The explosion in AI models like OpenAI’s DALL-E 2—programs trained to generate pictures of almost anything you ask for—has sent ripples through the creative industries, from fashion to filmmaking, by providing weird and wonderful images on demand.
The same technology behind these programs is also making a splash in biotech labs, which have started using this type of generative AI, known as a diffusion model, to conjure up designs for new types of protein never seen in nature.
AlphaFold can predict the shape of proteins to within the width of an atom. The breakthrough will help scientists design drugs and understand disease.
Today, two labs separately announced programs that use diffusion models to generate designs for novel proteins with more precision than ever before. Generate Biomedicines, a Boston-based startup, revealed a program called Chroma, which the company describes as the “DALL-E 2 of biology.”
At the same time, a team at the University of Washington led by biologist David Baker has built a similar program called RoseTTAFold Diffusion. In a preprint paper posted online today, Baker and his colleagues show that their model can generate precise designs for novel proteins that can then be brought to life in the lab. “We’re generating proteins with really no similarity to existing ones,” says Brian Trippe, one of the co-developers of RoseTTAFold.
These protein generators can be directed to produce designs for proteins with specific properties, such as shape or size or function. In effect, this makes it possible to come up with new proteins to do particular jobs on demand. Researchers hope that this will eventually lead to the development of new and more effective drugs. “We can discover in minutes what took evolution millions of years,” says Gevorg Grigoryan, CTO of Generate Biomedicines.
“What is notable about this work is the generation of proteins according to desired constraints,” says Ava Amini, a biophysicist at Microsoft Research in Cambridge, Massachusetts.
Proteins are the fundamental building blocks of living systems. In animals, they digest food, contract muscles, detect light, drive the immune system, and so much more. When people get sick, proteins play a part.
Proteins are thus prime targets for drugs. And many of today’s newest drugs are protein based themselves. “Nature uses proteins for essentially everything,” says Grigoryan. “The promise that offers for therapeutic interventions is really immense.”
But drug designers currently have to draw on an ingredient list made up of natural proteins. The goal of protein generation is to extend that list with a nearly infinite pool of computer-designed ones.
Computational techniques for designing proteins are not new. But previous approaches have been slow and not great at designing large proteins or protein complexes—molecular machines made up of multiple proteins coupled together. And such proteins are often crucial for treating diseases.
The two programs announced today are also not the first use of diffusion models for protein generation. A handful of studies in the last few months from Amini and others have shown that diffusion models are a promising technique, but these were proof-of-concept prototypes. Chroma and RoseTTAFold Diffusion build on this work and are the first full-fledged programs that can produce precise designs for a wide variety of proteins.
Namrata Anand, who co-developed one of the first diffusion models for protein generation in May 2022, thinks the big significance of Chroma and RoseTTAFold Diffusion is that they have taken the technique and supersized it, training on more data and more computers. “It may be fair to say that this is more like DALL-E because of how they’ve scaled things up,” she says.
Diffusion models are neural networks trained to remove “noise”—random perturbations added to data—from their input. Given a random mess of pixels, a diffusion model will try to turn it into a recognizable image.
In Chroma, noise is added by unraveling the amino acid chains that a protein is made from. Given a random clump of these chains, Chroma tries to put them together to form a protein. Guided by specified constraints on what the result should look like, Chroma can generate novel proteins with specific properties.
Baker’s team takes a different approach, though the end results are similar. Its diffusion model starts with an even more scrambled structure. Another key difference is that RoseTTAFold Diffusion uses information about how the pieces of a protein fit together provided by a separate neural network trained to predict protein structure (as DeepMind’s AlphaFold does). This guides the overall generative process.
Generate Biomedicines and Baker’s team both show off an impressive array of results. They are able to generate proteins with multiple degrees of symmetry, including proteins that are circular, triangular, or hexagonal. To illustrate the versatility of their program, Generate Biomedicines generated proteins shaped like the 26 letters of the Latin alphabet and the numerals 0 to 10. Both teams can also generate pieces of proteins, matching new parts to existing structures.
Most of these demonstrated structures would serve no purpose in practice. But because a protein’s function is determined by its shape, being able to generate different structures on demand is crucial.
Generating strange designs on a computer is one thing. But the goal is to turn these designs into real proteins. To test whether Chroma produced designs that could be made, Generate Biomedicines took the sequences for some of its designs—the amino acid strings that make up the protein—and ran them through another AI program. They found that 55% of them would be predicted to fold into the structure generated by Chroma, which suggests that these are designs for viable protein.
Baker’s team ran a similar test. But Baker and his colleagues have gone a lot further than Generate Biomedicines in evaluating their model. They have created some of RoseTTAFold Diffusion’s designs in their lab. (Generate Biomedicines says that it is also doing lab tests but is not yet ready to share results.) “This is more than just proof of concept,” says Trippe. “We’re actually using this to make really great proteins.”
IAN C HAYDON / UW INSTITUTE FOR PROTEIN DESIGN
For Baker, the headline result is the generation of a new protein that attaches to the parathyroid hormone, which controls calcium levels in the blood. “We basically gave the model the hormone and nothing else and told it to make a protein that binds to it,” he says. When they tested the novel protein in the lab, they found that it attached to the hormone more tightly than anything that could have been generated using other computational methods—and more tightly than existing drugs. “It came up with this protein design out of thin air,” says Baker.
Grigoryan acknowledges that inventing new proteins is just the first step of many. We’re a drug company, he says. “At the end of the day what matters is whether we can make medicines that work or not.” Protein based drugs need to be manufactured in large numbers, then tested in the lab and finally in humans. This can take years. But he thinks that his company and others will find ways to speed up those steps up as well.
“The rate of scientific progress comes in fits and starts,” says Baker. “But right now we’re in the middle of what can only be called a technological revolution.”
Seeding the oceans with nano-scale fertilizers could create a much-needed, substantial carbon sink. Credit: Stephanie King | Pacific Northwest National Laboratory
The urgent need to remove excess carbon dioxide from Earth’s environment could include enlisting some of our planet’s smallest inhabitants, according to an international research team led by Michael Hochella of the Department of Energy’s Pacific Northwest National Laboratory.
Hochella and his colleagues examined the scientific evidence for seeding the oceans with iron-rich engineered fertilizer particles near ocean plankton. The goal would be to feed phytoplankton, microscopic plants that are a key part of the ocean ecosystem, to encourage growth and carbon dioxide (CO2) uptake. The analysis article appears in the journal Nature Nanotechnology.
“The idea is to augment existing processes,” said Hochella, a Laboratory fellow at Pacific Northwest National Laboratory. “Humans have fertilized the land to grow crops for centuries. We can learn to fertilize the oceans responsibly.”
In nature, nutrients from the land reach oceans through rivers and blowing dust to fertilize plankton. The research team proposes moving this natural process one step further to help remove excess CO2 through the ocean. They studied evidence that suggests adding specific combinations of carefully engineered materials could effectively fertilize the oceans, encouraging phytoplankton to act as a carbon sink.
The organisms would take up carbon in large quantities. Then, as they die, they would sink deep into the ocean, taking the excess carbon with them. Scientists say this proposed fertilization would simply speed up a natural process that already safely sequesters carbon in a form that could remove it from the atmosphere for thousands of years.
“At this point, time is of the essence,” said Hochella. “To combat rising temperatures, we must decrease CO2 levels on a global scale. Examining all our options, including using the oceans as a CO2 sink, gives us the best chance of cooling the planet.”
Pulling insights from the literature
In their analysis, the researchers argue that engineered nanoparticles offer several attractive attributes. They could be highly controlled and specifically tuned for different ocean environments. Surface coatings could help the particles attach to plankton. Some particles also have light-absorbing properties, allowing plankton to consume and use more CO2.
