Philip Geoffrey Saffman, 77

Philip Geoffrey Saffman, an influential teacher and noted researcher in fluid mechanics, died peacefully after a long illness on Sunday, August 17, in Pasadena. He was 77 years old. 

Saffman, the Theodore von Kármán Professor of Applied Mathematics and Aeronautics, Emeritus, at the California Institute of Technology, studied vortex instability and the dynamics of arrays of vortices. In particular, he looked into the phenomenon of viscous fingering, which became known as the "Saffman-Taylor Instability." This occurs when a low-viscosity fluid is injected into a higher-viscosity fluid.

His work with vortices also led him to a new mathematical analysis of the wake turbulence caused by jets as they take off, resulting in a theory describing the conditions behind several aircraft accidents.

Saffman was born in Leeds, England, and received his BA, MA, and PhD from the University of Cambridge. In 1964 he accepted Caltech's appointment as a full professor in fluid mechanics within the Division of Engineering and Applied Science. He was named von Kármán Professor in 1995.

He was a Fellow of the American Academy of Arts and Sciences and in 1988 was elected a Fellow to the Royal Society, England's premiere scientific organization. He also received the Otto Laporte Award from the American Physical Society.

Saffman served as associate editor for both the Journal of Fluid Mechanics and Physical Review Letters and was most recently an editorial board member for the journal Studies in Applied Mathematics.

Saffman is survived by his wife, Ruth; children Louise, Mark, and Emma; and grandchildren Timothy, Gregory, Rae (née Sarah), Jenny, Nadine, Aaron, Miriam, and Alexandra.

Writer: 
Jon Weiner
Images: 
Writer: 
Exclude from News Hub: 
No
News Type: 
In Our Community

Caltech Researchers Awarded $10 Million for Molecular Programming Project: Collaborative project may lead to revolutionary changes

PASADENA, Calif.-- The National Science Foundation's Expeditions in Computing program has awarded $10 million to the Molecular Programming Project, a collaborative effort by researchers at the California Institute of Technology and the University of Washington to establish a fundamental approach to the design of complex molecular and chemical systems based on the principles of computer science. 

The focus of their study, molecular programs, are collections of molecules that may perform a computation, fabricate an object, or control a system of molecular sensors and actuators. The project aims to develop tools and theories for molecular programming--such as programming languages and compilers--that will enable systematic design and implementation in the laboratory.

Eventually, molecular programs could be used to manufacture nanoscale objects, to create biochemical circuitry to probe the inner workings of cells, and as "programmable therapies" placed within living cells to diagnose and directly respond to diseases.

"Our project is a response to the fact that the molecular systems people are building today are now so complex, and their behavior so intricate, that future progress hinges on developing the intellectual and practical tools for mastering that complexity, the kinds of tools that computer science has already developed for silicon computers," says Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at Caltech, and principal investigator on the project.

"The Molecular Programming Project is one of the 'outputs' from our investment in the Information Science and Technology (IST) initiative over the years," says co-investigator Richard M. Murray, the Thomas E. and Doris Everhart Professor of Control and Dynamical Systems and director of the IST program at Caltech. "The Expeditions program is intended to identify future directions in computing that have the potential to lead to 'revolutionary' changes. The collaborations between the various investigators, many of which were funded by IST, were instrumental in bringing together the team of researchers who are embarking on this project," he says. Examples include research projects and workshops funded by Caltech's Center for Biological Circuit Design, an IST initiative.

The Expeditions in Computing award, sponsored by the NSF's Directorate for Computer and Information Science and Engineering, is designed to provide investigators with the opportunity to pursue "ambitious, fundamental research agendas that promise to define the future of computing and information."

The other members of the collaboration are Jehoshua (Shuki) Bruck, the Gordon and Betty Moore Professor of Computation and Neural Systems and Electrical Engineering at Caltech; Niles A. Pierce, associate professor of applied and computational mathematics and bioengineering at Caltech; Paul W. Rothemund, senior research associate in bioengineering, computer science, and computation and neural systems at Caltech; and Eric Klavins, assistant professor of electrical engineering at the University of Washington in Seattle.

