[Editor's Note: This page has been optimized for Netscape
2 and later. If you are using a browser, such as Netscape 1.1, that does
not support the html tag for superscripts, please be aware that an
number like "2x109" is meant to be scientific notation for "2
times ten raised to the 9th power," and that "e2" means "e
There were many important papers presented at the Fourth Annual Foresight
Nanotechnology Conference. Since, however, the conference was summarized
in the Foresight Update
23, this column will focus on information from other sources.
Protein and Peptide Design
Protein synthesis is one technology currently available for building nanometer
scale systems. Its primary advantage is that it allows us to build macroscopic
quantities of (potentially) atomically perfect nanometer scale structures.
The primary disadvantage of protein synthesis is that we want to construct
3D structures, but we can only specify the sequence of amino acids directly.
The next three papers advance the state of the art in allowing design of
protein structures that fold into target 3D structures.
Helical Bundle Structures:
The current state of protein design is described by J. W. Bryson, S. F.
Betz, H. S. Lu, D. J. Suich, H. X. Zhou, K. T O'Neil, and W. F. DeGrado,
writing in [Science270: 935-941 10Nov95]. They focus on the
information that stability studies of synthetic proteins can yield about
protein energetics. "Designed, helical peptides provide model systems
for dissecting and quantifying the multiple interactions that stabilize
secondary structure formation. De novo design is also useful for exploring
the features that specify the stoichiometry and stability of alpha-helical
coiled coils, and for defining the requirements for folding into structures
that resemble native, functional proteins."
The authors describe predictions of structures as rather well established
in helical domains, with fairly good agreement (±0.3 kcal/mole out
of a range of roughly 0.0-1.0 kcal/mole) on the helical propensities of
the various amino acid residues, good understanding of "Specific hydrogen-bonded
interactions that 'cap' the ends of helices," and good information
on the pairwise "hydrogen bonding and electrostatic interactions between
amino acid side chains separated by a single alpha-helical turn."
The associations between these helices can be harder to predict, with the
authors citing one case where varying one pair of residues produced every
state of aggregation from dimers to hexamers. In a number of four-bundle
designs "the association of hydrophobic side chains provides a powerful
driving force for the formation and association of helices...However, both
lattice models as well as early design attempts lack the diversity of stabilizing
interactions and specificity found in natural proteins, which we believe
are essential for stabilizing native-like folds and function."
They describe a variant of the four-helix bundle ROP, where the hydrophobic
residues were packed "in layers consisting of two small and two large
side chains per stack" with the resulting protein behaving "in
all respects examined like a native protein." In contrast to the helical
peptides, beta sheets have had more experimental difficulties: "...the
exposed amides at the edges of beta sheets can hydrogen bond to other sheets,
leading to insoluble aggregates." One of the first de novo designed
proteins, Betabellin (which contains beta sheets), has had its solubility
increased by introducing a special type of turn using D-amino acids. The
authors write that "Recent progress in designing structural proteins
has set the stage for the engineering of functional proteins." They
describe an example of a "four-helix bundle protein with four bound
hemes," with spectroscopic properties consistent with the design.
In summary, the helical bundle proteins look like they may be ready for
use as structural elements in nanotechnology, with careful attention to
residue packing, while other structural motifs are being understood, but
A more successful use of beta sheets has been taking place in M. R. Ghadiri's
group at the Scripps Research Institute, as described by P. S. Zurer in
[C&EN 18-20 15Jan96]. Ghadiri's group has been synthesizing peptide
rings with alternating D- and L-amino acids. The "rings adopt flat
conformations with the amide carbonyls and NH groups pointing up and down,
perpendicular to the plane of the ring. These rings self-assemble into nanotubes
by stacking one on top of the other, linked by intermolecular hydrogen bonds
in a beta-pleated sheet motif."
