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Foresight Update 20 - Table of Contents |
A publication of the Foresight Institute
Today's feats are significant compared to the parlor
tricks of a year or two ago.
Nanoprobe instruments--such as the scanning tunneling microscope
(STM) and the atomic force microscope (AFM)--are misnamed. They
are proving to be just as adept at manipulating atoms as at
imaging them, and it always seems awkward to call them
"microscopes" while describing their latest feats of
construction. And today's feats are starting to be significant
compared to the parlor tricks of a year or two ago: spelling out
company logos with atoms, or gashing a surface with the probe
tip. Let's take a look at some recent developments:
Researchers at the Aono Atomcraft Project in Japan, using an STM,
are now able to extract a single silicon atom from the surface of
a silicon crystal and rebond it to the surface at a different
location. Atoms translocated in this manner can be re-removed
without disarranging the underlying atomic layers. Atoms brought
from afar can be used to repair holes in the silicon surface, or
they can be used to build structures on top of the surface. [J.
Vac. Sci. Technol. B 12(4): 2429-2433, Jul/Aug94]
Folks, this looks an awful lot like real nanotechnology.
An STM equipped with a platinum-rhodium tip enabled workers at
California's Lawrence Berkeley Laboratory to carry out chemical
reactions at localized sites on a substrate. The experiments took
place in a chamber containing hydrogen gas and a working surface
coated with unsaturated hydrocarbons - i.e., molecules containing
double bonds that can react with hydrogen. When the STM tip was
activated by voltage pulses, it began to act as a catalyst,
splitting nearby hydrogen molecules and transferring the hydrogen
atoms to hydrocarbons on the working surface. Areas of the
working surface that were scanned by this activated STM tip
underwent a characteristic change in texture, indicating that the
hydrocarbons in these areas had indeed been chemically
hydrogenated. The conversion appeared to be 100%, judging by the
pictures. [Science 265: 1415-1418, 2Sep94]
In this work no effort was made to restrict the chemical reaction
to a single site; instead, the probe was scanned over a
rectangular area containing many substrate molecules. Presumably
the hydrogenation could just as easily have been confined to a
much smaller area, and perhaps to a single substrate molecule.
The basic methods used here may work with certain other reactions
besides hydrogenation, and could provide a toolkit of useful
transformations for the construction of nano-objects.
AFMs are normally used to map the topography of a surface. But a
group of chemists at Harvard and M.I.T. have used one to map a
surface according to the types of molecular groups that are
attached to it. The key to this technique is to
"functionalize" the AFM probe by coating it with a
layer of molecules that will interact with the molecules on the
surface being mapped. As the probe tip is dragged across this
surface, the forces generated by the interaction will vary with
the nature of the molecular groups the tip encounters. These
forces, which can be measured, provide a chemical profile along
the track of the tip. If the surface has a pattern of several
different kinds of molecules, then the AFM should be able to form
an image of this pattern. And indeed, the images these
researchers obtained of their samples correctly showed the
molecular patterns they had put there. [Science 265:
2071-2074, 30Sep94]
Functionalizing the tips of nanoprobe instruments is an essential
step in turning them into useful molecular constructors. Of
course, randomly coating a probe tip with a layer of one
chemical, as was done here, is not the final answer. But even
this primitive functionalization may prove useful for such
applications as DNA sequencing, where the different nucleotides
would exert differing forces on the tip.
Physicists at the University of California at Santa Barbara have
made AFM images of the enzyme lysozyme that seem to show
the enzyme flexing as it interacts with a molecule of its
substrate. The motions probably correspond to conformational
changes which the enzyme undergoes as the substrate binds to it,
and these show up in an AFM image as height fluctuations. [Science
265: 1577-1579, 9Sep94]
At AT&T Bell Laboratories in New Jersey, researchers have
recorded the optical spectrum of single molecules at room
temperature. Molecules of a fluorescent compound were dispersed
on a thin plastic film and then examined with a near-field
scanning optical microscope. When the fluorescent molecules were
illuminated by an appropriate frequency of green light, they
absorbed and re-emitted the energy at a variety of frequencies
characteristic of their molecular structure and of their
immediate environment. From the spectra obtained from 28
individual molecules, the researchers concluded that the act of
observing a molecule does not perturb it sufficiently to
invalidate the spectral data obtained from it. They suggest that
this technique may be used to study the binding of enzymes with
their substrates. [Nature 369: 40-42, 5May94]
The ability to obtain meaningful spectral measurements from
single molecules (or even parts of a molecule) may be needed to
confirm certain kinds of structures that will someday be built
with nanoprobe instruments.
