The science of friction on graphene

Graphene, a two-dimensional form of carbon in sheets just one atom in thick, has been the subject of widespread research, in large part because of its unique combination of strength, electrical conductivity, and chemical stability. But despite many years of study, some of graphene’s fundamental properties are still not well-understood, including the way it behaves when something slides along its surface.

Now, using powerful computer simulations, researchers at MIT and elsewhere have made significant strides in understanding that process, including why the friction varies as the object sliding on it moves forward, instead of remaining constant as it does with most other known materials.

The findings are presented this week in the journal Nature, in a paper by Ju Li, professor of nuclear science and engineering and of materials science and engineering at MIT, and seven others at MIT, the University of Pennsylvania, and universities in China and Germany.

Graphite, a bulk material composed of many layers of graphene, is a well-known solid lubricant. (In other words, like oil, it can be added in between contacting materials to reduce friction.) Recent research suggests that even one or a few layers of graphene can also provide effective lubrication. This may be used in small-scale thermal and electrical contacts and other nanoscale devices. In such cases, an understanding of the friction between two pieces of graphene, or between graphene and another material, is important for maintaining a good electrical, thermal, and mechanical connection. Researchers had previously found that while one layer of graphene on a surface reduces friction, having a few more was even better. However, the reason for this was not well-explained before, Li says.

“There is this broad notion in tribology that friction depends on the true contact area,” Li says — that is, the area where two materials are really in contact, down to the atomic level. The “true” contact area is often substantially smaller than it would otherwise appear to be if observed at larger size scales. Determining the true contact area is important for understanding not only the degree of friction between the pieces, but also other characteristics such as the electrical conduction or heat transfer.

For example, explains co-author Robert Carpick of the University of Pennsylvania, “When two parts in a machine make contact, like two teeth of steel gears, the actual amount of steel in contact is much smaller than it appears, because the gear teeth are rough, and contact only occurs at the topmost protruding points on the surfaces. If the surfaces were polished to be flatter so that twice as much area was in contact, the friction would then be twice as high. In other words, the friction force doubles if the true area of direct contact doubles.”

But it turns out that the situation is even more complex than scientists had thought. Li and his colleagues found that there are also other aspects of the contact that influence how friction force gets transferred across it. “We call this the quality of contact, as opposed to the quantity of contact measured by the ‘true contact’ area,” Li explains.

Experimental observations had shown that when a nanoscale object slides along a single layer of graphene, the friction force actually increases at first, before eventually leveling off. This effect lessens and the leveled-off friction force decreases when sliding on more and more graphene sheets. This phenomenon was also seen in other layered materials including molybdenum disulfide. Previous attempts to explain this variation in friction, not seen in anything other than these two-dimensional materials, had fallen short.

To determine the quality of contact, it is necessary to know the exact position of each atom on each of the two surfaces. The quality of contact depends on how well-aligned the atomic configurations are in the two surfaces in contact, and on the synchrony of these alignments. According to the computer simulations, these factors turned out to be more important than the traditional measure in explaining the materials’ frictional behavior, according to Li.

“You cannot explain the increase in friction” as the material begins to slide “by just the contact area,” Li says. “Most of the change in friction is actually due to change in the quality of contact, not the true contact area.” The researchers found that the act of sliding causes graphene atoms to make better contact with the object sliding along it; this increase in the quality of contact leads to the increase in friction as sliding proceeds and eventually levels off. The effect is strong for a single layer of graphene because the graphene is so flexible that the atoms can move to locations of better contact with the tip.

A number of factors can affect the quality of contact, including rigidity of the surfaces, slight curvatures, and gas molecules that get in between the two solid layers, Li says. But by understanding the way the process works, engineers can now take specific steps to alter that frictional behavior to match a particular intended use of the material. For example, “prewrinkling” of the graphene material can give it more flexibility and improve the quality of contact. “We can use that to vary the friction by a factor of three, while the true contact area barely changes,” he says.

“In other words, it’s not just the material itself” that determines how it slides, but also its boundary condition — including whether it is loose and wrinkled or flat and stretched tight, he says. And these principles apply not just to graphene but also to other two-dimensional materials, such as molybdenum disulfide, boron nitride, or other single-atom or single-molecule-thick materials.

“Potentially, a moving mechanical contact could be used as a way to make very good power switches in small electronic devices,” Li says. But that is still some ways off; while graphene is a promising material being widely studied, “we’re still waiting to see graphene electronics and 2-D electronics take off. It’s an emerging field.”