The general approach could also be tuned to meet the needs of specific ocean environments. For example, one region might benefit most from iron-based particles, while silicon-based particles may be most effective elsewhere, they say.
The researchers’ analysis of 123 published studies showed that numerous non-toxic metal-oxygen materials could safely enhance plankton growth. The stability, Earth abundance, and ease of creation of these materials make them viable options as plankton fertilizers, they argue.
The team also analyzed the cost of creating and distributing different particles. While the process would be substantially more expensive than adding non-engineered materials, it would also be significantly more effective.
More information: Peyman Babakhani et al, Potential use of engineered nanoparticles in ocean fertilization for large-scale atmospheric carbon dioxide removal, Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01226-w
Nanoparticles are substances whose dimensions range from 1 nanometre to 100 nanometres and can be of any shape or colour. Simply put, nanoparticles are very tiny and ultra minute substances that are not visible through naked eyes and have their size range from 1 nm to 100 nm, where 1 nanometre is equal to one billionth of a metre. In fact, more than 500,000 nanoparticles can sit on a cross section of a human hair. Interestingly, If we compare the width of a human DNA helix that is 2nm to the size of a human body it is equivalent to the comparison of a human body to the size of the sun.
Nanoparticles are very different from bulk particles as they show very different Optical properties, Electrical properties, Mechanical properties, Magnetic properties and Catalytic properties.
Nanotechnology: a “maturing” new technology
Nanotechnology is the development and use of techniques which are targeted to study physical phenomena of nanoparticles and to develop new devices and material structure using nanoparticles. Similarly, Nanoscience is a term which identifies as the study and application of extremely tiny things that can be further useful for other science related fields. Presently, Nanotechnology or Nanotech is developing rapidly with scientists and developers deliberating about every possible field where Nanotech can be applied.
One of the unique features of Nanoparticles is their high surface-area-to-volume ratio. This feature enables them to have unique physicochemical properties, various functionalities and enhancement in reactivity.
Nanotech can also be understood as a technology which has the capabilities of controlling and modification of materials and substances at the nanometer-scale.
Nanotechnology in health care system
Nanotech is gradually gaining momentum in our healthcare system, with the creation of nanomicelle, colloidal structures useful for drug delivery systems along with Antiviral Nano-coatings that are applied on face masks and PPE kits being some of the prominent examples of Nanotech.
The technology is also being used to detect heart attacks with Nanotech detectors, along with Nanochips to check plaque in arteries and Nanocarriers for eye surgery, chemotherapy etc.
Nanotechnology in environment
Nanotech possesses vast potential for providing solutions to various environmental challenges. It could be one of the best possible ways to provide innovative solutions for reducing pollution, water treatment, environmental sensing and making alternative energy more cost-effective.
A prominent example could be a Nanogrid made of photocatalytic copper tungsten oxide nanoparticles, which is used when there is an Oil spill in oceans, rivers. These Nanoparticles break the oil down into biodegradable compounds when activated by sunlight and helps in conservation of water and aquatic animals.
Nanotech can be useful for water purification, sensing and detecting chemical and biological contamination at low concentration, separating carbon dioxide from waste gases which could contribute in cleansing of air.
Major Government initiatives
As per, Ministry of Electronics and Information Technology the government is taking various steps for the promotion of Nanotech, including establishment of Nanoelectronics centres, Indian Nanoelectronics Users Programme (INUP) which is being implemented at Centre of Excellence in Nanoelectronics (CEN) at IISc and IIT Bombay.
The Government of India has also launched a Mission on Nanoscience and Technology also known as Nano Mission in May 2007 with an aim to build capacity in the field of Nanotech in the country. The nodal agency of the Nano Mission is Department of Science and Technology with phase 2 of the initiative being commenced in the year 2014 with an allocation of 650 crore.
According to the Department of Science and Technology, India’s Nano Mission has achieved a significant milestone by securing the third position in the global rankings due to its contribution to the field of Nanoscience.
Vertically aligned carbon nanotubes growing from catalytic nanoparticles (gold color) on a silicon wafer on top of a heating stage (red glow). Diffusion of acetylene (black molecules) through the gas phase to the catalytic sites determines the growth rate in a cold-wall showerhead reactor. Credit: Image by Adam Samuel Connell/LLNL
Scientists at the Department of Energy’s Lawrence Livermore National Laboratory (LLNL) are scaling up the production of vertically aligned single-walled carbon nanotubes (SWCNT). This incredible material could revolutionize diverse commercial products ranging from rechargeable batteries, sporting goods, and automotive parts to boat hulls and water filters. The research was published recently in the journal Carbon.
Most carbon nanotube (CNT) production today is unorganized CNT architectures that is used in bulk composite materials and thin films. However, for many uses, organized CNT architectures, like vertically aligned forests, provide critical advantages for exploiting the properties of individual CNTs in macroscopic systems.
“Robust synthesis of vertically-aligned carbon nanotubes at large scale is required to accelerate deployment of numerous cutting-edge devices to emerging commercial applications,” said LLNL scientist and lead author Francesco Fornasiero. “To address this need, we demonstrated that the structural characteristics of single-walled CNTs produced at wafer scale in a growth regime dominated by bulk diffusion of the gaseous carbon precursor are remarkably invariant over a broad range of process conditions.”
The team of researchers discovered that the vertically oriented SWCNTs retained very high quality when increasing precursor concentration (the initial carbon) up to 30-fold, the catalyst substrate area from 1 cm2 to 180 cm2, growth pressure from 20 to 790 Mbar and gas flowrates up to 8-fold.
LLNL scientists derived a kinetics model that shows the growth kinetics can be accelerated by using a lighter bath gas to aid precursor diffusion. In addition, byproduct formation, which becomes progressively more important at higher growth pressure, could be greatly mitigated by using a hydrogen-free growth environment. The model also indicates that production throughput could be increased by 6-fold with carbon conversion efficiency of higher than 90% with the appropriate choice of the CNT growth recipe and fluid dynamics conditions.
“These model projections, along with the remarkably conserved structure of the CNT forests over a wide range of synthesis conditions, suggest that a bulk-diffusion-limited growth regime may facilitate preservation of vertically aligned CNT-based device performance during scale up,” said LLNL scientist and first author Sei Jin Park.
The team concluded that operating in a growth regime that is quantitatively described by a simple CNT growth kinetics model can facilitate process optimization and lead to a more rapid deployment of cutting-edge vertically-aligned CNT applications.
Applications include lithium-ion batteries, supercapacitors, water purification, thermal interfaces, breathable fabrics, and sensors.
Reference: “Synthesis of wafer-scale SWCNT forests with remarkably invariant structural properties in a bulk-diffusion-controlled kinetic regime” by Sei Jin Park, Kathleen Moyer-Vanderburgh, Steven F. Buchsbaum, Eric R. Meshot, Melinda L. Jue, Kuang Jen Wu and Francesco Fornasiero, 29 September 2022, Carbon. DOI: 10.1016/j.carbon.2022.09.068
Other LLNL authors are Kathleen Moyer-Vanderburgh, Steven Buchsbaum, Eric Meshot, Melinda Jue and Kuang Jen Wu. The work is funded by the Chemical and Biological Technologies Department of the Defense Threat Reduction Agency.
The electric vehicle revolution is well underway, with California banning the sale of new gas cars by 2035 and automakers increasing their lineup of EV offerings. While electric has plenty of supporters in the automotive, power, and charging industries, the issue of charging equity, or fair and equal access to charging, looms large.
