3D stretchable electronics with a multitude of functions while staying thin and small

By stacking and connecting layers of stretchable circuits on top of one another, engineers have developed an approach to build soft, pliable “3D stretchable electronics” that can pack a lot of functions while staying thin and small in size.

The work is published in the Aug. 13 issue of Nature Electronics.

As a proof of concept, a team led by the University of California San Diego has built a stretchable electronic patch that can be worn on the skin like a bandage and used to wirelessly monitor a variety of physical and electrical signals, from respiration, to body motion, to temperature, to eye movement, to heart and brain activity. The device, which is as small and thick as a U.S. dollar coin, can also be used to wirelessly control a robotic arm.

“Our vision is to make 3D stretchable electronics that are as multifunctional and high-performing as today’s rigid electronics,” said senior author Sheng Xu, a professor in the Department of NanoEngineering and the Center for Wearable Sensors, both at the UC San Diego Jacobs School of Engineering.

Xu was named among MIT Technology Review’s 35 Innovators Under 35 list in 2018 for his work in this area.

To take stretchable electronics to the next level, Xu and his colleagues are building upwards rather than outwards. “Rigid electronics can offer a lot of functionality on a small footprint—they can easily be manufactured with as many as 50 layers of circuits that are all intricately connected, with a lot of chips and components packed densely inside. Our goal is to achieve that with stretchable electronics,” said Xu.

The new device developed in this study consists of four layers of interconnected stretchable, flexible circuit boards. Each layer is built on a silicone elastomer substrate patterned with what’s called an “island-bridge” design. Each “island” is a small, rigid electronic part (sensor, antenna, Bluetooth chip, amplifier, accelerometer, resistor, capacitor, inductor, etc.) that’s attached to the elastomer. The islands are connected by stretchy “bridges” made of thin, spring-shaped copper wires, allowing the circuits to stretch, bend and twist without compromising electronic function.

Making connections

This work overcomes a technological roadblock to building stretchable electronics in 3D. “The problem isn’t stacking the layers. It’s creating electrical connections between them so they can communicate with each other,” said Xu. These electrical connections, known as vertical interconnect accesses or VIAs, are essentially small conductive holes that go through different layers on a circuit. VIAs are traditionally made using lithography and etching. While these methods work fine on rigid electronic substrates, they don’t work on stretchable elastomers.

So Xu and his colleagues turned to lasers. They first mixed silicone elastomer with a black organic dye so that it could absorb energy from a laser beam. Then they fashioned circuits onto each layer of elastomer, stacked them, and then hit certain spots with a laser beam to create the VIAs. Afterward, the researchers filled in the VIAs with conductive materials to electrically connect the layers to one another. And a benefit of using lasers, notes Xu, is that they are widely used in industry, so the barrier to transfer this technology is low.

Multifunctional ‘smart bandage’

The team built a proof-of-concept 3D stretchable electronic device, which they’ve dubbed a “smart bandage.” A user can stick it on different parts of the body to wirelessly monitor different electrical signals. When worn on the chest or stomach, it records heart signals like an electrocardiogram (ECG). On the forehead, it records brain signals like a mini EEG sensor, and when placed on the side of the head, it records eyeball movements. When worn on the forearm, it records muscle activity and can also be used to remotely control a robotic arm. The smart bandage also monitors respiration, skin temperature and body motion.

“We didn’t have a specific end use for all these functions combined together, but the point is that we can integrate all these different sensing capabilities on the same small bandage,” said co-first author Zhenlong Huang, who conducted this work as a visiting Ph.D. student in Xu’s research group.

And the researchers did not sacrifice quality for quantity. “This device is like a ‘master of all trades.’ We picked high quality, robust subcomponents—the best strain sensor we could find on the market, the most sensitive accelerometer, the most reliable ECG sensor, high quality Bluetooth, etc.—and developed a clever way to integrate all these into one stretchable device,” added co-first author Yang Li, a nanoengineering graduate student at UC San Diego in Xu’s research group.

