Self-powered microneedle patch offers blood-free biomarker monitoring

Researchers have developed a self-powered microneedle patch to monitor a range of health biomarkers without drawing blood or relying on batteries or external devices. In proof-of-concept testing with synthetic skin, the researchers demonstrated that the patches could collect biomarker samples over periods ranging from 15 minutes to 24 hours.

"Biomarkers are measurable indicators of biological processes, which can help us monitor health and diagnose medical conditions," says Michael Daniele, corresponding author of a paper on the work. "The vast majority of conventional biomarker testing relies on taking blood samples. In addition to being unpleasant for most people, blood samples also pose challenges for health professionals and technology developers. That's because blood is a complex system, and you need to remove the platelets, red blood cells, and so on before you can test the relevant fluid.

"The patch we've developed uses microneedles to sample the fluid that surrounds cells in the dermal and epidermal layers just below the very top layer of cells that make up your skin," says Daniele, who is a professor of electrical engineering at NC State and in the Lampe Joint Department of Biomedical Engineering at NC State and the University of North Carolina at Chapel Hill. "This is called dermal interstitial fluid (ISF), and it contains almost all of the same biomarkers found in blood. What's more, ISF makes for a 'cleaner' sample - it doesn't need to be processed the way blood does before you can test it. Essentially, it streamlines the biomarker testing process."

Specifically, Daniele and his collaborators have made a fully passive microneedle patch that doesn't rely on either batteries or external energy sources to take or store ISF samples. Here's how it works.

The patch consists of four layers: a polymer "housing" - which is effectively the part of the patch you can see; a layer of gel; a layer of paper; and the microneedles themselves. The microneedles are made of a material that swells when it touches the ISF. The ISF wicks through the microneedle - like water through a paper towel - until it comes into contact with the paper. As the paper begins absorbing the ISF, the fluid comes into contact with the gel that is on the other side of the paper. That gel contains a high concentration of glycerol. The imbalance of glycerol between the gel and the ISF creates osmotic pressure that pulls more ISF through the paper until the paper is saturated.

The paper is where the ISF is stored. When you take the patch off, you remove the paper strip and analyze the sample."

Michael Daniele, professor of electrical engineering, NC State

The researchers tested the patch on two synthetic skin models.

"It worked well," Daniele says. "The patches collected measurable results in as little as 15 minutes and were capable of storing the biomarker samples for at least 24 hours."

For the proof-of-concept testing, the researchers monitored for cortisol - which is a biomarker for stress that fluctuates over the course of the day.

"That means it's something people may want to monitor multiple times a day without having to draw blood repeatedly," Daniele says. "And there's no reason the patch wouldn't work for many of the biomarkers found in ISF."

Another attractive aspect of the patches is that they're made from relatively inexpensive materials that are widely available.

"The highest cost of the patches would be manufacturing the microneedles, but we think the price would be competitive with the costs associated with blood testing," Daniele says. "Drawing blood requires vials, needles and - usually - a phlebotomist. The patch doesn't require any of those things."

The researchers have already begun human testing with the patches and are developing electronic devices to "read" the paper strip from the microneedle patch.

"We've already developed an electronic device that can 'read' cortisol levels from the paper strip and are working on another device that evaluates a different biomarker," Daniele says.

"We're now looking for industry partners on two fronts. We'd love to talk with companies in the diagnostic space to explore additional applications, and we'd also like to talk with potential partners about scaling up production."

The paper, "Design and Characterization of a Self-Powered Microneedle Microfluidic System for Interstitial Fluid Sampling," is published open access in the journal Lab on a Chip. Co-lead authors are Christopher Sharkey, a Ph.D. student at NC State; Angélica Aroche, a Ph.D. student in the Lampe Joint Department of Biomedical Engineering at NC State and the University of North Carolina at Chapel Hill; and Isabella Agusta, an undergraduate in the joint biomedical engineering department. Co-authors are Hannah Nissan, a graduate student at NC State; Tamoghna Saha and Sneha Mukherjee, former Ph.D. students at NC State; Michael Dickey, Camille and Henry Dreyfus Professor of Chemical and Biomolecular Engineering at NC State; Orlin Velev, S. Frank and Doris Culberson Distinguished Professor of Chemical and Biomolecular Engineering at NC State; and Jack Twiddy, a postdoctoral researcher in the joint biomedical engineering department.

This work was done with support from the National Science Foundation's Center for Advanced Self-Powered Systems of Sensors and Technologies (ASSIST), the NC State Institute for Connected Sensor-Systems, the Chancellor's Innovation Fund at NC State, and SEMI-NBMC under grants NB18-21-26 and NB18-24-38.

Daniele is an officer and founder of DermiSense, Inc. (Cary, NC), which commercializes microneedle-based technologies.