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    Tiny magnetic beads produce an optical signal that could be used to quickly detect pathogens

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    Getting results from a blood test can take anywhere from one day to a week, depending on what a test is targeting. The same goes for tests of water pollution and food contamination. And in most cases, the wait time has to do with time-consuming steps in sample processing and analysis.

    Now, MIT engineers have identified a new optical signature in a widely used class of magnetic beads, which could be used to quickly detect contaminants in a variety of diagnostic tests. For example, the team showed the signature could be used to detect signs of the food contaminant Salmonella.

    The so-called Dynabeads are microscopic magnetic beads that can be coated with antibodies that bind to target molecules, such as a specific pathogen. Dynabeads are typically used in experiments in which they are mixed into solutions to capture molecules of interest. But from there, scientists have to take additional, time-consuming steps to confirm that the molecules are indeed present and bound to the beads.

    The MIT team found a faster way to confirm the presence of Dynabead-bound pathogens, using optics, specifically, Raman spectroscopy. This optical technique identifies specific molecules based on their “Raman signature,” or the unique way in which a molecule scatters light.

    The researchers found that Dynabeads have an unusually strong Raman signature that can be easily detected, much like a fluorescent tag. This signature, they found, can act as a “reporter.” If detected, the signal can serve as a quick confirmation, within less than one second, that a target pathogen is indeed present in a given sample. The team is currently working to develop a portable device for quickly detecting a range of bacterial pathogens, and their results will appear in an Emerging Investigators special issue of the Journal of Raman Spectroscopy.

    “This technique would be useful in a situation where a doctor is trying to narrow down the source of an infection in order to better inform antibiotic prescription, as well as for the detection of known pathogens in food and water,” says study co-author Marissa McDonald, a graduate student in the Harvard-MIT Program in Health Sciences and Technology. “Additionally, we hope this approach will eventually lead to expanded access to advanced diagnostics in resource-limited environments.”

    Study co-authors at MIT include Postdoctoral Associate Jongwan Lee; Visiting Scholar Nikiwe Mhlanga; Research Scientist Jeon Woong Kang; Tata Professor Rohit Karnik, who is also the associate director of the Abdul Latif Jameel Water and Food Systems Lab; and Assistant Professor Loza Tadesse of the Department of Mechanical Engineering.

    Oil and water

    Looking for diseased cells and pathogens in fluid samples is an exercise in patience.

    “It’s kind of a needle-in-a-haystack problem,” Tadesse says.

    The numbers present are so small that they must be grown in controlled environments to sufficient numbers, and their cultures stained, then studied under a microscope. The entire process can take several days to a week to yield a confident positive or negative result.

    Both Karnik and Tadesse’s labs have independently been developing techniques to speed up various parts of the pathogen testing process and make the process portable, using Dynabeads.

    Dynabeads are commercially available microscopic beads made from a magnetic iron core and a polymer shell that can be coated with antibodies. The surface antibodies act as hooks to bind specific target molecules. When mixed with a fluid, such as a vial of blood or water, any molecules present will glom onto the Dynabeads. Using a magnet, scientists can gently coax the beads to the bottom of a vial and filter them out of a solution. Karnik’s lab is investigating ways to then further separate the beads into those that are bound to a target molecule, and those that are not. “Still, the challenge is, how do we know that we have what we’re looking for?” Tadesse says.

    The beads themselves are not visible by eye. That’s where Tadesse’s work comes in. Her lab uses Raman spectroscopy as a way to “fingerprint” pathogens. She has found that different cell types scatter light in unique ways that can be used as a signature to identify them.

    In the team’s new work, she and her colleagues found that Dynabeads also have a unique and strong Raman signature that can act as a surprisingly clear beacon.

    “We were initially seeking to identify the signatures of bacteria, but the signature of the Dynabeads was actually very strong,” Tadesse says. “We realized this signal could be a means of reporting to you whether you have that bacteria or not.”

    Testing beacon

    As a practical demonstration, the researchers mixed Dynabeads into vials of water contaminated with Salmonella. They then magnetically isolated these beads onto microscope slides and measured the way light scattered through the fluid when exposed to laser light. Within half a second, they quickly detected the Dynabeads’ Raman signature — a confirmation that bound Dynabeads, and by inference, Salmonella, were present in the fluid.