A more interesting concept, however, is the inverse process:
feeding a designed spectral sequence to a single molecule (or
parts of a molecule) in order to control its behavior. This has
been tried in bulk chemistry as a way of controlling chemical
reactivity, but without much success--probably because the
molecules are flopping around randomly in solution in an
unsynchronized manner. But the technique might work better if it
were applied to a single molecule in the solid phase.
One approach to the problem of communicating with nanodevices is
to design them to receive, interpret, and generate messages
encoded as spectral sequences. The work described above could be
a small step in that direction. So, too, could the following:
Chemists at Stanford University and Indiana University have
detected individual fluorescent molecules in liquids, using a
confocal fluorescence microscope (CFM). The CFM differs from the
near-field microscope (NFM) in that the detection apparatus is
much further from the sample-- micrometers as opposed to 10
nanometers. Although this arrangement precludes high-resolution
measurements of a molecule's position, it offers some advantages:
a larger number of photons can be delivered to a sample molecule
to stimulate fluorescence, and this improves the time-resolution
of measurements; the CFM is less invasive than the NFM since the
apparatus is further from the sample; it operates in a
three-dimensional sample space rather than a two-dimensional one,
making possible the mapping of an extended sample by focusing at
a series of depths. [Science 266: 1018-1021,
11Nov94]
Calvin Quate, a physicist at Stanford University, recently made a
transistor in which one component (the gate) was created by using
the probe tip of an AFM to make scratches in appropriate places
on the silicon substrate. The resulting transistor performed
correctly. Although the gate was as large as those that can be
made by photolithography (about 100 nanometers wide), the AFM is
believed to be capable of making much smaller structures. Quate
envisions arrays of thousands of AFM tips working in unison to
construct the electronic circuits of the future. His team has
already begun experimenting with five-tip arrays. [Science
266: 543, 28Oct94]
The scratches made by the AFM in this experiment were not
atomically precise. But someday soon, they probably will be.
(We'll then have to call them something more dignified than
"scratches".) Quate's vision of arrays of busy AFM tips
bears a remarkable resemblance to the vision of arrays of
molecular robot arms in Eric Drexler's Engines of Creation.
Many biological macromolecules, such as enzymes, carry out
their tasks by going through machine-like motions: grabbing,
holding, pinching, twisting, pulling, releasing, etc. Biologists
would love to be able to watch these actions in detail as they
take place--or, at least, watch them in a movie in which the
motions are slowed down to a human time-scale. Now this dream is
becoming a reality.
Research groups at Los Alamos National Laboratory and at the
University of Chicago have captured the motions of the protein myoglobin
as it seized and released small molecules such as oxygen. A
standard recording technique was used: x-ray crystallography, in
which the protein being studied is crystallized and bombarded
with x-rays; an analysis of the scattered x-rays yields a
3-dimensional map of the protein. In the myoglobin work, the
researchers had to slow the activity of the molecule by cooling
it to 77 kelvins in order to get adequate x-ray exposures. In the
future they hope to have access to brighter x-ray sources, which
should drastically reduce exposure times and eliminate the need
for physiologically unrealistic low temperatures. [Science
266: 364-365, 21Oct94]
The structure of a remarkable biological machine has recently
been resolved in atomic detail. English biochemist John Walker
used x-ray crystallography to reveal the structure of the
catalytic portion of the enzyme ATP synthase. This enzyme,
found in the mitochondria of all cells, is a collection of
proteins responsible for making ATP, the energy transport
molecule.
To make a molecule of ATP, two precursor molecules (ADP and
phosphate) must be brought together and chemically joined. Since
the precursor molecules are floating in solution inside
mitochondria, the ATP synthase machines have easy access to them.
But exactly how does ATP synthase go about grabbing these
precursors, bringing them together, and then releasing the
product? The details are beginning to emerge from Walker's map of
the enzyme.
ATP synthase resembles a lumpy orange spinning on a long axle.
The "orange" has six segments - three alpha subunits,
and three beta subunits. The beta subunits are the ones
responsible for making ATP. The "axle" is actually a
tube, the other end of which is embedded in the mitochondrial
membrane; it contains the still-mysterious mechanisms responsible
for enabling the enzyme to spin. As the "orange" turns
on the axle, the subunits are pushed and pulled in a cyclical
pattern by the axle's irregularities; the resulting deformation
of the subunits manifests itself as the mechanical movements
required for making ATP. [Science 265: 1176-1177,
26Aug94]
One of the intriguing facts about this sophisticated enzyme is
that it is found in every kind of cell, from bacteria to plants
and animals. That presumably means that it is a very ancient
biological device that evolved with the early bacteria or even
before. It seems surprising that the creatures of that era
already had the use of such an elegant machine.