So far, the smart bandage can last for more than six months without any drop in performance, stretchability or flexibility. It can communicate wirelessly with a smartphone or laptop up to 10 meters away. The device runs on a total of about 35.6 milliwatts, which is equivalent to the power from 7 laser pointers.

The team will be working with industrial partners to optimize and refine this technology. They hope to test it in clinical settings in the future.

Learn more: ‘Building up’ Stretchable Electronics to be as Multipurpose as Your Smartphone

 

 

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Smart bandages for chronic wounds designed to monitor and tailor treatment

A smart bandage with wound covering component (right), containing sensors and a drug carrier, and a microprocessor (left) that interprets sensor input and triggers drug delivery

Bandages with integrated pH and temperature sensors and electronically triggered drug release are designed to improve healing

A team of engineers led by Tufts University has developed a prototype bandage designed to actively monitor the condition of chronic wounds and deliver appropriate drug treatments to improve the chances of healing. While the lab-tested bandages remain to be assessed in a clinical context, the research, published today in the journal Small, is aimed at transforming bandaging from a traditionally passive treatment into a more active paradigm to address a persistent and difficult medical challenge.

Chronic skin wounds from burns, diabetes, and other medical conditions can overwhelm the regenerative capabilities of the skin and often lead to persistent infections and amputations. With the idea of providing an assist to the natural healing process, the researchers designed the bandages with heating elements and thermoresponsive drug carriers that can deliver tailored treatments in response to embedded pH and temperature sensors that track infection and inflammation.

Non-healing chronic wounds are a significant medical problem – nearly 15 percent of Medicare beneficiaries require treatment for at least one type of chronic wound or infection at an annual cost of an estimated $28 billion, according to research published in Value in Health. Patients are often older, non-ambulatory, and limited in their ability to provide self-care, yet non-healing wounds are typically treated in an outpatient setting or at home. The smart bandages could provide real time monitoring and delivery of treatment with limited intervention from the patient or caregivers.

“We’ve been able to take a new approach to bandages because of the emergence of flexible electronics,” said Sameer Sonkusale, Ph.D. professor of electrical and computer engineering at Tufts University’s School of Engineering and corresponding co-author for the study. “In fact, flexible electronics have made many wearable medical devices possible, but bandages have changed little since the beginnings of medicine. We are simply applying modern technology to an ancient art in the hopes of improving outcomes for an intractable problem.”

The pH of a chronic wound is one of the key parameters for monitoring its progress. Normal healing wounds fall within the range of pH 5.5 to 6.5, whereas non-healing infected wounds can have pH well above 6.5. Temperature is also an important parameter, providing information on the level of inflammation in and around the wound. While the smart bandages in this study combine pH and temperature sensors, Sonkusale and his team of engineers have also developed flexible sensors for oxygenation – another marker of healing – which can be integrated into the bandage. Inflammation could also be tracked not just by heat, but by specific biomarkers as well.

A microprocessor reads the data from the sensors and can release drug on demand from its carriers by heating the gel. The entire construct is attached to a transparent medical tape to form a flexible bandage less than 3 mm thick. Components were selected to keep the bandage low cost and disposable, except for the microprocessor, which can be re-used.

“The smart bandage we created, with pH and temperature sensors and antibiotic drug delivery, is really a prototype for a wide range of possibilities,” said Sonkusale. “One can imagine embedding other sensing components, drugs, and growth factors that treat different conditions in response to different healing markers.”

The smart bandages have been created and tested successfully under in vitro conditions. Pre-clinical studies are now underway to determine their in vivo clinical advantages in facilitating healing compared to traditional bandages and wound care products.

Learn more: Smart bandages designed to monitor and tailor treatment for chronic wounds

 

 

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Fluorescent silk as an implantable and injectable wound healing material

The processing technology of fluorescent (mKate2) silk can be applied to developing smart medical bandages for wound healing on the human skin. (Purdue University image/Jung Woo Leem)

A silk hybrid material attacks bacteria when illuminated by a green light, thanks to a far-red fluorescent protein researchers transferred to its genetic makeup.

