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Breakthrough for tissue-interfaced bioelectronics

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Let’s call this a cold open,

This October 24, 2024 news item on ScienceDaily describes some of what is in the video

The ideal material for interfacing electronics with living tissue is soft, stretchable, and just as water-loving as the tissue itself–in short, a hydrogel. Semiconductors, the key materials for bioelectronics such as pacemakers, biosensors, and drug delivery devices, on the other hand, are rigid, brittle, and water-hating, impossible to dissolve in the way hydrogels have traditionally been built. Scientists have now solved this challenge that has long stymied researchers, reimagining the process of creating hydrogels to build a powerful semiconductor in hydrogel form. The result is a bluish gel that flutters like a sea jelly in water but retains the immense semiconductive ability needed to transmit information between living tissue and machine.

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An October 24, 2024 University of Chicago news release (also on EurekAlert) by Paul Dailing, which originated the news item, describes the breakthrough, Note: Links have been removed,

A paper published today in Science from the UChicago Pritzker School of Molecular Engineering (PME) has solved this challenge that has long stymied researchers, reimagining the process of creating hydrogels to build a powerful semiconductor in hydrogel form. Led by Asst. Prof. Sihong Wang’s research group, the result is a bluish gel that flutters like a sea jelly in water but retains the immense semiconductive ability needed to transmit information between living tissue and machine.

The material demonstrated tissue-level moduli as soft as 81 kPa, stretchability of 150% strain, and charge-carrier mobility up to 1.4 cm2 V-1 s-1. This means their material—both semiconductor and hydrogel at the same time—ticks all the boxes for an ideal bioelectronic interface.

“When making implantable bioelectronic devices, one challenge you must address is to make a device with tissue-like mechanical properties,” said Yahao Dai, the first author of the new paper. “That way, when it gets directly interfaced with the tissue, they can deform together and also form a very intimate bio-interface.”

Although the paper mainly focused on the challenges facing implanted medical devices such as biochemical sensors and pacemakers, Dai said the material also has many potential non-surgical applications, like better readings off the skin or improved care for wounds.

“It has very soft mechanical properties and a large degree of hydration similar to living tissue,” said UChicago PME Asst. Prof. Sihong Wang. “Hydrogel is also very porous, so it allows the efficient diffusion transport of different kinds of nutrition and chemicals. All these traits combine to make hydrogel probably the most useful material for tissue engineering and drug delivery.”

‘Let’s change our perspective’

The typical way of making a hydrogel is to take a material, dissolve it in water, and add the gelation chemicals to puff the new liquid into a gel form. Some materials simply dissolve in water, others require researchers to tinker and chemically modify the process, but the core mechanism is the same: No water, no hydrogel.

Semiconductors, however, don’t normally dissolve in water. Rather than find new, time-consuming means of trying to force the process, the UChicago PME team re-examined the question.

“We started to think, ‘Okay, let’s change our perspective,’ and we came up with a solvent exchange process,” Dai said.

Instead of dissolving the semiconductors in water, they dissolved them in an organic solvent that is miscible with water. They then prepared a gel from the dissolved semiconductors and hydrogel precursors. Their gel initially was an organogel, not a hydrogel.

“To eventually turn it into a hydrogel, we then immersed the whole material system into the water to let the organic solvent dissolve out and let the water come in,” Dai said.

An important benefit of such a solvent-exchange-based method is its broad applicability to different types of polymer semiconductors with different functions.

‘One plus one is greater than two’

The hydrogel semiconductor, which the team has patented and is commercializing through UChicago’s Polsky Center for Entrepreneurship and Innovation, is not merging a semiconductor with a hydrogel. It’s one material that is both semiconductor and hydrogel at the same time.

“It’s just one piece that has both semiconducting properties and hydrogel design, meaning that this whole piece is just like any other hydrogel,” Wang said.

Unlike any other hydrogel, however, the new material actually improved biological functions in two areas, creating better results than either hydrogel or semiconductor could accomplish on their own.

First, having a very soft material bond directly with tissue reduces the immune responses and inflammation typically triggered when a medical device is implanted.

Second, because hydrogels are so porous, the new material enables elevated biosensing response and stronger photo-modulation effects. With biomolecules being able to diffuse into the film to have volumetric interactions, the interaction sites for biomarkers-under-detection are significantly increased, which gives rise to higher sensitivity. Besides sensing, the responses to light for therapeutic functions at tissue surfaces also get increased from the more efficient transport of redox-active species. This benefits functions such as light-operated pacemakers or wound dressing that can be more efficiently heated with a flick of light to help speed healing.

