Friday, October 4, 2013

Undergraduate Teaching Assistant Orientation

Thursday, October 17, 2013
Athenaeum – The Athenaeum


Made-to-Order Materials

Caltech engineers focus on the nano to create strong, lightweight materials

The lightweight skeletons of organisms such as sea sponges display a strength that far exceeds that of manmade products constructed from similar materials. Scientists have long suspected that the difference has to do with the hierarchical architecture of the biological materials—the way the silica-based skeletons are built up from different structural elements, some of which are measured on the scale of billionths of meters, or nanometers. Now engineers at the California Institute of Technology (Caltech) have mimicked such a structure by creating nanostructured, hollow ceramic scaffolds, and have found that the small building blocks, or unit cells, do indeed display remarkable strength and resistance to failure despite being more than 85 percent air.

"Inspired, in part, by hard biological materials and by earlier work by Toby Schaedler and a team from HRL Laboratories, Caltech, and UC Irvine on the fabrication of extremely lightweight microtrusses, we designed architectures with building blocks that are less than five microns long, meaning that they are not resolvable by the human eye," says Julia R. Greer, professor of materials science and mechanics at Caltech. "Constructing these architectures out of materials with nanometer dimensions has enabled us to decouple the materials' strength from their density and to fabricate so-called structural metamaterials which are very stiff yet extremely lightweight."

At the nanometer scale, solids have been shown to exhibit mechanical properties that differ substantially from those displayed by the same materials at larger scales. For example, Greer's group has shown previously that at the nanoscale, some metals are about 50 times stronger than usual, and some amorphous materials become ductile rather than brittle. "We are capitalizing on these size effects and using them to make real, three-dimensional structures," Greer says.

In an advance online publication of the journal Nature Materials, Greer and her students describe how the new structures were made and responded to applied forces.

The largest structure the team has fabricated thus far using the new method is a one-millimeter cube. Compression tests on the the entire structure indicate that not only the individual unit cells but also the complete architecture can be endowed with unusually high strength, depending on the material, which suggests that the general fabrication technique the researchers developed could be used to produce lightweight, mechanically robust small-scale components such as batteries, interfaces, catalysts, and implantable biomedical devices.

Greer says the work could fundamentally shift the way people think about the creation of materials. "With this approach, we can really start thinking about designing materials backward," she says. "I can start with a property and say that I want something that has this strength or this thermal conductivity, for example. Then I can design the optimal architecture with the optimal material at the relevant size and end up with the material I wanted."

The team first digitally designed a lattice structure featuring repeating octahedral unit cells—a design that mimics the type of periodic lattice structure seen in diatoms. Next, the researchers used a technique called two-photon lithography to turn that design into a three-dimensional polymer lattice. Then they uniformly coated that polymer lattice with thin layers of the ceramic material titanium nitride (TiN) and removed the polymer core, leaving a ceramic nanolattice. The lattice is constructed of hollow struts with walls no thicker than 75 nanometers.

"We are now able to design exactly the structure that we want to replicate and then process it in such a way that it's made out of almost any material class we'd like—for example, metals, ceramics, or semiconductors—at the right dimensions," Greer says.

In a second paper, scheduled for publication in the journal Advanced Engineering Materials, Greer's group demonstrates that similar nanostructured lattices could be made from gold rather than a ceramic. "Basically, once you've created the scaffold, you can use whatever technique will allow you to deposit a uniform layer of material on top of it," Greer says.

In the Nature Materials work, the team tested the individual octahedral cells of the final ceramic lattice and found that they had an unusually high tensile strength. Despite being repeatedly subjected to stress, the lattice cells did not break, whereas a much larger, solid piece of TiN would break at much lower stresses. Typical ceramics fail because of flaws—the imperfections, such as holes and voids, that they contain. "We believe the greater strength of these nanostructured materials comes from the fact that when samples become sufficiently small, their potential flaws also become very small, and the probability of finding a weak flaw within them becomes very low," Greer says. So although structural mechanics would predict that a cellular structure made of TiN would be weak because it has very thin walls, she says, "we can effectively trick this law by reducing the thickness or the size of the material and by tuning its microstructure, or atomic configurations."