 

Writer: 
Kathy Svitil
Images: 
Writer: 
Exclude from News Hub: 
No
News Type: 
In Our Community

Caltech Bioengineers Develop "Microscope on a Chip"

PASADENA, Calif.--Researchers at the California Institute of Technology have turned science fiction into reality with their development of a super-compact high-resolution microscope, small enough to fit on a finger tip. This "microscopic microscope" operates without lenses but has the magnifying power of a top-quality optical microscope, can be used in the field to analyze blood samples for malaria or check water supplies for giardia and other pathogens, and can be mass-produced for around $10.

"The whole thing is truly compact--it could be put in a cell phone--and it can use just sunlight for illumination, which makes it very appealing for Third-World applications," says Changhuei Yang, assistant professor of electrical engineering and bioengineering at Caltech, who developed the device, dubbed an optofluidic microscope, along with his colleagues at Caltech.

The new instrument combines traditional computer-chip technology with microfluidics--the channeling of fluid flow at incredibly small scales. An entire optofluidic microscope chip is about the size of a quarter, although the part of the device that images objects is only the size of Washington's nose on that quarter.

"Our research is motivated by the fact that microscopes have been around since the 16th century, and yet their basic design has undergone very little change and has proven prohibitively expensive to miniaturize. Our new design operates on a different principle and allows us to do away with lenses and bulky optical elements," says Yang.

The fabrication of the microscopic chip is disarmingly simple. A layer of metal is coated onto a grid of charge-coupled device (CCD) sensor (the same sensors that are used in digital cameras). Then, a line of tiny holes, less than one-millionth of a meter in diameter, is punched into the metal, spaced five micrometers apart. Each hole corresponds to one pixel on the sensor array. A microfluidic channel, through which the liquid containing the sample to be analyzed will flow, is added on top of the metal and sensor array. The entire chip is illuminated from above; sunlight is sufficient.

When the sample is added, it flows--either by the simple force of gravity or drawn by an electric charge--horizontally across the line of holes in the metal. As cells or small organisms cross over the holes, one hole after another, the objects block the passage of light from above onto the sensor below. This produces a series of images, consisting of light and shadow, akin to the output of a pinhole camera.

Because the holes are slightly skewed, so that they create a diagonal line with respect to the direction of flow, the images overlap slightly. All of the images are then pieced together to create a surprisingly precise two-dimensional picture of the object.

Yang is now in discussion with biotech companies to mass-produce the chip. The platform into which the chip is integrated can vary depending upon the needs of the user. For example, health workers in rural areas could carry cheap, compact models to test individuals for malaria, and disposable versions could be carried into the battlefield. "We could build hundreds or thousands of optofluidic microscopes onto a single chip, which would allow many organisms to be imaged and analyzed at once," says Xiquan Cui, the lead graduate student on the project.

In the future, the microscope chips could be incorporated into devices that are implanted into the human body. "An implantable microscope analysis system can autonomously screen for and isolate rogue cancer cells in blood circulation, thus, providing important diagnostic information and helping arrest the spread of cancer," says Yang.

The paper, "Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging," was published July 28 in the early online edition of the Proceedings of the National Academy of Sciences. Yang's coauthors are graduate students Xiquan Cui and Lap Man Lee; postdoctoral research associates Xin Heng and Weiwei Zhong; Paul W. Sternberg, the Thomas Hunt Morgan Professor of Biology and an Investigator with the Howard Hughes Medical Institute; and Demetri Psaltis, the Thomas G. Myers Professor of Electrical Engineering at Caltech.

The work was funded by DARPA's Center for Optofluidic Integration at Caltech, the Wallace Coulter Foundation, the National Science Foundation, and the National Institutes of Health.

Writer: 
Kathy Svitil
Images: 
Writer: 

Three New Howard Hughes Medical Institute Investigators Named

PASADENA, Calif.--Every three years, the Howard Hughes Medical Institute (HHMI) appoints the nation's most creative biomedical scientists as investigators, giving them millions of dollars to unfetter their ambitious research plans. This year, three of the 56 newly named HHMI investigators come from the California Institute of Technology.