The group has sufficiently fine control over the structures formed that
they can add functions to their tubes. "For example, the chemists have
engineered a system in which evenly spaced carboxylic acid side chains on
the outside surface of the nanotube bind copper ions." Ghadiri's group
has also been successful in freezing their self-assembled structures in
place with covalent chemistry. "They incorporated two side chains bearing
terminal olefins into a ring composed of eight amino acids. In nonpolar
organic solvents, a Grubbs ruthenium catalyst initiates a ring closing reaction
that couples two cyclic peptides together. The products are two 38-membered
ring structures formed through a double metathesis [olefin exchange] reaction,
with none of the smaller bridged rings that would result from intramolecular
It would be interesting to see if the group could synthesize pairs
of cyclic peptides which would assemble into nanotubes, since this could
permit a Merrifield-style synthesis of distinct oligomers, as well as the
nanotubes that they can currently build, which are impressively long (200-300
µm), but have uncontrolled length.
Redesigning hydrophobic cores:
J. R. Desjarlais and T. M. Handel, writing in [Protein Science
4: 2006-2018 1995] describe a novel computational and experimental
approach to redesigning the hydrophobic cores of proteins. They "have
designed and engineered several variants of the 434 cro protein,
containing five, seven, or eight sequence changes to the hydrophobic core."
Prior to this work, "designed proteins generally lack a well-defined
and uniquely structured folded state. These proteins usually display weak
cooperativity in their unfolding transitions and poorly dispersed NMR spectra.
Because of the poorly structured nature of these proteins, determination
of high-resolution structures for these molecules has also been hampered."
The lack of high-resolution structural information is a particularly important
hurdle to cross, because this information is crucial in providing detailed
diagnostics for tuning the structures. We have to solidify the protein structures
well enough to get enough information to really debug them.
The authors' design methods start with the native protein. They build a
"custom" rotamer library for the hydrophobic core by removing
the core side chains from the protein, but retaining the backbone and the
non-core side chains. They examined rotamers at 5° increments of torsion
angles, retaining only 18 low energy configurations for each of the hydrophobic
residues examined. The selection of well-packed structures using this rotamer
library is a substantial computational task. "...for a small protein
with 10 core positions, more than 1018 structural solutions exist
with roughly 1010 sequence combinations."
The authors dealt with this combinational explosion by optimizing their
designs with a genetic algorithm. This step takes roughly 1 to 3 hours on
a 150-MHz processor, examining 50,000 candidate structures. The primary
result is that the authors were able to design two variations on 434 cro
which "are of comparable thermal stability to the C-1 native control."
Not all of the designs were this stable. Another variant, designed by the
same methods, was significantly destabilized relative to the native protein.
In addition to the thermal stability evidence, 1D proton NMR spectra were
examined for three of the proteins. "Designed proteins typically have
very poorly dispersed NMR spectra due to a combination of exchange broadening
and chemical shift averaging caused by a dynamic folded state." In
the spectra examined, the spectra are about as well dispersed as in the
native protein. "This implies that for these representative variants,
the folded state is well ordered."
Table of Contents - Foresight Update 24
One class of useful nanometer structures that can be constructed with protein
technology is that of catalytic antibodies. These proteins help extend synthetic
capabilities by controlling the orientation with which reactants encounter
each other, reducing the number of side reactions that take place, increasing
the purity of the products formed, and hence improving the synthetic utility
of the reactions. This is both an application area for nanotechnology and
potentially a mechanism for extending the variety of stiff, polycyclic building
blocks available to the nanotechnologist. The next two papers extend the
state of the art in this area.
Reactive Compound Immunogens:
Writing in [Science270: 1775-1782 15Dec95], P. Wirsching,
J. A. Ashley, C.-H. L. Lo, K. D. Janda, and R. A. Lerner describe an extension
to the technology of antibody catalysis. Previous work has generated catalytic
antibodies by inducing an immune response to an inert antigen that
models the transition state of a desired reaction. The antibody produced
then binds to the the transition state of the reaction, stabilizing this
transition state, reducing the activation energy of the reaction, accelerating
the reaction, and reducing the fraction of the substrates that undergo undesired
The current work uses "reactive compounds as immunogens designed to
promote specific chemistry in the antibody binding site, both in vivo
during antibody induction and then later in catalysis. Thus, at the time
of antibody-antigen encounter, a component of the binding energy results
from complex chemical reactivity as well as from simpler forms of complementarity
dependent on electrostatic and hydrophobic forces." There is a trade-off
required in using reactive immunogens, because "there must be sufficient
reactivity to undergo chemical reactions in the binding site of the antibody,
but not too [sic] much lability to be completely degraded by the many chemical
entities encountered in vivo during immunization."
