so, the researchers drilled tiny holes at precise locations in their mechanical beam so that when they directed laser light of a particular frequency down the length of the beam, the holes acted as mirrors, trapping the light in a cavity and causing it to interact strongly with the mechanical vibrations of the beam. 

Because a shift in the frequency of the light is directly related to the thermal motion of the mechanical object, the light—when it eventually escapes from the cavity—also carries with it information about the mechanical system, such as the motion and temperature of the beam. Thus, the researchers have created an efficient optical interface to a mechanical element—or an optomechanical transducer—that can convert information from the mechanical system into photons of light.

Importantly, since optical light, unlike microwaves or electrons, can be transmitted over large, kilometer-length distances without attenuation, such an optomechanical transducer could be useful for linking different quantum systems—a microwave system with an optical system, for example. While Painter's system involves an optical interface to a mechanical element, other teams have been developing systems that link a microwave interface to a mechanical element. What if those two mechanical elements were the same? "Then," says Painter, "I could imagine connecting the microwave world to the optical world via this mechanical conduit one photon at a time." 

The Caltech team isn't the first to cool a nanomechanical object to the quantum ground state; a group led by former Caltech postdoctoral scholar Andrew Cleland, now at the University of California, Santa Barbara, accomplished this in 2010 using more conventional refrigeration techniques, and, earlier this year, a group from the National Institute of Standards and Technology in Boulder, Colorado, cooled an object to the ground state using microwave radiation. The new work, however, is the first in which a nanomechanical object has been put into the ground state using optical light.

"This is an exciting development because there are so many established techniques for manipulating and measuring the quantum properties of systems using optics," Painter says.

The other cooling techniques used starting temperatures of approximately 20 millikelvin—more than a factor of 10,000 times cooler than room temperature. Ideally, to simplify designs, scientists would like to initiate these experiments at room temperature. Using laser cooling, Painter and his colleagues were able to perform their experiment at a much higher temperature—only about 10 times lower than room temperature.

Along with Painter and Chan, additional coauthors of the paper, "Laser cooling of a nanomechanical oscillator into its quantum ground state," include Caltech postdoctoral scholar T.P. Mayer Alegre and graduate students Amir Safavi-Naeini, Jeff Hill, and Alex Krause, along with postdoctoral scholar Simon Gröblacher and Markus Aspelmeyer of the Vienna Center for Quantum Science and Technology. The work was supported by Caltech's Kavli Nanoscience Institute; the Defense Advanced Research Projects Agency's Microsystems Technology Office through a grant from the Air Force Office of Scientific Research; the European Commission; the European Research Council; and the Austrian Science Fund.

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Caltech Engineers Build Smart Petri Dish

Device can be used for medical diagnostics, to image cell growth continuously

PASADENA, Calif.—The cameras in our cell phones have dramatically changed the way we share the special moments in our lives, making photographs instantly available to friends and family. Now, the imaging sensor chips that form the heart of these built-in cameras are helping engineers at the California Institute of Technology (Caltech) transform the way cell cultures are imaged by serving as the platform for a "smart" petri dish.

Dubbed ePetri, the device is described in a paper that appears online this week in the Proceedings of the National Academy of Sciences (PNAS).

Since the late 1800s, biologists have used petri dishes primarily to grow cells. In the medical field, they are used to identify bacterial infections, such as tuberculosis. Conventional use of a petri dish requires that the cells being cultured be placed in an incubator to grow. As the sample grows, it is removed—often numerous times—from the incubator to be studied under a microscope.

Not so with the ePetri, whose platform does away with the need for bulky microscopes and significantly reduces human labor time, while improving the way in which the culture growth can be recorded.

"Our ePetri dish is a compact, small, lens-free microscopy imaging platform. We can directly track the cell culture or bacteria culture within the incubator," explains Guoan Zheng, lead author of the study and a graduate student in electrical engineering at Caltech. "The data from the ePetri dish automatically transfers to a computer outside the incubator by a cable connection. Therefore, this technology can significantly streamline and improve cell culture experiments by cutting down on human labor and contamination risks."

The team built the platform prototype using a Google smart phone, a commercially available cell-phone image sensor, and Lego building blocks. The culture is placed on the image-sensor chip, while the phone's LED screen is used as a scanning light source. The device is placed in an incubator with a wire running from the chip to a laptop outside the incubator. As the image sensor takes pictures of the culture, that information is sent out to the laptop, enabling the researchers to acquire and save images of the cells as they are growing in real time. The technology is particularly adept at imaging confluent cells—those that grow very close to one another and typically cover the entire petri dish.

"Until now, imaging of confluent cell cultures has been a highly labor-intensive process in which the traditional microscope has to serve as an expensive and suboptimal workhorse," says Changhuei Yang, senior author of the study and professor of electrical engineering and bioengineering at Caltech. "What this technology allows us to do is create a system in which you can do wide field-of-view microscopy imaging of confluent cell samples. It capitalizes on the use of readily available image-sensor technology, which is found in all cell-phone cameras."

In addition to simplifying medical diagnostic tests, the ePetri platform may be useful in various other areas, such as drug screening and the detection of toxic compounds. It has also proved to be practical for use in basic research.

