An MIT team has improved upon its landmark technology
reported last year in which the researchers used a fingernail-sized lab on
a chip to image, perform surgery on and sort tiny worms to study nerve
regeneration.
The team has found a unique way to immobilize the animals while they are
still awake for several minutes with unprecedented stability, which then
allowed the researchers to conduct fast, detailed three-dimensional
imaging and to perform high-resolution laser nanosurgery on the animals.
The advance, which builds on a technology first reported last year, could
ultimately help researchers better understand the genetic underpinnings of
regeneration and degeneration in the nervous system-not just in the worm
but in more complex organisms including humans. That, in turn, could help
in treatments of neural injuries and diseases such as Parkinson’s and
Alzheimer’s.
Led by Mehmet Fatih Yanik, MIT assistant professor of electrical
engineering and computer science, the team reported its latest work in the
April 2 advanced online issue of the journal Lab on a Chip. The work
involves the C. elegans worm, one of the tiniest multi-cellular organisms
known. Smaller than a human hair, the worm is considered a key model for
investigating a variety of biological phenomena such as aging, fat
metabolism and neurological diseases.
Geneticists have been studying C. elegans since the 1960s, but the manual
processes they used to do so were painstaking and time-consuming. That
changed in a big way last year when Yanik and colleagues reported in the
Proceedings of the National Academy of Science that they had developed a
microfluidic chip to automate and accelerate research on the tiny worms.
Essentially, the tiny worms are flowed inside the chip, immobilized by
suction and imaged with a high-resolution microscope.
The research published this month goes one step further. Yanik and two
collaborators, lead authors Fei Zeng, a postdoctoral fellow in the
Research Laboratory of Electronics, and Christopher B. Rohde, a graduate
student in electrical engineering and computer science, said they were
able to render the animals motionless in the chip with an unprecedented
stability for several minutes instead of seconds. This then allowed them
not only to conduct three-dimensional imaging of the worms at the
sub-cellular resolution but also to reliably operate on the animals with a
high-precision surgery laser to study neural degeneration and regeneration
on the chip. Yanik’s team had previously demonstrated that neural
regeneration can be studied in C. elegans using femtosecond laser
micro-surgery.
“This new technology is allowing us to study the entire genome of the
animal in very short periods of time,” Yanik said. “We are currently
combining it with genetic and drug screens to study neural regeneration on
these animals.”
Yanik received the NIH Director’s Innovator Award last year for developing
the lab on a chip technology to screen whole animals and study neural
regeneration.
The research was funded by NIH Director’s New Innovator Award
(1-DP2-OD002989-01) and Packard Award in Engineering and Science, and
Merck & Co. Inc.
Greg Frost, MIT News Office
mit.edu