A wearable sensor can monitor levels of metabolites and nutrients in a person’s blood by analyzing their sweat

via Caltech

There are numerous things to dislike about going to the doctor: Paying a copay, sitting in the waiting room, out-of-date magazines, sick people coughing without covering their mouths. For many, though, the worst thing about a doctor’s visit is getting stuck with a needle. Blood tests are a tried-and-true way of evaluating what is going on with your body, but the discomfort is unavoidable. Or maybe not, say Caltech scientists.

In a new paper published in Nature Biotechnology, researchers led by Wei Gao, assistant professor of medical engineering, describe a mass-producible wearable sensor that can monitor levels of metabolites and nutrients in a person’s blood by analyzing their sweat. Previously developed sweat sensors mostly target compounds that appear in high concentrations, such as electrolytes, glucose, and lactate. Gao’s sweat sensor is more sensitive than current devices and can detect sweat compounds of much lower concentrations, in addition to being easier to manufacture, the researchers say.

The development of such sensors would allow doctors to continuously monitor the condition of patients with illnesses like cardiovascular disease, diabetes, or kidney disease, all of which result in abnormal levels of nutrients or metabolites in the bloodstream. Patients would benefit from having their physician better informed of their condition, while also avoiding invasive and painful encounters with hypodermic needles.

“Such wearable sweat sensors have the potential to rapidly, continuously, and noninvasively capture changes in health at molecular levels,” Gao says. “They could enable personalized monitoring, early diagnosis, and timely intervention.”

Gao’s work is focused on developing devices based on microfluidics, a name for technologies that manipulate tiny amounts of liquids, usually through channels less than a quarter of a millimeter in width. Microfluidics are ideal for an application of this sort because they minimize the influence of sweat evaporation and skin contamination on the sensing accuracy. As freshly supplied sweat flows through the microchannels, the device can make more accurate measurements of sweat and can capture temporal changes in concentrations.

Until now, Gao and his colleagues say, microfluidic-based wearable sensors were mostly fabricated with a lithography-evaporation process, which requires complicated and expensive fabrication processes. His team instead opted to make their biosensors out of graphene, a sheet-like form of carbon. Both the graphene-based sensors and the tiny microfluidics channels are created by engraving the plastic sheets with a carbon dioxide laser, a device that is now so common that it is available to home hobbyists.

The research team opted to have their sensor measure respiratory rate, heart rate, and levels of uric acid and tyrosine. Tyrosine was chosen because it can be an indicator of metabolic disorders, liver disease, eating disorders, and neuropsychiatric conditions. Uric acid was chosen because, at elevated levels, it is associated with gout, a painful joint condition that is on the rise globally. Gout occurs when high levels of uric acid in the body begin crystallizing in the joints, particularly those of the feet, causing irritation and inflammation.

To see how well the sensors performed, the researchers ran a series of tests with healthy individuals and patients. To check sweat tyrosine levels, which are influenced by a person’s physical fitness, they used two groups of people: trained athletes and individuals of average fitness. As expected, the sensors showed lower levels of tyrosine in the sweat of the athletes. To check uric acid levels, they took a group of healthy individuals and monitored their sweat while they were fasting as well as after they ate a meal rich in purines, compounds in food that are metabolized into uric acid. The sensor showed uric acid levels rising after the meal. Gao’s team also performed a similar test with gout patients. Their uric acid levels, the sensor showed, were much higher than those of healthy people.

To check the accuracy of the sensors, the researchers also drew blood samples from the gout patients and healthy subjects. The sensors’ measurements of uric acid levels strongly correlated with levels of the compound in the blood.

Gao says the high sensitivity of the sensors, along with the ease with which they can be manufactured, means they could eventually be used by patients at home to monitor conditions like gout, diabetes, and cardiovascular diseases. Having accurate real-time information about their health could even allow a patient to adjust their own medication levels and diet as required.

“Considering that abnormal circulating nutrients and metabolites are related to a number of health conditions, the information collected from such wearable sensors will be invaluable for both research and medical treatment,” Gao says.

Learn more: Wearable Sweat Sensor Detects Gout-Causing Compounds

 

 

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Promising new class of super-strong and conducting materials e.g. the world’s strongest silver

Inside a grain of silver, copper atom impurities (in green) have been segregated to a grain boundary (on the left) and into internal defects (long strings, streaming downward.)

