Quick ‘lab on a chip’ won’t mangle fragile cells

"With the gentle nature of low-power acoustic waves, I believe that our device has the best chance of preserving cell integrity, even for fragile, sensitive cells," says Tony Jun Huang. (Credit: "grip" via Shutterstock)

A new cell sorter based on acoustic waves—an inexpensive lab on a chip—can compete with existing fluorescence-activated cell sorters.

“The current benchtop cell sorters are too expensive, too unsafe, and too high-maintenance,” says Tony Jun Huang, professor of engineering science and mechanics at Penn State. “More importantly, they have very low biocompatibility.

“The cell-sorting process can reduce cell viability and functions by 30 to 99 percent for many fragile or sensitive cells such as neurons, stem cells, liver cells and sperm cells. We are developing an acoustic cell sorter that has the potential to address all these problems.”

Over the past decade, microfluidic cell sorters have emerged as a promising new tool for single cell sequencing, rare cell isolation, and drug screening. However, many of these microfluidic devices operate at only a few hundred cells per second, far too slow to compete with commercial devices that operate on the order of tens of thousands of operations per second.

The new system can sort about 3,000 cells per second, with the potential to sort more than 13,000 cells per second.

acoustic cell sorter
Above, the illustration depicts blood components being separated by sound waves. (Credit: Tony Jun Huang/Penn State)

Fragile cells

The researchers achieve the speed by using focused interdigital transducers to create standing surface acoustic waves. When the waves are not focused, the acoustic field spreads out, slowing the sorting process. The narrow field allows the sorting to take place at high speed while gently manipulating individual cells.

“The acoustic power intensity and frequency used in our device are in a similar range as those used in ultrasonic imaging, which has proven to be extremely safe for health monitoring, even during various stages of pregnancy,” says Huang.

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“With the gentle nature of low-power acoustic waves, I believe that our device has the best chance of preserving cell integrity, even for fragile, sensitive cells. Such an ability is important for numerous applications such as animal reproduction, cell immunotherapy, and biological research.”

The size of a cell phone

Because the device is built on a lab-on-a chip system, it is both compact and inexpensive—about the size and cost of a cell phone in its current configuration. With the addition of optics, the device would still be only as large as a book. The researchers fabricated the acoustic cell sorter in Penn State’s Nanofabrication Laboratory using standard lithography techniques.

“The focused acoustic waves have shown better performance in terms of sorting resolution and energy-efficiency than the existing acoustic methods,”says Liqiang Ren, a graduate student in Huang’s group. “To the best of our knowledge, our device demonstrates the fastest operation time among all existing acoustic cell sorters.”

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“Cell sorting is widely used in many areas of biology to characterize and separate cellular populations of interest,” says Philip McCoy of the National Heart, Lung, and Blood Institute. “The cytometer size, price, and biohazard concerns remain factors that have prevented this technology from being even more widespread.

“Microfluidic cell sorting is revolutionary for the fields of cell biology and immunology, as well as other fields in biology, in concomitantly overcoming all of these obstacles. It is quite easy to envision applications for this technology in diverse environments from a family doctor’s office to field studies in limnology.”

In future work, the researchers plan to integrate their acoustic cell-sorting unit with an optical cell-detecting unit with the goal of increasing throughput to 10,000 events per second.

The researchers, who are from Penn State, Ascent Bio-Nano Technologies, and the National Heart, Lung and Blood Institute of the National Institutes of Health, report their work in the journal Lab on a Chip.

The National Institutes of Health, the National Science Foundation, and the Penn State Center for Nanoscale Science supported this work. Portions of the work took place at the Penn State Nanofabrication Laboratory, a node of the NSF-funded National Nanotechnology Infrastructure Network.

Source: Penn State