David Chan, Michael Elowitz, and Grant Jensen were each chosen for their potential to "bring new and innovative ways of thinking about biology to the HHMI community," says Thomas R. Cech, president of HHMI. "They are poised to advance scientific knowledge dramatically in the coming years, and we are committed to providing them with the freedom and flexibility to do so," he adds.

Chan, an associate professor of biology, specializes in how mitochondria--often called the powerhouses of biological cells--interact with each other. While this field, called mitochondrial dynamics, is still in its infancy, its implications are far-reaching. Chan has found that the loss of mitochondrial dynamics in mice, for example, leads to defects in placental tissue, in neurons in the cerebellum, and in skeletal muscle. He also studies the connection between accumulating damage in human mitochondria and the process of aging.

"I was surprised and very honored to be selected as an HHMI investigator. I am deeply grateful to advisors and colleagues who supported my career and encouraged me to apply," Chan says. "This appointment will help us to aggressively pursue ongoing projects in the lab, and also to expand into a couple of new, exciting areas in mitochondrial biology."

Biology and physics form a natural combination for Michael Elowitz, who builds genetic circuits and inserts them into living bacteria. The bacteria execute the tasks they are programmed to do, such as blinking on and off like a twinkling light. As an assistant professor of biology and applied physics and a Bren Scholar, Elowitz is fundamentally interested in how cells' own genetic circuits dictate what type of cells they become.

In work that overturned the steadfast notion that genes and networks of genes operate in a predictable and fixed fashion, he and his colleagues showed that key properties of the cell--like how actively it turns out different proteins--are intrinsically random. To show that randomness is used to more accurately control the shapes and patterns that make organisms work, Elowitz is turning to larger and more complex animal cells. "I'm grateful to HHMI for the amazing opportunity this appointment presents to focus as much as possible on research. The funds will enable us to explore new directions, especially allowing us to expand approaches we've previously developed primarily in bacteria to mammalian cells."

Assistant Professor of Biology Grant Jensen combines emerging electron microscope technologies with biology to image biological structures that could, until recently, only be imagined. One example of such a structure is the motor that drives the flagella of spirochete bacteria. Jensen has also shown key structures of proteins in HIV and has demonstrated that, contrary to long-held convictions, bacteria have a cytoskeleton.

Going beyond the static images, Jensen has created animations for biological processes. Applying the same technology used in movies, he showed the process of HIV maturation and bacterial motility. "It has been exciting to begin thinking of the additional research we will now be able to do," says Jensen of the award. "We're going to move more quickly now into complementing our current electron microscopical methods with light microscopy, and also begin modeling our hypotheses computationally."

The selection of Chan, Elowitz, and Jensen brings to 10 the total number of HHMI investigators at Caltech, eight of whom are among the 36 total faculty of the Division of Biology. The HHMI promotes its principle of "people, not projects" by appointing scientists as investigators, rather than awarding research grants. Investigators are urged to take risks, to explore unproven avenues, and to embrace the unknown, even if it means uncertainty or the chance of failure.

A nonprofit medical research organization, HHMI was established in 1953 by the aviator-industrialist Howard Hughes. The institute, headquartered in Chevy Chase, Maryland, is one of the largest philanthropies in the world, with an endowment of $18.3 billion at the close of the 2007 fiscal year. HHMI spent $599 million in support of biomedical research and $86 million for support of a variety of grants programs in fiscal year 2007.

For more information on HHMI and this year's investigator's, please visit: http://www.hhmi.org/news/20080527.html

Writer: 
Elisabeth Nadin
Writer: 
Exclude from News Hub: 
Yes

New Rosen Bioengineering Center Funded

PASADENA, Calif.- Seeing a burgeoning new research field at the interface of biology and engineering, the Benjamin M. Rosen Family Foundation of New York has donated $18 million to the California Institute of Technology to establish the Donna and Benjamin M. Rosen Bioengineering Center.

"Ben and Donna Rosen are recognizing how critical bioengineering is to the future of Caltech, science, and society, and they also appreciate the power an endowment can have in sustaining such an initiative," said Caltech President Jean-Lou Chameau. "The Institute is fortunate to have them as friends."

