Progress in developing nanotechnology takes place across a broad front.
I find it convenient to factor this progress into several components:
Development of nanosensors--devices that make direct measurements
(of positions, motions, sizes, bond-strengths, or the like) on individual
atoms and molecules. The biological world is replete with such sensors:
every enzyme must have this capability in order recognize its proper substrate.
Development of nanoeffectors--devices that apply controlled forces
to individual atoms or molecules. Many such devices have evolved biologically--enzymes,
ribosomes, cell division apparatus, and flagellar motors, for example.
Modeling and design of nanosystems--making mathematical or other theoretical
representations of molecular interactions is a prerequisite to designing
Interscale communication--messages between the macro-world and the
nano-world. Upscale communication allows us to gather information from the
realm our nanomachines will inhabit, and to observe (measure) the results
of our activities. Downscale communication enables us to control nanomachines.
Cultural integration of nanotechnology--preparing society for nanotechnology
should occupy the attention of people in several disciplines: economics,
to name one.
Let us look at a few recent technological developments with these categories
One approach to nanosensing is provided by microscopy. Here we are concerned
solely with structure, rather than motions, since molecular motion is far
too rapid to be resolved with microscopy techniques. A new instrument, the
atomic force microscope (AFM), recently made its debut by producing images
with a resolution smaller than 0.5 nanometers. The AFM, though related in
a general way to the scanning tunneling microscope, is not limited to conductive
or semiconductive specimens. Initial tests have used polymerized monolayers
of a simple organic compound. These are dry, fairly rigid specimens. While
the developers are confident that the AFM will operate on samples in fluids,
it remains to be seen whether loose molecules, such as biological specimens
in their natural state, can be used.
The AFM "scans" a specimen by dragging a diamond stylus over it
very lightly. The stylus and the cantilever that holds it are deflected
as they move across the specimen (it is actually the specimen that does
the moving). This deflection, sensed by optical means or by measuring the
tunneling current between the cantilever and a platinum-iridium point, is
maintained at a constant level by raising and lowering the specimen using
a piezoelectric actuator. A record of the voltage required for this specimen
movement gives rise to a picture. The AFM is being developed by O. Marti,
H.O. Ribi, and others at Stanford and the Univ. of Calif. at Santa Barbara
(Science, 1Jan88, p50; Sci News, 9Jan88, p25).
While microscopy pursues spatial resolution at the expense of time resolution,
laser spectroscopy does just the opposite. Ahmed
Zewail's team at Caltech has been probing chemical reactions with laser
pulses of femtosecond duration. The reactant(s), sprayed into an evacuated
chamber, are exposed to a laser pulse of appropriate frequency to initiate
the desired reaction; a subsequent pulse of a different frequency elicits
a fluorescence response containing detailed information about the reaction
mechanism. By varying frequency and timing, the researchers can obtain a
series of "snapshots" of a chemical reaction from which they have
deduced the precise movements of individual atoms as they go through the
transition states of the reaction.
This new "femtosecond chemistry" provides the same kind of information
we may someday obtain from nanosensors, but does so by carefully combining
bulk technology and chemical theory. From this work will emerge an exact
understanding of the forces and motions experienced by atoms and molecules
when they interact, and this knowledge should play an important role in
the design of assemblers. Femtosecond light pulses might also form the basis
of a downscale communication channel (Science, 11Dec87, p1512).
Atomic-scale mapping of the structures of existing enzymes and other biological
nanomachines is an essential part of learning how to design new ones. Such
mapping has depended largely on X-ray diffraction techniques applied to
crystalline samples of the materials. But getting the materials to crystallize
into a usable form has often proved difficult or impossible.
McPherson of the Univ. of Calif. at Riverside and Paul Schlichta of
JPL now report that the surfaces of some minerals can greatly facilitate
the crystallization of proteins and, in some cases, even cause the proteins
to crystallize in forms better suited to X-ray diffraction mapping than
their usual ones. The technique relies on the ability of the mineral's crystal
lattice to influence the deposition and spacing of protein molecules as
they deposit onto a mineral face from a supersaturated solution (Science,
A recent report on enzymatic catalysis in supercritical
carbon dioxide should remind us that nanomachinery can be designed for
operation in nonaqueous environments. In fact, many biological nanomachines
already do operate at least partially in such environments: enzymes that
make their homes in membranes are examples. In principle, just about any
fluid should be able to host properly designed nanomachines. And, as T.W.
Randolph and collaborators at the Univ. of Calif. at Berkeley point out,
nonaqueous solvents offer higher solubilities for the compounds that certain
enzymes operate upon. They also may provide an escape from kinetic or equilibrium
restraints imposed by the use of water.
Randolph's experiments on the enzyme cholesterol oxidase are conducted
in an environment of carbon dioxide at a variety of temperatures and pressures
near the critical point of that solvent. The enzyme functions under such
conditions, and its performance is improved by the addition of certain cosolvents
such as tert-butyl alcohol (Science, 22Jan88, p389).
