Thomas H. LaBean

Logical computation using algorithmic self-assembly of DNA triple-crossover molecules

Recent work has demonstrated the self-assembly of designed periodic two-dimensional arrays composed of DNA tiles, in which the intermolecular contacts are directed by ‘sticky’ ends. In a mathematical context, aperiodic mosaics may be formed by the self-assembly of ‘Wang’ tiles, a process that emulates the operation of a Turing machine. Macroscopic self-assembly has been used to perform computations; there is also a logical equivalence between DNA sticky ends and Wang tile edges. This suggests that the self-assembly of DNA-based tiles could be used to perform DNA-based computation. Algorithmic aperiodic self-assembly requires greater fidelity than periodic self-assembly, because correct tiles must compete with partially correct tiles. Here we report a one-dimensional algorithmic self-assembly of DNA triple-crossover molecules that can be used to execute four steps of a logical (cumulative XOR) operation on a string of binary bits.

Programming DNA Tube Circumferences

Synthesizing molecular tubes with monodisperse, programmable circumferences is an important goal shared by nanotechnology, materials science, and supermolecular chemistry. We program molecular tube circumferences by specifying the complementarity relationships between modular domains in a 42-base single-stranded DNA motif. Single-step annealing results in the self-assembly of long tubes displaying monodisperse circumferences of 4, 5, 6, 7, 8, 10, or 20 DNA helices.

Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices

The programmed self-assembly of patterned aperiodic molecular structures is a major challenge in nanotechnology and has numerous potential applications for nanofabrication of complex structures and useful devices. Here we report the construction of an aperiodic patterned DNA lattice (barcode lattice) by a self-assembly process of directed nucleation of DNA tiles around a scaffold DNA strand. The input DNA scaffold strand, constructed by ligation of shorter synthetic oligonucleotides, provides layers of the DNA lattice with barcode patterning information represented by the presence or absence of DNA hairpin loops protruding out of the lattice plane. Self-assembly of multiple DNA tiles around the scaffold strand was shown to result in a patterned lattice containing barcode information of 01101. We have also demonstrated the reprogramming of the system to another patterning. An inverted barcode pattern of 10010 was achieved by modifying the scaffold strands and one of the strands composing each tile. A ribbon lattice, consisting of repetitions of the barcode pattern with expected periodicity, was also constructed by the addition of sticky ends. The patterning of both classes of lattices was clearly observable via atomic force microscopy. These results represent a step toward implementation of a visual readout system capable of converting information encoded on a 1D DNA strand into a 2D form readable by advanced microscopic techniques. A functioning visual output method would not only increase the readout speed of DNA-based computers, but may also find use in other sequence identification techniques such as mutation or allele mapping.

DNA-programmed assembly of nanostructures

DNA is a unique material for nanotechnology since it is possible to use base sequences to encode instructions for assembly in a predetermined fashion at the nanometre scale. Synthetic oligonucleotides are readily obtained by automated synthesis and numerous techniques have been developed for conjugating DNA with other materials. The exact spatial positioning of materials is crucial for the future development of complex nanodevices and the emerging field of DNA-nanotechnology is now exploring DNA-programmed processes for the assembly of organic compounds, biomolecules, and inorganic materials.

DNA-based Cryptography

Recent research has considered DNA as a medium for ultra-scale computation and for ultra-compact information storage. One potential key application is DNA-based, molecular cryptography systems. We present some procedures for DNA-based cryptography based on one-time-pads that are in principle unbreakable. Practical applications of cryptographic systems based on one-time-pads are limited in conventional electronic media by the size of the one-time-pad; however DNA provides a much more compact storage medium, and an extremely small amount of DNA suffices even for huge one-time-pads. We detail procedures for two DNA one-time-pad encryption schemes: (i) a substitution method using libraries of distinct pads, each of which defines a specific, randomly generated, pair-wise mapping; and (ii) an XOR scheme utilizing molecular computation and indexed, random key strings. These methods can be applied either for the encryption of natural DNA or for artificial DNA encoding binary data. In the latter case, we also present a novel use of chip-based DNA micro-array technology for 2D data input and output. Finally, we examine a class of DNA steganography systems, which secretly tag the input DNA and then hide it within collections of other DNA. We consider potential limitations of these steganographic techniques, proving that in theory the message hidden with such a method can be recovered by an adversary. We also discuss various modified DNA steganography methods which appear to have improved security.

Nanofabrication by DNA self-assembly

Molecular self-assembly strategies involve the formation of nanometer scale objects and materials in the absence of significant external control. One increasingly popular self-assembly approach makes use of the unique properties of deoxyribonucleic acid (DNA) including its diminutive size and high capacity for information storage. For many applications, DNA stands alone as the top choice for the programmable construction of supramolecular materials due to its specific and well-understood base-pairing interactions. In this review, we will discuss recent advances in the fabrication of materials via DNA based self-assembly.

Constructing novel materials with DNA

DNA, apart from being a natural biological information carrier, has also been recognized as a useful building material in the field of nanotechnology. Its miniature scale, geometric properties, and molecular recognition capacity make DNA an appealing candidate for the construction of novel nanomaterials. Here we summarize the latest developments and describe the challenges and emerging applications of this field.

Connecting the Nanodots: Programmable Nanofabrication of Fused Metal Shapes on DNA Templates

We present a novel method for producing complex metallic nanostructures of programmable design. DNA origami templates, modified to have DNA binding sites with a uniquely coded sequence, were adsorbed onto silicon dioxide substrates. Gold nanoparticles functionalized with the cDNA sequence were then attached. These seed nanoparticles were later enlarged, and even fused, by electroless deposition of silver. Using this method, we constructed a variety of metallic structures, including rings, pairs of bars, and H shapes.

Toward Larger DNA Origami

Structural DNA nanotechnology, and specifically scaffolded DNA origami, is rapidly developing as a versatile method for bottom-up fabrication of novel nanometer-scale materials and devices. However, lengths of conventional single-stranded scaffolds, for example, 7,249-nucleotide circular genomic DNA from the M13mp18 phage, limit the scales of these uniquely addressable structures. Additionally, increasing DNA origami size generates the cost burden of increased staple-strand synthesis. We addressed this 2-fold problem by developing the following methods: (1) production of the largest to-date biologically derived single-stranded scaffold using a λ/M13 hybrid virus to produce a 51 466-nucleotide DNA in a circular, single-stranded form and (2) inexpensive DNA synthesis via an inkjet-printing process on a chip embossed with functionalized micropillars made from cyclic olefin copolymer. We have experimentally demonstrated very efficient assembly of a 51-kilobasepair origami from the λ/M13 hybrid scaffold folded by chip-derived staple strands. In addition, we have demonstrated two-dimensional, asymmetric origami sheets with controlled global curvature such that they land on a substrate in predictable orientations that have been verified by atomic force microscopy.

Optimized fabrication and electrical analysis of silver nanowires templated on DNA molecules

We report on the electrical conductivity measurement of silver nanowires templated on native λ-bacteriophage and synthetic double-stranded DNA molecules. After an electroless chemical deposition, the metallized DNA wires have a diameter down to 15nm and are among the thinnest metallic nanowires available to date. Two-terminal I-V measurements demonstrating various conduction behaviors are presented. DNA templated functional nanowires may, in the near future, be targeted to connect at specific locations on larger-scale circuits and represent a potential breakthrough in the self-assembly of nanometer-scale structures for electronics layout.