The all-natural material would be safer than conventional photocatalytic, or light-activated, means to kill harmful pathogens such as bacteria, which use potentially biohazardous semiconductors and require cancer-causing ultraviolet light for activation. A silk alternative engineered by Purdue University and the Korean National Institute of Agricultural Research would instead use plasmonic photocatalyst-like biomaterials and visible light, which also aid in wound healing and environmental remediation including air and water purification. Their findings published in early view on March 12 in Advanced Science.

“Silk is an ancient and well-known biomaterial,” said Young Kim, Purdue associate professor of biomedical engineering. “It doesn’t have any issues with the human body. And the nice thing about green light is that it’s not harmful – the color corresponds to the strongest intensity of the solar spectrum.”

To combine the benefits of silk and green light, researchers inserted the gene for “mKate2,” a far-red fluorescent protein, into a silk host. Shining a green light on the resulting hybrid generates reactive oxygen species (ROS), which are effective radicals for breaking down organic contaminants and attacking the membrane and DNA of pathogens.

When E. coli on the fluorescent silk were illuminated by a weak green light for 60 minutes, the bacteria’s survival rate dropped to 45 percent.

The researchers found that the hybrid could be processed into a solution, film, bandage and fabric. “We’ve basically added fluorescence to silk to facilitate disinfection or decontamination using just visible light,” said Jung Woo Leem, a visiting scholar in Purdue’s school of biomedical engineering.

Kim’s team believes that green-light activated red fluorescent silk could be both more efficient and scalable than other plasmonic photocatalysts, in which metal nanoparticles hybridized from semiconductor materials also use visible light but could still pose negative environmental consequences.

“The silk photocatalysts would be easier and safer to produce than plasmonic ones since silkworms, rather than industrial facilities, provide the host for ROS-generating materials. It’s a completely new green manufacturing of nanomaterials,” Kim said.

Because ambient white light also includes green light, the researchers anticipate that the silk hybrid material should typically have a strong enough light source to generate ROS as long as a green light controls ROS generation.

Kim’s team plans to take advantage of silk’s biocompatibility with the human body both inside and out. “We’re thinking about some implantable and injectable wound healing materials that dissolve over time in the body. Then we wouldn’t need to do additional surgery to take it out,” Kim said.

Learn more: Far-red fluorescent silk can kill harmful bacteria as biomedical and environmental remedy

 

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A smartphone controlled smart bandage delivers precise medication

Advanced Functional Materials
A prototype of the team’s design.

SMARTPHONE-CONTROLLED DESIGN PRECISELY DELIVERS MEDICATION

Researchers from the University of Nebraska-Lincoln, Harvard Medical School and MIT have designed a smart bandage that could eventually heal chronic wounds or battlefield injuries with every fiber of its being.

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Advanced Functional Materials

The bandage consists of electrically conductive fibers coated in a gel that can be individually loaded with infection-fighting antibiotics, tissue-regenerating growth factors, painkillers or other medications.

A microcontroller no larger than a postage stamp, which could be triggered by a smartphone or other wireless device, sends small amounts of voltage through a chosen fiber. That voltage heats the fiber and its hydrogel, releasing whatever cargo it contains.

A single bandage could accommodate multiple medications tailored to a specific type of wound, the researchers said, while offering the ability to precisely control the dose and delivery schedule of those medications. That combination of customization and control could substantially improve or accelerate the healing process, said Ali Tamayol, assistant professor of mechanical and materials engineering at Nebraska.

“This is the first bandage that is capable of dose-dependent drug release,” Tamayol said. “You can release multiple drugs with different release profiles. That’s a big advantage in comparison with other systems. What we did here was come up with a strategy for building a bandage from the bottom up.

“This is a platform that can be applied to many different areas of biomedical engineering and medicine.”

