Monday, May 23, 2011

Novel Artificial Material Could Facilitate Wireless Power

This advance is made possible by the recent ability to fabricate exotic composite materials known as metamaterials, which are not so much a single substance, but an entire human-made structure that can be engineered to exhibit properties not readily found in nature. In fact, the metamaterial used in earlier Duke studies, and which would likely be used in future wireless power transmission systems, resembles a miniature set of tan Venetian blinds.

Theoretically, this metamaterial can improve the efficiency of"recharging" devices without wires. As power passes from the transmitting device to the receiving device, most if not all of it scatters and dissipates unless the two devices are extremely close together. However, the metamaterial postulated by the Duke researchers, which would be situated between the energy source and the"recipient" device, greatly refocuses the energy transmitted and permits the energy to traverse the open space between with minimal loss of power.

"We currently have the ability to transmit small amounts of power over short distances, such as in radio frequency identification (RFID) devices," said Yaroslav Urzhumov, assistant research professor in electrical and computer engineering at Duke's Pratt School of Engineering."However, larger amounts of energy, such as that seen in lasers or microwaves, would burn up anything in its path.

"Based on our calculations, it should be possible to use these novel metamaterials to increase the amount of power transmitted without the negative effects," Urzhumov said.

The results of the Duke research were published online in the journalPhysical Review B. Urzhumov works in the laboratory of David R. Smith, William Bevan Professor of electrical and computer engineering at Pratt School of Engineering. Smith's team was the first demonstrate that similar metamaterials could act as a cloaking device in 2006.

Just as the metamaterial in the cloaking device appeared to make a volume of space"disappear," in the latest work, the metamaterial would make it seem as if there was no space between the transmitter and the recipient, Urzhumov said. Therefore, he said, the loss of power should be minimal.

Urzhumov's research is an offshoot of"superlens" research conducted in Smith's laboratory. Traditional lenses get their focusing power by controlling rays as they pass through the two outside surfaces of the lens. On the other hand, the superlens, which is in fact a metamaterial, directs waves within the bulk of the lens between the outside surfaces, giving researchers a much greater control over whatever passes through it.

The metamaterial used in wireless power transmission would likely be made of hundreds to thousands -- depending on the application -- of individual thin conducting loops arranged into an array. Each piece is made from the same copper-on-fiberglass substrate used in printed circuit boards, with excess copper etched away. These pieces can then be arranged in an almost infinite variety of configurations.

"The system would need to be tailored to the specific recipient device, in essence the source and target would need to be 'tuned' to each other," Urzhumov said."This new understanding of how matematerials can be fabricated and arranged should help make the design of wireless power transmission systems more focused."

The analysis performed at Duke was inspired by recent studies at Mitsubishi Electric Research Labs (MERL), an industrial partner of the Duke Center for Metamaterials and Integrated Plasmonics. MERL is currently investigating metamaterials for wireless power transfer. The Duke researchers said that with these new insights into the effects of metamaterials, developing actual devices can be more targeted and efficient.

The Duke University research was supported by a Multidisciplinary University Research Initiative (MURI) grant through the Air Force Office of Scientific Research and the U.S. Army Research Office.


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Thursday, May 19, 2011

Autonomous Robot for Underwater Intervention Tasks Successfully Tested

The test was performed a few weeks ago at the Universitat de Girona, where there is a pool suitable for experimentation on underwater robotics. During the meeting, the researchers also tested the performance of the three parts involved in the experiment: the robotic arm, which is being improved by the UJI; the vehicle, in which the Universitat de Girona is working, and the computer vision techniques, which are being developed by the Universitat de les Illes Balears.

In the first part of the experiment the vehicle in which the robot was anchored descended to the bottom of the pool to survey the area using computer vision techniques and to draw a map. After that, the researchers asked the robot to recover an object (a black box), and the vehicle with the robotic arm plunged again, sought the object with the required characteristics, picked it up and pulled it to the surface.

The research group Interactive and Robotics Systems (IRS Lab) is composed by Prats, Juan Carlos García, José Javier Fernández and Raúl Marín and is led by Pedro Sanz. The team obtained the first results of manipulation underwater just two weeks ago, playing grip simulations with the robotic arm in a water tank installed in an office at the UJI before going to Girona to make the joint integration testing. The arm has four articulations, two at the shoulders, one at the elbow and the fourth at the wrist. It can also open its hand, which is claw-like but has T-shaped slots that enable to anchor on it cables or tools for picking up objects.

Achieving such a project would reduce the economic and human resources efforts which are attached to submarine operations, since support vessels or umbilical cables would not be necessary, nor ROV pilots responsible for teleoperation in conditions that involve fatigue and stress. Thus, this point would enable to carry out operations which would be impossible for teleoperated systems and which require a continuous connection through an umbilical cable to a support ship, a characteristic that affects the vehicle dynamics and limits the travel distance of the robot.

At present, the first application which more than 40 researchers are seeking is the recovery of black boxes with this autonomous action system, but some other potential application scenarios that could benefit from this project would be certain tasks associated with marine biology, performing routine practices such as taking samples (eg rock, water or sand); at permanent observatories, in lifesaving, in health care tasks to the diving teams such as lighting in a particular area, or assistance in the use of some kind of tool, to name only a few examples.

The project is funded with 530 000 euros by the Spanish Ministry of Science and Innovation, within the VI National Plan for Scientific Research, Development and Technological Innovation 2008-2011. Each one of the participating universities is responsible for a specific subproject. The UJI is the responsible for the mechanical integration of the robotic arm, the visual tracking of the object of interest, the control of the arm for handling tasks and the interface to specify these tasks.

The Universitat de Girona is the responsible for generating the navigation and mechatronics systems of the underwater vehicle where the robot is docked. The Universitat de les Illes Balears is the responsible for assisting in the planning and guiding of the movements necessary to achieve the autonomous navigation of the robot, using advanced computer vision techniques.


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Wednesday, May 18, 2011

Artificial Tissue Promotes Skin Growth in Wounds

These so-called dermal templates were engineered in the lab of Abraham Stroock, associate professor of chemical and biomolecular engineering at Cornell and member of the Kavli Institute at Cornell for Nanoscale Science, in collaboration with Dr. Jason A. Spector, assistant professor of surgery at Weill Cornell Medical College, and an interdisciplinary team of Ithaca and Weill scientists. The research was published online May 6 in the journalBiomaterials.

The biomaterials are composed of experimental tissue scaffolds that are about the size of a dime and have the consistency of tofu. They are made of a material called type 1 collagen, which is a well-regulated biomaterial used often in surgeries and other biomedical applications. The templates were fabricated with tools at the Cornell NanoScale Science and Technology Facility to contain networks of microchannels that promote and direct growth of healthy tissue into wound sites.

"The challenge was how to promote vascular growth and to keep this newly forming tissue alive and healthy as it heals and becomes integrated into the host," Stroock said.

The grafts promote the ingrowth of a vascular system -- the network of vessels that carry blood and circulate fluid through the body -- to the wounded area by providing a template for growth of both the tissue (dermis, the deepest layer of skin), and the vessels. Type I collagen is biocompatible and contains no living cells itself, reducing concerns about immune system response and rejection of the template.

A key finding of the study is that the healing process responds strongly to the geometry of the microchannels within the collagen. Healthy tissue and vessels can be guided to grow toward the wound in an organized and rapid manner.

Dermal templates are not new; the Johnson& Johnson product Integra, for example, is widely used for burns and other deep wounds, Spector said, but it falls short in its ability to encourage growth of healthy tissue because it lacks the microchannels designed by the Cornell researchers.

"They can take a long time to incorporate into the person you're putting them in," Spector said."When you're putting a piece of material on a patient and the wound is acellular, it has a big risk for infection and requires lots of dressing changes and care. Ideally you want to have a product or material that gets vascularized very rapidly."

In the clinic, Spector continued, patients often need significant reconstructive surgery to repair injuries with exposed vital structures like bone, tendon or orthopedic hardware. The experimental templates are specifically designed to improve vascularization over these"barren" areas, perhaps one day eliminating the need for such invasive surgeries and reducing the patient's discomfort and healing time.

Eventually, the scientists may try to improve their tissue grafts by, for example, reinforcing them with polymer meshes that could also act as a wound covering, Spector said.

Other collaborators include first author Ying Zheng, a former postdoctoral associate in Stroock's lab; Dr. Peter W. Henderson, chief research fellow at Weill Cornell's Laboratory for Bioregenerative Medicine and Surgery; graduate student Nak Won Choi; and Lawrence J. Bonassar, associate professor of biomedical engineering.

The work was supported by the Morgan Fund for Tissue Engineering and the New York State Office of Science, Technology and Academic Research.


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Monday, May 16, 2011

Autonomous Robots Made to Explore and Map Buildings

This isn't a future-tech scenario. This advanced autonomous capability has been developed by a team from the Georgia Institute of Technology, the University of Pennsylvania and the California Institute of Technology/Jet Propulsion Laboratory (JPL). A paper describing this capability and its present level of performance was presented in April at the SPIE Defense, Security and Sensing Conference in Orlando, Fla.

"When first responders -- whether it's a firefighter in downtown Atlanta or a soldier overseas -- confront an unfamiliar structure, it's very stressful and potentially dangerous because they have limited knowledge of what they're dealing with," said Henrik Christensen, a team member who is a professor in the Georgia Tech College of Computing and director of the Robotics and Intelligent Machines Center there."If those first responders could send in robots that would quickly search the structure and send back a map, they'd have a much better sense of what to expect and they'd feel more confident."

The ability to map and explore simultaneously represents a milestone in the Micro Autonomous Systems and Technology (MAST) Collaborative Technology Alliance Program, a major research initiative sponsored by the U.S. Army Research Laboratory. The five-year program is led by BAE Systems and includes numerous principal and general members comprised largely of universities.

MAST's ultimate objective is to develop technologies that will enable palm-sized autonomous robots to help humans deal with civilian and military challenges in confined spaces. The program vision is for collaborative teams of tiny devices that could roll, hop, crawl or fly just about anywhere, carrying sensors that detect and send back information critical to human operators.

