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Engineered viruses could fight drug resistance

Engineered viruses could fight drug resistance

In the battle against antibiotic resistance, many scientists have been trying to deploy naturally occurring viruses called bacteriophages that can infect and kill bacteria.

Bacteriophages kill bacteria through different mechanisms than antibiotics, and they can target specific strains, making them an appealing option for potentially overcoming multidrug resistance. However, quickly finding and optimizing well-defined bacteriophages to use against a bacterial target is challenging.

In a new study, MIT biological engineers showed that they could rapidly program bacteriophages to kill different strains of E. coli by making mutations in a viral protein that binds to host cells. These engineered bacteriophages are also less likely to provoke resistance in bacteria, the researchers found.

“As we’re seeing in the news more and more now, bacterial resistance is continuing to evolve and is increasingly problematic for public health,” says Timothy Lu, an MIT associate professor of electrical engineering and computer science and of biological engineering. “Phages represent a very different way of killing bacteria than antibiotics, which is complementary to antibiotics, rather than trying to replace them.”

The researchers created several engineered phages that could kill E. coli grown in the lab. One of the newly created phages was also able to eliminate two E. coli strains that are resistant to naturally occurring phages from a skin infection in mice.

Lu is the senior author of the study, which appears in the Oct. 3 issue of Cell. MIT postdoc Kevin Yehl and former postdoc Sebastien Lemire are the lead authors of the paper.

Engineered viruses

The Food and Drug Administration has approved a handful of bacteriophages for killing harmful bacteria in food, but they have not been widely used to treat infections because finding naturally occurring phages that target the right kind of bacteria can be a difficult and time-consuming process.

To make such treatments easier to develop, Lu’s lab has been working on engineered viral “scaffolds” that can be easily repurposed to target different bacterial strains or different resistance mechanisms.

“We think phages are a good toolkit for killing and knocking down bacteria levels inside a complex ecosystem, but in a targeted way,” Lu says.

In 2015, the researchers used a phage from the T7 family, which naturally kills E.coli, and showed that they could program it to target other bacteria by swapping in different genes that code for tail fibers, the protein that bacteriophages use to latch onto receptors on the surfaces of host cells.

While that approach did work, the researchers wanted to find a way to speed up the process of tailoring phages to a particular type of bacteria. In their new study, they came up with a strategy that allows them to rapidly create and test a much greater number of tail fiber variants.

From previous studies of tail fiber structure, the researchers knew that the protein consists of segments called beta sheets that are connected by loops. They decided to try systematically mutating only the amino acids that form the loops, while preserving the beta sheet structure.

“We identified regions that we thought would have minimal effect on the protein structure, but would be able to change its binding interaction with the bacteria,” Yehl says.

They created phages with about 10,000,000 different tail fibers and tested them against several strains of E. coli that had evolved to be resistant to the nonengineered bacteriophage. One way that E. coli can become resistant to bacteriophages is by mutating “LPS” receptors so that they are shortened or missing, but the MIT team found that some of their engineered phages could kill even strains of E. coli with mutated or missing LPS receptors.

This helps to overcome one of the limiting factors in using phages as antimicrobials, which is that bacteria can generate resistance by mutating receptors that the phages use to enter bacteria, says Rotem Sorek, a professor of molecular genetics at the Weizmann Institute of Science.

“Through deep understanding of the biology entailing the phage-bacteria recognition, together with smart bioengineering approaches, Lu and his team managed to design a large library of phage variants, each of which has the potential to recognize a slightly different receptor. They show that treating bacteria with this library rather than with a single phage limits the emergence of resistance,” says Sorek, who was not involved in the study.

Other targets

Lu and Yehl now plan to apply this approach to targeting other resistance mechanisms used by E. coli, and they also hope to develop phages that can kill other types of harmful bacteria. “This is just the beginning, as there are many other viral scaffolds and bacteria to target,” Yehl says. The researchers are also interested in using bacteriophages as a tool to target specific strains of bacteria that live in the human gut and cause health problems.

“Being able to selectively hit those nonbeneficial strains could give us a lot of benefits in terms of human clinical outcomes,” Lu says.

The research was funded by the Defense Threat Reduction Agency, the National Institutes of Health, the U.S. Army Research Laboratory/Army Research Office through the MIT Institute for Soldier Nanotechnologies, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Materials provided by Massachusetts Institute of Technology

Delivery system can make RNA vaccines more powerful

Delivery system can make RNA vaccines more powerful

Vaccines made from RNA hold great potential as a way to treat cancer or prevent a variety of infectious diseases. Many biotech companies are now working on such vaccines, and a few have gone into clinical trials.

One of the challenges to creating RNA vaccines is making sure that the RNA gets into the right immune cells and produces enough of the encoded protein. Additionally, the vaccine must stimulate a strong enough response that the immune system can wipe out the relevant bacteria, viruses, or cancer cells when they are subsequently encountered.

MIT chemical engineers have now developed a new series of lipid nanoparticles to deliver such vaccines. They showed that the particles trigger efficient production of the protein encoded by the RNA, and they also behave like an “adjuvant,” further boosting the vaccine effectiveness. In a study of mice, they used this RNA vaccine to successfully inhibit the growth of melanoma tumors.

“One of the key discoveries of this paper is that you can build RNA delivery lipids that can also activate the immune system in important ways,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

Anderson is the senior author of the study, which appears in the Sept. 30 issue of Nature Biotechnology. The lead authors of the study are former postdocs Lei Miao and Linxian Li and former research associate Yuxuan Huang. Other MIT authors include Derfogail Delcassian, Jasdave Chahal, Jinsong Han, Yunhua Shi, Kaitlyn Sadtler, Wenting Gao, Jiaqi Lin, Joshua C. Doloff, and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.

Vaccine boost

Most traditional vaccines are made from proteins produced by infectious microbes, or from weakened forms of the microbes themselves. In recent years, scientists have explored the idea of making vaccines using DNA that encodes microbial proteins. However, these vaccines, which have not been approved for use in humans, have so far failed to produce strong enough immune responses.

RNA is an attractive alternative to DNA in vaccines because unlike DNA, which has to reach the cell nucleus to become functional, RNA can be translated into protein as soon as it gets into the cell cytoplasm. It can also be adapted to target many different diseases.

“Another advantage of these vaccines is that we can quickly change the target disease,” he says. “We can make vaccines to different diseases very quickly just by tinkering with the RNA sequence.”

For an RNA vaccine to be effective, it needs to enter a type of immune cell called an antigen-presenting cell. These cells then produce the protein encoded by the vaccine and display it on their surfaces, attracting and activating T cells and other immune cells.

Anderson’s lab has previously developed lipid nanoparticles for delivering RNA and DNA for a variety of applications. These lipid particles form tiny droplets that protect RNA molecules and carry them to their destinations. The researchers’ usual approach is to generate libraries of hundreds or thousands of candidate particles with varying chemical features, then screen them for the ones that work the best.

“In one day, we can synthesize over 1,000 lipid materials with multiple different structures,” Miao says. “Once we had that very large library, we could screen the molecules and see which type of structures help RNA get delivered to the antigen-presenting cells.”

They discovered that nanoparticles with a certain chemical feature — a cyclic structure at one end of the particle — are able to turn on an immune signaling pathway called stimulator of interferon genes (STING). Once this pathway is activated, the cells produce interferon and other cytokines that provoke T cells to leap into action.