The team envisions its smart bandage being used initially to treat chronic skin wounds that stem from diabetes. More than 25 million Americans – and more than 25 percent of U.S. adults 65 and older – could suffer from such wounds. The Centers for Disease Control and Prevention has estimated that diabetes cases will double or triple by the year 2050.

Ali Tamayol
Ali Tamayol

“The medical cost associated with these types of wounds is tremendous,” Tamayol said. “So there is a big need to find solutions for that.”

Those wounded in combat might also benefit from the bandage’s versatility and customizability, Tamayol said, whether to stimulate faster healing of bullet and shrapnel wounds or prevent the onset of infection in remote environments.

“Soldiers on the battlefield may be suffering from a number of different injuries or infections,” he said. “They might be dealing with a number of different pathogens. Imagine that you have a variable patch that has antidotes or drugs targeted toward specific hazards in the environment.”

Bandage aid

Existing bandages range from basic dry patches to more advanced designs that can passively release an embedded medication over time. To evaluate the potential advantages of their smart bandage, Tamayol and his colleagues at Harvard ran a series of experiments.

In one, the researchers applied a smart bandage loaded with growth factor to wounded mice. When compared with a dry bandage, the team’s version regrew three times as much of the blood-rich tissue critical to the healing process.

Another experiment showed that an antibiotic-loaded version of the bandage could eradicate infection-causing bacteria. Collectively, Tamayol said, the experiments also demonstrated that the heat needed to release the medications did not affect their potency.

Though the researchers have patented their design, it will need to undergo further animal and then human testing before going to market. That could take several years, though the fact that most of the design’s components are already approved by the Food and Drug Administration should streamline the process, Tamayol said.

In the meantime, he said, the researchers are also working to incorporate thread-based sensors that can measure glucose, pH and other health-related indicators of skin tissue. Integrating that capability would allow the team to create a bandage that could autonomously deliver proper treatments.

Learn more: Smart bandage could promote better, faster healing

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Wound healing sensor bandage for chronic wounds could even allow monitoring at home

Using a UV lamp, the pH level in the wound can be verified without removing the bandage and the healing process can continue unimpeded. Image: Empa

A novel bandage alerts the nursing staff as soon as a wound starts healing badly. Sensors incorporated into the base material glow with a different intensity if the wound’s pH level changes. This way even chronic wounds could be monitored at home.

All too often, changing bandages is extremely unpleasant, even for smaller, everyday injuries. It stings and pulls, and sometimes a scab will even start bleeding again. And so we prefer to wait until the bandage drops off by itself.

It’s a different story with chronic wounds, though: normally, the nursing staff has to change the dressing regularly – not just for reasons of hygiene, but also to examine the wound, take swabs and clean it. Not only does this irritate the skin unnecessarily; bacteria can also get in, the risk of infection soars. It would be much better to leave the bandage on for longer and have the nursing staff “read” the condition of the wound from outside.

The idea of being able to see through a wound dressing gave rise to the project Flusitex (Fluorescence sensing integrated into medical textiles), which is being funded by the Swiss initiative Nano-Tera. Researchers from Empa teamed up with ETH Zurich, Centre Suisse d’Electronique et de Microtechnique (CSEM) and University Hospital Zurich to develop a high-tech system that is supposed to supply the nursing staff with relevant data about the condition of a wound. As Luciano Boesel from Empa’s Laboratory for Biomimetic Membranes and Textiles, who is coordinating the project at Empa, explains: “The idea of a smart wound dressing with integrated sensors is to provide continuous information on the state of the healing process without the bandages having to be changed any more frequently than necessary.” This would mean a gentler treatment for patients, less work for the nursing staff and, therefore, lower costs: globally, around 17 billion $ were spent on treating wounds last year.