As the EV market expands, however, equity will become a growing problem. In a report on the auto industry earlier this year, Morning Consult found that 83% of vehicle owners who make under $50,000 per year don’t have dedicated access to EV charging at home. In the same study, 39% of people in that income bracket expressed interest in buying an electric vehicle. Even now, EV owners who live in rentals must sometimes go to great lengths—including running electric cord extensions out their apartment windows—to get their cars charged.
For some companies, equity is front and center as EV charging infrastructure is built out. Dianne Martinez is chair of East Bay Community Energy, a public electric power agency in Northern California. The EBCE uses the buying power of ratepayers to procure clean energy for customers, and it’s working on a project to install fast charging in municipal lots—not just along highway corridors.
“When you look at EV charging infrastructure delivered through an equity lens, you have to consider how a community has been impacted negatively by the fossil fuel industry,” Martinez says. “Huge swaths of urban neighborhoods that suffer the ill health effects of pollution, from freeways, from ports and goods movement, from proximity to drilling and gas-powered plants. Instead of just looking to provide the same charging opportunities that we have to folks who already have more wealth, what if we found a metric that included and supported those who have been traditionally the last ones considered in the green revolution? What if we even put them first?”
A challenge for renters
EV owners Jason Mott of Venice, Calif., and Natacha Favry of Boston have gone to great lengths to charge their cars while living in rentals. Neither Mott nor Favry have charging access in their apartment or condo buildings, so they use a combination of public charging stations and, occasionally, power cords strung out of apartment windows. Charging an EV fully using a standard power cord can take as long as a week.
“There’s a lot of folks who don’t have parking,” Mott notes. “And you will see people with extension cords [running] over the sidewalk to a tree, so that when they can happen to grab that spot in front of their place, they can plug in their car. You see people putting down those little rubber cord protectors as you’re walking down the sidewalk, because people have their cord running out to their car.”
A longtime EV owner and environmentalist, Mott says he’s learned to lock his extension cord to his current vehicle, a new Rivian R1T, when he’s charging overnight since the heavy-duty extension cords he uses to charge regularly get stolen. Previously, Mott owned a Fiat 500e, and a Chevrolet Bolt.
Favry has owned an EV and rented flats both overseas and on the outskirts of Boston, where she and her family moved in January for work. She says that her charging experience in her native home of France was far more nerve-racking than it is in the U.S. She drives a Tesla Model 3 and uses a nearby proprietary Tesla supercharger at a local mall to keep her vehicle running. She says she’s asked the landlord of her building to install a charger, but her request was denied.
“There’s no plug in the garage,” Favry says. “And we were told by the owner that it’s not allowed.” Local and state incentives exist to help landlords install chargers in multifamily dwellings, but they don’t cover the costs of upgrading building power or wiring—and landlords don’t have a profit incentive to make the investment worthwhile.
Rentals comprise about one-third of American housing units, according to the U.S. Census. They are typically located in dense urban areas, and a majority were built in the 1970s and 1980s, according to a report from 2020 by the Urban Institute. Upgrading them to handle the charge required to power EVs is a costly endeavor.
“The reality is that 90% of the multifamily housing in our territory is 50 years or older, and 47% of our community here in our territory live in that multifamily housing,” says Martinez of EBCE. “It’s very hard to incentivize landlords to make the necessary upgrades to support their tenants in buying EVs.”
Businesses tackle charging equity
The good news for consumers is that a number of startups, utilities, and auto manufacturers are working to solve the charging equity problem.
Joseph Vellone is head of North America operations for Ev.energy, a London-based certified B Corporation whose software platform connects utilities, automakers, EV chargers, and drivers to streamline charging and make it more affordable and sustainable. About 80% of EV charging happens at home, which Vellone cites as a reason why charging equity must begin with increasing access at multifamily dwellings.
“Home charging access is very much a question of income level, and very quickly becomes a social equity issue,” he says.
To solve this, Ev.energy recently launched a first-of-its-kind smart charging cable and app, which allows multifamily unit occupants to manage their own individual power usage and get credits or incentives for charging in off-peak hours. The cord, called Smartenit, enables EV drivers without dedicated home charging to optimize their usage and access, as well as save money on home charging.
California-based charging-station company ChargePoint is also thinking about how to get landlords to embrace the EV revolution. The company primarily operates charging stations at stores and offices, with some stations in multifamily units. CEO Pasquale Romano says landlords should think of EV charging the same way they do cable or internet—as a must-have for modern living.
“The landlord doesn’t really make any money on cable TV or internet,” he says. “EV charging is going to be like Wi-Fi. Access is going to be required.”
Even large companies like General Motors, which is already heavily invested in the EV and electrification space, are working to tackle the charging equity question. The company has just announced a new business unit called GM Energy, which will offer everything from commercial battery and energy management solutions to individual home and multiunit solutions. By getting battery storage to multifamily units, landlords can then install EV chargers.
These solutions will be built on GM’s Ultium battery technology and utilize integrated energy management that will include bidirectional charging, vehicle-to-home and vehicle-to-grid solutions, as well as stationary storage, solar products, software applications, cloud management tools, microgrid solutions, hydrogen fuel cells, and more.
“The public charging infrastructure needs to grow, and grow rapidly, both on freeway infrastructure as well as multiunit dwellings and high-density living,” says Travis Hester, vice president of EV growth operations at GM. “We’re walking into this area where EVs are about to scale. They’re not there yet, but they’re about to, and this, we think, is an integral part of the electric vehicle ecosystem, but it’s also part of a non-vehicle ecosystem.”
On the utility and municipal side, the EBCE is focusing on working with state and local authorities to lease municipal parking lots and install chargers where, Martinez says, they are needed the most. “What we find to be the greatest bang for our buck is supporting DC [direct current] fast chargers in communities where there’s a high degree of multifamily housing,” Martinez says. She hopes that the EBCE’s efforts will help serve as a blueprint for other cities.
“Low-income and disadvantaged communities [are] not the first-wave adopters of electric vehicles. They have their minds set on keeping their households together, getting to work,” Martinez says. “It’s time to focus on that second wave of people who are thinking about their next small-car purchase.”
A topical gel that blocks the receptor for a metabolic byproduct called succinate treats gum disease by suppressing inflammation and changing the makeup of bacteria in the mouth. Credit: Yuqi Guo
A topical gel that blocks the receptor for a metabolic byproduct called succinate treats gum disease by suppressing inflammation and changing the makeup of bacteria in the mouth, according to a new study led by researchers at NYU College of Dentistry and published in Cell Reports.
The research, conducted in mice and using human cells and plaque samples, lays the groundwork for a non-invasive treatment for gum disease that people could apply to the gums at home to prevent or treat gum disease.
“No current treatment for gum disease simultaneously reduces inflammation, limits disruption to the oral microbiome, and prevents bone loss. There is an urgent public health need for more targeted and effective treatments for this common disease,” said Yuqi Guo, an associate research scientist in the Department of Molecular Pathobiology at NYU Dentistry and the study’s co-first author.
Past research has linked increased succinate—a molecule produced during metabolism—to gum disease, with higher succinate levels associated with higher levels of inflammation. Guo and her colleagues at NYU Dentistry also discovered in 2017 that elevated levels of succinate activate the succinate receptor and stimulate bone loss. These findings made the succinate receptor an appealing target for countering inflammation and bone loss—and potentially stopping gum disease in its tracks.
Strengthening the link between succinate and gum disease
The researchers started by examining dental plaque samples from humans and blood samples from mice. Using metabolomic analyses, they found higher succinate levels in people and mice with gum disease compared to those with healthy gums, confirming what previous studies have found.