“Broad applications”

The researchers tested the particles in two different mouse models of melanoma. First, they used mice with tumors engineered to produce ovalbumin, a protein found in egg whites. The researchers designed an RNA vaccine to target ovalbumin, which is not normally found in tumors, and showed that the vaccine stopped tumor growth and significantly prolonged survival.

Then, the researchers created a vaccine that targets a protein naturally produced by melanoma tumors, known as Trp2. This vaccine also stimulated a strong immune response that slowed tumor growth and improved survival rates in the mice.

Anderson says he plans to pursue further development of RNA cancer vaccines as well as vaccines that target infectious diseases such as HIV, malaria, or Ebola.

“We think there could be broad applications for this,” he says. “A particularly exciting area to think about is diseases where there are currently no vaccines.”

Materials provided by Massachusetts Institute of Technology

This flat structure morphs into shape of a human face when temperature changes

This flat structure morphs into shape of a human face when temperature changes

Researchers at MIT and elsewhere have designed 3-D printed mesh-like structures that morph from flat layers into predetermined shapes, in response to changes in ambient temperature. The new structures can transform into configurations that are more complex than what other shape-shifting materials and structures can achieve.

As a demonstration, the researchers printed a flat mesh that, when exposed to a certain temperature difference, deforms into the shape of a human face. They also designed a mesh embedded with conductive liquid metal, that curves into a dome to form an active antenna, the resonance frequency of which changes as it deforms.

The team’s new design method can be used to determine the specific pattern of flat mesh structures to print, given the material’s properties, in order to make the structure transform into a desired shape.

The researchers say that down the road, their technique may be used to design deployable structures, such as tents or coverings that automatically unfurl and inflate in response to changes in temperature or other ambient conditions.

Such complex, shape-shifting structures could also be of use as stents or scaffolds for artificial tissue, or as deformable lenses in telescopes. Wim van Rees, assistant professor of mechanical engineering at MIT, also sees applications in soft robotics.

“I’d like to see this incorporated in, for example, a robotic jellyfish that changes shape to swim as we put it in water,” says van Rees. “If you could use this as an actuator, like an artificial muscle, the actuator could be any arbitrary shape that transforms into another arbitrary shape. Then you’re entering an entirely new design space in soft robotics.”

Van Rees and his colleagues are publishing their results this week in the Proceedings of the National Academy of Sciences. His co-authors are J. William Boley of Boston University; Ryan Truby, Arda Kotikian, Jennifer Lewis, and L. Mahadevan of Harvard University; Charles Lissandrello of Draper Laboratory; and Mark Horenstein of Boston University.

Gift wrap’s limit

Two years ago, van Rees came up with a theoretical design for how to transform a thin flat sheet into a complex shape such as a human face. Until then, researchers in the field of 4-D materials — materials designed to deform over time — had developed ways for certain materials to change, or morph, but only into relatively simple structures.

“My goal was to start with a complex 3-D shape that we want to achieve, like a human face, and then ask, ‘How do we program a material so it gets there?’” van Rees says. “That’s a problem of inverse design.”

He came up with a formula to compute the expansion and contraction that regions of a bilayer material sheet would have to achieve in order to reach a desired shape, and developed a code to simulate this in a theoretical material. He then put the formula to work, and visualized how the method could transform a flat, continuous disc into a complex human face.

But he and his collaborators quickly found that the method wouldn’t apply to most physical materials, at least if they were trying to work with continuous sheets. While van Rees used a continuous sheet for his simulations, it was of an idealized material, with no physical constraints on the amount of expansion and contraction it could achieve. Most materials, in contrast, have very limited growth capabilities. This limitation has profound consequences on a property known as double curvature, meaning a surface that can curve simultaneously in two perpendicular directions — an effect that is described in an almost 200-year-old theorem by Carl Friedrich Gauss called the Theorema Egregium, Latin for “Remarkable Theorem.”

If you’ve ever tried to gift wrap a soccer ball, you’ve experienced this concept in practice: To transform paper, which has no curvature at all, to the shape of a ball, which has positive double curvature, you have to crease and crumple the paper at the sides and bottom to completely wrap the ball. In other words, for the paper sheet to adapt to a shape with double curvature, it would have to stretch or contract, or both, in the necessary places to wrap a ball uniformly.

To impart double curvature to a shape-shifting sheet, the researchers switched the basis of the structure from a continuous sheet to a lattice, or mesh. The idea was twofold: first, a temperature-induced bending of the lattice’s ribs would result in much larger expansions and contractions of the mesh nodes, than could be achieved in a continuous sheet. Second, the voids in the lattice can easily accommodate large changes in surface area when the ribs are designed to grow at different rates across the sheet.

The researchers also designed each individual rib of the lattice to bend by a predetermined degree in order to create the shape of, say, a nose rather than an eye-socket.

For each rib, they incorporated four skinnier ribs, arranging two to line up atop the other two. All four miniribs were made from carefully selected variations of the same base material, to calibrate the required different responses to temperature.

When the four miniribs were bonded together in the printing process to form one larger rib, the rib as a whole could curve due to the difference in temperature response between the materials of the smaller ribs: If one material is more responsive to temperature, it may prefer to elongate. But because it is bonded to a less responsive rib, which resists the elongation, the whole rib will curve instead.

The researchers can play with the arrangement of the four ribs to “preprogram” whether the rib as a whole curves up to form part of a nose, or dips down as part of an eye socket.

Shapes unlocked

To fabricate a lattice that changes into the shape of a human face, the researchers started with a 3-D image of a face — to be specific, the face of Gauss, whose principles of geometry underly much of the team’s approach. From this image, they created a map of the distances a flat surface would require to rise up or dip down to conform to the shape of the face. Van Rees then devised an algorithm to translate these distances into a lattice with a specific pattern of ribs, and ratios of miniribs within each rib.

The team printed the lattice from PDMS, a common rubbery material which naturally expands when exposed to an increase in temperature. They adjusted the material’s temperature responsiveness by infusing one solution of it with glass fibers, making it physically stiffer and more resistant to a change in temperature. After printing lattice patterns of the material, they cured the lattice in a 250-degree-Celsius oven, then took it out and placed it in a saltwater bath, where it cooled to room temperature and morphed into the shape of a human face.

Courtesy of the researchers

The team also printed a latticed disc made from ribs embedded with a liquid metal ink — an antenna of sorts, that changed its resonant frequency as the lattice transformed into a dome.

Van Rees and his colleagues are currently investigating ways to apply the design of complex shape-shifting to stiffer materials, for sturdier applications, such as temperature-responsive tents and self-propelling fins and wings.

This research was supported, in part, by the National Science Foundation, and Draper Laboratory.

Materials provided by Massachusetts Institute of Technology

Photovoltaic-powered sensors for the “internet of things”

Photovoltaic-powered sensors for the “internet of things”

By 2025, experts estimate the number of “internet of things” devices — including sensors that gather real-time data about infrastructure and the environment — could rise to 75 billion worldwide. As it stands, however, those sensors require batteries that must be replaced frequently, which can be problematic for long-term monitoring.

MIT researchers have designed photovoltaic-powered sensors that could potentially transmit data for years before they need to be replaced. To do so, they mounted thin-film perovskite cells — known for their potential low cost, flexibility, and relative ease of fabrication — as energy-harvesters on inexpensive radio-frequency identification (RFID) tags.

The cells could power the sensors in both bright sunlight and dimmer indoor conditions. Moreover, the team found the solar power actually gives the sensors a major power boost that enables greater data-transmission distances and the ability to integrate multiple sensors onto a single RFID tag.

