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Monday, February 11th, 2019
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| 10:59a | Acoustic waves can monitor stiffness of living cells MIT engineers have devised a new, noninvasive way to measure the stiffness of living cells using acoustic waves. Their technique allows them to monitor single cells over several generations and investigate how stiffness changes as cells go through the cell division cycle. This approach could also be used to study other biological phenomena such as programmed cell death or metastasis, the researchers say. “Noninvasive monitoring of single-cell mechanical properties could be useful for studying many different types of cellular processes,” says Scott Manalis, the Andrew and Erna Viterbi Professor in the MIT departments of Biological Engineering and Mechanical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. It could also be useful for analyzing how patients’ tumor cells respond to certain drugs, potentially helping doctors choose the best drugs for individual patients, the researchers say. Joon Ho Kang, an MIT graduate student, is the first author of the paper, which appears in the Feb. 11 issue of Nature Methods. Other authors include postdocs Teemu Miettinen and Georgios Katsikis, graduate student Lynna Chen, visiting scholar Selim Olcum, and professor of chemical engineering Patrick Doyle. A unique measurement The new measurement technique makes use of a technology that Manalis’ lab previously developed to measure the mass of cells. This device, known as the suspended microchannel resonator (SMR), can measure the mass of cells as they flow through a tiny fluid-filled cantilever that vibrates inside a vacuum cavity. As cells flow through the channel, their mass slightly alters the cantilever’s vibration frequency, and the mass of the cell can be calculated from that change in frequency. In the new study, the researchers discovered that they could also measure changes in stiffness to the cell — specifically, a cell structure called the cortex that lies just below the cell membrane. The cortex, which helps to determine the shape of a cell, is composed mainly of actin filaments. Contraction and relaxation of these filaments often occurs during processes such as cell division, metastasis, and programmed cell death, leading to changes in the stiffness of the cortex. Over the past couple of years, Manalis and his students realized that the vibration of the cantilever also creates an acoustic wave that can be used to measure the stiffness of the particle or cell flowing through the device. As a particle flows through the channel, it interacts with the acoustic waves, changing the overall energy balance. This alters the vibration of the cantilever, by an amount that varies depending on stiffness of the cell or particle. This allows the researchers to calculate the stiffness of the cell by measuring how much the vibration changes. The researchers confirmed that their technique is accurate by measuring hydrogel particles of known stiffnesses, created in Doyle’s lab, and measuring them as they flowed through the device. The acoustic waves used to generate these measurements disturb the cell by only about 15 nanometers, much less than the displacement produced by most existing techniques for measuring mechanical properties. Cell division The MIT team showed that they could use this technique to measure stiffness of a single cell repeatedly for over 20 hours as they flowed back and forth through the SMR device. During this time, they were able to monitor stiffness through two or more cell division cycles. They found that as cells enter mitosis, stiffness decreases, which the researchers believe is due to the swelling that occurs when the cells prepare to divide. By imaging the cells, they confirmed that the cell cortex becomes thinner as the cell swells. The researchers also found that cell stiffness dynamically changes just before it divides. Actin accumulates at the equatorial region, making the cell stiffer, while the polar regions become more relaxed as actins are temporarily depleted. “We can use our way of measuring stiffness to look at the dynamics of actin in a label-free, noninvasive way,” Kang says. The researchers plan to start using this technique to measure the stiffness of even smaller particles, such as viruses, and to explore whether that measurement might be correlated with a virus’s infectivity. “Measuring stiffness of submicron particles with meaningful throughput is currently not possible with existing approaches,” Manalis says. Such a capability could help researchers who are working on developing weakened viruses that could be tested as possible vaccines. This kind of measurement could also be used to help characterize tiny particles such as those used for drug delivery. Another possible application is combining the stiffness measurement with the mass and growth rate measurements that Manalis’ lab has been developing as a possible predictor of how individual cancer patients will respond to particular drugs. “When it comes to assays for precision medicine, measuring multiple functional properties from the same cell could help to make tests more predictive,” Manalis says. The research was funded by the Koch Institute Support Grant from the National Cancer Institute (NCI), the Ludwig Center for Molecular Oncology, the NCI Cancer Systems Biology Consortium, and the Institute for Collaborative Biotechnologies through the U.S. Army Research Office. |
