Previous research efforts in neuroscience have generally relied on
separate devices: needles to inject viral vectors for optogenetics,
optical fibers for light delivery, and arrays of electrodes for
recording, adding a great deal of complication and the need for tricky
alignments among the different devices.
For the first time ever, a single flexible fiber no bigger than a
human hair has successfully delivered a combination of optical,
electrical, and chemical signals back and forth into the brain, putting
into practice an idea first proposed two years ago.
‘A single flexible fiber has successfully delivered a combination of optical, electrical, and chemical signals back and forth into the brain.’
With some tweaking
to further improve its biocompatibility, the new approach could provide a
dramatically improved way to learn about the functions and
interconnections of different brain regions.
The new fibers were developed through a collaboration among material
scientists, chemists, biologists, and other specialists. The results
are reported in the journal Nature Neuroscience
, in a paper by
Seongjun Park, an MIT graduate student; Polina Anikeeva, the Class of
1942 Career Development Professor in the Department of Materials Science
and Engineering; Yoel Fink, a professor in the departments of Materials
Science and Engineering, and Electrical Engineering and Computer
Science; Gloria Choi, the Samuel A. Goldblith Career Development
Professor in the Department of Brain and Cognitive Sciences, and 10
others at MIT and elsewhere.
The fibers are designed to mimic the softness and flexibility of
brain tissue. This could make it possible to leave implants in place and
have them retain their functions over much longer periods than is
currently possible with typical stiff, metallic fibers, thus enabling
much more extensive data collection.
For example, in tests with lab
mice, the researchers were able to inject viral vectors that carried
genes called opsins, which sensitize neurons to light, through one of
two fluid channels in the fiber. They waited for the opsins to take
effect, then sent a pulse of light through the optical waveguide in the
center, and recorded the resulting neuronal activity, using six
electrodes to pinpoint specific reactions. All fof this was done through
a single flexible fiber just 200 micrometers across - comparable to
the width of a human hair.
Getting that alignment right in
practice was "somewhat probabilistic," Anikeeva says. "We said, wouldn't
it be nice if we had a device that could just do it all."
After years of effort, that's what the team has now successfully
demonstrated. "It can deliver the virus [containing the opsins] straight
to the cell, and then stimulate the response and record the activity -
and [the fiber] is sufficiently small and biocompatible so it can be
kept in for a long time," Anikeeva says.
Since each fiber is so small, "potentially, we could use many of
them to observe different regions of activity," she says. In their
initial tests, the researchers placed probes in two different brain
regions at once, varying which regions they used from one experiment to
the next, and measuring how long it took for responses to travel between
The key ingredient that made this multifunctional fiber possible was
the development of conductive "wires" that maintained the needed
flexibility while also carrying electrical signals well. After much
work, the team was able to engineer a composite of conductive
polyethylene doped with graphite flakes. The polyethylene was initially
formed into layers, sprinkled with graphite flakes, then compressed;
then another pair of layers was added and compressed, and then another,
and so on.
A member of the team, Benjamin Grena, a recent graduate in
materials science and engineering, referred to it as making "mille
feuille," (literally, "a thousand leaves," the French name for a
Napoleon pastry). That method increased the conductivity of the polymer
by a factor of four or five, Park says. "That allowed us to reduce the
size of the electrodes by the same amount."
One immediate question that could be addressed through such fibers
is that of exactly how long it takes for the neurons to become
light-sensitized after injection of the genetic material. Such
determinations could only be made by crude approximations before, but
now could be pinpointed more clearly, the team says. The specific
sensitizing agent used in their initial tests turned out to produce
effects after about 11 days.
The team aims to reduce the width of the fibers further, to make
their properties even closer to those of the neural tissue. "The next
engineering challenge is to use material that is even softer, to really
match" the adjacent tissue, Park says. Already, though, dozens of
research teams around the world have been requesting samples of the new
fibers to test in their own research.