Hypersonic Levitation Spinning Speeds Cell Isolation

Many of the most devastating diseases are similar black boxes science. Majority Cancer deaths, for example, are caused by the strain of the disease spreading throughout the body, fueled by the few tumor cells that can survive the journey to different parts of the body and form new growths. But biologists know relatively little about how these aggressive cells function, making it difficult to understand cancer progression and persistence.

Oncology is not the only field seeking valuable information about individual rare cells. Areas include developmental biology, immunology, stem cell biology, neurobiologyAnd infectious disease all require studying individual cells. By looking at cells individually rather than in groups, researchers can reveal their genetic structure and unique behavior, observing subtle but influential traits that would otherwise be hidden.

The key to breakthroughs in all these areas, experts say, is clear: improving single-cell sequencing technology.

To study rare cells, researchers need to separate individual cells from large clumps of human tissue, but this compromises the viability of the very cells they hope to analyze. Current cell isolation technologies often do this by sawing small pieces off a larger piece of tissue with a scalpel or razor, potentially damaging the cells and making them impossible to study properly. Other methods use enzymes to isolate cells, but these procedures are time-consuming and can compromise the beneficial properties of the cells. “And for rare cell types, every little loss matters,” says Katalin Sushtakwho studies chronic kidney disease at the University of Pennsylvania.

Hypersonic levitation in cellular isolation

A new method for isolating and suspending cells called hypersonic levitation and rotation (HLS), relies on acoustic resonators And microelectromechanical systems (MEMS) technologies that will lead to breakthroughs in biology. Group from Tianjin University China The person responsible for its development discovered that the tool was able to isolate more cells in significantly less time than traditional methods.

HLS uses a metal probe to transmit billions of vibrations per second into the water mixture surrounding human cancer tissue in a research laboratory. The resulting “jets of liquid” separate one cancer cell from thousands of others in a piece of tissue, and this is a completely non-contact process. The cell is held in place by fluid jets—suspended in the fluid but can rotate at any angle—allowing for full visual analysis from all angles using advanced technology. microscopy.

Xuexin Duanleading the team from Tianjin University, and his colleagues set out to invent a tool that would not only reduce the threat to cells during the isolation process, but also speed up the entire process. They started by considering the fact that living cells usually surrounded by water. “We asked: Can we use a finely tuned physical field within the liquid itself to act like a gentle invisible hand?” – says Duan.

They came up with a small high-frequency Ultrasound a probe that uses three MEMS-based resonators to vibrate tissue in a solution of water and enzymes. When the device is turned on, a signal generated at 2.49 gigahertz alerts the circuit board to send high frequency voltage. As soon as the voltage reaches MEMS resonators, reverse piezoelectric effect triggers, causing billions of vibrations per second that generate acoustic waves in the surrounding fluid.

Reflector under each resonator reflects the waves in a specific pattern, causing the water-enzyme mixture to quickly flow and spin, creating jets of liquid powerful enough to remove a single cell from a lump of tissue, but gentle enough to do so without worsening the condition. Once the cell is isolated, the same acoustic mechanisms allow it to float and rotate freely in the fluid.

While much of the design is unique, the HLS is more of an improvement than a completely new device. “This levitation method has been used before for other types of work,” says Z. Hui Fengbiomedical MEMS and microfluidics researcher at the University of Florida. He says a healthy lifestyle “is an improvement, not a drastic change.” Still, Fan believes the tool shows serious potential.

Researchers from Tianjin University tested their device on human kidney cancer tissue samples. Using HLS, the team was able to isolate 90 percent of the cells in 15 minutes, but with conventional methods they could only do the same with 70 percent of the cells in an hour. HLS works so well because it helps enzymes penetrate tissue and break down cells “without the need for harsh mechanical grinding or prolonged exposure to enzymes,” Duan says.

Concerns about HLS in single-cell research

Penn State's Sushtak's biggest concern is that HLS may pose a threat to cells sensitive to high frequencies. “Even small variations make a difference when working with individual cells,” she says. “Will acoustic fields disrupt cell biochemistry?”

Duan is confident that his team's design is safe for fragile cells because they are subjected to a controlled force rather than a harsh acoustic wave, he says. “This intense force field is confined to the fluid and not directly to the cell.”

External experts have more concerns about implementation. Sushtak notes that “biology labs are unforgiving,” so research instruments must be robust and reliable, and in-liquid MEMS devices tend to face drift and calibration issues. Cost and ease of access are concerns for Fan, although he believes both issues can be addressed through business efforts. “How mainstream it becomes really depends on commercialization,” he says.

For these reasons and more, Duan says his team turned HLS into a startup company, Convergency Biotech, with the goal of developing HLS workstations convenient enough for any lab. And he is optimistic about the enterprise. “We believe that MEMS-based acoustic instruments will become a major component of biological instrumentation,” he says.

Single-cell researchers show similar optimism, but with caution. Sushtak believes HLS is “a smart and promising tool,” she says, “but it needs to prove itself in the messy world of real-world biology.”