“Researchers have studied the unique frictional behavior of graphene for many years, but the complex mechanisms underlying these observations are still not fully understood,” says Ashlie Martini, an associate professor of engineering at the University of California at Merced, who was not involved in this work. “This paper tackles the challenge head on and provides new insights into the origins of friction on graphene that I anticipate will be applicable to two-dimensional materials in general.”

Martini adds: “The authors of the paper correctly suggest that their work could be used as a foundation for ‘tuning’ friction on graphene. Actually implementing this tuning has the potential for significant impact, and an exciting next step based on this research would be to implement the proposed tuning as a first step toward controllable friction in scientific and engineering applications.”

Besides Li and Carpick, the research team included former MIT and University of Pennsylvania visiting student Suzhi Li, now a Humboldt Research Fellow in Germany; Qunyang Li at Tsinghua University in China; Xin Liu at the University of Pennsylvania and now at Intel; Peter Gumbsch at Karlsruhe Institute of Technology in Germany; and Xiangdong Ding and Jun Sun at Xi’an Jiaotong University in China.

The work was supported by the National Science Foundation.

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Nylon fibers made to flex like muscles

Artificial muscles — materials that contract and expand somewhat like muscle fibers do — can have many applications, from robotics to components in the automobile and aviation industries. Now, MIT researchers have come up with one of the simplest and lowest-cost systems yet for developing such “muscles,” in which a material reproduces some of the bending motions that natural muscle tissues perform.

The key ingredient, cheap and ubiquitous, is ordinary nylon fiber.

The new approach to harnessing this basic synthetic fiber material lies in shaping and heating the fibers in a particular way, which is described in a new paper in the journal Advanced Materials by Seyed Mirvakili, a doctoral candidate, and Ian Hunter, the George N. Hatsopoulos Professor in the Department of Mechanical Engineering.

Previously, researchers had come up with the basic principle of using twisted coils of nylon filament to mimic basic linear muscle activity. They showed that for a given size and weight, such devices could extend and retract further, and store and release more energy, than natural muscles. But bending motions, such as those of human fingers and limbs, proved more challenging and had not yet been achieved in a simple and inexpensive system until the new work at MIT.

There are some existing materials that can be used to produce these kinds of bending motions, which could be useful for some biomedical devices or tactile displays. However, those tend to use “exotic materials to do the job, and they are very expensive and very difficult to make,” Mirvakili says. For example, carbon nanotube yarns can provide great longevity (more than a million linear contraction cycles) but are still too expensive for widespread use, and shape-memory alloys provide a strong contracting pull but have a poor cycle life (fewer than 1,000 cycles).

Cheap and simple

The new nylon-based system, by contrast, uses cheap material and a simple manufacturing process, and demonstrates very good cycling longevity. It all comes down to how the nylon fibers are shaped.

Some polymer fiber materials, including highly oriented nylon, have an unusual property: When heated, “they shrink in length but expand in diameter,” Mirvakili says, and this property has been harnessed to make some linear actuator devices. But to turn that linear shrinking motion into bending typically requires a mechanism such as a pulley and a takeup reel, adding extra size, complexity, and expense. The MIT team’s advance was to directly harness the motion without requiring extra mechanical parts.

One of the limitations on linear actuators made from such materials is that after being heated to trigger the contraction, they take some time to cool back down. “The cooling rate can be a limiting factor,” Mirvakili says. “But I realized it could be used to an advantage.” Selectively heating one side of the fiber, he says, causes that side to begin contracting faster than the heat can penetrate to the other side, and thus can produce a bending motion in the fiber. “You need a combination of these properties,” he says: “high strain [the pull of the shrinking motion] and low thermal conductivity.”

To make this system work effectively as an artificial muscle, the fiber’s cross-section needs to be carefully shaped. The team used ordinary nylon fishing line to start with, and compressed it to change its cross-section from round to rectangular or square. Then, selectively heating one side caused the fiber to bend in that direction. Changing the direction of the heating could also produce more complex motions; in their lab tests, the team used this heating technique to get the fibers to move in circles and figure-eights, and much more complex patterns of movement could easily be achieved, they say.

Various heat sources can be used on the fibers, including electric resistance heating, chemical reactions, or a laser beam that shines on the filament. For some of their tests, the researchers used a special conductive paint applied to the fibers and held in place by a resin binder; when a voltage was applied to the material, it selectively heated the portion of the fiber directly below the paint, causing the fiber to bend that way.

Long-lived material

The researchers have demonstrated that the material can maintain its performance after at least 100,000 bending cycles, and can bend and retract at a speed of at least 17 cycles per second.