The Rosen Center will advance both basic scientific exploration and development of engineering analysis and synthetic approaches. Innovations in these areas are resulting in rugged and inexpensive diagnostic devices, in new insights into the functioning of the heart, and in the engineering of molecular devices capable of recognizing and responding to disease processes in individual cells.

Bioengineering developed at Caltech in recognition of the fact that biology is becoming more accessible to approaches that are commonly used in engineering, including mathematical modeling, systems theory, computation, and abstraction-based synthesis. At each level of organization, from the molecule to the cell to the organ, the accelerating pace of discovery in the biological sciences reveals new design principles that are of fundamental importance in understanding living organisms, and that will have important practical applications in future synthetic biological and biomedical systems and devices.

"Bioengineering arose at Caltech from the grassroots efforts of a handful of committed faculty coming together to establish a graduate option with great enthusiasm," said Scott Fraser, the Anna L. Rosen Professor of Biology and professor of bioengineering, who will lead the new center. "This gift will endow the program allowing it to foster the most innovative collaborative research. Such funding fuels innovation by offering support to venturesome efforts far earlier than would be possible through conventional granting agencies."

"There are a few times in history when diverse sciences, technologies and researchers fortuitously come together at the same time and at the same place to make possible great achievements for mankind," said Rosen. "This is one of those times, and Caltech is one of those places. We're honored to be able to play a small part in helping start this exciting new Caltech Bioengineering Initiative."

According to Ed Stolper, Caltech's provost, "Our current challenge is to provide an intellectual and programmatic focus for our growing teaching and research programs in bioengineering, spanning synthetic, systems, and computational biology; biomechanics and bio-inspired design; and development of novel biotechnologies. The Rosen Center will provide such a focus and critical support for these activities, which span many of the Institute's existing programs."

"Caltech's Bioengineering Center will foster the foundational work that will blossom into the next generation of tissue regeneration and diagnostic instrumentation," said Fraser. "The results of these innovations will make tools once considered too futuristic for anything but science fiction films into practical devices that can be carried in a physician's rear pocket."

Ben Rosen was founding chairman of Compaq Computer Corp. and a founding partner of Sevin Rosen Funds, a venture capital firm that has provided initial financing for more than 100 technology companies. Previously, he was vice president and senior electronics analyst at Morgan Stanley & Co., and before that he was an electronics engineer at Raytheon and Sperry Gyroscope. In 1992, Computerworld chose Rosen as one of 25 people in the computer industry "who changed the world." Rosen joined Caltech's board of trustees in 1986 and became chairman in 2001. He is also a member of the board of overseers and managers of Memorial Sloan-Kettering Cancer Center, a member of the board of overseers of Columbia Business School, and a director of the New York Philharmonic. Rosen earned a bachelor's degree in electrical engineering at Caltech in 1954. He also earned a master's in electrical engineering from Stanford and an MBA from Columbia University.

Donna Rosen was the former owner/director of Galerie Simonne Stern in New Orleans for 23 years until she moved to New York in 2002. She pioneered the New Orleans Warehouse District as the "Art District of New Orleans." She is a national trustee of the New Orleans Museum of Art; vice chairman of the board of American Friends of the British Museum; board member of The Society of Memorial Sloan-Kettering Cancer Hospital; and trustee of Second Stage Theater.

 

Writer: 
Jill Perry
Images: 
Writer: 
Exclude from News Hub: 
No
News Type: 
In Our Community

One of Five Centers of Excellence for Predictive Science

PASADENA, Calif.--With a $17 million grant from the National Nuclear Security Administration (NNSA), the California Institute of Technology becomes one of five new centers of excellence that will focus on the emerging field of predictive science.

Michael Ortiz, the Dotty and Dick Hayman Professor of Aeronautics, professor of mechanical engineering, and director of Caltech's new Predictive Science Academic Alliance Program (PSAAP) Center, says Caltech will focus its efforts on the high-energy density dynamic response of materials, with demonstrations of hypervelocity impact response.

Hypervelocity impact is central to a number of scientific and application areas, including the design of protective shields for space structures and the understanding of meteorite impact cratering, Ortiz says. Accurate computer simulation is critical to the understanding of experiments that involve velocities reaching 10 kilometers per second, pressures in the megabar range, and extraordinarily high temperatures and deformation rates.

