Tag Archives: University of Chicago

2024 Kavli Prize Laureates: in the fields of astrophysics, nanoscience and neuroscience

The Kavli Prize has yet to acquire the lustre of a Nobel Prize (first awarded in 1901 as per its Wikipedia entry). By comparison the Kavli Prize is relatively new (established in 2005 as per its Wikipedia entry) but it appears to be achieving big deal status in the US.

This year’s crop of prize winners was listed in a June 12, 2024 Kavli Foundation news release on EurekAlert,

Eight scientists from three countries are honored for their research that has broadened our understanding of the big, the small and the complex.

June 12, 2024 (Oslo, Norway) — The Norwegian Academy of Science and Letters today announced the 2024 Kavli Prize Laureates in the fields of astrophysics, nanoscience and neuroscience. Eight scientists from three countries are honored for their research that has broadened our understanding of the big, the small and the complex. The laureates in each field will share $1 million USD. 

The 2024 Kavli Prizes recognize groundbreaking science for the discovery and characterization of extra-solar planets and their atmospheres; foundational research integrating synthetic nanoscale materials for biomedical use; and the localization of areas in the brain specialized for face recognition and processing.  

The 2024 Kavli Prize Laureates are:  

  • Kavli Prize in Astrophysics: David Charbonneau (Canada/USA) and Sara Seager (Canada/USA) 
  • Kavli Prize in Nanoscience: Robert S. Langer (USA), Armand Paul Alivisatos (USA) and Chad A. Mirkin (USA) 
  • Kavli Prize in Neuroscience: Nancy Kanwisher (USA), Winrich Freiwald (Germany), and Doris Tsao (USA) 

“The Kavli Prize 2024 honors outstanding researchers doing fundamental science that moves the world forward. They are exploring planets outside our solar system; they have broadened the scientific field of nanoscience towards biomedicine; and they are adding to our understanding of the neurological basis of face recognition,” said Lise Øvreås, president at The Norwegian Academy of Science and Letters.  

Astrophysics: Searching for life beyond Earth  

The 2024 Kavli Prize in Astrophysics honors Sara Seager and David Charbonneau for discoveries of exoplanets and the characterization of their atmospheres. They pioneered methods for the detection of atomic species in planetary atmospheres and the measurement of their thermal infrared emission, setting the stage for finding the molecular fingerprints of atmospheres around both giant and rocky planets. Their contributions have been key to the enormous progress seen in the last 20 years in the exploration of myriad exo-planets.  

“Humans have always looked towards the stars for discoveries. The pivotal research conducted by Seager and Charbonneau has been an important first step towards finding new planets and strong evidence of life elsewhere in the universe,” remarked Viggo Hansteen, Chair of the Astrophysics Committee.  

David Charbonneau led the team that used the transit method to discover a giant exoplanet (HD 209458b). He pioneered the application of space-based observatories to perform the first studies of the atmosphere of giant extrasolar planets. This new method measures the tiny amount of light blocked by such a planet as it passes in front of its host star. Charbonneau has also used the transit method to study exoplanetary atmospheres, measuring molecular spectra using both filtered starlight and infrared emission from the planets themselves. He demonstrated these two approaches with observations from the Hubble Space Telescope in 2002 and the Spitzer Space Telescope three years later.  

Sara Seager pioneered the theoretical study of planetary atmospheres and predicted the presence of atomic and molecular species detectable by transit spectroscopy, most notably the alkali gases. She predicted how transits could be used to measure atomic and molecular characteristics in exoplanetary atmospheres, which is crucial for identifying biomarkers – signs of life. Seager made outstanding contributions to the understanding of planets with masses below that of Neptune. She also carried out extensive research on starshades – enormous petal-like structures designed to shield space observatories from the glare of a faraway Sun-like star – and was among the first to recognize their importance in detecting and characterizing the faint light from any Earth-like planet orbiting the star. 

Nanoscience: Integrating nanomaterials for biomedical advances 

The 2024 Kavli Prize in Nanoscience honors Robert S. Langer, Armand Paul Alivisatos and Chad A. Mirkin who each revolutionized the field of nanomedicine by demonstrating how engineering nanoscale materials can advance biomedical research and application. Their discoveries contributed foundationally to the development of therapeutics, vaccines, bioimaging and diagnostics.   

“The three scientists, Langer, Alivisatos and Mirkin, have broadened the scientific field of nanoscience, building from fundamental research. By scientific curiosity they have become inventors for the future of nanoscience and biomedicine,” stated Bodil Holst, Chair of the Nanoscience Committee.  

Robert S. Langer was the first to develop nano-engineered materials that enabled the controlled release, or regular flow, of drug molecules. This capability has had an immense impact for the treatment of a range of diseases, such as aggressive brain cancer, prostate cancer and schizophrenia. His work also showed that tiny particles, containing protein antigens, can be used in vaccination, and was instrumental in the development of the delivery of mRNA vaccines. 

Armand Paul Alivisatos demonstrated that semiconductor nanocrystals, or quantum dots (nanoparticles that possess bright, size-dependent light-emitting properties), can be used as multicolor probes in bioimaging. Essential to this achievement was the synthesis of biocompatible nanocrystals. Semiconductor nanocrystals became the basis for the widely used research and diagnostic tools such as live cell tracking, labelling and in vivo imaging. 

Chad A. Mirkin engineered spherical nucleic acids (SNA) using a gold nanoparticle as the core, and a cloud of radially distributed DNA or RNA strands as the shell. He was then able to show how SNAs can be combined to create larger structures and how they can be used in biodiagnostics. His discovery led to the development of fast, automated point-of-care medical diagnostic systems.  

Neuroscience: Understanding recognition of faces 

The 2024 Kavli Prize in Neuroscience honors Nancy Kanwisher, Doris Tsao and Winrich Freiwald for the discovery of a specialized system within the brain to recognize faces. Their discoveries have provided basic principles of neural organization and made the starting point for further research on how the processing of visual information is integrated with other cognitive functions.  

“Kanwisher, Freiwald and Tsao together discovered a localized and specialized neocortical system for face recognition. Their outstanding research will ultimately further our understanding of recognition not only of faces, but objects and scenes,” commented Kristine Walhovd, Chair of the Neuroscience Committee.  

Nancy Kanwisher was the first to prove that a specific area in the human neocortex is dedicated to recognizing faces, now called the fusiform face area. Using functional magnetic resonance imaging (fMRI) she found individual differences in the location of this area and devised an analysis technique to effectively localize specialized functional regions in the brain. This technique is now widely used and applied to domains beyond the face recognition system.  

Elaborating on Kanwisher’s findings, Winrich Freiwald and Doris Tsao studied macaques and mapped out six distinct brain regions, known as the face patch system, including these regions’ functional specialization and how they are connected. By recording the activity of individual brain cells, they revealed how cells in some face patches specialize in faces with particular views.  

Tsao proceeded to identify how the face patches work together to identify a face, through a specific code that enables single cells to identify faces by assembling information of facial features. For example, some cells respond to the presence of hair, others to the distance between the eyes. 

Freiwald uncovered that a separate brain region, called the temporal pole, accelerates our recognition of familiar faces, and that some cells are selectively responsive to familiar faces. 

There’s a video of the official 2024 Kavli Prize announcement which despite the Kavli Foundation being headquartered in California, US, was held (as noted in the news release) at the Norwegian Academy of Science and Letters where the organization’s president, Lise Øvreås, revealed the 2024 Kavli Prize laureates..(I’ll get back to that choice of location.)

The 2024 Kavli Prize in Nanoscience

There are many posts here featuring work from Robert S. Langer (or Robert Langer), Armand Paul Alivisatos (or Paul Alivisatos or A. Paul Alivisatos) and Chad A. Mirkin (or Chad Mirkin).

Northwestern University (Chicago, Illinois) issued a June 12, 2024 news release (also received via email) by Maria Paul that provides a few more details about the nanoscience winners (main focus: Chad Mirkin), the prize, and the Kavli Foundation. Note: A link has been removed,

Northwestern University nanoscientist Chad Mirkin has been awarded The 2024 Kavli Prize in Nanoscience by The Norwegian Academy of Science and Letters. Mirkin is the first Northwestern scientist to receive the prestigious award.