Hunter suggests that ultimately, applications for such fibers might include clothes that contract to adjust snugly to the contours of an individual body, drastically reducing the number of different sizes a manufacturer would need to produce, while improving the comfort and fit. Or, the fibers might be used in shoes that would tighten themselves when put on or adjust their stiffness and shape during each stride.

The system may also allow for self-adjusting catheters or other biomedical devices. And in the longer run, it could even lead to mechanical systems such as vehicle exterior panels that adjust their aerodynamic shape to adapt to changes in speed and wind conditions, or automatic tracking systems for solar panels that would use excess heat generated by the panels themselves to keep the panels aimed at the sun.

This method “is novel and elegant, with very good experimental data supported by appropriate physics-based models,” says Geoffrey Spinks, a professor at the University of Wollongong in Australia, who was not connected with this research. “This is a simple idea that works really well. The materials are inexpensive. The manufacturing method is simple and versatile. The method of actuation is by simple electrical input. The bending actuation performance is impressive in terms of bending angle, force generated, and speed.”

Spinks adds, “Bending-type actuators are needed for robotic grippers, microscopic tools, and various machine components. These new bending actuators could have immediate application.”

These are “exciting and game-changing findings,” adds Andrew Taberner, an associate professor of bioengineering at the University of Auckland in New Zealand, who also was not involved in this research. “One can imagine many applications for this type of actuator in the medical and instrumentation fields,” he says. “I expect that this work will become highly cited.”

Seyed Mirvakili was supported by the Natural Sciences and Engineering Research Council of Canada.

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On their way to becoming American citizens

The process to become an American citizen probably isn’t something many of us think about unless we have personal experience with it.

On Wednesday, Nov. 16, more than 100 MIT employees had that personal experience. That day, MIT Human Resources (HR) sponsored a citizenship application workshop for MIT employees in collaboration with Project Citizenship, a Boston nonprofit that helps individuals who have green-cards and who meet other requirements to apply for citizenship. 

More than 60 volunteers from HR partnered with 55 eligible employees from across the Institute to fill out the application. This workshop evolved from a conversation Vice President for Human Resources Lorraine A. Goffe-Rush had with Project Citizenship last summer. “After learning more about the opportunity to assist our employees with the complicated task of applying for citizenship, it became clear it was a match with MIT’s core values and HR’s goal of participating in meaningful community service,” said Goffe-Rush.

Not surprisingly, the day-long workshop — consisting of three different shifts of volunteers and employees filling out applications — was profound for both sets of employees. MIT Research Scientist Islam Hussein and his wife Randa Azab attended the workshop and were grateful to both Project Citizenship and HR: “Project Citizenship’s expert input, friendly dialogue, and supportive attitude made the lengthy process of filling out our citizenship application a lot easier,” said Hussein. “We would like also to thank MIT Human Resources for hosting this excellent workshop; it is a great service for all MIT employees seeking citizenship.”

The employees from HR (and two employees from MIT Facilities) who volunteered their time took their assignments seriously. Chuck Pizzano, an HR senior business systems analyst, summed it up for many of the volunteers: “It isn’t an easy application to fill out, so I was glad I could help a fellow MIT colleague go through it. Despite the complexity of the task, it was fun.”

After the applications were filled out, the applicants met with lawyers who volunteer with Project Citizenship to finalize their applications. Now that the application workshop is over, the next steps take place over six to seven months and include fingerprinting, attending an interview and taking three tests, and participating in the naturalization ceremony where new citizens take the oath of allegiance. Safe to say that come springtime, there will be several MIT employees who will identify themselves as American citizens for the first time.

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“Uniting through Voice and Song” event celebrates values that connect the MIT community

On the evening of Nov. 17, MIT faculty, staff, and students came together to affirm — through words and music — the enduring values and purposes that unite the community. Some 150 people gathered in Lobby 10 for a program of music from many traditions, interwoven with reflections from faculty and students. Against the backdrop of a changing political landscape, themes of mutual respect, inclusivity, and dedication to making a better world echoed through the evening.

Melissa Nobles, the Kenan Sahin Dean of the School of Humanities, Arts and Social Sciences, whose office sponsored the event, opened the evening saying, “At this time of change, it is important that we lift up and celebrate our commitment at MIT to our ongoing values of discovery, freedom of expression and thought, and respect for all people.”