Caltech biologist Michael Elowitz, a coauthor on the study, has put the ePetri system to the test, using it to observe embryonic stem cells. Stem cells in different parts of a petri dish often behave differently, changing into various types of other, more specialized cells. Using a conventional microscope with its lens's limitations, a researcher effectively wears blinders and is only able to focus on one region of the petri dish at a time, says Elowitz. But by using the ePetri platform, Elowitz was able to follow the stem-cell changes over the entire surface of the device.

"It radically reconceives the whole idea of what a light microscope is," says Elowitz, a professor of biology and bioengineering at Caltech and a Howard Hughes Medical Institute investigator. "Instead of a large, heavy instrument full of delicate lenses, Yang and his team have invented a compact lightweight microscope with no lens at all, yet one that can still produce high-resolution images of living cells. Not only that, it can do so dynamically, following events over time in live cells, and across a wide range of spatial scales from the subcellular to the macroscopic."

Elowitz says the technology can capture things that would otherwise be difficult or impossible—even with state-of-the-art light microscopes that are both much more complicated and much more expensive.

"With ePetri, you can survey the entire field at once, but still maintain the ability to 'zoom in' to any cells of interest," he says. "In this regard, perhaps it's a bit like an episode of CSI where they zoom in on what would otherwise be unresolvable details in a photograph."  

Yang and his team believe the ePetri system is likely to open up a whole range of new approaches to many other biological systems as well. Since it is a platform technology, it can be applied to other devices. For example, ePetri could provide microscopy-imaging capabilities for other portable diagnostic lab-on-a-chip tools. The team is also working to build a self-contained system that would include its own small incubator. This advance would make the system more useful as a desktop diagnostic tool that could be housed in a doctor's office, reducing the need to send bacteria samples out to a lab for testing.

Seung Ah Lee, a graduate student in electrical engineering, and Yaron Antebi, a postdoctoral scholar in biology—both from Caltech—were also coauthors on the study, which is titled "The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM)." Funding support was provided by the Coulter Foundation.

Written by Katie Neith

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Caltech-Led Engineers Solve Longstanding Problem in Photonic Chip Technology

Findings Help Pave Way for Next Generation of Computer Chips

PASADENA, Calif.—Stretching for thousands of miles beneath oceans, optical fibers now connect every continent except for Antarctica. With less data loss and higher bandwidth, optical-fiber technology allows information to zip around the world, bringing pictures, video, and other data from every corner of the globe to your computer in a split second. But although optical fibers are increasingly replacing copper wires, carrying information via photons instead of electrons, today's computer technology still relies on electronic chips.

Now, researchers led by engineers at the California Institute of Technology (Caltech) are paving the way for the next generation of computer-chip technology: photonic chips. With integrated circuits that use light instead of electricity, photonic chips will allow for faster computers and less data loss when connected to the global fiber-optic network.

"We want to take everything on an electronic chip and reproduce it on a photonic chip," says Liang Feng, a postdoctoral scholar in electrical engineering and the lead author on a paper to be published in the August 5 issue of the journal Science. Feng is part of Caltech's nanofabrication group, led by Axel Scherer, Bernard A. Neches Professor of Electrical Engineering, Applied Physics, and Physics, and co-director of the Kavli Nanoscience Institute at Caltech.

In that paper, the researchers describe a new technique to isolate light signals on a silicon chip, solving a longstanding problem in engineering photonic chips.

An isolated light signal can only travel in one direction. If light weren't isolated, signals sent and received between different components on a photonic circuit could interfere with one another, causing the chip to become unstable. In an electrical circuit, a device called a diode isolates electrical signals by allowing current to travel in one direction but not the other. The goal, then, is to create the photonic analog of a diode, a device called an optical isolator. "This is something scientists have been pursuing for 20 years," Feng says.

Normally, a light beam has exactly the same properties when it moves forward as when it's reflected backward. "If you can see me, then I can see you," he says. In order to isolate light, its properties need to somehow change when going in the opposite direction. An optical isolator can then block light that has these changed properties, which allows light signals to travel only in one direction between devices on a chip.

"We want to build something where you can see me, but I can't see you," Feng explains. "That means there's no signal from your side to me. The device on my side is isolated; it won't be affected by my surroundings, so the functionality of my device will be stable."

To isolate light, Feng and his colleagues designed a new type of optical waveguide, a 0.8-micron-wide silicon device that channels light. The waveguide allows light to go in one direction but changes the mode of the light when it travels in the opposite direction.

A light wave's mode corresponds to the pattern of the electromagnetic field lines that make up the wave. In the researchers' new waveguide, the light travels in a symmetric mode in one direction, but changes to an asymmetric mode in the other. Because different light modes can't interact with one another, the two beams of light thus pass through each other.

Previously, there were two main ways to achieve this kind of optical isolation. The first way—developed almost a century ago—is to use a magnetic field. The magnetic field changes the polarization of light—the orientation of the light's electric-field lines—when it travels in the opposite direction, so that the light going one way can't interfere with the light going the other way. "The problem is, you can't put a large magnetic field next to a computer," Feng says. "It's not healthy."

The second conventional method requires so-called nonlinear optical materials, which change light's frequency rather than its polarization. This technique was developed about 50 years ago, but is problematic because silicon, the material that's the basis for the integrated circuit, is a linear material. If computers were to use optical isolators made out of nonlinear materials, silicon would have to be replaced, which would require revamping all of computer technology. But with their new silicon waveguides, the researchers have become the first to isolate light with a linear material.