Additional coauthors on the Nature Materials paper, "Fabrication and Deformation of Three-Dimensional Hollow Ceramic Nanostructures," are Dongchan Jang, who recently completed a postdoctoral fellowship in Greer's lab, Caltech graduate student Lucas Meza, and Frank Greer, formerly of the Jet Propulsion Laboratory (JPL). The work was supported by funding from the Dow-Resnick Innovation Fund at Caltech, DARPA's Materials with Controlled Microstructural Architecture program, and the Army Research Office through the Institute for Collaborative Biotechnologies at Caltech. Some of the work was carried out at JPL under a contract with NASA, and the Kavli Nanoscience Institute at Caltech provided support and infrastructure.

The lead author on the Advanced Engineering Materials paper, "Design and Fabrication of Hollow Rigid Nanolattices Via Two-Photon Lithography," is Caltech graduate student Lauren Montemayor. Meza is a coauthor. In addition to support from the Dow-Resnick Innovation Fund, this work received funding from an NSF Graduate Research Fellowship.

Kimm Fesenmaier
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Meet DALE: Solar Decathlon 2013 Construction is Under Way

Trading in their textbooks for power tools this summer, a group of nine Caltech students and recent graduates have had a unique opportunity to apply their classroom knowledge to real-world challenges. Along with students in architectural design from the Southern California Institute of Architecture (SCI-Arc), the Caltech students have spent their summer building the Dynamic Augmented Living Environment (DALE), a joint SCI-Arc/Caltech entry in the 2013 Solar Decathlon competition. DALE marks Caltech's second collaboration with SCI-Arc, following their Compact Hyper-Insulated Prototype (CHIP), the partnership's first Solar Decathlon entry, in 2011.

Sponsored by the Department of Energy, the biennial Solar Decathlon competition challenges collegiate teams to "design, build, and operate solar-powered houses that are cost-effective, energy-efficient, and attractive." Contest rules state that each entry must be a net-zero home, meaning that its solar panels must produce at least as much energy as the home uses.

Construction on the SCI-Arc/Caltech collaboration began in March, when DALE's cement foundation was poured. In April, the home's steel frames were dropped in, allowing the students (guided by a few construction professionals) to begin nailing the lumber into place.

As of August, the home is starting to take shape; the bathroom has been framed out, the kitchen cabinets are set for installation, and soon the house will be sporting a vinyl exterior and a set of moving canopies that will hold its solar panels.

Although construction work only began a few months ago, the Caltech students began planning for DALE last fall in an engineering project course called Introduction to Multidisciplinary Systems Engineering, taught by Melany Hunt, Dotty and Dick Hayman Professor of Mechanical Engineering and a vice provost.

"I really like this project because it's very hands-on," says DALE team member Zeke Millikan (BS '13, mechanical engineering). "A lot of classes at Caltech are very theoretical, and I'm more of a hands-on type of person. It's really satisfying to actually build something and see it come together."

"Prior to this summer," says DALE team member Sheila Lo ('16), "I didn't really have a lot of experience in construction, so I spent a lot of time learning the terminology and how to use which tools in certain situations. As one of the youngest members of the team, it's been a great privilege to work with upperclassmen and recent graduates because they've taught me a lot about dedication to a project and what it means to apply the skills you learn at Caltech."

And this dedication will be important in the coming weeks, as there is still plenty of work to be done for the early-October competition. Unlike the five previous Solar Decathlons, which were held in Washington, D.C., this year's event will take place in nearby Irvine, California. "Having the competition just right down the road from us inspired the design," says DALE team member Ella Seal (BS '13, mechanical engineering).

To capitalize on Southern California's mild climate, DALE is made up of two moving modules that can glide apart on warm sunny days, creating an open indoor courtyard that can triple the home's available living space. During inclement weather—and for enhanced safety and privacy—DALE's modules can also move together, creating an enclosed home of about 600 square feet.

The home's untraditional moving design—conceived by SCI-Arc team members—is more than just eye-catching. "It also will actually save energy and money over the course of the year," says Seal. By varying the configurations of DALE's modules and shade canopies—the same ones that will hold DALE's solar panels—the Caltech students were able to optimize energy efficiency during different times of the day without sacrificing comfort. "During the summer, the air-conditioning energy consumption drops by at least half when you are able to open up the house and adjust the shading depending on the weather outside," says Millikan.