The specific reactive system described in this paper was an organophosphonate
diester, RP=O(OR')2 and one of its hydrolysis products, RP=O(OR')O-.
The final antibody catalyzed the hydrolysis of an analogous carboxylic ester,
as well as the hydrolysis of the organophosphonate diester. The number of
turnovers of the phosphonate diester was limited (typically 1-3) because
the antibody can itself be phosphonated by the diester, inactivating it.
The net result of this work is to add a new option to catalytic antibody
technology, broadening the range of immunogens that can be used to trigger
formation of potentially useful antibodies.
Aldol Condensation with Catalytic Antibodies:
Writing in [Science270: 1797-1800 15Dec95], J. Wagner, R.
A. Lerner, and C. F. Barbas III describe catalytic antibodies that perform
the aldol condensation. The aldol condensation is formally an addition of
a ketone (or aldehyde) with an alpha hydrogen, R(C=O)CHR'R'' (the aldol
"donor") across the carbonyl of another ketone (or aldehyde) R'''(C=O)R''''
(the aldol "acceptor") to give R(C=O)CR'R''C(OH)R'''R''''. This
reaction "is, arguably, the most basic C-C bond forming reaction in
chemistry and biology." There are natural enzymes that catalyze this
reaction but "the most limiting aspect of the application of natural
enzymes in synthesis is their rather poor acceptance of a range of substrates.
Although natural enzymes display broad specificity with respect to the aldol
acceptor, the aldol donor is usually limited to the natural substrate. For
example, among the ketones studied for antibody catalysis only acetone is
a substrate for a natural enzyme. In contrast, antibody aldolases can use
various aldol donors and acceptors. The antibodies accept acetone, fluoroacetone,
chloroacetone, 2-butanone, 3-pentanone, 2-pentanone, and dihydroxyacetone
as aldol donor substrates." This flexibility has advantages and disadvantages
for applications of these antibodies to synthesis.
It is helpful to be able to catalyze a variety of reactions with one antibody,
but it is also helpful to have the catalytic antibody be sufficiently selective
to catalyze only one reaction amongst those reactions that can potentially
occur within the reaction mixture. The potential reactions include possibilities
due to various possible aldol condensations of the initial reactants (due
to the variety of alpha hydrogens on the aldol donor and to the possible
directions of attack of the aldol donor on the aldol acceptor) and due to
possible further reactions of the products of the initial reactions.
In cases where the variety of alpha hydrogens on the aldol donor allow for
a variety of possible products, for instance with "reactions with 2-butanone
and 2-pentanone, the antibodies exhibit some control of the regioselectivity
of the aldol addition by preferential formation of the most substituted
enamine [the activated form of the aldol donor within the catalytic antibody]."
These cases gave product ratios of 94:4 and 73:27, respectively, in favor
of the products formed from the most substituted enamines.
In a test of the selectivity of the direction of attack of an aldol donor
(acetone) on an unsymmetrical aldehyde acceptor, an 11:1 ratio of the two
possible products was formed under antibody catalysis, demonstrating the
stereoselectivity of the catalyzed reaction.
In a test of side reactions, monitoring the concentration of reactants and
the expected product during antibody catalyzed addition of acetone to a
branched 3-phenyl-propionaldehyde acceptor gave results where "the
perfect mass balance (top line [from Fig. 6 in the paper]) indicates that
no side reactions, such as elimination or polymerization, occurred over
that period [a 35 hour reaction run converting 90% of the acceptor to the
addition product]. Thus, the antibody-catalyzed aldol reaction is an exceptionally
mild method of C-C bond formation."
In summary, antibody catalyzed aldol condensations provide a promising technique
for exploiting protein technology to extend synthetic capabilities, supplying
both an application area for protein based nanostructures and possibly extending
the range of building blocks available for nanotechnology.
