Acoustic tweezers that manipulate cells could enable personalized cancer therapies

Mechanical engineers at Duke University are using two electronic “voices” singing a harmonic duet to control airborne particles and cells in new and valuable ways. Their prototype device can form and rotate a single-layer crystal from a group of particles, create arbitrary shapes with a given number of particles, and move pairs of biological cells together and back again hundreds of times.

These capabilities could serve a wide variety of fields, such as materials science, soft condensed matter physics, biophysics, life sciences, and medicine.

For example, the researchers showed that the device can selectively pair two individual cells and measure their adhesive strengths – a feat that doctors could use to determine treatment for cancer patients. Because of the dexterity and softness of the acoustic device, the researchers named it the HANDS platform. (Harmonic acoustics for non-contact, dynamic and selective particle manipulation.)

The results appear online March 24 in the journal Natural materials.

“The separation of paired particles or cells has been a major goal in the field of acoustic manipulation for many years,” said Tony Jun Huang, William Bevan Professor Emeritus of Mechanical Engineering and Materials Science at Duke. “Our HANDS platform is the first paired-object separation method, paving the way for cell-cell interaction studies that are widely needed in biophysics studies and drug discovery.”

Acoustic tweezers are a rapidly developing field that uses various sound wave physical phenomena to gently manipulate particles or cells suspended in liquids without touching them. Some examples pinch particles between two sound waves and adjust the phase or point of origin of the waves to move them. Others create patterns by combining two static standing sound waves to separate the particles into different formations, like a grid.

Now, researchers have added a new layer of complexity to these devices by introducing piezo melodies and harmonies into the setup. Where previous devices created static standing waves, the prototype HANDS platform uses a function generator to create complex standing waves that change rapidly. You would think that, rather than the machines singing a single note, they are now hitting the rapid ups and downs of a complicated opera with two singers.

The new device works by placing sound-creating transducers on either side of a small square chamber filled with liquid. These four transducers work in step with those directly facing them, forming two pairs. One creates patterns in the room horizontally and the other vertically. The interplay of these two complex and rapidly changing sound wave patterns creates dynamic capabilities never before demonstrated in the field.

“I simulated how these waves might combine to manipulate the particles in the chamber, and then conducted experiments to see the actual results,” said Shujie Yang, postdoctoral associate at the Huang lab. “It took a long time and a lot of trials, but eventually the simulations got good enough to start matching the results. And once the simulations were accurate, I could start predicting new abilities.

In the article, Yang demonstrates several new capabilities of the Harmonic Duo Acoustic Tweezers. In an experiment, he shows that the HANDS platform can flatten and mold a 3D cluster of 24 particles into a crystalline structure. He can spin those flat formations like a plate on his fingertips.

Moving on to the manipulation of individual particles, the article shows coaxed particles into three different formations bearing a striking resemblance to the letters O, D and K. The device then combines dozens of single particles like teenagers in a dance school and shows he can pull each pair and wind them over a thousand times.

In the final demonstration, Yang shows that the device can select a single pair of cells in an alignment, bring them together and pull them apart. He then uses this ability to measure the adhesive forces at work between two cells that touch each other.

According to the researchers, this is the most exciting capability of the HANDS platform, as it could enable detailed testing for personalized medicine.

“I’m thrilled with the capabilities of this platform, which is as gentle as a mother’s hands,” said Luke Lee, professor of medicine at Harvard Medical School, co-lead of the research. “Mother’s soft, sensitive hands allow us to lay the foundations for quantitative cell biology and translational precision medicine.”

“For example, we can systematically study T cell interactions with cancer cells at high throughput and obtain precision cell-cell interaction strengths,” Lee said. “It could help doctors find the most effective and patient-specific cell therapy as personalized precision medicine.”

Reference: Yang S, Tian Z, Wang Z, et al. Harmonic acoustics for dynamic and selective particle manipulation. Nat Mater. 2022:1-7. doi: 10.1038/s41563-022-01210-8

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