But a moving house also presents several engineering challenges, says Seal. Wires for electricity and pipes for plumbing had to be specially designed for their moving platform. Seal and Millikan were also tasked with creating a foolproof safety mechanism for DALE's movement systems. Applying their backgrounds in mechanical engineering, they created a system of laser beams, light curtains, and pressure sensors that acts "basically like a garage door sensor on steroids," says Millikan. "We think we've addressed pretty much every scenario where someone could get seriously hurt."

In addition to the movement systems, students from Caltech are responsible for designing the home's heating, ventilation, and air-conditioning system; hot water system; photovoltaic arrays; and other engineering aspects of the solar-powered home. As well as their technical contributions, the Caltech students will collaborate with their SCI-Arc teammates on publicity and fund-raising efforts and the compilation of a final written report.

"I appreciate the fact that it's not just engineering," says Seal. "I really like the fact that we have to write an engineering narrative, describing all of the really cool innovations that we've built into the house. It's not necessarily something that I would get to do if I took a different project class at Caltech."

This type of multidisciplinary and collaborative experience is important for Caltech students, notes Hunt. "Engineering students need experiences in which they design, create, build, and test," she says. "They also should have opportunities in which they work as part of a team. Most engineering projects require multiple perspectives with input coming from a range of individuals with different expertise and vision."

In addition to Millikan, Seal, and Lo, the DALE team includes current Caltech students Brynan Qui ('15), Do Hee Kim ('15), Sharon Wang ('16), as well as recent graduates Tony Wu (BS '13, mechanical engineering and business economics and management) and Christine Viveiros (BS '13, mechanical engineering), and project manager Andrew Gong (BS '12, chemical engineering [materials]). The SCI-Arc/Caltech project, along with other entries for this year's Solar Decathlon competition, will be open to the public October 3–6 and 10–13 at the Orange County Great Park in Irvine, California.

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Yeh and Schwab Named Kavli Nanoscience Institute Codirectors

Caltech professors Nai-Chang Yeh and Keith Schwab have been named codirectors of the Kavli Nanoscience Institute (KNI), a center supporting multidisciplinary nanoscience research on campus and beyond. Yeh and Schwab have both served as KNI board members and are the first to hold the title Fletcher Jones Foundation Codirector of the KNI; the position was recently endowed by a gift from The Fletcher Jones Foundation.

"I look forward to the energy and creativity that Nai-Chang and Keith will bring to the continued evolution of the KNI as a preeminent organization propelling nanoscience forward in diverse application areas ranging from medical engineering to nanophotonics," says Ares Rosakis, Otis Booth Leadership Chair of the Division of Engineering and Applied Science.

Yeh and Schwab follow in the footsteps of professors Michael Roukes and Oskar Painter (MS '95, PhD '01).

"It is an exciting time to conduct research in nanoscience and nanotechnology," Yeh says. "As the new codirectors of KNI, our vision is not only to maintain the current role of KNI but also to make KNI an intellectual hub that facilitates Caltech research in the areas of quantum frontiers, medical/bioengineering, and sustainability," she says.  "We look forward to working with the nanoresearch community on campus and the Caltech administration to advance frontiers of nanoscience and nanotechnology."

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Arnold Appointed New Director of Rosen Bioengineering Center

Now in its sixth year of exploring the intersection between biology and engineering, the Donna and Benjamin M. Rosen Bioengineering Center has chosen Caltech professor Frances Arnold as its new director. Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry began her tenure as director on June 1.

A recipient of the 2011 National Medal of Technology and Innovation, Arnold pioneered methods of "directed evolution" – processes now widely used to create biological catalysts that are important in the production of fuels from renewable resources. She was selected for the directorship because "of her demonstrated leadership in the field of bioengineering," says Stephen Mayo, William K. Bowes Jr. Foundation Chair of the Division of Biology and Biological Engineering.

The Rosen Center supports bioengineering research through the funding of fellows and faculty from many disciplines, including applied physics, chemical engineering, synthetic biology, and computer science.