“In the future, there could be billions of sensors all around us. With that scale, you’ll need a lot of batteries that you’ll have to recharge constantly. But what if you could self-power them using the ambient light? You could deploy them and forget them for months or years at a time,” says Sai Nithin Kantareddy, a PhD student in the MIT Auto-ID Laboratory. “This work is basically building enhanced RFID tags using energy harvesters for a range of applications.”

In a pair of papers published in the journals Advanced Functional Materials and IEEE Sensors, MIT Auto-ID Laboratory and MIT Photovoltaics Research Laboratory researchers describe using the sensors to continuously monitor indoor and outdoor temperatures over several days. The sensors transmitted data continuously at distances five times greater than traditional RFID tags — with no batteries required. Longer data-transmission ranges mean, among other things, that one reader can be used to collect data from multiple sensors simultaneously.

Depending on certain factors in their environment, such as moisture and heat, the sensors can be left inside or outside for months or, potentially, years at a time before they degrade enough to require replacement. That can be valuable for any application requiring long-term sensing, indoors and outdoors, including tracking cargo in supply chains, monitoring soil, and monitoring the energy used by equipment in buildings and homes.

Joining Kantareddy on the papers are: Department of Mechanical Engineering (MechE) postdoc Ian Mathews, researcher Shijing Sun, chemical engineering student Mariya Layurova, researcher Janak Thapa, researcher Ian Marius Peters, and Georgia Tech Professor Juan-Pablo Correa-Baena, who are all members of the Photovoltaics Research Laboratory; Rahul Bhattacharyya, a researcher in the AutoID Lab; Tonio Buonassisi, a professor in MechE; and Sanjay E. Sarma, the Fred Fort Flowers and Daniel Fort Flowers Professor of Mechanical Engineering.

Combining two low-cost technologies

In recent attempts to create self-powered sensors, other researchers have used solar cells as energy sources for internet of things (IoT) devices. But those are basically shrunken-down versions of traditional solar cells — not perovskite. The traditional cells can be efficient, long-lasting, and powerful under certain conditions “but are really infeasible for ubiquitous IoT sensors,” Kantareddy says.

Traditional solar cells, for instance, are bulky and expensive to manufacture, plus they are inflexible and cannot be made transparent, which can be useful for temperature-monitoring sensors placed on windows and car windshields. They’re also really only designed to efficiently harvest energy from powerful sunlight, not low indoor light.

Perovskite cells, on the other hand, can be printed using easy roll-to-roll manufacturing techniques for a few cents each; made thin, flexible, and transparent; and tuned to harvest energy from any kind of indoor and outdoor lighting.

The idea, then, was combining a low-cost power source with low-cost RFID tags, which are battery-free stickers used to monitor billions of products worldwide. The stickers are equipped with tiny, ultra-high-frequency antennas that each cost around three to five cents to make.

RFID tags rely on a communication technique called “backscatter,” that transmits data by reflecting modulated wireless signals off the tag and back to a reader. A wireless device called a reader — basically similar to a Wi-Fi router — pings the tag, which powers up and backscatters a unique signal containing information about the product it’s stuck to.

Traditionally, the tags harvest a little of the radio-frequency energy sent by the reader to power up a little chip inside that stores data, and uses the remaining energy to modulate the returning signal. But that amounts to only a few microwatts of power, which limits their communication range to less than a meter.

The researchers’ sensor consists of an RFID tag built on a plastic substrate. Directly connected to an integrated circuit on the tag is an array of perovskite solar cells. As with traditional systems, a reader sweeps the room, and each tag responds. But instead of using energy from the reader, it draws harvested energy from the perovskite cell to power up its circuit and send data by backscattering RF signals.

Efficiency at scale

The key innovations are in the customized cells. They’re fabricated in layers, with perovskite material sandwiched between an electrode, cathode, and special electron-transport layer materials. This achieved about 10 percent efficiency, which is fairly high for still-experimental perovskite cells. This layering structure also enabled the researchers to tune each cell for its optimal “bandgap,” which is an electron-moving property that dictates a cell’s performance in different lighting conditions. They then combined the cells into modules of four cells.

In the Advanced Functional Materials paper, the modules generated 4.3 volts of electricity under one sun illumination, which is a standard measurement for how much voltage solar cells produce under sunlight. That’s enough to power up a circuit — about 1.5 volts — and send data around 5 meters every few seconds. The modules had similar performances in indoor lighting. The IEEE Sensors paper primarily demonstrated wide‐bandgap perovskite cells for indoor applications that achieved between 18.5 percent and 21. 4 percent efficiencies under indoor fluorescent lighting, depending on how much voltage they generate. Essentially, about 45 minutes of any light source will power the sensors indoors and outdoors for about three hours.

The RFID circuit was prototyped to only monitor temperature. Next, the researchers aim to scale up and add more environmental-monitoring sensors to the mix, such as humidity, pressure, vibration, and pollution. Deployed at scale, the sensors could especially aid in long-term data-collection indoors to help build, say, algorithms that help make smart buildings more energy efficient.

“The perovskite materials we use have incredible potential as effective indoor-light harvesters. Our next step is to integrate these same technologies using printed electronics methods, potentially enabling extremely low-cost manufacturing of wireless sensors,” Mathews says.

Materials provided by Massachusetts Institute of Technology

Exotic physics phenomenon is observed for first time

Exotic physics phenomenon is observed for first time

An exotic physical phenomenon, involving optical waves, synthetic magnetic fields, and time reversal, has been directly observed for the first time, following decades of attempts. The new finding could lead to realizations of what are known as topological phases, and eventually to advances toward fault-tolerant quantum computers, the researchers say.

The new finding involves the non-Abelian Aharonov-Bohm Effect and is reported today in the journal Science by MIT graduate student Yi Yang, MIT visiting scholar Chao Peng (a professor at Peking University), MIT graduate student Di Zhu, Professor Hrvoje Buljan at University of Zagreb in Croatia, Francis Wright Davis Professor of Physics John Joannopoulos at MIT, Professor Bo Zhen at the University of Pennsylvania, and MIT professor of physics Marin Soljačić.

The finding relates to gauge fields, which describe transformations that particles undergo. Gauge fields fall into two classes, known as Abelian and non-Abelian. The Aharonov-Bohm Effect, named after the theorists who predicted it in 1959, confirmed that gauge fields — beyond being a pure mathematical aid — have physical consequences.

But the observations only worked in Abelian systems, or those in which gauge fields are commutative — that is, they take place the same way both forward and backward in time.  In 1975, Tai-Tsun Wu and Chen-Ning Yang generalized the effect to the non-Abelian regime as a thought experiment. Nevertheless, it remained unclear whether it would even be possible to ever observe the effect in a non-Abelian system. Physicists lacked ways of creating the effect in the lab, and also lacked ways of detecting the effect even if it could be produced. Now, both of those puzzles have been solved, and the observations carried out successfully.

The effect has to do with one of the strange and counterintuitive aspects of modern physics, the fact that virtually all fundamental physical phenomena are time-invariant. That means that the details of the way particles and forces interact can run either forward or backward in time, and a movie of how the events unfold can be run in either direction, so there’s no way to tell which is the real version. But a few exotic phenomena violate this time symmetry.

Creating the Abelian version of the Aharonov-Bohm effects requires breaking the time-reversal symmetry, a challenging task in itself, Soljačić says. But to achieve the non-Abelian version of the effect requires breaking this time-reversal multiple times, and in different ways, making it an even greater challenge.

