1.1 Nanowires used in Integrated Circuits
The demand for integrated circuits that will allow information be processed at even faster speeds remains undiminished. Currently, most integrated circuits are constructed by optical lithography, which in present commercial fabrication lines allows feature sizes to be constructed in the 30 nm range [Electronic News, 2006]. This is despite the fact that, as a result of miniaturization, the density of wires and switches that comprise such circuits has doubled every eighteen months, giving rise to Moore’s Law [Moore, 1965]. While it appears certain that Moore’s Law will hold true until 2016, it is not certain that it will hold true thereafter for two reasons.
The first reason is that to build smaller wires and switches using established fabrication and materials technologies will require major scientific and technological advances.
Specifically, it will require the development at great cost of new light sources and process tools; new mask and resist materials; and new high and low dielectric constant materials. The second reason is that as wires and switches become smaller the materials of which they are composed no longer exhibit bulk properties, but exhibit properties dominated by confinement and surface effects [Stanca et al., 2006]. As a consequence these wires and switches may exhibit novel characteristics. In other context this will represent a new opportunity; in this context it will represent a major challenge.
There have been two principal responses of the related scientific and engineering communities. The first response has been to develop alternative fabrication and materials technologies. The second response has been to propose new integrated circuit architectures that can accommodate or even exploit the novel characteristics exhibited by these smaller wires and switches.
When contemplating alternative fabrication technologies, one is attracted to the self
assembly in solution and self organization at a conventionally patterned silicon wafer substrate of nanoscale wires and switches. When contemplating alternative materials technologies, one is attracted to the use of biological molecules as templates and nanoparticles as building blocks. [Niemeyer et al., 2001; Parak et al., 2003]
1.2 The use of biological tools for nanotechnology
Many functional biological assemblies represent genuine nanotechnological systems and devices [Sarikaya et al., 2003]. These nano-objects are formed by the process of self-assembly, facilitated by molecular recognition events between building blocks, resulting in the formation of functional devices. Even the simplest living organism contains functional complex elements such as motors, pumps, and cables, all functioning at the nanoscale [Drexler, 1981]. Much research is being devoted to the use of nanotechnology tools for the advancement of biology (bionanotechnology) [Wilkinson, 2003]. This is directly related to the use of nanotechnology to address biological and medical needs. However, the reverse research direction is also very interesting and it involves the use of ordered biological building blocks for the fabrication of various non-biological nanostructures [Taton, 2003].
In recent years there has been increasing interest in the utilization of biological tools for nanotechnological applications that are not related to biology such as micro-electronics and nanoelectronics, microfluidics and nanofluidics, and microelectromechanical and nanoelectromechanical systems [Gazit, 2007]. The biological building blocks include proteins, peptides, nucleic acids, bacteriophages, and plant viruses. These biologically templated nanostructures may have applications in diverse fields that are very remote, such as electronics, telecommunication, and materials engineering.
1.3 DNA based nanobiotechnology
DNA-based nanobiotechnology holds the promise of allowing the bottom-up self
assembly of complex nanodevices. This great potential lies in the molecular recognition capability of DNA and the ability to synthesize DNA molecules having specific sequences.
Therefore, considerable effort has been dedicated to developing DNA templates nanostructures that can be integrated into more complex nanodevices. Self assembly of such devices could potentially reduce time and costs inherent in current nanofabrication methods and provide smaller, more reliable devices.
The linear dsDNA has a width of 2 nm and a length of 0.34 nm per nucleoside subunit. A wide range of molecular lengths, from nanometers to microns, can be realized with established technology in molecular biology, for example DNA ligation, enzymatic digestion, and polymerase chain reaction. DNA templated nanowires could be prepared with an almost unlimited range of aspect ratio. A DNA molecule has two classes of binding site: negatively charged phosphate group and aromatics bases [Gu et al., 2006]. The polyanionic backbone of the molecule, composed of alternating sugar and phosphate groups, binds metallic cations or cationic nanoparticles by electrostatic interaction. Various transition metal ions bind to the nitrogen atoms of the DNA bases and form metal DNA complexes by coordination coupling involving two d orbitals. For example, the N7 atoms of bases guanine and adenine form strong complexes with Pt(II) and Pd(II) ions [Takahara et al., 1995; Huang et al., 1995; Onoa et al., 1998], and the N3 atoms of the bases thymine and cytosine strongly interact with Pd(II) ions [Duguid et al., 1993]. Both classes of binding site have been utilized in nanowire fabrication [Braun et al., 1998; Becerril et al., 2004; Gu et al., 2005; Mertig et al., 2002;
Monson et al., 2003].
DNA is also uniquely suited to molecular recognition in the way known as Watson-Crick base pairing: A pairs specifically with T and G pairs specifically with C. The specific molecular recognition capability could possibly be used to localize DNA molecules to predetermined surface locations and to bind oligonucleotide-coupled nanoparticles to specific regions on DNA templates. Thus, DNA is ideally suited nanofabrication template material
[Stoltenberg et al., 2004].
1.4 Previous research in DNA coupling with metals particles
In the early work in this area, Alivisatos et al. (1996) and Mirkin et al. (1996) exploited the molecular recognition properties of DNA to assemble nanoparticles into organized structures with nanoscale precision. Later in 1998, Braun et al. used complementary ssDNA to bridge a 12 µm long, 100 nm wide conductive silver wires. Other seminal work paved the way to formed a gold nanowires based on the use of a DNA template. This was achieved by the intercalation of functional gold nanoparticles into dsDNA, followed by covalent photochemical attachment of the intercalater [Patolsky et al., 2002]. The use of metal-coated DNA molecules was also demonstrated for DNA-assisted wiring of Au electrodes on silicone wafers [Griffin et al., 2004] and for the specific metallization of a Y-shaped DNA that incorporated a central biotin moiety [Stanca et al., 2006]. These patterned and directed metallization schemes hold promises for novel applications in the design and manufacture of nanoelectronic devices in the future. Although lithography methods are constantly being improved, template-assisted nanowire formation may be very useful for making interconnections between lithographically defined elements [Shacham-Diamand et al., 2003].