"The range of complex physics that is set in motion during hypervelocity impact is staggering," Ortiz remarks. "It includes melting, vaporization, and plasmas; hydrodynamic instabilities, mixed-phase flows, and mixing; and fracture, fragmentation, spall, and ejecta.

"The modeling and simulation of each of these phenomena in isolation is a scientific challenge in itself, but the predictive simulation of their coupled integral behavior is truly at the grand-challenge level and provides an exceedingly exacting test of predictive science."

Predictive science is the application of verified and validated computational simulations to predict the behavior of complex systems where routine experiments are not feasible. The research effort, which involves Caltech and four other selected PSAAP centers, will focus on unclassified applications of interest to NNSA and its three national laboratories: Lawrence Livermore National Laboratory, Los Alamos National Laboratory, and Sandia National Laboratories.

"At the core of this game-changing 'predictive science' paradigm shift is the ability to quantify uncertainties in the performance of complex systems by means of concerted and highly integrated experimental, computational, and analytical programs," Ortiz remarks.

The PSAAP centers, named by NNSA on March 7, will develop models and software for their large-scale simulations, as well as methods associated with the emerging disciplines of verification and validation and uncertainty quantification. The centers will be administered by the office of Advanced Simulation and Computing (ASC), which has funded the ASC Center at Caltech for the past 10 years.

"Caltech is in a unique position to advance the field of predictive science because of its culture of close interdisciplinary work among its faculty and research groups, exemplified by the highly successful ASC center led by Dan Meiron, and because of its longstanding tradition of approaching modeling and simulation at its most fundamental level," Ortiz says.

Experiments will be performed at experimental facilities in Caltech's Graduate Aeronautical Laboratories (GALCIT), including the newly-constructed Small Particle Hypervelocity Impact Range (SPHIR), notes Ares Rosakis, the von Kármán Professor of Aeronautics, professor of mechanical engineering, and director of GALCIT.

The executive director of Caltech's PSAAP Center is Mark Stalzer, executive director of Caltech's Center for Advanced Computing Research (CACR). The PSAAP Center will coordinate activities in areas including computational fluid dynamics, led by Dan Meiron, the Jones Professor of Applied and Computational Mathematics and Computer Science; computational science and engineering, led by CACR's principal computational scientist, Michael Aivazis; experimental science, led by Rosakis; solid dynamics and materials, led by Ortiz; and uncertainty quantification, led by Houman Owhadi, assistant professor of applied and computational mathematics and control and dynamical systems.

For further details on PSAAP, visit http://www.sandia.gov/NNSA/ASC/univ/psaap.html. 

Writer: 
Elisabeth Nadin
Images: 
Writer: 
Exclude from News Hub: 
No
News Type: 
In Our Community

Mechanical Engineers Defy Gravity

PASADENA, Calif., and Cape Canaveral, Fl.--On the day that California Institute of Technology mechanical-engineering students will fling projectiles through the air in their annual design competition, two Caltech mechanical-engineering alumni will hurtle through space on the shuttle Endeavor.

The theme of this year's ME 72 Engineering Design Contest, the culmination of an engineering design laboratory for undergraduate students, is "fire and fly." It is fitting for a day on which astronauts and Caltech alumni Garrett Reisman and Robert Behnken lift off on the Endeavor space shuttle as part of a seven-man team en route to the International Space Station. The competition will be held on Tuesday, March 11, at 1 p.m. on Caltech's North Athletic Field, and the shuttle is scheduled for liftoff from Cape Canaveral, Florida.

Chris Brennen, Caltech's Hayman Professor of Mechanical Engineering, helped guide the ME 72 students through their test phases. He'll be at the shuttle launch on the day of their competition, but he remarks, "I was deeply torn between attending the space-shuttle launch and the ME 72 final contest." Reisman was his former student who became a close friend and married another mechanical engineering grad, Simone Francis.

Reisman, a space station flight engineer, will remain at the International Space Station for about six months and Behnken will return home after 16 days in orbit. A third Caltech alumnus, Greg Chamitoff, will then climb aboard Endeavor for the next launch, scheduled for March 28.

