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October 30, 1993
SCOPE.ASC
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This file shared with KeelyNet courtesy of Bert Pool.
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02-22-1993
New optical microscopes transcend limits of visible light
By John Markoff
New York Times News Service
A new generation of optical microscopes is emerging, capable of
resolving images far beyond the conventional limits imposed by
visible light.
These microscopes are known as near-field scanning optical
microscopes, or NSOM, and they may soon offer a wide variety of
remarkable applications ranging from detailed movies of the inner
workings of cells to vast increases in data storage capacity for the
computer industry. In theory the technique could pack information so
densely that two copies of "War and Peace" could be transcribed in
the area of a pinhead.
The renaissance of optical microscopy is a striking reversal of
recent trends in this three-century-old technology. Since the 1930s
conventional lens-based optical microscopes have increasingly lagged
behind two other kinds. One is the electron and X-ray microscopes
which resolve at far shorter wavelengths than optical systems; the
other is scanning probe instruments which, in the case of the
scanning tunneling microscope, can now routinely resolve objects as
tiny as individual atoms.
Yet despite the razor-sharp imaging ability of nonoptical systems
they have failed to replace traditional optical microscopy for many
applications because of what researchers call a Faustian bargain
struck by each technology. In both cases compromises must be made.
There are shortcomings in these powerful technologies ranging from
lack of viewing contrast to the destructiveness of techniques that
destroy biological material.
Despite its great promise, the new optical technique has been
developing slowly because of a variety of hurdles that are only now
being overcome.
Until now near-field scanning optical microscopes have been the
laggards of the field, said Eric Betzig, a physicist at AT&T Bell
Laboratories who is one of the leading developers of the
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instruments.
That is now changing quickly based on technical advances made in
Betzig's laboratory and by researchers at Cornell University and IBM
scientists in Zurich, Switzerland. Their hope is that the near-field
optical instruments now being perfected will take advantage of the
decades of experience gained with improving conventional optical
microscopes. Betzig said advantages like speed and the ease of
preparing specimens would enable scientists to adapt quickly to the
new technique.
Betzig's belief in the field's promise is echoed by some of the
leading figures in microscope research.
"Near-field optical extends the limits to a degree that is
unprecedented," said Calvin Quate, a Stanford University physicist
who is a pioneer in developing advanced microscope technologies. "If
you have two microscopes of similar resolution, the optical would
win out because of the power of photons."
Bell Laboratories researchers have already perfected near-field
scanning optical microscopes capable of resolving images down to
approximately 12 nanometers, or less than one 1,700,000-millionth of
an inch. This makes it easy to view objects like bacterial viruses
which are in the range of 70 nanometers across or about one
360,000th of an inch.
At the heart of the new technique is an ultra-fine fiber-optic probe
that can be steered over the surface of a sample with remarkable
accuracy while staying within several nanometers of the object's
surface.
The probe itself is created by heating and drawing a fiber-optic
wire and then sheering its tip. The probe is coated with aluminum
and a light is shined through it. As the probe is scanned over the
surface of an object, an image is built up line by line, much as a
television image is created.
The great advantage of the new technique is that it evades a basic
physics principle known as the diffraction limit, which holds that
details that are smaller than half the wavelength of light cannot be
resolved. The microscope can in fact resolve objects that are
dwarfed by the wavelength of light, which is around 500 nanometers.
To get around the diffraction barrier, the new instruments exploit
the fact that a light wave can be defined as the sum of a series of
waves with far shorter wavelengths. Because of the probe's extreme
proximity to the surface it is measuring, it can detect these
"evanescent" waves that are lost at greater distances.
Several applications for the new breed of optical microscopes are
now being explored. At Bell Laboratories Betzig and his co-workers
have used the instrument to view extremely thin tissue samples taken
from the hippocampus of a monkey's brain.