Although this work is just a proof-of-principle experiment, the researchers are already building an optical isolator that can be integrated onto a silicon chip. An optical isolator is essential for building the integrated, nanoscale photonic devices and components that will enable future integrated information systems on a chip. Current, state-of-the-art photonic chips operate at 10 gigabits per second (Gbps)—hundreds of times the data-transfer rates of today's personal computers—with the next generation expected to soon hit 40 Gbps. But without built-in optical isolators, those chips are much simpler than their electronic counterparts and are not yet ready for the market. Optical isolators like those based on the researchers' designs will therefore be crucial for commercially viable photonic chips.

In addition to Feng and Scherer, the other authors on the Science paper, "Non-reciprocal light propagation in a silicon photonic circuit," are Jingqing Huang, a Caltech graduate student; Maurice Ayache of UC San Diego and Yeshaiahu Fainman, Cymer Professor in Advanced Optical Technologies at UC San Diego; and Ye-Long Xu, Ming-Hui Lu, and Yan-Feng Chen of the Nanjing National Laboratory of Microstructures in China. This research was done as part of the Center for Integrated Access Networks (CIAN), one of the National Science Foundation's Engineering Research Centers. Fainman is also the deputy director of CIAN. Funding was provided by the National Science Foundation, and the Defense Advanced Research Projects Agency.

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Caltech Engineers Develop One-way Transmission System for Sound Waves

PASADENA, Calif.— While many hotel rooms, recording studios, and even some homes are built with materials to help absorb or reflect sound, mechanisms to truly control the direction of sound waves are still in their infancy. However, researchers at the California Institute of Technology (Caltech) have now created the first tunable acoustic diode-a device that allows acoustic information to travel only in one direction, at controllable frequencies.

The mechanism they developed is outlined in a paper published on July 24 in the journal Nature Materials.

Borrowing a concept from electronics, the acoustic diode is a component that allows a current—in this case a sound wave—to pass in one direction, while blocking the current in the opposite direction. "We exploited a physical mechanism that causes a sharp transition between transmitting and nontransmitting states of the diode," says Chiara Daraio, professor of aeronautics and applied physics at Caltech and lead author on the study. "Using experiments, simulations, and analytical predictions, we demonstrated the one-way transmission of sound in an audible frequency range for the first time."

This new mechanism brings the idea of true soundproofing closer to reality. Imagine two rooms labeled room A and room B. This new technology, Daraio explains, would enable someone in room A to hear sound coming from room B; however, it would block the same sound in room A from being heard in room B.    

"The concept of the one-way transmission of sound could be quite important in architectural acoustics, or the science and engineering of sound control within buildings," says Georgios Theocharis, a postdoctoral scholar in Daraio's laboratory and a co-author of the study.

The system is based on a simple assembly of elastic spheres—granular crystals that transmit the sound vibrations—that could be easily used in multiple settings, can be tuned easily, and can potentially be scaled to operate within a wide range of frequencies, meaning its application could reach far beyond soundproofing.

Similar systems have been demonstrated by other scientists, but they all feature smooth transitions between transmitting and nontransmitting states instead of the sharp transitions needed to be more effective at controlling the flow of sound waves. To obtain the sharp transition, the team created a periodic system with a small defect that supports this kind of quick change from an "on" to an "off" transmission state. According to Daraio, this means the system is very sensitive to small variations of operational conditions, like pressure and movement, making it useful in the development of ultrasensitive acoustic sensors to detect sound waves. The system can also operate at different frequencies of sound and is capable of downshifting, or reducing the frequency of the traveling signals, as needed. 

"We propose to use these effects to improve energy-harvesting technologies," she says. "For example, we may be able to scavenge sound energy from undesired structural vibrations in machinery by controlling the flow of sound waves away from the machinery and into a transducer. The transducer would then convert the sound waves into electricity." Daraio says the technology can also shift the undesired frequencies to a range that enables a more efficient conversion to electricity.

The team plans to continue studying the fundamental properties of these systems, focusing on their potential application to energy-harvesting systems. They also believe that these systems may be applicable to a range of technologies including biomedical ultrasound devices, advanced noise control, and even thermal materials aimed at temperature control.

"Because the concepts governing wave propagation are universal to many systems, we envision that the use of this novel way to control energy might enable the design of many advanced thermal and acoustic materials and devices," says Daraio.

The Nature Materials paper is titled "Bifurcation-based acoustic switching and rectification." Nicholas Boechler, a former Ph.D. student at Caltech, is also an author on the study.

The research was supported by the National Science Foundation, the Office of Naval Research, and the A. S. Onassis Benefit Foundation. 

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Caltech, Zcube Collaboration Will Bring Painless Transdermal Drug Delivery to Patients

 

Zcube Srl, a research venture of the Italian pharmaceutical company Zambon, and the California Institute of Technology (Caltech) have signed an exclusive research and option agreement to develop and commercialize skin patches that contain embedded carbon nanotubes for delivering drugs. The patches will first be developed to painlessly administer drugs through the skin; other applications are envisioned for future use. Mory Gharib, Hans W. Liepmann Professor of Aeronautics and professor of bioinspired engineering, is the principal investigator at Caltech.