MIT Chancellor Cynthia Barnhart PhD ’88, the next of six speakers, said, “We are actively uniting around our determination to educate, advocate, and care for every member of our community so that together we can continue our urgent work of making a better world.”

“At MIT,” she added, “we respect and celebrate our diversity. We seek the facts, believe in science, and roll up our sleeves to solve hard problems. We are open minded, inclusive, and kind. We listen intently and we speak up for what is right. We embrace our responsibility to invent a brighter future for all of humanity. These are MIT’s values and MIT’s path. They always have been — and I can promise you that nothing will change our course.”

Many students in the audience welcomed these statements of solidarity around MIT’s guiding values. “I have people in my life who currently don’t feel safe and don’t feel wanted,” said Riley Clubb, a second-year graduate student at the MIT Sloan School of Management. “That makes me sad, and I’m hoping that people will stand up [to protect others.]”

Listening

The musical program began with a performance of the majestic “Adante Festivo,” a single-movement hymnic work by Jean Sibelius. The tone poem, composed to give his country moral support, was performed with flowing, melodic nuance by members of the MIT Symphony Orchestra under the direction of Adam Boyles.

Members of the MIT Chamber Chorus and Concert Choir, under the direction of William Cutter, performed “The Reason Why the World,” composed by Professor Peter Child for MIT’s 150th anniversary, with text from Ralph Waldo Emerson’s “Nature.” “I chose the passage,” Child said, “because it extols the virtue of combining a sense of spirituality with scientific exploration, and says that each is incomplete without the other, that humans cannot be ‘naturalists,’ until we satisfy ‘all the demands of the spirit.’”

The MIT Vocal Jazz Ensemble, coached by Liz Tobias, performed “Thou Shalt,” by composer Naomi Crellin, a mesmerizing a cappella work of sustained vocal harmonies that were, by turns, hushed and full, with clear sweet sounds over a deep resonant rumbling.

Between the musical performances, students reflected upon the strengths of the MIT community and on how valuable it is to listen to one another in a spirit of mutual respect.

“Students of every historically oppressed group are scared and face outspoken threats,” said Billy Torres, sophomore in electrical engineering and computer science and head of Spanish House. "And yet at MIT, I see people smart enough to acknowledge the issues, and strong enough to overcome the fears facing them.”

Jonathan Hurowitz, a junior in earth, atmospheric, and planetary sciences and president of MITGOP, noted that “Some students are afraid to even voice their opinions without fear of discrimination.” To bridge ideological divides, Hurowitz urged everyone to “find one or two people with different political or social views than yourself and listen to them. Commit to an honest discussion and work to understand your peers.”

First-year graduate student Amro Alshareef also expressed confidence in the strength of the community's bond. "We here at MIT are a family of innovators, and that’s not going to change just because some of us voted one way or another," he said. "We will still remain humans; we will still remain collaborators; and we will still remain MIT."

Caroline H. Mak, a junior in electrical engineering and computer science and a member of MIT Democrats, offered a unique take on the Institute’s core values, speaking as if MIT itself were applying to attend the Institute. Responding to actual Admissions Office essay prompts such as "Which program or major appeals to you?" and "What personality attribute you are most proud of?,” Mak’s “MIT” replies were: “I am now 145 years old and I want to major in diversity. I want to continue making history in ways I can’t even imagine right now.”

Harmonizing

Introducing the Turkish-American, Grammy-nominated composer and performer Mehmet Ali Sanlikol and his duo partner Beth Bahia Cohen, Nobles observed that “MIT values immigrant voices, and, in fact, all the music we hear tonight comes out of a merging of one tradition or another into what we think of as American music. As we know, the Boston area and the MIT community are extremely rich in multicultural traditions, and we're fortunate to have a wonderful example of that with us here tonight, with our guests."

For the gathering, Mehmet, whose compositions merge Turkish themes, jazz, and classical music, transported the audience with a soaring performance from the meditative Turkish Sufi Mevlevi tradition. Afterwards, Mehmet noted that the reverberant Lobby 10 space helped produce the immersive listening experience this rich, moving musical tradition can generate.  

Mark Harvey of MIT Music introduced the final musical performance, by the MIT Festival Jazz Ensemble, led by Fred Harris, with guest musician Evan Ziporyn, MIT professor of music. The ensemble delivered Harvey’s composition “No Walls,” an anthem to inclusiveness inspired by Duke Ellington’s credo of living and making music “beyond category.” In “No Walls,” Harvey fuses musical acumen from South Africa, New Orleans, the classic American songbook, and some points unknown, into an original voice. The composition, he said, “seeks to inspire all of us toward what Ellington fervently hoped for: A new sound of harmony, common respect, and consideration for the dignity and freedom of all people.”