The technologies described in the papers above are useful, but they all
rely on diffusion of chemical species to a molecular machine such as a catalytic
antibody in order for useful work to be initiated. The paper below describes
a mechanism for thermal diffusion to trigger useful changes in a
molecular machine, which is a much faster mechanism, and which brings us
closer to being able to build molecular machines controlled by broadcast
signals (as in Merkle's replicator architecture) at a reasonable rate.
An advance in control of a protein's ligand binding ability comes from P.
S. Stayton, T. Shimoboji, C. Long, A. Chilkoti, G. Chen, J. M. Harris, and
A. S. Hoffmann, writing in [Nature378: 472-474 30Nov95].
They bound a temperature sensitive polymer (poly(N-isopropylacrylamide))
to a mutant streptavidin, a protein that normally binds biotin. "Normal
binding of biotin to the modified protein occurs below 32°C, whereas
above this temperature the polymer collapses and blocks binding. The collapse
of the polymer, and thus the enabling and disabling of binding, is reversible."
Below the transition temperature the polymer "adopts a hydrated coil
conformation" which spreads it out and keeps it from blocking the biotin
binding pocket, while above the transition temperature the polymer "is
a collapsed globule" which does block binding. Considered dynamically,
the collapsing polymer acts as a thermomechanical actuator to shove the
biotin molecule out of its binding pocket.
The authors suggest that this control of binding "could also be used
to remove inhibitors, toxins, or fouling agents from the recognition sites
of immobilized or free enzymes and affinity molecules, such as those used
in biosensors, diagnostic assays or affinity separations. This could be
used to 'regenerate' such recognition proteins for extended process use."
From a molecular manufacturing point of view, thermal control of affinity
is notable since it permits an engineered protein to grasp or discard a
feedstock molecule in response to a broadcast thermal signal. Unlike actuation
via binding of some "signalling" molecule, this mechanism does
not require movement of additional chemical species for each actuation cycle.
The current state of the art of protein design and fabrication in particular
- and the fabrication of nanometer scale structures in general - is still
far from the point where it would be feasible to design structures in the
absence of feedback on how successfully the target structure was actually
fabricated. The papers below describe advances in diagnostic techniques
which help provide this feedback.
Protein Crystal Growth:
Protein crystal growth is an important and difficult step in obtaining structural
information on proteins from x-ray diffraction measurements performed on
these crystals. A number of advances in protein crystal growth are described
in an article by D. Normile in [Science270: 1921-1922 22Dec95].
The article describes several different advances presented at the "Sixth
International Conference on Crystallization of Biological Macromolecules."
The first advance was a quantitative analysis of improved quality of protein
crystals grown in space. The analysis found that the "mosaicity"
of crystals grown in microgravity was reduced. Macroscopic protein crystals
are really composed of many small blocks of crystal which are somewhat misaligned.
Mosaicity is a measure of how severe this effect is. "Reduced mosaicity
can improve the signal-to-noise ratio and should result in improved precision
in determining crystal structures." In experiments where lysozyme crystals
were grown on Earth and in space under equivalent conditions, analysis of
diffraction data showed "that the Earth-grown crystals had a mosaicity
three times greater than the space-grown crystals."
A second advance was made in microbatch techniques, "in which crystals
are grown in 1 to 2 microliter drops of a mixture of a protein and a crystallizing
agent...Using even smaller droplets of solution isn't practical, because
the drops dry up before the protein crystallizes. By covering each droplet
with a layer of oil, Chayen and her colleagues found, they could prevent
evaporation of the tiny microliter droplets and also protect the sample
from contaminants in the air." In addition, the remaining evaporation
appears to go through the oil, allowing tuning of the rate by selecting
the type of oil and the thickness of the oil layer.
NMR Probe Spectra:
Writing in [Science270: 1967-1970 22Dec95], D.L. Olson, T.
L. Peck, A. G. Webb, R. L. Magin, and J. V. Sweedler describe a new NMR
probe that obtains spectra from samples which are a factor of 130 less massive
than those usable in a conventional NMR probe. "The microcoil is 1
mm long and encloses a sample of 5 nl within the [fused silica] capillary."
