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

    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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    Chemists discover why photosynthetic light-harvesting is so efficient

    When photosynthetic cells absorb light from the sun, packets of energy called photons leap between a series of light-harvesting proteins until they reach the photosynthetic reaction center. There, cells convert the energy into electrons, which eventually power the production of sugar molecules.

    This transfer of energy through the light-harvesting complex occurs with extremely high efficiency: Nearly every photon of light absorbed generates an electron, a phenomenon known as near-unity quantum efficiency.

    A new study from MIT chemists offers a potential explanation for how proteins of the light-harvesting complex, also called the antenna, achieve that high efficiency. For the first time, the researchers were able to measure the energy transfer between light-harvesting proteins, allowing them to discover that the disorganized arrangement of these proteins boosts the efficiency of the energy transduction.

    “In order for that antenna to work, you need long-distance energy transduction. Our key finding is that the disordered organization of the light-harvesting proteins enhances the efficiency of that long-distance energy transduction,” says Gabriela Schlau-Cohen, an associate professor of chemistry at MIT and the senior author of the new study.

    MIT postdocs Dihao Wang and Dvir Harris and former MIT graduate student Olivia Fiebig PhD ’22 are the lead authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences. Jianshu Cao, an MIT professor of chemistry, is also an author of the paper.

    Energy capture

    For this study, the MIT team focused on purple bacteria, which are often found in oxygen-poor aquatic environments and are commonly used as a model for studies of photosynthetic light-harvesting.

    Within these cells, captured photons travel through light-harvesting complexes consisting of proteins and light-absorbing pigments such as chlorophyll. Using ultrafast spectroscopy, a technique that uses extremely short laser pulses to study events that happen on timescales of femtoseconds to nanoseconds, scientists have been able to study how energy moves within a single one of these proteins. However, studying how energy travels between these proteins has proven much more challenging because it requires positioning multiple proteins in a controlled way.

    To create an experimental setup where they could measure how energy travels between two proteins, the MIT team designed synthetic nanoscale membranes with a composition similar to those of naturally occurring cell membranes. By controlling the size of these membranes, known as nanodiscs, they were able to control the distance between two proteins embedded within the discs.

    For this study, the researchers embedded two versions of the primary light-harvesting protein found in purple bacteria, known as LH2 and LH3, into their nanodiscs. LH2 is the protein that is present during normal light conditions, and LH3 is a variant that is usually expressed only during low light conditions.

    Using the cryo-electron microscope at the MIT.nano facility, the researchers could image their membrane-embedded proteins and show that they were positioned at distances similar to those seen in the native membrane. They were also able to measure the distances between the light-harvesting proteins, which were on the scale of 2.5 to 3 nanometers.

    Disordered is better

    Because LH2 and LH3 absorb slightly different wavelengths of light, it is possible to use ultrafast spectroscopy to observe the energy transfer between them. For proteins spaced closely together, the researchers found that it takes about 6 picoseconds for a photon of energy to travel between them. For proteins farther apart, the transfer takes up to 15 picoseconds.

    Faster travel translates to more efficient energy transfer, because the longer the journey takes, the more energy is lost during the transfer.

    “When a photon gets absorbed, you only have so long before that energy gets lost through unwanted processes such as nonradiative decay, so the faster it can get converted, the more efficient it will be,” Schlau-Cohen says.

    The researchers also found that proteins arranged in a lattice structure showed less efficient energy transfer than proteins that were arranged in randomly organized structures, as they usually are in living cells.

    “Ordered organization is actually less efficient than the disordered organization of biology, which we think is really interesting because biology tends to be disordered. This finding tells us that that may not just be an inevitable downside of biology, but organisms may have evolved to take advantage of it,” Schlau-Cohen says.

    Now that they have established the ability to measure inter-protein energy transfer, the researchers plan to explore energy transfer between other proteins, such as the transfer between proteins of the antenna to proteins of the reaction center. They also plan to study energy transfer between antenna proteins found in organisms other than purple bacteria, such as green plants.

    The research was funded primarily by the U.S. Department of Energy. More

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    Strengthening electron-triggered light emission

    The way electrons interact with photons of light is a key part of many modern technologies, from lasers to solar panels to LEDs. But the interaction is inherently a weak one because of a major mismatch in scale: A wavelength of visible light is about 1,000 times larger than an electron, so the way the two things affect each other is limited by that disparity.

    Now, researchers at MIT and elsewhere have come up with an innovative way to make much stronger interactions between photons and electrons possible, in the process producing a hundredfold increase in the emission of light from a phenomenon called Smith-Purcell radiation. The finding has potential implications for both commercial applications and fundamental scientific research, although it will require more years of research to make it practical.