They also saw that the succinate receptor was expressed in human and mouse gums. To test the connection between the succinate receptor and the components of gum disease, they genetically altered mice to inactivate, or “knock out,” the succinate receptor.
In “knockout” mice with gum disease, the researchers measured lower levels of inflammation in both the gum tissue and blood, as well as less bone loss. They also found different bacteria in their mouths: mice with gum disease had a greater imbalance of bacteria than did “knockout” mice.
This held true when the researchers administered extra succinate to both types of mice, which worsened gum disease in normal mice; however, “knockout” mice were protected against inflammation, increases in unhealthy bacteria, and bone loss.
“Mice without active succinate receptors were more resilient to disease,” said Fangxi Xu, an assistant research scientist in the Department of Molecular Pathobiology at NYU Dentistry and the study’s co-first author. “While we already knew that there was some connection between succinate and gum disease, we now have stronger evidence that elevated succinate and the succinate receptor are major drivers of the disease.”
A novel treatment
To see if blocking the succinate receptor could ameliorate gum disease, the researchers developed a gel formulation of a small compound that targets the succinate receptor and prevents it from being activated. In laboratory studies of human gum cells, the compound reduced inflammation and processes that lead to bone loss.
The compound was then applied as a topical gel to the gums of mice with gum disease, which reduced local and systemic inflammation and bone loss in a matter of days. In one test, the researchers applied the gel to the gums of mice with gum disease every other day for four weeks, which cut their bone loss in half compared to mice who did not receive the gel.
Mice treated with the gel also had significant changes to the community of bacteria in their mouths. Notably, bacteria in the Bacteroidetes family—which include pathogens that are known to be dominant in gum disease—were depleted in those treated with the gel.
“We conducted additional tests to see if the compound itself acted as an antibiotic, and found that it does not directly affect the growth of bacteria. This suggests that the gel changes the community of bacteria through regulating inflammation,” said Deepak Saxena, professor of molecular pathobiology at NYU Dentistry and the study’s co-senior author.
The researchers are continuing to study the gel in animal models to find the appropriate dosage and timing for application, as well as determine any toxicity. Their long-term goal is to develop a gel and oral strip that can be used at home by people with or at risk for gum disease, as well as a stronger, slow-release formulation that dentists can apply to pockets that form in the gums during gum disease.
“Current treatments for severe gum disease can be invasive and painful. In the case of antibiotics, which may help temporarily, they kill both good and bad bacteria, disrupting the oral microbiome. This new compound that blocks the succinate receptor has clear therapeutic value for treating gum disease using more targeted and convenient processes,” said Xin Li, professor of molecular pathobiology at NYU Dentistry and the study’s lead author.
Additional study authors include Scott Thomas, Yanli Zhang, Bidisha Paul, Sungpil Chae, Patty Li, Caleb Almeter, and Angela Kamer of NYU Dentistry; Satish Sakilam and Paramjit Arora of NYU Department of Chemistry; and Dana Graves of the University of Pennsylvania School of Dental Medicine.
A new nanophotonic material has broken records for high-temperature stability, potentially ushering in more efficient electricity production and opening a variety of new possibilities in the control and conversion of thermal radiation.
Developed by a University of Michigan-led team of chemical and materials science engineers, the material controls the flow of infrared radiation and is stable at temperatures of 2,000 degrees Fahrenheit in air, a nearly twofold improvement over existing approaches.
The material uses a phenomenon called destructive interference to reflect infrared energy while letting shorter wavelengths pass through. This could potentially reduce heat waste in thermophotovoltaic cells, which convert heat into electricity but can’t use infrared energy, by reflecting infrared waves back into the system. The material could also be useful in optical photovoltaics, thermal imaging, environmental barrier coatings, sensing, camouflage from infrared surveillance devices and other applications.
“It’s similar to the way butterfly wings use wave interference to get their color. Butterfly wings are made up of colorless materials, but those materials are structured and patterned in a way that absorbs some wavelengths of white light but reflects others, producing the appearance of color,” said Andrej Lenert, U-M assistant professor of chemical engineering and co-corresponding author of the study in Nature Photonics (“Nanophotonic control of thermal emission under extreme conditions”).
“This material does something similar with infrared energy. The challenging part has been preventing breakdown of that color-producing structure under high heat.”
The approach is a major departure from the current state of engineered thermal emitters, which typically use foams and ceramics to limit infrared emissions. These materials are stable at high temperature but offer very limited control over which wavelengths they let through. Nanophotonics could offer much more tunable control, but past efforts haven’t been stable at high temperatures, often melting or oxidizing (the process that forms rust on iron). In addition, many nanophotonic materials only maintain their stability in a vacuum.
The new material works toward solving that problem, besting the previous record for heat resistance among air-stable photonic crystals by more than 900 degrees Fahrenheit in open air. In addition, the material is tunable, enabling researchers to tweak it to modify energy for a wide variety of potential applications. The research team predicted that applying this material to existing TPVs will increase efficiency by 10% and believes that much greater efficiency gains will be possible with further optimization.
The team developed the solution by combining chemical engineering and materials science expertise. Lenert’s chemical engineering team began by looking for materials that wouldn’t mix even if they started to melt.
“The goal is to find materials that will maintain nice, crisp layers that reflect light in the way we want, even when things get very hot,” Lenert said. “So we looked for materials with very different crystal structures, because they tend not to want to mix.”
They hypothesized that a combination of rock salt and perovskite, a mineral made of calcium and titanium oxides, fit the bill. Collaborators at U-M and the University of Virginia ran supercomputer simulations to confirm that the combination was a good bet.
John Heron, co-corresponding author of the study and an assistant professor of materials science and engineering at U-M, and Matthew Webb, a doctoral student in materials science and engineering, then carefully deposited the material using pulsed laser deposition to achieve precise layers with smooth interfaces. To make the material even more durable, they used oxides rather than conventional photonic materials; the oxides can be layered more precisely and are less likely to degrade under high heat.
“In previous work, traditional materials oxidized under high heat, losing their orderly layered structure,” Heron said. “But when you start out with oxides, that degradation has essentially already taken place. That produces increased stability in the final layered structure.”
After testing confirmed that the material worked as designed, Sean McSherry, first author of the study and a doctoral student in materials science and engineering at U-M, used computer modeling to identify hundreds of other combinations of materials that are also likely to work. While commercial implementation of the material tested in the study is likely years away, the core discovery opens up a new line of research into a variety of other nanophotonic materials that could help future researchers develop a range of new materials for a variety of applications.
The nanocarrier’s hollow glass bubble (white, at left) is packed with irinotecan (green) and is covered by lipid layers (blue) that contain the immue-boosing drug 3M-052 (orange particles in close-up image on right). Credit: CNSI/UCLA
Over the past 30 years, progress in early detection and treatment of cancer has helped reduce the overall death rate by more than 30%. Pancreatic cancer, however, has remained difficult to treat. Only 1 in 9 people survive five years after diagnosis, in part because this cancer is protected by biological factors that help it resist treatment.
In hopes of turning the tide, UCLA researchers have developed a technology that delivers a combination therapy to pancreatic tumors using nanoscale particles loaded with irinotecan, a chemotherapy drug approved as part of a drug regimen for pancreatic cancer, and 3M-052, an investigational drug that can boost immune activity and help overcome tumors’ resistance.
In a study recently published in the journal ACS Nano, the research team showed that the simultaneously delivered combination outperformed the sum of its parts in a mouse model of pancreatic cancer.
“In my opinion, invoking the immune system will make a big difference in providing a much better treatment outcome for pancreatic cancer,” said corresponding author André Nel, a distinguished professor of medicine and director of research at the California NanoSystems Institute at UCLA. “That’s where I hope this research is taking us.”
