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Humans have long dreamed of melding electronics and machines with the body, but this usually trends toward the realm of science fiction: computer chips in the brain, bionic sight, robotic limbs and the like. We're a long way from this cyborg future, but research on electronic interfaces with the body that can diagnose and treat disease is already underway, and they're a lot smaller than you think.
In a paper published Friday, December 16, in the journal Science Advances, scientists from the University of Chicago describe how silicon nanowires, microscopic snippets of the same material used for computer chips, can be embedded inside individual cells. Once inside, the nanowires can be stimulated to take measurements, manipulate internal components of the cell, or deliver drugs and genetic therapies.
"You can treat it as a non-genetic, synthetic biology platform," said Bozhi Tian, PhD, assistant professor of chemistry and senior author of the new study. "Traditionally in biology we use genetic engineering and modify genetic parts. Now we can use silicon parts, and silicon can be internalized. You can target those silicon parts to specific parts of the cell and modulate that behavior with light."
In the new study, Tian and his team show how cells consume or internalize the nanowires through phagocytosis, the same process they use to engulf and ingest nutrients and other particles in their environment. The nanowires are simply added to cell media, the liquid solution the cells live in, the same way you might administer a drug, and the cells take it from there. Eventually, the goal would be to inject them into the bloodstream or package them into a pill.
Once inside, the nanowires can interact directly with individual parts of the cell, organelles like the mitochondria, nucleus and cytoskeletal filaments. Researchers can then stimulate the nanowires with light to see how individual components of the cell respond, or even change the behavior of the cell. They can last up to two weeks inside the cell before biodegrading.
Currently, the standard technology for recording and measuring electrical stimulation in a cell, called patch clamp, measures these signals across the entire cell membrane. This gives readings on cell behavior as a whole, but the nanowires would allow much more precise, targeted investigation of the cell.
Seeing how individual parts of a cell respond to stimulation could give researchers insight into how medical treatments that use electrical stimulation work at a more detailed level. For instance, deep brain stimulation helps treat tremors from movement disorders like Parkinson's disease by sending electrical signals to areas of the brain. Doctors know it works at the level of tissues and brain structures, but seeing how individual components of nerve cells react to these signals could help fine tune and improve the treatment.
The experiments in the study used umbilical vascular endothelial cells, which make up blood vessel linings in the umbilical cord. These cells readily took up the nanowires, but others, like cardiac muscle cells, did not. Knowing that some cells consume the wires and some don't could also prove useful in experimental settings and give researchers more ways to target specific cell types.
Tian and his team manufactures the nanowires in their lab with a chemical vapor deposition system that grows the silicon structures to different specifications. They can adjust size, shape, and electrical properties as needed, or even add defects on purpose for testing. They can also make wires with porous surfaces that could deliver drugs or genetic material to the cells. The process gives them a variety of ways to manipulate the properties of the nanowires for research.
"The studies here are really fundamental to understand how exactly these materials interact with cellular systems," said Ramya Parameswaran, a MD/PhD student in Tian's lab and co-author on the study. "The studies we did in this paper help us understand how certain cells internalize these nanowires so we can use them for many applications."
Research on silicon nanowire-based cellular interfaces has been underway for less than 10 years, so there is still much to learn about their potential for research and treatment. But Tian and his team see the technology as a potential alternative to more permanent genetic methods.
"If you can put in an electronic device that's transient, it's much more similar to a traditional drug model where you put something in the body and it goes away over time," said John Zimmerman, lead author of the study, a PhD recently graduated from Tian's lab and now at Harvard as a postdoctoral scholar. "We like that aspect of the nanowires because it allows us to have a more transient synthetic biology, rather than a permanent genetic modification."