Foresight Update 22
Page 3
A publication of the Foresight Institute
 Nanostructure
Research at Illinois's Beckman Institute
Since it opened in 1989, the Beckman Institute for
Advanced Science and Technology at the University of Illinois,
Urbana-Champaign, has taken great pride in its
interdisciplinary approach to basic research. When Hungarian Jiri Jonas
became the second director of the Institute, he brought research
efforts into focus in three "main research themes."
They include biological intelligence, human-computer intelligent
interaction, and-of note to Foresight members-molecular and
electronic nanostructures.
Several recent publications have high-lighted nanoscale efforts
underway at Beckman Institute. In a November 11, 1994 lead
editorial, Science
lauded Beckman's multidisciplinary approach and described its
nanostructure projects. "One is a study of self-organizing
structures formed from inorganic substances as well as from
protein and other molecules of interest to life scientists."
Science also notes "significant results from research using
the scanning tunneling microscope (STM) in fabricating
semiconductor nanostructures. A prerequisite was magnificent
equipment that facilitates conduct of STM manipulations under a
very high vacuum. In one experiment, a clean crystalline silicon
surface was exposed to atomic hydrogen with resultant coverage of
exposed surface silicon bonds. Later it was possible to
selectively remove a narrow band (0.001 micrometer) of the
hydrogen. The narrow band could react with other chemicals while
the hydrogen-covered silicon remained inert. The STM experiment
could be a step on the road to new devices."
Chemical &
Engineering News wrote extensively about Beckman's efforts in
its March 6, 1995, issue, writing that "nanostructure
research merges mechanics, reaction dynamics, optics and
electronics...with the merger the disciplines will lose their
conventional meaning. Moveover, overlapping interests in
chemistry, biochemistry, physics and electrical engineering have
aided in refocusing the group's research into fabrication and
self-assembly tools, visualization and dynamic probe techniques,
and numerical modeling and analysis."
"Experiments at the Beckman Institute seek to marry recent
advances in research with scanning probe microscopes for imaging
and pattern delineation, genetic engineering, complex synthetic
routes to molecules approaching mesoscopic dimensions, and
chemical characterizations capabilities that have now evolved to
a level permitting the examination of a single molecule."
Research topics include biomolecular electronics, theoretical
modeling of nanostructure devices, and protein engineering.
The Beckman Institute brochure, annual activities reports for
some research groups, the biannual newsletter, faculty research
profiles, and Institute technical reports may be obtained by
contacting: Office for External Relations, Beckman Institute,
University of Illinois at Urbana-Champaign, 405 N. Mathews Ave.,
Urbana, IL 61801 USA; tel 217-244-5582, fax 217-244-8371, email
jjones@director.beckman.uiuc.edu.
The Arnold O. and Mabel M. Beckman Institute for Science
& Technology at the University of Illinois,
Urbana-Champaign, houses multidisciplinary work contributing
to nanotechnology development. The 300,000-square-foot
building, which won the 1990 R&D Magazine
Laboratory of the Year Award, was designed by architects
Smith, Hinchman & Gryllis Associates and built with a $40
million donation from the Beckmans. (The company founded by
Arnold Beckman, Beckman
Instruments, is a consistent sponsor of the Foresight
conferences on nanotechnology.)
Recent
Progress: Steps Toward Nanotechnology
by Jeffrey Soreff
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Fabrication with Scanning Probes
For the first time: catalysis using an AFM tip
Scanning probe techniques-STM (scanning tunneling microscope) and
AFM (atomic force microscope)-have been used to modify individual
molecules. Their main advantage is that they let the experimenter
make a change at a precisely chosen location. In contrast,
chemical reactions in solution will, roughly speaking, react in
the same way at all chemically equivalent sites, allowing much
less geometrical control. The main disadvantages of probe
techniques are that they allow the building of only one molecule
at a time and that the set of reactions that can be performed is
currently much narrower than the set of reactions in
solution-phase chemistry. The research described below has
widened the set of reactions the scanning probe techniques can
cause.