To produce the effect, the researchers use photon polarization. Then, they produced two different kinds of time-reversal breaking. They used fiber optics to produce two types of gauge fields that affected the geometric phases of the optical waves, first by sending them through a crystal biased by powerful magnetic fields, and second by modulating them with time-varying electrical signals, both of which break the time-reversal symmetry. They were then able to produce interference patterns that revealed the differences in how the light was affected when sent through the fiber-optic system in opposite directions, clockwise or counterclockwise. Without the breaking of time-reversal invariance, the beams should have been identical, but instead, their interference patterns revealed specific sets of differences as predicted, demonstrating the details of the elusive effect.

The original, Abelian version of the Aharonov-Bohm effect “has been observed with a series of experimental efforts, but the non-Abelian effect has not been observed until now,” Yang says. The finding “allows us to do many things,” he says, opening the door to a wide variety of potential experiments, including classical and quantum physical regimes, to explore variations of the effect.

The experimental approach devised by this team “might inspire the realization of exotic topological phases in quantum simulations using photons, polaritons, quantum gases, and superconducting qubits,” Soljačić says. For photonics itself, this could be useful in a variety of optoelectronic applications, he says. In addition, the non-Abelian gauge fields that the group was able to synthesize produced a non-Abelian Berry phase, and “combined with interactions, it may potentially one day serve as a platform for fault-tolerant topological quantum computation,” he says.

At this point, the experiment is primarily of interest for fundamental physics research, with the aim of gaining a better understanding of some basic underpinnings of modern physical theory. The many possible practical applications “will require additional breakthroughs going forward,” Soljačić says.

For one thing, for quantum computation, the experiment would need to be scaled up from one single device to likely a whole lattice of them. And instead of the beams of laser light used in their experiment, it would require working with a source of single individual photons. But even in its present form, the system could be used to explore questions in topological physics, which is a very active area of current research, Soljačić says.

“The non-Abelian Berry phase is a theoretical gem that is the doorway to understanding many intriguing ideas in contemporary physics,” says Ashvin Vishwanath, a professor of physics at Harvard University, who was not associated with this work. “I am glad to see it getting the experimental attention it deserves in the current work, which reports a well-controlled and characterized realization. I expect this work to stimulate progress both directly as a building block for more complex architectures, and also indirectly in inspiring other realizations.”

Journal Reference: Synthesis and observation of non-Abelian gauge fields in real space

Materials provided by Massachusetts Institute of Technology

A comprehensive catalogue of human digestive tract bacteria

A comprehensive catalogue of human digestive tract bacteria

The human digestive tract is home to thousands of different strains of bacteria. Many of these are beneficial, while others contribute to health problems such as inflammatory bowel disease. Researchers from MIT and the Broad Institute have now isolated and preserved samples of nearly 8,000 of these strains, while also clarifying their genetic and metabolic context.

This data set (BIO-ML), which is available to other researchers who want to use it, should help to shed light on the dynamics of microbial populations in the human gut and may help scientists develop new treatments for a variety of diseases, says Eric Alm, director of MIT’s Center for Microbiome Informatics and Therapeutics and a professor of biological engineering and of civil and environmental engineering at MIT.

“There’s a lot of excitement in the microbiome field because there are associations between these bacteria and health and disease. But we’re lacking in being able to understand why that is, what’s the mechanism, and what are the functions of those bacteria that are causing them to associate with disease,” says Alm, who is the senior author of the study.

The researchers collected stool samples from about 90 people, for up to two years, allowing them to gain insight into how microbial populations change over time within individuals. This study focused on people living in the Boston area, but the research team is now gathering a larger diversity of samples from around the globe, in hopes of preserving microbial strains not found in people living in industrialized societies.

“More than ever before, modern techniques allow us to isolate previously uncultured human gut bacteria. Exploring this genetic and functional diversity is fascinating — everywhere we look, we discover new things. I’m convinced that enriching biobanks with a large diversity of strains from individuals living diverse lifestyles is essential for future advancements in human microbiome research,” says Mathilde Poyet, a senior postdoc at MIT and one of the lead authors of the study.

MIT research associate Mathieu Groussin and former postdoc Sean Gibbons are also lead authors of the study, which appears in the Sept. 2 issue of Nature Medicine. Ramnik Xavier, a professor of medicine at Harvard Medical School and member of the Broad Institute, is a senior author of the study along with Alm.

Microbiome dynamics

Humans have trillions of bacterial cells in their digestive tracts, and while scientists believe that these populations change and evolve over time, there has been little opportunity to observe this. Through the OpenBiome organization, which collects stool samples for research and therapeutic purposes, Alm and his colleagues at MIT and the Broad Institute had access to fecal samples from about 90 people.

For most of their analysis, the researchers focused on microbes found in about a dozen individuals who had provided samples over an extended period, up to two years.

“That was a unique opportunity, and we thought that would be a great set of individuals to really try to dig down and characterize the microbial populations more thoroughly,” Alm says. “To date there hadn’t been a ton of longitudinal studies, and we wanted to make that a key focus of our study, so we could understand what the variation is day-to-day.”

The researchers were able to isolate a total of 7,758 strains from the six major phyla of bacteria that dominate the human GI tract. For 3,632 of these strains, the researchers sequenced their full genomes, and they also sequenced partial genomes of the remaining strains.

Analyzing how microbial populations changed over time within single hosts allowed the researchers to discover some novel interactions between strains. In one case, the researchers found three related strains of Bacteroides vulgatus coexisting within a host, all of which appeared to have diverged from one ancestor strain within the host. In another case, one strain of Turicibacter sanguinis completely replaced a related strain of the same species nearly overnight.

“This is the first time we’re getting a glimpse of these really different dynamics,” Alm says.

Population variation

The researchers also measured the quantities of many metabolites found in the stool samples. This analysis revealed that variations in amino acid levels were closely linked with changes in microbial populations over time within a single person. However, differences between the composition of microbial populations in different people were more closely associated with varying levels of bile acids, which help with digestion.

The researchers don’t know exactly what produces these differences in amino acid and bile acid levels, but say they could be influenced by diet — a connection that they hope to investigate in future studies. They have also made all of their data available online and are offering samples of the strains of bacteria they isolated, allowing other scientists to study the functions of these strains and their potential roles in human health.

“Comprehensive and high-resolution collections of bacterial isolates open the possibility to mechanistically investigate how our lifestyle shapes our gut microbiome, metabolism, and inflammation. We aim to provide such a resource to the research community worldwide, including to lower-income research institutions,” Groussin says.

The researchers have also begun a larger-scale project to collect microbiome samples from a greater diversity of populations around the world. They are especially focusing on underrepresented populations who live in nonindustrialized societies, as their diet and microbiomes are expected to be very different from those of people living in industrialized societies.

“It may be that as populations that have been living traditional lifestyles start to switch to a more industrialized lifestyle, they may lose a lot of that biodiversity. So one of the main things we want to do is conserve it, and then later we can go back and characterize it as well,” Alm says.

Materials provided by Massachusetts Institute of Technology

Robotic thread is designed to slip through the brain’s blood vessels

Robotic thread is designed to slip through the brain’s blood vessels

MIT engineers have developed a magnetically steerable, thread-like robot that can actively glide through narrow, winding pathways, such as the labrynthine vasculature of the brain.

In the future, this robotic thread may be paired with existing endovascular technologies, enabling doctors to remotely guide the robot through a patient’s brain vessels to quickly treat blockages and lesions, such as those that occur in aneurysms and stroke.