An upsurge of interest in ribosomes is underway, thanks to the discovery
of RNA enzymes and to the application of cloning and sequencing techniques
to ribosomal RNAs. Ribosomes--the molecular devices that fabricate proteins
from genetic instructions--are nature's best approximation to our notion
of an assembler. Some think they preserve the basic structure and function
that primordial replicators must have possessed before the evolution of
cellular organisms. In this view, the ribosome is the central actor in the
biological drama; everything else is a set of supporting actors, props and
Investigators studying ribosomes have sequenced all of the 50+ ribosomal
proteins of E. coli, and all three of the ribosomal RNAs. The
arrangement of the proteins in the smaller of the two ribosomal subunits
is now known, as well as the position of 60% of the corresponding RNAs.
The secondary structure (that is, self-pairing) of the RNAs has been worked
out, and experiments are already being performed to study the effects of
sequence changes on the functions of ribosomal RNA. A great deal is known
about the mechanics of ribosomal translation, but not yet at the nanometer
scale (Nature, 21Jan88, p223; Science, 4Dec87,
The immune system provides us with a set of molecular devices that are easily
transformed into nanoeffectors: these are the antibodies. The trick, as
described by Richard
Lerner, et al., of Scripps Clinic, is to choose a stable molecule
that resembles in form an unstable, high-energy transitional state of the
chemical reaction one wants to catalyze. This choice depends upon having
a detailed theoretical understanding of the reaction in question. The molecular
"stand-in" is injected into an animal, where it elicits antibodies.
Among these antibodies are some that bind not only to the "stand-in"
but also to the transitional state of the desired chemical reaction. Using
the antibodies in the presence of the reaction's precursors lowers the activation
energy for the reaction--which is the essence of catalysis.
This technique is limited to those reactions which are well understood,
but may provide powerful tools for breaking nucleic acids and proteins at
specific sites or for linking them together in specific patterns (Sci.
Am., Mar88, p58).
A molecular-based transistor being developed by Mark S. Wrighton, Tracy
T. Jones, and Oliver M. Chyan at MIT links the sensitivity and selectivity
of certain "redox" polymers to the signal-carrying abilities of
electronics. A polymer bridge replaces the gate electrode found in traditional
transistors; the polymer changes conductivity in response to environmental
conditions, such as pH, thereby causing this device to act as a sensor.
The polymer bridge is about 50 nanometers across. To develop sensors for
other purposes would entail the substitution of different polymers, each
tailored for a specific task. Their size notwithstanding, these devices
are not nanosensors: they are fabricated by bulk-technological methods,
and they are not intended to provide data on the activities of individual
atoms. They do, however, demonstrate the upscale transport of information
from fairly deep in the microworld (Sci News, 132:214).
To predict the outcome of chemical experiments before performing them has
long been a goal of theoretical chemists. This difficult problem requires
large amounts of computation, but promises to make chemical research a faster
and more productive endeavor. Applied to the development of nanotechnology,
it will make the difference between being able to design nanomachines
and having to construct them by trial-and-error.
An indication of progress along these lines is the work of W. Koch and collaborators,
who have predicted from purely theoretical considerations that helium should
be able to combine with beryllium oxide to form the molecule HeBeO, and
that HeBeO should be stable with respect to dissociation back into helium
and BeO (Nature, 11Feb88, p487).
The next revolution in electronic miniaturization is being pursued at both
industrial and academic laboratories today, suggests Robert T. Bate of Texas
Instruments. Theoretical work on quantum-effect devices shows that a 100-fold
reduction in (linear) size of electronic components should be achievable,
with corresponding improvements in speed. Reliability would markedly increase
as well, thanks to the stability of quantum phenomena as compared with today's
larger devices that operate according to noisier principles. The quantum-effect
device is based on controlling the "tunneling" current in 20-nanometer
thick layers of doped AlGaAs. A small voltage applied to one terminal of
the device shifts quantum energy levels there so that they match levels
in another part of the device; this allows electrons to tunnel through the
intervening layer. A very small voltage change can eliminate the tunneling
current. A working prototype of a quantum-effect device is still a year
or more away. The theory is well understood, but formidable fabrication
problems remain to be solved since the devices will (initially) be made
by bulk methods rather than nanotechnological ones (Sci. Am.,
By studying small clusters of atoms, K. Rademann, C. Brechignac, and others
are learning how the atomic and molecular properties of substances scale
up into the properties of bulk materials. For example, the ionization potential
for mercury scales up into what is known as the "work function,"
as the number of atoms in a cluster grows from about 5 to about 70. Such
transformations of atomic properties into their corresponding bulk properties,
when examined in detail, reveal atomic and molecular structure and behavior
that has been inaccessible until now. Most work so far has dealt with metals;
the results cannot be extrapolated to organic materials since the bonding
is quite different (Nature, 14Jan88, p116).
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