"Bioengineering is an incredibly exciting field right now," Arnold says. "Solutions to some of the biggest problems in science, medicine, and sustainability will come from the interface between biology and engineering, and Caltech is well positioned to be at the forefront. The Rosen Center will help make that happen with innovative programs for bioengineering research and education."

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Caltech Team Produces Squeezed Light Using a Silicon Micromechanical System

One of the many counterintuitive and bizarre insights of quantum mechanics is that even in a vacuum—what many of us think of as an empty void—all is not completely still. Low levels of noise, known as quantum fluctuations, are always present. Always, that is, unless you can pull off a quantum trick. And that's just what a team led by researchers at the California Institute of Technology (Caltech) has done. The group has engineered a miniature silicon system that produces a type of light that is quieter at certain frequencies—meaning it has fewer quantum fluctuations—than what is usually present in a vacuum.

This special type of light with fewer fluctuations is known as squeezed light and is useful for making precise measurements at lower power levels than are required when using normal light. Although other research groups previously have produced squeezed light, the Caltech team's new system, which is miniaturized on a silicon microchip, generates the ultraquiet light in a way that can be more easily adapted to a variety of sensor applications.

"This system should enable a new set of precision microsensors capable of beating standard limits set by quantum mechanics," says Oskar Painter, a professor of applied physics at Caltech and the senior author on a paper that describes the system; the paper appears in the August 8 issue of the journal Nature. "Our experiment brings together, in a tiny microchip package, many aspects of work that has been done in quantum optics and precision measurement over the last 40 years."

The history of squeezed light is closely associated with Caltech. More than 30 years ago, Kip Thorne, Caltech's Richard P. Feynman Professor of Theoretical Physics, Emeritus, and physicist Carlton Caves (PhD '79) theorized that squeezed light would enable scientists to build more sensitive detectors that could make more precise measurements. A decade later, Caltech's Jeff Kimble, the William L. Valentine Professor and professor of physics, and his colleagues conducted some of the first experiments using squeezed light. Since then, the LIGO (Laser Interferometer Gravitational-Wave Observatory) Scientific Collaboration has invested heavily in research on squeezed light because of its potential to enhance the sensitivity of gravitational-wave detectors.

In the past, squeezed light has been made using so-called nonlinear materials, which have unusual optical properties. This latest Caltech work marks the first time that squeezed light has been produced using silicon, a standard material. "We work with a material that's very plain in terms of its optical properties," says Amir Safavi-Naeini (PhD '13), a graduate student in Painter's group and one of three lead authors on the new paper. "We make it special by engineering or punching holes into it, making these mechanical structures that respond to light in a very novel way. Of course, silicon is also a material that is technologically very amenable to fabrication and integration, enabling a great many applications in electronics."

In this new system, a waveguide feeds laser light into a cavity created by two tiny silicon beams. Once there, the light bounces back and forth a bit thanks to the engineered holes, which effectively turn the beams into mirrors. When photons—particles of light—strike the beams, they cause the beams to vibrate. And the particulate nature of the light introduces quantum fluctuations that affect those vibrations.

Typically, such fluctuations mean that in order to get a good reading of a signal, you would have to increase the power of the light to overcome the noise. But by increasing the power you also introduce other problems, such as introducing excess heat into the system.

Ideally, then, any measurements should be made with as low a power as possible. "One way to do that," says Safavi-Naeini, "is to use light that has less noise."

And that's exactly what the new system does; it has been engineered so that the light and beams interact strongly with each other—so strongly, in fact, that the beams impart the quantum fluctuations they experience back on the light. And, as is the case with the noise-canceling technology used, for example, in some headphones, the fluctuations that shake the beams interfere with the fluctuations of the light. They effectively cancel each other out, eliminating the noise in the light.

"This is a demonstration of what quantum mechanics really says: Light is neither a particle nor a wave; you need both explanations to understand this experiment," says Safavi-Naeini. "You need the particle nature of light to explain these quantum fluctuations, and you need the wave nature of light to understand this interference."