A key aspect of the new skin patches is an innovative technique that partially embeds the nanotubes into the flexible materials in which they are grown. This embedding technique allows one end of each nanotube to be anchored to the patch, while the other end protrudes from the patch to deliver drugs to the skin. Gharib's technique, which allows for the anchoring and alignment of the nanotubes, neatly overcomes a previous technological shortcoming and will enable new methods of drug delivery. It is envisioned that this approach will help these therapeutic nanotubes make their way to patient bedsides in a variety of medical applications.

An important benefit of the new patches is that they are painless—the nanotubes' diameter is too small for nerves in the skin to detect. It is also believed that drugs can be delivered more effectively via nanotubes than via current microneedle or traditional patch technologies because the sea of nanotubes in the skin patches can be dosed and designed for optimal effectiveness, efficiently delivering drugs across the densest layers of the skin. The nanotube-studded skin patches will therefore address an important medical need by releasing drugs more quickly, effectively, and deeply into the skin without causing pain.

"This innovative technology, based on nanoneedles, will change the administration of drugs through the skin," says Lorenzo Pradella, general manager of Zcube. "The exceptional properties of these devices—their mechanical strength, electrical and thermal conductivity, chemical inertness, and the way the skin can tolerate them—will allow us to do things with transdermal drug delivery we never dreamed of doing before."

“This is a promising new medical application of carbon nanotube technology that has the potential to deliver medication painlessly and more effectively than current drug delivery technologies," says Gharib. "We are hopeful that this collaboration will result in significant medical benefits for millions of patients worldwide.”

# # #

Zcube

Zcube is a global leader in translational medicine, with a strategic focus on the development and commercialization of novel drug-delivery systems (DDS) and medical devices. As the research venture of Zambon Company S.p.A., Zcube validates and invests in early-stage innovative technologies with the potential to generate new products and new technology ventures in therapeutic areas of strategic interest. Zcube has already established collaborations with universities in the United States, Europe and Israel.  Zcube is also a limited partner of Mission Bay Capital, LLC, the venture fund bolstering the fund’s ability to invest in promising bioscience companies emerging from the University of California, and is a member of the Quantitative Biosciences (QB3) Industrial Advisory Board in San Francisco. Zcube is among the investors in three start-up companies: PharmEste Srl (Ferrara, Italy), SuppreMol GmbH (Munich, Germany) and ProtAffin Biotechnologie AG (Graz, Austria). For further information please visit www.z-cube.it.

The California Institute of Technology
The California Institute of Technology (Caltech) is a small, private university in Pasadena that conducts instruction and research in science and engineering, with a student body of about 900 undergraduates and 1,200 graduate students. Recognized for its outstanding faculty, including several Nobel laureates, and such renowned off-campus facilities as the Jet Propulsion Laboratory, the W. M. Keck Observatory, and the Palomar Observatory, Caltech is one of the world’s preeminent research centers.

 

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debwms@caltech.edu

626-395-3227

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Carl Byoir & Associates

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Zcube Technology Intelligence - North America

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e-mail: andrea_mills@me.com

 

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Caltech Researchers Create the First Artificial Neural Network Out of DNA

Molecular Soup Exhibits Brainlike Behavior

PASADENA, Calif.—Artificial intelligence has been the inspiration for countless books and movies, as well as the aspiration of countless scientists and engineers. Researchers at the California Institute of Technology (Caltech) have now taken a major step toward creating artificial intelligence—not in a robot or a silicon chip, but in a test tube. The researchers are the first to have made an artificial neural network out of DNA, creating a circuit of interacting molecules that can recall memories based on incomplete patterns, just as a brain can.

"The brain is incredible," says Lulu Qian, a Caltech senior postdoctoral scholar in bioengineering and lead author on the paper describing this work, published in the July 21 issue of the journal Nature. "It allows us to recognize patterns of events, form memories, make decisions, and take actions. So we asked, instead of having a physically connected network of neural cells, can a soup of interacting molecules exhibit brainlike behavior?"

The answer, as the researchers show, is yes.

Consisting of four artificial neurons made from 112 distinct DNA strands, the researchers' neural network plays a mind-reading game in which it tries to identify a mystery scientist. The researchers "trained" the neural network to "know" four scientists, whose identities are each represented by a specific, unique set of answers to four yes-or-no questions, such as whether the scientist was British.

After thinking of a scientist, a human player provides an incomplete subset of answers that partially identifies the scientist. The player then conveys those clues to the network by dropping DNA strands that correspond to those answers into the test tube. Communicating via fluorescent signals, the network then identifies which scientist the player has in mind. Or, the network can "say" that it has insufficient information to pick just one of the scientists in its memory or that the clues contradict what it has remembered. The researchers played this game with the network using 27 different ways of answering the questions (out of 81 total combinations), and it responded correctly each time.

This DNA-based neural network demonstrates the ability to take an incomplete pattern and figure out what it might represent—one of the brain's unique features. "What we are good at is recognizing things," says coauthor Jehoshua "Shuki" Bruck, the Gordon and Betty Moore Professor of Computation and Neural Systems and Electrical Engineering. "We can recognize things based on looking only at a subset of features." The DNA neural network does just that, albeit in a rudimentary way.

