If you go canoeing through rapids, you’ve encountered standing waves—spots where the flow of water off various rocks and impediments creates diffraction patterns among the waves formed by the obstacles. A standing wave is a wave shape that stays in one place even though the water creating it continues to flow. If the standing wave is strong enough, it changes the direction of your canoe when you run up against it.
Tony Jun Huang, professor of materials science and mechanical engineering in the Pratt School of Engineering, is part of an international team that has created a device that uses the same principle to quickly, gently, and inexpensively sort tiny particles in fluids like blood, urine, saliva, and even breast milk. It uses sound to create standing waves, which sort particles in a fluid, moving them differently based on characteristics like size and density. Combining the fields of microfluidics and acoustics, Huang says, the nascent field is called acoustofluidics.
The group’s current research focuses on exosomes, particles on the scale of 100 nanometers—in the neighborhood of one five-hundredth the thickness of a human hair—secreted by virtually all cells. Exosomes facilitate intercell communication by transferring RNA and proteins, which carry information about cells and health. “By separating them and doing analysis of the proteins, you can get a lot of information,” Huang says. “Exosomes have been identified as a potentially transformative circulating biomarker for the diagnosis and prognosis of multiple diseases.” But it’s almost impossible to find exosomes from specific cell types; even a few drops of blood contain billions of cells and particles.
So how to isolate exosomes from the greater chaos? Currently most labs use a centrifuge, which requires highly trained staff and a lot of time. Plus, the force of all that spinning can damage the very exosomes you’re looking for.
Enter acoustofluidics. Using the device Huang and his team (including scientists from MIT, the University of Pittsburgh, and other institutions) have designed, a nurse will be able to draw a blood sample and feed it into a very small device—the components Huang brought out of an office cabinet to demonstrate fit neatly into a petri dish. The first of two pairs of tiny interdigital transducers creates a standing wave that separates out larger objects 1 micrometer or larger—red and white blood cells, for example. The second pair of interdigital transducers, working at a different wavelength, pushes objects smaller than 130 nanometers (like exosomes) into a separate channel. Not only are the exosomes chemically and physically unchanged by the procedure; the device yields samples with a yield of greater than 80 percent of the pre-separation exosome population, far higher than the purity yielded by centrifuges, which can be as low as 5 to 25 percent.
The inspiration for this approach was ultrasound. “Ultrasonic imaging is not the most powerful or the most high-resolution,” Huang says, but it is compact and inexpensive—and more, “it’s very gentle. We use it to monitor the health of pregnant mothers.” Acoustofluidics uses similar power intensities and wavelengths and is just as gentle. Plus looking for markers in cells in bodily fluids obviates the need for needles or other invasive procedures on, say, the placenta. Since placental exosomes will show up in the mother’s bloodstream, you can look for markers of placental problems by doing nothing more complex than taking a blood sample from the mother and using the device. Exosomes with markers for cancer, Alzheimer’s disease, and Parkinson’s disease are other candidates for pursuit, possibly enabling doctors to diagnose those conditions long before they show up clinically, allowing patient care to start far earlier.
The technology Huang is working on has great promise. “It’s noninvasive,” he says. “It can be very compact, very inexpensive, and very point-of-care.” And if the tiny people from Fantastic Voyage show up in someone’s bloodstream, they can have some fun canoeing.