A scanning probe fabrication advancement came from W.T. Muller,
D.L. Klein, T. Lee, J. Clarke, P.L. McEuen, and P.G. Schultz,
writing in [Science 268: 272-273 14Apr95].
They coated an AFM tip with platinum, submerged it in
hydrogen-saturated isopropanol, and scanned it over a surface
coated with a monolayer of an azide (-N3) compound.
This resulted "in the catalytic conversion of the azide
groups to amino groups...The amino groups formed by this process
can be selectively modified with a variety of reagents in a
second step to generate more complex structures." Currently,
the resolution of this technique has been measured by
derivatizing the amine with 40 nm latex beads, and the sharpness
of the pattern was limited by the bead diameter. "The free
amino groups generated in the catalytic reaction can be
derivatized in high yields by a variety of molecules, including
acids, aldehydes, and metal complexes." If it should prove
possible to modify a surface with atomic precision via this
technique, the flexible chemistry should permit derivatization
with reagents that introduce new azide groups into additional
layers, allowing construction of 3D covalent structures.
A new chemistry for atomically precise surface modification has
been introduced by T.-C. Shen, C. Wang, G.C. Abeln, J.R. Tucker,
J.W. Lyding, Ph. Avouris, and R.E. Walkup. They have used an STM
to desorb hydrogen from hydrogen-terminated silicon (100)
surfaces [Science 268: 1590-1592 16Jun95] [Microelec.
Eng. 27:23-26 1995]. They observed two modes for
this desorption. At high biases, >6.5 volts, the STM operates
in a field emission regime. In this regime, the lines drawn are
roughly 5 unit cells wide. At lower voltages, desorption becomes
less efficient but more selective. Individual rows of silicon
dimers could be dehydrogenated with an STM bias of 4.5 volts. In
addition, the lines can be reacted with O2 and NH3.
"The patterned linewidth appears to be unchanged after
oxygen exposure." The authors attribute the low bias
desorption process to vibrational excitation of Si-H bonds by
tunneling electrons. The bonds accumulate energy through a series
of excitations, so unfortunately the mechanism is limited to
materials with long vibrational lifetimes. The authors give the
vibrational lifetime for Si-H on Si (100) as ~10-8
sec, while on metals it is only ~10-12 sec.
Nonetheless, the ability to draw reactive lines two atoms wide is
promising, extending the ability to fabricate atomically precise
structures.
Self-Assembled Systems
These structures look promising for building stiff system
components
In contrast to scanning probe techniques where molecules are
built one at a time, large numbers of large, atomically precise
structures are routinely built in parallel by living organisms.
Enzymes, for instance, consist of one or more protein chains
(often containing other groups as well) which typically fold into
atomically precise 3D structures. These folds are produced by
fairly weak bonds, typically hydrogen bonds and adhesion of
hydrophobic (oily) parts of the protein molecule to each other in
water. The advantage of self-assembled structures is that large
numbers of them can be built at one time. This makes early
applications easier than for structures built with scanning
probes. Their disadvantages are that they are difficult to
design, because a 1D polymer can fold into many different 3D
shapes, so it it difficult to ensure that the desired one is
formed, and that they are much less stiff than 3D networks of
strong, covalent bonds. This makes it difficult to build
self-assembled structures which will move as precisely as
covalent ones. The research described below ameliorates some of
these factors and clarifies others.
R.S. Lokey and B.L. Iverson have synthesized molecules that
"fold in water into a pleated structure, as a result of
interactions between alternating electron-rich donor groups and
electron-deficient acceptor groups." [Nature 375:
303-305 25May95] This structure holds the promise of a class of
structures as general as peptides, but with a fixed, predictable
secondary structure. The authors appear to have provided us with
a structural motif with real backbone. The donor and acceptor
groups are rigid, aromatic ring systems,
"1,5-dialkoxynaphthalene and
1,4,5,8-naphthalenetetracarboxylic diimide," so undesirable
flexibility within these groups will be minimal. The structures
allow any (alpha)-amino acid to be placed between the donor and
acceptor groups. "They can be prepared by an easy, modular
synthetic route. As such, they define a new, and possibly general
approach to the construction of large synthetic macromolecules
with well-defined higher-order structure."