When it is used together with a conventional optical microscope, the
viewer can jump back and forth from a wide viewing area to focusing
in on extremely fine features that have traditionally only been
accessible to transmission electron microscopes. The Bell research
Page 2
suggests that the new instrument could become a cost-effective tool
for clinical pathology. MORE (Optional 2ndtake follows.)
In the laboratory of Michael S. Isaacson, a Cornell physicist who
led one of the three groups that originally developed the near-field
optical microscopes in the late 1970s and early 1980s, researchers
are using the devices as diagnose semiconductor lasers. With the
instrument's power, they can understand more precisely problems that
develop in the process of growing the lasers.
Despite early promise, some significant hurdles remain. In
biological fields, Isaacson said that the instrument's usefulness is
narrow so far.
"The technique may be restricted to a certain class of biological
objects," he said. Because the optical probe functions so close to
the surface of an object, it may be impossible to navigate across
cell surfaces that have many protruding receptors. But Isaacson said
that researchers at the University of Washington had already begun
using a near-field microscope to explore the structure of muscle
cells, which generally have smooth surfaces.
Indeed, the Bell Laboratories researchers, working with scientists
at the Center for Light Microscope Imaging and Biotechnology at
Carnegie Mellon University, have already demonstrated that the near-
field technique can obtain more detailed images of cell structures
than can other microscopic methods. The detailed cell images are
providing new insights into the mechanisms of wound repair, they
said.
They have also recently begun to view cells under water, a first
step toward creating images of living cells. It currently takes
about 45 minutes to obtain a 512 by 512 pixel image, far slower than
some of the living cell processes. In the future, however, Betzig
said the researchers believe that modifications to the current
system may make it possible to create several images per second.
There are also several research projects under way in nonbiological
areas. The Cornell Laboratory, in conjunction with IBM, is exploring
use of the NSOM to write ultra-thin circuit lines on silicon wafers
by scanning the probe tip over a light-sensitive semiconducting
material.
At present electronic circuits are etched on semiconductors by
shining ultraviolet light through masks that make it possible to
expose as many as 30 wafers an hour. Using a single NSOM probe would
take a prohibitive amount of time even to write the circuitry for a
single chip.
To overcome this barrier scientists are discussing the possibility
of creating arrays of tens of thousands of probes that could scan
across the surface of a wafer writing ultra-dense semiconductor
circuits.
"You can fabricate silicon structures that are almost comparable
with what you can do with electron beams," said Isaacson. "But in
order for it to be realistic in a manufacturing sense you would have
to do it in parallel."
Page 3
There may be intermediate applications in the semiconductor
manufacturing process, however. The Bell Laboratories researchers
are studying using the NSOM tools as an inexpensive means for
correcting defects in the masks that are used in the lithographic
process needed to make microchips. Potentially it will be possible
to microscopically "weld" defects in the delicate semiconductor
circuit pattern masks.
The Bell Laboratories researchers are also exploring the possibility
of using the NSOM as a device for storing and retrieving computer
data. Currently they have been able to read and write information at
densities of 45 billion bits per inch.
If that much information were in the form of recorded music, it
would take a disk the size of a quarter as much as eight days to
play it all. If it took the form of compressed high-density
television programming, a palm-sized disk could hold 17 hours'
worth.
Yet while such densities are more than 40 times greater than those
attained with state-of-the-art magnetic recording techniques, there
are competing technologies that may be even more promising. Last
year IBM scientists at the company's Almaden Research Center in San
Jose used an atomic force microscope probe in conjunction with a
laser to store and retrieve data at even higher storage densities.
It is still early but researchers are beginning to talk about the
advent of a golden age in the Lilliputian world of high-technology
microscopes.
"It's a fantastic time, its the golden age of microscopy," said
Kumar Wickramasinghe, manager of physical measurements at IBM's
Thomas J. Watson Research Center in Yorktown Heights, N.Y. "The
scanning tunneling microscope has taught me and a lot of others in
this field that by scanning probes around you can overcome the
limits to resolution. Now you're really limited only by the
ingenuity of the scientist designing the probe. We're all having
lots of fun."
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