WO2008063683A2

WO2008063683A2 - Electromagnetic heating of single walled carbon nanotubes in aqueous solutions and biological systems

Info

Publication number: WO2008063683A2
Application number: PCT/US2007/062916
Authority: WO
Inventors: Irene M. Marek; Howard K. Schmidt; W. Carter Kittrell; Robert H. Hauge; Paul Cherukuri; Valerie C. Moore; Richard E. Smalley
Original assignee: William Marsh Rice University
Priority date: 2006-02-27
Filing date: 2007-02-27
Publication date: 2008-05-29
Also published as: WO2008063683A3

Abstract

Disclosed herein is a new application of carbon nanotubes for biological environments. In various embodiments, electromagnetic field coupling of carbon nanotubes induces a local deposition of radio frequency (RF) energy along the nanotube and imparting the capability of RF ablation that can be used to target certain cells, tissues, and/or the like.

Description

ELECTROMAGNETIC HEATING OF SINGLE WALLED CARBON NANOTUBES IN AQUEOUS SOLUTIONS AND BIOLOGICAL SYSTEMS

GRANT INFORMATION

[0001] At least a portion of this invention was developed pursuant to NASA Contract No.

NNJ05HE75A.

RELATED DOCUMENTS

[0002] This application claims priority to US provisional titled "Electromagnetic Heating Of

Single Walled Carbon Nanotubes In Aqueous Solutions And Biological Systems", filed February

27, 2006, USSN 60/777,278.

INVENTORS

Richard E. Smalley of Houston, Texas;

Howard K. Schmidt of Houston, Texas; Carter Kittrell of Houston, Texas; Robert Hauge of Houston, Texas; Paul Cherukuri of Houston, Texas; and, Valerie Moore of Houston, Texas.

BACKGROUND OF THE INVENTION Field of the Invention.

[0003] Carbon nanotubes are nanoscale high-aspect-ratio cylinders consisting of hexagonal rings of carbon atoms that may assume either a semiconducting electronic state or a conducting electronic state. Semiconducting carbon nanotubes have been used to form hybrid devices, such as hybrid FET's. In particular, FET's have been fabricated using a single semiconducting carbon nanotube as a channel region. Typically, ohmic contacts at opposite ends of the semiconducting carbon nanotube extending between a source electrode and a drain electrode situated on the surface of a substrate.

[0004] Many methods exist for forming and/or creating nanotubes and nanotube arrays. A conventional method of forming carbon nanotubes utilizes a chemical vapor deposition (CVD) process. Specifically, the CVD process directs a flow of a carbonaceous reactant to a catalyst material located on the substrate, where the reactant is catalyzed to synthesize carbon nanotubes. The carbon nanotubes are capable of being lengthened by insertion of activated carbon atoms at the interface with the catalyst material. Typically, the carbon nanotubes are then collected for an end use or further processing.

[0005] Carbon nanotubes typically range from a few to tens of run in diameter, and are as long as a few centimeters in length. Because of its one-dimensional electronic properties due to this shape anisotropy, the carbon nanotube characteristically has a maximum current density allowing the flowing of current without disconnection of 1 ,000,000,000 A per square centimeter, which is 100 times or more as high as that of a copper interconnect. Further, with respect to heat conduction, the carbon nanotube is ten times as high in conductivity as copper. [0006] In terms of electric resistance, it has been reported that transportation without scattering due to impurities or lattice vibration (phonon) can be realized with respect to electrons flowing through the carbon nanotube. It is known that the axial resistance per carbon nanotube, in various instances, is approximately 6.45 kΩ per micron of length. However, other resistances are contemplated in various embodiments of the present invention.