“It’s a ‘one plus one is greater than two’ kind of combination,” Wang joked.

Researchers in the lab of UChicago Pritzker School of Engineering Asst. Prof. Sihong Wang (right), including PhD student Yahao Dai (left), have developed a hydrogel that retains the semiconductive ability needed to transmit information between living tissue and machine, which can be used both in implantable medical devices and non-surgical applications. (Photo by John Zich)

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

Soft hydrogel semiconductors with augmented biointeractive functions by Yahao Dai, Shinya Wai, Pengju Li, Naisong Shan, Zhiqiang Cao, Yang Li, Yunfei Wang, Youdi Liu, Wei Liu, Kan Tang, Yuzi Liu, Muchuan Hua, Songsong Li, Nan Li, Shivani Chatterji, H. Christopher Fry, Sean Lee, Cheng Zhang, Max Weires, Sean Sutyak, Jiuyun Shi, Chenhui Zhu, Jie Xu, Xiaodan Gu, Bozhi Tian, and Sihong Wang. Science 24 Oct 2024 Vol 386, Issue 6720 pp. 431-439 DOI: 10.1126/science.adp9314

This paper is behind a paywall.

Nanostructured materials and radiation

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If you’re planning on using nanostructured materials in a nuclear facility, you might want to check out this work (from a June 8, 2018 Purdue University (Indiana, US) news release by Brian L. Huchel,

A professor in the Purdue College of Engineering examined the potential use of various materials in nuclear reactors in an extensive review article in the journal Progress in Materials Science.

The article, titled “Radiation Damage in Nanostructured Materials,” was led by Xinghang Zhang, a professor of materials engineering. It will be published in the July issue of the journal.

Zhang said there is a significant demand for advanced materials that can survive high temperature and high doses of radiation. These materials contain significant amount of internal changes, called defect sinks, which are too small to be seen with the naked eye, but may form the next generation of materials used in nuclear reactors.

“Nanostructured materials with abundant internal defect sinks are promising as these materials have shown significantly improved radiation tolerance,” he said. “However, there are many challenges and fundamental science questions that remain to be solved before these materials can have applications in advanced nuclear reactors.”

The 100-page article, which took two years to write, focuses on metallic materials and metal-ceramic compounds and reviews types of internal material defects on the reduction of radiation damage in nanostructured materials.

Under the extreme radiation conditions, a large number of defects and their clusters are generated inside materials, and such significant microstructure damage often leads to degradation of the mechanical and physical properties of the materials

The article discusses the usage of a combination of defect sink networks to collaboratively improve the radiation tolerance of nanomaterials, while pointing out the need to improve the thermal and radiation stabilities of the defect sinks.

“The field of radiation damage in nanostructured materials is an exciting and rapidly evolving arena, enriched with challenges and opportunities,” Zhang said. “The integration of extensive research effort, resources and expertise in various fields may eventually lead to the design of advanced nanomaterials with unprecedented radiation tolerance.”

Jin Li, co-author of the review article and a postdoctoral fellow in the School of Materials Engineering, said researchers with different expertise worked collaboratively on the article, which contains more than 100 pages, 100 figures and 700 references.

The team involved in the research article included researchers from Purdue, Texas A&M University, Drexel University, the University of Nebraska-Lincoln and China University of Petroleum-Beijing, as well as Sandia National Laboratory, Los Alamos National Laboratory and Idaho National Laboratory.

Here’s an image illustrating the work,

Various imperfections in nanostructures, call defect sinks, can enhance the material’s tolerance to radiation. (Photo/Xinghang Zhang)

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

Radiation damage in nanostructured materials by Xinghang Zhang, Khalid Hattar, Youxing Chen, Lin Shao, Jin Li, Cheng Sun, Kaiyuan Yu, Nan Li, Mitra L.Taheri, Haiyan Wang, Jian Wang, Michael Nastasi. Progress in Materials Science Volume 96, July 2018, Pages 217-321 https://doi.org/10.1016/j.pmatsci.2018.03.002

This paper is behind a paywall.

ht/ to June 8, 2018 Nanowerk news item.