A sustantial improvement in sensitivity came from immersing the microcoil
in Fluorinert FC-43, which provides a match to the magnetic susceptibility
of the copper coil, thereby improving the uniformity of the magnetic field,
reducing the line widths of the signals, and improving sensitivity. "The
ability to acquire high-resolution spectra on 5-nl samples with improved
mass sensitivity enables a variety of uses for microscale NMR. Biological
applications will greatly benefit from the ability to structurally identify
molecules with submicrogram LODs [limits of detection]. As an example, a
microcoil NMR spectrum of a seven-amino acid peptide is shown..." From
the point of view of nanotechnology, this advance will assist in using NMR
to confirm synthetic protein geometries (for sufficiently rigid proteins),
or to screen synthetic proteins for rigidity based on the global dispersion
of their NMR spectra, even when the synthetic difficulties limit sample
In addition to using individual protein molecules for nanotechnological
applications, there are some larger scale components from biological systems
that may also be useful components for nanotechnology.
One phase of research on microtubules has been capped as Y. Zheng, M. L
Wong, B. Alberts, and T. Mitchison, writing in [Nature378:
578-583 7Dec95], identify a gamma-tubulin complex which "acts as an
active microtubule-nucleating unit which can cap the minus ends of microtubules
in vitro." The complex appears (via electron microscopy) to be a ring
25-28 nm in diameter ("similar to the outer diameter of a microtubule
(25nm)") with a thickness of about 10 nm. This is potentially useful
since microtubules are important structural elements in cells. More precise
knowledge of how to control their formation and orientation might allow
us to exploit them as structural members in early nanomachinery. The control
exerted by this complex may be quite precise. Microtubules which spontaneously
assemble typically have 14 protofilaments (lines of protein molecules stretched
out along the tubule) while those assembled in vivo (nucleated from the
centrosome) have 13. Essentially the control of the nucleation acts like
an initial circle of bricks in starting a spiral tower. It very precisely
sets the pattern for the tower as a whole, even though the bricks themselves
may permit several patterns.
Writing in [Science269: 496-512 28Jul95] J. C. Venter et.
al. (40 authors in total) describe the full sequencing of Haemophilus
Influenzae Rd. This genome of 1,830,137 base pairs is the first complete
genome sequence for a free-living organism. The strategy followed by this
group "eliminated the need for initial mapping efforts and is therefore
applicable to the vast array of microbial species for which genome maps
are unavailable." Rather than preorganize the genome with a mapping
approach, in this group's strategy "a single random DNA fragment library
may be prepared, and the ends of a sufficient number of randomly selected
fragments may be sequenced and assembled to produce the complete genome."
A large part of the problem solved was computational, there had been a "lack
of sufficient computational approaches that would enable the efficient assembly
of a large number (tens of thousands) of independent, random sequences into
a single assembly." From the point of view of nanotechnologists, the
main effect of this advance is to fully specify an existing system that
can replicate itself using simple feedstocks. The analysis of the genome
sequence has thus far yielded 1743 regions which appear to code for proteins.
These regions were matched against "a database of nonredundant bacterial
proteins (NRBP) created specifically for the annotation... NRBP is composed
of 21,445 sequences extracted from 23,751 GenBank sequences and 11,183 Swiss-Prot
sequences from 1099 different species." Of the 1743 possible proteins,
1007 were identified with sufficient accuracy to allow assignment of their
biological role. An additional 347 matched "hypothetical proteins"
in the database, and 389 are unidentified. Ideally, it would be useful to
know what function each of these proteins plays and to have tertiary structures
for all of them, but this is clearly going to take some time. Other regions
that have been identified in the genome include ribosomal RNA and transfer
In the analysis of proposed nanometer scale structures, a variety of analysis
methods are useful in evaluating the structures before attempts are made
to fabricate them. The most expensive of these methods, but the ones which
make the fewest approximations and are therefore potentially the most trustworthy,
are the quantum mechanical ab initio methods. The papers described
below extend these methods.
Writing in [C&EN 29 14Aug95], S. Borman describes an improved
ab initio technique called MEDLA (molecular electron density Lego
assembler) developed by P. G. Mezey and P. D. Walker of the University of
Saskatchewan, Saskatoon. "To demonstrate the technique, Mezey has published
ab initio electron density calculations for bovine insulin, which
contains 773 atoms, and for a bacteriophage protein containing more than
1,000 atoms." G. M. Maggiora, of Upjohn Research Laboratories, commented
that "People have tried to divide molecules up in various ways...to
estimate properties of larger molecules, but it's been largely unsuccessful.
