MIT Team Develops Mechanical Stimulation Technology
by James Cavuoto, editor
September 2020 issue
In recent issues of this publication, we have described a number of alternatives to electrical stimulation as potential neuromodulation modalities, including optical, magnetoelectric, ultrasonic, and iontronic technologies. Recently a team of researchers at MIT has developed a new technique that involves mechanical stimulation.
Neural cells are known to respond to mechanical effects, such as pressure or vibration. But these responses have been more difficult for researchers to study, because there has been no easily controllable method for inducing such mechanical stimulation of the cells. Unlike electrical stimulation systems, which require an external wire connection, the new system would be completely contact-free after an initial injection of particles, and could be reactivated at will through an externally applied magnetic field.
The finding was reported in the journal ACS Nano, in a paper by former MIT postdoc Danijela Gregurec, Alexander Senko, associate professor Polina Anikeeva, and nine others at MIT, at Boston’s Brigham and Women’s Hospital, and in Spain. This mechanical stimulation, which activates entirely different signaling pathways within the neurons themselves, could provide a significant area of study, the researchers say. They targeted a group of neurons within the dorsal root ganglion, which forms an interface between the central and peripheral nervous systems, because these cells are particularly sensitive to mechanical forces.
The applications of the technique could be similar to those being developed in the field of bioelectronic medicine, Senko said, but those require electrodes that are typically much bigger and stiffer than the neurons being stimulated, limiting their precision and sometimes damaging cells.
The key to the new process was developing minuscule discs with an unusual magnetic property, which can cause them to start fluttering when subjected to a certain kind of varying magnetic field. Though the particles themselves are only 100 or so nanometers across, roughly a hundredth of the size of the neurons they are trying to stimulate, they can be made and injected in great quantities, so that collectively their effect is strong enough to activate the cell’s pressure receptors. “We made nanoparticles that actually produce forces that cells can detect and respond to,” Senko said.
Anikeeva said that conventional magnetic nanoparticles would have required impractically large magnetic fields to be activated, so finding materials that could provide sufficient force with just moderate magnetic activation was “a very hard problem.” The solution proved to be a new kind of magnetic nanodiscs.
These discs, which are hundreds of nanometers in diameter, contain a vortex configuration of atomic spins when there are no external magnetic fields applied. This makes the particles behave as if they were not magnetic at all, making them exceptionally stable in solutions. When these discs are subjected to a very weak varying magnetic field of a few millitesla, with a low frequency of just several hertz, they switch to a state where the internal spins are all aligned in the disc plane. This allows these nanodiscs to act as levers—wiggling up and down with the direction of the field.
The team first considered using particles of a magnetic metal alloy that could provide the necessary forces, but these were not biocompatible materials, and they were prohibitively expensive. The researchers found a way to use particles made from hematite, a benign iron oxide, which can form the required disc shapes. The hematite was then converted into magnetite, which has the magnetic properties they needed and is known to be benign in the body.