New iron oxide nanoparticle as an MRI (magnetic resonance imaging) contrast agent

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This high-resolution transmission electron micrograph of particles made by the research team shows the particles’ highly uniform size and shape. These are iron oxide particles just 3 nanometers across, coated with a zwitterion layer. Their small size means they can easily be cleared through the kidneys after injection. Courtesy of the researchers

A Feb. 14, 2017 news item on ScienceDaily announces a new MRI (magnetic resonance imaging) contrast agent,

A new, specially coated iron oxide nanoparticle developed by a team at MIT [Massachusetts Institute of Technology] and elsewhere could provide an alternative to conventional gadolinium-based contrast agents used for magnetic resonance imaging (MRI) procedures. In rare cases, the currently used gadolinium agents have been found to produce adverse effects in patients with impaired kidney function.

A Feb. 14, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more technical detail,

 

The advent of MRI technology, which is used to observe details of specific organs or blood vessels, has been an enormous boon to medical diagnostics over the last few decades. About a third of the 60 million MRI procedures done annually worldwide use contrast-enhancing agents, mostly containing the element gadolinium. While these contrast agents have mostly proven safe over many years of use, some rare but significant side effects have shown up in a very small subset of patients. There may soon be a safer substitute thanks to this new research.

In place of gadolinium-based contrast agents, the researchers have found that they can produce similar MRI contrast with tiny nanoparticles of iron oxide that have been treated with a zwitterion coating. (Zwitterions are molecules that have areas of both positive and negative electrical charges, which cancel out to make them neutral overall.) The findings are being published this week in the Proceedings of the National Academy of Sciences, in a paper by Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT; He Wei, an MIT postdoc; Oliver Bruns, an MIT research scientist; Michael Kaul at the University Medical Center Hamburg-Eppendorf in Germany; and 15 others.

Contrast agents, injected into the patient during an MRI procedure and designed to be quickly cleared from the body by the kidneys afterwards, are needed to make fine details of organ structures, blood vessels, and other specific tissues clearly visible in the images. Some agents produce dark areas in the resulting image, while others produce light areas. The primary agents for producing light areas contain gadolinium.

Iron oxide particles have been largely used as negative (dark) contrast agents, but radiologists vastly prefer positive (light) contrast agents such as gadolinium-based agents, as negative contrast can sometimes be difficult to distinguish from certain imaging artifacts and internal bleeding. But while the gadolinium-based agents have become the standard, evidence shows that in some very rare cases they can lead to an untreatable condition called nephrogenic systemic fibrosis, which can be fatal. In addition, evidence now shows that the gadolinium can build up in the brain, and although no effects of this buildup have yet been demonstrated, the FDA is investigating it for potential harm.

“Over the last decade, more and more side effects have come to light” from the gadolinium agents, Bruns says, so that led the research team to search for alternatives. “None of these issues exist for iron oxide,” at least none that have yet been detected, he says.

The key new finding by this team was to combine two existing techniques: making very tiny particles of iron oxide, and attaching certain molecules (called surface ligands) to the outsides of these particles to optimize their characteristics. The iron oxide inorganic core is small enough to produce a pronounced positive contrast in MRI, and the zwitterionic surface ligand, which was recently developed by Wei and coworkers in the Bawendi research group, makes the iron oxide particles water-soluble, compact, and biocompatible.

The combination of a very tiny iron oxide core and an ultrathin ligand shell leads to a total hydrodynamic diameter of 4.7 nanometers, below the 5.5-nanometer renal clearance threshold. This means that the coated iron oxide should quickly clear through the kidneys and not accumulate. This renal clearance property is an important feature where the particles perform comparably to gadolinium-based contrast agents.

Now that initial tests have demonstrated the particles’ effectiveness as contrast agents, Wei and Bruns say the next step will be to do further toxicology testing to show the particles’ safety, and to continue to improve the characteristics of the material. “It’s not perfect. We have more work to do,” Bruns says. But because iron oxide has been used for so long and in so many ways, even as an iron supplement, any negative effects could likely be treated by well-established protocols, the researchers say. If all goes well, the team is considering setting up a startup company to bring the material to production.

For some patients who are currently excluded from getting MRIs because of potential side effects of gadolinium, the new agents “could allow those patients to be eligible again” for the procedure, Bruns says. And, if it does turn out that the accumulation of gadolinium in the brain has negative effects, an overall phase-out of gadolinium for such uses could be needed. “If that turned out to be the case, this could potentially be a complete replacement,” he says.

Ralph Weissleder, a physician at Massachusetts General Hospital who was not involved in this work, says, “The work is of high interest, given the limitations of gadolinium-based contrast agents, which typically have short vascular half-lives and may be contraindicated in renally compromised patients.”

