That is until now. In this week's issue of the journal Science, a team
of researchers at the National Institutes of Health (NIH) report on a powerful new technique,
called laser capture microdissection, that can pull out a small cluster of cells from a tissue
sample in as little as 8 seconds.
By taking these cells directly from the tissue, the scientists say they can immediately
analyze the cells' gene and enzyme activity with other research tools. Currently, scientists must
attempt to extract, or microdissect, cells either by trying to yank them free with a manual tool or
through a convoluted process of isolating and culturing the cells. Most scientists say they
consider both approaches to be tedious, time-consuming, and inefficient.
According to Lance Liotta, M.D., Ph.D., a scientist at the National
Cancer Institute (NCI) and senior author of the paper, the direct access to cells should lead to a
revolution in the understanding of the molecular basis of cancer and other diseases, helping
to lay the groundwork for earlier and more precise disease detection.
"Having this technique is the difference between being able to
investigate a crime in progress and going back two weeks later to the scene of the crime when much
of the evidence has vanished, as we typically do now," said Liotta. "Laser
capture microdissection gives us access to the disease, in a sense, while
the crime is still in the planning stages, and that's really powerful
information to have in designing strategies to halt the disease process."
Laser capture microdissection is a fully automated, one-step technique that, in today's
high-tech world, has emerged as a remarkably low-tech creation. It integrates a standard
laboratory microscope with a low-energy laser and a transparent ethylene
vinyl acetate polymerthermoplastic film--the same plastic seal in a
container of yogurt.
Michael Emmert-Buck, M.D., Ph.D., an NCI scientist and lead author of
the paper, said the group's prototype device works on the same basic aim-and-shoot principle
as an instamatic camera: Scientist looks through a microscope at a tissue biopsy, which
typically contains hundreds of different types of cells.
Upon spotting a group of tumor cells, for example, the scientist presses a button
attached to the side of the microscope. The button activates the laser, which
flashes a beam of light that has an intensity slightly greater than a laser pointer.
The beam of light passes through the plastic film placed above the tissue sample
and focuses onto the cells. In the process, the beam heats the plastic, giving it the
thermal qualities of a piece of scotch tape. The cells then stick to the plastic
directly above them, whereupon the cells are immediately extracted and ready for
Emmert-Buck said he and his colleagues purposely designed their device
with a camera in mind. "We wanted an instrument that any scientist could sit down and use
immediately," he said. "That meant creating a fully automated,
user-friendly device that was free of any tricky, manual manipulations to
complicate its operation. A camera seemed like a device that is simple and
familiar to most people. With this idea in mind, we spent about two years
creating a viable, one-step technique."
In the Science paper, Emmert-Buck and his colleagues report that laser capture
microdissection has successfully extracted cells in all tissues in which it
has been tested. These include kidney glomeruli, in situ breast carcinoma,
atypical ductal hyperplasia of the breast, prostatic interepithielial
neoplasia, and lymphoid follicles.
They reported no limitations in their ability to amplify DNA or RNA
from tumor cells extracted with laser capture microdissection. The scientists also found
they were able to recover enzymes from within the cells and test them for
Robert F. Bonner, Ph.D., a co-author on the paper and a scientist with
NIH's National Center for Research Resources, said laser capture microdissection, like all
emerging techniques, still has room for improvement. Bonner said with
further refinement of the plastic film and activation of a finer laser beam,
he could easily foresee the technique extracting single cells, rather than
the two or three cells at a time that it now yields.
Another likely role for the technique is in helping to record the patterns of gene expression
in various cell types, an emerging issue in medical research. For instance,
NCI's Cancer Genome Anatomy Project (CGAP) seeks, in part, to define the
patterns of gene expression in normal, pre-cancerous, and malignant cells.
In projects such as CGAP, laser capture microdissection fits in nicely
at the front end of the process as the tool that procures pure cell samples from tissue, feeding
the rest of the analytical process.
Given the technique's great potential to forward the study of biology
and medicine, the NCI has made plans to make the device widely available to researchers and
clinicians around the country. A demonstration project is already in the
works with Steven Bova, M.D., a scientist in the Departments of Urology and
Pathology at The Johns Hopkins University School of Medicine. Liotta said
the aim of this project is to receive input from fellow researchers on how
the device might be simplified even more, while also achieving the highest
standard of quality.
"As new information accrues about the genetics of cancer and other human diseases, it
opens up new opportunities for discovery, which will ultimately lead to more
targeted ways to diagnose and treat disease," said Richard Klausner, M.D., NCI director.
"The NCI recognizes that it has a commitment to place powerful, new research tools into the
hands of scientists to catalyze the discovery process. And, the NCI will make every effort to do
so with laser capture microdissection."
B-roll is available upon request from the NCI Press Office (301) 496-6641.
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