[0007] Further desirable attributes of a carbon nanotube electrode material include such factors as high surface area for the accumulation of charge at the electrode/electrolyte interface, good intra- and interparticle conductivity in the porous matrices, good electrolyte accessibility to the intrapore surface area, chemical stability and high electrical conductivity. Commonly used carbonaceous material used for the construction of electrolytic capacitor devices include such materials as activated carbon, carbon black, carbon fiber cloth, highly oriented pyrolytic graphite, graphite powder, graphite cloth, glassy carbon, carbon aerogel, and/or the like. [0008] Studies have shown that carpets (forests) of single-walled carbon nanotubes can be readily grown at atmospheric pressures with controlled mixtures containing various hydrocarbons and also in the presence of hydrogen and various hydrocarbons at sub- atmospheric pressures with activation of gas mixtures. Hata, et al., Science 2004, 306, 1362; Gyula, et al., J. Phys. Chem. B 2005, 109, 16684; Zhang, et al.,. PNAS 2005, 102, 16141; Iwasaki, et al., J. Phys. Chem. B 2005, 109, 19556; Zhong, et al, J. Appl. Phys, 2005, 44, 1558; Maruyama, et al., 1 2005, 403, 320; Huang et al., J. AmChem. Soc. 2003, 125, 5636. [0009] Much attention has been given to the use nanomaterials in semiconductor devices, but relatively little attention or commercial use has been given to nanotubes for use in a biological system and/or for medical applications. Although nanotubes have an enormous potential, it is hypothesized that the absence of study and/or application is primarily due to the lack of chemistries that are needed to establish true solubility of well-characterized nanotubes. Current chemical methods for water suspended nanotubes require intense sonochemical treatments in order to effectively disperse nanotube agglomerations. Primarily, surfaction is used to facilitate the solubilization of the nanotubes.

[0010] Formulations of surfactant solubilized nanotubes serve as the basis for numerous applications potentially impacting a wide spectrum of industries, such as, but not limited to energy, pharmaceutical, and electronics. However, it has not gone unnoticed that these nanotube solutions have demonstrated remarkable water solubility and are attractive as a new paradigm for biomedical applications. P. Cherukuri et al, J. Am. Chem. Soc, Near-Infrared Fluorescence Microscopy of Single- Walled Carbon Nanotubes in Phagocytic Cells. 2004, 126, 15638-15639. [0011] An example of a published study utilizing infra-red (IR) heating of nanotubes can be found at Kam N., et al. Carbon nanotubes as multifunctional biological transporters and near- infrared agents for selective cancer-cell destruction. Proc. Natl Acad. Sci. USA published online 8 August 2005. This study confirmed that biological systems are transparent to the window of 700- to 1,100-nm near-infrared (NIR) light. The study further indicated that the strong optical absorbance of single- walled carbon nanotubes (SWNTs) in this window, reported as an intrinsic property of SWNTs, are capable of use for optical stimulation of nanotubes inside living cells to afford multifunctional nanotube biological transporters. The results indicated that oligonucleotides transported into cells by nanotubes can translocate into cell nucleus upon endosomal rupture triggered by NIR laser pulses. Then, continuous NIR radiation can cause cell death because of excessive local heating of SWNT in vitro. However, NIR heating is limited in it's applications due to the poor depth penetration. NIR light is only capable of penetrating a few centimeters into a subject's or patient's body. Accordingly, the art field is in search of a method and/or system for the effective ablation of a target, such as at least one nanotube wherein the at least one nanotube targets a desired at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or component thereof, and/or the like. [0012] Photothermal ablation with gold silica nanoshells is known. Likewise, it is known that there is a dielectric response of SWNT in composites. B. Kim et al, J. Appl. Phys., Electrical Properties of Single- Wall Carbon Nanotube and Epoxy Composites, 2003, 94(10), 6724-6728; J. A. Roberts et al, J. Appl. Phys., Electromagnetic Wave Properties of Polymer Blends of Single Wall Carbon Nanotubes Using a Resonant Microwave Cavity as a Probe, 2004, 95(8), 4352-4356; J. Wu et al, Appl. Phys. Lett, High Microwave Permittivity of Multiwalled Carbon Nanotube Composites. 2004, 84(24), 4956-4958; M. Dragoman et al, Appl. Phys. Lett., Experimental Determination of Microwave Attenuation and Electrical Permittivity of Double- Walled Carbon Nanotubes. 2006, 88, 153108-1-153108-3; J. Kim et al, Physical Rev., Microwave Response of Individual Multiwall Carbon Nanotubes. 2004, 70, 153402-1-153402-3; Z. Zhang et al, J. Appl Phys., Alternating Current Dielectrophoresis of Carbon Nanotubes, 2005, 98, 056103-1-056103-3; Z. Zhang et al, Acta Physico-Chimica Sinica, Complex Permittivity and Permeability Spectra of Different Kinds of Carbon Nanotubes, 2006, 22(03), 296-300; N. Li et al, Nano Lett, Electromagnetic Interference (EMI) Shielding of Single- Walled Carbon NAnotube Epoxy Composites, 2006, 6(6), 1141-1145; J. Hao et al, IEEE Transactions on Nanotechnology, Infrared and Optical Properties of Carbon Nanotube Dipole Antennas, 2006, 5(6), 766-775; Z. Ye et al, Physical Rev., Microwave Absorption by an Array of Carbon Nanotubes: A Phenomenological Model, 2006, 74, 075425-1-075425-5; CF. Bohren, Am. J. Phys., How Can a Particle Absorb More Than the Light Incident On It?, 1983, 51, 323. [0013] Accordingly, there is a need for use of nanotubes for applications in biotech/biomedical applications, such as, but not limited to the fields of medicine, drug, gene delivery, and/or the like.