| 12:35p | Bose grants for 2018 fund research at the frontier of discovery Eight MIT faculty members have been awarded one of the Institute’s most respected honors: the Professor Amar G. Bose Research Grant, which supports work that is unorthodox, and potentially world-changing. The topics of the grants range from nanoscale textiles that purify drinking water, to revolutionary new approaches in catalysis, high-speed logic, and drug delivery. The awards are named for the late Amar G. Bose ’51, SM ’52, ScD ’56, a longtime MIT faculty member and the founder of the Bose Corporation. The Bose Research Fellows for 2018 are Dirk Englund, Laura L. Kiessling, Leonid S. Levitov, Nuno F. Loureiro, Elizabeth M. Nolan, Julia Ortony, Katharina Ribbeck, and Yuriy Román. Each of this year’s grants reflects the innovative thinking, intellectually adventurous spirit, curiosity, and enthusiasm that characterize the Bose grant program. They also embody the value and practice of interdisciplinary collaboration at MIT, which drives discovery and expands the intellectual horizons of individual researchers, their colleagues, and their students. An awards ceremony was hosted by MIT President L. Rafael Reif, and the awards were presented by MIT Provost Martin Schmidt, the Ray and Maria Stata Professor of Electrical Engineering and Computer Science. The fellows provided updates on their ongoing work at the ceremony. As President Reif noted in his remarks, the 2018 awards carry special meaning, because they are the first to be awarded since the untimely passing in November of Vanu Gopal Bose ’87, SM ’94, PhD ’99, the son of Amar Bose and a member of the MIT Corporation. In his professional life and his service to MIT, Vanu Bose was a champion of innovation and supported many others in their pursuit of knowledge and discovery. Novel electronic fluids for high-speed logic in quantum materials Three investigators from the fields of quantum physics, quantum mechanics, and nuclear science and engineering will pool their expertise to explore the wonder material known as graphene. Graphene is an atomically thin carbon sheet possessing unique properties that have made it the subject of intense interest, particularly for its applications in electronics. One of those properties, says Leonid Levitov, professor of physics, is the behavior of electrons in graphene, which travel through this material “like free particles, along straight lines, ballistically, over enormous distances, and showing robust quantum-mechanical behavior up to room temperature.” Dirk Englund, associate professor of electrical engineering and computer science, believes that insights gained from their study of graphene may advance the creation of a new logic device, capable of performing logic operations “many orders of magnitude faster and with much lower energy consumption” than the logic devices powering today’s electronics. “Moore’s Law is coming to an end and really new concepts are needed [to] go beyond the traditional computer architecture,” Englund notes. “A lot of incremental paths have been explored already and they haven’t given us ... another few orders of magnitude of performance. We have to look at radically new ideas.” Nuno Loureiro, associate professor of nuclear science and engineering, describes his role in the project as providing “a bridge between plasma physics” — his own area of expertise — “and the fluid-like dynamics of electrons in graphene.” In his discussions with Levitov, he has come to believe that “there are methods and ideas that can be ported from one system to the other.” “That would be a wonderful outcome” says Loureiro, particularly for exploring some of the astrophysical applications of plasma research. “It’s possible that the behavior of a graphene sheet can map directly to a pair plasma, and if we know how to read that map, we [might create] the first quote-unquote pair plasma in the lab.” He credits the Bose grant for giving him a chance to pursue this unorthodox idea, and stretch beyond his own research. “I’m reaching to something that is completely outside of my domain of expertise, and I’m going to learn a lot. I’m hoping those ideas can then be inspiring for things in my specific domain.” Levitov also appreciates the exchange of ideas that the project will yield. “To a theorist, this is all particularly appealing, as it provides a unique perspective on the developments in my field by connecting it to other fields and, of course, because of a possibly far-reaching outcome this collaboration can lead to.” Controlling infections using nature’s strategies Our bodies are home to trillions of microbes, the vast majority of which reside in the mucus that coats our respiratory tracts, digestive systems, and other bodily systems. Yet the exact functions and molecular structures of mucus remain largely a mystery. Laura Kiessling, professor of chemistry, and Katharina Ribbeck, the Hyman Career Development Professor in Biological Engineering, will use their Bose grant to explore how mucus protects against pathogens, and use that knowledge to create mimetic, bio-inspired materials. Ribbeck compares mucus’s long, thread-like polymers to “tiny bottle