The researchers’ double-loaded nanocarrier was more effective at shrinking tumors and preventing cancer metastasis in mice than either irinotecan without a nanocarrier or nanocarriers that delivered the two drugs independently. The combination therapy also attracted more cancer-killing immune cells to tumor sites and maintained drug levels in the blood for longer. There was no evidence of harmful side effects.
In addition to blocking cancer cells from growing, irinotecan sends a danger signal to the immune system‘s dendritic cells; these in turn mobilize killer T cells, which travel to tumor sites and destroy cancer cells. But because dendritic cells are often functionally impaired in patients with pancreatic cancer, 3M-052 provides extra assistance, helping them better marshal killer T cells both at the cancer site and in nearby lymph nodes.
Combination therapies for cancer are not new, but packaging drugs together in the same nanocarrier has proven difficult. Only one dual-delivery nanocarrier for chemotherapy has been approved by the Food and Drug Administration. However, over the past seven years, the Nel lab has developed an approach for simultaneous delivery, and the current findings provide further evidence that their innovative nanocarrier design enables the drugs to work in tandem more effectively than if they were delivered separately.
Most nanocarriers are composed of layers of lipid molecules made up of fatty substances, similar to a cell membrane, with spaces into which drugs can be packaged. With the new device, that double layer of lipids surrounds a core glass bubble made of silica whose hollow interior can be filled with irinotecan. In an ingenious twist, UCLA postdoctoral researcher and first author Lijia Luo figured out that the 3M-052 molecule’s fatty tail could be used for integrating the second drug directly into these outer lipid layers.
The structural design of the carrier, which is so small that it would take 1,000 of them to span the width of a human hair, helps prevent drug leakage and toxicity while the device enters a formidable ropelike barrier protecting the pancreatic cancer and travels to the tumor site. The glass bubbles offer additional protection from leakage, enabling the carrier to deliver more irinotecan to the tumor site, compared to other drug carriers.
The team will conduct further preclinical experiments to test their treatment in large-animal models and confirm quality-control for large-scale manufacturing of their silica nanocarriers.
“It traditionally takes 10 to 20 years for new breakthrough technologies to reach the marketplace,” said Nel, who is also founder and chief of UCLA’s nanomedicine division and director of the University of California’s Center for Environmental Implications of Nanotechnology. “Nanocarriers have been around for almost 20 years. While lipid-based nanocarriers are leading the way, the silica-based carrier decorated with lipid layers stands a good chance of speeding up the rate of discovery and improving cancer immunotherapy.”
The growth of recycling plants in Europe is a necessary environmental response to the increasing demand for batteries for electric vehicles and the gigafactory industry that will develop in the coming years.
*** Contributed by: M. Guitierrez of CICenergiGUNE
The entire world is currently immersed in an energy transition that involves, among other things, a complete electrification of the mobility sector and the promotion of renewable energies. As a result, the demand for batteries has grown steadily by 30% annually in recent years and the outlook for the coming years is exponential.
The main driver of this growth is the electric vehicle, which is expected to represent more than 88% of the demand compared to other types of applications. Moreover, it is estimated that two out of three vehicles will be electric by 2040. Hence, Europe, which seeks to be a benchmark in this new scenario, is taking positions through the creation of more and more gigafactories.
However, this increase in the manufacture and use of batteries for electric cars requires the development of a new and increasingly necessary sector: the recycling of these batteries. Above all, taking into account that the energy transition to be faced in the coming years is linked to the circular economy which is essential for the desired change towards sustainability.
According to a Greenpeace study, almost 13 million tons of batteries from electric vehicles will reach the end of their life between 2021 and 2030. This represents a huge environmental impact due to the amount of critical materials (lithium, cobalt, nickel…) that will have to be disposed of. And even more so, taking into account that the manufacture of new batteries will require the extraction of around 10 million tons of new materials.
The current situation in Europe in terms of material recycling is still far from what is desirable, given that today only 22% of cobalt, 16% of nickel, 12% of aluminum and 8% of manganese are recycled.
That is why, as we have seen in previous blog articles, great efforts are being made to study how these materials can be reused and/or recycled, in order to promote a circular economy.
Source: ReCell Center
Europe seeks to regulate this macro-industry through a new regulatory framework
One of the major efforts made in recent months has been focused, in a forward-looking approach, on the development of regulations to control the end of the life of these batteries.
It is a proposal that includes thirteen major blocks of measures covering the entire value chain of the industry with special emphasis on the efficiency levels of recycling and recovery of materials. The objective is to contribute to the protection, preservation and improvement of the quality of the environment by minimizing the negative impact of batteries and capacitors and their waste.
To achieve these goals, the European Directive prohibits the placing of batteries containing certain hazardous substances on the market and defines measures to establish systems aimed at achieving a high level of collection and recycling. It also aims to improve the environmental performance of all operators involved in the life cycle of batteries, such as producers, distributors and end users and, in particular, operators directly participating in the treatment and recycling of waste batteries and capacitors.
The U.S. regulation, on the other hand, complains about the absence of a standardized procedure for the design, materials and chemistries of the batteries that are manufactured. Their proposal includes the introduction of a standardized procedure for battery recycling to help manufacturers understand which materials and designs are most easily recyclable. This is known as the “Designed for Recycling” concept.
In this regard, Spain has the Royal Decree 20/2017, of January 20, which obliges manufacturers to inform consumers about the criteria that will be adopted to ensure that the vehicle they are purchasing will be treated responsibly at the end of its useful life.
Leading international players join the recycling wave
The battery recycling sector requires a transformation and there are many European players that are betting on it to boost the circular economy and create a competitive advantage associated with the knowledge of this growing industry.
One of them is ERMA (European Raw Materials Alliance); an alliance that includes companies, associations, universities and research centers –among them CIC energiGUNE– focused on the recycling industry, and whose activities include, among others, supporting the capacity of the European raw materials industry to extract, design, manufacture and recycle materials.
Among the agents belonging to ERMA, we find the RECHARGEassociation, which mainly brings together large companies and some associations related to the materials used in batteries, with the intention of promoting and defending the interests of the entire value chain.
Another player, this time directly linked to battery recycling, is Reneos. This is the first European platform for the collection and recycling of electric vehicle batteries. This platform focuses its activity on the collection of batteries and waste in compliance with European guidelines, before giving them a second life through reuse or disassembly for recycling.
Finally, it is worth mentioning other alliances or initiatives that defend to a greater or lesser extent the interests of the recycling industry. Some of them are Eucobat, the European association of national battery collection systems; EBRA, a grouping that aims to develop the highest levels of professionalism in the battery recycling industry; and EuRIC, which, thanks to its strong network of European and national recycling associations, acts as a trusted interface between the industry and the European Union for the exchange of best practices in all matters related to recycling.
Europe´s proliferation of recycling plants
Given the need, sustainability and also the profitability of the battery recycling industry, more and more companies are commercializing new processes for the collection, discharge and dismantling of these batteries.
Not surprisingly, according to a study by the consulting firm Yole Development, during the period from 2020 to 2025 a CAGR of 25% is estimated in the global value of the recycled materials industry for lithium-ion batteries. This would mean, in economic terms, a total market value of close to $1.2 billion by 2025, and some even forecast that, by 2040, this market will reach a value of almost $24 billion.
In Europe, this spread of battery recycling projects is spearheaded by the factory that SMS Group wants to set up together with the Australian company Neometals. It is called “Primobius” and promises effective recycling of lithium-ion batteries.
Meanwhile, Solvay and Veolia are continuing to advance their battery recycling partnership, which began in September 2020, and have announced the establishment of a demonstration plant for recycling battery materials.