    The findings are reported today in the journal Nature, in a paper by MIT postdocs Yi Yang (now an assistant professor at the University of Hong Kong) and Charles Roques-Carmes, MIT professors Marin Soljačić and John Joannopoulos, and five others at MIT, Harvard University, and Technion-Israel Institute of Technology.

    In a combination of computer simulations and laboratory experiments, the team found that using a beam of electrons in combination with a specially designed photonic crystal — a slab of silicon on an insulator, etched with an array of nanometer-scale holes — they could theoretically predict stronger emission by many orders of magnitude than would ordinarily be possible in conventional Smith-Purcell radiation. They also experimentally recorded a one hundredfold increase in radiation in their proof-of-concept measurements.

    Unlike other approaches to producing sources of light or other electromagnetic radiation, the free-electron-based method is fully tunable — it can produce emissions of any desired wavelength, simply by adjusting the size of the photonic structure and the speed of the electrons. This may make it especially valuable for making sources of emission at wavelengths that are difficult to produce efficiently, including terahertz waves, ultraviolet light, and X-rays.

    The team has so far demonstrated the hundredfold enhancement in emission using a repurposed electron microscope to function as an electron beam source. But they say that the basic principle involved could potentially enable far greater enhancements using devices specifically adapted for this function.

    The approach is based on a concept called flatbands, which have been widely explored in recent years for condensed matter physics and photonics but have never been applied to affecting the basic interaction of photons and free electrons. The underlying principle involves the transfer of momentum from the electron to a group of photons, or vice versa. Whereas conventional light-electron interactions rely on producing light at a single angle, the photonic crystal is tuned in such a way that it enables the production of a whole range of angles.

    The same process could also be used in the opposite direction, using resonant light waves to propel electrons, increasing their velocity in a way that could potentially be harnessed to build miniaturized particle accelerators on a chip. These might ultimately be able to perform some functions that currently require giant underground tunnels, such as the 30-kilometer-wide Large Hadron Collider in Switzerland.

    “If you could actually build electron accelerators on a chip,” Soljačić says, “you could make much more compact accelerators for some of the applications of interest, which would still produce very energetic electrons. That obviously would be huge. For many applications, you wouldn’t have to build these huge facilities.”

    The new system could also potentially provide a highly controllable X-ray beam for radiotherapy purposes, Roques-Carmes says.

    And the system could be used to generate multiple entangled photons, a quantum effect that could be useful in the creation of quantum-based computational and communications systems, the researchers say. “You can use electrons to couple many photons together, which is a considerably hard problem if using a purely optical approach,” says Yang. “That is one of the most exciting future directions of our work.”

    Much work remains to translate these new findings into practical devices, Soljačić cautions. It may take some years to develop the necessary interfaces between the optical and electronic components and how to connect them on a single chip, and to develop the necessary on-chip electron source producing a continuous wavefront, among other challenges.

    “The reason this is exciting,” Roques-Carmes adds, “is because this is quite a different type of source.” While most technologies for generating light are restricted to very specific ranges of color or wavelength, and “it’s usually difficult to move that emission frequency. Here it’s completely tunable. Simply by changing the velocity of the electrons, you can change the emission frequency. … That excites us about the potential of these sources. Because they’re different, they offer new types of opportunities.”

    But, Soljačić concludes, “in order for them to become truly competitive with other types of sources, I think it will require some more years of research. I would say that with some serious effort, in two to five years they might start competing in at least some areas of radiation.”

    The research team also included Steven Kooi at MIT’s Institute for Soldier Nanotechnologies, Haoning Tang and Eric Mazur at Harvard University, Justin Beroz at MIT, and Ido Kaminer at Technion-Israel Institute of Technology. The work was supported by the U.S. Army Research Office through the Institute for Soldier Nanotechnologies, the U.S. Air Force Office of Scientific Research, and the U.S. Office of Naval Research. More

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    More sensitive X-ray imaging

    Scintillators are materials that emit light when bombarded with high-energy particles or X-rays. In medical or dental X-ray systems, they convert incoming X-ray radiation into visible light that can then be captured using film or photosensors. They’re also used for night-vision systems and for research, such as in particle detectors or electron microscopes.

    Researchers at MIT have now shown how one could improve the efficiency of scintillators by at least tenfold, and perhaps even a hundredfold, by changing the material’s surface to create certain nanoscale configurations, such as arrays of wave-like ridges. While past attempts to develop more efficient scintillators have focused on finding new materials, the new approach could in principle work with any of the existing materials.