J. Fredericks, J. Yang, S. J. Geib, and A. D. Hamilton describe a
variety of self-assembled structures in [Proc. Indian Acad
Sci. (Chem Sci) 106: 923-935 Oct94]. These include
a wide variety of structures which self-assemble via hydrogen
bonds. Many of their structures resembled the hydrogen-bonded
base pairs in DNA. Most of the component molecules contained
aromatic cores, usually heterocycles which contained at least
some of the hydrogen-bonding groups within the cores. These
structures look promising as a design strategy for building stiff
components for molecular systems. They have far fewer
freely-rotating bonds than do peptides with a similar number of
atoms. This reduces the analysis effort needed to predict the
structures that can self-assemble. For example, one of the
structures described is a cyclic trimer of a pyridoquinoline,
which itself consists of three fused six-membered rings. The
advantages of such a structure for nanotechnology are that it is
inherently quite stiff, with no freely rotating bonds, and that
it has 6 positions per monomer where substituents might be
attached. The disadvantage of the structure is that it is a
symmetrical trimer, so there is currently no way to select which
modified monomer would go into which position. This symmetry is
typical of the structures described in this paper. Further work
to synthesize similar structures, with unique positions for each
constituent monomer, would be helpful in extending the design
freedom of structures like these.
A general survey of self-assembled systems appeared in [Nature
375: 101-102 11May95]. "A covalent network might have
the robustness of diamond, but mistakes in connectivity are
frozen in. A complex system of any sort gains tremendously from
the capacity for error correction." The survey goes on to
cite equilibration of ligands and reversibility of certain
organomercury bondings as examples. In order to form atomically
precise systems, the final geometries of structures must be
stable. What can be useful is for rigid pieces such as
heterocyclic bases to be interconnected with multiple weak bonds,
such as hydrogen bonds, so that partial alignment of the pieces
does not result in irreversible misalignments, even though the
final bond between the pieces as wholes may be essentially
irreversible. The advantage of multiple weak bonds is essentially
the specificity that it provides, most obviously in DNA sequence
binding, as in N. Seemans's
polyhedral DNA structures.
In [Nature 374: 495-496 6Apr95], J.S. Moore
reports on some work, primarily by J. Wuerst and co-workers, on
organic nanoporous solids. These structures are useful because
they provide structured environments for reactions. Wuerst is
building them out of organic compounds that hydrogen bond to each
other. "Although the topology of a single network can
reasonably be predicted from the geometry of its constituents, it
is nearly impossible to predict the fine details of the
interpenetrated structure." As with proteins, the
noncovalent self-assembly lets us create structures which are
larger than our largest rigid covalent structures, but the
control of the 3D structure needs to be improved.
The structures formed by weak bonds can be imperfect. J.A.Ernst,
R.T.Clubb, H.-X.Zhou, A.M. Gronenborn, and G.M. Clore have shown
that there is positionally disordered water present in a protein
cavity [Science 267: 1813-1817 24Mar95]. They
bounded the residence time to be between 1 nanosecond and 100
microseconds. Unfortunately, this range of time scales includes
time scales which are desirable for movement of nanostructures.
If the water equilibrates much faster than a structure operates,
it will just act as an additional potential term for the
structures's degrees of freedom. If it equilibrates much slower
than operation times, then it will act like an ice member in the
structure. If it equilibrates on a time scale comparable to
movement, however, it introduces another energy dissipation
mechanism into the structure. In the experiments described in the
paper, the water is present in a hydrophobic cavity, so designing
a structure to eliminate it may require systematically filling
even these cavities.
In [Science 267: 1619-1620 17Mar95] P.G.
Wolynes, J.N. Onuchic, and D. Thirumalai survey some recent work
on the kinetics of protein folding. The essential point is that,
for a protein to fold in a reasonable time, the folding
temperature must be well above the glass transition temperature
which "is equivalent to maximizing the 'stability gap'
between the native state and disordered collapsed structures
measured in units of the ruggedness [of the potential surface for
the disordered structures]." E.I. Shakhnovich investigated
the stability gap in simulated 80-mer model proteins [Phys.Rev.Let.