Mirkin is recognized for his discovery of spherical nucleic acids (SNAs), nanostructures comprised of a nanoparticle core and a shell of radially distributed DNA or RNA strands. These globular forms of nucleic acids have become the cornerstones of the burgeoning fields of nanomedicine and colloidal crystal engineering with DNA. They allow scientists to construct new forms of matter using particle “atoms” as the basic building blocks and DNA “bonds” as particle interconnects, and they are the basis for powerful tools that allow researchers and clinicians to track and treat disease in new ways. In particular, SNAs have led to the development of fast, automated point-of-care medical diagnostic systems and new experimental drugs for treating many forms of cancer, neurological disorders, and diseases of the skin.

Mirkin is one of three laureates in nanoscience recognized by The Norwegian Academy for revolutionizing the field of nanomedicine by demonstrating how engineering nanoscale structures can advance biomedical research and application. The other two are Robert Langer of the Massachusetts Institute of Technology and Paul Alivisatos of the University of Chicago [emphasis mine]. The scientists’ discoveries “contributed foundationally to the development of therapeutics, vaccines, bioimaging and diagnostics,” The Norwegian Academy said in a release. They will share the $1 million award.

“When I first found out I won The Kavli Prize, there was both excitement but also relief, because I consider Northwestern to be the ultimate center for nanotechnology research,” Mirkin said. “To be recognized with this award, along with my incredible co-awardees, was great validation of what we’ve been trying to do at Northwestern. While I’m proud of what we’ve accomplished, the best is yet to come.”

The laureates will be awarded the prize on Sept. 3 during a ceremony in Oslo, Norway, presided over the by The Royal Family. The Kavli Prizes thus far have honored 65 scientists from 13 countries. Ten laureates received the Nobel Prize after receiving The Kavli Prize. [emphasis mine]

“I am thrilled for Chad, for the International Institute for Nanotechnology and for Northwestern,” Northwestern President Michael Schill said. “Chad has earned this prestigious and influential award in a pathbreaking area of science that is aligned with two of the University’s key priorities — to lead in decarbonization, renewable energy and sustainability, and innovating in the biosciences to help prolong lives and make the world a healthier place.

“Through groundbreaking research and hard work, Chad and his team have made Northwestern a leading center for nanotechnology research and investment. The fact that he is sharing this award with President Alivisatos at U of C further emphasizes how the Chicago area has become an international hub for nano research.”

The vision for The Kavli Prize comes from Fred Kavli, a Norwegian-American entrepreneur and philanthropist [emphasis mine] who turned his lifelong fascination with science into a lasting legacy for recognizing scientific breakthroughs and supporting basic research.

Since the first awards in 2008, The Kavli Prize has recognized innovative scientific research — from the discovery of CRISPR-Cas9 to the detection of gravitational waves — transforming our understanding of the big, the small and the complex.

Mirkin’s discovery of SNAs has far-reaching implications for biology and medicine. SNAs, which have no known natural equivalents, interact uniquely with living systems compared to nucleic acids of other forms. Mirkin was the first to synthesize SNAs and elucidate the distinctive chemical and physical properties that underpin their use in transformative techniques and technologies in medicine and the life sciences. This work has led to the development of the first commercialized molecular medical diagnostic systems of the modern nanotechnology era, such as the Food and Drug Administration-cleared Verigene System, used in over half of the world’s top hospitals to detect diseases with high sensitivity and selectivity.

Illinois Gov. JB Pritzker praised Mirkin for his extraordinary contributions to the field of nanotechnology and how his innovations have helped find solutions to some of society’s biggest challenges.

“Academic institutions in Chicago and across Illinois have become the biggest drivers in nanoscience and technology over the last three decades,” Pritzker said. “Chad Mirkin and his Northwestern colleagues have made outstanding scientific discoveries that change how we view the world around us.”

In 1996, Mirkin created the first SNAs with DNA shells on gold nanoparticle cores. Over the years, he has developed numerous other types of SNAs with other shells and cores, including proteins, liposomes and FDA-approved materials, as well as core-less, hollow structures composed entirely of nucleic acids. These cores impart unique properties to the SNAs, such as optical and magnetic characteristics, while also serving as scaffolds to densely arrange the oligonucleotides, which participate in binding. This dense arrangement gives rise to the novel functional properties that differentiate SNAs from the natural linear and two-dimensional nucleic acids and make them particularly effective in interacting with certain biological structures within cells and tissues. SNAs, unlike conventional DNA and RNA, are naturally taken up by cells without the need for toxic, positively charged co-carriers, making them highly effective in RNA interference (RNAi), antisense gene regulation, and gene editing pathways.

Mirkin’s pioneering work on SNAs has also advanced the development of immunotherapeutics, structures capable of stimulating a patient’s immune response to fight both infectious diseases and certain forms of cancer. Using SNAs, Mirkin has pioneered the concept of rational vaccinology, where he demonstrated that the structure of a vaccine, rather than the components alone, is crucial for dictating its therapeutic effectiveness. This insight and these “structural nanomedicines” have opened new possibilities for developing curative treatments by rearranging known components into more effective structures at the nanoscale. Mirkin founded Flashpoint Therapeutics to commercialize these innovations, focusing on nucleic acid-based nanostructure cancer vaccines. Mirkin also invented the first SNA-based antiviral vaccine, using COVID-19 as a model. These SNAs, featuring the spike protein’s RBD subunit in the core, achieved a 100% survival rate in humanized mice challenged with the live virus. These structures and concepts for designing such vaccines are poised to move vaccine development beyond the current mRNA vaccines.

In addition, Mirkin invented dip-pen nanolithography, initially a technique for molecular writing with nanometer-scale precision that has evolved into a powerful platform for tip-based materials synthesis that, when combined with artificial intelligence, is revolutionizing how materials important for many sectors, especially clean energy, are discovered. Dip-pen nanolithography, which has spurred subsequent techniques that now use tens of millions of tiny tips to rapidly synthesize materials to be explored for such purposes, was recognized by National Geographic as one of the “top 100 scientific discoveries that changed the world.” These innovations are being commercialized by Mattiq, Inc., another venture-backed company Mirkin cofounded. Mirkin and his students also invented high-area rapid printing, an additive manufacturing technology, that is being commercialized by Azul 3D and being used to disrupt the microelectronics and optical lens industries.

Mirkin’s research has progressed SNA drugs through seven human clinical trials so far for treating various cancers, including glioblastoma multiforme and Merkel cell carcinoma. One SNA drug has shown remarkable potential in stimulating the immune system, proving effective in models of breast, colorectal and bladder cancers, lymphoma and melanoma. This drug has achieved complete tumor elimination in a subset of patients with Merkel cell carcinoma during Phase 1b/2 clinical trials, earning FDA fast-track and orphan drug status. It was recently licensed to Bluejay Therapeutics to treat hepatitis.

In 2000, Mirkin founded the International Institute for Nanotechnology (IIN) at Northwestern University, which he also directs. Research at the IIN has led to over 2,000 new commercial products sold globally and the creation of more than 40 startup companies. The IIN has collectively brought together over $1.2 billion to support research, education and infrastructure at Northwestern since its inception.

Mirkin is the George B. Rathmann Professor of Chemistry and a professor of medicine, chemical and biological engineering, biomedical engineering, and materials science and engineering at Northwestern. He is among an elite group of scientists elected to all three branches of the U.S. National Academies — the National Academy of Sciences, the National Academy of Engineering and the National Academy of Medicine. He is a member of the American Academy of Arts and Sciences. Mirkin served on President Obama’s Council of Advisors on Science and Technology for eight years.

Congratulations to all of the winners in all of the categories!

As for the Norway announcement, it makes a bit of sense given that Fred Kavli was a Norwegian American. However, it’s a little hard to avoid the suspicion that there might be some regional and prize rivalry between Norway with its Kavli and Sweden its Nobel..

After pretending to be Marie Curie girls stick with science

Researchers have found that pretending to be Marie Curie in a science game can lead to greater persistence when playing. From a September 27, 2022 Duke University news release (also on EurekAlert but published on September 29, 2022) by Dan Vahaba,

Fake it ‘til you make is true for children too, it turns out: Young girls embracing the role of a successful female scientist, like Marie Curie, persist longer at a challenging science game.

