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Injectable Nanowires Monitor Mouse Brains for Months

Implantable device could teach about brain development and disease

2 min read
Monitoring a mouse with nanowire meshes injected into its brain
The mouse, which was free to roam across its environment, is shown with a voltage amplifier attached near its head. A flexible serial peripheral interface cable was used to transmit the amplified signals to the researchers' data acquisition systems.
Photo: Lieber Group/Harvard University

Want to understand what happens to the brain as it ages, or figure out how people learn to recognize faces? Neurologists asking such questions, or struggling to deal with brain degeneration caused by Parkinson’s and Alzheimer’s, might get some insight from detailed observations of the brain’s circuitry over time. But so far, such information has been hard to come by.

Now researchers at Harvard have shown that they can track brain activity, at the level of individual neurons, for months at a time, using a tiny electronic mesh that can be injected directly into the brain. A group led by Charles Lieber, a chemistry professor at Harvard, reports in this week’s Nature Methods that they were able to record the neural activity of mice over eight months, long enough to see how the animals’ brains changed as they entered the mouse version of middle age.

“This really brings us the ability to pick apart the circuits that are involved in fundamental information processing with the brain as they develop,” Lieber says.

The team builds the mesh out of very thin silicon wires coated in a polymer, with crossing lines made entirely of polymer; together they form simple field-effect transistors. The mesh naturally curls up when it’s put in a liquid, and can be drawn into a syringe and injected. Once in the brain, the mesh uncurls and sits on top of the neurons.

Implantable electrodes already exist, of course; doctors place them in the brains of some Parkinson’s patients to provide deep brain stimulation, which can help control tremors. But such devices are large and stiff and tend to irritate the brain tissue. The brain responds by engulfing them in a layer of cells, which insulates them and makes receiving or transmitting electrical signals more difficult.

By contrast, Lieber’s meshes are soft and flexible, and the transistors they form are smaller than the brain cells; they don’t provoke an immune response and they stay where they’re put. Where other implants lose their usefulness in days or weeks, the Harvard team’s meshes kept functioning for the entire length of the eight-month experiment.

The researchers also included some electrodes that could provide electrical stimulation to the brain. Lieber’s hope is that, if scientists can identify what goes wrong in the brain’s circuitry—leading to, say, Parkinson’s—at an early stage, they could use some sort of stimulation to alter or at least slow the process.

Statistical analysis of the signals they recorded showed that they were picking up activity from individual neurons, and that they could follow the same neurons over time. This ability could provide neurologists with a detailed map of what’s going on in, say, the visual cortex during learning, or let them watch the process by which memories are formed and how that process degrades with age.

Lieber would also like to use the devices in other parts of the nervous system. A mesh over the retina might yield some information about what’s happening in the eye and how that ties into what the neurons are doing. A set of electrodes in the spinal cord might provide new information, or even a new form of therapy, in cases of traumatic injury.

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A photo showing machinery in a lab

Foundries such as the Edinburgh Genome Foundry assemble fragments of synthetic DNA and send them to labs for testing in cells.

Edinburgh Genome Foundry, University of Edinburgh

In the next decade, medical science may finally advance cures for some of the most complex diseases that plague humanity. Many diseases are caused by mutations in the human genome, which can either be inherited from our parents (such as in cystic fibrosis), or acquired during life, such as most types of cancer. For some of these conditions, medical researchers have identified the exact mutations that lead to disease; but in many more, they're still seeking answers. And without understanding the cause of a problem, it's pretty tough to find a cure.

We believe that a key enabling technology in this quest is a computer-aided design (CAD) program for genome editing, which our organization is launching this week at the Genome Project-write (GP-write) conference.

With this CAD program, medical researchers will be able to quickly design hundreds of different genomes with any combination of mutations and send the genetic code to a company that manufactures strings of DNA. Those fragments of synthesized DNA can then be sent to a foundry for assembly, and finally to a lab where the designed genomes can be tested in cells. Based on how the cells grow, researchers can use the CAD program to iterate with a new batch of redesigned genomes, sharing data for collaborative efforts. Enabling fast redesign of thousands of variants can only be achieved through automation; at that scale, researchers just might identify the combinations of mutations that are causing genetic diseases. This is the first critical R&D step toward finding cures.

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