Tag Archives: Duke University

Grow better organ-like tissues by using silkworms

A June 6, 2024 news item on ScienceDaily describes a technique, which could lead to better organ-on-a-chip (OOC) systems,

Biomedical engineers at Duke University [North Carolina, US] have developed a silk-based, ultrathin membrane that can be used in organ-on-a-chip models to better mimic the natural environment of cells and tissues within the body. When used in a kidney organ-on-a-chip platform, the membrane helped tissues grow to recreate the functionality of both healthy and diseased kidneys.

By allowing the cells to grow closer together, this new membrane helps researchers to better control the growth and function of the key cells and tissues of any organ, enabling them to more accurately model a wide range of diseases and test therapeutics.

A June 6, 2024 Duke University news release (also on EurekAlert), which originated the news item, describes the OOC system and the problem these researchers are seeking to solve,

Often no larger than a USB flash drive, organ-on-a-chip (OOC) systems have revolutionized how researchers study the underlying biology of the human body, whether it’s creating dynamic models of tissue structures, studying organ functions or modeling diseases. These platforms are designed to stimulate cell growth and differentiation in a way that best mimics the organ of interest. Researchers can even populate these tools with human stem cells to generate patient-specific organ models for pre-clinical studies.

But as the technology has evolved, problems in the chip’s design have also emerged –– most notably with the materials used to create the membranes that form the support structure for the specialized cells to grow on. These membranes are typically composed of polymers that don’t degrade, creating a permanent barrier between cells and tissues. While the extracellular membranes in human organs are often less than one micron thick, these polymer membranes are anywhere from 30 to 50 microns, hindering communication between cells and limiting cell growth.

“We want to handle the tissues in these chips just like a pathologist would handle biopsy samples or even living tissues from a patient, but this wasn’t possible with the standard polymer membranes because the extra thickness prevented the cells from forming structures that more closely resemble tissues in the human body,” said Samira Musah, an assistant professor of biomedical engineering and medicine at Duke. “We thought, ‘Wouldn’t it be nice if we could get a protein-based material that mimics the structure of these natural membranes and is thin enough for us to slice and study?’”

This question led Musah and George (Xingrui) Mou, a PhD student in Musah’s lab and first author on the paper, to silk fibroin, a protein created by silkworms that can be electronically spun into a membrane. When examined under a microscope, silk fibroin looks like spaghetti or a Jackson Pollock painting. Made out of long, intertwining fibers, the porous material better mimics the structure of the extracellular matrix found in human organs, and it has previously been used to create scaffolds for purposes like wound healing.

“The silk fibroin allowed us to bring the membrane thickness down from 50 microns to five or fewer, which gets us an order of magnitude closer to what you’d see in a living organism,” explained Mao.

To test this new membrane, Musah and Mao applied the material to their kidney chip models. Made out of a clear plastic and roughly the size of a quarter, this OOC platform is meant to resemble a cross section of a human kidney––specifically the glomerular capillary wall, a key structure in the organ made from clusters of blood vessels that is responsible for filtering blood.

Once the membrane was in place, the team added human induced pluripotent stem cell derivatives into the chip. They observed that these cells were able to send signals across the ultrathin membrane, which helped the cells differentiate into glomerular cells, podocytes and vascular endothelial cells. The platform also triggered the development of endothelial fenestrations in the growing tissue, which are holes that allow for the passage of fluid between the cellular layers.

By the end of the test, these different kidney cell types had assembled into a glomerular capillary wall and could efficiently filter molecules by size.

“The new microfluidic chip system’s ability to simulate in vivo-like tissue-tissue interfaces and induce the formation of specialized cells, such as fenestrated endothelium and mature glomerular podocytes from stem cells, holds significant potential for advancing our understanding of human organ development, disease progression, and therapeutic development,” said Musah.

As they continue to optimize their model, Musah and colleagues are hoping to use this technology to better understand the mechanisms behind kidney disease. Despite affecting more than 15 percent of American adults, researchers lack effective models for the disease. Patients are also often not diagnosed until the kidneys have been substantially damaged, and they are often required to undergo dialysis or receive a kidney transplant.

“Using this platform to develop kidney disease models could help us discover new biomarkers of the disease,” said Mao. “This could also be used to help us screen for drug candidates for several kidney disease models. The possibilities are very exciting.”

“This technology has implications for all organ-on-a-chip models,” said Musah. “Our tissues are made up of membranes and interfaces, so you can imagine using this membrane to improve models of other organs, like the brain, liver, and lungs, or other disease states. That’s where the power of our platform really lies.”

This work was supported by a Whitehead Scholarship in Biomedical Research, Chair’s Research Award from the Department of Medicine at Duke University, MEDx Pilot Grant on Biomechanics in Injury or Injury Repair, Burroughs Wellcome Fund PDEP Career Transition Ad Hoc Award, Duke Incubation Fund from the Duke Innovation & Entrepreneurship Initiative, Genetech Research Award, a George M. O’Brien Kidney Center Pilot Grant (P30 DK081943), an NIH [National Institutes of Health] Director’s New Innovator Grant (DP2DK138544).

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

An Ultrathin Membrane Mediates Tissue-Specific Morphogenesis and Barrier Function in a Human Kidney Chip by Xingrui Mou, Jessica Shah, Yasmin Roye, Carolyn Du, Samira Musah. Science Advances. June 4, 2024 Vol 10, Issue 23 DOI: https://doi.org/10.1126/sciadv.adn2689

This paper is open access.