The wheeled platforms used in this experiment measure about one foot square. But MAST researchers are working toward platforms small enough to be held in the palm of one hand. Fully autonomous and collaborative, these tiny robots could swarm by the scores into hazardous situations.

The MAST program involves four principal research teams: integration, microelectronics, microsystems mechanics, and processing for autonomous operation. Georgia Tech researchers are participating in every area except microelectronics. In addition to the College of Computing, researchers from the Georgia Tech Research Institute (GTRI), the School of Aerospace Engineering and the School of Physics are involved in MAST work.

The experiment -- developed by the Georgia Tech MAST processing team -- combines navigation technology developed by Georgia Tech with vision-based techniques from JPL and network technology from the University of Pennsylvania.

In addition to Christensen, members of the Georgia Tech processing team involved in the demonstration include Professor Frank Dellaert of the College of Computing and graduate students Alex Cunningham, Manohar Paluri and John G. Rogers III. Regents professor Ronald C. Arkin of the College of Computing and Tom Collins of GTRI are also members of the Georgia Tech processing team.

In the experiment, the robots perform their mapping work using two types of sensors -- a video camera and a laser scanner. Supported by onboard computing capability, the camera locates doorways and windows, while the scanner measures walls. In addition, an inertial measurement unit helps stabilize the robot and provides information about its movement.

Data from the sensors are integrated into a local area map that is developed by each robot using a graph-based technique called simultaneous localization and mapping (SLAM). The SLAM approach allows an autonomous vehicle to develop a map of either known or unknown environments, while also monitoring and reporting on its own current location.

SLAM's flexibility is especially valuable in areas where global positioning system (GPS) service is blocked, such as inside buildings and in some combat zones, Christensen said. When GPS is active, human handlers can use it to see where their robots are. But in the absence of global location information, SLAM enables the robots to keep track of their own locations as they move.

"There is no lead robot, yet each unit is capable of recruiting other units to make sure the entire area is explored," Christensen explained."When the first robot comes to an intersection, it says to a second robot, 'I'm going to go to the left if you go to the right.'"

Christensen expects the robots' abilities to expand beyond mapping soon. One capability under development by a MAST team involves tiny radar units that could see through walls and detect objects -- or humans -- behind them. Infrared sensors could also support the search mission by locating anything giving off heat. In addition, a MAST team is developing a highly flexible"whisker" to sense the proximity of walls, even in the dark.

The processing team is designing a more complex experiment for the coming year to include small autonomous aerial platforms for locating a particular building, finding likely entry points and then calling in robotic mapping teams. Demonstrating such a capability next year would culminate progress in small-scale autonomy during MAST's first five years, Christensen said.

In addition to the three universities, other MAST team participants are North Carolina A&T State University, the University of California Berkeley, the University of Maryland, the University of Michigan, the University of New Mexico, Harvard University, the Massachusetts Institute of Technology, and two companies: BAE Systems and Daedalus Flight Systems.

Research was sponsored by the Army Research Laboratory under Cooperative Agreement Number W911NF-08-2-0004.


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Sunday, May 15, 2011

New Calculations on Blackbody Energy Set the Stage for Clocks With Unprecedented Accuracy

Precision timekeeping is one of the bedrock technologies of modern science and technology. It underpins precise navigation on Earth and in deep space, synchronization of broadband data streams, precision measurements of motion, forces and fields, and tests of the constancy of the laws of nature over time.

"Using our calculations, researchers can account for a subtle effect that is one of the largest contributors to error in modern atomic timekeeping," says lead author Marianna Safronova of the University of Delaware, the first author of the presentation."We hope that our work will further improve upon what is already the most accurate measurement in science: the frequency of the aluminum quantum-logic clock," adds co-author Charles Clark, a physicist at the Joint Quantum Institute, a collaboration of the National Institute of Standards and Technology (NIST) and the University of Maryland.

The paper was presented at the 2011 Conference on Lasers and Electro-Optics in Baltimore, Md.

The team studied an effect that is familiar to anyone who has basked in the warmth of a campfire: heat radiation. Any object at any temperature, whether the walls of a room, a person, the Sun or a hypothetical perfect radiant heat source known as a"black body," emits heat radiation. Even a completely isolated atom senses the temperature of its environment. Just as heat swells the air in a hot-air balloon, so-called"blackbody radiation" (BBR) enlarges the size of the electron clouds within the atom, though to a much lesser degree -- by one part in a hundred trillion, a size that poses a severe challenge to precision measurement.

This effect comes into play in the world's most precise atomic clock, recently built by NIST researchers. This quantum-logic clock, based on atomic energy levels in the aluminum ion, Al+, has an uncertainty of 1 second per 3.7 billion years, translating to 1 part in 8.6 x 10-18, due to a number of small effects that shift the actual tick rate of the clock.

To correct for the BBR shift, the team used the quantum theory of atomic structure to calculate the BBR shift of the atomic energy levels of the aluminum ion. To gain confidence in their method, they successfully reproduced the energy levels of the aluminum ion, and also compared their results against a predicted BBR shift in a strontium ion clock recently built in the United Kingdom. Their calculation reduces the relative uncertainty due to room-temperature BBR in the aluminum ion to 4 x 10-19, or better than 18 decimal places, and a factor of 7 better than previous BBR calculations.

Current aluminum-ion clocks have larger sources of uncertainty than the BBR effect, but next-generation aluminum clocks are expected to greatly reduce those larger uncertainties and benefit substantially from better knowledge of the BBR shift.


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Saturday, May 14, 2011

Developing Advanced Biofuels: Researchers Counteract Biofuel Toxicity in Microbes

Researchers at the U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI) have provided a solution to this problem by developing a library of microbial efflux pumps that were shown to significantly reduce the toxicity of seven representative biofuels in engineered strains of Escherichia coli.

"Working with all available microbial genome sequence data, we generated a library of largely uncharacterized genes and were able to devise a simple but highly effective strategy to identify efflux pumps that could alleviate biofuel toxicity in E. coli and, as a consequence, help improve biofuel production," says Aindrila Mukhopadhyay, a chemist with JBEI's Fuels Synthesis Division, who led this research.

Mukhopadhyay, who also holds an appointment with the Lawrence Berkeley National Laboratory (Berkeley Lab)'s Physical Biosciences Division, is the corresponding author on a paper published in the journalMolecular Systems Biology. Co-authoring the paper with Mukhopadhyay were Mary Dunlop, Zain Dossani, Heather Szmidt, Hou-Cheng Chu, Taek Soon Lee, Jay Keasling and Masood Hadi.

Research efforts are underway at JBEI and elsewhere to engineer microorganisms, such as E. coli, to produce advanced biofuels in a cost effective manner. These fuels, which encompass short-to-medium carbon-chain alcohols, such as butanol, isopentanol and geraniol, can replace gasoline on a gallon-for-gallon basis and be used in today's infrastructures and engines, unlike ethanol. Biofuels made from branched carbon-chain compounds, such as geranyl acetate and farnesyl hexanoate, would also be superior to today's biodiesel, which is made from esters of linear fatty acids. Cyclic alkenes, such as limonene and pinene, could serve as precursors to jet fuel. Although biosynthetic pathways to the production of these carbon compounds in microbes have been identified, product toxicity to microbes is a common problem in strain engineering for biofuels and other biotechnology applications.

"In order for microbial biofuel production to be cost effective, yields must exceed native microbial tolerance levels, necessitating the development of stress-tolerant microbe strains," Mukhopadhyay says."It is crucial that we improve tolerance in parallel with the development of metabolic pathways for the production of next-generation biofuels."

Microbes employ various strategies for addressing cell toxicity but perhaps the most effective are efflux pumps, proteins in the cytoplasmic membrane of cells whose function is to transport toxic substances out of the cell. This is done actively, using proton motive force. However, to date very few of these have been characterized for efficacy against biofuel like compounds.

"Sequenced bacterial genomes include many efflux pumps but remain a largely unexplored resource for use in engineering fuel tolerance," Mukhopadhyay says."We took a systematic approach to screen a library of primarily uncharacterized heterologous pumps for engineering biofuel tolerant host strains. We were then able to demonstrate that expression of a heterologous pump can increase the yield of a biofuel in the production strain."

Since all known solvent-resistant efflux pumps in Gram-negative bacteria fall into the hydrophobe/amphiphile efflux (HAE1) family, Mukhopadhyay and her colleagues constructed a datab

ase of all HAE1 pumps from sequenced bacterial genomes. They then performed a bioinformatics screen to compare regions predicted to be responsible for substrate specificity to those of TtgB, a well-characterized solvent-resistant efflux pump.

"This metric allowed us to rank the complete set of pumps and select a subset that represented a uniform distribution of candidate genes," says Mukhopadhyay."To construct the library, we amplified efflux pump operons from the genomic DNA of the selected bacteria, cloned them into a vector, and transformed the vector into an E. coli host strain."

In a series of survival competitions, the two microbial efflux pumps that performed best were the native E. coli pump AcrAB and a previously uncharacterized pump from a marine microbe Alcanivorax borkumensis.

"We focused on the A. borkumensis pump and tested it in a strain of host microbe engineered to produce the limonene jet fuel precursor," Mukhopadhyay says."Microbes expressing the pump produced significantly more limonene than those with no pump, providing an important proof of principle demonstration that efflux pumps that increase tolerance to exogenous biofuel can also improve the yield of a production host."

Mukhopadhyay and her JBEI colleagues have begun evaluating microbial efflux pumps for other important compounds as well as inhibitors present in the carbon source from lignocellulose. They are also looking to improve the A. borkumensis pump and other high performers in their current library, and to optimize the systems by which pump genes are expressed in engineered biofuel-producing microbial strains.

"We believe our bioprospecting strategy for biofuel tolerance mechanisms is going to be a valuable and widely applicable tool in the biotechnology field for engineering new microbial production strains," Mukhopadhyay says.

This research was supported by JBEI through the DOE Office of Science.


