Magnetic nano-probe explores the inside of human cells

Microscopic nano-probe device could be used to diagnose and treat cancer say researchers at the University of Toronto.

Robots that can manipulate individual cells are, surprisingly, not new. Those designed and built over the last 20 years by Professor Yu Sun’s lab at the University of Toronto, for example, have been used in a number of helpful procedures like in-vitro fertilisation and personalised diagnosis. The problem is that the applications have so far been limited.

Sun and his team hope to remedy this, having published a study in Science Robotics [1] that shows how they have been able to take their technology one giant micro-leap further: to the insides of the cell itself.

Longevity.Technology: Nanotechnology in medicine has been getter smaller, quicker and now has even greater control. Nano-bots that can be steered to where we want them to be, could be seen as the next new asset in medicine. With greater control comes greater precision and ultimately a more efficient way to understand and alter conditions in vivo.

The TRL score for this Longevity.Technology domain is currently set at: ‘Principles are demonstrated through experimentation.’
The TRL score for the technology addressed in this article is: ‘Principles are demonstrated through experimentation.’

“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 Professor Yu Sun [2]. “We wanted to deploy a robot in the building and probe all the rooms and structures.”

There are a handful of methods to probe live cells being used by scientists. Acoustic techniques create pressure waves that push nanobots into position but are often too imprecise for the measurements required. Lasers are also a popular recourse following the 2018 Nobel Prize, which pioneered the ‘optical tweezers’ method of manipulating tiny objects with light. The team’s problem with this, however, was that the force a laser beam generated was not large enough for the kinds of mechanical manipulation and measurement they wanted to perform. “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 Xian Wang [2], the PhD student who conducted the research. The simple fact is that the technique the team needed didn’t exist. So they invented one.

Their system uses a magnetic iron bead, measuring about 700nm (about one hundred times thinner than a human hair) in diameter. Once taken inside the cellular membrane of a live cancer cell, the bead is controlled by a system of six magnetic coils, which Wang uses alongside visual feedback from confocal microscopy imaging. The magnetic coils steer the bead, using computer inputs, by an algorithm that varies the electrical current through each of them, warping the magnetic field to channel the bead to any desired location within the cell.

Their technique turned out to not only be capable of more effective manipulation of nano-scale objects, but also of greater precision. “We can control the position to within a couple of hundred nano-meters down the Brownian motion limit,” says Wang. “We can exert forces an order of magnitude higher than would be possible with lasers.”

The team put their new technique to work in studying early to late-stage bladder cancer cells, whose nuclei they were able to study for the first time within the cell itself. In collaboration with Dr Helen McNeil and Yonit Tsatskis at Mount Sinai Hospital and Dr Sevan Hopyan at The Hospital for Sick Children, they were able to show that the cell nucleus is not equally stiff in all directions, alongside measuring how much stiffer it got when prodded. The team identified a list of proteins that were potentially responsible for this reaction, a preliminary result that could point the way towards new methods of cancer diagnosis.

“We know that in the later-stage cells, the stiffening response is not as strong,” says Wang. “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 Sun, the applications of their technology could go even further, into a realm previously only explored by science fiction. “You could imagine bringing in whole swarms of these nano-bots, and using them to either starve a tumour by blocking the blood vessels into the tumor, or destroy it directly via mechanical ablation,” says Sun. “This would offer a way to treat cancers that are resistant to chemotherapy, radiotherapy and immunotherapy.”

They are already in process of early animal experiments with Dr Xi Huang at The Hospital for Sick Children. “It’s not quite Fantastic Voyage yet,” he says, referencing the 1966 film about a microscopic voyage into the human body. “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!”