Engineers have built microrobots to perform all sorts of tasks in the body, and can now add to that list another key skill: delivering stem cells. In a paper published today in Science Robotics, researchers describe propelling a magnetically-controlled, stem-cell-carrying bot through a live mouse.
Under a rotating magnetic field, the microrobots moved with rolling and corkscrew-style locomotion. The researchers, led by Hongsoo Choi and his team at the Daegu Gyeongbuk Institute of Science & Technology (DGIST), in South Korea, also demonstrated their bot’s moves in slices of mouse brain, in blood vessels isolated from rat brains, and in a multi-organ-on-a chip.
The invention provides an alternative way to deliver stem cells, which are increasingly important in medicine. Such cells can be coaxed into becoming nearly any kind of cell, making them great candidates for treating neurodegenerative disorders such as Alzheimer’s.
But delivering stem cells typically requires an injection with a needle, which lowers the survival rate of the stem cells, and limits their reach in the body. Microrobots, however, have the potential to deliver stem cells to precise, hard-to-reach areas, with less damage to surrounding tissue, and better survival rates, says Jin-young Kim, a principle investigator at DGIST-ETH Microrobotics Research Center, and an author on the paper.
The virtues of microrobots have inspired several research groups to propose and test different designs in simple conditions, such as microfluidic channels and other static environments. A group out of Hong Kong last year described a burr-shaped bot that carried cells through live, transparent zebrafish.
The new research presents a magnetically-actuated microrobot that successfully carried stem cells through a live mouse. In additional experiments, the cells, which had differentiated into brain cells such as astrocytes, oligodendrocytes, and neurons, transferred to microtissues on the multi-organ-on-a-chip. Taken together, the proof-of-concept experiments demonstrate the potential for microrobots to be used in human stem cell therapy, says Kim.
The team fabricated the robots with 3D laser lithography, and designed them in two shapes: spherical and helical. Using a rotating magnetic field, the scientists navigated the spherical-shaped bots with a rolling motion, and the helical bots with a corkscrew motion. These styles of locomotion proved more efficient than that from a simple pulling force, and were more suitable for use in biological fluids, the scientists reported.
The big challenge in navigating microbots in a live animal (or human body) is being able to see them in real time. Imaging with fMRI doesn’t work, because the magnetic fields interfere with the system. “To precisely control microbots in vivo, it is important to actually see them as they move,” the authors wrote in their paper.
That wasn’t possible during experiments in a live mouse, so the researchers had to check the location of the microrobots before and after the experiments using an optical tomography system called IVIS. They also had to resort to using a pulling force with a permanent magnet to navigate the microrobots inside the mouse, due to the limitations of the IVIS system.
Kim says he and his colleagues are developing imaging systems that will enable them to view in real time the locomotion of their microrobots in live animals.