A new study, appearing Sept. 28 [2022] in the journal Psychological Science, suggests that science role-playing may help tighten the gender gap in science, technology, engineering, and math (STEM) education and careers for women simply by improving their identity as scientists.

Frustrated by the gender gap in STEM, in which some fields employ at least three times more men than women, Cornell graduate student Reut Shachnai wanted to do something about it. Shachnai, who is now continuing her studies at Yale, said the idea to help foster young girls’ interest in science came to her during a lecture in a class she was taking on “Psychology of Imagination.”

“We read a paper on how children pretending to be a superhero did better at self-control tasks (the so-called ‘Batman effect’),” said Tamar Kushnir, Ph.D., who taught the class and is now a Duke professor of psychology & neuroscience as well as a fellow author on the new paper. “Reut wondered if this would also work to encourage girls to persist in science.”

Along with Lin Bian, Ph.D., an assistant professor of psychology at the University of Chicago, Shachnai and Kushnir devised an experiment to test if assuming the role of a successful scientist would improve girls’ persistence in a “sink or float” science game.

The game itself was simple yet challenging: a computer screen projected a slide with an object in the center hovering above a pool of water. Kids then had to predict whether that object — be it an anchor, basketball, balloon, or others — would sink or float. After making their choice, they learned if they made the right choice as they watched the object either plunge or stay afloat.

The researchers recruited 240 four- to seven-year-olds for the experiment, because this is around the time kids first develop their sense of identity and capabilities.

“Children as early as age 6 start to think boys are smarter and better at science than girls,” said Bian, whose previous work identified this critical period.

Boys and girls were assigned to three different groups: the baseline group were told they would be scientists for the day and then got to play the game.

Children in the “story” group received the same information, but also learned about the successes and struggles of a gender-matched scientist before playing the game. Boys heard about Isaac Newton, and girls were told about Marie Curie. They also had to take a two-question pop quiz after the story to make sure they were paying attention (they were).

Finally, children in the “pretend” group did all the same things as the “story” group, with one important twist: these children were told to assume the identity of the scientist they just learned about, and were referred to as such during the game (“What’s your prediction, Dr. Marie?”).

All kids played at least one round of the game, after which they were asked if they wanted to play more or do something else. Once the kids tapped out, they were asked to rate how good they thought they were at the game and as a scientist.

No matter what group they were in, girls got the answers right just as often as boys — nearly 70% of the time. Boys, however didn’t really benefit from the stories or make-believe.

“Boys were kind of maxed out,” Kushnir said. “They were about at ceiling performance no matter what we did.”

Girls, on the other hand, benefited immensely from playing pretend.

Without being exposed to Marie Curie, girls called it quits after six trials. However, girls pretending to be Dr. Marie persisted twice as long at the sink-or-float game, playing just as much as the boys did (about 12 trials on average).

While there wasn’t much benefit to just hearing a story about Marie Curie for extending game play, it did boost girls’ ratings of themselves as science gamers.

Kushnir and her colleagues’ work poses many new questions for researchers, such as if children assuming the role of successful scientists matched by race and ethnicity might also benefit (the participants were mostly white in this study).

“Our findings suggest that we may want to take representation one step further,” Shachnai said. “Rather than merely hearing about role models, children may benefit from actively performing the type of actions they see role models perform. In other words, taking a few steps in the role model’s shoes, instead of merely observing her walk.”

A screen grab from the game,

Caption: Participants played a sink-or-float game on the computer during the study.. Credit:: Reut Shachnai, Tamar Kushnir, and Lin Bian https://osf.io/qfjk9

Here’s a link to and a citation for the paper,

Walking In Her Shoes: Pretending To Be a Female Role Model Increases Young Girls’ Persistence in Science by Shachnai, Reut, Kushnir, Tamar, Bian, Lin. Psychological Science DOI: 10.1177/09567976221119393 First published online: Sept. 28, 2022

This paper is behind a paywall.

Skin-like computing device analyzes health data with brain-mimicking artificial intelligence (a neuromorphic chip)

The wearable neuromorphic chip, made of stretchy semiconductors, can implement artificial intelligence (AI) to process massive amounts of health information in real time. Above, Asst. Prof. Sihong Wang shows a single neuromorphic device with three electrodes. (Photo by John Zich)

Does everything have to be ‘brainy’? Read on for the latest on ‘brainy’ devices.

An August 4, 2022 University of Chicago news release (also on EurekAlert) describes work on a stretchable neuromorphic chip, Note: Links have been removed,

It’s a brainy Band-Aid, a smart watch without the watch, and a leap forward for wearable health technologies. Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have developed a flexible, stretchable computing chip that processes information by mimicking the human brain. The device, described in the journal Matter, aims to change the way health data is processed.

“With this work we’ve bridged wearable technology with artificial intelligence and machine learning to create a powerful device which can analyze health data right on our own bodies,” said Sihong Wang, a materials scientist and Assistant Professor of Molecular Engineering.

Today, getting an in-depth profile about your health requires a visit to a hospital or clinic. In the future, Wang said, people’s health could be tracked continuously by wearable electronics that can detect disease even before symptoms appear. Unobtrusive, wearable computing devices are one step toward making this vision a reality. 

A Data Deluge
The future of healthcare that Wang—and many others—envision includes wearable biosensors to track complex indicators of health including levels of oxygen, sugar, metabolites and immune molecules in people’s blood. One of the keys to making these sensors feasible is their ability to conform to the skin. As such skin-like wearable biosensors emerge and begin collecting more and more information in real-time, the analysis becomes exponentially more complex. A single piece of data must be put into the broader perspective of a patient’s history and other health parameters.

Today’s smart phones are not capable of the kind of complex analysis required to learn a patient’s baseline health measurements and pick out important signals of disease. However, cutting-edge artificial intelligence platforms that integrate machine learning to identify patterns in extremely complex datasets can do a better job. But sending information from a device to a centralized AI location is not ideal.

“Sending health data wirelessly is slow and presents a number of privacy concerns,” he said. “It is also incredibly energy inefficient; the more data we start collecting, the more energy these transmissions will start using.”

Skin and Brains
Wang’s team set out to design a chip that could collect data from multiple biosensors and draw conclusions about a person’s health using cutting-edge machine learning approaches. Importantly, they wanted it to be wearable on the body and integrate seamlessly with skin.

“With a smart watch, there’s always a gap,” said Wang. “We wanted something that can achieve very intimate contact and accommodate the movement of skin.”

Wang and his colleagues turned to polymers, which can be used to build semiconductors and electrochemical transistors but also have the ability to stretch and bend. They assembled polymers into a device that allowed the artificial-intelligence-based analysis of health data. Rather than work like a typical computer, the chip— called a neuromorphic computing chip—functions more like a human brain, able to both store and analyze data in an integrated way.

Testing the Technology
To test the utility of their new device, Wang’s group used it to analyze electrocardiogram (ECG) data representing the electrical activity of the human heart. They trained the device to classify ECGs into five categories—healthy or four types of abnormal signals. Then, they tested it on new ECGs. Whether or not the chip was stretched or bent, they showed, it could accurately classify the heartbeats.

More work is needed to test the power of the device in deducing patterns of health and disease. But eventually, it could be used either to send patients or clinicians alerts, or to automatically tweak medications.

“If you can get real-time information on blood pressure, for instance, this device could very intelligently make decisions about when to adjust the patient’s blood pressure medication levels,” said Wang. That kind of automatic feedback loop is already used by some implantable insulin pumps, he added.

He already is planning new iterations of the device to both expand the type of devices with which it can integrate and the types of machine learning algorithms it uses.

“Integration of artificial intelligence with wearable electronics is becoming a very active landscape,” said Wang. “This is not finished research, it’s just a starting point.”

Here’s a link to and a citation for the paper,

Intrinsically stretchable neuromorphic devices for on-body processing of health data with artificial intelligence by Shilei Dai, Yahao Dai, Zixuan Zhao, Jie Xu, Jia Huang, Sihong Wang. Matter DOI:https://doi.org/10.1016/j.matt.2022.07.016 Published: August 04, 2022

This paper is behind a paywall.