“Stroke is the number five cause of death and a leading cause of disability in the United States. If acute stroke can be treated within the first 90 minutes or so, patients’ survival rates could increase significantly,” says Xuanhe Zhao, associate professor of mechanical engineering and of civil and environmental engineering at MIT. “If we could design a device to reverse blood vessel blockage within this ‘golden hour,’ we could potentially avoid permanent brain damage. That’s our hope.”

Zhao and his team, including lead author Yoonho Kim, a graduate student in MIT’s Department of Mechanical Engineering, describe their soft robotic design today in the journal Science Robotics. The paper’s other co-authors are MIT graduate student German Alberto Parada and visiting student Shengduo Liu.

In a tight spot

To clear blood clots in the brain, doctors often perform an endovascular procedure, a minimally invasive surgery in which a surgeon inserts a thin wire through a patient’s main artery, usually in the leg or groin. Guided by a fluoroscope that simultaneously images the blood vessels using X-rays, the surgeon then manually rotates the wire up into the damaged brain vessel. A catheter can then be threaded up along the wire to deliver drugs or clot-retrieval devices to the affected region.

Kim says the procedure can be physically taxing, requiring surgeons, who must be specifically trained in the task, to endure repeated radiation exposure from fluoroscopy.

“It’s a demanding skill, and there are simply not enough surgeons for the patients, especially in suburban or rural areas,” Kim says.

The medical guidewires used in such procedures are passive, meaning they must be manipulated manually, and are typically made from a core of metallic alloys, coated in polymer, a material that Kim says could potentially generate friction and damage vessel linings if the wire were to get temporarily stuck in a particularly tight space.

The team realized that developments in their lab could help improve such endovascular procedures, both in the design of the guidewire and in reducing doctors’ exposure to any associated radiation.

Threading a needle

Over the past few years, the team has built up expertise in both hydrogels — biocompatible materials made mostly of water — and 3-D-printed magnetically-actuated materials that can be designed to crawl, jump, and even catch a ball, simply by following the direction of a magnet.

In this new paper, the researchers combined their work in hydrogels and in magnetic actuation, to produce a magnetically steerable, hydrogel-coated robotic thread, or guidewire, which they were able to make thin enough to magnetically guide through a life-size silicone replica of the brain’s blood vessels.

The core of the robotic thread is made from nickel-titanium alloy, or “nitinol,” a material that is both bendy and springy. Unlike a clothes hanger, which would retain its shape when bent, a nitinol wire would return to its original shape, giving it more flexibility in winding through tight, tortuous vessels. The team coated the wire’s core in a rubbery paste, or ink, which they embedded throughout with magnetic particles.

Finally, they used a chemical process they developed previously, to coat and bond the magnetic covering with hydrogel — a material that does not affect the responsiveness of the underlying magnetic particles and yet provides the wire with a smooth, friction-free, biocompatible surface.

They demonstrated the robotic thread’s precision and activation by using a large magnet, much like the strings of a marionette, to steer the thread through an obstacle course of small rings, reminiscent of a thread working its way through the eye of a needle.

The researchers also tested the thread in a life-size silicone replica of the brain’s major blood vessels, including clots and aneurysms, modeled after the CT scans of an actual patient’s brain. The team filled the silicone vessels with a liquid simulating the viscosity of blood, then manually manipulated a large magnet around the model to steer the robot through the vessels’ winding, narrow paths.

Kim says the robotic thread can be functionalized, meaning that features can be added — for example, to deliver clot-reducing drugs or break up blockages with laser light. To demonstrate the latter, the team replaced the thread’s nitinol core with an optical fiber and found that they could magnetically steer the robot and activate the laser once the robot reached a target region.

When the researchers ran comparisons between the robotic thread coated versus uncoated with hydrogel, they found that the hydrogel gave the thread a much-needed, slippery advantage, allowing it to glide through tighter spaces without getting stuck. In an endovascular surgery, this property would be key to preventing friction and injury to vessel linings as the thread works its way through.

“One of the challenges in surgery has been to be able to navigate through complicated blood vessels in the brain, which has a very small diameter, where commercial catheters can’t reach,” says Kyujin Cho, professor of mechanical engineering at Seoul National University. “This research has shown potential to overcome this challenge and enable surgical procedures in the brain without open surgery.”

And just how can this new robotic thread keep surgeons radiation-free? Kim says that a magnetically steerable guidewire does away with the necessity for surgeons to physically push a wire through a patient’s blood vessels. This means that doctors also wouldn’t have to be in close proximity to a patient, and more importantly, the radiation-generating fluoroscope.

In the near future, he envisions endovascular surgeries that incorporate existing magnetic technologies, such as pairs of large magnets, the directions of which doctors can manipulate from just outside the operating room, away from the fluoroscope imaging the patient’s brain, or even in an entirely different location.

“Existing platforms could apply magnetic field and do the fluoroscopy procedure at the same time to the patient, and the doctor could be in the other room, or even in a different city, controlling the magnetic field with a joystick,” Kim says. “Our hope is to leverage existing technologies to test our robotic thread in vivo in the next step.”

Materials provided by Massachusetts Institute of Technology

For first time, astronomers catch asteroid in the act of changing color

For first time, astronomers catch asteroid in the act of changing color

Last December, scientists discovered an “active” asteroid within the asteroid belt, sandwiched between the orbits of Mars and Jupiter. The space rock, designated by astronomers as 6478 Gault, appeared to be leaving two trails of dust in its wake — active behavior that is associated with comets but rarely seen in asteroids.

While astronomers are still puzzling over the cause of Gault’s comet-like activity, an MIT-led team now reports that it has caught the asteroid in the act of changing color, in the near-infrared spectrum, from red to blue. It is the first time scientists have observed a color-shifting asteroid, in real-time.

“That was a very big surprise,” says Michael Marsset, a postdoc in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS). “We think we have witnessed the asteroid losing its reddish dust to space, and we are seeing the asteroid’s underlying, fresh blue layers.”

Marsset and his colleagues have also confirmed that the asteroid is rocky — proof that the asteroid’s tail, though seemingly comet-like, is caused by an entirely different mechanism, as comets are not rocky but more like loose snowballs of ice and dust.

“It’s the first time to my knowledge that we see a rocky body emitting dust, a little bit like a comet,” Marsset says. “It means that probably some mechanism responsible for dust emission is different from comets, and different from most other active main-belt asteroids.”

Marsset and his colleagues, including EAPS Research Scientist Francesca DeMeo and Professor Richard Binzel, have published their results today in the journal Astrophysical Journal Letters.

A rock with tails

Astronomers first discovered 6478 Gault in 1988 and named the asteroid after planetary geologist Donald Gault. Until recently, the space rock was seen as relatively average, measuring about 2.5 miles wide and orbiting along with millions of other bits of rock and dust within the inner region of the asteroid belt, 214 million miles from the sun.

In January, images from various observatories, including NASA’s Hubble Space Telescope, captured two narrow, comet-like tails trailing the asteroid. Astronomers estimate that the longer tail stretches half a million miles out, while the shorter tail is about a quarter as long. The tails, they concluded, must consist of tens of millions of kilograms of dust, actively ejected by the asteroid, into space. But how? The question reignited interest in Gault, and studies since then have unearthed past instances of similar activity by the asteroid.

“We know of about a million bodies between Mars and Jupiter, and maybe about 20 that are active in the asteroid belt,” Marsset says. “So this is very rare.”