In Northern Europe, Sweden has announced the project of a new battery recycling plant, with an investment of more than €24 million by Stena Recycling and will be located in the town of Halmstad.
At the same time, in Central Europe, Volkswagen has recently opened a pilot plant in Salzgitter (Germany) and also, the recycling company Elemental Holding has announced an investment of 182 million euros for the treatment of batteries and other metals containing waste in Poland.
If we focus on southern Europe, recently, the companies Endesa and Urbaser have announced that Spain will have its own battery recycling plant in León in 2023. A project that promises the treatment of 8,000 tons of batteries per year that will be processed through a separation and shredding procedure that will allow the recycling of the materials of the storage system.
In addition to those already mentioned, other plans have been announced for the creation of recycling plants. One of them is Northvolt, which intends to start up a factory capable of recycling 25,000 tons of batteries per year, and also, the one of BASF in Germany, both with the intention of being operational next year.
The alternative to recycling: the second life of batteries
Another trend that has arisen as a result of the increased use of batteries is the possibility of reconditioning electric vehicle batteries as an energy storage solution for other applications. This is known as “Second Life Batteries“.
Indeed, if the useful life of an electric vehicle battery is estimated at around 8 years, the energy remaining inside the battery cells can be extended by 5 to 10 years, depending on the application in which it is used, until it finally reaches its end of life.
This has led to initiatives such as the one of Enel Group, which has used 90 used Nissan Leaf batteries in an energy storage facility in Melilla. Meanwhile, the energy company Powervault has announced its partnership with Renault to equip domestic energy storage systemsbased on batteries from retired electric vehicles.
Not only that, Spain has also been a pioneer in Europe by installing the first chargers powered by second-life batteries on the highway linking Madrid and Valencia.
One way or another, the premise is clear. It is necessary to find a solution for the recycling of around 50,000 tons of batteries that are expected to be discarded from 2027; a figure that could even multiply and reach 700,000 tons in 2035.
Hence, one of the main focuses of work and research at centers such as CIC energiGUNE is the advancement of techniques and solutions that promote the development of the recycling industry. Even more so if we want to ensure that the battery sector becomes a reference in terms of sustainability.
Below, as a summary, from CIC energiGUNE we have gathered the classification of the main agents that have announced to be associated to battery recycling:
This article focuses on the design and fabrication of flexible textile-based protein sensors to be embedded in wound dressings.
Chronic wounds require continuous monitoring to prevent further complications and to determine the best course of treatment in the case of infection. As proteins are essential for the progression of wound healing, they can be used as an indicator of wound status. Through measuring protein concentrations, the sensor can assess and monitor the wound condition continuously as a function of time.
The protein sensor consists of electrodes that are directly screen printed using both silver and carbon composite inks on polyester nonwoven fabric which was deliberately selected as this is one of the common backing fabric types currently used in wound dressings. These sensors were experimentally evaluated and compared to each other by using albumin protein solution of pH 7. A comprehensive set of cyclic voltammetry measurements was used to determine the optimal sensor design the measurement of protein in solution. As a result, the best sensor design is comprised of silver conductive tracks but a carbon layer as the working and counter electrodes at the interface zone. This design prevents the formation of silver dioxide and protects the sensor from rapid decay, which allows for the recording of consecutive measurements using the same sensor.
The chosen printed protein sensor was able to detect bovine serum albumin at concentrations ranging from 30 to 0.3 mg/mL with a sensitivity of 0.0026𝜇0.0026μA/M. Further testing was performed to assess the sensor’s ability to identify BSA from other interferential substances usually present in wound fluids and the results show that it can be distinguishable.
Skin is a crucial organ of the human body as it acts as a barrier to protect the rest of the body’s tissues and organs1, therefore when it suffers an injury, other essential and healthy organs could become infected or injured2,3. While in most minor wound cases, minimal intervention is required such as placing a bandage or medical gauze to prevent further damage to the wound and to prevent it being overrun by infectious microorganisms. However, many chronic wounds need to be monitored and retreated constantly over long periods of time.
The cost of treating wounds is a critical issue as it is estimated to account for at least 3%3% of the total healthcare expenditure in most developed countries4. Since 2018, it is estimated that the UK is managing approximately 3.8 million patients with a wound in a clinical setting annually5. It was estimated that health services in 2012 spent ££5.1 billion on costs associated with wound care management6 which provided a compelling case for improvement in the current standard of wound dressings not only to reduce healthcare costs but also to improve patient quality of life7. However, better and effective means of reporting quantitative information about the wound condition in real time is required to inform and guide treatment decisions as improved wound care will deliver improved public health and healthcare costs8,9.
The wound healing process can be monitored by repeatedly determining the multiple physiological changes that occur including but not limited to pH, alkalization, temperature, uric acid and specific protein types such as albumin and fibrinogen whilst tissue repair progresses2. Detection of these biomarkers with minimally invasive techniques can provide an effective way for the real-time monitoring of the condition of a wound. In addition, remote wound monitoring could keep the patient informed about their condition, improve their quality of life and reduce the frequency of face-to-face consultations and treatments with healthcare providers10.
Higher precision in wound detection treatment is advancing more rapidly as presented recently3where an integrated wound recognition strategy is conducted by extracting patterns of specific irregular wounds. This work was implemented on a bandage, but others have investigated different textiles to allow flexibility of wearable medical devices11,12,13. Integrating electronics with textiles has advanced medical care by facilitating multiple physiological parameters and the body’s biomolecular state to be monitored remotely through minimal or noninvasive techniques and sometimes with reduced direct contact with the human body13,14. Improved flexibility and durability allow electronic devices to be more suitable for wearable biosensors as they can be embedded into clothing to realize electronic textiles15. These emerging technologies in wearable electronics have made using smart textiles in the design of flexible patches using textiles11 which made wound dressings more achievable and is leading to major advances in healthcare monitoring, personalized therapy, and human-machine interaction12. The aim of wearable textile biosensors is to indirectly detect critical physiological changes in the body through measuring indirect stimuli that can be readily detected from outside the body despite the uncontrolled environment surrounding the body16. However, to be embedded in wound dressings, not only does it have to be miniaturized but it also needs to be flexible and lightweight to make positioning around the wound feasible and as comfortable to wear as possible regardless of the location of the wound17. To provide better flexibility the ink used in fabricating the biosensor plays a critical role as adding a bendable layer to a textile can provide fabric reinforcement and make it mechanically bendable18.This is one of the challenges that were addressed in this paper and will be discussed in the later section.
The design of the protein sensor is based on the structure of an electrochemical cell that uses a three-electrode configuration to perform the cyclic voltammetry measurements19,20,21.
Electrochemical sensors are generally preferred because they can provide rapid real time monitoring of change and wound conditions, they are also relatively inexpensive and can be miniaturized and embedded within textiles22. Categorically the device should be a potentiometric biosensor which works by measuring the voltage produced when electric current flows through the solution under static conditions23,24,25,26,27,28.
Screen printing technology has been used to fabricate electrochemical electrodes on ceramic or plastic based substrates29,30,31.This technique involves forcing suitable ink formulations in paste form through a patterned stencil or screened mesh of a specific size and shaped using a squeegee to form the desired design on a substrate32. Screen printing provides greater design freedom in that the printed layers can have any orientation on the fabric and do not need to follow the yarn directions. In addition, screen printing provides the ability to produce arrays of the same or different devices in a straightforward fashion; screen printing is inherently a batch process producing multiple devices from a single screen design.