Team creates metal that breaks decades-old theoretical limit, promising new class of super-strong and conducting materials.

A team of scientists has made the strongest silver ever—42 percent stronger than the previous world record. But that’s not the important point.

“We’ve discovered a new mechanism at work at the nanoscale that allows us to make metals that are much stronger than anything ever made before—while not losing any electrical conductivity,” says Frederic Sansoz, a materials scientist and mechanical engineering professor at the University of Vermont who co-led the new discovery.

This fundamental breakthrough promises a new category of materials that can overcome a traditional trade-off in industrial and commercial materials between strength and ability to carry electrical current.

The team’s results were published on September 23 in the journal Nature Materials.

Rethinking the defect

All metals have defects. Often these defects lead to undesirable qualities, like brittleness or softening. This has led scientists to create various alloys or heavy mixtures of material to make them stronger. But as they get stronger, they lose electrical conductivity.

“We asked ourselves, how can we make a material with defects but overcome the softening while retaining the electroconductivity,” said Morris Wang, a lead scientist at Lawrence Livermore National Laboratory and co-author of the new study.

By mixing a trace amount of copper into the silver, the team showed it can transform two types of inherent nanoscale defects into a powerful internal structure. “That’s because impurities are directly attracted to these defects,” explains Sansoz. In other words, the team used a copper impurity—a form of doping or “microalloy” as the scientists style it—to control the behavior of defects in silver. Like a kind of atomic-scale jiu-jitsu, the scientists flipped the defects to their advantage, using them to both strengthen the metal and maintain its electrical conductivity.

To make their discovery, the team—including experts from UVM, Lawrence Livermore National Lab, the Ames Laboratory, Los Alamos National Laboratory and UCLA—started with a foundational idea of materials engineering: as the size of a crystal—or grain—of material gets smaller, it gets stronger. Scientists call this the Hall-Petch relation. This general design principle has allowed scientists and engineers to build stronger alloys and advanced ceramics for over 70 years. It works very well.

Until it doesn’t. Eventually, when grains of metal reach an infinitesimally tiny size—under tens of nanometers wide—the boundaries between the grains become unstable and begin to move. Therefore, another known approach to strengthening metals like silver uses nanoscale “coherent twin boundaries,” which are a special type of grain boundary. These structures of paired atoms—forming a symmetrical mirror-like crystalline interface—are exceedingly strong to deformation. Except that these twin boundaries, too, become soft when their interspacing falls under a critical size of a few nanometers, due to imperfections.

Unprecedented properties

Very roughly speaking, nanocrystals are like patches of cloth and nanotwins are like strong but tiny threads in the cloth. Except they’re at the atomic scale. The new research combines both approaches to make what the scientists call a “nanocrystalline-nanotwinned metal,” that has “unprecedented mechanical and physical properties,” the team writes.

That’s because the copper atoms, slightly smaller than the atoms of silver, move into defects in both the grain boundaries and the twin boundaries. This allowed the team—using computer simulations of atoms as a starting point and then moving into real metals with advanced instruments at the National Laboratories—to create the new super-strong form of silver. The tiny copper impurities within the silver inhibit the defects from moving, but are such a small amount of metal—less than one percent of the total—that the rich electrical conductivity of silver is retained. “The copper atom impurities go along each interface and not in between,” Sansoz explains. “So they don’t disrupt the electrons that are propagating through.”

Not only does this metal overcome the softening previously observed as grains and twin boundaries get too small—the so-called “Hall-Petch breakdown”—it even exceeds the long-standing theoretical Hall-Petch limit. The team reports an “ideal maximum strength” can be found in metals with twin boundaries that are under seven nanometers apart, just a few atoms. And a heat-treated version of the team’s copper-laced silver has a hardness measure above what had been thought to be the theoretical maximum.

“We’ve broken the world record, and the Hall-Petch limit too, not just once but several times in the course of this study, with very controlled experiments,” says Sansoz.

Sansoz is confident that the team’s approach to making super-strong and still-conductive silver can be applied to many other metals. “This is a new class of materials and we’re just beginning to understand how they work,” he says. And he anticipates that the basic science revealed in the new study can lead to advances in technologies—from more efficient solar cells to lighter airplanes to safer nuclear power plants. “When you can make material stronger, you can use less of it, and it lasts longer,” he says, “and being electrically conductive is crucial to many applications.”

