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Skin patches to diagnose diseases, monitor soldiers’ health, and stress levels in combat

Biomedical sensors present an exciting opportunity to measure human physiologic parameters in a continuous, real-time, and nonintrusive manner by leveraging semiconductor and flexible electronics packaging technology. These sensors incorporate a broad range of advances in microelectromechanical (MEMS), biological and chemical sensing, electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG)-based neural sensing platforms. Biological and chemical sensors are increasingly viewed as promising alternatives to expensive analytical instruments in the health care industry when specificity and selectivity criteria are met.


Wearable Biosensors are being developed that measure EEG, ECG, and EMG (electroencephalograms, electrocardiograms, and electromyography, tests which monitor brain, heart, and muscle activity). Fitness trackers that monitor heart rate and step count are very popular, but wearable, non-invasive biosensors would be extremely beneficial for managing diseases.


The next generation Wearable sensors employ lightweight, highly elastic materials attached directly onto the skin for more sensitive, precise measurements. Printed and Flexible electronics has started to revolutionize medical field with medical test strips with diagnostic electrodes. Engineers at the University of California San Diego have developed a flexible wearable sensor that can accurately measure a person’s blood alcohol level from sweat and transmit the data wirelessly to a laptop, smartphone or other mobile device.


At the Seoul National University in Korea researchers have created a highly flexible electronic patch capable of doing basic ECG monitoring while amplifying and storing the data locally within novel nanocrystal floating gates. The patch is made of a flexible and stretchable silicon membrane on top of which gold nanoparticles are placed so as to draw the conductive components. This eliminates conductive films that have their unique limitations while increasing the memory capacity of the device.


A soft, flexible skin patch that monitors biomarkers in sweat can determine whether the wearer is dehydrated, measure the person’s blood sugar level and even detect disease. The invention is part of an emerging field of wearable diagnostics. Human sweat contains many of the same biomarkers as blood; however, analyzing sweat using a skin patch doesn’t hurt like a needle stick, and the results can be obtained more quickly.


“Cosmetics companies are interested in sweat using these devices in their research labs to evaluate their antiperspirants and deodorants and so on,” Rogers said. “So sweat loss and sweat chemistry is interesting in that domain, as well. And then we have contracts with the military that are interested sort of in continuous monitoring of health status of war fighters.”


Researchers at Binghamton University, State University of New York, have developed skin-inspired electronics to conform to the skin, allowing for long-term, high-performance, real-time wound monitoring in users. “We eventually hope that these sensors and engineering accomplishments can help advance healthcare applications and provide a better quantitative understanding in disease progression, wound care, general health, fitness monitoring and more,” said Matthew Brown, a PhD student at Binghamton University.

Skin Patch Uses Sweat to Monitor Health

The skin patch, described in the journal Science Translational Medicine, is made of flexible material, and is about the size and thickness of a U.S. quarter. The so-called microfluidic device sticks to the forearm or back like an adhesive bandage, collecting and analyzing sweat. The first-of-its-kind patch is aimed primarily at athletes, but the flexible electronics device will in all likelihood find a place in medicine and even the cosmetics industry.


“We’ve been interested in the development of skin-like technologies that can mount directly on the body, to capture important information that relates to physiological health,” said John Rogers, a materials scientist and bioengineer at Northwestern University in Illinois, and one of a number of developers of the skin patch. “And what we’ve demonstrated here is a technology that allows for the precise collection, capture and chemical analysis of biomarkers in sweat and perspiration.”


The sweat is routed through microscopic tubules to four different reservoirs that measure pH and chloride, important indicators of hydration levels, lactate — which reveals exercise tolerance — and glucose. It can also track the perspiration rate. The skin patch could potentially be used to diagnose the lung disease cystic fibrosis by analyzing the chloride content in sweat. Wireless electronics transmit the color-coded results to a smartphone app, which analyzes them.