In the experiment, a detector measuring the noise in the light as a function of frequency showed that in a frequency range centered around 28 MHz, the system produces light with less noise than what is present in a vacuum—the standard quantum limit. "But one of the interesting things," Safavi-Naeini adds, "is that by carefully designing our structures, we can actually choose the frequency at which we go below the vacuum." Many signals are specific to a particular frequency range—a certain audio band in the case of acoustic signals, or, in the case of LIGO, a frequency intimately related to the dynamics of astrophysical objects such as circling black holes. Because the optical squeezing occurs near the mechanical resonance frequency where an individual device is most sensitive to external forces, this feature would enable the system studied by the Caltech team to be optimized for targeting specific signals.

"This new way of 'squeezing light' in a silicon micro-device may provide new, significant applications in sensor technology," said Siu Au Lee, program officer at the National Science Foundation, which provided support for the work through the Institute for Quantum Information and Matter, a Physics Frontier Center. "For decades, NSF's Physics Division has been supporting basic research in quantum optics, precision measurements and nanotechnology that laid the foundation for today's accomplishments."

The paper is titled "Squeezed light from a silicon micromechanical resonator." Along with Painter and Safavi-Naeini, additional coauthors on the paper include current and former Painter-group researchers Jeff Hill (PhD '13), Simon Gröblacher (both lead authors on the paper with Safavi-Naeini), and Jasper Chan (PhD '12), as well as Markus Aspelmeyer of the Vienna Center for Quantum Science and Technology and the University of Vienna. The work was also supported by the Gordon and Betty Moore Foundation, by DARPA/MTO ORCHID through a grant from the Air Force Office of Scientific Research, and by the Kavli Nanoscience Institute at Caltech.

Kimm Fesenmaier
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India Establishes Caltech Aerospace Fellowship

The Indian Department of Space / Indian Space Research Organisation (ISRO) has established a fellowship at the California Institute of Technology (Caltech) in the name of Satish Dhawan (1920–2002), a Caltech alumnus (Eng '49, PhD '51) and a pioneer of India's space program.

The Satish Dhawan Fellowship enables one aerospace engineering graduate per year from the Indian Institute of Space Science and Technology (IIST) to study at the Graduate Aerospace Laboratories at Caltech (GALCIT), as Dhawan himself did more than 60 years ago, when GALCIT was the Guggenheim Aeronautical Laboratory. Dhawan went on to serve as the director of the Indian Institute of Science (IISc), chairman of the Indian Space Commission and the ISRO, and president of the Indian Academy of Sciences. In 1969 he was named a Caltech Distinguished Alumnus.

Chaphalkar Aaditya Nitin, an IIST graduate with a Bachelor of Technology degree in aerospace engineering, has been named the first student to receive the fellowship and will start classes at GALCIT in October.

According to GALCIT director Guruswami (Ravi) Ravichandran, the John E. Goode, Jr., Professor of Aerospace and professor of mechanical engineering, ISRO established the fellowship to create a permanent pipeline of aerospace engineering leaders who will guide India's space program into the future.

"India has a very strong domestically grown space program," explains Ravichandran. "The ISRO is hoping to maintain its momentum by training students in much the same way that Dhawan was trained when he went through GALCIT decades ago."

The first three directors of what is now India's National Aerospace Laboratories were GALCIT alumni—Parameswar Nilakantan (MS '42), S. R. Valluri (MS '50, PhD '54), and Roddam Narasimha (PhD '61 "The ISRO is honoring Dhawan and Caltech with this fellowship, and it is also recognizing the historical connections between engineers and scientists in the United States and India," says Ares Rosakis, Caltech's Theodore von Kármán Professor of Aeronautics and Mechanical Engineering and Otis Booth Leadership Chair, Division of Engineering and Applied Science. "It is an endorsement of GALCIT's fundamental research approach and rigorous curriculum.

"Most academic fellowships come from private philanthropy. It is extremely rare for a government institution to endow a fellowship intended for a private research institution such as Caltech," he says.

"GALCIT has had impact on aeronautics and aerospace development in the United States and abroad, not by training engineers in large numbers but by training engineering leaders," Rosakis says. "GALCIT graduates include CEOs of aerospace companies and the heads of departments at places like MIT, Georgia Tech, and the University of Illinois. If we were to create one von Kármán every half century, as well as a few aerospace CEOs, and a few Dhawans, we would be happy."