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Friday, May 13, 2011

Controling Robotic Arms Is Child's Play

"The input device contains various movement sensors, also called inertial sensors," says Bernhard Kleiner of the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart, who leads the project. The individual micro-electromechanical systems themselves are not expensive. What the scientists have spent time developing is how these sensors interact."We have developed special algorithms that fuse the data of individual sensors and identify a pattern of movement. That means we can detect movements in free space," summarizes Kleiner.

What may at first appear to be a trade show gimmick, is in fact a technology that offers numerous advantages in industrial production and logistical processes. The system could be used to simplify the programming of industrial robots, for example. To date, this has been done with the aid of laser tracking systems: An employee demonstrates the desired motion with a hand-held baton that features a white marker point. The system records this motion by analyzing the light reflected from a laser beam aimed at the marker. Configuring and calibrating the system takes a lot of time. The new input device should eliminate the need for these steps in the future -- instead, employees need only pick up the device and show the robot what it is supposed to do.

The system has numerous applications in medicine, as well. Take, for example, gait analysis. Until now, cameras have made precise recordings of patients as they walk back and forth along a specified path. The films reveal to the physician such things as how the joints behave while walking, or whether incorrect posture in the knees has been improved by physical therapy. Installing the cameras, however, is complex and costly, and patients are restricted to a predetermined path. The new sensor system can simplify this procedure: Attached to the patient's upper thigh, it measures the sequences and patterns of movement -- without limiting the patient's motion in any way.

"With the inertial sensor system, gait analysis can be performed without a frame of reference and with no need for a complex camera system," explains Kleiner. In another project, scientists are already working on comparisons of patients' gait patterns with those patterns appearing in connection with such diseases as Parkinson's.

Another medical application for the new technology is the control of active prostheses containing numerous small actuators. Whenever the patient moves, the prosthesis in turn also moves; this makes it possible for a leg prosthesis to roll the foot while walking. Here, too, the sensor could be attached to the patient's upper thigh and could analyze the movement, helping to regulate the motors of the prosthesis. Research scientists are currently working on combining the inertial sensor system with an electromyographic (EMG) sensor. Electromyography is based on the principle that when a muscle tenses, it produces an electrical voltage which a sensor can then measure by way of an electrode. If the sensor is placed, for example, on the muscle responsible for lifting the patient's foot, the sensor registers when the patient tenses this muscle -- and the prosthetic foot lifts itself. EMG sensors like this are already available but are difficult to position.

"While standard EMG sensors consist of individual electrodes that have to be positioned precisely on the muscle, our system is made up of many small electrodes that attach to a surface area. This enables us to sense muscle movements much more reliably," says Kleiner.


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Wednesday, May 11, 2011

Drive Test: Super-Stable Laser Shines in Minivan Experiment

The experiment shows how advanced lasers can be made both stable and transportable enough for field use in geodesy, hydrology, improved radar and space-based tests of fundamental physics.

The drive tests, limited to a short excursion of five meters across the grass at the NIST Boulder, Colo., campus, are described inOptics Express. Scientists evaluated the infrared fiber laser's performance with the vehicle stationary, with the motor alternately off and idling, and moving over uneven ground at speeds of less than 1 meter per second (i.e., 3.6 km/hr). The laser frequency remained stable enough with the car parked -- the most likely situation in the field -- to be used in some applications now, says David Leibrandt, a NIST post-doctoral researcher.

"Our group has been building and using ultra-stable lasers for more than 10 years, but they're large and delicate," Leibrandt explains."The ones we use for our optical atomic clocks occupy a small room and have to be very carefully isolated from seismic and acoustic vibrations. This paper presents a new design that is less sensitive to vibrations and could be made much smaller."

NIST scientists stabilized the test laser's frequency using a common technique -- locking it to the extremely consistent length of an optical glass cavity. This sphere, about the size of a small orange, hangs in a customized mount with just the right stiffness. The scientists also designed a system to correct the laser frequency when the vehicle moves. Six accelerometers surrounding the cavity measure its linear and rotational acceleration. The accelerometers' signals are routed to a programmable computer chip that predicts and corrects the laser frequency in less than 100 microseconds.

The new laser will make it easier to use advanced atomic clocks for geodesy (measurements of Earth), an application envisioned by the same NIST research group. The laser also might be used on moving platforms, perhaps in space-based physics experiments or on Earth generating low-noise signals for radar. Study results indicate the laser is roughly 10 times more resistant to undesirable effects from vibration or acceleration than the best radio frequency crystal oscillators. Improved mechanical design and higher-bandwidth accelerometers could make the laser even more stable in the future, the researchers say.

The research is supported by the Office of Naval Research, Air Force Office of Scientific Research, and Defense Advanced Research Projects Agency.


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Tuesday, May 10, 2011

Bats Lend an Ear to Sonar Engineering

Published on May 10, in IOP Publishing's journalBioinspiration& Biomimetics, the study provides key insights into the variability of the shapes of bat ears that exists between different species, and shows how this variability may affect the functionality of one of the most impressive navigational systems in nature.

Bats are one of a few animal groups that demonstrate biosonar -- the ability to generate and emit ultrasonic pulses and gauge the reflections to obtain detailed information on their surroundings.

Bats use biosonar as a way of navigating and hunting for food, however researchers have seen its potential to inspire new ways of engineering where manipulating outgoing or incoming waves with structures is a principal component.

Lead author Professor Rolf Müller, of Virginia Tech, said:"Using physical shapes to manipulate an outgoing or a received wave has application in many areas of engineering. Besides the obvious analogues of SONAR and RADAR, such principles could also find application in biomedical ultrasound, non-destructive testing, wireless communications, and sensory systems for autonomous robots and nodes in sensor networks."

The ear of a bat plays a crucial role in the overall sensing system by acting as a baffle to diffract the incoming waves therefore determining the ear's pattern of sensitivity to direction and frequency.

The researchers, working in a joint research laboratory of Shandong University and Virginia Tech, created 3D computer models of 100 bat pinnae -- the visible part of the ear that resides outside of the head -- from 59 different species, and transformed the models into cylindrical representations.

The representations were statistically analysed using principal component analysis -- a method that has previously been applied to analyse human faces, palms, and ears -- and were shown to vary in the opening angle of the pinna, breaks of symmetry between the right and left sides, and changes in width at both the top and bottom.

The researchers also demonstrated how this variability can affect the properties of beamforming -- the process by which the incoming signal is diffracted by the shape of the pinna to create a"beampattern" through which the bat sees it environment.

The variability occurs as a result of the evolution of bats whose habitats range from environments with virtually no structures, to those with simple structures (calm water surfaces), to habitats with very complicated structures (dense forests).

The researchers found, for example, that a group of bats that hunts for prey in dense vegetation with trains of long, closely-spaced objects are separated from other bats by the widths of their pinna openings, demonstrating how biodiversity can provide a useful insight into how a general principal can be customised to fit different needs.

Professor Müller continued,"In order for this to happen, the ears of bats must be studied further. An example would be to expand the sample to include more diversity and find more specific relationships between pinna shape and beamforming across different species. Small local shape features that are hard to capture by the present analysis can also have a big impact on the function."


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Monday, May 9, 2011

Robotics: A Tiltable Head Could Improve the Ability of Undulating Robots to Navigate Disaster Debris

Researchers at the Georgia Institute of Technology recently built a robot that can penetrate and"swim" through granular material. In a new study, they show that varying the shape or adjusting the inclination of the robot's head affects the robot's movement in complex environments.

"We discovered that by changing the shape of the sand-swimming robot's head or by tilting its head up and down slightly, we could control the robot's vertical motion as it swam forward within a granular medium," said Daniel Goldman, an assistant professor in the Georgia Tech School of Physics.

Results of the study will be presented on May 10 at the 2011 IEEE International Conference on Robotics and Automation in Shanghai. Funding for this research was provided by the Burroughs Wellcome Fund, National Science Foundation and Army Research Laboratory.

The study was conducted by Goldman, bioengineering doctoral graduate Ryan Maladen, physics graduate student Yang Ding and physics undergraduate student Andrew Masse, all from Georgia Tech, and Northwestern University mechanical engineering adjunct professor Paul Umbanhowar.

"The biological inspiration for our sand-swimming robot is the sandfish lizard, which inhabits the Sahara desert in Africa and rapidly buries into and swims within sand," explained Goldman."We were intrigued by the sandfish lizard's wedge-shaped head that forms an angle of 140 degrees with the horizontal plane, and we thought its head might be responsible for or be contributing to the animal's ability to maneuver in complex environments."

For their experiments, the researchers attached a wedge-shaped block of wood to the head of their robot, which was built with seven connected segments, powered by servo motors, packed in a latex sock and wrapped in a spandex swimsuit. The doorstop-shaped head -- which resembled the sandfish's head -- had a fixed lower length of approximately 4 inches, height of 2 inches and a tapered snout. The researchers examined whether the robot's vertical motion could be controlled simply by varying the inclination of the robot's head.

Before each experimental run in a test chamber filled with quarter-inch-diameter plastic spheres, the researchers submerged the robot a couple inches into the granular medium and leveled the surface. Then they tracked the robot's position until it reached the end of the container or swam to the surface.

The researchers investigated the vertical movement of the robot when its head was placed at five different degrees of inclination. They found that when the sandfish-inspired head with a leading edge that formed an angle of 155 degrees with the horizontal plane was set flat, negative lift force was generated and the robot moved downward into the media. As the tip of the head was raised from zero to 7 degrees relative to the horizontal, the lift force increased until it became zero. At inclines above 7 degrees, the robot rose out of the medium.

"The ability to control the vertical position of the robot by modulating its head inclination opens up avenues for further research into developing robots more capable of maneuvering in complex environments, like debris-filled areas produced by an earthquake or landslide," noted Goldman.

The robotics results matched the research team's findings from physics experiments and computational models designed to explore how head shape affects lift in granular media.

"While the lift forces of objects in air, such as airplanes, are well understood, our investigations into the lift forces of objects in granular media are some of the first ever," added Goldman.

