Scientists use nano or microneedles to provide quicker diagnosis of major illness.
Testing for diseases today typically involves analyzing signals in blood or urine. But methods for collecting these biological fluids can be relatively slow, ineffective, or painful. Now, scientists from Sandia National Laboratories and the University of New Mexico are leveraging a new medium for an easier, less invasive method of diagnostics: the extraction of dermal interstitial fluid, which is the gel that surrounds cells and ferries material between blood and tissue, with a new type of nano or microneedle.
Interstitial fluid is rife with biomarkers—glucose, lactose, salts, proteins, metabolites, and RNA. The researchers believe mining this biofluid could eventually give doctors a minimally invasive way to diagnose conditions like cancer or flu, potentially before a patient’s symptom arises.
“We think that it could actually be a very powerful, overlooked biofluid,” said team leader Ronen Polsky.
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In October, the team presented a proof-of-concept array of five microneedles, each only a few hair strands in diameter and roughly one mm (about the width of a penny) long. Because these needles do not penetrate very far into the skin, they are painless. In fact, patients could wear them all day and hardly notice their presence.
Interstitial fluid extraction has been tricky: its components are easily disrupted, and unlike blood or urine, it exists in tiny, hard-to-access areas.
While researchers have used microneedles to sample interstitial fluid before, this new array provides roughly four times the fluid volume that previous extractions have delivered. As a result, it offers many more diagnostic clues to analyze.
“In the past, it was really challenging to extract a volume larger than five microliters,” said Joseph Wang, the chair of the nanoengineering department at the University of California at San Diego. “Usually, that required special blistering or suction.”
Wang, who was not affiliated with this work, was impressed that this array delivers larger samples without external suction. More fluid is central to providing the kind of diagnostic oomph Polsky and his team are aiming for.
“If you just want to test glucose levels, you don’t need a large volume,” Wang said. To use RNA and protein levels to detect disease, samples need to be much larger, he said.
To draw larger samples, the research team deployed an array of five microneedles. Rather than use suction to draw the interstitial fluid, researchers mount the microneedles in a housing that strategically applies pressure to the surrounding tissue to coax the fluid into the needles.
The approach is similar to a process used to deliver glucose via microneedles, but in reverse. In fact, the researchers tried to use off-the-shelf glucose delivery microneedles. Unfortunately, they are surrounded by a hydrophobic coating that suppresses the capillary action needed to assist with the extraction.
To pull fluid into the needles, Polsky and his team 3D printed small circular cuffs for the needles to stand in. Because the housing applies pressure in a concentric ring around each microneedle, it essentially forces the fluid into the microneedle. An attached glass capillary tube collects fluid from the microneedle.
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So far, Polsky and his team have used this set-up to sample around 20 microliters of interstitial fluid from volunteers’ forearms. It takes about an hour or two with repeated draws from different spots.
Eventually, Polsky suggested, the technology might evolve into some kind of microneedle array attached to a self-contained cartridge. Patients could potentially administer a microneedle cartridge themselves and either send samples into a lab or insert the cartridge to a local detection device.
There are still many factors to optimize before commercialization, including needle density and array placement. In addition, next-generation diagnostics will require a better understanding of dermal interstitial fluid itself. As a first step, Polsky and his team have begun characterizing interstitial fluid biomolecules in rat models.
Meanwhile, they’re also working on incorporating sensors to measure electrolytes into the microneedle housing to take samples and receive instantaneous or continuous feedback from a patient. They’ve partnered with an Australian company, Microfluidics Biomedical, to develop this technology for diagnostics.
“We're starting with metabolites like glucose and lactate, and eventually we want to detect as many different classes of biomolecules as we can,” Polsky said.
As for other applied projects, tuning the needle arrays and sensors to detect influenza is high on Polsky’s list. But there are many more areas—from exercise physiology to agricultural plant monitoring—that could potentially benefit from this kind of microneedle sampling.
Menaka Wilhelm is an independent writer.
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