Learn more: Inventing the World’s Strongest Silver

 

The Latest on: Nanocrystalline-nanotwinned metal
  • Scientists invent world’s strongest silver
    on October 6, 2019 at 11:20 am

    Their work, thus, focused on combining both approaches to make a “nanocrystalline-nanotwinned metal” that has “unprecedented mechanical and physical properties.” What happens is that the copper atoms, ...

  • Inventing the World's Strongest Silver
    on October 3, 2019 at 6:06 am

    Except they're at the atomic scale. The new research combines both approaches to make what the scientists call a "nanocrystalline-nanotwinned metal," that has "unprecedented mechanical and physical ...

  • Superstrong silver may herald new era for metals
    on October 3, 2019 at 4:53 am

    “So they don’t disrupt the electrons that are propagating through.” The team called the new type of alloy a “nanocrystalline-nanotwinned metal” and in their paper they claim that these have ...

  • Inventing The World’s Strongest Silver
    on October 2, 2019 at 8:57 pm

    Except they’re at the atomic scale. The new research combines both approaches to make what the scientists call a “nanocrystalline-nanotwinned metal,” that has “unprecedented mechanical and physical ...

  • Inventing the world's strongest silver
    on October 2, 2019 at 3:52 pm

    Except they're at the atomic scale. The new research combines both approaches to make what the scientists call a "nanocrystalline-nanotwinned metal," that has "unprecedented mechanical and physical ...

  • Inventing the world's strongest silver
    on October 2, 2019 at 1:37 pm

    Except they're at the atomic scale. The new research combines both approaches to make what the scientists call a "nanocrystalline-nanotwinned metal," that has "unprecedented mechanical and physical ...

  • Inventing the world's strongest silver
    on October 2, 2019 at 1:05 pm

    Except they're at the atomic scale. The new research combines both approaches to make what the scientists call a "nanocrystalline-nanotwinned metal," that has "unprecedented mechanical and physical ...

  • Inventing the world's strongest silver
    on October 2, 2019 at 1:05 pm

    Except they’re at the atomic scale. The new research combines both approaches to make what the scientists call a “nanocrystalline-nanotwinned metal,” that has “unprecedented mechanical and physical ...

  • Ideal maximum strengths and defect-induced softening in nanocrystalline-nanotwinned metals
    on September 22, 2019 at 5:00 pm

    Different softening mechanisms are considered to occur for nanocrystalline and nanotwinned materials. Here, we report nanocrystalline-nanotwinned Ag materials that exhibit two strength transitions ...

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New device generates electricity at night from the cold night sky

In this photograph, the thermoelectric generator harnesses temperature differences to produce renewable electricity without active heat input. Here it is generating light. CREDIT Aaswath Raman

An inexpensive thermoelectric device harnesses the cold of space without active heat input, generating electricity that powers an LED at night, researchers report September 12 in the journal Joule.

“Remarkably, the device is able to generate electricity at night, when solar cells don’t work,” says lead author Aaswath Raman (@aaraman), an assistant professor of materials science and engineering at the University of California, Los Angeles. “Beyond lighting, we believe this could be a broadly enabling approach to power generation suitable for remote locations, and anywhere where power generation at night is needed.”

While solar cells are an efficient source of renewable energy during the day, there is currently no similar renewable approach to generating power at night. Solar lights can be outfitted with batteries to store energy produced in daylight hours for night-time use, but the addition drives up costs.

The device developed by Raman and Stanford University scientists Wei Li and Shanhui Fan sidesteps the limitations of solar power by taking advantage of radiative cooling, in which a sky-facing surface passes its heat to the atmosphere as thermal radiation, losing some heat to space and reaching a cooler temperature than the surrounding air. This phenomenon explains how frost forms on grass during above-freezing nights, and the same principle can be used to generate electricity, harnessing temperature differences to produce renewable electricity at night, when lighting demand peaks.

Raman and colleagues tested their low-cost thermoelectric generator on a rooftop in Stanford, California, under a clear December sky. The device, which consists of a polystyrene enclosure covered in aluminized mylar to minimize thermal radiation and protected by an infrared-transparent wind cover, sat on a table one meter above roof level, drawing heat from the surrounding air and releasing it into the night sky through a simple black emitter. When the thermoelectric module was connected to a voltage boost convertor and a white LED, the researchers observed that it passively powered the light. They further measured its power output over six hours, finding that it generated as much as 25 milliwatts of energy per square meter.