Brian Bell
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Figuring Out Flow Dynamics

Engineers gain insight into turbulence formation and evolution in fluids

Turbulence is all around us—in the patterns that natural gas makes as it swirls through a transcontinental pipeline or in the drag that occurs as a plane soars through the sky. Reducing such turbulence on say, an airplane wing, would cut down on the amount of power the plane has to put out just to get through the air, thereby saving fuel. But in order to reduce turbulence—a very complicated phenomenon—you need to understand it, a task that has proven to be quite a challenge.

Since 2006, Beverley McKeon, professor of aeronautics and associate director of the Graduate Aerospace Laboratories at the California Institute of Technology (Caltech) and collaborator Ati Sharma, a senior lecturer in aerodynamics and flight mechanics at the University of Southampton in the U.K., have been working together to build models of turbulent flow. Recently, they developed a new and improved way of looking at the composition of turbulence near walls, the type of flow that dominates our everyday life.

Their research could lead to significant fuel savings, as a large amount of energy is consumed by ships and planes, for example, to counteract turbulence-induced drag. Finding a way to reduce that turbulence by 30 percent would save the global economy billions of dollars in fuel costs and associated emissions annually, says McKeon, a coauthor of a study describing the new method published online in the Journal of Fluid Mechanics on July 8.

"This kind of turbulence is responsible for a large amount of the fuel that is burned to move humans, freight, and fluids such as water, oil, and natural gas, around the world," she says. "[Caltech physicist Richard] Feynman described turbulence as 'one of the last unsolved problems of classical physics,' so it is also a major academic challenge."

Wall turbulence develops when fluids—liquid or gas—flow past solid surfaces at anything but the slowest flow rates. Progress in understanding and controlling wall turbulence has been somewhat incremental because of the massive range of scales of motion involved—from the width of a human hair to the height of a multi-floor building in relative terms—says McKeon, who has been studying turbulence for 16 years. Her latest work, however, now provides a way of analyzing a large-scale flow by breaking it down into discrete, more easily analyzed bits. 

McKeon and Sharma devised a new method of looking at wall turbulence by reformulating the equations that govern the motion of fluids—called the Navier-Stokes equations—into an infinite set of smaller, simpler subequations, or "blocks," with the characteristic that they can be simply added together to introduce more complexity and eventually get back to the full equations. But the benefit comes in what can be learned without needing the complexity of the full equations. Calling the results from analysis of each one of those blocks a "response mode," the researchers have shown that commonly observed features of wall turbulence can be explained by superposing, or adding together, a very small number of these response modes, even as few as three. 

In 2010, McKeon and Sharma showed that analysis of these blocks can be used to reproduce some of the characteristics of the velocity field, like the tendency of wall turbulence to favor eddies of certain sizes and distributions. Now, the researchers also are using the method to capture coherent vortical structure, caused by the interaction of distinct, horseshoe-shaped spinning motions that occur in turbulent flow. Increasing the number of blocks included in an analysis increases the complexity with which the vortices are woven together, McKeon says. With very few blocks, things look a lot like the results of an extremely expensive, real-flow simulation or a full laboratory experiment, she says, but the mathematics are simple enough to be performed, mode-by-mode, on a laptop computer.

"We now have a low-cost way of looking at the 'skeleton' of wall turbulence," says McKeon, explaining that similar previous experiments required the use of a supercomputer. "It was surprising to find that turbulence condenses to these essential building blocks so easily. It's almost like discovering a lens that you can use to focus in on particular patterns in turbulence."

Using this lens helps to reduce the complexity of what the engineers are trying to understand, giving them a template that can be used to try to visually—and mathematically—identify order from flows that may appear to be chaotic, she says. Scientists had proposed the existence of some of the patterns based on observations of real flows; using the new technique, these patterns now can be derived mathematically from the governing equations, allowing researchers to verify previous models of how turbulence works and improve upon those ideas.

Understanding how the formulation can capture the skeleton of turbulence, McKeon says, will allow the researchers to modify turbulence in order to control flow and, for example, reduce drag or noise.

"Imagine being able to shape not just an aircraft wing but the characteristics of the turbulence in the flow over it to optimize aircraft performance," she says. "It opens the doors for entirely new capabilities in vehicle performance that may reduce the consumption of even renewable or non-fossil fuels."

