296 CATALYZING INQUIRY
Once the structure is completed, a number of methods can be used to obtain the output if necessary.
The first is to image the resulting structure, for example, with an atomic force microscope or transmis-
sion electron microscope. In some cases, the structure by itself is visible; in others, tiles can be made
distinguishable by reflectivity or the presence of extra atoms such as gold or fluorescents possibly
added to a turn of the strand that extends out of the plane. Second, with the use of certain tiles, a
“reporter” strand of DNA can be included in such a way that when all the tiles are connected, the single
reporter strand winds through all of them. Once the tiling structure completes assembly, that strand can
then be isolated and sequenced by PCR or another technique to determine the ordering of the tiles.
8.4.3.2 Applications
DNA self-assembly has a wide range of potential applications, drawing on its ability to create
arbitrary, programmable structures. Self-assembled structures can encode data (especially array data
such as images); act as a layout foundation for nanoscale structures such as circuits; work as part of a
molecular machine; and perform computations.
Since a tiled assembly can be programmed to form in an arbitrary pattern, it is potentially a useful
way to store data or designs. In one dimension, this can be accomplished by synthesizing a sequence of
DNA bases that encode the data; then, in the self-assembly step, tiles join to the input strand, extending
the encoding into the second dimension. This two-dimensional striped assembly can be inspected
visually using microscopy, enabling a useful way to read out data. To store two-dimensional data, the
input strand is designed with a number of hairpin turns so that the strand weaves across every other
line of the assembly; the tiles then attach between adjacent turns of the input strand. The resulting
assembly can encode any two-dimensional pattern, and in principle this approach could be extended to
three dimensions.
This approach can also be used to create a foundation for nanometer-scale electronic circuits. For
this application, the DNA tiles would contain some extra materials, such as tiny gold beads, possibly in
a strand fragment that extended above the plain of the tile. After the tiles have formed the desired
configuration, chemical deposition would be used to coat the gold beads, increasing their size, until
they merge and form a wire. Box 8.5 describes a fantasy regarding a potential application to circuit
fabrication.
DNA has been used as a scaffold for the fabrication of nanoscale devices.^142 In crystalline form,
DNA has enabled the precise and closely spaced placement of gold nanoparticles (at distances of 10-20
angstroms). Gold nanoparticles might function as a single-electron storage device for one bit, and other
nanoparticles might be able to hold information as well (e.g., in the form of electric charge or spin). At
one bit per nanoparticle, the information density would be on the order of 10^13 to 10^14 bits per square
centimeter.
Computation through self-assembly is an attractive alternative to traditional exhaustive search DNA
computation. Although traditional DNA computation, such as performed by Adleman, required a linear
number of steps with the input size, in algorithmic self-assembly, the computation occurs in a single step.
In current experiments with self-assembly, a series of tiles are provided as input, and computation tiles
and output tiles form into position around the input. For example, in an experiment that used DNA tiles
to calculate cumulative XOR, input tiles represented the Boolean values of four inputs, while output tiles,
designed such that a tile representing the value 0 would connect to two identical inputs, and a tile
representing the value of 1 would connect to two dissimilar inputs, formed alongside the input tiles. Then,
the reporter strand is ligated, extracted, and amplified to read out the answer.^143
(^142) S. Xiao, F. Liu, A.E. Rosen, J.F. Hainfeld, N.C. Seeman, K. Musier-Forsyth, and R.A. Kiehl, “Assembly of Nanoparticle
Arrays by DNA Scaffolding,” Journal of Nanoparticle Research 4:313-317, 2002.
(^143) C. Mao, T.H. LaBean, J.H. Reif, and N.C. Seeman, “Logical Computation Using Algorithmic Self-assembly of DNA Triple-
crossover Molecules,” Nature 407:493-496, 2000.