Brennen has close ties to NASA. He advised the agency on the shuttle's liquid-oxygen pumps and developed a lab at Caltech for creating and testing the main engine turbo pumps. When that facility was decommissioned several years ago, NASA disassembled it and moved it to the Marshall Space Flight Center in Huntsville, Alabama.

Brennen has spent much of his career investigating phenomena related to fluid flow, which he says was particularly useful in prepping students for ME 72 this year. "This year's ME 72 is different from previous contests because it involves some aerodynamics and fluid dynamics. It requires significantly more analysis of the mechanics of the device and the flight of the projectile in order to maximize the performance," he says.

On contest day, Brennen leaves the students in the hands of Joel Burdick, a professor of mechanical engineering and bioengineering at Caltech, who also helped them prepare. "We've had two contests already and tested and made adjustments. They're ready to go," Brennen says.

The competition centers on two basic constructions. The first is a ground-level launching device. The second is its 50-gram payload, "a projectile or flying device that will rise from a ground-level launcher, fly over a rope hurdle and then glide or be projected as far as possible over clear ground," according to the project description.

What happens after launch will be anybody's guess. In accordance with ME 72 tradition, the students may turn their machines on each other, navigating the airborne projectiles via remote control to tackle opponents' devices. According to the contest rules, "special admiration and an extra bonus" go to those payloads that land in a specially marked, two-meter-wide circular region beyond the basic target zone.

For further contest specifications, visit http://robotics.caltech.edu/~me72/. For more on Endeavor, go to http://www.nasa.gov/mission_pages/shuttle/main/. 

Writer: 
Elisabeth Nadin
Writer: 

New Method for Creating Tough Metallic Glass Composites

PASADENA, Calif.--Scientists at the California Institute of Technology have developed a new strategy for creating "liquid metal" that makes it able to bend significantly without breaking, while retaining a strength twice that of titanium. It is among the toughest, or least brittle, known materials, and could be used anywhere that strong metal alloys are traditionally found, but may prove most useful in the aerospace industry, where lower density means fuel savings.

When commercialized metallic glass known as Liquidmetal and Vitreloy hit the market several years ago in the forms of golf clubs and baseball bats, it was too brittle to withstand much duress. Now, says Douglas Hofmann, a Caltech materials science graduate student and lead author of a paper presenting the method for making the new material, it can be made to flex and can be produced at relatively low cost. "Metallic glasses now have among the highest toughness of any materials," he says.

Like window glass, metallic glass has no crystalline structure, but it is made with combinations of zirconium, titanium, copper, nickel, platinum, or other metals. Although the random arrangement of elements makes the material as strong as some of the strongest known metals, it also makes it very brittle. Most other metals deform plastically, meaning that under a heavy load, the deformation before ultimate fracture is permanent. Metallic glass behaves like an elastic band, which regains its original shape when released, but snaps when stretched past a certain point. A piece of metallic glass with any substantial thickness shattered easily when it was bent, and, Hofmann points out, "you couldn't build a bridge out of it. It breaks with no visual precursor.

"Many researchers in metallic glasses are trying to make them useful in structural applications," Hofmann says. He and his colleagues at Caltech have finally accomplished exactly that. They experimented with different combinations of metals to create a new version by manipulating the ratios of starting materials. They were guided by previous work by coauthor William Johnson, Caltech's Mettler Professor of Engineering and Applied Science, and his collaborators. Over the past two decades, these scientists had found that ductility--the ability of a material to deform in tension before breaking--was linked to the formation of branching, crystalline structures called dendrites within the metallic glass.

The team experimented first with the size of the dendrites. Hofmann and Johnson started by noting that when metallic glasses are bent, 10-nanometer-wide features called shear bands rip right through glass that is thicker than one millimeter, but are stabilized in thin glass. "The bending experiments told us that the size of the particles we need to add is proportional to the length scale of the shear bands before they become catastrophic," Hofmann describes.

In this time of exploding interest in nanotechnology, Hofmann was surprised to find that the dendrites had to be on the order of hundreds of microns in size, many thousands of times the size of the shear bands. The second major insight was that they also had to be softer than the surrounding metallic glass.

