Sandia Labs advances research on microneedles
Technology can be used to monitor diabetes
Blood may be the number one fluid in our bodies, but there are other important helpers, one of which is called interstitial fluid.
The National Cancer Institute says it’s the fluid found in the spaces around cells. “It comes from substances that leak out of blood capillaries and helps bring oxygen and nutrients to cells and to remove waste products,” according to NCI’s website.
A major diabetes forum, diabetes.co.uk, cites the importance of interstitial fluid in monitoring glucose levels in people with diabetes.
Now interstitial fluid is set to meet microneedles.
Sandia National Laboratories is at the forefront of research into microneedles, which can measure two to three times the diameter of human hair. Microneedles penetrate the outer skin layer, but they don’t reach nerve endings. It turns out they can sample interstitial fluids from under the skin and help measure several circulating biomarkers.
“People have known about interstitial fluid,” said Ronen Polsky, who has led Sandia’s work in microneedles. “It’s just that there has been a lot of difficulty in accessing interstitial fluid and analyzing it and that’s where a lot of our work has focused on — we’ve developed a device that can more easily detect the fluid and has allowed us to explore this area.”
It’s a level up from wearable sensors in use now.
“When we started work in this field in 2011, our goal was to develop microneedles as a wearable sensor, as an alternate to blood samples,” Polsky said. “People wear continuous glucose monitors for blood sugar measurements. We want to expand this to a whole range of other conditions to take advantage of this minimally invasive sampling using microneedles.
“The main point is we’re trying to replace blood drives that are done now for this analysis, so this will reduce the burden on the health care worker and it may be more comfortable for the patient and lead to improved health outcomes.”
In addition to detecting more, microneedle technology would be a leap forward compared to wearable devices when it comes to speed and comfort.
“Those (wearable monitoring devices) don’t use microneedles,” Polsky said. “They use fairly long 45 mm probes that measure in the subcutaneous fat. And so this causes a significant delay by the time the glucose can reach the sensors, sometimes for up to 15 minutes, so there’s a lot of corrective algorithms that these devices use to enable their continuous monitoring.”
So, unlike current wearables, microneedle devices would be better suited for monitoring a suite of biomarkers because of their ability to tap into interstitial fluid and because microneedles measure the dermis, the upper layer of the skin. They would be barely intrusive. Polsky said that upper layer of the skin “is much more favorable environment and that produces a faster and more accurate detection.
“We have been really looking at immune markers in the skin, and the skin has a much different immune function than blood, so infectious diseases is one of the applications that we’re excited about — by following these different immune proteins in the skin — we wanted to tailor these devices to do earlier detection of infectious diseases like COVID or influenza,” he said.
Commercialization
Sandia recently received a patent for a microneedle sensor that Polsky and his team are trying to commercialize.
“We basically will bring the diagnostic lab to the patient in the form of a wearable device,” he said.
Sandia partners with SRI International, Adaptyx Biosciences and the University of California-Berkley.
SRI is an independent nonprofit research institute of 1,500 researchers headquartered in Menlo Park, California, according to Will Brubaker of SRI. The company works with government and commercial customers to develop and transition emerging technologies and innovations out of the laboratory and to commercial use.
One of the projects with SRI has succeeded in significantly improving the extraction of interstitial fluid.
Engineers made changes to improve the extraction technique, including modifying the shape of the needle holders, which are 3D printed at Sandia’s Advanced Materials Laboratory.
“With microneedles, we have engineering and comfort concerns, which play into how we design them,” said Adam Bolotsky, a Sandia engineer. “We get feedback from participants as we’re updating the design. We believe we’ve found the optimal depth for collecting the most fluid with the least discomfort.”
Viral or bacterial?
Brubaker said improving the interstitial fluid extraction method helps potentially expand the use of microneedles.
“When we collect more
samples in a shorter amount of time, we can recruit more people to these kinds of studies,” Brubaker said. “The improvement in the collection method opens up a lot of doors to other applications.”
One such application involves using microneedles to distinguish between bacterial and viral infections. It’s another project that Sandia and SRI are collaborating on.
“Making a distinction as to whether an infection is bacterial or viral would help doctors make informed decisions much quicker to get you treated at the earliest possible stage,” Sandia’s Polsky said.
Brubaker said there’s still a lot that needs to be done before seeking FDA approval.
“There’s a very clear place where this test could eventually be used for the general public,” Brubaker said.
Sandia is also working with Adaptyx Biosciences under a Cooperative Research and Development Agreement.
“Adaptyx Biosciences is a biotechnology startup and Stanford University spinoff located in Menlo Park, Calif.,” said Alex Yoshikawa, co-founder of Adaptyx. “Adaptyx Biosciences is focused on commercializing innovative molecular sensing technologies.”
The company is hoping to get a better understanding of what biomarkers can be identified in interstitial fluid.
“We want to broadly understand the components in interstitial fluid and how those components correlate to blood measurements,” Yoshikawa said. “We’re leveraging Sandia’s existing technology for foundational physiological studies.”
As part of this collaboration, Sandia is extracting interstitial fluid on-site from volunteers using the improved method developed with SRI.
Adaptyx is working to develop continuous monitoring devices for general public use, Yoshikawa said.
And, with microneedle technology, the process has proven to be much easier than previous techniques.
“It’s much easier to recruit volunteers who only need to dedicate 15 minutes of their time versus two hours,” said Sandia’s Brittany Humphrey, who coordinates and oversees the extractions. “The extraction basically requires little to no work on their part.” Electrolyte sensors
Another Sandia partner is the University of CaliforniaBerkeley.
Their work on continuous electrolyte monitoring, similar to a wearable glucose meter, could help manage cardiovascular functions, hydration levels and electrolyte imbalances for a variety of conditions.
“Studying interstitial fluid is not easy,” Polsky said. “Sandia has made a mark in this area, and we are known as world leaders for this work. It’s turned into this interdepartmental collaborative effort with a lot of other people.
“You can actually see this in the market itself ... microneedles have gotten pretty advanced for the delivery of drugs and pharmaceuticals.”