Bioengineers create sweat-based sensor to monitor glucose

Researchers at The University of Texas at Dallas have developed a wearable device that can monitor an individual’s glucose level via perspiration on the skin. In a study recently published online in the journal Sensors and Actuators B: Chemical, Dr. Shalini Prasad, professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science, and her co-authors demonstrated the capabilities of a biosensor they designed to reliably detect and quantify glucose in human sweat.


“Fitness trackers that monitor heart rate and step count are very popular, but wearable, non-invasive biosensors would be extremely beneficial for managing diseases,” said Prasad, the Cecil H. and Ida Green Professor in Systems Biology Science. But for diabetics and those at risk for diabetes, self-monitoring of blood glucose, or blood sugar, is an important part of managing their conditions.


Typical home-use blood glucose monitors require a user to obtain a small blood sample, usually through the prick of a finger and often several times a day. However, the UT Dallas textile-based sensor detects glucose in the small amount of ambient sweat on a person’s skin. The team has previously demonstrated that their technology can detect cortisol in perspiration.


“In our sensor mechanism, we use the same chemistry and enzymatic reaction that are incorporated into blood glucose testing strips,” Prasad said. “But in our design, we had to account for the low volume of ambient sweat that would be present in areas such as under a watch or wrist device, or under a patch that lies next to the skin.” For now, the skin patch is intended for use by sweaty athletes to measure biomarkers of performance, and Rogers sees the patch being sold with sports drinks; but, he said, a number of industries have expressed an interest in the sweat-based technology.


Nanomesh technology results in inflammation-free, on-skin health monitoring electronics

Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. The lack of breathability is deemed unsafe for long-term use: dermatological tests show the fine, stretchable materials prevent sweating and block airflow around the skin, causing irritation and inflammation, which ultimately could lead to lasting physiological and psychological effects.


According to a new study in Nature Nanotechnology, a new approach to this technology using a nanomesh structure could have positive implications for long-term health monitoring.The new sensors are inflammation-free, are very gas permeable, and they’re thin and lightweight, without the use of any pesky substrates that can contribute to skin discomfort. That means they can be directly laminated onto human skin for longer periods of time.


The sensors’ mesh structure is made of biocompatible polyvinyl alcohol, which enables that gas permeability without blocking sweat glands, and it’s stretchable without causing any additional discomfort, even if it’s affixed for a considerable amount of time. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.


They’re also versatile. The mesh conductors can attach to irregular skin surfaces — say, the tip of a person’s finger — and maintain their functionality even when a person’s natural body movements folds and elongates the skin. Nanofibres with a diameter of 300 to 500 nm were prepared by electrospinning a PVA solution, and were intertwined to form a mesh-like sheet. When the nanomesh conductors were placed on the skin and sprayed with water, the PVA nanofibers easily dissolved, and the nanomesh conductor attached to the skin.


According to the study, the approach has opened up a new possibility for the integration of electronic devices with skin for continuous, long-term health monitoring. “We learned that devices that can be worn for a week or longer for continuous monitoring were needed for practical use in medical and sports applications,” says Professor Takao Someya at the University of Tokyo’s Graduate School of Engineering whose research group had previously developed an on-skin patch that measured oxygen in blood.


Furthermore, the scientists proved the device’s mechanical durability through repeated bending and stretching, exceeding 10,000 times, of a conductor attached on the forefinger; they also established its reliability as an electrode for electromyogram recordings when its readings of the electrical activity of muscles were comparable to those obtained through conventional gel electrodes.


“It will become possible to monitor patients’ vital signs without causing any stress or discomfort,” says Someya about the future implications of the team’s research. In addition to nursing care and medical applications, the new device promises to enable continuous, precise monitoring of athletes’ physiological signals and bodily motion without impeding their training or performance.