Communicating thoughts by means of brain implants?

The Australian military announced mind-controlled robots in Spring 2023 (see my June 13, 2023 posting) and, recently, scientists at Duke University (North Carolina, US) have announced research that may allow people who are unable to speak to communicate their thoughts, from a November 6, 2023 news item on ScienceDaily,

A speech prosthetic developed by a collaborative team of Duke neuroscientists, neurosurgeons, and engineers can translate a person’s brain signals into what they’re trying to say.

Appearing Nov. 6 [2023] in the journal Nature Communications, the new technology might one day help people unable to talk due to neurological disorders regain the ability to communicate through a brain-computer interface.

One more plastic brain for this blog,

Caption: A device no bigger than a postage stamp (dotted portion within white band) packs 128 microscopic sensors that can translate brain cell activity into what someone intends to say. Credit: Dan Vahaba/Duke University

A November 6, 2023 Duke University news release (also on EurekAlert), which originated the news item, provides more detail, Note: Links have been removed,

“There are many patients who suffer from debilitating motor disorders, like ALS (amyotrophic lateral sclerosis) or locked-in syndrome, that can impair their ability to speak,” said Gregory Cogan, Ph.D., a professor of neurology at Duke University’s School of Medicine and one of the lead researchers involved in the project. “But the current tools available to allow them to communicate are generally very slow and cumbersome.”

Imagine listening to an audiobook at half-speed. That’s the best speech decoding rate currently available, which clocks in at about 78 words per minute. People, however, speak around 150 words per minute.

The lag between spoken and decoded speech rates is partially due the relatively few brain activity sensors that can be fused onto a paper-thin piece of material that lays atop the surface of the brain. Fewer sensors provide less decipherable information to decode.

To improve on past limitations, Cogan teamed up with fellow Duke Institute for Brain Sciences faculty member Jonathan Viventi, Ph.D., whose biomedical engineering lab specializes in making high-density, ultra-thin, and flexible brain sensors.

For this project, Viventi and his team packed an impressive 256 microscopic brain sensors onto a postage stamp-sized piece of flexible, medical-grade plastic. Neurons just a grain of sand apart can have wildly different activity patterns when coordinating speech, so it’s necessary to distinguish signals from neighboring brain cells to help make accurate predictions about intended speech.

After fabricating the new implant, Cogan and Viventi teamed up with several Duke University Hospital neurosurgeons, including Derek Southwell, M.D., Ph.D., Nandan Lad, M.D., Ph.D., and Allan Friedman, M.D., who helped recruit four patients to test the implants. The experiment required the researchers to place the device temporarily in patients who were undergoing brain surgery for some other condition, such as  treating Parkinson’s disease or having a tumor removed. Time was limited for Cogan and his team to test drive their device in the OR.

“I like to compare it to a NASCAR pit crew,” Cogan said. “We don’t want to add any extra time to the operating procedure, so we had to be in and out within 15 minutes. As soon as the surgeon and the medical team said ‘Go!’ we rushed into action and the patient performed the task.”

The task was a simple listen-and-repeat activity. Participants heard a series of nonsense words, like “ava,” “kug,” or “vip,” and then spoke each one aloud. The device recorded activity from each patient’s speech motor cortex as it coordinated nearly 100 muscles that move the lips, tongue, jaw, and larynx.

Afterwards, Suseendrakumar Duraivel, the first author of the new report and a biomedical engineering graduate student at Duke, took the neural and speech data from the surgery suite and fed it into a machine learning algorithm to see how accurately it could predict what sound was being made, based only on the brain activity recordings.

For some sounds and participants, like /g/ in the word “gak,”  the decoder got it right 84% of the time when it was the first sound in a string of three that made up a given nonsense word.

Accuracy dropped, though, as the decoder parsed out sounds in the middle or at the end of a nonsense word. It also struggled if two sounds were similar, like /p/ and /b/.

Overall, the decoder was accurate 40% of the time. That may seem like a humble test score, but it was quite impressive given that similar brain-to-speech technical feats require hours or days-worth of data to draw from. The speech decoding algorithm Duraivel used, however, was working with only 90 seconds of spoken data from the 15-minute test.

Duraivel and his mentors are excited about making a cordless version of the device with a recent $2.4M grant from the National Institutes of Health.

“We’re now developing the same kind of recording devices, but without any wires,” Cogan said. “You’d be able to move around, and you wouldn’t have to be tied to an electrical outlet, which is really exciting.”

While their work is encouraging, there’s still a long way to go for Viventi and Cogan’s speech prosthetic to hit the shelves anytime soon.

“We’re at the point where it’s still much slower than natural speech,” Viventi said in a recent Duke Magazine piece about the technology, “but you can see the trajectory where you might be able to get there.”

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

High-resolution neural recordings improve the accuracy of speech decoding by Suseendrakumar Duraivel, Shervin Rahimpour, Chia-Han Chiang, Michael Trumpis, Charles Wang, Katrina Barth, Stephen C. Harward, Shivanand P. Lad, Allan H. Friedman, Derek G. Southwell, Saurabh R. Sinha, Jonathan Viventi & Gregory B. Cogan. Nature Communications volume 14, Article number: 6938 (2023) DO: Ihttps://doi.org/10.1038/s41467-023-42555-1 Published: 06 November 2023

This paper is open access.