72: 3907-3910 13Jun94] and found that there was a
stability gap for proteins designed with a simulated annealing
process when 20 residue types were used, but no stability gap was
found when only 2 residue types were used. This shows that
simplifying the model of protein residues to
hydrophobic/hydrophilic is inadequate. It also shows that in
order to use nonprotein 1D polymer systems to build 3D
structures, more than 2 residue types will be needed.
Analysis and Design Techniques
While most of the research described above extends the ability
to build molecules, it is also important and difficult to choose
which molecules to attempt to build in order to fulfill some
purpose, and to analyze proposed molecules to see if they really
do what the designer wants them to do. The research described
below extends these abilities.
Y.S. Smetanich, Y.B. Kazanovich, and V.V. Kornilov wrote a paper
[Discrete Applied Mathematics 57: 45-65
Feb95] which analyzes which sets of components and self-assembly
rules give unique structures. They make a number of assumptions
which make their results valuable primarily for stiff structures.
They model self-assembly as the formation of structures from a
set of subunits, where each bond between a pair of subunits
follows a specific assembly rule. They model each specific
assembly rule as a precise relative position and orientation of
the two subunits. In essence, their default is to treat each
bonding site as being specific to one other subunit, with the
bonding site sufficiently rigid to hold the new subunit in a
single position and orientation. I view this as a reasonable
approximation to bonds between large and irregular surfaces, as
between pairs of proteins. If the bonds are not stiff enough,
there are problems with self-assembly that are not covered by
this approximation. Most notably, assembly steps that should form
cycles may fail to close them, forming extended polymers instead
[R. Merkle, private
communication]. The authors' approximation is clearly not good
where a bond between subunits allows free rotation, for instance
where a bond between subunits consists of a single hydrogen bond.
It is also not a reasonable approximation in a case like a
bearing, where a bond must have a degree of freedom in order to
function. The authors treat the subunits as rigid bodies, using
information about their shape to eliminate structures that would
require intersection or distortion of subunits. Overall, I see
this approach as potentially helpful in assisting with the
high-level design of a self-assembling structure, essentially at
the stage where we wish to try a variety of ways to partition the
desired structure into subunits. This approach requires the
ability to design subunits so that their bonds are fairly rigid,
and do not bend or rotate enough to seriously distort a structure
at room temperature.
A. Roitberg, R. B. Gerber, R. Elber, and M. A. Ratner wrote a
paper [Science 268: 1319-1322 2 June95] which
can assist with calibrating molecular mechanics for proteins and
similar molecules. One way to calibrate the potential energy
surfaces for these molecules is to calculate the vibrational
spectrum and compare it with experiment. The authors showed that
anharmonic terms in the potential have quite a dramatic effect on
the predicted spectrum for transitions from the vibrational
ground state. They also showed that the effect of these terms is
very largely confined to anharmonic corrections within modes,
with very little net shift in the energies of modes due to
interactions with other modes. This is different from the results
seen in small molecules. The authors attribute the difference to
the interaction between any given mode and all of the other modes
averaging to zero for large molecules. This work can help make
the calibration of potential energy models from vibrational
measurements more accurate, while keeping the calibration
computationally efficient.
J.F.Y. Brookfield writes in [Nature 375: 449
8Jun95] on the application of "forced evolution"
(generating and selecting large number of candidate structures by
combinational techniques) to solving "problems in the design
and optimization of new molecules." The key problem to using
this for nanotechnology is that "The experimenter still has
to test alternative proteins, however, and retain the genes
encoding the best." This appears to be very natural when
maximizing the stability of an interface between an existing
protein and a new one. One can simply use the binding of a
fluorescent derivative of the old protein to assay the new one.
It is less clear, however, how to assay for a specific shape of
the new protein, and that will often be equally important in
building nanostructures.