Abdie Dirie ’16, a master's candidate in computer science and electrical engineering, said the “No Walls” performance was one highlight of the evening for him. “It was pointed, with a very good message,” he said. Dirie said he had received a lot of heartfelt calls recently from family and friends who are Muslim. While feeling “anxious for himself and people I know,” Dirie said he was reassured by the evening’s messages, and found “every bit of the event beneficial.”

Helen Elaine Lee, professor of writing and head of the MIT Women’s and Gender Studies Program, brought the evening to a close. “I want to say something to you today about love and struggle,” she said, “about resilience, and the power of art to heal.” With readings from three American writers — James Baldwin, Denise Levertov, and Toni Morrison — Lee encouraged the audience to “love and change the world.”

And what is love? Lee invoked Baldwin, “who reminds us that love is a matter of commitment, grueling self-interrogation, discomfort, hard and ongoing work. And that’s what we must do now,” she said, “Do your transformative work, make and seek out art, and fight for the values you believe in.”

“Uniting through Voice and Song” was sponsored by the School of Humanities, Arts, and Social Sciences Dean's Office and MIT Music and Theater Arts, with support from the Office of the Chancellor and MIT Events. The event was organized and shaped by Fred Harris Jr., Agustin Rayo, Evan Ziporyn, Clarise Snyder, and Joe Coen, in collaboration with Adam Boyles, Gayle Gallagher, Mark Harvey, Lianne Scott, Meredith Sibley, the MIT Campus Activities Complex, and MIT SHASS Communications.

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Meeting of the minds for machine intelligence

Surviving breast cancer changed the course of Regina Barzilay’s research. The experience showed her, in stark relief, that oncologists and their patients lack tools for data-driven decision making. That includes what treatments to recommend, but also whether a patient’s sample even warrants a cancer diagnosis, she explained at the Nov. 10 Machine Intelligence Summit, organized by MIT and venture capital firm Pillar. 

“We do more machine learning when we decide on Amazon which lipstick you would buy,” said Barzilay, the Delta Electronics Professor of Electrical Engineering and Computer Science at MIT. “But not if you were deciding whether you should get treated for cancer.”

Barzilay now studies how smarter computing can help patients. She wields the powerful predictive approach called machine learning, a technique that allows computers, given enough data and training, to pick out patterns on their own — sometimes even beyond what humans are capable of pinpointing.

Machine learning has long been vaunted in consumer contexts — Apple’s Siri can talk with us because machine learning enables her to understand natural human speech — yet the summit gave a glimpse of the approach’s much broader potential. Its reach could offer not only better Siris (e.g., Amazon’s “Alexa”), but improved health care and government policies.

Machine intelligence is “absolutely going to revolutionize our lives,” said Pillar co-founder Jamie Goldstein ’89. Goldstein and Anantha Chandrakasan, head of the MIT Department of Electrical Engineering and Computer Science (EECS) and the Vannevar Bush Professor of Electrical Engineering and Computer Science, organized the conference to bring together industry leaders, venture capitalists, students, and faculty from the Computer Science and Artificial Intelligence (CSAIL), Institute for Data, Systems, and Society (IDSS), and the Laboratory for Information and Decision Systems (LIDS) to discuss real-world problems and machine learning solutions.

Barzilay is already thinking along those lines. Her group’s work aims to help doctors and patients make more informed medical decisions with machine learning. She has a vision for the future patient in the oncologist’s office: “If you’re taking this treatment, [you’ll see] how your chances are going to be changed.”

Machine senses

Machine learning has already proven powerful. But Antonio Torralba, professor of electrical engineering and computer science, believes that machines can learn faster, and thereby do more. His team’s approach mimics the way humans learn in infancy. “We just start playing with things and seeing how they feel,” Torralba said. To illustrate, he showed the room a video of a baby turning over squeaky bubble wrap in her hands. Importantly, we notice the noises things make when we move them around, he said.

To give machines a similar sensory experience of the world, a student of Torralba’s recorded himself tapping more than a thousand objects with a wooden drumstick. Called “Greatest Hits,” the sound collection captured the drumstick clanging ceramic cups, ruffling bushes, and splashing water. After feasting on these videos, a computer could start predicting the sounds of the world — essentially reflecting a grasp of its physics — all without explicit instruction.