For the physics experiments, the researchers dragged wedge-shaped blocks through a granular medium. Blocks with leading edges that formed angles with the horizontal plane of less than 90 degrees resembled upside-down doorstops, the block with a leading edge equal to 90 degrees was a square, and blocks with leading edges greater than 90 degrees resembled regular doorstops.

They found that blocks with leading edges that formed angles with the horizontal plane less than 80 degrees generated positive lift forces and wedges with leading edges greater than 120 degrees created negative lift. With leading edges between 80 and 120 degrees, the wedges did not generate vertical forces in the positive or negative direction.

Using a numerical simulation of object drag and building on the group's previous studies of lift and drag on flat plates in granular media, the researchers were able to describe the mechanism of force generation in detail.

"When the leading edge of the robot head was less than 90 degrees, the robot's head experienced a lift force as it moved forward, which resulted in a torque imbalance that caused the robot to pitch and rise to the surface," explained Goldman.

Since this study, the researchers have attached a wedge-shaped head on the robot that can be dynamically modulated to specific angles. With this improvement, the researchers found that the direction of movement of the robot is sensitive to slight changes in orientation of the head, further validating the results from their physics experiments and computational models.

Being able to precisely control the tilt of the head will allow the researchers to implement different strategies of head movement during burial and determine the best way to wiggle deep into sand. The researchers also plan to test the robot's ability to maneuver through material similar to the debris found after natural disasters and plan to examine whether the sandfish lizard adjusts its head inclination to ensure a straight motion as it dives into the sand.

This material is based on research sponsored by the Burroughs Wellcome Fund, the National Science Foundation (NSF) under Award Number PHY-0749991, and the Army Research Laboratory (ARL) under Cooperative Agreement Number W911NF-08-2-0004.


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Saturday, May 7, 2011

Engineers Patch a Heart: Tissue-Engineering Platform Enables Heart Tissue to Repair Itself

Led by Gordana Vunjak-Novakovic, Professor of Biomedical Engineering at Columbia University's Fu Foundation School of Engineering and Applied Science, the researchers developed a novel cell therapy to treat myocardial infarction (heart damage that follows a heart attack). They were able, for the first time, to combine the use of human repair cells that were conditioned during in-vitro culture to maximize their ability to revascularize and improve blood flow to the infarcted tissue with a fully biological composite scaffold designed to deliver these cells to the damaged heart. With this platform, they could both keep the cells within the infarct bed (in contrast to the massive cell loss associated with infusion of cells alone) and enhance cell survival and function in the infarct bed, where most of the cells would have died because of the obstruction of their blood supply.

"We are very excited about this new technique," said Dr. Vunjak-Novakovic."This platform is very adaptable and we believe it could be readily extended to the delivery of other types of human stem cells we are interested in to rebuild the heart muscle and further our research of the mechanisms underlying heart repair."

In effect, the Columbia Engineering team (with Amandine Godier-Fournemont and Timothy Martens as lead authors) removed the cells of a human heart muscle -- the myocardium -- leaving a protein scaffold with intact architecture and mechanical properties. They filled the scaffold with human mesenchymal progenitors (stem cells that can differentiate into many cell types) and then applied the patches to damaged heart tissue. The patches promoted the growth of new blood vessels and released proteins that stimulated the native tissue to repair itself. Moreover, the team also used this controllable platform to identify the signaling mechanisms involved in the repair process, and expand our knowledge about the role of cells and scaffold design on heart repair.

"It really is encouraging to make progress with 'instructing' cells to form human tissues by providing them with the right environments," noted Dr. Vunjak-Novakovic."The cells are the real 'tissue engineers' -- we only design the environments so they can do their work. Because these environments need to mimic the native developmental milieu, the progress in the field is really driven by the interdisciplinary work of bioengineers, stem cell biologists, and clinicians. By enabling regeneration and replacement of our damaged tissues, we can help people live longer and better."

Dr. Vunjak-Novakovic and her team already have several active research projects that continue this line of work. They are now investigating the formation of a contractile cardiac patch using human stem cells that can give rise to both the muscle and vascular compartments of the heart muscle. They are also studying how the cells within such a cardiac patch, when implanted on infarcted heart tissue, develop their ability to generate mechanical force and electrical conduction, and how these functions can be modulated by in-vitro culture.

"Ultimately, we envision this system as a possible point of care approach," said Dr. Vunjak-Novakovic,"with components actually produced and assembled in the operating room to most effectively target-signaling mechanisms involved in the repair process of someone's damaged heart."

The Columbia Engineering study has been supported by the NIH (National Institutes of Health).


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Thursday, May 5, 2011

Solar-Thermal Flat-Panels That Generate Electric Power: Researchers See Broad Residential and Industrial Applications

Two technologies have dominated efforts to harness the power of the sun's energy. Photovoltaics convert sunlight into electric current, while solar-thermal power generation uses sunlight to heat water and produce thermal energy. Photovoltaic cells have been deployed widely as flat panels, while solar-thermal power generation employs sunlight-absorbing surfaces feasible in residential and large-scale industrial settings.

Because of limited material properties, solar thermal devices have heretofore failed to economically generate enough electric power. The team's introduced two innovations: a better light-absorbing surface through enhanced nanostructured thermoelectric materials, which was then placed within an energy-trapping, vacuum-sealed flat panel. Combined, both measures added enhanced electricity-generating capacity to solar-thermal power technology, said Boston College Professor of Physics Zhifeng Ren, a co-author of the paper.

"We have developed a flat panel that is a hybrid capable of generating hot water and electricity in the same system," said Ren."The ability to generate electricity by improving existing technology at minimal cost makes this type of power generation self-sustaining from a cost standpoint."

Using nanotechnology engineering methods, the team combined high-performance thermoelectric materials and spectrally-selective solar absorbers in a vacuum-sealed chamber to boost conversion efficiency, according to the co-authors, which include MIT's Soderberg Professor of Power Engineering Gang Chen, Boston College and MIT graduate students and researchers at GMZ Energy, a Massachusetts clean energy research company co-founded by Ren and Chen.

The findings open up a promising new approach that has the potential to achieve cost-effective conversion of solar energy into electricity, an advance that should impact the rapidly expanding residential and industrial clean energy markets, according to Ren.

"Existing solar-thermal technologies do a good job generating hot water. For the new product, this will produce both hot water and electricity," said Ren."Because of the new ability to generate valuable electricity, the system promises to give users a quicker payback on their investment. This new technology can shorten the payback time by one third."


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Wednesday, May 4, 2011

New Way to Control Conductivity: Reversible Control of Electrical and Thermal Properties Could Find Uses in Storage Systems

"It's a new way of changing and controlling the properties" of materials -- in this case a class called percolated composite materials -- by controlling their temperature, says Gang Chen, MIT's Carl Richard Soderberg Professor of Power Engineering and director of the Pappalardo Micro and Nano Engineering Laboratories. Chen is the senior author of a paper describing the process that was published online on April 19 and will appear in a forthcoming issue ofNature Communications. The paper's lead authors are former MIT visiting scholars Ruiting Zheng of Beijing Normal University and Jinwei Gao of South China Normal University, along with current MIT graduate student Jianjian Wang. The research was partly supported by grants from the National Science Foundation.

The system Chen and his colleagues developed could be applied to many different materials for either thermal or electrical applications. The finding is so novel, Chen says, that the researchers hope some of their peers will respond with an immediate,"I have a use for that!"

One potential use of the new system, Chen explains, is for a fuse to protect electronic circuitry. In that application, the material would conduct electricity with little resistance under normal, room-temperature conditions. But if the circuit begins to heat up, that heat would increase the material's resistance, until at some threshold temperature it essentially blocks the flow, acting like a blown fuse. But then, instead of needing to be reset, as the circuit cools down the resistance decreases and the circuit automatically resumes its function.

Another possible application is for storing heat, such as from a solar thermal collector system, later using it to heat water or homes or to generate electricity. The system's much-improved thermal conductivity in the solid state helps it transfer heat.

Essentially, what the researchers did was suspend tiny flakes of one material in a liquid that, like water, forms crystals as it solidifies. For their initial experiments, they used flakes of graphite suspended in liquid hexadecane, but they showed the generality of their process by demonstrating the control of conductivity in other combinations of materials as well. The liquid used in this research has a melting point close to room temperature -- advantageous for operations near ambient conditions -- but the principle should be applicable for high-temperature use as well.

The process works because when the liquid freezes, the pressure of its forming crystal structure pushes the floating particles into closer contact, increasing their electrical and thermal conductance. When it melts, that pressure is relieved and the conductivity goes down. In their experiments, the researchers used a suspension that contained just 0.2 percent graphite flakes by volume. Such suspensions are remarkably stable: Particles remain suspended indefinitely in the liquid, as was shown by examining a container of the mixture three months after mixing.

By selecting different fluids and different materials suspended within that liquid, the critical temperature at which the change takes place can be adjusted at will, Chen says.

"Using phase change to control the conductivity of nanocomposites is a very clever idea," says Li Shi, a professor of mechanical engineering at the University of Texas at Austin. Shi adds that as far as he knows"this is the first report of this novel approach" to producing such a reversible system.

"I think this is a very crucial result," says Joseph Heremans, professor of physics and of mechanical and aerospace engineering at Ohio State University."Heat switches exist," but involve separate parts made of different materials, whereas"here we have a system with no macroscopic moving parts," he says."This is excellent work."


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Sunday, May 1, 2011

Pier Review: Comparing Ultra High-Resolution Photographs from the Past and the Present Could Hold the Key to Restoring Hastings' Fire-Damaged Pier

Prior to the fire, NPL, the UK's National Measurement Institute, had been surveying the pier to support redevelopment plans and to monitor long-term changes in the pier. The project was part of the development of a world leading low-cost technique to assess long-term degradation of structures.

The technique is called Digital Image Correlation. It has been used in the laboratory for some time but NPL have recently been pioneering its use for looking at civil engineering structures. It involves taking ultra high-resolution panoramic photos -- images up to 1.4 Giga Pixels in size -- at two different times to identify structural changes. Advanced mathematical programs then analyse the pair of images to identify changes in the structure pixel by pixel. Using this information, engineers can understand how large structures change over time.

