Foresight Update 3
page 3
A publication of the Foresight Institute
 Steps
in the Right Direction
Technical Advances and Encouraging Developments
by Russell Mills
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 nanomachines.
- 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 in mind.
Developing nanosensors
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).
[A
web primer on atomic force microscopy] [A few AFM
images of DNA (not atomic resolution)]
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).
Developing nanoeffectors
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.
Alexander
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, 22Jan88, p385).
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 assistants.
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, p1403).
[The
RNA World monograph]
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.
[An example of
antigen design to obtain catalytic antibodies]
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).
Interscale communication
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).
[Recent
achievement: a
functioning molecular wire]
Modeling and design of nanosystems
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., Mar88, p96).
[A
Web page about quantum dots]
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).
[A web page
on clusters]
Dr. Mills has a degree in biophysics and runs a business in
Palo Alto, California. He is also the designer and assembler of
issues 2 and 3 of Foresight Update.
Journal
Monitoring
Many of you have been sending in journal articles and magazine
clippings relevant to nanotechnology, major AI advances,
hypertext publishing, and other topics of interest to FI. To
ensure broader coverage and avoid duplication, Jerry Fass will be
coordinating these efforts. If you would like to participate,
please contact Jerry to discuss which journal(s) or magazine(s)
you would like to monitor: 2975 N. Oakland Ave., Milwaukee, WI
53211; phone 414-332-6387.
From Foresight Update 3, originally
published 30 April 1988.
Foresight thanks Dave Kilbridge for converting Update 3 to
html for this web page.
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