Patent Application
20090053425
1. Field of the Invention
The present invention generally relates to the field of nano-technology and nano-particles, and more particularly, to a method for assembling nano-particle patterns with single-particle resolution using DNA-mediated charge trapping techniques, and applications thereof.
2. Description of the Related Art
The technology associated with synthesizing nano-particles is well known. In addition, the physical properties of nano-particles have been thoroughly studied. Both of these factors has led to the nano-particle being considered one of the key building blocks for nano-devices.
Nano-particle devices that includes electronics are described in Wu et al. Applied Physics Letters, Vol. 81, pg. 4595 (2002). Other nano-particle devices that include electronics are described in Weiss et al. Applied Physics Letters, Vol. 88, pg. 143507 (2006) and Andres et al. Science, Vol. 272, pg. 1323 (1996). Nano-particle devices including photonics are described in Krenn et al. Physical Review Letters, Vol. 82, pg. 2590 (1999) and Lu et al. Advance Materials, Vol. 13, pg. 34 (2001). Such nano-particle devices have attracted a considerable level of attention. In addition, the techniques for arranging nano-particles in specific predetermined locations are beginning to play an important role with respect to the integration of nano-devices and circuits.
Conventional techniques that are utilized to achieve such an integration fall into two main categories, i.e., the atomic force microscope (AFM) tip manipulation of nano-particles and the self-assembly method, which invokes inter-particle or particle/substrate interactions. Self-assembly is of particular interest because of its superior functionality and prevailing fabrication speed. Various interaction mechanisms have been utilized for particle assembly or binding. However, electrostatic interaction of the particles is one of the preferred methods for particle assembly. The electrostatic interaction of this preferred method can be exerted between vast varieties of materials, and is much more general and reliable than other specific binding methods.
Several research groups have recently used electrostatic interaction mechanisms to assemble particles, and to thereby adduce evidence to support this seemingly promising approach. The use of an electron beam to generate trapped charges, which can then induce a dielectrophoretic force for particle assembly, is discussed in Fudouzi et al. Nanopart. Res., Vol. 3, pg. 193 (2001). The development of a nano-xerography technique in which nano-particles were assembled onto the charge patterns produced by injecting charge through nano-contacts is described in Jacobs et al. Advanced Materials, Vol. 14, pg. 1553 (2002). An electrostatic force microscopy that is used to create high-resolution electrostatic patterns, which can then attract particles in solution, is discussed in Tzeng et al. Advanced Materials, Vol. 18, pg. 1147 (2006). The particle line resolutions achieved in each of these conventional methods ranges between 30 and 100 nm, and are limited by multiple particles that are present in the cross-section of the particle line. However, no line patterns with a single particle resolution were achieved using any of these known methods.
It is known to combine the electrostatic trapping method with a selective molecular binding method so as to permit the formation of sophisticated nano-particle superstructures. One example of such a use is during the fabrication of molecular electronics, which holds great promise in complimenting present-day semiconductor devices due to its advantages with respect to high packing density, low power consumption, as well as low manufacturing costs. Numerous examples of molecular electronics made by selective binding exist. A thiol-gold colloidal particles composite, which is one of the most commonly used systems, is described in Mirkin et al. Nature, Vol. 382, 607-609 (1996). Other conventional methods for selective binding have been directed towards utilizing DNA as a template for assembling materials. See Braun et al. Nature, Vol. 391, pg. 775 (1998); Keren et al. Science Vol. 302, pg. 1380 (2003); Nakao, et al. Nano Letters. Vol. 3, pg. 1391 (2003); Lin et al. Advanced Materials, Vol. 18, pg. 1517 (2004); and Warner et al. Nature Materials, Vol. 2, pg. 272 (2003). Self-assembly with DNA molecules possesses unrivaled advantages because of the accurate level of synthesis and highly specific hybridization characteristics associated with DNA. (See Seeman, Nature, Vol. 421, pg. 427 (2003)). However, it is still not possible to achieve a resolution to a single particle at a desired position using most of the foregoing methods.