At least to my knowledge, this is the first example where something of this
accuracy has been accomplished." Maggiora further commented that Mezey
and Walker "calculate the smaller fragments that fit into large molecules
in a very high level way...So for those molecules, they have information
equivalent to the whole quantum mechanical wave function, the electron density,
and any other properties (such as the molecular electrostatic potential)
that can be derived from it." From the point of view of nanotechnologists,
this should permit tip reaction calculations to be extended to much larger
neighborhoods of the reaction center than has previously been possible,
extending our confidence in these analyses.
Writing in [Scanning Microscopy9: 381-386 1995] K. Cho and
J. D. Joannopoulos describe ab initio simulations of interactions
between a tungsten tip and a silicon (100) surface. Their simulations used
"a state-of-the-art density functional pseudopotential conjugate gradient
scheme." The simulation "results predict that the tip can be used
to flip dimers on the surface, from one buckled configuration to the other,
reversibly, and without inducing damage to either the intrinsic surface
or the tip." The top layer of a silicon (100) surface consists of a
layer of silicon dimers, and authors' simulations show that the dimers can
reside on the surface with a tilt of about 20° in either direction
with respect to the surface. In the absence of a tip, there is a barrier
of about 0.1 eV between the two tilted geometries.
Calculations of the tip-surface system showed that the silicon atom underneath
the apex of the tip is stabililized by about 0.2 eV in the configuration
which tilts it up, closer to the tip atom. "Consequently, the tip always
measures a dimer atom in the up-flip geometry, resulting in a symmetric
STM image of the dimer." The calculations indicate that gradually moving
the tip up, while keeping it centered on one atom of the dimer, leaves the
dimer with that atom elevated. At room temperature, thermal transitions
would soon randomize the dimer between its two possible states. At low temperatures
the authors suggest that "Since each dimer can be manipulated to exist
in one of two equivalent states, it conceivably can be used to write and
read one bit of information." This work advances nanotechnology because
the authors' calculations, though fully quantum mechanical like Musgraves'
tool work, extend those calculations towards a system which is currently
experimentally accessible. In addition, the authors' calculations uncovered
a mode of operation which may be directly useful in information storage.
Carbon nanotubes, also known as fullerine tubes or graphitic tubes, are
potentially useful to nanotechnologists in a variety of ways. Nested nanotubes
may prove useful as bearings; nanotubes have been proposed as pores in nanostructures;
and nanotubes are strong and stiff enough to be useful in a variety of structural
roles. In the nearer term, nanotubes with well-characterized terminations
would be attractive probe tips for scanning microscopy. The papers below
describe studies of electron emission from nanotubes, which is sensitive
to the details of nanotube terminations, and may help to drive control of
Nanotube Field Emitters:
Writing in [Science270: 1179-1180 17Nov95], W. A. de Heer,
A. Châtelain, and D. Ugarte describe a carbon nanotube field emission
electron source, with a current density of 100mA/cm2, that is
potentially useful for flat screen display applications. The utility of
the nanotubes comes directly from their sharp tips, which concentrate the
effective field strength by a factor of as much as 1300 above the uniform
field in which the tubes are immersed. By contrast, conventional field emitters
typically concentrate the field by a factor of 10. This group has recently
been able to align arrays of nanotubes, allowing this technique to be used
for large area cathodes. "The large field amplification factors are
related to the geometry of the tube terminations. As shown by Iijima et.al. [Nature 356: 776 1992], the terminations have a variety
of structures and are often conical with 20° opening angles, with radii
of curvature at the tips that may be <1 nm. The density of emitting tips
is estimated to be on the order of 105 cm-2. Because
this is only a small fraction of the nanotube density (approx. 108
cm-2), only those tubes with particularly sharp tips that are
favorably situated on the film emit efficiently." Since nanotubes with
sharp, well-controlled terminations would be ideal for proximal probe work,
it will be interesting to see if this group's developments become applicable
to that area.