[0014] Applicant currently shows that this unique combination of water solubility and electromagnetic polarizability under radio frequencies presents a novel and non-obvious application.

[0015] Accordingly, the art field is in search of improved methods of manufacturing semiconductor devices out of nanotube material, such as carbon nanotubes, especially improved methods of production a predominantly single walled decreased diameter arrays/forests of nanotubes.

SUMMARY OF THE INVENTION

[0016] These and other features and advantages of the invention will be apparent to those skilled in the art from the following detailed description of various embodiments, taken together with the accompanying figures and claims, in which:

[0017] In general, various embodiments of the present invention generally relate to methods and systems for the heating a target, such as at least one nanotube wherein the at least one nanotube targets a desired at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or component thereof, and/or the like. In an embodiment, a nanotube is injected about the target and radio frequency (RF) radiation is directed at or about the nanotube such that the nanotube is heated, hi various embodiments, the nanotube is heated to a temperature sufficient to kill the target. In alternate embodiment, the nanotube is heated to a temperature sufficient to modify the target, hi alternate embodiment, the nanotube is heated to a temperature sufficient to ablate the target. In general, the sufficient temperature can be any temperature capable of performing the required task.

[0018] Methods of the present invention generally comprise the steps of a. dispersing at least one nanotube in a solution; injecting said solution into a medium containing a target; and, applying radio frequency (RF) radiation towards the at least one tube for a sufficient time to at least one of kill the target, ablate the target, modify the target, and/or the like.

[0019] Very generally, Applicants have illustrated, for the first time, that various nanotubes resonant absorptions extend up through radio frequency (RF). In various embodiments, such frequencies are about within the range of 0.1 to several GHz. Such absorptions have not previously been shown to be effective and/or possible.

[0020] Various embodiments comprise various nanotube formulations, hi an embodiment, the nanotubes are solubilized.

[0021] Various embodiments comprise nanotubes of varied components. In an embodiment, the nanotubes are carbon nanotubes. In various further embodiments, the nanotubes are single walled nanotubes (SWNTs).

[0022] It is expected that various embodiments of the present invention will produce at least one of the following benefits:

[0023] 1) targeting of the nanotubes such that the nanotubes are capable of use with both as contrast and therapeutic agents;

[0024] 2) essentially one-dimensional, linear xenobiotic particles;

[0025] 3) the use of frequencies below infra-red (IR);

[0026] 4) covalent functionalization of the nanotubes to assist in solubilization; and/or,

[0027] 5) achieving non-ionic functionalization to inhibit and/or prevent flocculation by charge screening in the presence of salts that are capable of being present in biological fluids. DETAILED DESCRIPTION OF THE INVENTION

[0028] The particulars shown herein are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of various embodiments of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for the fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

[0029] The following definitions and explanations are meant and intended to be controlling in any future construction unless clearly and unambiguously modified in the following examples or when application of the meaning renders any construction meaningless or essentially meaningless. In cases where the construction of the term would render it meaningless or essentially meaningless, the definition should be taken from Webster's Dictionary, 3^rd Edition.

[0030] As used herein, the term "attached, or any conjugation thereof describes and refers the at least partial connection of two items.

[0031] As used herein, a "fluid" is a continuous, amorphous substance whose molecules move freely past one another and that has the tendency to assume the shape of its container, for example, a liquid or a gas.

[0032] As used herein, the term "integral" means and refers to a non-jointed body.

[0033] As used herein, the term "optical anisotropy" means and refers to a the property of being optically directionally dependent. Stated another way, it is the behavior of a medium, or of a single molecule, whose effect on electromagnetic radiation depends on the direction of propagation of the radiation.