Biochemical systems with artificial intelligence—or at least some basic, decision-making capabilities—could have powerful applications in medicine, chemistry, and biological research, the researchers say. In the future, such systems could operate within cells, helping to answer fundamental biological questions or diagnose a disease. Biochemical processes that can intelligently respond to the presence of other molecules could allow engineers to produce increasingly complex chemicals or build new kinds of structures, molecule by molecule.

"Although brainlike behaviors within artificial biochemical systems have been hypothesized for decades," Qian says, "they appeared to be very difficult to realize."

The researchers based their biochemical neural network on a simple model of a neuron, called a linear threshold function. The model neuron receives input signals, multiplies each by a positive or negative weight, and only if the weighted sum of inputs surpass a certain threshold does the neuron fire, producing an output. This model is an oversimplification of real neurons, says paper coauthor Erik Winfree, professor of computer science, computation and neural systems, and bioengineering. Nevertheless, it's a good one. "It has been an extremely productive model for exploring how the collective behavior of many simple computational elements can lead to brainlike behaviors, such as associative recall and pattern completion."

To build the DNA neural network, the researchers used a process called a strand-displacement cascade. Previously, the team developed this technique to create the largest and most complex DNA circuit yet, one that computes square roots.

This method uses single and partially double-stranded DNA molecules. The latter are double helices, one strand of which sticks out like a tail. While floating around in a water solution, a single strand can run into a partially double-stranded one, and if their bases (the letters in the DNA sequence) are complementary, the single strand will grab the double strand's tail and bind, kicking off the other strand of the double helix. The single strand thus acts as an input while the displaced strand acts as an output, which can then interact with other molecules.

Because they can synthesize DNA strands with whatever base sequences they want, the researchers can program these interactions to behave like a network of model neurons. By tuning the concentrations of every DNA strand in the network, the researchers can teach it to remember the unique patterns of yes-or-no answers that belong to each of the four scientists. Unlike with some artificial neural networks that can directly learn from examples, the researchers used computer simulations to determine the molecular concentration levels needed to implant memories into the DNA neural network.

While this proof-of-principle experiment shows the promise of creating DNA-based networks that can—in essence—think, this neural network is limited, the researchers say. The human brain consists of 100 billion neurons, but creating a network with just 40 of these DNA-based neurons—ten times larger than the demonstrated network—would be a challenge, according to the researchers. Furthermore, the system is slow; the test-tube network took eight hours to identify each mystery scientist. The molecules are also used up—unable to detach and pair up with a different strand of DNA—after completing their task, so the game can only be played once. Perhaps in the future, a biochemical neural network could learn to improve its performance after many repeated games, or learn new memories from encountering new situations. Creating biochemical neural networks that operate inside the body—or even just inside a cell on a Petri dish—is also a long way away, since making this technology work in vivo poses an entirely different set of challenges.

Beyond technological challenges, engineering these systems could also provide indirect insight into the evolution of intelligence. "Before the brain evolved, single-celled organisms were also capable of processing information, making decisions, and acting in response to their environment," Qian explains. The source of such complex behaviors must have been a network of molecules floating around in the cell. “Perhaps the highly evolved brain and the limited form of intelligence seen in single cells share a similar computational model that's just programmed in different substrates.”

"Our paper can be interpreted as a simple demonstration of neural-computing principles at the molecular and intracellular levels," Bruck adds. "One possible interpretation is that perhaps these principles are universal in biological information processing.

"The research described in the Nature paper, "Neural network computation with DNA strand displacement cascades," is supported by a National Science Foundation grant to the Molecular Programming Project and by the Human Frontiers Science Program.

View the researchers' videos (part 1, part 2) that explain their work.

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Caltech Scientist Awarded Grant to Develop Solar-Powered Sanitation System

PASADENA, Calif.—Environmental scientist and engineer Michael Hoffmann of the California Institute of Technology (Caltech) has received a $400,000 grant from the Bill & Melinda Gates Foundation to build a solar-powered portable toilet that could help solve a major health problem in developing countries. The grant, announced July 19 at the AfricaSan 3 sanitation and hygiene conference in Rwanda, will be used to complete the initial design, development, and testing of the unique sustainable system. Designed for use by up to 500 people per day with minimal maintenance, the sanitation unit will have the added benefit of turning waste into fuel.

Hoffmann's concept, called a "Self-Contained, PV-Powered Domestic Toilet and Wastewater Treatment System," is one of eight projects funded through the foundation's "Reinvent the Toilet Challenge." The Bill & Melinda Gates Foundation announced this grant as part of more than $40 million in new investments launching its Water, Sanitation, & Hygiene strategy. According to the World Health Organization (WHO) and UNICEF, about 2.6 billion people—approximately 40 percent of the world's population—lack access to safe sanitation, and nearly half of them practice open defecation. In addition, WHO estimates that 1.5 million children die each year from diarrheal disease, which is often caused by poor sanitation.

"Life expectancy correlates to the accessibility of clean water and proper sanitation practices," says Hoffmann, the James Irvine Professor of Environmental Science at Caltech, who has been working for years on the electrochemical technology to create a sustainable toilet and waste-treatment system. "All of our efforts in biomedicine may go for naught if we don't take care of sanitation."