Visualization of RNA structures at near-atomic resolution enabled by nanotechnology

The illustration that accompanies the research is both fascinating and baffling as its caption,

Caption: This illustration is inspired by the Paleolithic rock painting in the Lascaux cave, signifying the acronym of our method, ROCK. Figuratively, the patterns of the rock art in the background (brown) are the 2D projections of the engineered dimeric construct of the Tetrahymena group I intron, while the main object in the front (blue) is the reconstructed 3D cryo-EM map of the dimer, with one monomer in focus and refined to the high resolution that allowed the collaborators to build an atomic model of the RNA. Credit: Wyss Institute at Harvard University

This May 2, 2022 news item on ScienceDaily announces the research into RNA molecules made possible by ROCK (the technology being illustrated in the above),

We live in a world made and run by RNA [ribonucleic acid], the equally important sibling of the genetic molecule DNA. In fact, evolutionary biologists hypothesize that RNA existed and self-replicated even before the appearance of DNA and the proteins encoded by it. Fast forward to modern day humans: science has revealed that less than 3% of the human genome is transcribed into messenger RNA (mRNA) molecules that in turn are translated into proteins. In contrast, 82% of it is transcribed into RNA molecules with other functions many of which still remain enigmatic.

To understand what an individual RNA molecule does, its 3D structure needs to be deciphered at the level of its constituent atoms and molecular bonds. Researchers have routinely studied DNA and protein molecules by turning them into regularly packed crystals that can be examined with an X-ray beam (X-ray crystallography) or radio waves (nuclear magnetic resonance). However, these techniques cannot be applied to RNA molecules with nearly the same effectiveness because their molecular composition and structural flexibility prevent them from easily forming crystals.

Now, a research collaboration led by Wyss Core Faculty member Peng Yin, Ph.D. at the Wyss Institute for Biologically Inspired Engineering at Harvard University, and Maofu Liao, Ph.D. at Harvard Medical School (HMS), has reported a fundamentally new approach to the structural investigation of RNA molecules. ROCK, as it is called, uses an RNA nanotechnological technique that allows it to assemble multiple identical RNA molecules into a highly organized structure, which significantly reduces the flexibility of individual RNA molecules and multiplies their molecular weight. Applied to well-known model RNAs with different sizes and functions as benchmarks, the team showed that their method enables the structural analysis of the contained RNA subunits with a technique known as cryo-electron microscopy (cryo-EM). Their advance is reported in Nature Methods.

A May 2, 2022 Wyss Institute for Biologically Inspired Engineering at Harvard University news release (also on EurekAlert) by Benjamin Boettner, which originated the news item, delves further into the imaging technology, Note: Links have been removed,

“ROCK is breaking the current limits of RNA structural investigations and enables 3D structures of RNA molecules to be unlocked that are difficult or impossible to access with existing methods, and at near-atomic resolution,” said Yin, who together with Liao led the study. “We expect this advance to invigorate many areas of fundamental research and drug development, including the burgeoning field of RNA therapeutics.” Yin also is a leader of the Wyss Institute’s Molecular Robotics Initiative and Professor in the Department of Systems Biology at HMS.

Gaining control over RNA

Yin’s team at the Wyss Institute has pioneered various approaches that enable DNA and RNA molecules to self-assemble into large structures based on different principles and requirements, including DNA bricks and DNA origami. They hypothesized that such strategies could also be used to assemble naturally occurring RNA molecules into highly ordered circular complexes in which their freedom to flex and move is highly restricted by specifically linking them together. Many RNAs fold in complex yet predictable ways, with small segments base-pairing with each other. The result often is a stabilized “core” and “stem-loops” bulging out into the periphery. 

“In our approach we install ‘kissing loops’ that link different peripheral stem-loops belonging to two copies of an identical RNA in a way that allows a overall stabilized ring to be formed, containing multiple copies of the RNA of interest,” said Di Liu, Ph.D., one of two first-authors and a Postdoctoral Fellow in Yin’s group. “We speculated that these higher-order rings could be analyzed with high resolution by cryo-EM, which had been applied to RNA molecules with first success.”

Picturing stabilized RNA

In cryo-EM, many single particles are flash-frozen at cryogenic temperatures to prevent any further movements, and then visualized with an electron microscope and the help of computational algorithms that compare the various aspects of a particle’s 2D surface projections and reconstruct its 3D architecture. Peng and Liu teamed up with Liao and his former graduate student François Thélot, Ph.D., the other co-first author of the study. Liao with his group has made important contributions to the rapidly advancing cryo-EM field and the experimental and computational analysis of single particles formed by specific proteins.

“Cryo-EM has great advantages over traditional methods in seeing high-resolution details of biological molecules including proteins, DNAs and RNAs, but the small size and moving tendency of most RNAs prevent successful determination of RNA structures. Our novel method of assembling RNA multimers solves these two problems at the same time, by increasing the size of RNA and reducing its movement,” said Liao, who also is Associate Professor of Cell Biology at HMS. “Our approach has opened the door to rapid structure determination of many RNAs by cryo-EM.” The integration of RNA nanotechnology and cryo-EM approaches led the team to name their method “RNA oligomerization-enabled cryo-EM via installing kissing loops” (ROCK).

To provide proof-of-principle for ROCK, the team focused on a large intron RNA from Tetrahymena, a single-celled organism, and a small intron RNA from Azoarcus, a nitrogen-fixing bacterium, as well as the so-called FMN riboswitch. Intron RNAs are non-coding RNA sequences scattered throughout the sequences of freshly-transcribed RNAs and have to be “spliced” out in order for the mature RNA to be generated. The FMN riboswitch is found in bacterial RNAs involved in the biosynthesis of flavin metabolites derived from vitamin B2. Upon binding one of them, flavin mononucleotide (FMN), it switches its 3D conformation and suppresses the synthesis of its mother RNA.  

“The assembly of the Tetrahymena group I intron into a ring-like structure made the samples more homogenous, and enabled the use of computational tools leveraging the symmetry of the assembled structure. While our dataset is relatively modest in size, ROCK’s innate advantages allowed us to resolve the structure at an unprecedented resolution,” said Thélot. “The RNA’s core is resolved at 2.85 Å [one Ångström is one ten-billions (US) of a meter and the preferred metric used by structural biologists], revealing detailed features of the nucleotide bases and sugar backbone. I don’t think we could have gotten there without ROCK – or at least not without considerably more resources.” 

Cryo-EM also is able to capture molecules in different states if they, for example, change their 3D conformation as part of their function. Applying ROCK to the Azoarcus intron RNA and the FMN riboswitch, the team managed to identify the different conformations that the Azoarcus intron transitions through during its self-splicing process, and to reveal the relative conformational rigidity of the ligand-binding site of the FMN riboswitch.

“This study by Peng Yin and his collaborators elegantly shows how RNA nanotechnology can work as an accelerator to advance other disciplines. Being able to visualize and understand the structures of many naturally occurring RNA molecules could have tremendous impact on our understanding of many biological and pathological processes across different cell types, tissues, and organisms, and even enable new drug development approaches,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

The study was also authored by Joseph Piccirilli, Ph.D., an expert in RNA chemistry and biochemistry and Professor at The University of Chicago. It was supported by the National Science Foundation (NSF; grant# CMMI-1333215, CCMI-1344915, and CBET-1729397), Air Force Office of Scientific Research (AFOSR; grant MURI FATE, #FA9550-15-1-0514), National Institutes of Health (NIH; grant# 5DP1GM133052, R01GM122797, and R01GM102489), and the Wyss Institute’s Molecular Robotics Initiative.

Here’s a link to and a citation for the paper,

Sub-3-Å cryo-EM structure of RNA enabled by engineered homomeric self-assembly by Di Liu, François A. Thélot, Joseph A. Piccirilli, Maofu Liao & Peng Yin. Nature Methods (2022) DOI: https://doi.org/10.1038/s41592-022-01455-w Published: 02 May 2022

This paper is behind a paywall.

Shaving the ‘hairs’ off nanocrystals for more efficient electronics

A March 24, 2022 news item on phys.org announced research into nanoscale crystals and how they might be integrated into electronic devices, Note: A link has been removed,

You can carry an entire computer in your pocket today because the technological building blocks have been getting smaller and smaller since the 1950s. But in order to create future generations of electronics—such as more powerful phones, more efficient solar cells, or even quantum computers—scientists will need to come up with entirely new technology at the tiniest scales.

One area of interest is nanocrystals. These tiny crystals can assemble themselves into many configurations, but scientists have had trouble figuring out how to make them talk to each other.  