    “This is something that can be used to rapidly give a positive or negative answer: Is there a contaminant or not?” Tadesse says. “Because even a handful of pathogens can cause clinical symptoms.”

    The team’s new technique is significantly faster than conventional methods and uses elements that could be adapted into smaller, more portable forms — a goal that the researchers are currently working toward. The approach is also highly versatile.

    “Salmonella is the proof of concept,” Tadesse says. “You could purchase Dynabeads with E.coli antibodies, and the same thing would happen: It would bind to the bacteria, and we’d be able to detect the Dynabead signature because the signal is super strong.”

    The team is particularly keen to apply the test to conditions such as sepsis, where time is of the essence, and where pathogens that trigger the condition are not rapidly detected using conventional lab tests.

    “There are a lot cases, like in sepsis, where pathogenic cells cannot always be grown on a plate,” says Lee, a member of Karnik’s lab. “In that case, our technique could rapidly detect these pathogens.”

    This research was supported, in part, by the MIT Laser Biomedical Research Center, the National Cancer Institute, and the Abdul Latif Jameel Water and Food Systems Lab at MIT. More

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      in Energy

      New materials could enable longer-lasting implantable batteries

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      For the last few decades, battery research has largely focused on rechargeable lithium-ion batteries, which are used in everything from electric cars to portable electronics and have improved dramatically in terms of affordability and capacity. But nonrechargeable batteries have seen little improvement during that time, despite their crucial role in many important uses such as implantable medical devices like pacemakers.

      Now, researchers at MIT have come up with a way to improve the energy density of these nonrechargeable, or “primary,” batteries. They say it could enable up to a 50 percent increase in useful lifetime, or a corresponding decrease in size and weight for a given amount of power or energy capacity, while also improving safety, with little or no increase in cost.

      The new findings, which involve substituting the conventionally inactive battery electrolyte with a material that is active for energy delivery, are reported today in the journal Proceedings of the National Academy of Sciences, in a paper by MIT Kavanaugh Postdoctoral Fellow Haining Gao, graduate student Alejandro Sevilla, associate professor of mechanical engineering Betar Gallant, and four others at MIT and Caltech.

      Replacing the battery in a pacemaker or other medical implant requires a surgical procedure, so any increase in the longevity of their batteries could have a significant impact on the patient’s quality of life, Gallant says. Primary batteries are used for such essential applications because they can provide about three times as much energy for a given size and weight as rechargeable batteries.

      That difference in capacity, Gao says, makes primary batteries “critical for applications where charging is not possible or is impractical.” The new materials work at human body temperature, so would be suitable for medical implants. In addition to implantable devices, with further development to make the batteries operate efficiently at cooler temperatures, applications could also include sensors in tracking devices for shipments, for example to ensure that temperature and humidity requirements for food or drug shipments are properly maintained throughout the shipping process. Or, they might be used in remotely operated aerial or underwater vehicles that need to remain ready for deployment over long periods.

      Pacemaker batteries typically last from five to 10 years, and even less if they require high-voltage functions such as defibrillation. Yet for such batteries, Gao says, the technology is considered mature, and “there haven’t been any major innovations in fundamental cell chemistries in the past 40 years.”

      The key to the team’s innovation is a new kind of electrolyte — the material that lies between the two electrical poles of the battery, the cathode and the anode, and allows charge carriers to pass through from one side to the other. Using a new liquid fluorinated compound, the team found that they could combine some of the functions of the cathode and the electrolyte in one compound, called a catholyte. This allows for saving much of the weight of typical primary batteries, Gao says.

      While there are other materials besides this new compound that could theoretically function in a similar catholyte role in a high-capacity battery, Gallant explains, those materials have lower inherent voltages that do not match those of the remainder of the material in a conventional pacemaker battery, a type known as CFx. Because the overall output from the battery can’t be more than that of the lesser of the two electrode materials,  the extra capacity would go to waste because of the voltage mismatch. But with the new material, “one of the key merits of our fluorinated liquids is that their voltage aligns very well with that of CFx,” Gallant says.