brushes, and the bristles of these brushes are sugar molecules.” These glycoproteins regulate microbial physiology by suppressing harmful pathogens and supporting the body’s diverse microbiota. “It's hard to get down to a molecular-level understanding of how our bodies do that,” says Kiessling, but by fabricating bio-inspired materials, “we can alter their properties systematically, and ask those molecular questions that are much harder to investigate with natural materials.” Ribbeck says her team will identify which glycoproteins have the most important effects. That knowledge then “will become the tools for [Kiessling], who will begin to build mimetic, synthetic versions of these molecular structures.” With the rise of antibiotic-resistant infections, they see enormous potential in disarming pathogens rather than killing them with antibiotics (thereby creating evolutionary pressure to become antibiotic-resistant). Instead, as Ribbeck puts it, they are “identifying nature’s strategies and then implementing them with creative chemistry.” Kiessling and Ribbeck say that the Bose grant has enabled them to form a dynamic partnership, and pursue a high-risk, high-reward idea. “As a scientist, you have your dreams, the stuff that keeps you awake at night,” says Ribbeck, and the research she will conduct with Bose grant support is one such project. “I am immensely grateful.” Kiessling is also excited to work on a project with broad applications: “If we can change how people think about treating infectious disease, and [move] toward exploiting natural mechanisms, that could be really transformative.” A heavy-metal Trojan horse One of the most serious threats to human health is the lack of new antibiotics and the rise of antibiotic-resistant disease. To tackle this problem, Elizabeth Nolan, an associate professor of chemistry, will use the Bose research grant to explore the design and delivery of nontraditional antibiotics using a Trojan horse strategy that takes advantage of the mechanisms used by bacteria to obtain iron. “Our idea is that, since these bacteria are expressing machinery that enables iron acquisition, maybe we can take advantage of that machinery as a way to target and deliver antibacterial or toxic cargo, in a species- or strain-selective manner.” The Bose grant will enable her to “build upon [previous work] and start delivering nontraditional toxic cargo into the cell, masked as a beneficial iron chelator to the bacteria.” This precision targeting could minimize the toxicity of drugs to the host, while addressing the problem of antibiotic resistance. It’s the type of unconventional approach that Nolan says can be challenging to fund with traditional sources. Gathering enough preliminary data to support the feasibility of a high-risk idea can be especially challenging, she adds. With the Bose grant, Nolan can take that step, creating avenues for future research in her own lab as well as “tremendous opportunity for collaboration” with researchers in other areas of inquiry. She uses the metaphor of a tree: “We need to build the trunk right now, by making the molecules, and then once we have those, we can branch off in many different directions.” Nolan and her colleagues have been hoping to pursue these ideas for several years, and now, she says, “we can hit the ground running. I’m delighted and very grateful.” Functional textiles for water purification With the support of a Bose research grant, Julia Ortony, the Finmeccanica Career Development Professor of Engineering, hopes to create simple, yet powerful, nanoscale solutions to the problem of arsenic-contaminated drinking water, a threat to the health and lives of millions in Bangladesh and other parts of South Asia. “In our lab, we design small molecules that spontaneously self-assemble in water,” says Ortony. Their goal is to match the mechanical properties of each nanostructure with particular applications. Arsenic removal requires “very high surface area to remove trace amounts of toxins, and very robust structures so that we have very little molecular exchange.” Current methods for removing arsenic are bulky, costly, and hard to maintain. A fabric made of nanoscale fibers would provide the surface area necessary to remove arsenic and could be functionalized with a chemical to grab arsenic ions. It would be simple to distribute and use, and could even be recharged. “We could easily modify this material remove lead or other metals,” she adds. One inspiration behind Ortony’s proposal is a solution devised for guinea worm disease, a parasitic illness spread through drinking water. This disease was eradiated with an astoundingly simple solution: filtering drinking water through nylon fabric. Though contaminants like arsenic and lead are much more complicated to remove, Ortony believes a simple, cost-effective method utilizing nanoscale fabrics is within reach. The Bose grant has allowed her to think more expansively about her research, created exciting opportunities for her students, and enabled her to pursue a project that engages multiple disciplines, including some that are completely new to her. “You learn a lot that way. You can bring very different ideas together, and I think that’s how a lot of discoveries and inventions are made,” she says. Breaking away from mainstream catalysis “The Bose grant is itself like a catalyst,” says