He and his colleagues joined the search for answers to Gault’s activity in March, when they secured observation time at NASA’s Infrared Telescope Facility (IRTF) on Mauna Kea, Hawaii. Over two nights, they observed the asteroid and used a high-precision spectrograph to divide the asteroid’s incoming light into various frequencies, or colors, the relative intensities of which can give scientists an idea of an object’s composition.

From their analysis, the team determined that the asteroid’s surface is composed mainly of silicate, a dry, rocky material, similar to most other asteroids, and, more importantly, not at all like most comets.

Comets typically come from the far colder edges of the solar system. When they approach the sun, any surface ice instantly sublimates, or vaporizes into gas, creating the comet’s characteristic tail. Since Marsset’s team has found 6478 Gault is a dry, rocky body, this means it likely is generating dust tails by some other active mechanism.

A fresh change

As the team observed the asteroid, they discovered, to their surprise, that the rock was changing color in the near-infrared, from red to blue.

“We’ve never seen such a dramatic change like this over such a short period of time,” says co-author DeMeo.

The scientists say they are likely seeing the asteroid’s surface dust, turned red over millions of years of exposure to the sun, being ejected into space, revealing a fresh, less irradiated surface beneath, that appears blue at near-infrared wavelengths.

“Interestingly, you only need a very thin layer to be removed to see a change in the spectrum,” DeMeo says. “It could be as thin as a single layer of grains just microns deep.”

So what could be causing the asteroid to turn color? The team and other groups studying 6478 Gault believe the reason for the color shift, and the asteroid’s comet-like activity, is likely due to the same mechanism: a fast spin. The asteroid may be spinning fast enough to whip off layers of dust from its surface, through sheer centrifugal force. The researchers estimate it would need to have about a two-hour rotation period, spinning around every couple of hours, versus Earth’s 24-hour period.

“About 10 percent of asteroids spin very fast, meaning with a two- to three-hour rotation period, and it’s most likely due to the sun spinning them up,” says Marsset.

This spinning phenomenon is known as the YORP effect (or, the Yarkovsky-O’Keefe-Radzievskii-Paddack effect, named after the scientists who discovered it), which refers to the effect of solar radiation, or photons, on small, nearby bodies such as asteroids. While asteroids reflect most of this radiation back into space, a fraction of these photons is absorbed, then reemitted as heat, and also momentum. This creates a small force that, over millions of years, can cause the asteroid to spin faster.

Astronomers have observed the YORP effect on a handful of asteroids in the past. To confirm a similar effect is acting on 6478 Gault, researchers will have to detect its spin through light curves — measurements of the asteroid’s brightness over time. The challenge will be to see through the asteroid’s considerable dust tail, which can obscure key portions of the asteroid’s light.

Marsset’s team, along with other groups, plan to study the asteroid for further clues to activity, when it next becomes visible in the sky.

“I think [the group’s study] reinforces the fact that the asteroid belt is a really dynamic place,” DeMeo says. “While the asteroid fields you see in the movies, all crashing into each other, is an exaggeration, there is definitely a lot happening out there every moment.”

Materials provided by Massachusetts Institute of Technology

MIT engineers build advanced microprocessor out of carbon nanotubes

MIT engineers build advanced microprocessor out of carbon nanotubes

After years of tackling numerous design and manufacturing challenges, MIT researchers have built a modern microprocessor from carbon nanotube transistors, which are widely seen as a faster, greener alternative to their traditional silicon counterparts.

The microprocessor, described today in the journal Nature, can be built using traditional silicon-chip fabrication processes, representing a major step toward making carbon nanotube microprocessors more practical.

Silicon transistors — critical microprocessor components that switch between 1 and 0 bits to carry out computations — have carried the computer industry for decades. As predicted by Moore’s Law, industry has been able to shrink down and cram more transistors onto chips every couple of years to help carry out increasingly complex computations. But experts now foresee a time when silicon transistors will stop shrinking, and become increasingly inefficient.

Making carbon nanotube field-effect transistors (CNFET) has become a major goal for building next-generation computers. Research indicates CNFETs have properties that promise around 10 times the energy efficiency and far greater speeds compared to silicon. But when fabricated at scale, the transistors often come with many defects that affect performance, so they remain impractical.

The MIT researchers have invented new techniques to dramatically limit defects and enable full functional control in fabricating CNFETs, using processes in traditional silicon chip foundries. They demonstrated a 16-bit microprocessor with more than 14,000 CNFETs that performs the same tasks as commercial microprocessors. The Nature paper describes the microprocessor design and includes more than 70 pages detailing the manufacturing methodology.

The microprocessor is based on the RISC-V open-source chip architecture that has a set of instructions that a microprocessor can execute. The researchers’ microprocessor was able to execute the full set of instructions accurately. It also executed a modified version of the classic “Hello, World!” program, printing out, “Hello, World! I am RV16XNano, made from CNTs.”

“This is by far the most advanced chip made from any emerging nanotechnology that is promising for high-performance and energy-efficient computing,” says co-author Max M. Shulaker, the Emanuel E Landsman Career Development Assistant Professor of Electrical Engineering and Computer Science (EECS) and a member of the Microsystems Technology Laboratories. “There are limits to silicon. If we want to continue to have gains in computing, carbon nanotubes represent one of the most promising ways to overcome those limits. [The paper] completely re-invents how we build chips with carbon nanotubes.”

Joining Shulaker on the paper are: first author and postdoc Gage Hills, graduate students Christian Lau, Andrew Wright, Mindy D. Bishop, Tathagata Srimani, Pritpal Kanhaiya, Rebecca Ho, and Aya Amer, all of EECS; Arvind, the Johnson Professor of Computer Science and Engineering and a researcher in the Computer Science and Artificial Intelligence Laboratory; Anantha Chandrakasan, the dean of the School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science; and Samuel Fuller, Yosi Stein, and Denis Murphy, all of Analog Devices.

Fighting the “bane” of CNFETs

The microprocessor builds on a previous iteration designed by Shulaker and other researchers six years ago that had only 178 CNFETs and ran on a single bit of data. Since then, Shulaker and his MIT colleagues have tackled three specific challenges in producing the devices: material defects, manufacturing defects, and functional issues. Hills did the bulk of the microprocessor design, while Lau handled most of the manufacturing.

For years, the defects intrinsic to carbon nanotubes have been a “bane of the field,” Shulaker says. Ideally, CNFETs need semiconducting properties to switch their conductivity on an off, corresponding to the bits 1 and 0. But unavoidably, a small portion of carbon nanotubes will be metallic, and will slow or stop the transistor from switching. To be robust to those failures, advanced circuits will need carbon nanotubes at around 99.999999 percent purity, which is virtually impossible to produce today.

The researchers came up with a technique called DREAM (an acronym for “designing resiliency against metallic CNTs”), which positions metallic CNFETs in a way that they won’t disrupt computing. In doing so, they relaxed that stringent purity requirement by around four orders of magnitude — or 10,000 times — meaning they only need carbon nanotubes at about 99.99 percent purity, which is currently possible.

Designing circuits basically requires a library of different logic gates attached to transistors that can be combined to, say, create adders and multipliers — like combining letters in the alphabet to create words. The researchers realized that the metallic carbon nanotubes impacted different pairings of these gates differently. A single metallic carbon nanotube in gate A, for instance, may break the connection between A and B. But several metallic carbon nanotubes in gates B may not impact any of its connections.