1.5 Overview of research project
Because of DNA has low inherent conductivity [Merkoci, 2007], electrical activation of DNA is essential for the construction of nanowires in DNA based nanocircuitry. So there are two key issues needing to be solved: (1) specifically depositing and aligning DNA molecules on surfaces and (2) modifying those molecules to create conductive nanowires [Stolenberg et al., 2004].
My research focused on the first issue concerning about how to specifically depositing dsDNA molecules on the surface by using either magnetic beads or Au particles anchored at
the both ends of DNA. Magnetic beads and Au particles seem to be the most desired particles because of their unique native properties [Kouassi et al., 2006].
Magnetic beads owe their popularity to their numerous attributes such as their magnetic properties that enable them to be directed by an external magnetic field, the possibility to separate them from a reaction mixture, in addition to their low toxicity and biocompatibility [Kouassi et al., 2006].
Considerable interest over the past two decades has been directed toward the using of Au particles with biotechnology because of their excellent biocompatibility, stability and established manufacturing protocols. Furthermore, the use of thiol chemistry on a gold surface allows the attachment of molecules with a relative with using a variety of thiol linker [Minard-Basquin et al., 2005; Demers et al., 2000].
1.6 Linkage between DNA to Magnetic beads
In this study, the interaction between biotin and streptavidin was used to anchor both ends of DNA to magnetic beads. Streptavidin is a 60 kilo-dalton tetrameric protein isolated in crystalline form from culture filtrates of Streptomycetes avidinii [Chaiet et al., 1964].
Streptavidin has no carbohydrate and an acidic isoelectric point of 5. Streptavidin is much less soluble in water than avidin and can be crystallized from water or 50% isopropanol.
Streptavidin is rich in tryptophan [Hoffman et al., 1980] and is highly resistant to denaturation by acids or proteolytic enzymes. It is even more resistant than avidin to dissociation into subunits by guanidine hydrochloride.
Biotin is a 244 dalton vitamin found in tissue and blood and binds with high affinity to streptavidin. The structure of the streptavidin-biotin complex has been described by several groups [Weber et al., 1989; Hendrickson et al., 1989], showing a β-barrel structure of streptavidin binding biotin into its interior. The streptavidin-biotin interaction is the strongest known noncovalent, biological recognition with dissociation constant Kd = 4*10-14 M. The
bond formation between biotin and streptavidin is very rapid and once formed is unaffected by extremes of pH, organic solvents and other denaturing agents [Tong et al., 1992]. The strong interaction has led to a large number of research and diagnostic applications using streptavidin-biotin technology. The strength and reliability of the interaction underlie its importance in biotechnology, but the interaction is also a model for high affinity receptor ligand binding. In most assays, streptavidin is coupled to a solid phase, such as magnetic bead, a microtiter plate or a biosensor chip, while biotin is coupled to the moiety of the interest, often a nucleic acid, protein or antibody [Holmberg et al., 2005].
1.7 Linkage between DNA to Au particles
Another technique is to use the linkage between thiol and Au to anchor both ends of DNA to Au particles. The Au-thiolate bond is a strong-homolytic bond strength 44 kcal/mol - and contributes to the stability of the SAMs together with the Van der Waals forces between adjacent methylene groups, which amount to 1.4-1.8 kcal/mol [Rong et al., 2001]. Hence, Au binds thiols with high affinity and it does not undergo any unusual reactions with them, e.g., the formation of a substitutional sulfide interphase. The strong interaction has led to a large number of research and diagnostic applications using Au-thiol technology.
Therefore, by using a thiol modified nucleotides incorporated into the templated DNA in my research, the DNA will be possible to link to Au and for further analyzed.
1.8 Stretching DNA for nanowire fabrication
At equilibrium, a DNA molecule in aqueous solution will usually be randomly structured as a result of thermal fluctuations. Entropy will shorten the end-to-end distance, often to a much smaller size than the contour length. A DNA molecule therefore must be stretched to serve as a nanowire template. Many approaches have been used to stretch and align DNA molecules, including molecular combing [Gueroui et al., 2001; Otobe et al., 2001; Yokota et
al., 1997], electrophoretic stretching [Kaji et al., 2002; Namasivayam et al., 2002], hydrodynamic stretching [Ye et al., 2000], and van der Waals interaction [Bezryadin et al., 2004].
Molecular combing is the simplest method of stretching DNA templates in nanowire fabrication and thus the most widely used one. No chemical modification of DNA molecules is required. Combing can be done on various hydrophobic and hydrophilic surfaces, and it can yield well dispersed and strongly bound to the substrate, a situation favorable for subsequent metallization and characterization of nanowires. Both direct current (DC) and alternating current (AC) electric fields can be used to stretch DNA. An advantage of the electrophoretic approach is that nanowire templates can be stretched and positioned directly between electrodes. After metallization, electrical properties of nanowires connecting two electrodes can readily be characterized. DNA must be modified by thiolation or biotinylated to be stretched by a DNA field. Otherwise, optical tweezers must be used to tether one end of a DNA molecule before stretching. Stretching by dielectrophoresis does not require chemical modification. Spin stretching is a simplified hydrodynamic stretching without the requirement of chemical modification of DNA.