[0034] As used herein, the term "permittivity" means and refers to a characteristic of space, and the relative permittivity or dielectric constant is a way to characterize the reduction in effective field because of the polarization of the dielectric.

[0035] As used herein, the term "semiconductor device" means and refers at least one device used in or with a formation of transistors, capacitors, interconnections, batteries, supercapacitors, and/or the like, particularly various memory devices, such as, but not limited to DRAM, SRAM,

SCRAM, EDRAM, VDRAM, NVSRAM, NVDRAM, DPSRAM, PSDRAM, transistor/capacitor cell devices, vias or interconnects, and vertical stacks of logic gates. However, other devices utilizing transistors at least one transistors, capacitors, interconnections, and/or the like are to be included within this definition.

[0036] As used herein, the term "target" means and refers to at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or components thereof, and/or the like.

[0037] As used herein, the term The term "trace" is not intended to be limiting to any particular geometry or fabrication technique and instead is intended to broadly cover an electrically conductive path.

[0038] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein are to be understood as modified in all instances by the term "about".

[0039] References herein to terms such as "vertical" and "horizontal" are made by way of example to establish a frame of reference. The term "horizontal" as used herein is defined as a plane parallel to the conventional plane or surface of substrate. The term "vertical" refers to a direction perpendicular to the horizontal, as defined above. Terms, such as "on", "above",

"below", "side" (as in "sidewall"), "higher", "lower", "over", "beneath" and "under", are defined with respect to the horizontal plane.

[0040] Applicant has now invented a new non-obvious application of nanotubes in biological environments. In an embodiment, the electromagnetic (EM) field coupling of nanotubes induces a local deposition of RF energy isotropically along the nanotube. It has been observed in various embodiments that nanotubes polarize in RF fields in a similar fashion to straight, lossy antennas, with the loss primarily due to electron-phonon scattering as the charge oscillates along the nanotubes in near-synchrony with the applied electric component of the EM wave.

[0041] As such, various embodiments of the present invention comprise a method of treating a target comprising the steps of dispersing at least one nanotube in a solution; injecting said at least one nanotube into a medium containing a target; and, applying radio frequency (RF) radiation towards the at least one tube for a sufficient time to at least one of kill the target, ablate the target, modify the target, and/or the like.

[0042] Various further embodiments relate to systems for at least one of killing a target, ablating a target, modifying a target, and/or the like. [0043] The radio frequency energy is coupled with the solution and tissues either directly with an electrode or externally via a radiating antenna. The strong EM coupling and the subsequent super-polarizability of these SWNTs gives rise to the thermal response that Applicant has experimentally determined and this significant clinical implications as a new targeted technology in cell-specific therapies for the ablation of tumors or other focal pathologies.

[0044] RF-based thermal ablation has been a promising clinical technique for the removal of surgically nonresectable pathologies (e.g., malignant tumors, atherosclerotic plaques). Thermal ablation has provided a minimally invasive alternative to classical resection, however thermal ablation studies have shown the technique to be problematic. Specifically, selectively heating cell specific pathologies is not possible unless RF thermal ablation is coupled with a molecularly targeted approach.

[0045] In various embodiments, therefore, various nanotubes for use with embodiments of the present invention couple both targeting, such as through antibody for various cellular pathologies, peptide labeled for various cellular pathologies, and/or the like for various cellular pathologies, as well strong absorbers in the RF.

[0046] Various further embodiments are designed such that the nanotubes penetrate the fenestrations of tumors and/or plaques.

[0047] As such, an embodiment of the present invention comprises the steps of:

[0048] a. dispersing at least one nanotube;

[0049] b. injecting the at least one nanotube into a medium containing a at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, and/or the like; and,

[0050] c. applying radio frequency radiation towards the at least one tube for a sufficient time to ablate the target.