The invention relates to a method for assembling nano-particle patterns with single-particle resolution using DNA-mediated charge trapping techniques, and applications thereof. In accordance with the invention, gold nano-particle chains are produced by Coulomb attraction of biotinated DNA molecules and attachment of nano-particles. In accordance with the method of the invention, the underlying charge patterns are generated by a focused and accurately positioned electron beam source at controlled dosage levels. Here, the chains serve as interconnecting wires or single-electron transistors.
In accordance with the inventive method, charge trapping of biotinated DNA molecules and thiol-Au colloidal binding are used to produce nano-particle patterns at pre-designed locations to a resolution of a single-particle. In the preferred embodiment, the diameter of the Au particles used is about 13 nm. Utilizing electron beam writing, charge patterns are created on Si substrates to immobilize small clustered oligonucleotides, which in turn are attached to individual Au particles and, thus, form single-line patterns.
The present inventors have determined that the introduction of oligonucleotides during the inventive method is a key factor in obtaining the advantageous results of the present invention. Without the oligonucleotides, it is not possible to achieve the desired resolution using known, conventional electrostatic trapping methods.
The contemplated method of the invention permits the production of one-dimensional arrays of inter-particle linear tunnel junctions with high or low transparencies, which can function as interconnecting wires and single electron devices, respectively. In addition, the method permits the construction of functional devices, such as nano-scale waveguiding arrays, sensors and optoelectronics at specific desired locations.
The method of the invention thus provides a way to make individual nano-devices and construct nano-scale assemblies using a minimum number of lithographic steps. That is a way of provided to construct single line particle chains at designated nano-metric locations. Small amounts of a positive charge are implanted within a nano-metric region and used to attract small clusters of biotinated DNA molecules using an appropriate application level of the electron beam. These biotinated DNA molecules are consequently bound with Au particles to form desired patterns. For applications in electronics, the contemplated method of the invention bridges the Au particles to create conductive nano-wires. The development of interconnecting wires and single electron transistors for use in nano-electronics and integrated devices are exemplary applications of the method of the invention.
Other objects and features of the present invention will become apparent from the following detailed description considered in conjunction with the accompanying drawings. It is to be understood, however, that the drawings are designed solely for purposes of illustration and not as a definition of the limits of the invention, for which reference should be made to the appended claims. It should be further understood that the drawings are not necessarily drawn to scale and that, unless otherwise indicated, they are merely intended to conceptually illustrate the structures and procedures described herein.
The foregoing and other advantages and features of the invention will become more apparent from the detailed description of the preferred embodiments of the invention given below with reference to the accompanying drawings in which:
a) thru 1(g) are illustrations of scanning electron microscope (SEM) images of fabricated Au-nano-particle single-line patterns;
a) thru 3(g) are illustrations of SEM images of fabricated one dimensioned Au particle arrays and nano-wires;
a) thru 5(c) is a graphical illustration of the I-Vb characteristics of a connected nano-particle wire; and
The invention relates to a method for assembling nano-particle patterns with single-particle resolution using DNA-mediated charge trapping techniques, and applications thereof. In accordance with the invention, gold nano-particle chains are produced by Coulomb attraction of biotinated DNA molecules and attachment of nano-particles. In accordance with the method of the invention, the underlying charge patterns are generated by a focused and accurately positioned electron beam at controlled dosage levels. Here, the chains serve as interconnecting wires or single-electron transistors.
In accordance with the inventive method, charge trapping of biotinated DNA molecules and thiol-Au colloidal binding are used to produce nano-particle patterns at pre-designed locations to a resolution of a single-particle. In the preferred embodiment, the diameter of the Au particles used is about 13 nm. Utilizing electron beam writing, charge patterns are created on Si substrates to immobilize small clustered oligonucleotides, which in turn are attached to individual Au particles and, thus, form single-line patterns.