Applications
DNA computation doesn't seem to extend our 3D control of
synthesis
There are two proposals in progress that could very loosely be
considered early applications of nanotechnology to data
processing. One applies DNA binding to computation, and the other
applies internal movements in a protein called bacteriorhodopsin
to data storage.
There has been a flurry of interest in DNA-based
computation recently, based on L.M. Adleman's demonstration
of a computation of a Hamiltonian path. R. J. Lipton has
described a way to extend this work to finding solutions of the
satisfaction problem. [Science 268: 542-545
28Apr95]
In general, I find proposals such as Lipton's, where the total
amount of external information that must be translated into DNA
is small, to be more plausible than proposals like E. B. Baum's [Science
268: 583-585 28Apr95], which suggest using DNA as a
readout mechanism from a database. While the matching process in
Baum's proposal is indeed fast, the construction of the database
from external data must go through DNA synthesis. Changes to the
database would have to be exceedingly rare in order for Baum's
proposal to be attractive.
The core of the capability that DNA computation provides is a
highly parallel matching capability, evaluating ~1020
alternatives against a constraint in ~102 seconds. By
comparison, specialized electronic chips now have around 106
gates, and operate at ~108 Hertz. If ~103
gates are needed for each matching engine, then a chip could
perform ~1011 matches per second. A DNA matching
engine would approximately equal the speed of 107
current day chips. Is this sufficient to be worthwhile? Further
work may tell.
I find it difficult to assess the implications of a practical DNA
computing application on nanotechnology in general. On the
positive side, such a development would create a routine use of
atomically precisely encoded data.
It is unclear whether it would create an incentive to extend DNA
synthesis. Current capabilities seem adequate to make the
limiting factor in DNA computation be the volume of material
required rather than the number of bases that can be strung
together. This work doesn't seem to extend our three-dimensional
control of synthesis. The matching in it is essentially
one-dimensional.
There have been a number of articles on bacteriorhodopsin optical
storage elements for computers recently (M. Freemantle [C&EN
24-26 22May95] R.R.
Birge [Sci. Am. 272: 90-95 Mar95]). The
basic idea is that this protein has a number of metastable
states, notably a "Q" state "which is stable for
extended periods, even up to several years."
Bacteriorhodopsin can be switched from state to state by
irradiating it with light of the proper frequency. Some of the
transitions require absorbtion of several different photons, so
they can be used to limit transitions to the intersection of
several beams, allowing 3D memories. The implications for
nanotechnology are somewhat hazy. As it stands, an ensemble of
molecules in roughly a cubic micron volume is being used to store
each bit. From a molecular viewpoint, this isn't extremely
different from magneto-optical storage, for instance. On the
other hand, bacteriorhodopsin is a protein, so it could be
tailored at many sites for various desirable properties:
lifetimes of states, absorbtion spectra, and so on. This would
amount to use of the states of a complex molecule for information
storage. Over a longer term, if variations on the protein could
be designed to store multiple bits, perhaps acting as nanometer
scale shift registers, they would provide an incentive to design
structures with a number of moving parts. However,
bacteriorhodopsin's "unique photophysical properties were
discovered in the early 1970s." Waiting for nanotechnology
to be driven by multi-bit versions of this protein could leave
nanotechnologists looking for light at the end of a long tunnel.
Instrumentation
While a variety of scanning probe techniques now allow
reactions with single molecules, they are not yet at the point
where one can assume that a reaction has succeeded without
checking. The scanning probe microscopes themselves can detect
certain reactions, but it is often helpful to have a variety of
instruments which can confirm whether a reaction took place, and
help an experimenter see if they built the structure that they
intended to build. The research described below extends these
abilities.
T. Funatsu, Y Harada, M Tokunaga, K. Salto, and T Yanagida have
improved the sensitivity of a fluorescent detection technique to
the point where they can detect single molecules, and detect
whether they are bound to a surface or diffusing in liquid. [Nature
374: 555-559 6Apr95] The sensitivity of this technique may
help confirm construction of individual molecules with STMs or
AFMs. This is not a technique that images features within a
single molecule, but it can confirm that a single molecule has
been successfully modified. The most sensitive technique that the
authors developed, total internal reflection fluorescence
microscopy, confines the exciting laser beam to a thin, 150 nm
evanescent layer. The emitted fluorescence is currently detected
from the other side of the sample, so this technique requires a
transparent sample, and access to both the top and bottom of it.