A new study introduces a breakthrough in making nanocrystals function together electronically. Published March 25 [2022] in Science, the research may open the doors to future devices with new abilities. 

A March 25, 2022 University of Chicago news release (also on EurekAlert but published on March 24, 2022), which originated the news item, expands on the possibilities the research makes possible, Note: Links have been removed,

“We call these super atomic building blocks, because they can grant new abilities—for example, letting cameras see in the infrared range,” said University of Chicago Prof. Dmitri Talapin, the corresponding author of the paper. “But until now, it has been very difficult to both assemble them into structures and have them talk to each other. Now for the first time, we don’t have to choose. This is a transformative improvement.”  

In their paper, the scientists lay out design rules which should allow for the creation of many different types of materials, said Josh Portner, a Ph.D. student in chemistry and one of the first authors of the study. 

A tiny problem

Scientists can grow nanocrystals out of many different materials: metals, semiconductors, and magnets will each yield different properties. But the trouble was that whenever they tried to assemble these nanocrystals together into arrays, the new supercrystals would grow with long “hairs” around them. 

These hairs made it difficult for electrons to jump from one nanocrystal to another. Electrons are the messengers of electronic communication; their ability to move easily along is a key part of any electronic device. 

The researchers needed a method to reduce the hairs around each nanocrystal, so they could pack them in more tightly and reduce the gaps in between. “When these gaps are smaller by just a factor of three, the probability for electrons to jump across is about a billion times higher,” said Talapin, the Ernest DeWitt Burton Distinguished Service Professor of Chemistry and Molecular Engineering at UChicago and a senior scientist at Argonne National Laboratory. “It changes very strongly with distance.”

To shave off the hairs, they sought to understand what was going on at the atomic level. For this, they needed the aid of powerful X-rays at the Center for Nanoscale Materials at Argonne and the Stanford Synchrotron Radiation Lightsource at SLAC National Accelerator Laboratory, as well as powerful simulations and models of the chemistry and physics at play. All these allowed them to understand what was happening at the surface—and find the key to harnessing their production.

Part of the process to grow supercrystals is done in solution—that is, in liquid. It turns out that as the crystals grow, they undergo an unusual transformation in which gas, liquid and solid phases all coexist. By precisely controlling the chemistry of that stage, they could create crystals with harder, slimmer exteriors which could be packed in together much more closely. “Understanding their phase behavior was a massive leap forward for us,” said Portner. 

The full range of applications remains unclear, but the scientists can think of multiple areas where the technique could lead. “For example, perhaps each crystal could be a qubit in a quantum computer; coupling qubits into arrays is one of the fundamental challenges of quantum technology right now,” said Talapin. 

Portner is also interested in exploring the unusual intermediate state of matter seen during supercrystal growth: “Triple phase coexistence like this is rare enough that it’s intriguing to think about how to take advantage of this chemistry and build new materials.”

The study included scientists with the University of Chicago, Technische Universität Dresden, Northwestern University, Arizona State University, SLAC, Lawrence Berkeley National Laboratory, and the University of California, Berkeley.

Here’s a link to and a citation for the paper,

Self-assembly of nanocrystals into strongly electronically coupled all-inorganic supercrystals by Igor Coropceanu, Eric M. Janke, Joshua Portner, Danny Haubold, Trung Dac Nguyen, Avishek Das, Christian P. N. Tanner, James K. Utterback, Samuel W. Teitelbaum¸ Margaret H. Hudson, Nivedina A. Sarma, Alex M. Hinkle, Christopher J. Tassone, Alexander Eychmüller, David T. Limmer, Monica Olvera de la Cruz, Naomi S. Ginsberg and Dmitri V. Talapin. Science • 24 Mar 2022 • Vol 375, Issue 6587 • pp. 1422-1426 • DOI: 10.1126/science.abm6753

This paper is behind a paywall.

‘Nanotraps’ for catching and destroying coronavirus

‘Nanotraps’ are not vaccines although they do call the immune system into play. They represent a different way for dealing with COVID-19. (This work reminds of my June 24, 2020 posting Tiny sponges lure coronavirus away from lung cells where the researchers have a similar approach with what they call ‘nanosponges’.)

An April 27, 2021 news item on Nanowerk makes the announcement,

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body’s own immune system to destroy it.

These “Nanotraps” attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

A scanning electron microscope image of a nanotrap (orange) binding a simulated SARS-CoV-2 virus (dots in green). Scientists at the University of Chicago created these nanoparticles as a potential treatment for COVID-19. Image courtesy Chen and Rosenberg et al.

An April 27, 2021 University of Chicago news release (also on EurekAlert) by Emily Ayshford, which originated the news item, describes the work in more detail,

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Asst. Prof. Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Designing the perfect trap

To design the Nanotrap, the research team – led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg – looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell’s ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA [US Food and Drug Administration]-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter – much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus – a less potent model of a virus that doesn’t replicate – in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle – which in tests took about 10 minutes after injection – the nanoparticles used a molecule that calls the body’s macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system – a pair of donated lungs that is kept alive with a ventilator – and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.

A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

“This is the starting point,” Huang said. “We want to do something to help the world.”

The research involved collaborators across departments, including chemistry, biology, and medicine.

Here’s a link to and a citation for the paper,

Nanotraps for the containment and clearance of SARS-CoV-2 by Min Chen, Jillian Rosenberg, Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glenn Randall, Pablo Penaloza-MacMaster, Bozhi Tian, Maria Lucia Madariaga, Jun Huang. Matter, April 19, 2021, DOI: https://doi.org/10.1016/j.matt.2021.04.005

This paper appears to be open access.

You mean Fitbit makes mistakes? More accuracy with ‘drawn-on-skin’ electronics

A July 30, 2020 news item on ScienceDaily announces news about more accurate health monitoring with electronics applied directly to your skin,

A team of researchers led by Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston, has developed a new form of electronics known as “drawn-on-skin electronics,” allowing multifunctional sensors and circuits to be drawn on the skin with an ink pen.

The advance, the researchers report in Nature Communications, allows for the collection of more precise, motion artifact-free health data, solving the long-standing problem of collecting precise biological data through a wearable device when the subject is in motion.

The imprecision may not be important when your FitBit registers 4,000 steps instead of 4,200, but sensors designed to check heart function, temperature and other physical signals must be accurate if they are to be used for diagnostics and treatment.

A July 30, 2020 University of Houston news release (also on EurekAlert) by Jeannie Kever, which originated the news item, goes on to explain why you might want to have electronics ‘drawn on your skin’,

The drawn-on-skin electronics are able to seamlessly collect data, regardless of the wearer’s movements.  

They also offer other advantages, including simple fabrication techniques that don’t require dedicated equipment.

“It is applied like you would use a pen to write on a piece of paper,” said Yu. “We prepare several electronic materials and then use pens to dispense them. Coming out, it is liquid. But like ink on paper, it dries very quickly.”

Wearable bioelectronics – in the form of soft, flexible patches attached to the skin – have become an important way to monitor, prevent and treat illness and injury by tracking physiological information from the wearer. But even the most flexible wearables are limited by motion artifacts, or the difficulty that arises in collecting data when the sensor doesn’t move precisely with the skin.

The drawn-on-skin electronics can be customized to collect different types of information, and Yu said it is expected to be especially useful in situations where it’s not possible to access sophisticated equipment, including on a battleground.

The electronics are able to track muscle signals, heart rate, temperature and skin hydration, among other physical data, he said. The researchers also reported that the drawn-on-skin electronics have demonstrated the ability to accelerate healing of wounds.

In addition to Yu, researchers involved in the project include Faheem Ershad, Anish Thukral, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang and Peng Wang, all from the University of Houston, and Jiping Yue and Xiaoyang Wu from the University of Chicago.

The drawn-on-skin electronics are actually comprised of three inks, serving as a conductor, semiconductor and dielectric.

“Electronic inks, including conductors, semiconductors, and dielectrics, are drawn on-demand in a freeform manner to develop devices, such as transistors, strain sensors, temperature sensors, heaters, skin hydration sensors, and electrophysiological sensors,” the researchers wrote.

This research is supported by the Office of Naval Research and National Institutes of Health.

