Nano-Sized Bot Can Probe Inside Human Cells

Researchers at the University of Toronto have developed a nano-sized bot that can probe directly inside human cells to further cancer and other disease research and treatments.

Scientists have already developed technology on the nano-scale for exploring and treating conditions inside the human body. Now researchers have taken this to the next level with the development of technology that can place a nano-scaled robot inside a actual human cell for more targeted diagnosis and treatment of cancer and other diseases.

A team of engineers at the University of Toronto engineers developed a set of magnetic “tweezers” that can position a nano-bot inside a human cell in three dimensions with unprecedented precision, said Xian Wang, a PhD candidate who primarily conducted the research.

Xian Wang, a PhD candidate at the University of Toronto, has developed a magnetic nano-scale robot that can be moved anywhere inside a human cell. The tool could be used to study cancer and potentially enhance its diagnosis and treatment. (Image source: Tyler Irving, University of Toronto)

Building Robots for 20 Years

Researchers at the university have already have been building robots that can manipulate individual cells for about 20 years under the direction of Professor Yu Sun, who oversaw Wang’s work. These creations have the ability to manipulate and measure single cells, which is useful in procedures such as in vitro fertilization and personalized medicine.

With the latest technology researchers can now work inside the cell itself rather than merely move cells around and work with them, Wang told Design News.

“The capability of achieving sub-micron resolution position control and pico-Newton force control on a submicron diameter magnetic bead is new, making the system capable of performing intracellular measurements and manipulation,” he said.

Magnetic Tweezers

The specific technology the team developed comes in the form of a set of magnetic tweezers comprised of 6 magnetic coils with sharp poles, Wang explained. When electric current is applied to each of the coils, it generates a magnetic gradient field, he said.

“A magnetic bead with a sub-micrometer diameter is internalized into the cell through endocytosis,” Wang said. “The bead position and magnetic force on the bead are controlled through controlling the six electric current inputs to the magnetic tweezers device.”

Once the nano-bot is inside a cell, Wang controlled its position using real-time feedback from confocal microscopy imaging. He also used a computer-controlled algorithm to vary the electrical current through each of the coils, shaping the magnetic field in three dimensions and coaxing the bot into any desired position within the cell.

Measurements Directly Inside the Cell

This is significant because now researchers can measure the properties of organelles and intracellular structures, which play important roles in regulating cell functions, and are related to diseases, Wang told us.

“Directly measuring and manipulating intracellular structures inside single cells would help better understanding of subcellular and organelle level activities, diagnosing diseases, and development of new therapeutic approaches,” he said.

Wang used the example of the cell nucleus, which is biggest organelle—or cellular structure performing a specific function—found inside the cell. In his example, he described how the nucleus shows altered mechanical properties in cancer cells.

“Directly interrogating the mechanical properties of the cell nucleus inside single cells would help understand the differences between the diseased and healthy cells,” he explained.

Previously, to study cell nuclei required their extraction of from cells, Wang said. Using their invention, Wang and Sun measured cell nuclei in intact cells without the need to break apart the cell membrane or cytoskeleton, demonstrating that the nucleus is not equally stiff in all directions. This is significant for future cancer research, Wang told us.

Practical Applications

“Our data revealed that the cell nucleus stiffens after repeated mechanical loading,” he explained. “The results also showed that the early-stage bladder cancer cells exhibit stronger stiffening effects than late-stage bladder cancer cells. During cancer metastasis, the cell needs to squeeze through tiny space in vivo, and subjects to repeated mechanical force loading.”

What researchers demonstrated in their results then, is that the nucleus of early-stage cancer cells stiffens after subject to force, which may prevent them from further traveling and metastasis, Wang said. The late-stage cancer cells, however, do not stiffen much after force stimulation, making it easier for them to continue the invasion path, he said. Researchers published a paper on their work in the journal Science Robotics.

While the team has a long way to go before the technology can be used on human patients, they plan to continue their research to explore its use for cancer diagnostics, with animal experiments to follow soon, Wang said.

“The capability of high-precision position and force control gained in this work is being used to pursue diagnostics by using swarms of sub-micrometer magnetic beads, and developing new tumor surgical approaches by triggering apoptosis by magnetic force application,” he said. 

Elizabeth Montalbano is a freelance writer who has written about technology and culture for more than 20 years. She has lived and worked as a professional journalist in Phoenix, San Francisco and New York City. In her free time she enjoys surfing, traveling, music, yoga and cooking. She currently resides in a village on the southwest coast of Portugal.

 

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