      In a conventional  CFx battery, the liquid electrolyte is essential because it allows charged particles to pass through from one electrode to the other. But “those electrolytes are actually chemically inactive, so they’re basically dead weight,” Gao says. This means about 50 percent of the battery’s key components, mainly the electrolyte, is inactive material. But in the new design with the fluorinated catholyte material, the amount of dead weight can be reduced to about 20 percent, she says.

      The new cells also provide safety improvements over other kinds of proposed chemistries that would use toxic and corrosive catholyte materials, which their formula does not, Gallant says. And preliminary tests have demonstrated a stable shelf life over more than a year, an important characteristic for primary batteries, she says.

      So far, the team has not yet experimentally achieved the full 50 percent improvement in energy density predicted by their analysis. They have demonstrated a 20 percent improvement, which in itself would be an important gain for some applications, Gallant says. The design of the cell itself has not yet been fully optimized, but the researchers can project the cell performance based on the performance of the active material itself. “We can see the projected cell-level performance when it’s scaled up can reach around 50 percent higher than the CFx cell,” she says. Achieving that level experimentally is the team’s next goal.

      Sevilla, a doctoral student in the mechanical engineering department, will be focusing on that work in the coming year. “I was brought into this project to try to understand some of the limitations of why we haven’t been able to attain the full energy density possible,” he says. “My role has been trying to fill in the gaps in terms of understanding the underlying reaction.”

      One big advantage of the new material, Gao says, is that it can easily be integrated into existing battery manufacturing processes, as a simple substitution of one material for another. Preliminary discussions with manufacturers confirm this potentially easy substitution, Gao says. The basic starting material, used for other purposes, has already been scaled up for production, she says, and its price is comparable to that of the materials currently used in CFx batteries. The cost of batteries using the new material is likely to be comparable to the existing batteries as well, she says. The team has already applied for a patent on the catholyte, and they expect that the medical applications are likely to be the first to be commercialized, perhaps with a full-scale prototype ready for testing in real devices within about a year.

      Further down the road, other applications could likely take advantage of the new materials as well, such as smart water or gas meters that can be read out remotely, or devices like EZPass transponders, increasing their usable lifetime, the researchers say. Power for drone aircraft or undersea vehicles would require higher power and so may take longer to be developed. Other uses could include batteries for equipment used at remote sites, such as drilling rigs for oil and gas, including devices sent down into the wells to monitor conditions.

      The team also included Gustavo Hobold, Aaron Melemed, and Rui Guo at MIT and Simon Jones at Caltech. The work was supported by MIT Lincoln Laboratory and the Army Research Office. More

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      in Energy

      A lasting — and valuable — legacy

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      Betar Gallant, MIT associate professor and Class of 1922 Career Development Chair in Mechanical Engineering, grew up in a curious, independently minded family. Her mother had multiple jobs over the years, including in urban planning and in the geospatial field. Her father, although formally trained in English, read textbooks of all kinds from cover to cover, taught himself numerous technical fields including engineering, and worked successfully in them. When Gallant was very young, she and her father did science experiments in the basement.

      It wasn’t until she was in her teenage years, though, that she says she got drawn into science. Her father, who had fallen ill five years before, died when Gallant was 16, and while grieving, “when I was missing him the most,” she started to look at what had captivated her father.

      “I started to take a deeper interest in the things he had spent his life working on as a way to feel closer to him in his absence,” Gallant says. “I spent a few long months one summer looking through some of the things he had worked on, and found myself reading physics textbooks. That was enough, and I was hooked.”

      The love for independently finding and understanding solutions, that she had apparently inherited from her parents, eventually took her to the professional love of her life: electrochemistry.

      As an undergraduate at MIT, Gallant did an Undergraduate Research Opportunities Program project with Professor Yang Shao-Horn’s research group that went from her sophomore year through her senior thesis. This was Gallant’s first official exposure to electrochemistry.

      “When I met Yang, she showed me very quickly how challenging and enriching electrochemistry can be, and there was real conviction and excitement in how she and her group members talked about research,” Gallant says. “It was totally eye-opening, and I’m fortunate that she was a (relatively rare) electrochemist in a mechanical engineering department, or else I likely would not have been able to go down that road.”