When wounds heal, the body produces specific substances in a complex sequence of biochemical processes, which leads to a significant variation in a number of metabolic parameters. For instance, the amount of glucose and oxygen rises and falls depending on the phase of the healing process; likewise does the pH level change. All these variations can be detected with specialized sensors. With this in mind, Empa teamed up with project partner CSEM to develop a portable, cheap and easy-to-use device for measuring fluorescence that is capable of monitoring several parameters at once. It should enable nursing staff to keep tabs on the pH as well as on glucose and oxygen levels while the wound heals. If these change, conclusions about other key biochemical processes involved in wound healing can be drawn.

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The bandage reveals its measurings under UV light. Image: Empa / CSEM
A high pH signals chronic wounds

The pH level is particularly useful for chronic wounds. If the wound heals normally, the pH rises to 8 before falling to 5 or 6. If a wound fails to close and becomes chronic, however, the pH level fluctuates between 7 and 8. Therefore, it would be helpful if a signal on the bandage could inform the nursing staff that the wound pH is permanently high. If the bandage does not need changing for reasons of hygiene and pH levels are low, on the other hand, they could afford to wait.

But how do the sensors work? The idea: if certain substances appear in the wound fluid, “customized” fluorescent sensor molecules respond with a physical signal. They start glowing and some even change color in the visible or ultra-violet (UV) range. Thanks to a color scale, weaker and stronger changes in color can be detected and the quantity of the emitted substance be deduced.

Empa chemist Guido Panzarasa from the Laboratory for Biomimetic Membranes and Textiles vividly demonstrates how a sample containing sensor molecules begins to fluoresce in the lab. He carefully drips a solution with a pH level of 7.5 into a dish. Under a UV light, the change is plain to see. He adds another solution and the luminescence fades. A glance at the little bottle confirms it: the pH level of the second solution is lower.

Luminous molecules under UV

The Empa team designed a molecule composed of benzalkonium chloride and pyranine. While benzalkonium chloride is a substance also used for conventional medical soap to combat bacteria, fungi and other microorganisms, pyranine is a dye found in highlighters that glows under UV light. “This biomarker works really well,” says Panzarasa; “especially at pH levels between 5.5 and 7.5. The colors can be visualized with simple UV lamps available in electronics stores.” The Empa team recently published their results in the journal “Sensors and Actuators”.

The designer molecule has another advantage: thanks to the benzalkonium chloride, it has an antimicrobial effect, as researchers from Empa’s Laboratory for Biointerfaces confirmed for the bacteria strain Staphylococcus aureus. Unwelcome bacteria might potentially also be combatted by selecting the right bandage material in future. As further investigations, such as on the chemical’s compatibility with cells and tissues, are currently lacking, however, the researchers do not yet know how their sensor works in a complex wound.

Keen interest from industry

In order to illustrate what a smart wound dressing might actually look like in future, Boesel places a prototype on the lab bench. “You don’t have to cover the entire surface of wound dressings with sensors,” he explains. “It’s enough for a few small areas to be impregnated with the pyranine benzalkonium molecules and integrated into the base material. This means the industrial wound dressings won’t be much pricier than they are now – only up to 20% more expensive.” Empa scientists are currently working on this in the follow-up project FlusiTex-Gateway in cooperation with industrial partners Flawa, Schöller, Kenzen and Theranoptics.
Panzarasa now drips various liquids with different pH levels onto all the little

cylinders on the wound pad prototype. Sure enough, the lighter and darker dots are also clearly discernible as soon as the UV lamp is switched on. They are even visible to the naked eye and glow in bright yellow if liquids with a high pH come into contact with the sensor. The scientists are convinced: since the pH level is so easy to read and provides precise information about the acidic or alkaline state of the sample, this kind of wound dressing is just the ticket as a diagnostic tool. Using the fluorescence meter developed by CSEM, more accurate, quantitative measure-ments of the pH level can be accomplished for medical purposes.

According to Boesel, it might one day even be possible to read the signals with the aid of a smartphone camera. Combined with a simple app, nursing staff and doctors would have a tool that enables them to easily and conveniently read the wound status “from outside”, even without a UV lamp. And patients would then also have the possibility of detecting the early onset of a chronic wound at home.

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