Mending a broken heart with hydrogels and cellulose nanocrystals (CNC)

Courtesy: University of Waterloo

This February 12, 2024 news item on ScienceDaily highlights work from the University of Waterloo,

You can mend a broken heart this valentine’s day now that researchers invented a new hydrogel that can be used to heal damaged heart tissue and improve cancer treatments.

University of Waterloo chemical engineering researcher Dr. Elisabeth Prince teamed up with researchers from the University of Toronto and Duke University to design the synthetic material made using cellulose nanocrystals [CNC], which are derived from wood pulp.

A February 12, 2024 University of Waterloo news release (also on EurekAlert), which originated the news item, fills in some details,

The material is engineered to replicate the fibrous nanostructures and properties of human tissues, thereby recreating its unique biomechanical properties.

“Cancer is a diverse disease and two patients with the same type of cancer will often respond to the same treatment in very different ways,” Prince said. “Tumour organoids are essentially a miniaturized version of an individual patient’s tumour that can be used for drug testing, which could allow researchers to develop personalized therapies for a specific patient.”

As director of the Prince Polymer Materials Lab, Prince designs synthetic biomimetic hydrogels for biomedical applications. The hydrogels have a nanofibrous architecture with large pores for nutrient and waste transport, which affect mechanical properties and cell interaction. 

Prince, a professor in Waterloo’s Department of Chemical Engineering, utilized these human-tissue mimetic hydrogels to promote the growth of small-scale tumour replicas derived from donated tumour tissue. 

She aims to test the effectiveness of cancer treatments on the mini-tumour organoids before administering the treatment to patients, potentially allowing for personalized cancer therapies. This research was conducted alongside Professor David Cescon at the Princess Margaret Cancer Center.

Prince’s research group at Waterloo is developing similar biomimetic hydrogels to be injectable for drug delivery and regenerative medical applications as Waterloo researchers continue to lead health innovation in Canada.

Her research aims to use injected filamentous hydrogel material to regrow heart tissue damaged after a heart attack. She used nanofibers as a scaffolding for the regrowth and healing of damaged heart tissue. 

“We are building on the work that I started during my PhD to design human-tissue mimetic hydrogels that can be injected into the human body to deliver therapeutics and repair the damage caused to the heart when a patient suffers a heart attack,” Prince said.

Prince’s research is unique as most gels currently used in tissue engineering or 3D cell culture don’t possess this nanofibrous architecture. Prince’s group uses nanoparticles and polymers as building blocks for materials and develops chemistry for nanostructures that accurately mimic human tissues.

The next step in Prince’s research is to use conductive nanoparticles to make electrically conductive nanofibrous gels that can be used to heal heart and skeletal muscle tissue.

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

Nanocolloidal hydrogel mimics the structure and nonlinear mechanical properties of biological fibrous networks by Elisabeth Prince, Sofia Morozova, Zhengkun Chen, and Eugenia Kumacheva. Proceedings of the National Academy of Sciences (PNAS) December 13, 2023 120 (51) e2220755120 DOI: https://doi.org/10.1073/pnas.2220755120

This paper is behind a paywall.

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.

Lab-made cartilage gel for stiff, achy knees

Researchers claim their lab-made cartilage is better than the real thing in an August 11, 2022 news item on phys.org, Note: Links have been removed,

Over-the-counter pain relievers, physical therapy, steroid injections—some people have tried it all and are still dealing with knee pain.

Often knee pain comes from the progressive wear and tear of cartilage known as osteoarthritis, which affects nearly one in six adults—867 million people—worldwide. For those who want to avoid replacing the entire knee joint, there may soon be another option that could help patients get back on their feet fast, pain-free, and stay that way.

Writing in the journal Advanced Functional Materials, a Duke University-led team says they have created the first gel-based cartilage substitute that is even stronger and more durable than the real thing.

Caption: Duke researchers have developed a gel-based cartilage substitute to relieve achy knees that’s even stronger and more durable than the real thing. Clinical trials to start next year. Credit: Canva Credit: Benjamin Wiley, Duke University

Here’s the August 11, 2022 Duke University news release (also on EurekAlert), which originated the news item, where you’ll find more details about the research, Note: Links have been removed,

Mechanical testing reveals that the Duke team’s hydrogel — a material made of water-absorbing polymers — can be pressed and pulled with more force than natural cartilage, and is three times more resistant to wear and tear.

Implants made of the material are currently being developed by Sparta Biomedical and tested in sheep. Researchers are gearing up to begin clinical trials in humans next year.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,” said Duke chemistry professor Benjamin Wiley, who led the research along with Duke mechanical engineering and materials science professor Ken Gall.

To make this material, the Duke team took thin sheets of cellulose fibers and infused them with a polymer called polyvinyl alcohol — a viscous goo consisting of stringy chains of repeating molecules — to form a gel.

The cellulose fibers act like the collagen fibers in natural cartilage, Wiley said — they give the gel strength when stretched. The polyvinyl alcohol helps it return to its original shape. The result is a Jello-like material, 60% water, which is supple yet surprisingly strong.

Natural cartilage can withstand a whopping 5,800 to 8,500 pounds per inch of tugging and squishing, respectively, before reaching its breaking point. Their lab-made version is the first hydrogel that can handle even more. It is 26% stronger than natural cartilage in tension, something like suspending seven grand pianos from a key ring, and 66% stronger in compression — which would be like parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley said.