Since the radiative cooler consists of a simple aluminum disk coated in paint, and all other components can be purchased off the shelf, Raman and the team believe the device can be easily scaled for practical use. The amount of electricity it generates per unit area remains relatively small, limiting its widespread applications for now, but the researchers predict it can be made twenty times more powerful with improved engineering–such as by suppressing heat gain in the radiative cooling component to increase heat-exchange efficiency–and operation in a hotter, drier climate.

“Our work highlights the many remaining opportunities for energy by taking advantage of the cold of outer space as a renewable energy resource,” says Raman. “We think this forms the basis of a complementary technology to solar. While the power output will always be substantially lower, it can operate at hours when solar cells cannot.”

Learn more: Device generates light from the cold night sky

 

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Intelligent cameras could be possible utilizing an optical neural network

In this recent study, published in the open access journal Advanced Photonics, the UCLA researchers have significantly increased the system’s accuracy by adding a second set of detectors to the system, and therefore each object type is now represented with two detectors rather than one. The researchers aimed to increase the signal difference between a detector pair assigned to an object type. Intuitively, this is similar to weighing two stones simultaneously with the left and right hands – it is easier this way to differentiate if they are of similar weight or have different weights. This differential detection scheme helped UCLA researchers improve their prediction accuracy for unknown objects that were seen by their optical neural network.

UCLA engineers have made major improvements on their design of an optical neural network –a device inspired by how the human brain works – that can identify objects or process information at the speed of light.

The development could lead to intelligent camera systems that figure out what they are seeing simply by the patterns of light that run through a 3D engineered material structure. Their new design takes advantage of the parallelization and scalability of optical-based computational systems.

For example, such systems could be incorporated into self-driving cars or robots, helping them make near-instantaneous decisions faster and using less power than computer-based systems that need additional time to identify an object after it’s been seen.

The technology was first introduced by the UCLA group in 2018. The system uses a series of 3D-printed wafers or layers with uneven surfaces that transmit or reflect incoming light – they’re reminiscent in look and effect to frosted glass. These layers have tens of thousands of pixel points – essentially these are artificial neurons that form an engineered volume of material that computes all-optically. Each object will have a unique light pathway through the 3D fabricated layers.

Behind those layers are several light detectors, each previously assigned in a computer to deduce what the input object is by where the most light ends up after traveling through the layers.

For example, if it’s trained to figure out handwritten digits, then the detector programmed to identify a “5” will see the most of the light hit that detector after the image of a “5” has traveled through the layers.

In this recent study, published in the open access journal Advanced Photonics, the UCLA researchers have significantly increased the system’s accuracy by adding a second set of detectors to the system, and therefore each object type is now represented with two detectors rather than one. The researchers aimed to increase the signal difference between a detector pair assigned to an object type. Intuitively, this is similar to weighing two stones simultaneously with the left and right hands – it is easier this way to differentiate if they are of similar weight or have different weights.

This differential detection scheme helped UCLA researchers improve their prediction accuracy for unknown objects that were seen by their optical neural network.

In this recent study, published in the open access journal Advanced Photonics, the UCLA researchers have significantly increased the system’s accuracy by adding a second set of detectors to the system, and therefore each object type is now represented with two detectors rather than one. The researchers aimed to increase the signal difference between a detector pair assigned to an object type. Intuitively, this is similar to weighing two stones simultaneously with the left and right hands – it is easier this way to differentiate if they are of similar weight or have different weights.

This differential detection scheme helped UCLA researchers improve their prediction accuracy for unknown objects that were seen by their optical neural network.

“Such a system performs machine-learning tasks with light-matter interaction and optical diffraction inside a 3D fabricated material structure, at the speed of light and without the need for extensive power, except the illumination light and a simple detector circuitry,” said Aydogan Ozcan, Chancellor’s Professor of Electrical and Computer Engineering and the principal investigator on the research. “This advance could enable task-specific smart cameras that perform computation on a scene using only photons and light-matter interaction, making it extremely fast and power efficient.”

The researchers tested their system’s accuracy using image datasets of hand-written digits, items of clothing, and a broader set of various vehicles and animals known as the CIFAR-10 image dataset. They found image recognition accuracy rates of 98.6%, 91.1% and 51.4% respectively.