The present inventors have determined that the introduction of oligonucleotides during the inventive method is a key factor in obtaining the advantageous results of the present invention. Without the oligonucleotides, it is not possible to achieve the desired resolution using known, conventional electrostatic trapping methods.
The contemplated method of the invention permits the production of one-dimensional arrays of inter-particle linear tunnel junctions with high or low transparencies, which can function as interconnecting wires and single electron devices, respectively. In addition, the method permits the construction of functional devices, such as nano-scale waveguiding arrays, sensors and optoelectronics at specific desired locations. The method of the invention thus provides a way to make individual nano-devices and construct nano-scale assemblies using a minimum number of lithographic steps.
A focused electron beam generated by an electron gun source and directed by a computer controlled digital-to-analog converter (DAC) is commonly used to generate very fine patterns on electron beam resists for further lithographic processes. This electron beam lithographic technique is one of the few mask-less lithographic systems available in the semiconductor fabrication industry. In contrast to exposure on resists, the method of the invention utilizes a focused, directional electron beam to generate trapped charges on dummy SiO2-coated silicon wafers. When an insulating substrate is irradiated by an electron beam, electron-hole pairs are created as the charge carriers. Here, a portion of the charge carriers are recombined or trapped by impurities, defects or cracks, while others, at this time, may escape from the surface of the substrate. The resultant electrostatic imbalance that is created is such that the insulator is either negatively or positively charged.
It is well known that DNA molecules carry slightly negative charges in common buffer solutions. As described in Renoud et al. Phys. Status Solidi. a 2004, 201, 2119, an insulator irradiated by an electron beam often becomes negatively charged. As a result, use of an insulator irradiated in such a manner pursuant to immobilizing DNA molecules is not performed. However, as described in Cazaux, J. Appl. Phys. Vol. 95, pg. 731 (2004), upon electron beam irradiation on an insulating surface, a layer of highly localized positive charges with a thickness about the electron mean escape depth (5-20 nm) is created at the irradiated location, although the net charge in the region of irradiation is negative. As described in Chi et al. Nanotechnology, Vol. 17, pg. 4854 (2006), the localized charges are quite stable and do not decay with the passage of time, as long as high temperatures and a high electric field are not present.
Chi et al. further describes that in an ionic solution, the negatively charged particles close to the irradiated area may overcome the shielding potential and attach to the insulating surface. However, it is known that the charged lines in such a situation will generally be broadened due to random scattering of secondary electrons that occurs. As a result, multiple particle line width is generated. Small levels of exposure to the electron beam help to narrow the charged line at the expense of reducing the force of attraction to a level that is below the threshold value for holding Au particles together.
Here, small amounts of biotinated DNA molecules were attracted by charges generated by a finely focused low level application of electron beam. Au particles were then attached to the thiol in the biotin. In accordance with the method of the invention, the problem associated with the attraction force between the Au particles and the substrate is solved by the use of oligonucleotides, because of their small size and light weight in comparison to the Au particles.
a) thru
g) shows a magnified image of a single-line Au-particle chain with an average separation between two adjacent particles that is roughly equal to the particle size. Here, testing with an electron beam at various pulse intervals resulted in no corresponding change in particle separation. As a result, the separation of the particles is mainly due to a weak repulsive force between Au particles, rather than the discreteness of the charge distribution, and the present inventors have determined that such a conclusion is reasonable.