The team has already made hydrogels with remarkable properties. In 2020, they reported that they had created the first hydrogel strong enough for knees, which feel the force of two to three times body weight with each step.

Putting the gel to practical use as a cartilage replacement, however, presented additional design challenges. One was achieving the upper limits of cartilage’s strength. Activities like hopping, lunging, or climbing stairs put some 10 Megapascals of pressure on the cartilage in the knee, or about 1,400 pounds per square inch. But the tissue can take up to four times that before it breaks.

“We knew there was room for improvement,” Wiley said.

In the past, researchers attempting to create stronger hydrogels used a freeze-thaw process to produce crystals within the gel, which drive out water and help hold the polymer chains together. In the new study, instead of freezing and thawing the hydrogel, the researchers used a heat treatment called annealing to coax even more crystals to form within the polymer network.

By increasing the crystal content, the researchers were able to produce a gel that can withstand five times as much stress from pulling and nearly twice as much squeezing relative to freeze-thaw methods.

The improved strength of the annealed gel also helped solve a second design challenge: securing it to the joint and getting it to stay put.

Cartilage forms a thin layer that covers the ends of bones so they don’t grind against one another. Previous studies haven’t been able to attach hydrogels directly to bone or cartilage with sufficient strength to keep them from breaking loose or sliding off. So the Duke team came up with a different approach.

Their method of attachment involves cementing and clamping the hydrogel to a titanium base. This is then pressed and anchored into a hole where the damaged cartilage used to be. Tests show the design stays fastened 68% more firmly than natural cartilage on bone.

“Another concern for knee implants is wear over time, both of the implant itself and the opposing cartilage,” Wiley said.

Other researchers have tried replacing damaged cartilage with knee implants made of metal or polyethylene, but because these materials are stiffer than cartilage they can chafe against other parts of the knee.

In wear tests, the researchers took artificial cartilage and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using a high-resolution X-ray scanning technique called micro-computed tomography (micro-CT), the scientists found that the surface of their lab-made version held up three times better than the real thing. Yet because the hydrogel mimics the smooth, slippery, cushiony nature of real cartilage, it protects other joint surfaces from friction as they slide against the implant.

Natural cartilage is remarkably durable stuff. But once damaged, it has limited ability to heal because it doesn’t have any blood vessels, Wiley said.

In the United States, osteoarthritis is twice as common today than it was a century ago. Surgery is an option when conservative treatments fail. Over the decades surgeons have developed a number of minimally invasive approaches, such as removing loose cartilage, or making holes to stimulate new growth, or transplanting healthy cartilage from a donor. But all of these methods require months of rehab, and some percentage of them fail over time.

Generally considered a last resort, total knee replacement is a proven way to relieve pain. But artificial joints don’t last forever, either. Particularly for younger patients who want to avoid major surgery for a device that will only need to be replaced again down the line, Wiley said, “there’s just not very good options out there.”

“I think this will be a dramatic change in treatment for people at this stage,” Wiley said.

This work was supported in part by Sparta Biomedical and by the Shared Materials Instrumentation Facility at Duke University. Wiley and Gall are shareholders in Sparta Biomedical.

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

A Synthetic Hydrogel Composite with a Strength and Wear Resistance Greater than Cartilage by Jiacheng Zhao, Huayu Tong, Alina Kirillova, William J. Koshut, Andrew Malek, Natasha C. Brigham, Matthew L. Becker, Ken Gall, Benjamin J. Wiley. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.202205662 First published: 04 August 2022

This paper is behind a paywall.

You can find Sparta Biomedical here.

In Brazil: Applications open for July 3 – 15, 2023 School of Advanced Science on Nanotechnology, Agriculture and Environment

According to the December 15, 2022 Fundação de Amparo à Pesquisa do Estado de São Paulo press release on EurekAlert applications will be received until February 5, 2023,

The São Paulo School of Advanced Science on Nanotechnology, Agriculture and Environment (SPSAS NanoAgri&Enviro) will be held on July 3-15 at the Brazilian Center for Research in Energy and Materials (CNPEM) in Campinas, São Paulo state, Brazil. 

Reporters are invited to reach the organizing committee through the email eventos@cnpem.br, for opportunities to visit the school and sessions.

Designed to meet an increasing level of content depth and complexity, the SPSAS NanoAgri&Enviro will cover the following topics: i) Nanotechnology, innovation, and sustainability; ii) Synthesis, functionalization, and characterization of nanomaterials; iii) Characterization of nanoparticles in complex matrices; iv) Synchrotron Light for nano-agri-environmental research; v) Biological and environmental applications of nanoparticles; vi) Nanofertilizers and Nanoagrochemicals; vii) Ecotoxicology, geochemistry and nanobiointerfaces; viii) Nanosafety and Nanoinformatics; ix) International harmonization and regulatory issues; x) Environmental implications of nanotechnology.

Discussions regarding those topics will benefit from the participation of internationally renowned scientists as speakers, including Mark V. Wiesner (Duke University), Iseult Lynch (University of Birmingham), Leonardo F. Fraceto (São Paulo State University – UNESP), Gregory V. Lowry (Carnegie Mellon University), Marisa N. Fernandes (Federal University of São Carlos – UFSCar), Caue Ribeiro (Brazilian Agricultural Research Corporation – EMBRAPA), and others.

The program also comprise didactic activities programmed among theoretical interactive classes, practical experiments (hands-on), and technical visits to world-class facilities and specialized laboratories from several institutions in São Paulo state.