Videos of everyday scenes (sans drumstick) also prove deft teachers. Machines are usually guided to pick out objects by training them on annotated images. That means people would meticulously outline a photograph’s individual objects, such as people, lamps, and bar stools, so that computers could learn to identify them. But Torralba and his team have found that by giving computers video complete with objects’ sounds — such as a street’s ambient noise or people talking — a machine’s neural network could begin to pick out objects without any guidance at all.

Torralba recounted how a machine trained this way begins to identify water, the sky, and people’s faces. Machines become remarkably adroit at identifying infants, because “they make a very special noise,” Torralba said. The recognition of sounds resides in a machine’s artificial neurons called units. He continued: “There were a lot of units devoted to babies.”

Decision helpers

Once a machine is educated, it can help experts make better decisions.

Stefanie Jegelka, an assistant professor of electrical engineering and computer science, presented how to make machines learn faster and make predictions more reliably, by identifying maximally informative data. Her team has recently developed new techniques that make this process much more practical.

Alternatively, savvy machines can help us evaluate policies. Tamara Broderick, an assistant professor of electrical engineering and computer science, showed how this works. In collaboration with MIT economist Rachael Meager, her team focused on the question of quickly and accurately quantifying uncertainty. For instance, is microlending, or giving people small loans to jumpstart businesses, is actually helping alleviate poverty. We need to understand the variation in returns on these loans to say.

When we ask a computer to tell us how much more value a loan creates — for instance, $4 made for $3 invested — we can also use machine learning to evaluate how robust that outcome is. What would happen if we were to tweak the model? Broderick asked. “Are we going to get the same number out at the end? Or are we going to get fundamentally different numbers and therefore fundamentally different decisions about what to do — what policy to make?” Machine learning can guide the way.

To our health

But the application of machine intelligence most discussed at the summit was in health care. Mandy Korpusik, a graduate student in CSAIL who shared her work during a pitch session, described an app called Lana that serves as a personal nutritionist. You can tell her what you ate for lunch, and she can recommend what nutrient-rich foods to have in your next meal.

Barzilay, the cancer survivor, wants not only to feed computers clinical reports, but medical scans. These images contain a wealth of information humans alone might be unable to articulate, she said. For example, a machine might be able to discern that given your mammogram, a particular treatment might be 90 percent likely to be effective.

With colleague Tommi Jaakkola, professor of computer science and engineering, Barzilay is also working on extracting the machine’s reasoning, a murkier but necessary endeavor. “Doctors, at least the ones at [Massachusetts General Hospital], are not happy just getting a number at the end,” Barzilay said. “They need to know why.”

Intelligent machines can aid decision making beyond the doctor’s office. Data scientists capable of implementing machine learning have become ubiquitous in government agencies, said Aman Bhandari in a fireside chat-style interview with Ash Ashutoush, CEO of information technology firm Actifio. Bhandari is now at pharmaceutical developer Merck, but worked at the White House in President Barack Obama’s Office of Science and Technology Policy. During his tenure, the administration heavily pushed digitizing all medical records.

“If you think about health care, we’ve moved from — and we’re still moving from — this stone age of data collection, capture, production, and analysis into this possibly ‘industrial era’ of all of those things,” Bhandari said. “So, the first phase is digitizing the system. The next phase is unleashing data from the U.S. government across every single sector."

Jacqueline Xi, an electrical engineering and computer science senior, came away feeling enthusiastic about machine learning’s possibilities. “Just to see everyone in the same room, and people who are founding startups, all here discussing these bigger ideas about how we can connect machine learning across all these groups, is really eye-opening,” she said. “It’s inspiring.”

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Toward X-ray movies

Ultrashort bursts of electrons have several important applications in scientific imaging, but producing them has typically required a costly, power-hungry apparatus about the size of a car.

In the journal Optica, researchers at MIT, the German Synchrotron, and the University of Hamburg in Germany describe a new technique for generating electron bursts, which could be the basis of a shoebox-sized device that consumes only a fraction as much power as its predecessors.

Ultrashort electron beams are used to directly gather information about materials that are undergoing chemical reactions or changes of physical state. But after being fired down a particle accelerator a half a mile long, they’re also used to produce ultrashort X-rays.

Last year, in Nature Communications, the same group of MIT and Hamburg researchers reported the prototype of a small “linear accelerator” that could serve the same purpose as the much larger and more expensive particle accelerator. That technology, together with a higher-energy version of the new “electron gun,” could bring the imaging power of ultrashort X-ray pulses to academic and industry labs.