Hoffmann's toilet system could fit inside the typical portable sanitation unit often found at construction sites and recreation areas, but the comparison ends there. It starts with a photovoltaic or solar panel, which converts the sun's rays into enough energy to power an electrochemical reactor that Hoffmann designed to break down water and human waste material into hydrogen gas. The hydrogen gas can then be stored in hydrogen fuel cells to provide a backup energy source for nighttime operation or for use under low-sunlight conditions. Hoffmann also envisions equipping the units with self-cleaning toilets that would also be powered by the energy from the sun and fuel cells.

Hoffmann says that he can build a workable unit for $2,000, but that the cost would come down significantly if the toilets were produced in volume. Following production of a prototype under the Gates Foundation grant, Hoffmann hopes to continue the project to refine the system and reduce its cost. In August 2012, all "Reinvent the Toilet Challenge" grantees will present their prototypes, with winning projects to receive additional funding for product development, industrial production, and commercialization.

"To address the needs of the 2.6 billion people who don't have access to safe sanitation, we not only must reinvent the toilet, we also must find safe, affordable, and sustainable ways to capture, treat, and recycle human waste," says Sylvia Mathews Burwell, president of the Global Development Program at the Bill & Melinda Gates Foundation. "Most importantly, we must work closely with local communities to develop lasting sanitation solutions that will improve their lives."

A member of the Caltech faculty since 1980, Hoffmann was honored in 2010 by the National Taiwan University as a Distinguished Visiting Chair Professor and by the State of Kerala, India, as an Erudite Distinguished Scholar. Earlier this year, Hoffmann was elected to the National Academy of Engineering. He is the organizing chair of the upcoming International Conference on the Photochemical Conversion and Storage of Solar Energy, which will be held on the Caltech campus at the end of July 2012. 

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Wind-turbine Placement Produces Tenfold Power Increase, Caltech Researchers Say

PASADENA, Calif.—The power output of wind farms can be increased by an order of magnitude—at least tenfold—simply by optimizing the placement of turbines on a given plot of land, say researchers at the California Institute of Technology (Caltech) who have been conducting a unique field study at an experimental two-acre wind farm in northern Los Angeles County.

A paper describing the findings—the results of field tests conducted by John Dabiri, Caltech professor of aeronautics and bioengineering, and colleagues during the summer of 2010—appears in the July issue of the Journal of Renewable and Sustainable Energy.

Dabiri's experimental farm, known as the Field Laboratory for Optimized Wind Energy (FLOWE), houses 24 10-meter-tall, 1.2-meter-wide vertical-axis wind turbines (VAWTs)—turbines that have vertical rotors and look like eggbeaters sticking out of the ground. Half a dozen turbines were used in the 2010 field tests.

Despite improvements in the design of wind turbines that have increased their efficiency, wind farms are rather inefficient, Dabiri notes. Modern farms generally employ horizontal-axis wind turbines (HAWTs)—the standard propeller-like monoliths that you might see slowly turning, all in the same direction, in the hills of Tehachapi Pass, north of Los Angeles.

In such farms, the individual turbines have to be spaced far apart—not just far enough that their giant blades don't touch. With this type of design, the wake generated by one turbine can interfere aerodynamically with neighboring turbines, with the result that "much of the wind energy that enters a wind farm is never tapped," says Dabiri. He compares modern farms to "sloppy eaters," wasting not just real estate (and thus lowering the power output of a given plot of land) but much of the energy resources they have available to them.

Designers compensate for the energy loss by making bigger blades and taller towers, to suck up more of the available wind and at heights where gusts are more powerful. "But this brings other challenges," Dabiri says, such as higher costs, more complex engineering problems, a larger environmental impact. Bigger, taller turbines, after all, mean more noise, more danger to birds and bats, and—for those who don't find the spinning spires visually appealing—an even larger eyesore.

The solution, says Dabiri, is to focus instead on the design of the wind farm itself, to maximize its energy-collecting efficiency at heights closer to the ground. While winds blow far less energetically at, say, 30 feet off the ground than at 100 feet, "the global wind power available 30 feet off the ground is greater than the world's electricity usage, several times over," he says. That means that enough energy can be obtained with smaller, cheaper, less environmentally intrusive turbines—as long as they're the right turbines, arranged in the right way.

VAWTs are ideal, Dabiri says, because they can be positioned very close to one another. This lets them capture nearly all of the energy of the blowing wind and even wind energy above the farm. Having every turbine turn in the opposite direction of its neighbors, the researchers found, also increases their efficiency, perhaps because the opposing spins decrease the drag on each turbine, allowing it to spin faster (Dabiri got the idea for using this type of constructive interference from his studies of schooling fish).

In the summer 2010 field tests, Dabiri and his colleagues measured the rotational speed and power generated by each of the six turbines when placed in a number of different configurations. One turbine was kept in a fixed position for every configuration; the others were on portable footings that allowed them to be shifted around.

The tests showed that an arrangement in which all of the turbines in an array were spaced four turbine diameters apart (roughly 5 meters, or approximately 16 feet) completely eliminated the aerodynamic interference between neighboring turbines. By comparison, removing the aerodynamic interference between propeller-style wind turbines would require spacing them about 20 diameters apart, which means a distance of more than one mile between the largest wind turbines now in use.

The six VAWTs generated from 21 to 47 watts of power per square meter of land area; a comparably sized HAWT farm generates just 2 to 3 watts per square meter.

