294 CATALYZING INQUIRY
Box 8.4
Enabling Technologies for DNA Self-replication
DNA Surface Arrays
Current DNA array technologies based on spotting techniques or photolithography extend down to pixel sizes
on the order of 1 micron.^1 Examples of these arrays are those produced by Affymetrix and Nanogen.^2 The
creation of DNA arrays on the nanometer scale require new types of non-photolithographic fabrication tech-
nologies, and a number of methods utilizing scanning probe microscopic techniques and self-assembled
systems have been reported.
DNA Microchannels
The separation and analysis of DNA by electrophoresis is one of the driving technologies of the entire genom-
ics area. The miniaturization of these analysis technologies with micron-sized fluidic channels has been
vigorously pursued with the end goal of creating “lab on a chip” devices. Examples are the products of Caliper
Technologies and Aclara Biosciences.^3 The next generation of these devices will target the manipulation of
single DNA molecules through nanometer-sized channels. Attempts to make such channels both lithograph-
ically and with carbon nanotubes have been reported.
DNA Attachment and Enzyme Chemistry
Robust attachment of DNA, RNA, and PNA onto surfaces and nanostructures is an absolute necessity for the
construction of nanoscale objects—both to planar surfaces and to nanoparticles. The primary strategy is to use
modified oligonucleotides (e.g., thiol, amine-containing derivatives) that can be reacted either chemically or
enzymatically. The manipulation of DNA sequences by enzymatic activity has the potential to be a very
sequence-specific methodology for the fabrication of DNA nanostructures.^4
DNA-modified Nanoparticles
Nanoscale objects that incorporate DNA molecules have been used successfully to create biosensor materi-
als. In one example, the DNA is attached to a nanometer-sized gold particle, and then the nucleic acid is used
to provide biological functionality,while the optical properties of the gold nanoparticles are used to report
particle-particle interactions.^5 Semiconductor particles can also be used, and recently the attachment of DNA
to dendrimers or polypeptide nanoscale particles has been exploited for both sensing and drug delivery.^6
DNA Code Design
To successfully self-assemble nucleic acid nanostructures by hybridization, the DNA sequences (often re-
ferred to as DNA words) must be “well behaved” (i.e., they must not interact with incorrect sequences). The
creation of large sets of well behaved DNA molecules is important not only for DNA materials research by
also for large-scale DNA array analysis. An example of the work in this area is the DNA word design by
Professor Anne Condon at the University of British Columbia.^7
DNA and RNA Secondary Structure
The secondary structure of nucleic acid objects beyond simple DNA Watson-Crick duplex formation, whether
they are simple single strands of RNA or the complex multiple junctions of Ned Seeman, have to be under-
stood by a combination of experimental methods and computer modeling. The incorporation of nucleic acid
structures that include mismatches (e.g., bulges, hairpins) will most likely be an important piece of the self-
assembly process of DNA nanoscale objects.^8