Military requirements

Many militaries including those of US, China and others have expressed the desire to cut their manpower, along with stagnant growth or cuts in military budgets. On the other hands the increase in threat levels and employment of militaries in diverse and complex kind of missions has led to manifold increase in number of missions. Technological advances, such as night vision devices, have led to increase in duration of missions; militaries now operate around the clock during times of conflict.  Some of the missions the soldiers perform can take weeks, away from in difficult terrain like deserts and mountains which requires maintaining an incredibly high level of physical fitness.


Krueger (1991) reported that the efficiency of combatants in sustained operations can be significantly compromised by inadequate sleep. Vigilance and attention suffer, reaction time is impaired, mood declines, and some personnel begin to experience perceptual disturbances. Naitoh and Kelly (1992) warned that poor sleep management in extended operations quickly leads to motivational decrements, impaired attention, short-term memory loss, carelessness, reduced physical endurance, degraded verbal communication skills, and impaired judgment. Angus and Heslegrave (1985) noted that cognitive abilities suffer 30 percent reductions after only 1 night without sleep, and 60 percent reductions after a second night.


Around the world, armies are recognizing the importance of maximizing the effectiveness of Soldiers physically, perceptually, and cognitively. Militaries are therefore studying effects of frustration, mental workload, stress, fear and fatigue on both cognitive and physical performance. In November 2017, the Office of Naval Research awarded a $150,000 grant to Titus and the tech firm Sentience Science to develop tools that could monitor an individual’s stress levels in combat and automatically generate alerts when they reach dangerous levels.


Army and academic researchers are looking at how to monitor Soldier health and performance in real-time, by developing unique biorecognition receptors. These future bioreceptors are small, simple to produce, inexpensive, and robust to environmental stresses. Once integrated into wearable biosensors, data can be selectively captured from a complex mixture of sources in theater, like blood, sweat or saliva.


“Current Army programs are on-going to determine important biological markers correlating to soldier health and performance, so establishing the capability for rapid development of receptors will allow the lab to keep up with and advance the biomarker discovery and analysis,” he says.


“The Army will need to be more adaptive, more expeditionary and have a near-zero logistic demand while optimizing individual to squad execution in multifaceted operational environments,” said Dr. Matt Coppock, chemist and team lead. “It can be envisioned that real-time health and performance monitoring, as well as sensing current and emerging environmental threats, could be a key set of tools to make this possible.” The Army of the future may use these wearable sensors to monitor environmental biothreats and health diagnostics, all with great benefits to the Soldier.

ARL is developing Wearable sensors that could leverage biotechnology to monitor personal, environmental data

In an effort to enhance Soldier lethality, Army researchers are developing biorecognition receptors capable of consistent performance in multi-domain environments with the ability to collect real-time assessments of Soldier health and performance.


“The Army will need to be more adaptive, more expeditionary and have a near-zero logistic demand while optimizing individual to squad execution in multifaceted operational environments,” says Dr. Matt Coppock, chemist and team lead for the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory, the Army’s corporate research laboratory known as ARL.  “It can be envisioned that real-time health and performance monitoring, as well as sensing current and emerging environmental threats, could be a key set of tools to make this possible.”


U.S. Army Research Laboratory (ARL) scientists, in collaboration with researchers from the California Institute of Technology and Indi Molecular, Inc., developed a protein catalyzed capture (PCC) agent technology that improves previous versions of receptors and could enable the monitoring of personal and environmental data from soldiers in the field. The research, funded by the Army’s Institute of Collaborative Biotechnologies since 2012, is presented in a comprehensive review article for Chemical Reviews.


“PCC technology has demonstrated improvements in receptor stability, adaptability and manufacturability over standard antibody receptors, and supports the Soldier Lethality Cross-Functional Team as a potentially viable technology to monitor Soldier performance via relevant biomarkers collectable from wearable sensors,” Coppock said. Biological receptors are integrated into a biosensor to selectively capture a target of interest from a complex mixture like blood, sweat, salvia, etc., to produce the measurable effect by the sensor, he said. “Without the receptor, it would be impossible to know you are detecting what you want to detect,” Coppock said.