"Dabiri's bioinspired engineering research is challenging the status quo in wind-energy technology," says Ares Rosakis, chair of Caltech's Division of Engineering and Applied Science and the Theodore von Kármán Professor of Aeronautics and professor of mechanical engineering. "This exemplifies how Caltech engineers' innovative approaches are tackling our society's greatest problems."

"We're on the right track, but this is by no means 'mission accomplished,'" Dabiri says. "The next steps are to scale up the field demonstration and to improve upon the off-the-shelf wind-turbine designs used for the pilot study." Still, he says, "I think these results are a compelling call for further research on alternatives to the wind-energy status quo."

This summer, Dabiri and colleagues are studying a larger array of 18 VAWTs to follow up last year's field study. Video and images of the field site can be found at http://dabiri.caltech.edu/research/wind-energy.html.

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Kathy Svitil
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Going with the Flow: Caltech Researchers Find Compaction Bands in Sandstone are Permeable

Findings could aid in the development of better technologies for hydraulic fracturing and other fluid extraction techniques from the earth

PASADENA, Calif.—When geologists survey an area of land for the potential that gas or petroleum deposits could exist there, they must take into account the composition of rocks that lie below the surface. Take, for instance, sandstone—a sedimentary rock composed mostly of weakly cemented quartz grains. Previous research had suggested that compaction bands—highly compressed, narrow, flat layers within the sandstone—are much less permeable than the host rock and might act as barriers to the flow of oil or gas. 

Now, researchers led by José Andrade, associate professor of civil and mechanical engineering at the California Institute of Technology (Caltech), have analyzed X-ray images of Aztec sandstone and revealed that compaction bands are actually more permeable than earlier models indicated. While they do appear to be less permeable than the surrounding host rock, they do not appear to block the flow of fluids. Their findings were reported in the May 17 issue of Geophysical Research Letters.

The study includes the first observations and calculations that show fluids have the ability to flow in sandstone that has compaction bands. Prior to this study, there had been inferences of how permeable these formations were, but those inferences were made from 2D images. This paper provides the first permeability calculations based on actual rock samples taken directly from the field in the Valley of Fire, Nevada. From the data they collected, the researchers concluded that these formations are not as impermeable as previously believed, and that therefore their ability to trap fluids—like oil, gas, and CO2—should be measured based on 3D images taken from the field.

"These results are very important for the development of new technologies such as CO2 sequestration—removing CO2 from the atmosphere and depositing it in an underground reservoir—and hydraulic fracturing of rocks for natural gas extraction," says Andrade. "The quantitative connection between the microstructure of the rock and the rock's macroscopic properties, such as hydraulic conductivity, is crucial, as physical processes are controlled by pore-scale features in porous materials. This work is at the forefront of making this quantitative connection."

Compaction bands at multiple scales ranging from the field scale to the specimen scale to the meso and grain scale. At the field scale, picture shows the presence of narrow tabular structures within the host rock in the Valley of Fire. At the grain scale, images show clear differences in porosity (dark spots) density. This research aims at quantifying the impact of grain scale features in macroscopic physical properties that control behavior all the way to the field scale.
Credit: Jose Andrade/Caltech

The research team connected the rocks' 3D micromechanical features—such as grain size distribution, which was obtained using microcomputed tomography images of the rocks to build a 3D model—with quantitative macroscopic flow properties in rocks from the field, which they measured on many different scales. Those measurements were the first ever to look at the three-dimensional ability of compaction bands to transmit fluid. The researchers say the combination of these advanced imaging technologies and multiscale computational models will lead to unprecedentedly accurate measurements of crucial physical properties, such as permeability, in rocks and similar materials. 

Andrade says the team wants to expand these findings and techniques. "An immediate idea involves the coupling of solid deformation and chemistry," he says. "Accounting for the effect of pressures and their potential to exacerbate chemical reactions between fluids and the solid matrix in porous materials, such as compaction bands, remains a fundamental problem with multiple applications ranging from hydraulic fracturing for geothermal energy and natural gas extraction, to applications in biological tissue for modeling important processes such as osteoporosis. For instance, chemical reactions take place as part of the process utilized in fracturing rocks to enhance the extraction of natural gas."

Other coauthors of the paper, "Connecting microstructural attributes and permeability from 3D tomographic images of in situ shear-enhanced compaction bands using multiscale computations," are WaiChing Sun, visiting scholar at Caltech; John Rudnicki, professor of civil and environmental engineering at Northwestern University; and Peter Eichhubl, research scientist in the Bureau of Economic Geology at the University of Texas at Austin.

The work was partially funded by the Geoscience Research Program of the U.S. Department of Energy.

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Katie Neith
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Caltech Researchers Build Largest Biochemical Circuit Out of Small Synthetic DNA Molecules

PASADENA, Calif.—In many ways, life is like a computer. An organism's genome is the software that tells the cellular and molecular machinery—the hardware—what to do. But instead of electronic circuitry, life relies on biochemical circuitry—complex networks of reactions and pathways that enable organisms to function. Now, researchers at the California Institute of Technology (Caltech) have built the most complex biochemical circuit ever created from scratch, made with DNA-based devices in a test tube that are analogous to the electronic transistors on a computer chip.