Following the devastating fire, NPL scientists returned to Hastings to take their second set of photos. They were then required to develop more advanced analysis techniques, which could deal with the much larger than anticipated changes to the Pier, and produce meaningful information about the structure. This work is proving more valuable than expected as considerable change has now taken place. In addition, the large panoramic images provide a snapshot of the structure in time, which is useful for archival purposes.

Up to 45 images were stitched together to produce an ultra high-resolution final image 80,000 pixels wide -- 300-400 times more detailed than a typical camera-phone photograph. Processing a pair of these images, one before the fire and one after, can help highlight where the structure has apparently changed because of the fire.

Results have been very positive. Whilst the super-structure has been severely damaged and there are large visual changes, the cast iron framework -- or sub-structure -- seems much less affected. The sub-structure on the west side of the Pier appears to be remarkably similar pre and post fire. On the East side there are small areas where there are some changes, and one localised area of the sub-structure about half way along showing significant distortion. But the vast majority of the sub-structure seems largely unchanged. The area showing the most distortion -- presumably caused by the extreme heat -- was at a downwind point where anecdotally the fire was seen to be fiercest.

Digital Image Correlation allows the computer to effectively carry out the laborious checking of the whole structure. This means quicker and cheaper identification of areas which have been deformed or damaged, and hence may need closer inspection. This is important on large structures such as piers as it allows civil engineers to focus their efforts on the parts that most need attention, dramatically speeding the inspection process and reducing the cost of repair.

The project has also helped prove the concept of Digital Image Correlation for the measurement of changes in large structures, by providing NPL with a real-life case study enabling development of key analysis software.

Nick McCormick, Principle Research Scientist at NPL, said:"It was fortunate that we began the project before the fire, as the results will be invaluable in regenerating the pier when restoration funding is secured. From a scientific point of view, the scale of the changes actually proved very interesting, although challenging, and required us to develop far more advanced analysis techniques than originally intended. These will be hugely important in our work to develop low cost monitoring solutions for other structures. Obviously we hope the next one won't be so badly damaged part way through our study. For most applications we work on we would expect to monitor much less significant changes over time -- for example small cracks appearing in bridges or building subsidence -- so that problems can be remedied before they escalate to cause such serious damage."

Digital Image Correlation is one of a number of techniques that NPL is developing for low-cost examination of large civil engineering structures such as bridges, buildings, tunnels and piers.


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Saturday, April 30, 2011

Caterpillars Inspire New Movements in Soft Robots

Some caterpillars have the extraordinary ability to rapidly curl themselves into a wheel and propel themselves away from predators. This highly dynamic process, called ballistic rolling, is one of the fastest wheeling behaviours in nature.

Researchers from Tufts University, Massachusetts, saw this as an opportunity to design a robot that mimics this behaviour of caterpillars and to develop a better understanding of the mechanics behind ballistic rolling.

The study, published on April 27, in IOP Publishing's journalBioinspiration& Biomimetics, also includes a video of both the caterpillar and robot in action and can be found athttp://www.youtube.com/watch?v=wZe9qWi-LUo.

To simulate the movement of a caterpillar, the researchers designed a 10cm long soft-bodied robot, called GoQBot, made out of silicone rubber and actuated by embedded shape memory alloy coils. It was named GoQBot as it forms a"Q" shape before rolling away at over half a meter per second.

The GoQBot was designed to specifically replicate the functional morphologies of a caterpillar, and was fitted with 5 infrared emitters along its side to allow motion tracking using one of the latest high speed 3D tracking systems. Simultaneously, a force plate measured the detailed ground forces as the robot pushed off into a ballistic roll.

In order to change its body conformation so quickly, in less than 100 ms, GoQBot benefits from a significant degree of mechanical coordination in ballistic rolling. Researchers believe such coordination is mediated by the nonlinear muscle coupling in the animals.

The researchers were also able to explain why caterpillars don't use the ballistic roll more often as a default mode of transport; despite its impressive performance, ballistic rolling is only effective on smooth surfaces, demands a large amount of power, and often ends unpredictably.

Not only did the study provide an insight into the fascinating escape system of a caterpillar, it also put forward a new locomotor strategy which could be used in future robot development.

Many modern robots are modelled after snakes, worms and caterpillars for their talents in crawling and climbing into difficult spaces. However, the limbless bodies severely reduce the speeds of the robots in the opening. On the other hand, there are many robots that employ a rolling motion in order to travel with speed and efficiency, but they struggle to gain access to difficult spaces.

Lead author Huai-Ti Lin from the Department of Biology, Tufts University, said:"GoQBot demonstrates a solution by reconfiguring its body and could therefore enhance several robotic applications such as urban rescue, building inspection, and environmental monitoring."

"Due to the increased speed and range, limbless crawling robots with ballistic rolling capability could be deployed more generally at a disaster site such as a tsunami aftermath. The robot can wheel to a debris field and wiggle into the danger for us."


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Friday, April 29, 2011

NASA Technology Looks Inside Japan's Nuclear Reactor

The iRobot PackBot employs technologies used previously in the design of"Rocky-7," which served as a terrestrial test bed at JPL for the current twin Mars rovers, Spirit and Opportunity. PackBot's structural features are modeled after Rocky-7, including the lightweight, high-torque actuators that control the rover; and its strong, lightweight frame structure and sheet-metal chassis.

PackBot's other"ancestor," called Urbie, was an urban reconnaissance robot with military and disaster response applications. Urbie's lightweight structure and rugged features also made it useful in emergency response situations; for example, at sites contaminated with radiation and chemical spills, and at buildings damaged by earthquakes. Urbie's physical structure was designed by iRobot Corp., Bedford, Mass., while JPL was responsible for the intelligent robot's onboard sensors and vision algorithms, which helped the robot factor in obstacles and determine an appropriate driving path. Following the success of Urbie's milestones, the team at iRobot created its successor: PackBot.

Since 2002, iRobot has delivered variations of the PackBot model to the U.S. Army, U.S. Air Force and U.S. Navy. The tactical robot's first military deployment was to Afghanistan in July 2002, to assist soldiers by providing"eyes and ears" in the most dangerous or inaccessible areas. It was also used to search through debris at Ground Zero after the Sept. 11, 2001 attacks in New York.

Recently, iRobot provided two PackBots to help after the devastating March 11, 2011, earthquake and tsunami in Japan. The PackBot models, currently taking radioactivity readings in the damaged Fukushima Daiichi nuclear power plant buildings, are equipped with multiple cameras and hazard material sensors. The images and readings provided by the PackBots indicated radiation levels are still too high to allow human repair crews to safely enter the buildings.

Urbie was a joint effort of the Defense Advanced Research Project's Agency's (DARPA) Tactical Mobile Robot program, JPL, iRobot Corp., the Robotics Institute of Carnegie Mellon University, and the University of Southern California's Robotics Research Laboratory. JPL is managed for NASA by the California Institute of Technology in Pasadena.

For more information on the history of the partnership between iRobot and JPL, visit:http://www.sti.nasa.gov/tto/Spinoff2005/ps_1.html.


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Thursday, April 28, 2011

Origami Not Just for Paper Anymore: DNA, Folded Into Complex Shapes, Could Have a Big Impact on Nanotechnology

Trying to build DNA structures on a large scale was once considered unthinkable. But about five years ago, Caltech computational bioengineer Paul Rothemund laid out a new design strategy called DNA origami: the construction of two-dimensional shapes from a DNA strand folded over on itself and secured by short"staple" strands. Several years later, William Shih's lab at Harvard Medical School translated this concept to three dimensions, allowing design of complex curved and bent structures that opened new avenues for synthetic biological design at the nanoscale.

A major hurdle to these increasingly complex designs has been automation of the design process. Now a team at MIT, led by biological engineer Mark Bathe, has developed software that makes it easier to predict the three-dimensional shape that will result from a given DNA template. While the software doesn't fully automate the design process, it makes it considerably easier for designers to create complex 3-D structures, controlling their flexibility and potentially their folding stability.

"We ultimately seek a design tool where you can start with a picture of the complex three-dimensional shape of interest, and the algorithm searches for optimal sequence combinations," says Bathe, the Samuel A. Goldblith Assistant Professor of Applied Biology."In order to make this technology for nanoassembly available to the broader community -- including biologists, chemists, and materials scientists without expertise in the DNA origami technique -- the computational tool needs to be fully automated, with a minimum of human input or intervention."

Bathe and his colleagues described their new software in the Feb. 25 issue ofNature Methods. In that paper, they also provide a primer on creating DNA origami with collaborator Hendrik Dietz at the Technische Universitaet Muenchen."One bottleneck for making the technology more broadly useful is that only a small group of specialized researchers are trained in scaffolded DNA origami design," Bathe says.

Programming DNA

DNA consists of a string of four nucleotide bases known as A, T, G and C, which make the molecule easy to program. According to nature's rules, A binds only with T, and G only with C."With DNA, at the small scale, you can program these sequences to self-assemble and fold into a very specific final structure, with separate strands brought together to make larger-scale objects," Bathe says.

Rothemund's origami design strategy is based on the idea of getting a long strand of DNA to fold in two dimensions, as if laid on a flat surface. In his first paper outlining the method, he used a viral genome consisting of approximately 8,000 nucleotides to create 2-D stars, triangles and smiley faces.

That single strand of DNA serves as a"scaffold" for the rest of the structure. Hundreds of shorter strands, each about 20 to 40 bases in length, combine with the scaffold to hold it in its final, folded shape.

"DNA is in many ways better suited to self-assembly than proteins, whose physical properties are both difficult to control and sensitive to their environment," Bathe says.

Bathe's new software program interfaces with a software program from Shih's lab called caDNAno, which allows users to manually create scaffolded DNA origami from a two-dimensional layout. The new program, dubbed CanDo, takes caDNAno's 2-D blueprint and predicts the ultimate 3-D shape of the design. This resulting shape is often unintuitive, Bathe says, because DNA is a flexible object that twists, bends and stretches as it folds to form a complex 3-D shape.