Caption: A new form of electronics known as “drawn-on-skin electronics” allows multifunctional sensors and circuits to be drawn on the skin with an ink pen. Credit: University of Houston

Here’s a link to and a citation for the paper,

Ultra-conformal drawn-on-skin electronics for multifunctional motion artifact-free sensing and point-of-care treatment by Faheem Ershad, Anish Thukral, Jiping Yue, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang, Peng Wang, Xiaoyang Wu & Cunjiang Yu. Nature Communications volume 11, Article number: 3823 (2020) DOI: https://doi.org/10.1038/s41467-020-17619-1

This paper is open access.

Touchy robots and prosthetics

I have briefly speculated about the importance of touch elsewhere (see my July 19, 2019 posting regarding BlocKit and blockchain; scroll down about 50% of the way) but this upcoming news bit and the one following it put a different spin on the importance of touch.

Exceptional sense of touch

Robots need a sense of touch to perform their tasks and a July 18, 2019 National University of Singapore press release (also on EurekAlert) announces work on an improved sense of touch,

Robots and prosthetic devices may soon have a sense of touch equivalent to, or better than, the human skin with the Asynchronous Coded Electronic Skin (ACES), an artificial nervous system developed by a team of researchers at the National University of Singapore (NUS).

The new electronic skin system achieved ultra-high responsiveness and robustness to damage, and can be paired with any kind of sensor skin layers to function effectively as an electronic skin.

The innovation, achieved by Assistant Professor Benjamin Tee and his team from the Department of Materials Science and Engineering at the NUS Faculty of Engineering, was first reported in prestigious scientific journal Science Robotics on 18 July 2019.

Faster than the human sensory nervous system

“Humans use our sense of touch to accomplish almost every daily task, such as picking up a cup of coffee or making a handshake. Without it, we will even lose our sense of balance when walking. Similarly, robots need to have a sense of touch in order to interact better with humans, but robots today still cannot feel objects very well,” explained Asst Prof Tee, who has been working on electronic skin technologies for over a decade in hope of giving robots and prosthetic devices a better sense of touch.

Drawing inspiration from the human sensory nervous system, the NUS team spent a year and a half developing a sensor system that could potentially perform better. While the ACES electronic nervous system detects signals like the human sensor nervous system, it is made up of a network of sensors connected via a single electrical conductor, unlike the nerve bundles in the human skin. It is also unlike existing electronic skins which have interlinked wiring systems that can make them sensitive to damage and difficult to scale up.

Elaborating on the inspiration, Asst Prof Tee, who also holds appointments in the NUS Department of Electrical and Computer Engineering, NUS Institute for Health Innovation & Technology (iHealthTech), N.1 Institute for Health and the Hybrid Integrated Flexible Electronic Systems (HiFES) programme, said, “The human sensory nervous system is extremely efficient, and it works all the time to the extent that we often take it for granted. It is also very robust to damage. Our sense of touch, for example, does not get affected when we suffer a cut. If we can mimic how our biological system works and make it even better, we can bring about tremendous advancements in the field of robotics where electronic skins are predominantly applied.”

ACES can detect touches more than 1,000 times faster than the human sensory nervous system. For example, it is capable of differentiating physical contacts between different sensors in less than 60 nanoseconds – the fastest ever achieved for an electronic skin technology – even with large numbers of sensors. ACES-enabled skin can also accurately identify the shape, texture and hardness of objects within 10 milliseconds, ten times faster than the blinking of an eye. This is enabled by the high fidelity and capture speed of the ACES system.

The ACES platform can also be designed to achieve high robustness to physical damage, an important property for electronic skins because they come into the frequent physical contact with the environment. Unlike the current system used to interconnect sensors in existing electronic skins, all the sensors in ACES can be connected to a common electrical conductor with each sensor operating independently. This allows ACES-enabled electronic skins to continue functioning as long as there is one connection between the sensor and the conductor, making them less vulnerable to damage.

Smart electronic skins for robots and prosthetics

ACES’ simple wiring system and remarkable responsiveness even with increasing numbers of sensors are key characteristics that will facilitate the scale-up of intelligent electronic skins for Artificial Intelligence (AI) applications in robots, prosthetic devices and other human machine interfaces.

“Scalability is a critical consideration as big pieces of high performing electronic skins are required to cover the relatively large surface areas of robots and prosthetic devices,” explained Asst Prof Tee. “ACES can be easily paired with any kind of sensor skin layers, for example, those designed to sense temperatures and humidity, to create high performance ACES-enabled electronic skin with an exceptional sense of touch that can be used for a wide range of purposes,” he added.

For instance, pairing ACES with the transparent, self-healing and water-resistant sensor skin layer also recently developed by Asst Prof Tee’s team, creates an electronic skin that can self-repair, like the human skin. This type of electronic skin can be used to develop more realistic prosthetic limbs that will help disabled individuals restore their sense of touch.

Other potential applications include developing more intelligent robots that can perform disaster recovery tasks or take over mundane operations such as packing of items in warehouses. The NUS team is therefore looking to further apply the ACES platform on advanced robots and prosthetic devices in the next phase of their research.

For those who like videos, the researchers have prepared this,

Here’s a link to and a citation for the paper,

A neuro-inspired artificial peripheral nervous system for scalable electronic skins by Wang Wei Lee, Yu Jun Tan, Haicheng Yao, Si Li, Hian Hian See, Matthew Hon, Kian Ann Ng, Betty Xiong, John S. Ho and Benjamin C. K. Tee. Science Robotics Vol 4, Issue 32 31 July 2019 eaax2198 DOI: 10.1126/scirobotics.aax2198 Published online first: 17 Jul 2019:

This paper is behind a paywall.

Picking up a grape and holding his wife’s hand

This story comes from the Canadian Broadcasting Corporation (CBC) Radio with a six minute story embedded in the text, from a July 25, 2019 CBC Radio ‘As It Happens’ article by Sheena Goodyear,

The West Valley City, Utah, real estate agent [Keven Walgamott] lost his left hand in an electrical accident 17 years ago. Since then, he’s tried out a few different prosthetic limbs, but always found them too clunky and uncomfortable.

Then he decided to work with the University of Utah in 2016 to test out new prosthetic technology that mimics the sensation of human touch, allowing Walgamott to perform delicate tasks with precision — including shaking his wife’s hand. 

“I extended my left hand, she came and extended hers, and we were able to feel each other with the left hand for the first time in 13 years, and it was just a marvellous and wonderful experience,” Walgamott told As It Happens guest host Megan Williams. 

Walgamott, one of seven participants in the University of Utah study, was able to use an advanced prosthetic hand called the LUKE Arm to pick up an egg without cracking it, pluck a single grape from a bunch, hammer a nail, take a ring on and off his finger, fit a pillowcase over a pillow and more. 

While performing the tasks, Walgamott was able to actually feel the items he was holding and correctly gauge the amount of pressure he needed to exert — mimicking a process the human brain does automatically.

“I was able to feel something in each of my fingers,” he said. “What I feel, I guess the easiest way to explain it, is little electrical shocks.”

Those shocks — which he describes as a kind of a tingling sensation — intensify as he tightens his grip.

“Different variations of the intensity of the electricity as I move my fingers around and as I touch things,” he said. 

To make that [sense of touch] happen, the researchers implanted electrodes into the nerves on Walgamott’s forearm, allowing his brain to communicate with his prosthetic through a computer outside his body. That means he can move the hand just by thinking about it.

But those signals also work in reverse.

The team attached sensors to the hand of a LUKE Arm. Those sensors detect touch and positioning, and send that information to the electrodes so it can be interpreted by the brain.

For Walgamott, performing a series of menial tasks as a team of scientists recorded his progress was “fun to do.”

“I’d forgotten how well two hands work,” he said. “That was pretty cool.”

But it was also a huge relief from the phantom limb pain he has experienced since the accident, which he describes as a “burning sensation” in the place where his hand used to be.

A July 24, 2019 University of Utah news release (also on EurekAlert) provides more detail about the research,

Keven Walgamott had a good “feeling” about picking up the egg without crushing it.

What seems simple for nearly everyone else can be more of a Herculean task for Walgamott, who lost his left hand and part of his arm in an electrical accident 17 years ago. But he was testing out the prototype of a high-tech prosthetic arm with fingers that not only can move, they can move with his thoughts. And thanks to a biomedical engineering team at the University of Utah, he “felt” the egg well enough so his brain could tell the prosthetic hand not to squeeze too hard.