Funding for the research outlined in the Journal of Fluid Mechanics paper, titled "On coherent structure in wall turbulence," was provided by the Air Force Office of Scientific Research. The paper is the subject of a "Focus on Fluids" feature article that will appear in an upcoming print issue of the same journal and was written by Joseph Klewicki of the University of New Hampshire. 

Katie Neith
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Pushing Microscopy Beyond Standard Limits

Caltech engineers show how to make cost-effective, ultra-high-performance microscopes

Engineers at the California Institute of Technology (Caltech) have devised a method to convert a relatively inexpensive conventional microscope into a billion-pixel imaging system that significantly outperforms the best available standard microscope. Such a system could greatly improve the efficiency of digital pathology, in which specialists need to review large numbers of tissue samples. By making it possible to produce robust microscopes at low cost, the approach also has the potential to bring high-performance microscopy capabilities to medical clinics in developing countries.

"In my view, what we've come up with is very exciting because it changes the way we tackle high-performance microscopy," says Changhuei Yang, professor of electrical engineering, bioengineering and medical engineering at Caltech.  

Yang is senior author on a paper that describes the new imaging strategy, which appears in the July 28 early online version of the journal Nature Photonics.

Until now, the physical limitations of microscope objectives—their optical lenses— have posed a challenge in terms of improving conventional microscopes. Microscope makers tackle these limitations by using ever more complicated stacks of lens elements in microscope objectives to mitigate optical aberrations. Even with these efforts, these physical limitations have forced researchers to decide between high resolution and a small field of view on the one hand, or low resolution and a large field of view on the other. That has meant that scientists have either been able to see a lot of detail very clearly but only in a small area, or they have gotten a coarser view of a much larger area.

"We found a way to actually have the best of both worlds," says Guoan Zheng, lead author on the new paper and the initiator of this new microscopy approach from Yang's lab. "We used a computational approach to bypass the limitations of the optics. The optical performance of the objective lens is rendered almost irrelevant, as we can improve the resolution and correct for aberrations computationally."

Indeed, using the new approach, the researchers were able to improve the resolution of a conventional 2X objective lens to the level of a 20X objective lens. Therefore, the new system combines the field-of-view advantage of a 2X lens with the resolution advantage of a 20X lens. The final images produced by the new system contain 100 times more information than those produced by conventional microscope platforms. And building upon a conventional microscope, the new system costs only about $200 to implement.

"One big advantage of this new approach is the hardware compatibility," Zheng says, "You only need to add an LED array to an existing microscope. No other hardware modification is needed. The rest of the job is done by the computer."  

The new system acquires about 150 low-resolution images of a sample. Each image corresponds to one LED element in the LED array. Therefore, in the various images, light coming from known different directions illuminates the sample. A novel computational approach, termed Fourier ptychographic microscopy (FPM), is then used to stitch together these low-resolution images to form the high-resolution intensity and phase information of the sample—a much more complete picture of the entire light field of the sample.

Yang explains that when we look at light from an object, we are only able to sense variations in intensity. But light varies in terms of both its intensity and its phase, which is related to the angle at which light is traveling.

"What this project has developed is a means of taking low-resolution images and managing to tease out both the intensity and the phase of the light field of the target sample," Yang says. "Using that information, you can actually correct for optical aberration issues that otherwise confound your ability to resolve objects well."

The very large field of view that the new system can image could be particularly useful for digital pathology applications, where the typical process of using a microscope to scan the entirety of a sample can take tens of minutes. Using FPM, a microscope does not need to scan over the various parts of a sample—the whole thing can be imaged all at once. Furthermore, because the system acquires a complete set of data about the light field, it can computationally correct errors—such as out-of-focus images—so samples do not need to be rescanned.

"It will take the same data and allow you to perform refocusing computationally," Yang says.

The researchers say that the new method could have wide applications not only in digital pathology but also in everything from hematology to wafer inspection to forensic photography. Zheng says the strategy could also be extended to other imaging methodologies, such as X-ray imaging and electron microscopy.

The paper is titled "Wide-field, high-resolution Fourier ptychographic microscopy." Along with Yang and Zheng, Caltech graduate student Roarke Horstmeyer is also a coauthor. The work was supported by a grant from the National Institutes of Health.

Kimm Fesenmaier
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