According to Rothemund, the CanDo program should allow DNA origami designers to more thoroughly test their DNA structures and tweak them to fold correctly."While we have been able to design the shape of things, we have had no tools to easily design and analyze the stresses and strains in those shapes or to design them for specific purposes," he says.

At the molecular-level, stress in the double helix of DNA decreases the folding stability of the structure and introduces local defects, both of which have hampered progress in the scaffolded DNA origami field.

Postdoctoral researcher Do-Nyun Kim and graduate student Matthew Adendorff, both of the Bathe lab, are now furthering CanDo's capabilities and optimizing the scaffolded DNA origami design process.

Building nanoscale tools

Once scientists have a reliable way to assemble DNA structures, the next question is what to do with them. One application scientists are excited about is a"DNA carrier" that can transport drugs to specific destinations in the body such as tumors, where the carrier would release the cargo based on a specific chemical signal from the target cancer cell.

Another possible application of scaffolded DNA origami could help reproduce part of the light-harvesting apparatus of photosynthetic plant cells. Researchers hope to recreate that complex series of about 20 protein subunits, but to do that, components must be held together in specific positions and orientations. That's where DNA origami could come in.

"DNA origami enables the nanoscale construction of very precise architectural arrangements. Researchers are exploiting this unique property to pursue a number of applications at the nanoscale, including a synthetic photocell," Bathe says."While applications such as this are still quite far off on the horizon, we believe that predictive engineering software tools are essential for progress in this direction."

Novel applications may also grow out of a new competition being held at Harvard this summer, called BIOMOD. Undergraduate teams from about a dozen schools, including MIT, Harvard and Caltech, will try to design nanoscale biomolecules for robotics, computing and other applications.

In the meantime, Bathe is focusing on further developing CanDo to enable automated DNA origami design."Once you have an automated computational tool that allows you to design complex shapes in a precise way, I think we're in a much better position to exploit this technology for interesting applications," he says.

For DNA origami to have a broad impact, it needs to become routine to simply order up DNA parts to build any configuration you can dream up, Bathe says. He notes:"Once non-specialists can design arbitrary 3-D nanostructures using DNA origami, their imaginations can run free."


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Wednesday, April 27, 2011

Neurorobotics Reveals Brain Mechanisms of Self-Consciousness

Recent theories of self-consciousness highlight the importance of integrating many different sensory and motor signals, but it is not clear how this type of integration induces subjective states such as self-location ("Where am I in space?") and the first-person perspective ("From where do I perceive the world?"). Studies of neurological patients reporting out-of-body experiences have provided some evidence that brain damage interfering with the integration of multisensory body information may lead to pathological changes of the first-person perspective and self-location. However, it is still not known how to examine brain mechanisms associated with self-consciousness.

"Recent behavioral and physiological work, using video-projection and various visuo-tactile conflicts showed that self-location can be manipulated in healthy participants," explains senior study author, Dr. Olaf Blanke, from the Ecole Polytechnique Fédérale de Lausanne in Switzerland."However, so far these experimental findings and techniques do not allow for the induction of changes in the first-person perspective and have not been integrated with neuroimaging, probably because the experimental set-ups require participants to sit, stand, or move. This makes it very difficult to apply and film the visuo-tactile conflicts on the participant's body during standard brain imaging techniques."

Making use of inventive neuroimaging-compatible robotic technology that was developed by Dr. Gassert's group at the Swiss Federal Institute of Technology in Zurich, Dr. Blanke and colleagues studied healthy subjects and employed specific bodily conflicts that induced changes in self-location and first-person perspective while simultaneously monitoring brain activity with functional magnetic resonance imaging. They observed that TPJ activity reflected experimental changes in self-location and first-person perspective. The researchers also completed a large study of neurological patients with out-of-body experiences and found that brain damage was localized to the TPJ.

"Our results illustrate the power of merging technologies from engineering with those of neuroimaging and cognitive science for the understanding of the nature of one of the greatest mysteries of the human mind: self-consciousness and its neural mechanisms," concludes Dr. Blanke."Our findings on experimentally and pathologically induced altered states of self-consciousness present a powerful new research technology and reveal that TPJ activity reflects one of the most fundamental subjective feelings of humans: the feeling that 'I' am an entity that is localized at a position in space and that 'I' perceive the world from here."


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Tuesday, April 26, 2011

Fat Turns Into Soap in Sewers, Contributes to Overflows

"We found that FOG deposits in sewage collection systems are created by chemical reactions that turn the fatty acids from FOG into, basically, a huge lump of soap," says Dr. Joel Ducoste, a professor of civil, construction and environmental engineering at NC State and co-author of a paper describing the research. Collection systems are the pipes and pumping stations that carry wastewater from homes and businesses to sewage-treatment facilities.

These hardened FOG deposits reduce the flow of wastewater in the pipes, contributing to sewer overflows -- which can cause environmental and public-health problems and lead to costly fines and repairs.

The research team used a technique called Fourier Transform Infrared (FTIR) spectroscopy to determine what the FOG deposits were made of at the molecular level. FTIR spectroscopy shoots a sample material with infrared light at various wavelengths. Different molecular bonds vibrate in response to different wavelengths. By measuring which infrared wavelengths created vibrations in their FOG samples, researchers were able to determine each sample's molecular composition.

Using this technique, researchers confirmed that the hardened deposits were made of calcium-based fatty acid salts -- or soap.

"FOG itself cannot create these deposits," Ducoste says."The FOG must first be broken down into its constituent parts: glycerol and free fatty acids. These free fatty acids -- specifically, saturated fatty acids -- can react with calcium in the sewage collection system to form the hardened deposits.

"Until this point we did not know how these deposits were forming -- it was just a hypothesis," Ducoste says."Now we know what's going on with these really hard deposits."

The researchers are now focused on determining where the calcium in the collection system is coming from, and how quickly these deposits actually form. Once they've resolved those questions, Ducoste says, they will be able to create numerical models to predict where a sewage system may have"hot spots" that are particularly susceptible to these blockages.

Ultimately, Ducoste says,"if we know how -- and how quickly -- these deposits form, it may provide scientific data to support policy decisions related to preventing sewer overflows."

The research was funded by the Water Resources Research Institute and the U.S. Environmental Protection Agency.


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Monday, April 25, 2011

Development in Fog Harvesting Process May Make Water Available to the World’s Poor

What nature has developed, Shreerang Chhatre wants to refine, to help the world's poor. Chhatre is an engineer and aspiring entrepreneur at MIT who works on fog harvesting, the deployment of devices that, like the beetle, attract water droplets and corral the runoff. This way, poor villagers could collect clean water near their homes, instead of spending hours carrying water from distant wells or streams. In pursuing the technical and financial sides of his project, Chhatre is simultaneously a doctoral candidate in chemical engineering at MIT; an MBA student at the MIT Sloan School of Management; and a fellow at MIT's Legatum Center for Development and Entrepreneurship.

Access to water is a pressing global issue: the World Health Organization and UNICEF estimate that nearly 900 million people worldwide live without safe drinking water. The burden of finding and transporting that water falls heavily on women and children."As a middle-class person, I think it's terrible that the poor have to spend hours a day walking just to obtain a basic necessity," Chhatre says.

A fog-harvesting device consists of a fence-like mesh panel, which attracts droplets, connected to receptacles into which water drips. Chhatre has co-authored published papers on the materials used in these devices, and believes he has improved their efficacy."The technical component of my research is done," Chhatre says. He is pursuing his work at MIT Sloan and the Legatum Center in order to develop a workable business plan for implementing fog-harvesting devices.

Interest in fog harvesting dates to the 1990s, and increased when new research on Stenocara gracilipes made a splash in 2001. A few technologists saw potential in the concept for people. One Canadian charitable organization, FogQuest, has tested projects in Chile and Guatemala.

Chhatre's training as a chemical engineer has focused on the wettability of materials, their tendency to either absorb or repel liquids (think of a duck's feathers, which repel water). A number of MIT faculty have made advances in this area, including Robert Cohen of the Department of Chemical Engineering; Gareth McKinley of the Department of Mechanical Engineering; and Michael Rubner of the Department of Materials Science and Engineering. Chhatre, who also received his master's degree in chemical engineering from MIT in 2009, is co-author, with Cohen and McKinley among other researchers, of three published papers on the kinds of fabrics and coatings that affect wettability.

One basic principle of a good fog-harvesting device is that it must have a combination of surfaces that attract and repel water. For instance, the shell of Stenocara gracilipes has bumps that attract water and troughs that repel it; this way, drops collects on the bumps, then run off through the troughs without being absorbed, so that the water reaches the beetle's mouth.

To build fog-harvesting devices that work on a human scale, Chhatre says,"The idea is to use the design principles we developed and extend them to this problem."

To build larger fog harvesters, researchers generally use mesh, rather than a solid surface like a beetle's shell, because a completely impermeable object creates wind currents that will drag water droplets away from it. In this sense, the beetle's physiology is an inspiration for human fog harvesting, not a template."We tried to replicate what the beetle has, but found this kind of open permeable surface is better," Chhatre says."The beetle only needs to drink a few micro-liters of water. We want to capture as large a quantity as possible."

In some field tests, fog harvesters have captured one liter of water (roughly a quart) per one square meter of mesh, per day. Chhatre and his colleagues are conducting laboratory tests to improve the water collection ability of existing meshes.

FogQuest workers say there is more to fog harvesting than technology, however."You have to get the local community to participate from the beginning," says Melissa Rosato, who served as project manager for a FogQuest program that has installed 36 mesh nets in the mountaintop village of Tojquia, Guatemala, and supplies water for 150 people."They're the ones who are going to be managing and maintaining the equipment." Because women usually collect water for households, Rosato adds,"If women are not involved, chances of a long-term sustainable project are slim."