While pH and temperature have been used as parameters in assessing wound status33,34,35, detecting protein concentrations helps to identify wound healing stages36 as it is less likely to be affected by the active external environment surrounding the exudate. Albumin was the protein determined in this research work, which has been modelled and measured previously37,38 as it is the most abundant protein in blood plasma (it represents 50%50% of total protein)39, previous research has shown a relation between the wellness of a person and the albumin concentration40, establishing albumin concentration as a good marker of protein concentrations in wounds. Albumin concentrations in wounds have been used as indicator of wound severity conditions, for which a concentration of >15>15 mg/mL is in inflamed wounds41. While the protein level in a healing wound is around 9 mg/mL, compared to levels of 35 mg/mL for chronic slow healing wounds42.
Bovine serum albumin (BSA) was used to prepare standard solutions of albumin43. The use of BSA as a protein source specifically when testing electro-chemical sensors has been previously reported by others44 because the concentration can be easily standardized and altered precisely to evaluate the detection range. Most importantly, the properties of BSA are very similar to human serum albumin with respect to other proteins as discussed in a recent paper38.
For the first time in literature, this research presents a unique approach to integrate protein sensors in fabric which improves the sensors durability, comfort, flexibility and wearability and performance within specification. Although a similar approach was presented recently8,45, where screen printed electrodes (SPEs) were printed on a paper and placed inside a bandage but measure pH and uric acid to monitor chronic wounds.
In this research, three designs were investigated to determine the optimal biosensor design for integration into wound dressings. These designs were fabricated by screen printing. Each design was printed directly on 3 different types of fabric with different surface roughness and layer thickness. The conductive tracks were made from silver flake-based ink and carbon ink. UV curable dielectric ink was used to smooth out the textile surface and to provide an even surface for further printing. The same UV ink was used as the encapsulation. 2-point resistance measurement was conducted on printed layers to ensure continuity and cyclic voltammetry measurements were performed to determine sensitivity and selectivity.
Results and discussion
The research had two main stages. The first stage encompassed the design and fabrication of the textile based sensors and the second stage covered the testing of the sensors using a previously established empirical technique reported by the authors37.
Fabrication of textile based screen printed electrodes
The process of screen printing on fabric involves four stages as illustrated in Fig. 1 which shows an exploded view of the three designs. The first design purely consisted of silver layer as both the conductive tracks and electrodes; the second consisted of a mix of both silver and carbon layers; the third design had a carbon layer as part of the electrodes in the region where the sensor encounters the fluid under test at the interface zone. In all three designs, there were three electrodes (working, counter, reference electrodes). The dimensions of the sensors are shown in Fig. 2.
The sensors were printed onto three textiles, two of which are medical fabric types. The first one (Type A) was a polypropylene non-woven fabric and has areal surface roughness (Sa = 119.24 119.24 µm), the second (Type B) is a blend of cotton/polyester woven fabric and has areal surface roughness (Sa = 59.37 59.37 µm) while the third one (Type C) is made from polyester non-woven fabric and has areal surface roughness (Sa = 151.52 151.52µm). Each fabric was placed and adhered in turn onto an alumina tile which provided a rigid platform for printing. The sensors were successfully printed on all three fabric types but it is discovered that printing on the cotton/polyester fabric was easier, while Type A fabric was more difficult to print on because it started to tear apart. However, using polyester non-woven fabric (Type C), which is similar to the one used in wound dressings, prevented the initial substrate layer from cracking. Upon fabrication, the final printed sensors are shown in Fig. 3. After printing, the resistance between two end points of printed track was measured using a multimeter. The resistance observed in design A and B (shown in Fig. 1) was less than 1 ohm on average, while design C always had a much higher resistance (in the range of 260–410 ohms). Microscopic images of the three designs are shown in Fig. 1 in that the tracks were well defined.
The main challenge in the printing process was to maintain the correct alignment when printing each layer to prevent short circuit and to preserve the sensor design. To resolve this issue, a trial print was deposited on a transparent laminate sheet before every deposit to make sure the patterns were all perfectly aligned before printing directly on fabric. The second main challenge faced repeatedly was the roughness of each printed layer. To print several layers on top of each other, all layers need to be smooth with no pin holes on the surface as this affected the roughness of the final finishing layer. To address this issue, the smooth side of the fabric was initially shaved to enable the surface to be as uniform as possible. The dielectric layer was then printed several times with varying printing gaps to reduce any pin holes and to provide an even platform for printing conductive layers. The third challenge was that the fabric could not be easily removed from the alumina (supporting platform). It was observed that this only occurred when using thin fabric such as Type A fabric shown in Fig. 3. To avoid this issue, two layers of the same fabric were adhered and fixed on top of each other. This strengthened the fabric layer but also eased the removal of fabric after printing.
The printed layers after each stage are shown in Fig. 4. Initially, in the first stage shown in (A), the polymer interface layer was deposited six times to create a smooth platform for subsequent layers to be printed on top. The interface layer was then cured under UV light to produce a thickness of 110 110 µm. Next, the silver conductive electrodes were printed as shown in (B) and cured in the oven for 15 minutes at 100 ∘∘C. The silver layer was printed twice to produce a thickness of 16 16 µm. The carbon layer was then printed only on the second and third designs as shown in Fig. 4C and cured in the oven for 15 minutes at 100 ∘∘C. The print was repeated twice to create a thickness of 26 26 µm. Finally, the same material used for the interface layer was printed to protect the conductive tracks of the sensors as shown in (D) and was cured under UV light to produce a thickness of 14 14 µm. A microscopic image of the interface for each design before being tested is shown in Fig. 5. The images captured show how the electrodes in delicate area of the interface zone are clearly separated from each other and how the layers are well aligned and printed on top of each other and there is no short circuit occurring.
Upon fabrication, the sensors were highly flexible and can be easily bent as shown in Fig. 6, where the sensor was wrapped around cylinders with a diameter ranging from 1 mm to 10 mm to mimic the bending when worn on patient. The results showed that all designs could wrap around these diameters without causing cracks in any of printed layers. This was further cross validated through continuity measurement, proving the conductivity of printed sensors is intact. This feature is of great significance because of the nature of the targeted application as the exact positioning of a wound is unpredictable, and the dressing does need to be wrapped and bent around the human body. To test the bendability of the sensor, an experimental setup was prepared as shown in Fig. 7. This was achieved using a Shimadzu AG-X Universal Testing Machine with custom 3D printed attachments to grip the printed sensors. The two attachments were initially set at 21mm apart which is the maximum distance from two opposite sides of the sensor.
These attachments were them moved towards each other and stopped at mm apart to avoid damage to machine and attachment. The cyclic test was repeated 5 times with 3 sensors. The measured force to bend the sensor ranges from 0 to 2.5 N depending on compression position and there was no damage to the integrity of all designs which was subsequently cross-validated through continuity measurement. This mechanical test demonstrated a quantifiable measure of the sensor ability to bend with minimal force without affecting the sensor’s structure. After the test was conducted, the conductivity of the electrodes was measured and remained unchanged and unaffected by the test.
Cyclic voltammetry (CV) measurements
The fabric around the bottom edge of the sensor was removed in order to be connected to the AUTOLAB Dropsens adaptor which includes an insertion connector with 3 pins. BSA with 8 concentrations ranging from 0.3 – 30 mg/mL were used as the protein sources. Initially, the experiment was conducted on three sensor designs on all three types of fabric to establish the most suitable design. For each measurement, the current at the oxidation peak was observed and recorded and a best fit line of all the measurements was then plotted in Fig. 8. The SPE design with only silver layer at the interface zone (SPE design (A)) stopped functioning when testing a solution with concentration below 3 mg/mL. As shown in Fig. 8, the two cycles conducted using SPE with only carbon were close to each other in terms of gradient as there was less than 8%8% difference in comparison with design A and B where the differences in measurements between two cycles were 32%32% and 41%41%, respectively. This demonstrated that design C was the most stable and reliable design as it provided reproducible and comparable results each time. The results show a clear relationship between BSA concentration and current peak obtained at the working electrode. This happens because the increase in concentration gradient near the surface of the working electrode causes an increase in the current observed at the oxidation peak. This is a result of the increase in the amount of electroactive proteins adsorption at the interface when the concentration of BSA increases, leading to increase in surface charge density which drives higher current at the oxidation peak46.