From top-right to bottom-left, the four writings of “DNA” in
In order to create electrical components, it is required that Au particles are closely linked to permit electrical conduction, as illustrated in
a) thru 3(g) are illustrations of SEM images of fabricated single dimensioned Au particle arrays and nano-wires, where
a) is a graphical plot of the I-Vb characteristic of a connected nano-particle wire with resistance of 1.5K ohms. With reference to
In reality, however, the actual junction resistance is preferably smaller than the estimated junction resistance value, because lead resistance (measured to be approximately 150 ohms), lead-particle contact resistance and the internal resistance of the Au particles are not taken into account during the estimation. Linear current-voltage characteristics, together with a high current density, permit the wires made using the method of the invention to perform as well as interconnecting cooper wires.
b) is a graphical plot of gate-voltage modulations of source-drain currents at various bias voltages for a wire having a resistance of approximately 33 M ohms at room temperature. The graphical plots shown in
c) is a graphical plot of the I-Vb characteristics of the same interconnected wires, but measured at substrate temperatures between 5K (the lower region of the curve) and 85K (the upper region of the curve). It should be noted that within the illustrated graphical plot of
As for the stability of the bound particles, the particle structures will remain intact, even as the substrate temperature is varied between 6K and 523K (250° C.). By careful SEM inspection of samples stored for an extended time period, such as up to 6 months, the present inventors have determined that even heavy washing with water or acetone does not move or remove any gold particles from the samples. Consequently, it is apparent that a strong adhesion between the Au particles and the substrate, as well as a high level of inter particle binding is advantageously achieved.
Outside of the field of electronics, such nano-particle chain structures also have the potential for applications in nano-photonics with selective frequency response by surface plasmon resonance, and can also be used to construct nano-scale waveguides, switches, sensors and the like. In physics, the plasmon is the quasiparticle that results from the quantization of plasma oscillations, similarly to the photons and phonons which are quantizations of light and sound waves. Consequently, plasmons are collective oscillations of the free electron gas density, often at optical frequencies. It is also possible for plasmons to couple with a photon to create a third quasiparticle called a plasma polariton.
The excitation of surface plasmons by light is called a surface plasmon resonance (SPR) for planar surfaces or localized surface plasmon resonance (LSPR) for nano-meter-sized metallic structures. This phenomenon is the basis of many standard tools for measuring adsorption of material onto planar metal surfaces (e.g., gold and silver) or onto the surface of metal nano-particles. The phenomenon is behind many color based biosensor applications and different lab-on-a-chip sensors.
It is known that gold nano-particles possess large scattering cross-sections at optical wavelengths due to the resonant excitations of collective oscillations of conduction electrons within particles. As a result, a single particle dimensioned gold nano-particle chain or wire has great potential for guiding electromagnetic energy due to local-field enhancement and strong scattering. The ability of a single particle dimensioned gold nano-particle chain or wire to convert optical mode into non-radiating surface plasmons, and to guide light below a diffraction limit is unique and cannot be achieved using conventional waveguides or photonic crystals. However, the inventive method of the invention advantageously provides a way to fabricate such a gold particle chain or wire with precise, spatial control of the design. As a result, the realization of functional optical devices is made possible.
A surface plasmon resonant image of a 42 nm gold nano-particle wire is illustrated in
An exemplary method of the invention utilizes two types of biotin-modified oligonucleotides, such as 5 μM 5′-biotin-(A)20-3′ and 5 μM 5′-biotin-(T)7-3′ (MDBio, Inc., Taiwan) (i.e., biotin-20A and biotin-7T). Each of the biotin-modified oligonucleotides is suspended in a 1.0 M KH2PO4 solution having a specific pH. In the preferred embodiment, the pH is 4.3. Here, as described in Herne et al. Chem. Soc., Vol. 119, pg. 8916 (1997), the buffer concentration has an important role in the thiol-Au interaction. In order to link biotin to DNA molecules, the biotin is then attached with a (CH2)6-segment that provides bonding to the 5′-end of the DNA molecules. As a result, a biotin-DNA structure or biotinated-DNA is achieved. It is relevant to note that biotin contains a thiol group that allows strong binding to Au-nano-particles.
The colloidal Au used in accordance with the exemplary implementation of the inventive method is prepared by citrate reduction of HAuC4□3H2O, in accordance with the procedure described in Grabaret al. Anal. Chem., Vol. 67, pg. 735 (1995). A substrate comprising silicon chips 7×7 mm covered with 400 nm thick, thermally oxidized SiO2 layer are also used.