The São Paulo Research Foundation (FAPESP) is supporting the event through its São Paulo School of Advanced Science Program (SPSAS http://espca.fapesp.br/home). Undergraduate students, postdoctoral fellows and researchers who are already working on subjects relating to the school can apply to receive financial support to cover the cost of air travel, accommodation and meals. Applications must be submitted by February 5, 2023.

More information: https://pages.cnpem.br/spsasnano/.

I looked up the criteria for eligible applicants and found this among the other criteria (from the Applications page),

Participating students must be enrolled in undergraduate or graduate courses in Brazil or abroad, being potential candidates for Master’s, Doctoral or Post-Doctoral internships in higher education and research institutions in the state of São Paulo. Doctors may also be accepted. [emphases mine]

If I read that correctly, it means that people who are considering or planning to further their studies in the state of São Paulo are being invited to apply.

I recognized two of the speakers’ names, Mark Wiesner and Iseult Lynch both of whom have been mentioned here a number of times as has Gregory V. Lowry. (Wiesner very kindly helped with an art/sci project I was involved with [Steep] a number of years ago.)

Good luck with your application!

Controlling the tiniest particles with sound-induced electrical fields

I find the use of sound as a research tool in this June 23, 2021 news item on ScienceDaily to be fascinating,

Engineers at Duke University [North Carolina, USL] have devised a system for manipulating particles approaching the miniscule 2.5 nanometer diameter of DNA using sound-induced electric fields. Dubbed “acoustoelectronic nanotweezers,” the approach provides a label-free, dynamically controllable method of moving and trapping nanoparticles over a large area. The technology holds promise for applications in the fields ranging from condensed matter physics to biomedicine.

A June 22, 2021 Duke University news release (also on EurekAlert) by Ben Kingery, which originated the news item, explains the interest in precise control and the use of sound in more detail,

Precisely controlling nanoparticles is a crucial ability for many emerging technologies. For example, separating exosomes and other tiny biological molecules from blood could lead to new types of diagnostic tests for the early detection of tumors and neurodegenerative diseases. Placing engineered nanoparticles in a specific pattern before fixing them in place can help create new types of materials with highly tunable properties.

For more than a decade, Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke, has pursued acoustic tweezer systems that use sound waves to manipulate particles. However, it becomes difficult to push things around with sound when their profile drops below that of some of the smallest viruses.

“Although we’re still fundamentally using sound, our acoustoelectronic nanotweezers use a very different mechanism than these previous technologies,” said Joseph Rufo, a graduate student working in Huang’s laboratory. “Now we’re not only exploiting acoustic waves, but electric fields with the properties of acoustic waves.”

Instead of using sound waves to directly move the nanoparticles, Huang, Rufo and Peiran Zhang, a postdoc in Huang’s laboratory, use sound waves to create electric fields that provide the push. The new acoustoelectronic tweezer approach works by placing a piezoelectric substrate–a thin material that creates electricity in response to mechanical stress–beneath a small chamber filled with liquid. Four transducers are aligned on the chamber’s sides, which send sound waves into the piezoelectric substrate.

These sound waves bounce around and interact with one another to create a stable pattern. And because the sound waves are creating stresses within the piezoelectric substrate, they also create electrical fields. These couple with the acoustic waves in a way that creates electric field patterns within the chamber above.

“The vibrations of the sound waves also make the electric field dynamically alternate between positive and negative charges,” said Zhang. “This alternating electric field polarizes the nanoparticles in liquid, which serves as a handle to manipulate them.”

The result is a mechanism that mixes some of the strengths of other nanoparticle manipulators. Because the acoustoelectronic nanotweezers induce an electromagnetic response in the nanomaterials, the nanoparticles do not need to be conductive on their own or tagged with any sort of modifier. And because the patterns are created with sound waves, their positions and properties can be quickly and easily modified to create a variety of options.

In the prototype, the researchers show nanoparticles placed into striped and checkerboard patterns. They even push individual particles around in an arbitrary manner dynamically, spelling out letters such as D, U, K and E [emphasis mine]. The researchers then demonstrate that these aligned nano-patterns can be transferred onto dry films using delicate nanoparticles such as carbon nanotubes, 3.5-nanometer proteins and 1.4-nanometer dextran often used in biomedical research. And they show that all of this can be accomplished on a working area that is tens to hundreds of times larger than current state-of-the-art nanotweezing technologies [emphasis mine].

Nanotweezing technologies? This concept is new to me.How will I work it into my next conversation?

As for spelling out D, U, K, and E, that brings to mind Don Eigler (from his Wikipedia entry),

In 1989, Eigler was the first to use a scanning tunneling microscope tip to arrange individual atoms on a surface, famously spelling out the letters “IBM” with 35 xenon atoms.

Perhaps the Duke University researchers intended an ‘hommage’? or ‘tip of the hat’?

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

Acoustoelectronic nanotweezers enable dynamic and large-scale control of nanomaterials by Peiran Zhang, Joseph Rufo, Chuyi Chen, Jianping Xia, Zhenhua Tian, Liying Zhang, Nanjing Hao, Zhanwei Zhong, Yuyang Gu, Krishnendu Chakrabarty & Tony Jun Huang. Nature Communications volume 12, Article number: 3844 (2021) DOI: https://doi.org/10.1038/s41467-021-24101-z Published 22 June 2021

This paper is open access.