Indeed, while the electron bursts reported in the new paper have a duration measured in hundreds of femtoseconds, or quadrillionths of a second (which is about what the best existing electron guns can manage), the researchers’ approach has the potential to lower their duration to a single femtosecond. An electron burst of a single femtosecond could generate attosecond X-ray pulses, which would enable real-time imaging of cellular machinery in action.

“We’re building a tool for the chemists, physicists, and biologists who use X-ray light sources or the electron beams directly to do their research,” says Ronny Huang, an MIT PhD student in electrical engineering and first author on the new paper. “Because these electron beams are so short, they allow you to kind of freeze the motion of electrons inside molecules as the molecules are undergoing a chemical reaction. A femtosecond X-ray light source requires more hardware, but it utilizes electron guns.”

In particular, Huang explains, with a technique called electron diffraction imaging, physicists and chemists use ultrashort bursts of electrons to investigate phase changes in materials, such as the transition from an electrically conductive to a nonconductive state, and the creation and dissolution of bonds between molecules in chemical reactions.

Ultrashort X-ray pulses have the same advantages that ordinary X-rays do: They penetrate more deeply into thicker materials. The current method for producing ultrashort X-rays involves sending electron bursts from a car-sized electron gun through a billion-dollar, kilometer-long particle accelerator that increases their velocity. Then they pass between two rows of magnets — known as an “undulator” — that converts them to X-rays.

In the paper published last year — on which Huang was a coauthor — the MIT-Hamburg group, together with colleagues from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg and the University of Toronto, described a new approach to accelerating electrons that could shrink particle accelerators to tabletop size. “This is supposed to complement that,” Huang says, about the new study.

Franz Kärtner, who was a professor of electrical engineering at MIT for 10 years before moving to the German Synchrotron and the University of Hamburg in 2011, led the project. Kärtner remains a principal investigator at MIT’s Research Laboratory of Electronics and is Huang’s thesis advisor. He and Huang are joined on the new paper by eight colleagues from both MIT and Hamburg.

Subwavelength confinement

The researchers’ new electron gun is a variation on a device called an RF gun. But where the RF gun uses radio frequency (RF) radiation to accelerate electrons, the new device uses terahertz radiation, the band of electromagnetic radiation between microwaves and visible light.

The researchers’ device, which is about the size of a matchbox, consists of two copper plates that, at their centers, are only 75 micrometers apart. Each plate has two bends in it, so that it looks rather like a trifold letter that’s been opened and set on its side. The plates bend in opposite directions, so that they’re farthest apart — 6 millimeters — at their edges.

At the center of one of the plates is a quartz slide on which is deposited a film of copper that, at its thinnest, is only 30 nanometers thick. A short burst of light from an ultraviolet laser strikes the film at its thinnest point, jarring loose electrons, which are emitted on the opposite side of the film.

At the same time, a burst of terahertz radiation passes between the plates in a direction perpendicular to that of the laser. All electromagnetic radiation can be thought of as having electrical and magnetic components, which are perpendicular to each other. The terahertz radiation is polarized so that its electric component accelerates the electrons directly toward the second plate.

The key to the system is that the tapering of the plates confines the terahertz radiation to an area — the 75-micrometer gap — that is narrower than its own wavelength. “That’s something special,” Huang says. “Typically, in optics, you can’t confine something to below a wavelength. But using this structure we were able to. Confining it increases the energy density, which increases the accelerating power.”

Because of that increased accelerating power, the device can make do with terahertz beams whose power is much lower than that of the radio-frequency beams used in a typical RF gun. Moreover, the same laser can generate both the ultraviolet beam and, with a few additional optical components, the terahertz beam.

According to James Rosenzweig, a professor of physics at the University of California at Los Angeles, that’s one of the most attractive aspects of the researchers’ system. “One of the main problems you have with ultrafast sources like this is timing jitter between, say, the laser and accelerating field, which produces all sorts of systematic effects that make it harder to do time-resolved electron diffraction,” Rosezweig says.

“In the case of Kärtner’s device, the laser produces the terahertz and also produces the photoelectrons, so the jitter is highly suppressed. You could do pump-probe experiments where the laser is the driver and the electrons would be the probe, and they would be more successful than what you have right now. And of course it would be a very small-sized and modest-cost device. So it might turn out to be very important as far as that scenario goes.”

The researchers’ work was funded by the U.S. Air Force Office of Scientific Research and by the European Research Council. Ronny Huang was supported by a National Defense Science and Engineering Graduate fellowship.

