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New Skin Patch Monitors Glucose and Delivers Diabetes Drugs

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The wearable sweat monitoring patch on the skin. Image Credit: Hyunjae Lee and Changyeong Song

 
People with diabetes need to closely monitor their blood glucose levels multiple times every day, usually using a device that pricks their finger for a blood test to assess whether they need insulin shots or other drugs. Since blood collection and shots can be painful, not all patients do it as regularly as they need to—which can lead to dangerous fluctuations in their blood glucose levels.

Researchers have worked for years on methods to improve and even automate blood glucose monitoring and insulin/drug delivery. For example, insulin pumps make drug delivery easier, and recently designed artificial pancreas systems offer closed-loop monitoring and drug delivery. Now, researchers in Korea have just developed a wearable, and potentially disposable, glucose monitoring and drug-delivery system that uses sweat, not blood, to determine glucose levels.

The results, published today in Science Advances, suggest it’s a major upgrade. There are several differences between the artificial pancreas and the sweat-based monitoring system, according to lead author Hyunjae Lee, of Seoul National University in the Republic of Korea. While both devices can check blood glucose in real time and deliver necessary drugs, the artificial pancreas’s drug-delivery needles are permanently embedded subcutaneously, and the device itself is made of rigid plastic, which "might cause discomfort," Lee tells mental_floss.

The sweat-based system, on the other hand, is transfer-printed onto a thin silicone skin patch. It’s made of flexible and stretchable electronics, a series of stretchable graphene sensors—humidity, glucose, pH, and temperature—packed as closely as possible. The sensors’ electrodes are made from porous gold nanoparticles, whose structure helps create an electrochemically active surface area in order to analyze what’s in your sweat. Above a heating strip, which helps create humidity and generate sweat more quickly, is a film strip of drug-loaded microneedles, 0.6 inches by 0.8 inches. These are loaded with metformin, a drug used to control glucose in Type 2 diabetes. (At present, the sweat-based patch has not been tested on insulin, whose molecules are too big for delivery through the microneedles, though Lee hopes to work on designing one that can work with insulin in the future.)

Detail of the wearable sweat-analysis sensors. Image Credit: Hyunjae Lee and Changyeong Song

 
Sweat accumulates in the porous sweat-uptake layer of the patch, which also helps screen out negatively charged molecules, including drugs that may interfere with the glucose sensing. A waterproof band helps prevent the patch from peeling away from the skin. When the sweat covers the glucose and pH sensors, the measurements begin. "When blood glucose is high, [the] therapeutic part activates microneedle-based drug delivery," automatically, Lee explains.

Researchers adhered the patch to five healthy human subjects, ages 20 to 60. It takes 10–15 minutes for the device to generate enough sweat to measure glucose levels, though exercise could speed that process up. However, Lee says they took into account that for some people with diabetes, "sweat generation through exercise could be a burden." He adds, "Considering [that] point, we miniaturized sensor design that allows for reliable sweat analysis even with an infinitesimal amount of sweat."

The participants’ blood glucose levels were tested using a commercial glucose meter one hour before and after a meal as a comparison. The researchers found that the sweat-glucose sensor measurements were comparable to those of a commercial blood glucose assay kit.

Human clinical trials are not yet scheduled for the drug-delivery process, so to test this part of the system, Lee’s team turned to mice. They took 16 diabetic mice, 8 to 12 weeks old, and fasted them overnight before the experiment. They attached drug-loaded microneedles to their shaved abdomens, which had been stained with a special blue dye. Then, they used an embedded heating element to activate the microneedles, since the mice can’t produce enough sweat to do so. The microneedles' successful penetration of the skin was made visible by the blue dye.

The experimental groups of mice that received the drug delivery of metformin showed a significant decrease in blood glucose levels compared to the control groups that did not receive the drug. "In the animal experiment, we could confirm that blood glucose was continuously decreased and continued for six hours after microneedle therapy," Lee says.

While the system shows great success, Lee acknowledges there are adjustments to be made. "The sensor should be more sensitive and reliable to enhance accuracy of sweat-based glucose monitoring system," he says. In order to control the amount of drug delivered, they will also need to study "the correlation between sweat and blood glucose levels more thoroughly."

Despite the need for further research, Lee feels their device "can surely contribute to improve the quality of life of diabetic patients."

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Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
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Bill Gates is Spending $100 Million to Find a Cure for Alzheimer's
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Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation

Not everyone who's blessed with a long life will remember it. Individuals who live into their mid-80s have a nearly 50 percent chance of developing Alzheimer's, and scientists still haven't discovered any groundbreaking treatments for the neurodegenerative disease [PDF]. To pave the way for a cure, Microsoft co-founder and philanthropist Bill Gates has announced that he's donating $100 million to dementia research, according to Newsweek.