An electronics-free, soft robotic dragonfly

From the description on YouTube,

With the ability to sense changes in pH, temperature and oil, this completely soft, electronics-free robot dubbed “DraBot” could be the prototype for future environmental sentinels. …

Music: Joneve by Mello C from the Free Music Archive

A favourite motif in the Art Nouveau movement (more about that later in the post), dragonflies or a facsimile thereof feature in March 25, 2021 Duke University news release (also on EurekAlert) by Ken Kingery,

Engineers at Duke University have developed an electronics-free, entirely soft robot shaped like a dragonfly that can skim across water and react to environmental conditions such as pH, temperature or the presence of oil. The proof-of-principle demonstration could be the precursor to more advanced, autonomous, long-range environmental sentinels for monitoring a wide range of potential telltale signs of problems.

The soft robot is described online March 25 [2021] in the journal Advanced Intelligent Systems.

Soft robots are a growing trend in the industry due to their versatility. Soft parts can handle delicate objects such as biological tissues that metal or ceramic components would damage. Soft bodies can help robots float or squeeze into tight spaces where rigid frames would get stuck.

The expanding field was on the mind of Shyni Varghese, professor of biomedical engineering, mechanical engineering and materials science, and orthopaedic surgery at Duke, when inspiration struck.

“I got an email from Shyni from the airport saying she had an idea for a soft robot that uses a self-healing hydrogel that her group has invented in the past to react and move autonomously,” said Vardhman Kumar, a PhD student in Varghese’s laboratory and first author of the paper. “But that was the extent of the email, and I didn’t hear from her again for days. So the idea sort of sat in limbo for a little while until I had enough free time to pursue it, and Shyni said to go for it.”

In 2012, Varghese and her laboratory created a self-healing hydrogel that reacts to changes in pH in a matter of seconds. Whether it be a crack in the hydrogel or two adjoining pieces “painted” with it, a change in acidity causes the hydrogel to form new bonds, which are completely reversible when the pH returns to its original levels.

Varghese’s hastily written idea was to find a way to use this hydrogel on a soft robot that could travel across water and indicate places where the pH changes. Along with a few other innovations to signal changes in its surroundings, she figured her lab could design such a robot as a sort of autonomous environmental sensor.

With the help of Ung Hyun Ko, a postdoctoral fellow also in Varghese’s laboratory, Kumar began designing a soft robot based on a fly. After several iterations, the pair settled on the shape of a dragonfly engineered with a network of interior microchannels that allow it to be controlled with air pressure.

They created the body–about 2.25 inches long with a 1.4-inch wingspan–by pouring silicon into an aluminum mold and baking it. The team used soft lithography to create interior channels and connected with flexible silicon tubing.

DraBot was born.

“Getting DraBot to respond to air pressure controls over long distances using only self-actuators without any electronics was difficult,” said Ko. “That was definitely the most challenging part.”

DraBot works by controlling the air pressure coming into its wings. Microchannels carry the air into the front wings, where it escapes through a series of holes pointed directly into the back wings. If both back wings are down, the airflow is blocked, and DraBot goes nowhere. But if both wings are up, DraBot goes forward.

To add an element of control, the team also designed balloon actuators under each of the back wings close to DraBot’s body. When inflated, the balloons cause the wings to curl upward. By changing which wings are up or down, the researchers tell DraBot where to go.

“We were happy when we were able to control DraBot, but it’s based on living things,” said Kumar. “And living things don’t just move around on their own, they react to their environment.”

That’s where self-healing hydrogel comes in. By painting one set of wings with the hydrogel, the researchers were able to make DraBot responsive to changes in the surrounding water’s pH. If the water becomes acidic, one side’s front wing fuses with the back wing. Instead of traveling in a straight line as instructed, the imbalance causes the robot to spin in a circle. Once the pH returns to a normal level, the hydrogel “un-heals,” the fused wings separate, and DraBot once again becomes fully responsive to commands.

To beef up its environmental awareness, the researchers also leveraged the sponges under the wings and doped the wings with temperature-responsive materials. When DraBot skims over water with oil floating on the surface, the sponges will soak it up and change color to the corresponding color of oil. And when the water becomes overly warm, DraBot’s wings change from red to yellow.

The researchers believe these types of measurements could play an important part in an environmental robotic sensor in the future. Responsiveness to pH can detect freshwater acidification, which is a serious environmental problem affecting several geologically-sensitive regions. The ability to soak up oils makes such long-distance skimming robots an ideal candidate for early detection of oil spills. Changing colors due to temperatures could help spot signs of red tide and the bleaching of coral reefs, which leads to decline in the population of aquatic life.

The team also sees many ways that they could improve on their proof-of-concept. Wireless cameras or solid-state sensors could enhance the capabilities of DraBot. And creating a form of onboard propellant would help similar bots break free of their tubing.

“Instead of using air pressure to control the wings, I could envision using some sort of synthetic biology that generates energy,” said Varghese. “That’s a totally different field than I work in, so we’ll have to have a conversation with some potential collaborators to see what’s possible. But that’s part of the fun of working on an interdisciplinary project like this.”

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

Microengineered Materials with Self‐Healing Features for Soft Robotics by Vardhman Kumar, Ung Hyun Ko, Yilong Zhou, Jiaul Hoque, Gaurav Arya, Shyni Varghese. Advanced Intelligent Systems DOI: https://doi.org/10.1002/aisy.202100005 First published: 25 March 2021

This paper is open access.

