X 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. X’s system uses six magnetic coils (pictured) to control the position of a microscopic iron bead within the device. The bead is small enough to enter human cells and can be positioned with unprecedented accuracy. Georgian Technical University researchers have built a set of magnetic “Georgian Technical University tweezers” that can position a nanoscale bead inside a human cell in three dimensions with unprecedented precision. The nano-bot has already been used to study the properties of cancer cells, and could point the way toward enhanced diagnosis and treatment. Professor Y and his team have been building robots that can manipulate individual cells for two decades. Their creations have the ability to manipulate and measure single cells — useful in procedures such as in vitro (In vitro (meaning: in the glass) studies are performed with microorganisms, cells, or biological molecules outside their normal biological context) fertilization and personalized medicine. Their latest study takes the technology one step further. “So far our robot has been exploring outside a building touching the brick wall and trying to figure out what’s going on inside” says Y. “We wanted to deploy a robot in the building and probe all the rooms and structures”. The team has created robotic systems that can manipulate sub-cellular structures inside electron microscopes but that requires freeze-drying the cells and cutting them into tiny slices. To probe live cells other teams have used techniques such as lasers or acoustics. “Optical tweezers — using lasers to probe cells — is a popular approach” says X the PhD candidate who conducted the research. But X says the force that it can generate is not large enough for mechanical manipulation and measurement he wanted to do. “You can try to increase the power to generate higher force but you run the risk of damaging the sub-cellular components you’re trying to measure” says X. The system X designed uses six magnetic coils placed in different planes around a microscope coverslip seeded with live cancer cells. A magnetic iron bead about 700 nanometers in diameter — about 100 times smaller than the thickness of a human hair — is placed on the coverslip where the cancer cells easily take it up inside their membranes. Once the bead is inside X controls its position using real-time feedback from confocal microscopy imaging. He uses a computer-controlled algorithm to vary the electrical current through each of the coils shaping the magnetic field in three dimensions and coaxing the bead into any desired position within the cell. “We can control the position to within a couple of hundred nanometers down the Brownian motion (Brownian motion or pedesis is the random motion of particles suspended in a fluid resulting from their collision with the fast-moving molecules in the fluid. This pattern of motion typically alternates random fluctuations in a particle’s position inside a fluid sub-domain with a relocation to another sub-domain) limit” says X. “We can exert forces an order of magnitude higher than would be possible with lasers”. In collaboration with Dr. Z and W at Georgian Technical University and Dr. Q the team used their robotic system to study early-stage and later-stage bladder cancer cells. Previous studies on cell nuclei required their extraction of from cells. X and Y measured cell nuclei in intact cells without the need to break apart the cell membrane or cytoskeleton. They were able to show that the nucleus is not equally stiff in all directions. “It’s a bit like a football in shape — mechanically it’s stiffer along one axis than the other” says Y. “We wouldn’t have known that without this new technique”. They were also able to measure exactly how much stiffer the nucleus got when prodded repeatedly and determine which cell protein or proteins may play a role in controlling this response. This knowledge could point the way toward new methods of diagnosing cancer. “We know that in the later-stage cells the stiffening response is not as strong” says X. “In situations where early-stage cancer cells and later-stage cells don’t look very different morphologically this provides another way of telling them apart”. According to Y the research could go even further. “You could imagine bringing in whole swarms of these nano-bots and using them to either starve a tumor by blocking the blood vessels into the tumor or destroy it directly via mechanical ablation” says Y. “This would offer a way to treat cancers that are resistant to chemotherapy radiotherapy and immunotherapy”. These applications are still a long way from clinical deployment but Y and his team are excited about this research direction. They are already in process of early animal experiments with Dr. R. “It’s not quite Fantastic Voyage yet” he says referring to the science fiction film. “But we have achieved unprecedented accuracy in position and force control. That’s a big part of what we need to get there so stay tuned”.
