The University of Toronto engineering researchers have established a magnetic "scorpion" that can position nano-scale beads in three-dimensionally in human cells with unprecedented precision. Nanobots have been used to study the characteristics of cancer cells and can point to ways to enhance diagnosis and treatment.
Professor Yu Sun and his team have been building robots that can manipulate a single cell for twenty years. Their creation has the ability to manipulate and measure single cells – useful in procedures such as in vitro fertilization and personalized medicine. The latest research they published today in Science Robotics takes the technology one step further.
"So far, our robots have been exploring outside the building, touching brick walls and trying to figure out what's going on inside," Sun said. “We want to deploy robots in buildings and detect all rooms and structures.”
The team has created a robotic system that can manipulate subcellular structures within an electron microscope, but this requires freezing the cells and cutting them into small pieces. In order to detect live cells, other teams have used techniques such as laser or acoustics.
"Optical Tweezers – Using Lasers to Detect Cells – Is a Popular Approach," said Dr. Wang, the Ph.D. candidate responsible for the study. The technology won the Nobel Prize in Physics in 2018, but Wang said that the power it can produce is not enough for the mechanical manipulation and measurement he wants.
"You can try to increase your power to produce more power, but you may damage the subcellular components you are trying to measure," Wang said.
The system designed by Wang uses six magnetic coils placed on different planes around the microscope coverslip, which are filled with living cancer cells. Magnet beads about 700 nanometers in diameter – about 100 times smaller than the thickness of human hair – are placed on coverslips, which are easily absorbed by cancer cells into the membrane.
Once the beads are inside, the king uses real-time feedback from the confocal microscope to control its position. He uses a computer-controlled algorithm to change the current through each coil, shaping the three-dimensional magnetic field and introducing the magnetic beads into any desired location within the cell.
"We can control the position within a few hundred nanometers below the Brownian motion limit," Wang said. "We can apply a higher power than the laser."
The team worked with Dr. Helen McNeil and Dr. Yonit Tsatskis at the Mount Sinai Hospital and Dr. Sevan Hopyan from SickKids to study early and late stage bladder cancer cells using their robotic systems.
Previous studies on the nucleus required extraction from cells. Wang and Sun measure nuclei in intact cells without destroying the cell membrane or cytoskeleton. They can prove that the nucleus is not as stiff in all directions.
"It's a bit like the shape of a football – mechanically, it's harder along one axis than the other," Sun said. "If there is no such new technology, we will not know."
They are also able to accurately measure the hardness of the nucleus after repeated stimulation of the nucleus and determine which cellular proteins may play a role in controlling this response. This knowledge can point the way to new ways of diagnosing cancer.
"We know that in late cells, the stiff response is not strong," Wang said. "In the case where early cancer cells and late cells look different in morphology, this provides another way to distinguish them."
According to Sun, the study may go a step further.
"You can imagine bringing in a large number of these nanobots and using them to starve the tumor by blocking blood vessels from entering the tumor, or destroy it directly by mechanical ablation," Sun said. "This will provide a way to treat cancers that are resistant to chemotherapy, radiation and immunotherapy."
These applications have a long way to go before clinical deployment, but Sun and his team are excited about this research direction. They have conducted early animal experiments with Dr. Huang Wei of SickKids.
"This is not a very magical voyage," he said, referring to the 1966 science fiction movie. “But we have achieved unprecedented accuracy in position and power control. This is a big part of what we need to achieve our goals, so stay tuned!”
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