“Virtual pillars” separate and sort blood-based nanoparticles
A graphical representation of the sound wave forces at work that create “virtual pillars” to gently separate and sort nanoparticles from biofluids. Credit: Jinxin Zhang, Duke University

A device that uses sound waves to separate and sort tiny particles in blood has been developed by engineers at Duke University. Both scientific research and medical applications could benefit from the technology.

Small biological particles called sEVs are released from every cell in the body and are thought to play a large role in cell-to-cell communication and disease transmission. The new technology, dubbed AcousticNanoscale Separation via Wavepillar- Excitation Resonance, or ANSWER for short, pulls these particles from biofluids in under 10 minutes and sorts them into size categories believed to have distinct biological roles.

The results were published in the journal.

"These nanoparticles have significant potential in medical diagnosis and treatment, but the current technologies for separating and sorting them take several hours or days, are inconsistent, produce low yield or purity, suffer from contamination and sometimes damage the nanoparticles," said Tony Jun Huang, the William Bevan distinguished professor of mechanical engineering

"We want to make it easy to extract and sort high-quality sEVs by pushing a button and getting the desired samples faster than taking a shower," he said.

A single sound wave creates a series of “virtual pillars” down the middle of a fluid-filled channel, gently moving nanoparticles within to the side. The technology can separate and sort medically important nanoparticles from biofluids, which could be used to detect diseases such as cancer or Alzheimer's disease. Credit: Jinxin Zhang, Duke University

Recent research shows that sEVs are made up of several different groups with different sizes. The size is thought to have different properties.

The recent discovery of sEV subpopulations has excited researchers because of their potential to change the field of non-invasive diagnostics. The particles haven't been used in clinical settings.

The difficulties associated with isolating the sEV subpopulations is the main reason for this. The ANSWER platform was developed by Huang and his students at UCLA and Harvard.

A standing sound wave can be generated by a single pair of transducers. The standing sound wave interacts with the leaking sound wave through the channel walls. The resonance that forms along the center of the channel is created by the careful design of the wall thickness, channel size and sound frequencies.

A half-egg shaped region of high pressure is what each of these virtual pillars is made of. Particles are pushed toward the edges of the channel as they try to cross over the pillars. The push is bigger when the particles are larger. By tuning the series of virtual pillars to create nuanced forces on the traveling nanoparticles, the researchers can sort them by size into different groups.

Watch as a single sound wave creates a series of “virtual pillars” down the middle of a fluid-filled channel. Credit: Jinxin Zhang, Duke University

The ANSWER EV fractionation technology is the most advanced that can be used for precise EV fractionation.

In the new paper, the researchers show that the ANSWER platform can sort sEVs into three different groups with 98% accuracy for the smallest particles. The number of groupings and ranges of sizes are adjusted with simple updates to the sound wave parameters. Ultra-centrifugation can take hours or days, whereas each of the experiments only took 10 minutes.

ANSWER's contact-free nature makes it a good choice for the separation of biological nanoparticles. "I said so." The cutoff diameter of ANSWER can be changed by varying the input acoustic power.

The ANSWER technology will continue to be improved so that it can be used to purify other biologically relevant particles.

There is a solution to the biophysical fractionation of extracellular vesicles. There is a book titled "Sci Adv.ade0640."

Journal information: Science Advances