Carbon Atomic Wire Emitters:
Writing in [Science269: 1550-1553 15Sep95], A. G. Rinzler,
J. H. Hafner, P. Nikolaev, L. Lou, S. G. Kim, D. Tománek, P. Nordlander,
D. T. Colbert, and R. E. Smalley describe some electron emission experiments
from individual nanotubes. They argue that the active field emitters are
"individual linear carbon chains -- Cn atomic wires -- that
have been pulled out from the open edges of the graphene sheets of the nanotube
as shown in Fig. 4 and are held taut under the influence of the electric
field." At room temperature the field emission current was 0.4-0.8
microamp. Oddly enough, the emission goes down sharply on heating the nanotube
with a laser to approx. 1500°C, an effect that the authors attribute
to "thermally induced evaporation of C3 and other small
carbon radicals from the tip of the chain until chain is so short that the
electric field is no longer sufficient to produce efficient emission. We
expect that there is a steep temperature dependence of the effective resistance
of the carbon chain, with nearly ballistic transport when the chain is cool,
but frequent scattering and consequent chain heating and further increase
in resistance once the vibrations of the chain become excited." The
authors suggest that the chains "may turn out to be excellent coherent
point sources of monochromatic electron beams and to have wide applications
as probes, emitters, and connectors on the nanometer scale."
Fabrication with scanning probes has the advantage of giving the experimenter
direct control over the position where the modification occurs, at the cost
of fabricating structures one at a time. Most of the atomically precise
techniques using scanning probes, however, have used feedback from an STM
current to determine if a selected atom has been moved. They are therefore
limited to conducting substrates. The new technique described below relies
on a novel feedback mechanism which avoids this limitation.
Writing in [Science 270: 1639-1641 8Dec95], E. S. Snow and P. M.
Campbell described a novel nanometer scale fabrication method. The authors
anodically oxidized a Ti film with an electrically biased (-10 volts with
respect to the substrate) silicon AFM tip. The innovation in their technique
was to monitor the electrical resistance of their structure during fabrication,
automatically switching off the bias when the target resistance was reached.
The current flow in the anodic oxidation itself is sufficiently low that
it does not interfere with the resistance measurement. Thus far, the narrowest
wire that the authors have fabricated "was obtained with a resistance
increase that corresponds to a final wire width of 3 nm." It will be
interesting to see if the authors are able to extend this technique to produce
atomic scale constrictions. Unlike most fabrication techniques, the introduction
of feedback into this technique might allow atom-by-atom monitoring of the
oxidation process as a target structure is approached.
There have been many articles over the last several years about nanometer
scale particles. Typically, these articles have described particles with
a fairly narrow distribution of diameters, but with curved surfaces that
imply a fairly wide distribution of surface structures. These particles
have interesting and potentially useful electronic properties, but consist
of too broad a range of isomers to be attractive building blocks for atomically
precise structures. The article below presents some experimental evidence
for better control, which might make the new particles plausible components
for atomically precise structures.
Writing in [MRS Bulletin 23-32 Aug95], A. P. Alivisatos describes
some work on nanometer-scale (1nm-5nm, in various experiments) crystallites,
mostly of CdSe, with some Si and some HgS examples. Most of the article
was on spectroscopy, but what I found notable was that many of the micrographs
of the nanocrystals showed not merely well ordered interiors but also well-defined
facets. "The crystallite, at 350 °C, has been made in just the
right way in that the temperature is high enough that it will become crystalline
inside and that, even during the few seconds during which it is formed,
there is enough time for it to arrange itself and to facet." These
crystallites may be potentially useful as building blocks for nanotechnology.
The bonds in a crystal latticecan be considered
to form a rigid, polycyclic molecule. The open question is whether a useful
concentration of a single isomer of these molecules can be produced. The
rounded crystallites that have appeared in many previous articles looked
quite unpromising, considering the range of local structures that must be
energetically or kinetically accessible to produce such a surface. Faceted
crystallites, on the other hand, must include a much more limited range
of surface structures, perhaps a range sufficiently small to make isolating
a single species approachable.
Jeffrey Soreff is a researcher at IBM with an interest in nanotechnology.