Because they are crystalline, the dendrites deform plastically, and their size blocks a single shear band from growing into a catastrophic crack. "It takes more energy to move a shear band forward than it takes to form a new shear band," notes Hofmann. "We took an alloy that broke with one shear band and made it make countless shear bands.

"We took a metallic glass, which is considered a brittle material, and showed that by making a designed composite out of it, we can span the entire space of toughness," Hofmann remarks. "The tougher it is, the harder it is to drive a crack through it. Now we have ductility and toughness," he claims.

Because the new metallic glass is tough and strong and has relatively low density, its obvious applications would be in any structure that incorporates titanium. In aerospace technology, these properties are crucial to minimizing weight and saving fuel costs.

But, says Hofmann, "we're not trying to replace titanium; we're trying to find applications where a stronger material would be useful," particularly because the material is still difficult to make. Still, he points to one particularly alluring quality: "you can use less of it because it's stronger."

The paper appears in the February 28 issue of the journal Nature. All experiments were performed in Caltech's Keck Laboratory of Engineering Materials. The other authors are material scientists Jin-Yoo Suh, Aaron Wiest, and Gang Duan, Caltech graduate students; Mary-Laura Lind, a visiting scientist; and Marios D. Demetriou, a senior research fellow. 

Writer: 
Elisabeth Nadin
Writer: 

New Technique Makes Tissues Transparent

PASADENA, Calif.-- If humans had see-through skin like a jellyfish, spotting disease like cancer would be a snap: Just look, and see a tumor form or grow.

But humans, of course, are not remotely diaphanous. "The reason a person is not transparent is that their tissues are highly scattering," sending light waves careening through the tissue instead of straight through, as they would through the tissue of that jellyfish, explains Changhuei Yang of the California Institute of Technology.

This scattering, in addition to rendering all of us opaque, makes the detection of disease a much trickier issue, requiring a host of diagnostic tests and procedures. But not, perhaps, for much longer, thanks to a new optical trick developed by Yang, an assistant professor of electrical engineering and bioengineering, and his colleagues, that counteracts the scattering of light and removes the distortion it creates in images.

A study describing the process appears in the February issue of the journal Nature Photonics.

It is well known that light scattering in a material is not exactly the random and unpredictable process one might imagine. In fact, scattering is deterministic, which means that the path that a beam of light takes as it traverses a particular slice of tissue and bounces and rebounds off of individual cells, is entirely predictable; if you again bounce light through that same swath of cells, it will scatter in exactly the same way.

The process is even reversible; if the individual photons of light that scattered through the tissue could be collected and sent back through the tissue, they'd bounce back along the same path and converge at the original spot from which they were sent. "The process is similar to the scattering of billiard balls on a pool table. If you can precisely reverse the paths and velocities of the billiard balls, you can cause the billiard balls to reassemble themselves into a rack," Yang explains.

Yang, along with his colleagues at Caltech, École Polytechnique Fédérale de Lausanne in Switzerland, and MIT, exploited this phenomenon to offset the murky nature of our tissues.

Their technique, called turbidity suppression by optical phase conjugation (TSOPC), is surprisingly simple. The scientists used a holographic crystal to record the scattered light pattern emerging from a 0.46-mm-thick piece of chicken breast. They then holographically played the pattern back through the tissue section to recover the original light beam. "This is similar to grabbing hold of the direction of time flow and turning it around; the time-reversed photons must retrace their trajectories through the tissue," Yang says. "The task is formidable though, as this is comparable to starting with a rack of 10 to the 18th power billiard balls (or photons), scattering them around the table, and attempting to reassemble them into a rack."

"Until we did this study, it wasn't clear that the effect will be observable with biological tissues. We were pleasantly surprised that the effect was readily observable and remarkably robust," Yang says. "This study opens up numerous possibilities in the use of optical time reversal in biomedicine."

One possible use of the technique is in photodynamic therapy, in which a highly focused beam of light is aimed at cancerous cells that have absorbed cell-killing light-sensitive compounds. When the light hits the cells, the compounds are activated and destroy the cells. Photodynamic therapy is most effective in treating cancers on the skin surface. Yang's technique, however, offers a way to concentrate light onto cancer-killing compounds located more deeply within tissue.