Nanotubes are forerunners of self-assembling structures
that will help us modify cells
As discussed in this column in Foresight Update 18,
researchers at Scripps Research Institute in 1993 designed rings
of amino acids that self-assemble into nanotubes. The same
researchers have recently taken this work a step further by
creating self-assembling nanotubes that form channels through
lipid membranes similar to those found in cells.
These new nanotubes are based on two design principles: first,
the amino acids in each ring must form hydrogen bonds with the
amino acids in adjacent rings so as to hold the nanotube
together; and second, the exterior of the nanotube must attract
(rather than repel) the lipid molecules that make up the
membrane--otherwise the membrane would eject the nanotube.
Membrane-spanning channels are standard features of living cells.
They usually contain valves to regulate the flow of molecules
across the membrane. The Scripps researchers showed
experimentally that their nanotubes were very effective channels
for ion flow across the artificial membranes they were using.
They suggest that such nanotubes may be useful for delivering
drugs into cells in the body. [Nature 369: 301-304
& 276-277, 26May94; C&EN 26May94: 4-5]
The idea of using nanotubes to deliver drugs into cells, without
first developing a valve to close the channel after the drug has
entered, sounds like a bad idea. Punching holes in cell membranes
and letting material pass freely through the holes is a tactic
used by some toxic organisms to kill cells.
On the brighter side, it seems safe to say that these nanotubes
are the forerunners of a large class of self-assembling
structures that will help us to modify cells and make them do our
bidding.
Dr. Russell Mills is research director at KAH Sciences in
California.
Prof.
Ari Requicha is leading a new effort in molecular robotics at USC.
Prof. Requicha of the University of Southern California taught
the first course using Nanosystems as a textbook (see Update
18). Here he describes his new inter-disciplinary laboratory
in nanotechnology:
Molecular Robotics is an emerging and highly interdisciplinary
field that seeks to produce new materials and devices at a
nanometer scale by direct interaction with atomic structures.
Whereas conventional chemistry relies on bulk phenomena such as
diffusion to create self-assembling structures, Molecular
Robotics manipulates structures by applying external forces and
precisely positioning atoms and molecules.
It is a revolutionary technology, which attempts to provide fine
control over the structure of matter, analogous to the fine
control we can now exert upon the bits and bytes of information
structures. Future applications range from very fast and small
computers to nanorobots and self-replicating machines. Nanorobots
might be programmed to recognize and repair specific kinds of
cells, and to perform a large variety of other tasks that are now
impossible to accomplish. Large structures might be built by
using massive parallelism.
The technology has the potential for major scientific and
practical breakthroughs. However, today we lack most of the tools
necessary for realizing the dreams of Molecular Robotics.
Research opportunities abound.
The Laboratory for Molecular Robotics was established at USC in
late Fall 1994 with primary support from the Zohrab A. Kaprielian
Technology Innovation Fund. The initial focus of the laboratory
is on sensing and manipulation using Scanning Probe Microscope
(SPM) technology. SPMs are capable of atomic-level imaging, and
of manipulation with the precision required for positioning atoms
and molecules. These instruments can be viewed as robots with
sensory feedback, whose probe tip must be equipped with
grippers--specially-designed molecules--so as to manipulate
atomic-level structures in an environment that has significant
spatial uncertainty, making and breaking chemical bonds, or
providing chemical sensitivity, as in the lock-and-key model for
enzyme action.
Our interdisciplinary team is tackling problems of tip design and
construction for Scanning Tunneling Microscopes (STMs) and Atomic
Force Microscopes (AFMs); computer control and programming of
these devices; design and visualization aids; design and
construction of substrates that serve
as"nanoworkbenches"; methods for attaching specific
molecules to a tip; designing probes and tips that distinguish
between molecules by tactile affinity; and determining the
structure of materials by tactile probing.
We are working in the context of a specific, intermediate-term
goal: the construction of "nanoarrays" composed of
nanoscale entities, such as organic or biological molecules of
interest in optical computing and related applications, placed on
a regular array of microscale semiconductor mesas. In the long
run we expect to address even more challenging problems such as
sensing and manipulation of biomaterials, and especially DNA.
Senior personnel associated with the new laboratory include Bruce
Koel, Professor of Chemistry; Aristides A. G. Requicha, Professor
of Computer Science and Electrical Engineering, Lab Director;
Anupam Madhukar, Professor of Materials Science and Physics; and
Peter Will, Division Leader, USC Information Sciences Institute.
Address inquiries to Professor Requicha at Laboratory for
Molecular Robotics, Computer Science Department, University of
Southern California, Los Angeles, CA 90089-0781. Internet:
lmr@lipari.usc.edu; tel (213) 740-4502; fax (213) 740-7512.
From Foresight Update 20, originally
published 1 February 1995.
Foresight Update 20 - Table of Contents |
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