In accordance with the method of the invention, the substrate is initially cleaned in acetone before being blow-dried with nitrogen. This step is then followed by oxygen-plasma treatment in a reactive ion etcher for a predetermined time period. In the preferred embodiment, the predetermined time period is 1 minute. The plasma treatment serves a dual purpose. Firstly, it serves to remove residual organic compounds. Secondly, it serves to create a slightly negatively charged surface to prevent non-specific binding of DNA molecules.
Next, a focused electron beam from a modified field-emission scanning electron microscope, such as a FEI Sirion 200, is directed onto the specific areas by a computer controlled DAC, such as a DAC provided by NPGS, so as to generate a pattern of embedded charges. Here, caution must be exhibited to avoid any unwanted electron exposure during alignment procedures, because a trace amount of exposure may cause undesired embedded charges and consequent particle attachment.
A small sample of biotin-20A solution is then placed onto the substrate sample and maintained there for an extended time period to permit electrostatic attraction of the DNA molecules. Subsequently, the sample substrate is washed with de-ionized water and blow dried before adding the prepared gold particle solution to the biotin-20A solution on the substrate. In the preferred embodiment, the extended time period is 15 minutes.
After waiting for another predetermined time period to permit binding between the Au particles and sulfur atoms in the biotins, the sample substrate is rewashed with de-ionized water and blow dried for further SEM inspections. In the preferred embodiment, the predetermined time period is 30 minutes.
In accordance with a contemplated embodiment of the invention, a bridging cycle method for closely connecting Au particles in the chains is implemented, such as in the manner illustrated in
Next, biotin-20A solution is added to the single-strand biotin-7T. Here, the biotin-20A either hybridizes with the single-strand biotin-7T on the Au particles or directly binds to immobilized Au particles. Finally, an additional Au particle solution is added to fill inter-particle gaps. It should be noted that after each step, the sample substrate is subjected to washing and drying procedures. In this manner, a bridging cycle for inserting Au particles into existing Au-chains is achieved.
The method of the invention provides a way to construct single line particle chains at designated nano-metric locations. With an appropriate application level of the electron beam, small amounts of a positive charge are implanted within a nano-metric region and used to attract small clusters of biotinated DNA molecules. These biotinated DNA molecules are consequently bound with Au particles to form desired patterns. For applications in electronics, the contemplated method of the invention bridges the Au particles to create conductive nano-wires. The development of interconnecting wires and single electron transistors for use in nano-electronics and integrated devices are exemplary applications of the method of the invention. Moreover, it should be readily appreciated that the contemplated embodiments of the inventive method are applicable to other particles that can be modified with biotin, such as iron-oxide, Carbon-60 (C60) or carbon nano-particles. In addition, the contemplated embodiments of the method are not limited to only the above discussed substrates, but are equally applicable to other substrates, including all insulating substrates or conductive substrates that are coated with an insulating layer. Lastly, the contemplated embodiments of the method of invention are equally application to more than the above discussed DNA molecules, for example, they may be applied to other molecules, such as polypeptides or DNA fragments.
Thus, while there have shown and described and pointed out fundamental novel features of the invention as applied to a preferred embodiment thereof, it will be understood that various omissions and substitutions and changes in the form and details of the devices illustrated, and in their operation, may be made by those skilled in the art without departing from the spirit of the invention. For example, it is expressly intended that all combinations of those elements which perform substantially the same function in substantially the same way to achieve the same results are within the scope of the invention. Moreover, it should be recognized that structures and/or elements shown and/or described in connection with any disclosed form or embodiment of the invention may be incorporated in any other disclosed or described or suggested form or embodiment as a general matter of design choice. It is the intention, therefore, to be limited only as indicated by the scope of the claims appended hereto.