Whatever Chhatre's success in the laboratory, he agrees it will not be easy to turn fog-harvesting technology into a viable enterprise."My consumer has little monetary power," he notes. As part of his Legatum fellowship and Sloan studies, Chhatre is analyzing which groups might use his potential product. Chhatre believes the technology could also work on the rural west coast of India, north of Mumbai, where he grew up.

Another possibility is that environmentally aware communities, schools or businesses in developed countries might try fog harvesting to reduce the amount of energy needed to obtain water."As the number of people and businesses in the world increases and rainfall stays the same, more people will be looking for alternatives," says Robert Schemenauer, the executive director of FogQuest.

Indeed, the importance of water-supply issues globally is one reason Chhatre was selected for his Legatum fellowship.

"We welcomed Shreerang as a Legatum fellow because it is an important problem to solve," notes Iqbal Z. Quadir, director of the Legatum Center."About one-third of the planet's water that is not saline happens to be in the air. Collecting water from thin air solves several problems, including transportation. If people do not spend time fetching water, they can be productively employed in other things which gives rise to an ability to pay. Thus, if this technology is sufficiently advanced and a meaningful amount of water can be captured, it could be commercially viable some day."

Quadir also feels that if Chhatre manages to sell a sufficient number of collection devices in the developed world, it could contribute to a reduction in price, making it more viable in poor countries."The aviation industry in its infancy struggled with balloons, but eventually became a viable global industry," Quadir adds."Shreerang's project addresses multiple problems at the same time and, after all, the water that fills our rivers and lakes comes from air."

That said, fog harvesting remains in its infancy, technologically and commercially, as Chhatre readily recognizes."This is still a very open problem," he says."It's a work in progress."


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Sunday, April 24, 2011

Starting a New Metabolic Path: New Technique Will Help Metabolic Engineering

"Metabolic engineers and synthetic biologists can use our directed proteomic technique to get useful information about protein levels in their organisms, which in turn can be used to direct valuable followup experiments," says Christopher Petzold, chemist and deputy director for proteomics at JBEI, who led this research."We believe that targeted proteomics is a useful tool that fills a much needed gap in efforts to engineer new metabolic pathways for microbes."

Petzold, who also holds an appointment with the Lawrence Berkeley National Laboratory (Berkeley Lab)'s Physical Biosciences Division, is the corresponding author on a paper describing this research that was published in the journalMetabolic Engineering.

Metabolic engineering is the practice of altering genes and chemical pathways within a cell or microorganism to increase production of a specific chemical substance. It is fast becoming one of the principal techniques of modern biotechnology for the microbial production of chemicals that are currently derived from non-renewable resources or from natural resources that are limited. Critical to the success of metabolic engineering efforts are techniques that enable researchers to assemble and optimize novel metabolic pathways in microbes. Given that such pathways often involve multiple different factors, performance- hampering problems, such as the abundance of proteins and messenger RNA, or the activity of enzymes, are not always evident simply by measuring the amount of final product obtained.

"Synthetic biologists and metabolic engineers will utilize a variety of analytical methods to identify the parts of a metabolic pathway that limit production," Petzold says."At the metabolite level, for example, monitoring all pathway intermediates helps identify bottlenecks where further engineering could improve the final product titer. However, pathways that divert intermediates to native processes at the cost of final product formation may disguise the actual location of a bottleneck."

Researchers have tried developing assays to evaluate every intermediate in a given metabolic pathway but this has been a major challenge because intermediates often degrade rapidly or are isomers, and because there are few available standards for such evaluations.

"Engineers are often left to guess at the metabolite levels in parts of the pathway," Petzold says.

Targeted proteomics is based on a variation of mass spectrometry called selected-reaction monitoring (SRM) that can be used to rapidly detect and quantify multiple target proteins within complex protein mixtures, such as those found in cells or microbes. When coupled to liquid chro­matography (LC),SRM mass spectrometry analysis provides high selectivity and sensitivity through the elimination of background signal and noise even in the most complex mix of proteins. This is made possible by selecting only two points of mass for monitoring -- a peptide mass and a specific fragment mass -- rather than scanning the entire mass range.

"Carrying out targeted proteomics through SRM mass spectrometry analysis is most useful when quantification of multiple proteins in a single sample is desired," Petzold says."Working with protein-specific peptides, you can analyze 20 or more targeted proteins in an hour, and entire engineered metabolic pathways can be quantified in a single experiment, something that isn't practical with conventional immunoblot analysis."

Petzold and his co-authors demonstrated the effectiveness of their targeted proteomics technique when they used it to measure protein levels inEscherichia colithat were engineered with yeast proteins to produce amorpha-4,11-diene, a member of the family of plant chemicals known as sesquiterpenes. Strains ofE. colicontaining a high flux mevalonate pathway have the potential to provide a vast range of high value sesquiterpenes and other isoprenoid-based chemical compounds, which today are typically obtained from petrochemical or plant sources.

Our analysis identified two mevalonate pathway proteins, mevalonate kinase and phosphomevalonate kinase, both from yeast, as potential bottlenecks," Petzold says."Codon-optimization of the genes encoding mevalonate kinase and phosphomevalonate kinase, and expression from a stronger promoter led to significantly improved levels of these two proteins and a more than three-fold improvement in the final amorpha-4,11-diene titer, greater than 500 milligrams per liter."

Petzold and his JBEI colleagues are now in the process of implementing"scheduled-SRM," a variation of the SRM mass spectrometry analysis that would allow them to easily detect and quantify 100 proteins in a single experiment that can be completed in less than two hours.

This research was supported by JBEI through the DOE Office of Science. JBEI is one of three Bioenergy Research Centers funded by the U.S. Department of Energy to advance the development of the next generation of biofuels.


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Saturday, April 23, 2011

Scientists Engineer Nanoscale Vaults to Encapsulate 'Nanodisks' for Drug Delivery

The development of new methods that use engineered nanomaterials to transport drugs and release them directly into cells holds great potential in this area. And while several such drug-delivery systems -- including some that use dendrimers, liposomes or polyethylene glycol -- have won approval for clinical use, they have been hampered by size limitations and ineffectiveness in accurately targeting tissues.

Now, researchers at UCLA have developed a new and potentially far more effective means of targeted drug delivery using nanotechnology.

In a study to be published in the May 23 print issue of the journalSmall, they demonstrate the ability to package drug-loaded"nanodisks" into vault nanoparticles, naturally occurring nanoscale capsules that have been engineered for therapeutic drug delivery. The study represents the first example of using vaults toward this goal.

The UCLA research team was led by Leonard H. Rome and included his colleagues Daniel C. Buehler and Valerie Kickhoefer from the UCLA Department of Biological Chemistry; Daniel B. Toso and Z. Hong Zhou from the UCLA Department of Microbiology, Immunology and Molecular Genetics; and the California NanoSystems Institute (CNSI) at UCLA.

Vault nanoparticles are found in the cytoplasm of all mammalian cells and are one of the largest known ribonucleoprotein complexes in the sub-100-nanometer range. A vault is essentially barrel-shaped nanocapsule with a large, hollow interior -- properties that make them ripe for engineering into a drug-delivery vehicles. The ability to encapsulate small-molecule therapeutic compounds into vaults is critical to their development for drug delivery.

Recombinant vaults are nonimmunogenic and have undergone significant engineering, including cell-surface receptor targeting and the encapsulation of a wide variety of proteins.

"A vault is a naturally occurring protein particle and so it causes no harm to the body," said Rome, CNSI associate director and a professor of biological chemistry."These vaults release therapeutics slowly, like a strainer, through tiny, tiny holes, which provides great flexibility for drug delivery."

The internal cavity of the recombinant vault nanoparticle is large enough to hold hundreds of drugs, and because vaults are the size of small microbes, a vault particle containing drugs can easily be taken up into targeted cells.

With the goal of creating a vault capable of encapsulating therapeutic compounds for drug delivery, UCLA doctoral student Daniel Buhler designed a strategy to package another nanoparticle, known as a nanodisk (ND), into the vault's inner cavity, or lumen.

"By packaging drug-loaded NDs into the vault lumen, the ND and its contents would be shielded from the external medium," Buehler said."Moreover, given the large vault interior, it is conceivable that multiple NDs could be packaged, which would considerably increase the localized drug concentration."

According to researcher Zhou, a professor of microbiology, immunology and molecular genetics and director of the CNSI's Electron Imaging Center for NanoMachines, electron microscopy and X-ray crystallography studies have revealed that both endogenous and recombinant vaults have a thin protein shell enclosing a large internal volume of about 100,000 cubic nanometers, which could potentially hold hundreds to thousands of small-molecular-weight compounds.

"These features make recombinant vaults an attractive target for engineering as a platform for drug delivery," Zhou said."Our study represents the first example of using vaults toward this goal."

"Vaults can have a broad nanosystems application as malleable nanocapsules," Rome added.

The recombinant vaults are engineered to encapsulate the highly insoluble and toxic hydrophobic compound all-trans retinoic acid (ATRA) using a vault-binding lipoprotein complex that forms a lipid bilayer nanodisk.

The research was supported by the UC Discovery Grant Program, in collaboration with the research team's corporate sponsor, Abraxis Biosciences Inc., and by the Mather's Charitable Foundation and an NIH/NIBIB Award.


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Friday, April 22, 2011

Functioning Synapse Created Using Carbon Nanotubes: Devices Might Be Used in Brain Prostheses or Synthetic Brains

The team, which was led by Professor Alice Parker and Professor Chongwu Zhou in the USC Viterbi School of Engineering Ming Hsieh Department of Electrical Engineering, used an interdisciplinary approach combining circuit design with nanotechnology to address the complex problem of capturing brain function.

In a paper published in the proceedings of the IEEE/NIH 2011 Life Science Systems and Applications Workshop in April 2011, the Viterbi team detailed how they were able to use carbon nanotubes to create a synapse.

Carbon nanotubes are molecular carbon structures that are extremely small, with a diameter a million times smaller than a pencil point. These nanotubes can be used in electronic circuits, acting as metallic conductors or semiconductors.