Yang's idea is to inject strongly light-scattering particles that are coated with light-activated cancer-killing drugs into diseased tissue. Shine a beam of light into the tissue, and it would be reflected off the scattering compounds as it bounces through the tissue. Some of the scattered light would return to the source, where it could be recorded as a hologram.

This hologram would contain information about the path that the scattered light took through the tissue, and, in effect, describe the optimal path BACK toward the light-scattering molecule--and the cancer-killing compounds. Playing back the signal with a stronger burst of light will then activate the therapeutic drugs, which kill the cancer cells.

In addition, the technique could offer a way to power miniature implants buried deep within tissues. "If you take a quick survey of what is out there at present, you will see that implants are fairly large," Yang says. "For example, a pacemaker is about the size of a cell phone. Why are they so big? A large part of the reason is because they need to carry their own power sources."

The key to making smaller implants, then--say, the size of a pen tip--is to eliminate the power sources. "I think implants that carry photovoltaic receivers are particularly promising," he says. "The effect can be applied to tailor light-delivery mechanisms to efficiently channel light into tissues and onto these implants."

Zahid Yaqoob, a postdoctoral fellow in electrical engineering at Caltech, performed most of the experiments reported in the paper. The other authors of the paper are Demetri Psaltis, professor of optics and dean of engineering, École Polytechnique Fédérale de Lausanne in Switzerland, and Michael S. Feld, a professor of physics at MIT. 

Writer: 
Kathy Svitil
Writer: 

Programming Biomolecular Self-Assembly Pathways

PASADENA, Calif.--Nature knows how to make proteins and nucleic acids (DNA and RNA) dance to assemble and sustain life. Inspired by this proof of principle, researchers at the California Institute of Technology have demonstrated that it is possible to program the pathways by which DNA strands self-assemble and disassemble, and hence to control the dynamic function of the molecules as they traverse these pathways.

The team invented a versatile DNA motif with three modular domains that can be made to interact with complementary domains in other species of the same motif. Rewiring these relationships changes the dynamic function of the system. To make it easier to design such systems, the researchers developed a graphical abstraction of the motif that can be used to write "molecular programs." As described in the January 17 issue of the journal Nature, the team experimentally demonstrated the execution of four such programs, each illustrating a different class of dynamic function.

The study was performed by a team of four at Caltech: Niles Pierce, associate professor of applied and computational mathematics and bioengineering; Peng Yin, senior postdoctoral scholar in bioengineering and computer science; Harry Choi, graduate student in bioengineering; and Colby Calvert, research technician.

Programming pathways is a bit like planning a road trip. The final destination might be important, but the true enjoyment is picking and traveling the route. In the test tube, the goal is not solely to direct the molecules to assemble into a target structure, but to engage them in a sequence of maneuvers so as to implement a prescribed dynamic function before the system reaches equilibrium. The energy to power the reactions is stored in the molecules themselves. Each molecule is initially trapped in a high-energy state so that it can release this energy as it engages in handshakes with other molecules.

A molecular program is written and executed in four steps. First, the intended assembly and disassembly pathways are described using a graphical abstraction called a "reaction graph." This molecular program is then translated into molecular mechanisms described at the level of base pairing between individual complementary bases. Computational design algorithms developed in the group are then used to encode this mechanism into the DNA sequences. Finally, the program is executed by mixing the physical molecules.

To demonstrate this approach, the team experimentally demonstrated a variety of dynamic functions: catalytic formation of branched junctions, cross-catalytic circuitry with exponential system kinetics, triggered dendritic growth of molecular "trees," and autonomous locomotion of a molecular bipedal walker.

As Pierce describes it, these results take them closer to achieving a long-term goal of creating a "compiler for biomolecular function"--an automated design tool that takes as input a molecular program and provides as output a set of biomolecules that execute the desired function. He remarks, "It's about time for the stone age of molecular compilers to begin." 

Writer: 
Elisabeth Nadin
Writer: 

Pages

Subscribe to RSS - EAS