In chip design, there are many ways to implement code onto a circuit. The researchers ran simulations to find all the different gate combinations that would be robust and wouldn’t be robust to any metallic carbon nanotubes. They then customized a chip-design program to automatically learn the combinations least likely to be affected by metallic carbon nanotubes. When designing a new chip, the program will only utilize the robust combinations and ignore the vulnerable combinations.

“The ‘DREAM’ pun is very much intended, because it’s the dream solution,” Shulaker says. “This allows us to buy carbon nanotubes off the shelf, drop them onto a wafer, and just build our circuit like normal, without doing anything else special.”

Exfoliating and tuning

CNFET fabrication starts with depositing carbon nanotubes in a solution onto a wafer with predesigned transistor architectures. However, some carbon nanotubes inevitably stick randomly together to form big bundles — like strands of spaghetti formed into little balls — that form big particle contamination on the chip.

To cleanse that contamination, the researchers created RINSE (for “removal of incubated nanotubes through selective exfoliation”). The wafer gets pretreated with an agent that promotes carbon nanotube adhesion. Then, the wafer is coated with a certain polymer and dipped in a special solvent. That washes away the polymer, which only carries away the big bundles, while the single carbon nanotubes remain stuck to the wafer. The technique leads to about a 250-times reduction in particle density on the chip compared to similar methods.

Lastly, the researchers tackled common functional issues with CNFETs. Binary computing requires two types of transistors: “N” types, which turn on with a 1 bit and off with a 0 bit, and “P” types, which do the opposite. Traditionally, making the two types out of carbon nanotubes has been challenging, often yielding transistors that vary in performance. For this solution, the researchers developed a technique called MIXED (for “metal interface engineering crossed with electrostatic doping”), which precisely tunes transistors for function and optimization.

In this technique, they attach certain metals to each transistor — platinum or titanium — which allows them to fix that transistor as P or N. Then, they coat the CNFETs in an oxide compound through atomic-layer deposition, which allows them to tune the transistors’ characteristics for specific applications. Servers, for instance, often require transistors that act very fast but use up energy and power. Wearables and medical implants, on the other hand, may use slower, low-power transistors.

The main goal is to get the chips out into the real world. To that end, the researchers have now started implementing their manufacturing techniques into a silicon chip foundry through a program by Defense Advanced Research Projects Agency, which supported the research. Although no one can say when chips made entirely from carbon nanotubes will hit the shelves, Shulaker says it could be fewer than five years. “We think it’s no longer a question of if, but when,” he says.

After years of tackling numerous design and manufacturing challenges, MIT researchers have built a modern microprocessor from carbon nanotube transistors, which are widely seen as a faster, greener alternative to their traditional silicon counterparts.

The microprocessor, described today in the journal Nature, can be built using traditional silicon-chip fabrication processes, representing a major step toward making carbon nanotube microprocessors more practical.

Silicon transistors — critical microprocessor components that switch between 1 and 0 bits to carry out computations — have carried the computer industry for decades. As predicted by Moore’s Law, industry has been able to shrink down and cram more transistors onto chips every couple of years to help carry out increasingly complex computations. But experts now foresee a time when silicon transistors will stop shrinking, and become increasingly inefficient.

Making carbon nanotube field-effect transistors (CNFET) has become a major goal for building next-generation computers. Research indicates CNFETs have properties that promise around 10 times the energy efficiency and far greater speeds compared to silicon. But when fabricated at scale, the transistors often come with many defects that affect performance, so they remain impractical.

The MIT researchers have invented new techniques to dramatically limit defects and enable full functional control in fabricating CNFETs, using processes in traditional silicon chip foundries. They demonstrated a 16-bit microprocessor with more than 14,000 CNFETs that performs the same tasks as commercial microprocessors. The Nature paper describes the microprocessor design and includes more than 70 pages detailing the manufacturing methodology.

The microprocessor is based on the RISC-V open-source chip architecture that has a set of instructions that a microprocessor can execute. The researchers’ microprocessor was able to execute the full set of instructions accurately. It also executed a modified version of the classic “Hello, World!” program, printing out, “Hello, World! I am RV16XNano, made from CNTs.”

“This is by far the most advanced chip made from any emerging nanotechnology that is promising for high-performance and energy-efficient computing,” says co-author Max M. Shulaker, the Emanuel E Landsman Career Development Assistant Professor of Electrical Engineering and Computer Science (EECS) and a member of the Microsystems Technology Laboratories. “There are limits to silicon. If we want to continue to have gains in computing, carbon nanotubes represent one of the most promising ways to overcome those limits. [The paper] completely re-invents how we build chips with carbon nanotubes.”

Joining Shulaker on the paper are: first author and postdoc Gage Hills, graduate students Christian Lau, Andrew Wright, Mindy D. Bishop, Tathagata Srimani, Pritpal Kanhaiya, Rebecca Ho, and Aya Amer, all of EECS; Arvind, the Johnson Professor of Computer Science and Engineering and a researcher in the Computer Science and Artificial Intelligence Laboratory; Anantha Chandrakasan, the dean of the School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science; and Samuel Fuller, Yosi Stein, and Denis Murphy, all of Analog Devices.

Fighting the “bane” of CNFETs

The microprocessor builds on a previous iteration designed by Shulaker and other researchers six years ago that had only 178 CNFETs and ran on a single bit of data. Since then, Shulaker and his MIT colleagues have tackled three specific challenges in producing the devices: material defects, manufacturing defects, and functional issues. Hills did the bulk of the microprocessor design, while Lau handled most of the manufacturing.

For years, the defects intrinsic to carbon nanotubes have been a “bane of the field,” Shulaker says. Ideally, CNFETs need semiconducting properties to switch their conductivity on an off, corresponding to the bits 1 and 0. But unavoidably, a small portion of carbon nanotubes will be metallic, and will slow or stop the transistor from switching. To be robust to those failures, advanced circuits will need carbon nanotubes at around 99.999999 percent purity, which is virtually impossible to produce today.

The researchers came up with a technique called DREAM (an acronym for “designing resiliency against metallic CNTs”), which positions metallic CNFETs in a way that they won’t disrupt computing. In doing so, they relaxed that stringent purity requirement by around four orders of magnitude — or 10,000 times — meaning they only need carbon nanotubes at about 99.99 percent purity, which is currently possible.

Designing circuits basically requires a library of different logic gates attached to transistors that can be combined to, say, create adders and multipliers — like combining letters in the alphabet to create words. The researchers realized that the metallic carbon nanotubes impacted different pairings of these gates differently. A single metallic carbon nanotube in gate A, for instance, may break the connection between A and B. But several metallic carbon nanotubes in gates B may not impact any of its connections.

In chip design, there are many ways to implement code onto a circuit. The researchers ran simulations to find all the different gate combinations that would be robust and wouldn’t be robust to any metallic carbon nanotubes. They then customized a chip-design program to automatically learn the combinations least likely to be affected by metallic carbon nanotubes. When designing a new chip, the program will only utilize the robust combinations and ignore the vulnerable combinations.

“The ‘DREAM’ pun is very much intended, because it’s the dream solution,” Shulaker says. “This allows us to buy carbon nanotubes off the shelf, drop them onto a wafer, and just build our circuit like normal, without doing anything else special.”

Exfoliating and tuning

CNFET fabrication starts with depositing carbon nanotubes in a solution onto a wafer with predesigned transistor architectures. However, some carbon nanotubes inevitably stick randomly together to form big bundles — like strands of spaghetti formed into little balls — that form big particle contamination on the chip.