Antibodies collected from animals injected with the target of interest are used as receptors in biological sensors due to their high binding strengths and selectivity for the target. “The gold standard receptor work is based around antibodies, which are fantastic at target capture and selectivity, but their detection capabilities are somewhat limited due to their instability, limited shelf life and batch-to-batch performance variation,” Coppock said.


The research team developed a different and more innovative approach. “As an alternative, peptide-based receptors are smaller, simpler to produce, inexpensive and much more robust to environmental stresses, while still retaining the desirable binding properties of an antibody,” Coppock said. Receptors used by the research team are capable of retaining nearly all activity after being heated for one hour at 90 degrees Celsius, whereas many antibodies are completely inactive within minutes after heating up to greater than 70 degrees Celsius.


“We utilize an entirely synthetic approach to receptor development, which allows for much more control over the incorporation of unique building blocks to guarantee stability and permit straightforward modifications for sensor integration,” Coppock said. The team built a full infrastructure of capabilities that allows them to fully develop the synthetic, peptide-based receptors in house at the laboratory, on-demand and in whatever quantities are needed through widely available peptide synthesizers.


“All aspects of the technology have progressed throughout the collaboration culminating in a high-throughput development methodology,” Coppock adds in an Army press release. “These aspects included rethinking targeting strategies, upgrading library constructs, automating screening steps and simultaneously characterizing the performance of up to 100 different peptide sequences.”


“Current Army programs are on-going to determine important biological markers correlating to soldier health and performance, so establishing the capability for rapid development of receptors will allow the lab to keep up with and advance the biomarker discovery and analysis,” he says. Other potential applications of these receptors include environmental biothreat surveillance, health diagnostics and therapeutics, which could significantly impact the warfighter.


This technology has drawn much interest across the Army science and technology community, such as fellow researchers at CCDC Soldier Center, CCDC Chemical Biological Center and the Army Medical Command. This collaborative research has matured biological receptors from Technology Readiness Level (TRL-2) to TRL-4, including the successful integration into multiple assay platforms for ruggedized biological sensing in austere environments and reagent transition to the CCDC CBC.



Wearable Sensors Mimic Skin To Help With Wound Healing Process

Biosensors are analytical devices that combine a biological component with a physiochemical detector to observe and analyze a chemical substance and its reaction in the body. Conventional biosensor technology, while a great advancement in the medical field, still has limitations to overcome and improvements to be made to enhance their functionality. Researchers at Binghamton University’s Intimately Bio-Integrated Biosensors lab have developed a skin-inspired, open-mesh electromechanical sensor that is capable of monitoring lactate and oxygen on the skin.


“We are focused on developing next-generation platforms that can integrate with biological tissue (e.g. skin, neural and cardiac tissue),” said Brown. Under the guidance of Assistant Professor of Biomedical Engineering Ahyeon Koh, Brown, master’s students Brandon Ashely and Youjoong Park, and undergraduate student Sally Kuan designed a sensor that is structured similarly to that of the skin’s micro architecture. This wearable sensor is equipped with gold sensor cables capable of exhibiting similar mechanics to that of skin elasticity.


The researchers hope to create a new mode of sensor that will meld seamlessly with the wearer’s body to maximize body analysis to help understand chemical and physiological information. “This topic was interesting to us because we were very interested in real-time, on-site evaluation of wound healing progress in a near future,” said Brown. “Both lactate and oxygen are critical biomarkers to access wound-healing progression.”


They hope that future research will utilize this skin-inspired sensor design to incorporate more biomarkers and create even more multifunctional sensors to help with wound healing. They hope to see these sensors being developed incorporated into internal organs to gain an increased understanding about the diseases that affect these organs and the human body.


“The bio-mimicry structured sensor platform allows free mass transfer between biological tissue and bio-interfaced electronics,” said Koh. “Therefore, this intimately bio-integrated sensing system is capable of determining critical biochemical events while being invisible to the biological system or not evoking an inflammatory response.”





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