The research team included researchers in MIT’s chemistry, biological engineering, nuclear science and engineering, brain and cognitive sciences, and materials science and engineering departments and its program in Health Sciences and Technology; and at the University Medical Center Hamburg-Eppendorf; Brown University; and the Massachusetts General Hospital. It was supported by the MIT-Harvard NIH Center for Cancer Nanotechnology, the Army Research Office through MIT’s Institute for Soldier Nanotechnologies, the NIH-funded Laser Biomedical Research Center, the MIT Deshpande Center, and the European Union Seventh Framework Program.

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

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents by He Wei, Oliver T. Bruns, Michael G. Kaul, Eric C. Hansen, Mariya Barch, Agata Wiśniowsk, Ou Chen, Yue Chen, Nan Li, Satoshi Okada, Jose M. Cordero, Markus Heine, Christian T. Farrar, Daniel M. Montana, Gerhard Adam, Harald Ittrich, Alan Jasanoff, Peter Nielsen, and Moungi G. Bawendi. PNAS February 13, 2017 doi: 10.1073/pnas.1620145114 Published online before print February 13, 2017

This paper is behind a paywall.

Tweet your nano

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Researchers at the University of Wisconsin-Madison have published a study titled, “Tweeting nano: how public discourses about nanotechnology develop in social media environments,”  which analyses, for the first time, nanotechnology discourse on Twitter social media. From the Life Sciences Communication University of Wisconsin-Madison research webpage,

The study, “Tweeting nano: how public discourses about nanotechnology develop in social media environments,” mapped social media traffic about nanotechnology, finding that Twitter traffic expressing opinion about nanotechnology is more likely to originate from states with a federally-funded National Nanotechnology Initiative center or network than states without such centers.

Runge [Kristin K. Runge, doctoral student] and her co-authors used computational linguistic software to analyze a census of all English-language nanotechnology-related tweets expressing opinion posted on Twitter over one calendar year. In addition to mapping tweets by state, the team coded sentiment along two axes: certain vs. uncertain, and optimistic-neutral-pessimistic. They found 55% of nanotechnology-related opinions expressed certainty, 41% expressed pessimistic outlooks and 32% expressed neutral outlooks.

In addition to shedding light on how social media is used in communicating about an emerging technology, this study is believed to be the first published study to use a census of social media messages rather than a sample.

“We likely wouldn’t have captured these results if we had to rely on a sample rather than a complete census,” said Runge. “That would have been unfortunate, because the distinct geographic origins of the tweets and the tendency toward certainty in opinion expression will be useful in helping us understand how key online influencers are shaping the conversation around nanotechnology.”

It’s not obvious from this notice or the title of the study but it is stated clearly in the study that the focus is the world of US nano, not the English language world of nano. After reading the study (very quickly), I can say it’s interesting and, hopefully, will stimulate more work about public opinion that takes social media into account. (I’d love to know how they limited their study to US tweets only and how they determined the region that spawned the tweet. )

The one thing which puzzles me is they don’t mention retweets (RTs) specifically. Did they consider only original tweets? If not, did they take into account the possibility that someone might RT an item that does not reflect their own opinion? I occasionally RT something that doesn’t reflect my opinion when there isn’t sufficient space to include comment indicating otherwise because I want to promote discussion and that doesn’t necessarily take place on Twitter or in Twitter’s public space. This leads to another question, did the researchers include direct messages in their study? Unfortunately, there’s no mention in the two sections  (Discussion and Implications for future research) of the conclusion.

For those who would like to see the research for themselves (Note: The article is behind a paywall),

Tweeting nano: how public discourses about nanotechnology develop in social media environments by Kristin K. Runge, Sara K. Yeo, Michael Cacciatore, Dietram A. Scheufele, Dominique Brossard, Michael Xenos, Ashley Anderson, Doo-hun Choi, Jiyoun Kim, Nan Li, Xuan Liang, Maria Stubbings, and Leona Yi-Fan Su. Journal of Nanoparticle Research; An Interdisciplinary Forum for Nanoscale Science and Technology© Springer 10.1007/s11051-012-1381-8. Published online Jan. 4, 2013

It’s no surprise to see Dietram Scheufele and Dominique Brossard who are both located the University of Wisconsin-Madison and publish steadily on the topic of nanotechnology and public opinion listed as authors.