Yuriy Román, associate professor of chemical engineering. Román’s research centers on heterogeneous catalysis, with the goal of making chemical reactions faster, more stable, and more efficient. With the support of the Bose research grant, he will embark on a new exploration: the potential of electric fields to impact molecular interactions on catalytic gas-solid surfaces. “In our lab we work on developing strategies to enable renewable energy, implement renewable chemicals and to replace critical materials, but we have never engaged in this idea of joining the fields of electrochemistry and traditional high-temperature catalysis. It’s a completely new direction.” The primary aims in catalysis, Román explains, are maximizing carbon economy, minimizing reactor downtime, and maximizing stability. The use of electric fields offers “an additional handle to control the catalytic process” with a high level of precision. Román was pleased to find the very possibility he is exploring described in papers published in the 1970s by Constantinos G. Vayenas, a former professor of chemical engineering at MIT. By using today’s cutting-edge tools to examine the phenomena that Vayenas observed, Román and his team can expand Vayenas’s work, while adding new insights of their own. While research into the unknown is a bit unnerving, Román says it also “reignites excitement” for discovery for everyone in the lab. He is grateful for the generosity of the Bose family and for the example of Professor Amar Bose, whose wide-ranging contributions and fearless spirit are inspiring. “I'm very happy that we might continue his legacy in some way.” |
| 3:00p | Using artificial intelligence to engineer materials’ properties Applying just a bit of strain to a piece of semiconductor or other crystalline material can deform the orderly arrangement of atoms in its structure enough to cause dramatic changes in its properties, such as the way it conducts electricity, transmits light, or conducts heat. Now, a team of researchers at MIT and in Russia and Singapore have found ways to use artificial intelligence to help predict and control these changes, potentially opening up new avenues of research on advanced materials for future high-tech devices. The findings appear this week in the Proceedings of the National Academy of Sciences, in a paper authored by MIT professor of nuclear science and engineering and of materials science and engineering Ju Li, MIT Principal Research Scientist Ming Dao, and MIT graduate student Zhe Shi, with Evgeni Tsymbalov and Alexander Shapeev at the Skolkovo Institute of Science and Technology in Russia, and Subra Suresh, the Vannevar Bush Professor Emeritus and former dean of engineering at MIT and current president of Nanyang Technological University in Singapore. Already, based on earlier work at MIT, some degree of elastic strain has been incorporated in some silicon processor chips. Even a 1 percent change in the structure can in some cases improve the speed of the device by 50 percent, by allowing electrons to move through the material faster. Recent research by Suresh, Dao, and Yang Lu, a former MIT postdoc now at City University of Hong Kong, showed that even diamond, the strongest and hardest material found in nature, can be elastically stretched by as much as 9 percent without failure when it is in the form of nanometer-sized needles. Li and Yang similarly demonstrated that nanoscale wires of silicon can be stretched purely elastically by more than 15 percent. These discoveries have opened up new avenues to explore how devices can be fabricated with even more dramatic changes in the materials’ properties. Strain made to order Unlike other ways of changing a material’s properties, such as chemical doping, which produce a permanent, static change, strain engineering allows properties to be changed on the fly. “Strain is something you can turn on and off dynamically,” Li says. But the potential of strain-engineered materials has been hampered by the daunting range of possibilities. Strain can be applied in any of six different ways (in three different dimensions, each one of which can produce strain in-and-out or sideways), and with nearly infinite gradations of degree, so the full range of possibilities is impractical to explore simply by trial and error. “It quickly grows to 100 million calculations if we want to map out the entire elastic strain space,” Li says. That’s where this team’s novel application of machine learning methods comes to the rescue, providing a systematic way of exploring the possibilities and homing in on the appropriate amount and direction of strain to achieve a given set of properties for a particular purpose. “Now we have this very high-accuracy method” that drastically reduces the complexity of the calculations needed, Li says. “This work is an illustration of how recent advances in seemingly distant fields such as material physics, artificial intelligence, computing, and machine learning can be brought together to advance scientific knowledge that has strong implications for industry application,” Suresh says. The new method, the researchers say, could open up possibilities for creating materials tuned precisely for electronic, optoelectronic, and photonic devices that could find uses for communications, information processing, and energy applications.