      Play video

      Gallant earned three degrees at MIT (’08, SM ’10, and PhD ’13). Before joining the MIT faculty in 2016, she was a Kavli Nanoscience Institute Prize Postdoctoral Fellow at Caltech in the Division of Chemistry and Chemical Engineering.

      Her passion for electrochemistry is enormous. “Electrons are just dazzling — they power so much of our everyday world, and are the key to a renewable future,” she says, explaining that despite electrons’ amazing potential, isolated electrons cannot be stored and produced on demand, because “nature doesn’t allow excessive amounts of charge imbalances to accumulate.”

      Electrons can, however, be stored on molecules, in bonds and in metal ions or nonmetal centers that are able to lose and gain electrons — as long as positive charge transfers occur to accommodate the electrons.

      “Here’s where chemistry rears its head,” Gallant says. “What types of molecules or materials can behave in this way? How do we store as much charge as possible while making the weight and volume as low as possible?”

      Gallant points out that early battery developers using lithium and ions built a technology that “has arguably shaped our modern world more than any other.

      “If you look at some early papers, the concepts of how a lithium-ion battery or a lithium metal anode worked were sketched out by hand — they had been deduced to be true, before the field even had the tools to prove all the mechanisms were actually occurring — yet even now, those ideas are still turning out to be right!”

      Gallant says, “that’s because if you truly understand the basic principles of electrochemistry, you can start to intuit how systems will behave. Once you can do that, you can really begin to engineer better materials and devices.”

      Truly her father’s daughter, Gallant’s emphasis is on independently finding solutions.

      “Ultimately, it’s a race to have the best mental models,” she says. “A great lab and lots of funding and personnel to run it are very nice, but the most valuable tools in the toolbox are solid mental models and a way of thinking about electrochemistry, which is actually very personalized depending on the researcher.”

      She says one project with immediate impact that’s coming out of her Gallant Energy and Carbon Conversion Lab relates to primary (non-rechargeable) battery work that she and her team are working to commercialize. It involves injecting new electrochemically active electrolytes into leading high-energy batteries as they’re being assembled. Replacing a conventional electrolyte with the new chemistry decreases the normally inactive weight of the battery and boosts the energy substantially, Gallant says. One important application of such batteries would be for medical devices such as pacemakers.

      “If you can extend lifetime, you’re talking about longer times between invasive replacement surgeries, which really affects patient quality of life,” she says.

      Gallant’s team is also leading efforts to enable higher-energy rechargeable lithium-ion batteries for electric vehicles. Key to a step-change in energy, and therefore driving range, is to use a lithium metal anode in place of graphite. Lithium metal is highly reactive, however, with all battery electrolytes, and its interface needs to be stabilized in ways that still elude researchers. Gallant’s team is developing design guidelines for such interfaces, and for next-generation electrolytes to form and sustain these interfaces. Gallant says that applying the technology to that purpose and commercializing it would be “a bit longer-term, but I believe this change to lithium anodes will happen, and it’s just a matter of when.”

      About six years ago, when Gallant founded her lab, she and her team started introducing carbon dioxide into batteries as a way to experiment with electrochemical conversion of the greenhouse gas. She says they realized that batteries do not present the best practical technology to mitigate CO2, but their experimentation did open up new paths to carbon capture and conversion. “That work allowed us to think creatively, and we started to realize that there is tremendous potential to manipulate CO2 reactions by carefully designing the electrochemical environment.” That led her team to the idea of conducting electrochemical transformations on CO2 from a captured state bound to a capture sorbent, replacing the energy-intense regeneration step of today’s capture processes and streamlining the process.  

      “Now we’re seeing other researchers working on that, too, and taking this idea in exciting directions — it’s a very challenging and very rich topic,” she says.

      Gallant has won awards including an MIT Bose Fellowship, the Army Research Office Young Investigator Award, the Scialog Fellowship in Energy Storage and in Negative Emissions Science, a CAREER award from the National Science Foundation, the Ruth and Joel Spira Award for Distinguished Teaching at MIT, the Electrochemical Society (ECS) Battery Division Early Career award, and an ECS-Toyota Young Investigator Award.