The status of the sensors after CV measurement performed was investigated to ensure no printed material was damaged. This was achieved by examining each sensor post measurement under the microscope. During the measurement process, the formation of a dark grey color coating (Silver dioxide) was observed at the working electrode when using SPE design (A) as shown in Fig. 9A. This indicated that the silver electrode was damaged before the end of the cycle and could lead to unreliable results. In order to examine the underlying silver layer in design B, the carbon layer was manually removed to expose the silver layer. SPE design (B) where the carbon layer was scratched in SPE design (B) to make the silver layer more visible as shown in Fig. 9B. The image illustrates how silver layer was still oxidized, but was far less visibly damaged than design (A) because it is protected by the carbon layer as it is noncorrosive. The SPE design (C) remained unchanged as there was no silver present at the interface zone. SPE design (C) was then observed using a scanning electron microscope (SEM) and a cross-sectional micrograph including the conductive tracks, the encapsulation layer, interface layer and the textile is shown in Fig. 10. The image shown demonstrates the continuity and consistency of the multiple layers present in design of the sensor around the interface zone.
Further empirical testing was only conducted using SPE design (C). The CV measurement obtained after the redox reaction is shown in Fig. 11 when 30 mg/mL BSA was used. After repeating each test three time with new sensor on each fabric type, there was a correlation observed after the first cycle between cycle 2 and 3. The equation of the line for the sensors with three different fabric types are included in Table 1.Table 1 The relationship between number of cycles and CV measurements.
The CV experiment was then repeated three times on the same sensor and performed on all three types of fabric. The results obtained using the three types of fabric overlapped each other and were within the same current range at the working electrode (0.06–0.15A). Therefore, the effect of fabric type on the redox reaction was minimal. Type (C) fabric was more repeatable as clearly shown in the graph (the undashed lines) and was chosen as the standard in the fabrication of the sensor because it is also commonly used for medical wound dressings. In addition, the first CV cycle was always lower in magnitude than the measurements obtained in the subsequent cycles. The second and third cycles were consistently closer to each other in comparison with the initial cycle. This is more visible when all peaks of several concentrations of each cycle were compared to each other as shown in Fig. 12. Therefore, as a standard it is best to take the average of the second and third cycles when comparing the results.
Since the combination of type (C) fabric and SPE design (C) was ideal, eight BSA concentrations were used to examine the sensitivity of this combination. The current observed at the oxidation peaks were recorded, shown in Fig. 12. The best fit line was drawn based on the average value around each solution of each cycle. While the initial cycle was consistently lower in gradient as presented in Table 2 than the second and third cycles conducted on the same un-replaced sensor which illustrates that SPE design (C) is the most reproducible.
After testing the sensitivity of the chosen SPE sensor, it was important to analyse the selectivity of printed sensor in comparison with other substances present in wounds. Therefore, the SPE was tested against several potentially interfering substances such as creatin, hydrogen peroxide, glucose and absorbic acid and the results are shown in Fig. 13 similar to a study achieved previously47. In Fig. 13 the shape and range of the redox reaction obtained through CV of BSA is different from the other tested solutions tested which eliminates the effect of interference.
The sensor was fabricated using the screen printing technique and consisted of four layers: an interface layer, silver electrodes, carbon conducting interface area and an encapsulation layer. The sensor relied on quantifying the protein concentration by measuring changes to conducting cyclic voltammetry measurements. After testing three sensor designs with different silver and carbon combinations, it was concluded that that the design with only carbon material presented at the interface zone was the optimal design as not only it provided the most reproducible and consistent results upon testing, but also it remained unaffected by oxidation. The sensor was printed on three different fabric types, and all presented promising results, one of which was wound dressing fabric which was chosen as the substrate as it is commonly used medically. During the screen printing process, precise alignment is a key aspect in the fabrication process to prevent any short circuit of the electrodes and to provide efficient performance of the sensors. Upon further cyclic voltammetry empirical testing and result analysis conducted using carbon only sensors (design (C)) and on Type C fabric, it was determined that to compare the outcome of different BSA concentrations it is best to take the average of the second and third cycles conducted on the same sensor.
The CV measurements demonstrated that the screen printed protein sensor could accurately monitor BSA concentrations from 0.3 to 30 mg/mL with a sensitivity of 0.0026𝜇0.0026μA/M. Additionally, an SEM image was captured and presented in the paper to demonstrate the consistency and continuity of the different layers making up the texture of the final fabricated design. The final design also demonstrated its ability to bend easily around different diameters without breaking. Further testing was conducted to assess the sensor’s ability to detect BSA from other interferential substances present in a wound. The measured results show that the chosen SPE type (C) can successfully distinguishes BSA in the range of 3 to 30 mg/mL from others.
Screen printing process
To design the protein sensors shown in Fig. 6, the sensor consisted of four printed layers. Initially, a layer was built to create an interface for the electrode conductive tracks. Silver layer was then deposited over the interface layer. In two of the designs (design B and C), carbon conductive ink was deposited over the interface zone. Finally, an encapsulation layer was deposited on top of the sensor tracks and around the interface zone to protect the sensor electrodes and to prevent any short circuit. In this work, three different designs were considered when designing the carbon conductive layer.
Three types of inks were used: a UV curable polymer ink from ElectraPolymers Ltd was used to act as the interface and encapsulation, carbon and silver inks from Henkel were used as the electrodes and conductive tracks, respectively.
Three different fabric types were tested: 1) a non-woven polypropylene fabric (Type A), 2) a woven polyester/cotton fabric (65%65%/35%35%) (Type B), 3) a non-woven polyester fabric (Type C). Type A and C are commonly used in used in wound dressings and therefore are more favorable. Although the woven polyester/cotton (Type B) fabric is the most ideal type of fabric for printing because it is relatively smoother than the others (has areal surface roughness (Sa) = 59.37 59.37 µm), yet it is not commonly used in wound dressings. We only use Type C as a comparison.
Protein solution preparation
The protein used to test the printed sensors was BSA powder as it is considered as a standard for protein quantification (Sigma-Aldrich, Steinheim, Germany). In this research, 8 samples of BSA solutions were prepared with different concentrations and diluted using deionized water: 30, 23, 18, 11, 7, 3, 1, 0.3 mg/mL with a pH value of 7. Initially, 30 mg/mL was prepared by putting 3 grams of BSA powder in 100 mL of deionized water, and then the rest of the solutions were prepared by diluting the original stock solution.
A setup similar to the methodology discussed in the previous work by the authors was implemented. The objective is to evaluate the sensitivity shown in Table 2 of the developed textile-based screen printed carbon electrodes as shown in Fig. 14. The printed protein sensor was connected the Metrohm Dropsens device. A glass filled with ice was placed within a close proximity to the sensors to provide humid environment and to prevent evaporation of the BSA samples. This was achieved by conducting a series of cyclic voltammetry experiments on different protein solutions using an AUTOLAB potentiostat device (PGSTAT101). The setup parameters are listed in Table 3.
Table 3 Parameters of cyclic voltammetry measurement setup.