When a small amount of strain is applied to a crystalline material like silicon, its properties can change dramatically; for example, it can shift from blocking electrical current to conducting it freely like a metal. Credit: Frank Shi The team studied the effects of strain on the bandgap, a key electronic property of semiconductors, in both silicon and diamond. Using their neural network algorithm, they were able to predict with high accuracy how different amounts and orientations of strain would affect the bandgap. “Tuning” of a bandgap can be a key tool for improving the efficiency of a device, such as a silicon solar cell, by getting it to match more precisely the kind of energy source that it is designed to harness. By fine-tuning its bandgap, for example, it may be possible to make a silicon solar cell that is just as effective at capturing sunlight as its counterparts but is only one-thousandth as thick. In theory, the material “can even change from a semiconductor to a metal, and that would have many applications, if that’s doable in a mass-produced product,” Li says. While it’s possible in some cases to induce similar changes by other means, such as putting the material in a strong electric field or chemically altering it, those changes tend to have many side effects on the material’s behavior, whereas changing the strain has fewer such side effects. For example, Li explains, an electrostatic field often interferes with the operation of the device because it affects the way electricity flows through it. Changing the strain produces no such interference. Diamond’s potential Diamond has great potential as a semiconductor material, though it’s still in its infancy compared to silicon technology. “It’s an extreme material, with high carrier mobility,” Li says, referring to the way negative and positive carriers of electric current move freely through diamond. Because of that, diamond could be ideal for some kinds of high-frequency electronic devices and for power electronics. By some measures, Li says, diamond could potentially perform 100,000 times better than silicon. But it has other limitations, including the fact that nobody has yet figured out a good and scalable way to put diamond layers on a large substrate. The material is also difficult to “dope,” or introduce other atoms into, a key part of semiconductor manufacturing. By mounting the material in a frame that can be adjusted to change the amount and orientation of the strain, Dao says, “we can have considerable flexibility” in altering its dopant behavior. Whereas this study focused specifically on the effects of strain on the materials’ bandgap, “the method is generalizable” to other aspects, which affect not only electronic properties but also other properties such as photonic and magnetic behavior, Li says. From the 1 percent strain now being used in commercial chips, many new applications open up now that this team has shown that strains of nearly 10 percent are possible without fracturing. “When you get to more than 7 percent strain, you really change a lot in the material,” he says. “This new method could potentially lead to the design of unprecedented material properties,” Li says. “But much further work will be needed to figure out how to impose the strain and how to scale up the process to do it on 100 million transistors on a chip [and ensure that] none of them can fail.” “This innovative new work demonstrates potential to significantly accelerate the engineering of exotic electronic properties in ordinary materials via large elastic strains,” says Evan Reed, an associate professor of materials science and engineering at Stanford University, who was not involved in this research. “It sheds light on the opportunities and limitations that nature exhibits for such strain engineering, and it will be of interest to a broad spectrum of researchers working on important technologies.” The work was supported by the MIT-Skoltech program and Nanyang Technological University. |
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