The authors intend for their methods to "be extended to
simultaneous measurement of the ATPase reaction and
force/movement by single myosin molecules," presumably with
AFM techniques. One physical effect that adds both an advantage
and a disadvantage to this technique is photobleaching. Under the
authors' conditions, the lifetime of their fluorophores is ~15
seconds. On the one hand this limits the maximum observation time
for a molecule. On the other hand "The high-rate imaging
allowed to see clearly the time course of stepwise photobleaching
of fluorescence from two dye molecules, probably bound to a
single HMM [a myosin fragment]." One concern that this
raises in using the technique to confirm a mechanosynthetic step
is that the reactive fragment of a photobleached fluorophore must
not react with the workpiece in the AFM in a damaging way.
J. Kohler, A.C.J. Brouwer, E.J.J. Groenen, and J. Schmidt
describe a technique that uses the fluorescence of a single
molecule to observe the spin of a single 13C nucleus in that
molecule. [Science 268: 1457-1460 9Jun95].
The observation mechanism is rather intricate, involving two
triplet states with different lifetimes, a microwave-induced
transition between them (which has the effect of extending the
average triplet lifetime), and the ground and first excited
singlet state, which are responsible for the fluorescence. The
experiment was done with deuterated pentacene, present in a
dilute solution in deuterated p-terphenyl crystals. The spectrum
of the microwave resonance depends on the existence and location
of 13C nuclei in the pentacene molecule, and on the strength of
the externally applied field. It is analogous to measuring
spin-spin coupling strengths in NMR, a standard technique used in
determining molecular structures. This technique therefore holds
the potential for confirming the identity of individual nuclei in
selected locations in individual molecules, a capability not
directly available from STM or AFM techniques.
A number of papers described extensions to scanning probe
techniques. S. Fujisawa, E. Kishi, Y. Sugawara, and S. Morita
described observation of atomically resolved friction
measurements on a NaF (100) surface [Nanotechnology 6:
8-11 Jan95]. This work used an Si3N4 tip on
the NaF substrate, with tip loadings from 4.9-14 nN. The authors
chose NaF rather than a layered material in order to avoid
generating flakes and dragging them with the scanning tip, which
would generate periodic signals which don't directly reflect
atomic scale imaging, because they average across the flake. In
this paper, both the periodicity and the amplitude of the
friction signals are explained by the surface atom positions. A
paper on a similar system, an AFM measurement on an LiF (100)
surface, by E. Meyer, H. Heinzelmann, D. Brodbeck, G. Overney, L.
Howard, H. Hug, T. Jung, H.-R. Hidber, and H.-J. Guntherodt
appeared in [J.Vac.Sci.Technol. B 9:
1329-1332 Mar/Apr91]. They also used ~10nN loadings, but the
earlier paper imaged the lattice with vertical, rather than
lateral, deflection. Both techniques should prove useful in
analyzing sufficiently stiff workpieces.
On more flexible substrates, F.A. Schabert, C. Henn, and A. Engel
imaged phospholipid/membrane protein crystals with an AFM in
liquid [Science 268: 92-94 7Apr95]. Since
these crystals are much more flexible than the alkali fluorides
described above, the AFM loadings used were much lower, 0.1-0.3
nN, and the lateral resolutions are much coarser, ~1nm. A good
deal of this paper's information came from scans which averaged
over the three-fold symmetry of the crystal. If complex,
asymmetrical, soft nanostructures (perhaps built through
self-assembly) are to be examined with AFMs, this sort of
averaging will generally not be feasible. In order to confirm the
construction of some structures, it may be necessary to design
them to be easy to image, perhaps with some multi-nm features
present purely for imaging.
Jeffrey Soreff is a researcher at IBM with an interest in
nanotechnology.
From Foresight Update 22, originally
published 15 October 1995.
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