Engineering these circuits allows researchers to explore the principles of information processing in biological systems, and to design biochemical pathways with decision-making capabilities. Such circuits would give biochemists unprecedented control in designing chemical reactions for applications in biological and chemical engineering and industries. For example, in the future a synthetic biochemical circuit could be introduced into a clinical blood sample, detect the levels of a variety of molecules in the sample, and integrate that information into a diagnosis of the pathology.

"We're trying to borrow the ideas that have had huge success in the electronic world, such as abstract representations of computing operations, programming languages, and compilers, and apply them to the biomolecular world," says Lulu Qian, a senior postdoctoral scholar in bioengineering at Caltech and lead author on a paper published in the June 3 issue of the journal Science.

Along with Erik Winfree, Caltech professor of computer science, computation and neural systems, and bioengineering, Qian used a new kind of DNA-based component to build the largest artificial biochemical circuit ever made. Previous lab-made biochemical circuits were limited because they worked less reliably and predictably when scaled to larger sizes, Qian explains. The likely reason behind this limitation is that such circuits need various molecular structures to implement different functions, making large systems more complicated and difficult to debug. The researchers' new approach, however, involves components that are simple, standardized, reliable, and scalable, meaning that even bigger and more complex circuits can be made and still work reliably.

"You can imagine that in the computer industry, you want to make better and better computers," Qian says. "This is our effort to do the same. We want to make better and better biochemical circuits that can do more sophisticated tasks, driving molecular devices to act on their environment."

To build their circuits, the researchers used pieces of DNA to make so-called logic gates—devices that produce on-off output signals in response to on-off input signals. Logic gates are the building blocks of the digital logic circuits that allow a computer to perform the right actions at the right time. In a conventional computer, logic gates are made with electronic transistors, which are wired together to form circuits on a silicon chip. Biochemical circuits, however, consist of molecules floating in a test tube of salt water. Instead of depending on electrons flowing in and out of transistors, DNA-based logic gates receive and produce molecules as signals. The molecular signals travel from one specific gate to another, connecting the circuit as if they were wires.

Winfree and his colleagues first built such a biochemical circuit in 2006. In this work, DNA signal molecules connected several DNA logic gates to each other, forming what's called a multilayered circuit. But this earlier circuit consisted of only 12 different DNA molecules, and the circuit slowed down by a few orders of magnitude when expanded from a single logic gate to a five-layered circuit. In their new design, Qian and Winfree have engineered logic gates that are simpler and more reliable, allowing them to make circuits at least five times larger.

Their new logic gates are made from pieces of either short, single-stranded DNA or partially double-stranded DNA in which single strands stick out like tails from the DNA's double helix. The single-stranded DNA molecules act as input and output signals that interact with the partially double-stranded ones.

"The molecules are just floating around in solution, bumping into each other from time to time," Winfree explains. "Occasionally, an incoming strand with the right DNA sequence will zip itself up to one strand while simultaneously unzipping another, releasing it into solution and allowing it to react with yet another strand." Because the researchers can encode whatever DNA sequence they want, they have full control over this process. "You have this programmable interaction," he says.

Qian and Winfree made several circuits with their approach, but the largest—containing 74 different DNA molecules—can compute the square root of any number up to 15 (technically speaking, any four-bit binary number) and round down the answer to the nearest integer. The researchers then monitor the concentrations of output molecules during the calculations to determine the answer. The calculation takes about 10 hours, so it won't replace your laptop anytime soon. But the purpose of these circuits isn't to compete with electronics; it's to give scientists logical control over biochemical processes.

Their circuits have several novel features, Qian says. Because reactions are never perfect—the molecules don't always bind properly, for instance—there's inherent noise in the system. This means the molecular signals are never entirely on or off, as would be the case for ideal binary logic. But the new logic gates are able to handle this noise by suppressing and amplifying signals—for example, boosting a signal that's at 80 percent, or inhibiting one that's at 10 percent, resulting in signals that are either close to 100 percent present or nonexistent.

All the logic gates have identical structures with different sequences. As a result, they can be standardized, so that the same types of components can be wired together to make any circuit you want. What's more, Qian says, you don't have to know anything about the molecular machinery behind the circuit to make one. If you want a circuit that, say, automatically diagnoses a disease, you just submit an abstract representation of the logic functions in your design to a compiler that the researchers provide online, which will then translate the design into the DNA components needed to build the circuit. In the future, an outside manufacturer can then make those parts and give you the circuit, ready to go.

The circuit components are also tunable. By adjusting the concentrations of the types of DNA, the researchers can change the functions of the logic gates. The circuits are versatile, featuring plug-and-play components that can be easily reconfigured to rewire the circuit. The simplicity of the logic gates also allows for more efficient techniques that synthesize them in parallel.  

"Like Moore's Law for silicon electronics, which says that computers are growing exponentially smaller and more powerful every year, molecular systems developed with DNA nanotechnology have been doubling in size roughly every three years," Winfree says. Qian adds, "The dream is that synthetic biochemical circuits will one day achieve complexities comparable to life itself."

The research described in the Science paper, "Scaling up digital circuit computation with DNA strand displacement cascades," is supported by a National Science Foundation grant to the Molecular Programming Project and by the Human Frontier Science Program.

View the researchers' video that explains this work.

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Marcus Woo
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