That’s because the team, led by U biomedical engineering associate professor Gregory Clark, has developed a way for the “LUKE Arm” (so named after the robotic hand that Luke Skywalker got in “The Empire Strikes Back”) to mimic the way a human hand feels objects by sending the appropriate signals to the brain. Their findings were published in a new paper co-authored by U biomedical engineering doctoral student Jacob George, former doctoral student David Kluger, Clark and other colleagues in the latest edition of the journal Science Robotics. A copy of the paper may be obtained by emailing robopak@aaas.org.

“We changed the way we are sending that information to the brain so that it matches the human body. And by matching the human body, we were able to see improved benefits,” George says. “We’re making more biologically realistic signals.”

That means an amputee wearing the prosthetic arm can sense the touch of something soft or hard, understand better how to pick it up and perform delicate tasks that would otherwise be impossible with a standard prosthetic with metal hooks or claws for hands.

“It almost put me to tears,” Walgamott says about using the LUKE Arm for the first time during clinical tests in 2017. “It was really amazing. I never thought I would be able to feel in that hand again.”

Walgamott, a real estate agent from West Valley City, Utah, and one of seven test subjects at the U, was able to pluck grapes without crushing them, pick up an egg without cracking it and hold his wife’s hand with a sensation in the fingers similar to that of an able-bodied person.

“One of the first things he wanted to do was put on his wedding ring. That’s hard to do with one hand,” says Clark. “It was very moving.”

Those things are accomplished through a complex series of mathematical calculations and modeling.

The LUKE Arm

The LUKE Arm has been in development for some 15 years. The arm itself is made of mostly metal motors and parts with a clear silicon “skin” over the hand. It is powered by an external battery and wired to a computer. It was developed by DEKA Research & Development Corp., a New Hampshire-based company founded by Segway inventor Dean Kamen.

Meanwhile, the U’s team has been developing a system that allows the prosthetic arm to tap into the wearer’s nerves, which are like biological wires that send signals to the arm to move. It does that thanks to an invention by U biomedical engineering Emeritus Distinguished Professor Richard A. Normann called the Utah Slanted Electrode Array. The array is a bundle of 100 microelectrodes and wires that are implanted into the amputee’s nerves in the forearm and connected to a computer outside the body. The array interprets the signals from the still-remaining arm nerves, and the computer translates them to digital signals that tell the arm to move.

But it also works the other way. To perform tasks such as picking up objects requires more than just the brain telling the hand to move. The prosthetic hand must also learn how to “feel” the object in order to know how much pressure to exert because you can’t figure that out just by looking at it.

First, the prosthetic arm has sensors in its hand that send signals to the nerves via the array to mimic the feeling the hand gets upon grabbing something. But equally important is how those signals are sent. It involves understanding how your brain deals with transitions in information when it first touches something. Upon first contact of an object, a burst of impulses runs up the nerves to the brain and then tapers off. Recreating this was a big step.

“Just providing sensation is a big deal, but the way you send that information is also critically important, and if you make it more biologically realistic, the brain will understand it better and the performance of this sensation will also be better,” says Clark.

To achieve that, Clark’s team used mathematical calculations along with recorded impulses from a primate’s arm to create an approximate model of how humans receive these different signal patterns. That model was then implemented into the LUKE Arm system.

Future research

In addition to creating a prototype of the LUKE Arm with a sense of touch, the overall team is already developing a version that is completely portable and does not need to be wired to a computer outside the body. Instead, everything would be connected wirelessly, giving the wearer complete freedom.

Clark says the Utah Slanted Electrode Array is also capable of sending signals to the brain for more than just the sense of touch, such as pain and temperature, though the paper primarily addresses touch. And while their work currently has only involved amputees who lost their extremities below the elbow, where the muscles to move the hand are located, Clark says their research could also be applied to those who lost their arms above the elbow.

Clark hopes that in 2020 or 2021, three test subjects will be able to take the arm home to use, pending federal regulatory approval.

The research involves a number of institutions including the U’s Department of Neurosurgery, Department of Physical Medicine and Rehabilitation and Department of Orthopedics, the University of Chicago’s Department of Organismal Biology and Anatomy, the Cleveland Clinic’s Department of Biomedical Engineering and Utah neurotechnology companies Ripple Neuro LLC and Blackrock Microsystems. The project is funded by the Defense Advanced Research Projects Agency and the National Science Foundation.

“This is an incredible interdisciplinary effort,” says Clark. “We could not have done this without the substantial efforts of everybody on that team.”

Here’s a link to and a citation for the paper,

Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand by J. A. George, D. T. Kluger, T. S. Davis, S. M. Wendelken, E. V. Okorokova, Q. He, C. C. Duncan, D. T. Hutchinson, Z. C. Thumser, D. T. Beckler, P. D. Marasco, S. J. Bensmaia and G. A. Clark. Science Robotics Vol. 4, Issue 32, eaax2352 31 July 2019 DOI: 10.1126/scirobotics.aax2352 Published online first: 24 Jul 2019

This paper is definitely behind a paywall.

The University of Utah researchers have produced a video highlighting their work,

The roles mathematics and light play in cellular communication

These are two entirely different types of research but taken together they help build a picture about how the cells in our bodies function.

Cells and light

An April 30, 2018 news item on phys.org describes work on controlling biology with light,

Over the past five years, University of Chicago chemist Bozhi Tian has been figuring out how to control biology with light.

A longterm science goal is devices to serve as the interface between researcher and body—both as a way to understand how cells talk among each other and within themselves, and eventually, as a treatment for brain or nervous system disorders [emphasis mine] by stimulating nerves to fire or limbs to move. Silicon—a versatile, biocompatible material used in both solar panels and surgical implants—is a natural choice.

In a paper published April 30 in Nature Biomedical Engineering, Tian’s team laid out a system of design principles for working with silicon to control biology at three levels—from individual organelles inside cells to tissues to entire limbs. The group has demonstrated each in cells or mice models, including the first time anyone has used light to control behavior without genetic modification.

“We want this to serve as a map, where you can decide which problem you would like to study and immediately find the right material and method to address it,” said Tian, an assistant professor in the Department of Chemistry.

Researchers built this thin layer of silicon lace to modulate neural signals when activated by light. Courtesy of Yuanwen Jiang and Bozhi Tian

An April 30, 2018 University of Chicago news release by Louise Lerner, which originated the news item, describes the work in greater detail,

The scientists’ map lays out best methods to craft silicon devices depending on both the intended task and the scale—ranging from inside a cell to a whole animal.

For example, to affect individual brain cells, silicon can be crafted to respond to light by emitting a tiny ionic current, which encourages neurons to fire. But in order to stimulate limbs, scientists need a system whose signals can travel farther and are stronger—such as a gold-coated silicon material in which light triggers a chemical reaction.

The mechanical properties of the implant are important, too. Say researchers would like to work with a larger piece of the brain, like the cortex, to control motor movement. The brain is a soft, squishy substance, so they’ll need a material that’s similarly soft and flexible, but can bind tightly against the surface. They’d want thin and lacy silicon, say the design principles.

The team favors this method because it doesn’t require genetic modification or a power supply wired in, since the silicon can be fashioned into what are essentially tiny solar panels. (Many other forms of monitoring or interacting with the brain need to have a power supply, and keeping a wire running into a patient is an infection risk.)

They tested the concept in mice and found they could stimulate limb movements by shining light on brain implants. Previous research tested the concept in neurons.

“We don’t have answers to a number of intrinsic questions about biology, such as whether individual mitochondria communicate remotely through bioelectric signals,” said Yuanwen Jiang, the first author on the paper, then a graduate student at UChicago and now a postdoctoral researcher at Stanford. “This set of tools could address such questions as well as pointing the way to potential solutions for nervous system disorders.”

Other UChicago authors were Assoc. Profs. Chin-Tu Chen and Chien-Min Kao, Asst. Prof Xiaoyang, postdoctoral researchers Jaeseok Yi, Yin Fang, Xiang Gao, Jiping Yue, Hsiu-Ming Tsai, Bing Liu and Yin Fang, graduate students Kelliann Koehler, Vishnu Nair, and Edward Sudzilovsky, and undergraduate student George Freyermuth.