Those results compare very favorably to earlier generations of all-electronic deep neural nets. While more recent electronic systems have better performance, the researchers suggest that all-optical systems have advantages in inference speed, low-power, and can be scaled up to accommodate and identify many more objects in parallel.

Learn more: Optical neural network could lead to intelligent cameras

 

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Improved therapies for Duchenne muscular dystrophy?

Parvatiyar and her colleagues found that sarcospan can help stabilize cardiac cell membranes, which become fragile in patients with DMD.

A new multi-institution study spearheaded by researchers at Florida State University and the University of California, Los Angeles suggests a tiny protein could play a major role in combating heart failure related to Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder among children.

In collaboration with scientists from across the nation, FSU researchers found that increased levels of the protein sarcospan improve cardiac function by reinforcing cardiac cell membranes, which become feeble in patients with DMD.

Their findings were published in the journal JCI Insight.

The condition, which typically afflicts young boys, is caused by a mutation that prevents the body from producing dystrophin, a protein crucial to the health of skeletal, respiratory and cardiac muscles. Advances in treatment for certain types of DMD-related muscle degradation have helped to prolong patients’ lifespans. However, as DMD patients age, their heart function declines dramatically.

“Patients typically live to 20 or 30 years of age,” said lead author Michelle Parvatiyar, an assistant professor in the Department of Nutrition, Food and Exercise Sciences in FSU’s College of Human Sciences. “There have been important improvements in respiratory care, which used to be what a majority of patients would succumb to. Now, in their 20s and 30s, they’re often succumbing to cardiomyopathy. The heart is functioning with a major component of the cell membrane missing. Over time, it wears out.”

The study was part of continued efforts by UCLA biologist Rachelle H. Crosbie, the study’s corresponding author, who previously identified sarcospan as a protein that could improve mechanical support in skeletal cell membranes lacking dystrophin. Her finding buoyed DMD researchers and affirmed sarcospan’s potential as an effective tool in the fight against the condition.

“But nobody had really looked at how increasing the levels of this protein might affect the heart,” Parvatiyar said.

Using a unique mouse model with a dearth of dystrophin, Parvatiyar and her collaborators did just that.

In their study, the team found that while it’s is not a like-for-like replacement for dystrophin, an overexpression of sarcospan in cardiac cells seems to do the job of stabilizing cell membranes. Even under stress, researchers found, sarcospan overexpression was able to improve the membrane defect in dystrophin-deficient cells.

“Sarcospan doesn’t quite do the job of dystrophin, but it acts as a glue to stabilize the membrane and hold protein complexes together when dystrophin is lacking,” said Parvatiyar, explaining a concept developed by Crosbie.

Cardiac measurements confirmed that sarcospan does protect the cell membrane even when the heart is placed under stress. Study co-author and FSU College of Medicine Associate Professor Jose Pinto performed the measurements, along with FSU graduate student Karissa Dieseldorff Jones and University of Miami Miller School of Medicine research assistant Rosemeire Takeuchi Kanashiro.

In addition to serving as a kind of stabilizing glue, researchers said sarcospan could also act as a scaffold that supports other essential proteins at the cell membrane. That function could allow sarcospan to carry mini versions of dystrophin — which, in its normal state, has a long and unwieldy genetic code — to the edges of cardiac cells, where they could buttress the fragile membranes.

“The idea is that you could administer the sarcospan and the dystrophin at the same time, and the sarcospan could facilitate mini dystrophin localizing to the cell membrane and help hold those complexes in place,” Parvatiyar said.

Sarcospan’s two possible functions could augment existing DMD treatments, Parvatiyar said, or they could give rise to novel therapies that fortify weakened cardiac cell membranes and improve the quality of life for people with DMD.

In her previous position at UCLA, Parvatiyar had frequent interactions with DMD patients and their families. She said these interactions, and the unshakeable hope she’s witnessed in those suffering from DMD, continue to drive her and her colleagues in the search for new ways to combat this debilitating condition.

“Those were the first times in my life I’d ever had someone come up to me and thank me for my work,” she said. “Sometimes you can feel removed from it in the laboratory day after day. You see incremental progress. But to see people who are really yearning for help is motivating. Their positivity is incredibly inspiring.”

Learn more: Researchers’ discovery could lead to improved therapies for Duchenne muscular dystrophy

 

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