The earlier reference to Art Nouveau gives me an excuse to introduce this March 7, 2020 (?) essay by Bex Simon (artist blacksmith) on her eponymous website.

Dragonflies, in particular, are a very poplar subject matter in the Art Nouveau movement. Art Nouveau, with its wonderful flowing lines and hidden fantasies, is full of symbolism.  The movement was a response to the profound social changes and industrialization of every day life and the style of the moment was, in part, inspired by Japanese art.

Simon features examples of Art Nouveau dragonfly art along with examples of her own take on the subject. She also has this,

[downloaded from https://www.bexsimon.com/dragonflies-and-butterflies-in-art-nouveau/]

This is a closeup of a real dragonfly as seen on Simon’s website. If you have an interest, reading her March 7, 2020 (?) essay and gazing at the images won’t take much time.

Point-of-care diagnostics made easier to read with silver nanocubes

Researchers have shown that plasmonics can enhance the fluorescent markers used to signal positive samples in certain types of tests for diseases. A polymer brush coating keeps unwanted biomolecules away while a capture antibody (red) catches biomarkers of disease (clear). A detection antibody (blue) then latches on to the biomarker and emits light from an attached fluorophore (sphere). All of this is sandwiched by a thin layer of gold and a silver nanocube that is attached by a third antibody (green), creating conditions for the fluorophore to emit brighter light. Courtesy: Duke University

A May 12, 2020 news item on Nanowerk announces new work from scientists at Duke University on making point-of-care diagnostics easier to use by making the readouts brighter,

Engineers at Duke University [North Carolina, US] have shown that nanosized silver cubes can make diagnostic tests that rely on fluorescence easier to read by making them more than 150 times brighter. Combined with an emerging point-of-care diagnostic platform already shown capable of detecting small traces of viruses and other biomarkers, the approach could allow such tests to become much cheaper and more widespread.

A May 12, 2020 Duke University news release (also on EurekAlert), which originated the news item, provides more detail about the work,

Plasmonics is a scientific field that traps energy in a feedback loop called a plasmon onto the surface of silver nanocubes. When fluorescent molecules are sandwiched between one of these nanocubes and a metal surface, the interaction between their electromagnetic fields causes the molecules to emit light much more vigorously. Maiken Mikkelsen, the James N. and Elizabeth H. Barton Associate Professor of Electrical and Computer Engineering at Duke, has been working with her laboratory at Duke to create new types of hyperspectral cameras and superfast optical signals using plasmonics for nearly a decade.

At the same time, researchers in the laboratory of Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering, have been working on a self-contained, point-of-care diagnostic test that can pick out trace amounts of specific biomarkers from biomedical fluids such as blood. But because the tests rely on fluorescent markers to indicate the presence of the biomarkers, seeing the faint light of a barely positive test requires expensive and bulky equipment.

“Our research has already shown that plasmonics can enhance the brightness of fluorescent molecules tens of thousands of times over,” said Mikkelsen. “Using it to enhance diagnostic assays that are limited by their fluorescence was clearly a very exciting idea.”

“There are not a lot of examples of people using plasmon-enhanced fluorescence for point-of-care diagnostics, and the few that exist have not been yet implemented into clinical practice,” added Daria Semeniak, a graduate student in Chilkoti’s laboratory. “It’s taken us a couple of years, but we think we’ve developed a system that can work.”

In the new paper, researchers from the Chilkoti lab build their super-sensitive diagnostic platform called the D4 Assay onto a thin film of gold, the preferred yin to the plasmonic silver nanocube’s yang. The platform starts with a thin layer of polymer brush coating, which stops anything from sticking to the gold surface that the researchers don’t want to stick there. The researchers then use an ink-jet printer to attach two groups of molecules tailored to latch on to the biomarker that the test is trying to detect. One set is attached permanently to the gold surface and catches one part of the biomarker. The other is washed off of the surface once the test begins, attaches itself to another piece of the biomarker, and flashes light to indicate it’s found its target.

After several minutes pass to allow the reactions to occur, the rest of the sample is washed away, leaving behind only the molecules that have managed to find their biomarker matches, floating like fluorescent beacons tethered to a golden floor.

“The real significance of the assay is the polymer brush coating,” said Chilkoti. “The polymer brush allows us to store all of the tools we need on the chip while maintaining a simple design.”

While the D4 Assay is very good at grabbing small traces of specific biomarkers, if there are only trace amounts, the fluorescent beacons can be difficult to see. The challenge for Mikkelsen and her colleagues was to place their plasmonic silver nanocubes above the beacons in such a way that they supercharged the beacons’ fluorescence.

But as is usually the case, this was easier said than done.

“The distance between the silver nanocubes and the gold film dictates how much brighter the fluorescent molecule becomes,” said Daniela Cruz, a graduate student working in Mikkelsen’s laboratory. “Our challenge was to make the polymer brush coating thick enough to capture the biomarkers–and only the biomarkers of interest–but thin enough to still enhance the diagnostic lights.”

The researchers attempted two approaches to solve this Goldilocks riddle. They first added an electrostatic layer that binds to the detector molecules that carry the fluorescent proteins, creating a sort of “second floor” that the silver nanocubes could sit on top of. They also tried functionalizing the silver nanocubes so that they would stick directly to individual detector molecules on a one-on-one basis.