On his blog, Gates explained that Alzheimer's disease places a financial burden on both families and healthcare systems alike. "This is something that governments all over the world need to be thinking about," he wrote, "including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise."

Gates's interest in Alzheimer's is both pragmatic and personal. "This is something I know a lot about, because men in my family have suffered from Alzheimer’s," he said. "I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you're experiencing a gradual death of the person that you knew."

Experts still haven't figured out quite what causes Alzheimer's, how it progresses, and why certain people are more prone to it than others. Gates believes that important breakthroughs will occur if scientists can understand the condition's etiology (or cause), create better drugs, develop techniques for early detection and diagnosis, and make it easier for patients to enroll in clinical trials, he said.

Gates plans to donate $50 million to the Dementia Discovery Fund, a venture capital fund that supports Alzheimer's research and treatment developments. The rest will go to research startups, Reuters reports.

[h/t Newsweek]

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Eye Doctors Still Use This 100-Year-Old Test for Color Blindness

You may have seen them at your ophthalmologist's office: large circular diagrams made up of colored dots. People with normal vision are able to discern a number among the dots of contrasting colors. People who are color blind might see only a field of spots.

These elegant, deceptively modern drawings were published 100 years ago by a Japanese ophthalmologist, Shinobu Ishihara. Thanks to the designs' simplicity and diagnostic accuracy, the Ishihara test is still the most popular and efficient way to identify patients with color vision deficiencies.

Born in Tokyo in 1879, Ishihara studied medicine at the prestigious Tokyo Imperial University on a military scholarship, which required him to serve in the armed forces. After graduating in 1905, he worked for three years as a physician specializing in surgery in the Imperial Japanese Army, and then returned to the university for postgraduate studies in ophthalmology. In his research, Ishihara focused on identifying and recruiting soldiers with superior vision, thereby increasing the overall effectiveness of the military. And that became of prime importance to Japan beginning in 1914.

As World War I spread across Europe, Asia, and the Pacific, the Japanese army asked Ishihara to develop a better way to screen draftees for color vision problems. The most popular method at the time was the Stilling test, invented by German ophthalmologist Jakob Stilling in 1878 as the first clinical color vision test. (Previous tools had asked patients to identify the colors of wool skeins or illuminated lanterns—useful skills for sailors and railway conductors, but an imprecise method for diagnosing vision issues.)

"Though popular, 'the Stilling' retained a distinctly 19th-century flavor, more treatise-like and less diagnostically incisive," according to Eye magazine.


Shinobu Ishihara
Wellcome Images // CC BY 4.0

Japanese army officials requested a new diagnostic tool that was easier to administer and interpret. The test Ishihara began to develop was based, like Stilling's, on the principle of pseudo-isochromatism—a phenomenon in which two or more colors are seen as the same (or isochromatic) when they're actually different. A person with normal vision could easily see the difference, while people with red-green deficiency, the most common form of color blindness, would have difficulty distinguishing those two opposing colors. Those with blue-yellow color blindness, a less common type, would have a hard time discerning reds, greens, blues, or yellows.

Ishihara hand-painted circular designs comprised of small dots of different areas and colors so that variations in the design could be discerned only by color and not shape, size, or pattern. Hidden in the field of dots was a figure of a contrasting color that people with normal vision could see, while those with deficiencies could not. Other plates in the series were designed to show figures that would be visible only to people with deficiencies. When physicians displayed the diagrams, patients said or traced the visible figure within the circle without needing to use ambiguous color names, which standardized the possible results.

The earliest sets of Ishihara plates, produced in 1916, were reserved exclusively for the army's use and featured Japanese characters within the diagrams. In 1917, in an effort to sell the series internationally, Ishihara redesigned it with the now-familiar Arabic numerals and published a set of 16 plates as Tests for Colour Deficiency.

The tests were adopted throughout the world beginning in the early 1920s, and eventually grew into a set of 38 plates. But their popularity almost led to their undoing. Unauthorized publishers printed their own version of the plates to meet demand, throwing the accuracy of the diagnostic colors into doubt. "The plates have been duplicated along with an easily memorized key by cheap color processes in the tabloid press, and exposed in public places, reducing the fifth edition [of the collection] to a parlor game," one psychologist warned in the Journal of the Optical Society of America in 1943.

Despite those obstacles, the tests proved indispensable for both practicing physicians and researchers. Ishihara continued to refine the designs and improve the color accuracy of the images into the late 1950s, while he also served as the chair of the ophthalmology department and then dean of the medical school at Tokyo Imperial University. In addition to Tests for Colour Deficiency, he also published an atlas, textbook, lectures, and research studies on eye diseases. But he is remembered most for the iconic charts that seamlessly blend art and science.

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