Other researchers on the paper hailed from Northwestern University, the University of Illinois at Chicago and Hong Kong Polytechnic University.

The researchers have also made this video illustrating their work,

via Gfycat Tiny silicon nanowires (in blue), activated by light, trigger activity in neurons. (Courtesy Yuanwen Jiang and Bozhi Tian)

Here’s a link to and a citation for the paper,

Rational design of silicon structures for optically controlled multiscale biointerfaces by Yuanwen Jiang, Xiaojian Li, Bing Liu, Jaeseok Yi, Yin Fang, Fengyuan Shi, Xiang Gao, Edward Sudzilovsky, Ramya Parameswaran, Kelliann Koehler, Vishnu Nair, Jiping Yue, KuangHua Guo, Yin Fang, Hsiu-Ming Tsai, George Freyermuth, Raymond C. S. Wong, Chien-Min Kao, Chin-Tu Chen, Alan W. Nicholls, Xiaoyang Wu, Gordon M. G. Shepherd, & Bozhi Tian. Nature Biomedical Engineering (2018) doi:10.1038/s41551-018-0230-1 Published: 30 April 2018

This paper is behind a paywall.

Mathematics and how living cells ‘think’

This May 2, 2018 Queensland University of Technology (QUT; Australia) press release is also on EurekAlert,

How does the ‘brain’ of a living cell work, allowing an organism to function and thrive in changing and unfavourable environments?

Queensland University of Technology (QUT) researcher Dr Robyn Araujo has developed new mathematics to solve a longstanding mystery of how the incredibly complex biological networks within cells can adapt and reset themselves after exposure to a new stimulus.

Her findings, published in Nature Communications, provide a new level of understanding of cellular communication and cellular ‘cognition’, and have potential application in a variety of areas, including new targeted cancer therapies and drug resistance.

Dr Araujo, a lecturer in applied and computational mathematics in QUT’s Science and Engineering Faculty, said that while we know a great deal about gene sequences, we have had extremely limited insight into how the proteins encoded by these genes work together as an integrated network – until now.

“Proteins form unfathomably complex networks of chemical reactions that allow cells to communicate and to ‘think’ – essentially giving the cell a ‘cognitive’ ability, or a ‘brain’,” she said. “It has been a longstanding mystery in science how this cellular ‘brain’ works.

“We could never hope to measure the full complexity of cellular networks – the networks are simply too large and interconnected and their component proteins are too variable.

“But mathematics provides a tool that allows us to explore how these networks might be constructed in order to perform as they do.

“My research is giving us a new way to look at unravelling network complexity in nature.”

Dr Araujo’s work has focused on the widely observed function called perfect adaptation – the ability of a network to reset itself after it has been exposed to a new stimulus.

“An example of perfect adaptation is our sense of smell,” she said. “When exposed to an odour we will smell it initially but after a while it seems to us that the odour has disappeared, even though the chemical, the stimulus, is still present.

“Our sense of smell has exhibited perfect adaptation. This process allows it to remain sensitive to further changes in our environment so that we can detect both very feint and very strong odours.

“This kind of adaptation is essentially what takes place inside living cells all the time. Cells are exposed to signals – hormones, growth factors, and other chemicals – and their proteins will tend to react and respond initially, but then settle down to pre-stimulus levels of activity even though the stimulus is still there.

“I studied all the possible ways a network can be constructed and found that to be capable of this perfect adaptation in a robust way, a network has to satisfy an extremely rigid set of mathematical principles. There are a surprisingly limited number of ways a network could be constructed to perform perfect adaptation.

“Essentially we are now discovering the needles in the haystack in terms of the network constructions that can actually exist in nature.

“It is early days, but this opens the door to being able to modify cell networks with drugs and do it in a more robust and rigorous way. Cancer therapy is a potential area of application, and insights into how proteins work at a cellular level is key.”

Dr Araujo said the published study was the result of more than “five years of relentless effort to solve this incredibly deep mathematical problem”. She began research in this field while at George Mason University in Virginia in the US.

Her mentor at the university’s College of Science and co-author of the Nature Communications paper, Professor Lance Liotta, said the “amazing and surprising” outcome of Dr Araujo’s study is applicable to any living organism or biochemical network of any size.

“The study is a wonderful example of how mathematics can have a profound impact on society and Dr Araujo’s results will provide a set of completely fresh approaches for scientists in a variety of fields,” he said.

“For example, in strategies to overcome cancer drug resistance – why do tumours frequently adapt and grow back after treatment?

“It could also help understanding of how our hormone system, our immune defences, perfectly adapt to frequent challenges and keep us well, and it has future implications for creating new hypotheses about drug addiction and brain neuron signalling adaptation.”

Hre’s a link to and a citation for the paper,

The topological requirements for robust perfect adaptation in networks of any size by Robyn P. Araujo & Lance A. Liotta. Nature Communicationsvolume 9, Article number: 1757 (2018) doi:10.1038/s41467-018-04151-6 Published: 01 May 2018

This paper is open access.

Quantum entanglement in near-macroscopic objects

Researchers at Finland’s Aalto University seem excited in an April 25, 2018 news item on phys.org,

Perhaps the strangest prediction of quantum theory is entanglement, a phenomenon whereby two distant objects become intertwined in a manner that defies both classical physics and a common-sense understanding of reality. In 1935, Albert Einstein expressed his concern over this concept, referring to it as “spooky action at a distance.”

Today, entanglement is considered a cornerstone of quantum mechanics, and it is the key resource for a host of potentially transformative quantum technologies. Entanglement is, however, extremely fragile, and it has previously been observed only in microscopic systems such as light or atoms, and recently in superconducting electric circuits.

In work recently published in Nature, a team led by Prof. Mika Sillanpää at Aalto University in Finland has shown that entanglement of massive objects can be generated and detected.

The researchers managed to bring the motions of two individual vibrating drumheads—fabricated from metallic aluminium on a silicon chip—into an entangled quantum state. The macroscopic objects in the experiment are truly massive compared to the atomic scale—the circular drumheads have a diametre similar to the width of a thin human hair.

An April 20,2018 Aalto University press release (also on EurekAlert), which originated the news item, provides more detail,

‘The vibrating bodies are made to interact via a superconducting microwave circuit. The electromagnetic fields in the circuit carry away any thermal disturbances, leaving behind only the quantum mechanical vibrations’, says Professor Sillanpää, describing the experimental setup.

Eliminating all forms of external noise is crucial for the experiments, which is why they have to be conducted at extremely low temperatures near absolute zero, at –273 °C. Remarkably, the experimental approach allows the unusual state of entanglement to persist for long periods of time, in this case up to half an hour. In comparison, measurements on elementary particles have witnessed entanglement to last only tiny fractions of a second.

‘These measurements are challenging but extremely fascinating. In the future, we will attempt to teleport the mechanical vibrations. In quantum teleportation, properties of physical bodies can be transmitted across arbitrary distances using the channel of “spooky action at a distance”. We are still pretty far from Star Trek, though,’ says Dr. Caspar Ockeloen-Korppi, the lead author on the work, who also performed the measurements.

The results demonstrate that it is now possible to have control over the most delicate properties of objects whose size approaches the scale of our daily lives. The achievement opens doors for new kinds of quantum technologies, where the entangled drumheads could be used as routers or sensors. The finding also enables new studies of fundamental physics in, for example, the poorly understood interplay of gravity and quantum mechanics.

The team also included scientists from the University of New South Wales in Australia, the University of Chicago in the USA, and the University of Jyväskylä in Finland, whose theoretical innovations paved the way for the laboratory experiment.

An illustration has been made available,

An illustration of the 15-micrometre-wide drumheads prepared on silicon chips used in the experiment. The drumheads vibrate at a high ultrasound frequency, and the peculiar quantum state predicted by Einstein was created from the vibrations. Image: Aalto University / Petja Hyttinen & Olli Hanhirova, ARKH Architects.

Here’s a link to and a citation for the paper,

Stabilized entanglement of massive mechanical oscillators by C. F. Ockeloen-Korppi, E. Damskägg, J.-M. Pirkkalainen, M. Asjad, A. A. Clerk, F. Massel, M. J. Woolley & M. A. Sillanpää. Nature volume 556, pages478–482 (2018) doi:10.1038/s41586-018-0038-x Published online: 25 April 2018

This paper is behind a paywall.