While both approaches succeeded in boosting the amount of light coming from the beacons, the former showed the best improvement, increasing its fluorescence by more than 150 times. However, this method also requires an extra step of creating a “second floor,” which adds another hurdle to engineering a way to make this work on a commercial point-of-care diagnostic rather than only in a laboratory. And while the fluorescence didn’t improve as much in the second approach, the test’s accuracy did.

“Building microfluidic lab-on-a-chip devices through either approach would take time and resources, but they’re both doable in theory,” said Cassio Fontes, a graduate student in the Chilkoti laboratory. “That’s what the D4 Assay is moving toward.”

And the project is moving forward. Earlier in the year, the researchers used preliminary results from this research to secure a five-year, $3.4 million R01 research award from the National Heart, Lung, and Blood Institute. The collaborators will be working to optimize these fluorescence enhancements while integrating wells, microfluidic channels and other low-cost solutions into a single-step diagnostic device that can run through all of these steps automatically and be read by a common smartphone camera in a low-cost device.

“One of the big challenges in point-of-care tests is the ability to read out results, which usually requires very expensive detectors,” said Mikkelsen. “That’s a major roadblock to having disposable tests to allow patients to monitor chronic diseases at home or for use in low-resource settings. We see this technology not only as a way to get around that bottleneck, but also as a way to enhance the accuracy and threshold of these diagnostic devices.”

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

Ultrabright Fluorescence Readout of an Ink-Jet Printed Immunoassay Using Plasmonic Nanogap Cavities by Daniela F. Cruz, Cassio M. Fontes, Daria Semeniak, Jiani Huang, Angus Hucknall, Ashutosh Chilkoti, Maiken H. Mikkelsen. Nano Lett. 2020, XXXX, XXX, XXX-XXX DOI: https://doi.org/10.1021/acs.nanolett.0c01051 Publication Date:May 6, 2020 Copyright © 2020 American Chemical Society

This paper is behind a paywall.

Gold nanoparticles not always always biologically stable

It’s usually silver nanoparticles (with a nod to titanium dioxide as another problem nanoparticle) which star in scenarios regarding environmental concerns, especially with water. According to an Aug. 28, 2018 news item on Nanowerk, gold nanoparticles under certain conditions could also pose problems,

It turns out gold isn’t always the shining example of a biologically stable material that it’s assumed to be, according to environmental engineers at Duke’s Center for the Environmental Implications of NanoTechnology (CEINT).

In a nanoparticle form, the normally very stable, inert, noble metal actually gets dismantled by a microbe found on a Brazilian aquatic weed.

While the findings don’t provide dire warnings about any unknown toxic effects of gold, they do provide a warning to researchers on how it is used in certain experiments.

Here’s an image of one of the researchers standing in the test bed where they made their discovery (the caption will help to make sense of the reference to mesocosms in the news release, which follows,,

Mark Wiesner stands with rows of mesocosms—small, manmade structures containing different plants and microorganisms meant to represent a natural environment with experimental controls. Courtesy: Duke University

An August 28, 2018 Duke University news release (also on EurekAlert) by Ken Kingery, which originated the news item, provides more detail about gold nanoparticle instability,

CEINT researchers from Duke, Carnegie Mellon and the University of Kentucky were running an experiment to investigate how nanoparticles used as a commercial pesticide affect wetland environments in the presence of added nutrients. Although real-world habitats often receive doses of both pesticides and fertilizers, most studies on the environmental effects of such compounds only look at a single contaminant at a time.

For nine months, the researchers released low doses of nitrogen, phosphorus and copper hydroxide nanoparticles into wetland mesocosms [emphasis mine]– small, manmade structures containing different plants and microorganisms meant to represent a natural environment with experimental controls. The goal was to see where the nanoparticle pesticides ended up and how they affected the plant and animal life within the mesocosm.

The researchers also released low doses of gold nanoparticles as tracers, assuming the biologically inert nanoparticles would remain stable while migrating through the ecosystem. This would help the researchers interpret data on the pesticide particles that partly dissolve by showing them how a solid metal particle acts within the system.

But when the researchers went to analyze their results, they found that many of the gold nanoparticles had been oxidized and dissolved.

“We were taken completely by surprise,” said Mark Wiesner, the James B. Duke Professor and chair of civil and environmental engineering at Duke. “The nanoparticles that were supposed to be the most stable turned out to be the least stable of all.”

After further inspection, the researchers found the culprit — the microbiome growing on a common Brazilian waterweed called Egeria densa. Many bacteria secrete chemicals to essentially mine metallic nutrients from their surroundings. With their metabolism spiked by the experiment’s added nutrients, the bacteria living on the E. densa were catalyzing the reaction to dissolve the gold nanoparticles.

This process wouldn’t pose any threat [emphasis mine] to humans or other animal species in the wild. But when researchers design experiments with the assumption that their gold nanoparticles will remain intact, the process can confound the interpretation of their results.

“The assumption that gold is inert did not hold in these experiments,” said Wiesner. “This is a good lesson that underscores how real, complex environments, that include for example the bacteria growing on leaves, can give very different results from experiments run in a laboratory setting that do not include these complexities.”

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

Gold nanoparticle biodissolution by a freshwater macrophyte and its associated microbiome by Astrid Avellan, Marie Simonin, Eric McGivney, Nathan Bossa, Eleanor Spielman-Sun, Jennifer D. Rocca, Emily S. Bernhardt, Nicholas K. Geitner, Jason M. Unrine, Mark R. Wiesner, & Gregory V. Lowry. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0231-y Published

This paper is behind a paywall.