    Though it will require more time and effort to integrate their scintillators into existing X-ray machines, the team believes that this method might lead to improvements in medical diagnostic X-rays or CT scans, to reduce dose exposure and improve image quality. In other applications, such as X-ray inspection of manufactured parts for quality control, the new scintillators could enable inspections with higher accuracy or at faster speeds.

    The findings are described today in the journal Science, in a paper by MIT doctoral students Charles Roques-Carmes and Nicholas Rivera; MIT professors Marin Soljacic, Steven Johnson, and John Joannopoulos; and 10 others.

    While scintillators have been in use for some 70 years, much of the research in the field has focused on developing new materials that produce brighter or faster light emissions. The new approach instead applies advances in nanotechnology to existing materials. By creating patterns in scintillator materials at a length scale comparable to the wavelengths of the light being emitted, the team found that it was possible to dramatically change the material’s optical properties.

    To make what they coined “nanophotonic scintillators,” Roques-Carmes says, “you can directly make patterns inside the scintillators, or you can glue on another material that would have holes on the nanoscale. The specifics depend on the exact structure and material.” For this research, the team took a scintillator and made holes spaced apart by roughly one optical wavelength, or about 500 nanometers (billionths of a meter).

    “The key to what we’re doing is a general theory and framework we have developed,” Rivera says. This allows the researchers to calculate the scintillation levels that would be produced by any arbitrary configuration of nanophotonic structures. The scintillation process itself involves a series of steps, making it complicated to unravel. The framework the team developed involves integrating three different types of physics, Roques-Carmes says. Using this system they have found a good match between their predictions and the results of their subsequent experiments.

    The experiments showed a tenfold improvement in emission from the treated scintillator. “So, this is something that might translate into applications for medical imaging, which are optical photon-starved, meaning the conversion of X-rays to optical light limits the image quality. [In medical imaging,] you do not want to irradiate your patients with too much of the X-rays, especially for routine screening, and especially for young patients as well,” Roques-Carmes says.

    “We believe that this will open a new field of research in nanophotonics,” he adds. “You can use a lot of the existing work and research that has been done in the field of nanophotonics to improve significantly on existing materials that scintillate.”

    “The research presented in this paper is hugely significant,” says Rajiv Gupta, chief of neuroradiology at Massachusetts General Hospital and an associate professor at Harvard Medical School, who was not associated with this work. “Nearly all detectors used in the $100 billion [medical X-ray] industry are indirect detectors,” which is the type of detector the new findings apply to, he says. “Everything that I use in my clinical practice today is based on this principle. This paper improves the efficiency of this process by 10 times. If this claim is even partially true, say the improvement is two times instead of 10 times, it would be transformative for the field!”

    Soljacic says that while their experiments proved a tenfold improvement in emission could be achieved in particular systems, by further fine-tuning the design of the nanoscale patterning, “we also show that you can get up to 100 times [improvement] in certain scintillator systems, and we believe we also have a path toward making it even better,” he says.

    Soljacic points out that in other areas of nanophotonics, a field that deals with how light interacts with materials that are structured at the nanometer scale, the development of computational simulations has enabled rapid, substantial improvements, for example in the development of solar cells and LEDs. The new models this team developed for scintillating materials could facilitate similar leaps in this technology, he says.

    Nanophotonics techniques “give you the ultimate power of tailoring and enhancing the behavior of light,” Soljacic says. “But until now, this promise, this ability to do this with scintillation was unreachable because modeling the scintillation was very challenging. Now, this work for the first time opens up this field of scintillation, fully opens it, for the application of nanophotonics techniques.” More generally, the team believes that the combination of nanophotonic and scintillators might ultimately enable higher resolution, reduced X-ray dose, and energy-resolved X-ray imaging.

    This work is “very original and excellent,” says Eli Yablonovitch, a professor of Electrical Engineering and Computer Sciences at the University of California at Berkeley, who was not associated with this research. “New scintillator concepts are very important in medical imaging and in basic research.”

    Yablonovitch adds that while the concept still needs to be proven in a practical device, he says that, “After years of research on photonic crystals in optical communication and other fields, it’s long overdue that photonic crystals should be applied to scintillators, which are of great practical importance yet have been overlooked” until this work.

    The research team included Ali Ghorashi, Steven Kooi, Yi Yang, Zin Lin, Justin Beroz, Aviram Massuda, Jamison Sloan, and Nicolas Romeo at MIT; Yang Yu at Raith America, Inc.; and Ido Kaminer at Technion in Israel. The work was supported, in part, by the U.S. Army Research Office and the U.S. Army Research Laboratory through the Institute for Soldier Nanotechnologies, by the Air Force Office of Scientific Research, and by a Mathworks Engineering Fellowship. More