"This is a necessary first step in the process," said Parker, who began the looking at the possibility of developing a synthetic brain in 2006."We wanted to answer the question: Can you build a circuit that would act like a neuron? The next step is even more complex. How can we build structures out of these circuits that mimic the function of the brain, which has 100 billion neurons and 10,000 synapses per neuron?"

Parker emphasized that the actual development of a synthetic brain, or even a functional brain area is decades away, and she said the next hurdle for the research centers on reproducing brain plasticity in the circuits.

The human brain continually produces new neurons, makes new connections and adapts throughout life, and creating this process through analog circuits will be a monumental task, according to Parker.

She believes the ongoing research of understanding the process of human intelligence could have long-term implications for everything from developing prosthetic nanotechnology that would heal traumatic brain injuries to developing intelligent, safe cars that would protect drivers in bold new ways.

For Jonathan Joshi, a USC Viterbi Ph.D. student who is a co-author of the paper, the interdisciplinary approach to the problem was key to the initial progress. Joshi said that working with Zhou and his group of nanotechnology researchers provided the ideal dynamic of circuit technology and nanotechnology.

"The interdisciplinary approach is the only approach that will lead to a solution. We need more than one type of engineer working on this solution," said Joshi."We should constantly be in search of new technologies to solve this problem."


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Thursday, April 21, 2011

RNA Nanoparticles Constructed to Safely Deliver Long-Lasting Therapy to Cells

In two new publications in the journal Molecular Therapy, University of Cincinnati (UC) biomedical engineering professor Peixuan Guo, PhD, details successful methods of producing large RNA nanoparticles and testing their safety in the delivery of therapeutics to targeted cells.

The articles, in advance online publication, represent"two very important milestones in RNA nanotherapy," says Guo.

"One problem in RNA therapy is the requirement for the generation of relatively large quantities of RNA," he says."In this research, we focused on solving the most challenging problem of industry-scale production of large RNA molecules by a bipartite approach, finding that pRNA can be assembled from two pieces of smaller RNA modules."

Guo, Dane and Mary Louise Miller Endowed Chair of biomedical engineering, serves as director of the National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Program at UC. He has focused his research on RNA for decades, pioneering its use as a versatile building block for nanotechnology, or for the engineering of functional systems at the molecular scale. In 1987, he discovered a packaging RNA (pRNA) in the bacteriophage phi29 virus which can gear a motor to package DNA into the viral protein shell. In 1998, his lab discovered that pRNA can self-assemble or be engineered into nanoparticles to gear the motor.

In his most recent research, Guo and colleagues detail multiple approaches for the construction of a functional 117-base pRNA molecule containing small interfering RNA (siRNA). siRNA has already been shown to be an efficient tool for silencing genes in cells, but previous attempts have produced chemically modified siRNA lasting only 15-45 minutes in the body and often inducing undesired immune responses.

"The pRNA particles we constructed to harbor siRNA have a half life of between five and 10 hours in animal models, are non-toxic and produce no immune response," says Guo."The tenfold increase of circulation time in the body is important in drug development and paves the way towards clinical trials of RNA nanoparticles as therapeutic drugs."

Guo says the size of the constructed pRNA molecule is crucial for the effective delivery of therapeutics to diseased tissues.

"RNA nanoparticles must be within the range of 15 to 50 nanometers," he says,"large enough to be retained by the body and not enter cells randomly, causing toxicity, but small enough to enter the targeted cells with the aid of cell surface receptions.

In the paper,"Assembly of Therapeutic pRNA-siRNA Nanoparticles Using Bipartite Approach," Guo and his colleagues used two synthetic RNA fragments to create the 117-base pRNA, which was able to further assemble with other pRNA molecules and function in the bacteriophage phi29 viral motor to package DNA.

"The two-piece approach in pRNA synthesis overcame challenges of size limitations in chemical synthesis of RNA nanoparticles," Guo wrote."The resulting nanoparticles were competent in delivering and releasing therapeutics to cells and silencing the genes within them. The ability to chemically synthesize these nanoparticles allows for further chemical modification of RNA for stability and specific targeting."

The second publication,"Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery," builds on that research, demonstrating that modified three-dimensional pRNA nanoparticles were readily manufactured through the two-piece approach. The modified nanoparticles were resistant to common enzymes that can attack and degrade RNA and remained chemically and metabolically stable.

Furthermore, when delivered to target cells in an animal model, the nanoparticles were non-toxic and did not induce an immune response, enabling the nanoparticles to bind to cancer cells in vivo.

Previous studies have encased therapeutic siRNA in a polymer coating or liposome for delivery to cells.

"To our knowledge, this is the first naked RNA nanoparticles to have been comprehensively examined pharmacologically in vivo and demonstrated to be safe, as well as deliver itself to tumor tissues by a specific targeting mechanism," he says."It suggests that the pRNA nanoparticles without coating have all the preferred pharmacological features to serve as an efficient nanodelivery platform for broad medical applications."

Co-authors of"Assembly of Therapeutic pRNA-siRNA Nanoparticles Using Bipartite Approach" include Yi Shu, Mathieu Cinier, Sejal Fox and Nira Ben-Johnathan of the University of Cincinnati.

Co-authors of"Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery" include Sherine Abdelmawla and Songchuan Guo of Kylin Therapeutics and Purdue University, Limin Zhang, Sai M Pulukuri, Prithviraj Patankar, Patrick Conley, Joseph Trebley and Qi-Xiang Li of Kylin Therapeutics.

This study was funded by National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Institute of General Medical Sciences and Kylin Therapeutics Inc. Guo is co-founder of Kylin Therapuetics.


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Wednesday, April 20, 2011

New Biosensor Microchip Could Speed Up Drug Development, Researchers Say

A single centimeter-sized array of the nanosensors can simultaneously and continuously monitor thousands of times more protein-binding events than any existing sensor. The new sensor is also able to detect interactions with greater sensitivity and deliver the results significantly faster than the present"gold standard" method.

"You can fit thousands, even tens of thousands, of different proteins of interest on the same chip and run the protein-binding experiments in one shot," said Shan Wang, a professor of materials science and engineering, and of electrical engineering, who led the research effort.

"In theory, in one test, you could look at a drug's affinity for every protein in the human body," said Richard Gaster, MD/PhD candidate in bioengineering and medicine, who is the first author of a paper describing the research that is in the current issue ofNature Nanotechnology,available online now.

The power of the nanosensor array lies in two advances. First, the use of magnetic nanotags attached to the protein being studied -- such as a medication -- greatly increases the sensitivity of the monitoring.

Second, an analytical model the researchers developed enables them to accurately predict the final outcome of an interaction based on only a few minutes of monitoring data. Current techniques typically monitor no more than four simultaneous interactions and the process can take hours.

"I think their technology has the potential to revolutionize how we do bioassays," said P.J. Utz, associate professor of medicine (immunology and rheumatology) at Stanford University Medical Center, who was not involved in the research.

A microchip with a nanosensor array (orange squares) is shown with a different protein (various colors) attached to each sensor. Four proteins of a potential medication (blue Y-shapes), with magnetic nanotags attached (grey spheres), have been added. One medication protein is shown binding with a protein on a nanosensor.

Members of Wang's research group developed the magnetic nanosensor technology several years ago and demonstrated its sensitivity in experiments in which they showed that it could detect a cancer-associated protein biomarker in mouse blood at a thousandth of the concentration that commercially available techniques could detect. That research was described in a 2009 paper inNature Medicine.

The researchers tailor the nanotags to attach to the particular protein being studied. When a nanotag-equipped protein binds with another protein that is attached to a nanosensor, the magnetic nanotag alters the ambient magnetic field around the nanosensor in a small but distinct way that is sensed by the detector.

"Let's say we are looking at a breast cancer drug," Gaster said."The goal of the drug is to bind to the target protein on the breast cancer cells as strongly as possible. But we also want to know: How strongly does that drug aberrantly bind to other proteins in the body?"

To determine that, the researchers would put breast cancer proteins on the nanosensor array, along with proteins from the liver, lungs, kidneys and any other kind of tissue that they are concerned about. Then they would add the medication with its magnetic nanotags attached and see which proteins the drug binds with -- and how strongly.

"We can see how strongly the drug binds to breast cancer cells and then also how strongly it binds to any other cells in the human body such as your liver, kidneys and brain," Gaster said."So we can start to predict the adverse affects to this drug without ever putting it in a human patient."

It is the increased sensitivity to detection that comes with the magnetic nanotags that enables Gaster and Wang to determine not only when a bond forms, but also its strength.

"The rate at which a protein binds and releases, tells how strong the bond is," Gaster said. That can be an important factor with numerous medications.

"I am surprised at the sensitivity they achieved," Utz said."They are detecting on the order of between 10 and 1,000 molecules and that to me is quite surprising."

The nanosensor is based on the same type of sensor used in computer hard drives, Wang said.

"Because our chip is completely based on existing microelectronics technology and procedures, the number of sensors per area is highly scalable with very little cost," he said.

Although the chips used in the work described in theNature Nanotechnologypaper had a little more than 1,000 sensors per square centimeter, Wang said it should be no problem to put tens of thousands of sensors on the same footprint.

"It can be scaled to over 100,000 sensors per centimeter, without even pushing the technology limits in microelectronics industry," he said.

Wang said he sees a bright future for increasingly powerful nanosensor arrays, as the technology infrastructure for making such nanosensor arrays is in place today.

"The next step is to marry this technology to a specific drug that is under development," Wang said."That will be the really killer application of this technology."

Other Stanford researchers who participated in the research and are coauthors of theNature Nanotechnologypaper are Liang Xu and Shu-Jen Han, both of whom were graduate students in materials science and engineering at the time the research was done; Robert Wilson, senior scientist in materials science and engineering; and Drew Hall, graduate student in electrical engineering. Other coauthors are Drs. Sebastian Osterfeld and Heng Yu from MagArray Inc. in Sunnyvale. Osterfeld and Yu are former alumni of the Wang Group.

Funding for the research came from the National Cancer Institute, the National Science Foundation, the Defense Advanced Research Projects Agency, the Gates Foundation and National Semiconductor Corporation.


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