To cleanse that contamination, the researchers created RINSE (for “removal of incubated nanotubes through selective exfoliation”). The wafer gets pretreated with an agent that promotes carbon nanotube adhesion. Then, the wafer is coated with a certain polymer and dipped in a special solvent. That washes away the polymer, which only carries away the big bundles, while the single carbon nanotubes remain stuck to the wafer. The technique leads to about a 250-times reduction in particle density on the chip compared to similar methods.

Lastly, the researchers tackled common functional issues with CNFETs. Binary computing requires two types of transistors: “N” types, which turn on with a 1 bit and off with a 0 bit, and “P” types, which do the opposite. Traditionally, making the two types out of carbon nanotubes has been challenging, often yielding transistors that vary in performance. For this solution, the researchers developed a technique called MIXED (for “metal interface engineering crossed with electrostatic doping”), which precisely tunes transistors for function and optimization.

In this technique, they attach certain metals to each transistor — platinum or titanium — which allows them to fix that transistor as P or N. Then, they coat the CNFETs in an oxide compound through atomic-layer deposition, which allows them to tune the transistors’ characteristics for specific applications. Servers, for instance, often require transistors that act very fast but use up energy and power. Wearables and medical implants, on the other hand, may use slower, low-power transistors.

The main goal is to get the chips out into the real world. To that end, the researchers have now started implementing their manufacturing techniques into a silicon chip foundry through a program by Defense Advanced Research Projects Agency, which supported the research. Although no one can say when chips made entirely from carbon nanotubes will hit the shelves, Shulaker says it could be fewer than five years. “We think it’s no longer a question of if, but when,” he says.

Materials provided by Massachusetts Institute of Technology

A battery-free sensor for underwater exploration

A battery-free sensor for underwater exploration

To investigate the vastly unexplored oceans covering most our planet, researchers aim to build a submerged network of interconnected sensors that send data to the surface — an underwater “internet of things.” But how to supply constant power to scores of sensors designed to stay for long durations in the ocean’s deep?

MIT researchers have an answer: a battery-free underwater communication system that uses near-zero power to transmit sensor data. The system could be used to monitor sea temperatures to study climate change and track marine life over long periods — and even sample waters on distant planets. They are presenting the system at the SIGCOMM conference this week, in a paper that has won the conference’s “best paper” award.

The system makes use of two key phenomena. One, called the “piezoelectric effect,” occurs when vibrations in certain materials generate an electrical charge. The other is “backscatter,” a communication technique commonly used for RFID tags, that transmits data by reflecting modulated wireless signals off a tag and back to a reader.

In the researchers’ system, a transmitter sends acoustic waves through water toward a piezoelectric sensor that has stored data. When the wave hits the sensor, the material vibrates and stores the resulting electrical charge. Then the sensor uses the stored energy to reflect a wave back to a receiver — or it doesn’t reflect one at all. Alternating between reflection in that way corresponds to the bits in the transmitted data: For a reflected wave, the receiver decodes a 1; for no reflected wave, the receiver decodes a 0.

“Once you have a way to transmit 1s and 0s, you can send any information,” says co-author Fadel Adib, an assistant professor in the MIT Media Lab and the Department of Electrical Engineering and Computer Science and founding director of the Signal Kinetics Research Group. “Basically, we can communicate with underwater sensors based solely on the incoming sound signals whose energy we are harvesting.”

The researchers demonstrated their Piezo-Acoustic Backscatter System in an MIT pool, using it to collect water temperature and pressure measurements. The system was able to transmit 3 kilobytes per second of accurate data from two sensors simultaneously at a distance of 10 meters between sensor and receiver.

Applications go beyond our own planet. The system, Adib says, could be used to collect data in the recently discovered subsurface ocean on Saturn’s largest moon, Titan. In June, NASA announced the Dragonfly mission to send a rover in 2026 to explore the moon, sampling water reservoirs and other sites.

“How can you put a sensor under the water on Titan that lasts for long periods of time in a place that’s difficult to get energy?” says Adib, who co-wrote the paper with Media Lab researcher JunSu Jang. “Sensors that communicate without a battery open up possibilities for sensing in extreme environments.”


Preventing deformation

Inspiration for the system hit while Adib was watching “Blue Planet,” a nature documentary series exploring various aspects of sea life. Oceans cover about 72 percent of Earth’s surface. “It occurred to me how little we know of the ocean and how marine animals evolve and procreate,” he says. Internet-of-things (IoT) devices could aid that research, “but underwater you can’t use Wi-Fi or Bluetooth signals … and you don’t want to put batteries all over the ocean, because that raises issues with pollution.”

That led Adib to piezoelectric materials, which have been around and used in microphones and other devices for about 150 years. They produce a small voltage in response to vibrations. But that effect is also reversible: Applying voltage causes the material to deform. If placed underwater, that effect produces a pressure wave that travels through the water. They’re often used to detect sunken vessels, fish, and other underwater objects.

“That reversibility is what allows us to develop a very powerful underwater backscatter communication technology,” Adib says.

Communicating relies on preventing the piezoelectric resonator from naturally deforming in response to strain. At the heart of the system is a submerged node, a circuit board that houses a piezoelectric resonator, an energy-harvesting unit, and a microcontroller. Any type of sensor can be integrated into the node by programming the microcontroller. An acoustic projector (transmitter) and underwater listening device, called a hydrophone (receiver), are placed some distance away.

Say the sensor wants to send a 0 bit. When the transmitter sends its acoustic wave at the node, the piezoelectric resonator absorbs the wave and naturally deforms, and the energy harvester stores a little charge from the resulting vibrations. The receiver then sees no reflected signal and decodes a 0.

However, when the sensor wants to send a 1 bit, the nature changes. When the transmitter sends a wave, the microcontroller uses the stored charge to send a little voltage to the piezoelectric resonator. That voltage reorients the material’s structure in a way that stops it from deforming, and instead reflects the wave. Sensing a reflected wave, the receiver decodes a 1.

Long-term deep-sea sensing

The transmitter and receiver must have power but can be planted on ships or buoys, where batteries are easier to replace, or connected to outlets on land. One transmitter and one receiver can gather information from many sensors covering one area or many areas.

“When you’re tracking a marine animal, for instance, you want to track it over a long range and want to keep the sensor on them for a long period of time. You don’t want to worry about the battery running out,” Adib says. “Or, if you want to track temperature gradients in the ocean, you can get information from sensors covering a number of different places.”

Another interesting application is monitoring brine pools, large areas of brine that sit in pools in ocean basins, and are difficult to monitor long-term. They exist, for instance, on the Antarctic Shelf, where salt settles during the formation of sea ice, and could aid in studying melting ice and marine life interaction with the pools. “We could sense what’s happening down there, without needing to keep hauling sensors up when their batteries die,” Adib says.

Polly Huang, a professor of electrical engineering at Taiwan National University, praised the work for its technical novelty and potential impact on environmental science. “This is a cool idea,” Huang says. “It’s not news one uses piezoelectric crystals to harvest energy … [but is the] first time to see it being used as a radio at the same time [which] is unheard of to the sensor network/system research community. Also interesting and unique is the hardware design and fabrication. The circuit and the design of the encapsulation are both sound and interesting.”

While noting that the system still needs more experimentation, especially in sea water, Huang adds that “this might be the ultimate solution for researchers in marine biography, oceanography, or even meteorology — those in need of long-term, low-human-effort underwater sensing.”

Next, the researchers aim to demonstrate that the system can work at farther distances and communicate with more sensors simultaneously. They’re also hoping to test if the system can transmit sound and low-resolution images.