      These days, Gallant does some of her best thinking while brainstorming with her research group members and with her husband, who is also an academic. She says being a professor at MIT means she has “a queue of things to think about,” but she sometimes gets awarded with a revelation.

      “My brain gets overloaded because I can’t think through everything instantaneously; ideas have to get in line! So there’s a lot going on in the background at all times,” she say. “I don’t know how it works, but sometimes I’ll be going for a walk or doing something else, and an idea breaks through. Those are the fun ones.” More

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      in Security

      Meet the 2021-22 Accenture Fellows

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      Launched in October of 2020, the MIT and Accenture Convergence Initiative for Industry and Technology underscores the ways in which industry and technology come together to spur innovation. The five-year initiative aims to achieve its mission through research, education, and fellowships. To that end, Accenture has once again awarded five annual fellowships to MIT graduate students working on research in industry and technology convergence who are underrepresented, including by race, ethnicity, and gender.

      This year’s Accenture Fellows work across disciplines including robotics, manufacturing, artificial intelligence, and biomedicine. Their research covers a wide array of subjects, including: advancing manufacturing through computational design, with the potential to benefit global vaccine production; designing low-energy robotics for both consumer electronics and the aerospace industry; developing robotics and machine learning systems that may aid the elderly in their homes; and creating ingestible biomedical devices that can help gather medical data from inside a patient’s body.

      Student nominations from each unit within the School of Engineering, as well as from the four other MIT schools and the MIT Schwarzman College of Computing, were invited as part of the application process. Five exceptional students were selected as fellows in the initiative’s second year.

      Xinming (Lily) Liu is a PhD student in operations research at MIT Sloan School of Management. Her work is focused on behavioral and data-driven operations for social good, incorporating human behaviors into traditional optimization models, designing incentives, and analyzing real-world data. Her current research looks at the convergence of social media, digital platforms, and agriculture, with particular attention to expanding technological equity and economic opportunity in developing countries. Liu earned her BS from Cornell University, with a double major in operations research and computer science.

      Caris Moses is a PhD student in electrical engineering and computer science specializing inartificial intelligence. Moses’ research focuses on using machine learning, optimization, and electromechanical engineering to build robotics systems that are robust, flexible, intelligent, and can learn on the job. The technology she is developing holds promise for industries including flexible, small-batch manufacturing; robots to assist the elderly in their households; and warehouse management and fulfillment. Moses earned her BS in mechanical engineering from Cornell University and her MS in computer science from Northeastern University.

      Sergio Rodriguez Aponte is a PhD student in biological engineering. He is working on the convergence of computational design and manufacturing practices, which have the potential to impact industries such as biopharmaceuticals, food, and wellness/nutrition. His current research aims to develop strategies for applying computational tools, such as multiscale modeling and machine learning, to the design and production of manufacturable and accessible vaccine candidates that could eventually be available globally. Rodriguez Aponte earned his BS in industrial biotechnology from the University of Puerto Rico at Mayaguez.

      Soumya Sudhakar SM ’20 is a PhD student in aeronautics and astronautics. Her work is focused on theco-design of new algorithms and integrated circuits for autonomous low-energy robotics that could have novel applications in aerospace and consumer electronics. Her contributions bring together the emerging robotics industry, integrated circuits industry, aerospace industry, and consumer electronics industry. Sudhakar earned her BSE in mechanical and aerospace engineering from Princeton University and her MS in aeronautics and astronautics from MIT.

      So-Yoon Yang is a PhD student in electrical engineering and computer science. Her work on the development of low-power, wireless, ingestible biomedical devices for health care is at the intersection of the medical device, integrated circuit, artificial intelligence, and pharmaceutical fields. Currently, the majority of wireless biomedical devices can only provide a limited range of medical data measured from outside the body. Ingestible devices hold promise for the next generation of personal health care because they do not require surgical implantation, can be useful for detecting physiological and pathophysiological signals, and can also function as therapeutic alternatives when treatment cannot be done externally. Yang earned her BS in electrical and computer engineering from Seoul National University in South Korea and her MS in electrical engineering from Caltech. More