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Biomarker could help guide cancer therapy, avoid drug resistance

MIT biologists have identified a new biomarker that can reveal whether patients with a particularly aggressive type of breast cancer will be helped by paclitaxel (commercially known as Taxol), one of the drugs most commonly used to treat this cancer.

The findings could offer doctors a new way to choose drugs for this type of breast cancer, known as triple-negative because it lacks the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2 protein. The biomarker, a protein called Mena, has previously been shown to help cancer cells spread through the body.

The researchers also showed that combining paclitaxel with another drug that interferes with Mena’s effects can kill the cells much more effectively than paclitaxel alone.

“Drugs that target that pathway restore paclitaxel sensitivity to cells expressing Mena,” says Frank Gertler, an MIT professor of biology and a member of the Koch Institute for Integrative Cancer Research. “The study also suggests that during the course of treatment it might be worth monitoring the level of Mena. If the levels begin to increase, it might suggest that switching to another type of therapy could be useful.”

Gertler is the senior author of the study, which appears in the journal Molecular Cancer Therapeutics. Madeleine Oudin, a Koch Institute postdoc, is the paper’s lead author.

How cells survive

The Mena protein is known to interact with a cell’s cytoskeleton in ways that help the cell to become mobile. Many cancer patients have an alternative form of the protein known as Mena invasive or Mena^INV, which helps cancer cells to spread from their original location through a process known as metastasis. Gertler’s research group has previously found that breast cancer patients who have high levels of the protein’s invasive form tend to have more metastasis and lower survival rates.

The researchers wondered if Mena might also play a role in cancer cell resistance to chemotherapy. Between 30 to 70 percent of triple-negative breast cancer patients respond well to chemotherapy, but the disease reappears within six to 10 months, on average.

“We know we have good drugs that can kill a lot of cancers, but some people don’t respond to them, and some people do respond but only for a short amount of time,” Oudin says.

They tested several different chemotherapy drugs on triple-negative breast cancer cells with varying levels of Mena, and found that those cells with the highest Mena levels were resistant to paclitaxel. However, Mena levels did not affect sensitivity to two other commonly used chemotherapy drugs, doxorubicin and cisplatin.

Paclitaxel, which is also used to treat ovarian cancer, works by interfering with microtubules — small tubular proteins that make up the cell’s cytoskeleton and help with cell division. Microtubules can be either dynamic or stable, and the dynamic version is necessary for cell division. Paclitaxel stabilizes the microtubules, interfering with cell division and killing the cells.

After giving paclitaxel to mice with metastatic triple-negative tumors, the researchers found that tumors with the highest levels of Mena showed the worst response: The drug did not slow growth of either the original tumors or metastases. This effect was the same whether the tumors expressed the invasive form of Mena or the original version.

The researchers also showed that cancer cells with high Mena levels had more dynamic microtubules than cells with low Mena levels. This increase in dynamic microtubules makes it easier for the cells to divide and allows them to resist the effects of paclitaxel.

Countering resistance

Previous studies have shown that paclitaxel treatment also affects a cellular pathway known as ERK signaling, which is often overactive in cancer cells and drives cell proliferation. Paclitaxel treatment turns on this pathway, which helps cancer cells to survive the treatment, but if an inhibitor of ERK signaling is given at the same time, the treatment is more successful.

In the Molecular Cancer Therapeutics study, the MIT team tried the paclitaxel-ERK pathway inhibitor combination in breast cancer cells with high levels of Mena and found that it killed cells much more effectively than paclitaxel alone. Clinical trials are already underway to test this combination of drugs in breast cancer.

“Our work would suggest that for a certain subset of patients that have high levels of Mena, that could be an efficient combination to try,” Oudin says.

The findings could also help doctors choose treatments for patients based on the levels of Mena in their tumors. To pursue that possibility, the researchers now hope to do studies with human tumor samples to see if they show the same relationship between Mena levels, paclitaxel sensitivity, and patient outcome. This work may be done in collaboration with MetaStat, a company that Gertler and others founded to develop diagnostic tests based on Mena and other biomarkers.

“The hope is it may also provide more information on therapeutic choice and potentially spare some patients treatment with a chemotherapy that is likely to be less effective,” Gertler says.

The researchers also hope to uncover more of the mechanism of how Mena affects microtubules, and to see if the same interaction plays a role in drug resistance in other types of cancer, such as ovarian cancer.

The research was funded by the Department of Defense Breast Cancer Research Program, ENS-Cachan, the Ludwig Center at MIT, the National Institutes of Health and National Cancer Institute, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, and the Koch Institute National Cancer Institute core grant.

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