[0051] Methods and procedures for growing nanotubes are common in the art. Suitable examples include those disclosed in Maruyama, et al., Chem.Phys.Lett. 2002, 360, 229 and

Murakami et al., Chem. Phys. Lett. 2003, 377, 49; Talapatrala, et al., "Direct Growth of aligned carbon nanotubes on bulk metals," Department of Material Science & Engineering, Rensselaer

Poytechnic Institute, 22 October 2006; Hata et al., "Water-Assisted Highly Efficient Synthesis of

Impurity-Free Single-Walled Carbon Nanotubes," Science 2004, 306, 1362-1364; Murakami et al., "Growth of vertically aligned single-walled carbon nanotube films on quartz substrates and their optical anisotropy," Chemical Physics Letters 2004, 385, 298-303; Xu et al.. "Vertical Array Growth of Small Diameter Single-Walled Carbon Nanotubes," Jam Chem Soc 2006, 128, 6560-6561; and/or the like. Such methods are common in the art and in general are not critical to the invention. Various embodiments of the invention require a nanotube in whatever fashion grown. In various embodiments, the nanotube is a single walled nanotube. In an alternate embodiment, the nanotube is a multi-walled nanotube. Further, while carbon nanotubes are preferred, various embodiments are possible with other nanotube compositions, such as silicone and/or the like.

[0052] In an embodiment, the step of dispersing at least one nanotube is performed using ultrasound in a fluidic substance or solution, such as, for example, water. In various embodiments, the fluidic substance contains a surfactant. The surfactant assists in inhibiting agglomeration of the at least one nanotube. Other suitable methods of water solubilizing nanotubes include wrapping the nanotubes in strands of soluble polymers, such as, but not limited to either DNA, polyethylene glycol (PEG), acid etching, and/or the like. J. Liu et al, Science, Fullerene Pipes. 1998, 280, 1253-1256.

[0053] hi various embodiments, at least a portion of the nanotubes remain agglomerated and a further centrifugation step is required to remove bundled nanotubes. In an embodiment, the agglomerated nanotubes are sent for further processing.

[0054] Further embodiments comprise functionalizing the at least one nanotube. hi an embodiment, the nanotube is functionalized with at least one moiety to generate a covalent sheath around the at least one nanotube. In an embodiment, the moiety are cross-linkable In various further embodiments, a cross-linkable moiety is selected from compounds such as using a di-block polymer like poly-butylene, poly-ethylene glycol, and the like. In general, any moiety can be used that generates a covalent sheath.

[0055] Yet further embodiments comprise functionalizing the at least one nanotube. Functionalization of nanotube formations is common in the art. Suitable examples of methods for functionalizing are disclosed in Wong, et al., "Covalently Functionalized Nanotubes as Nanometer Probes for Chemistry and Biology" Nature 394, 52 55 (1998) and Wong, et al., "Covalently-Functionalized Single- Walled Carbon Nanotube Probe Tips for Chemical Force Microscopy" J. Am. Chem. Soc. 120, 8557 8558 (1998). In general, nanotubes are capable of being created with acidic functionality, with basic or hydrophobic functionality, or with biomolecular probes. Typically, this functionality is on the open end of the nanotube. Various embodiments of a functionalized nanotube of the present invention comprise at least one of non- covalent functionalization, defect functionalization, Il-stacking, sidewall functionalization, endohedral functionalization, and/or the like. In general, functionalizing nanotubes is known in the art. Functionalizing nanotubes is known in the art, for example, see Ashcroft et al "Functionalization of individual ultra-short single-walled carbon nanotubes" Nanotechnology, 2006:17, 5033-5037. Further examples of attaching genes are disclosed in Pantarotto et al. Chem. Int. Ed. 2004: 43, 5242 and Singh et al. J. Am. Chem. Soc. 2005:127, 4388; M. Strano et al., J. Nanosci. Nanoteck, The Role of Surfactant Adsorption during Ultrasonication in the Dispersion of Single- Walled Carbon Nanotubes, 2003, 3, 81-86; MJ. O'Connell et al., Science, Band Gap Fluorescence from Individual Single- Walled Carbon Nanotubes, 2002, 297, 593-596; V. Moore et al, Nano Lett, Individually Suspended Single- Walled Carbon Nanotubes in Various Surfactants. 2003, 3(10), 1379-1382; MJ. O'Connell et al, Chem. Phys. Lett., Reversible Water-Solubilization of Single- Walled Carbon Nanotubes by Polymer Wrapping, 2001, 342, 265-271.

[0056] However, various embodiments of the present invention comprise nanotubes that are not functionalized and yet are solubilized. Examples of such nanotubes are available from Brewer Science, Inc, St. Louis, Missouri.

[0057] Further embodiments comprise attaching a targeting agent to the at least one nanotube wherein the at least one nanotube targets a desired at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or component thereof, and/or the like.

[0058] To improve the specificity and targeting of the nanotubes, in various embodiments, targeting agents are added. In various embodiments, the targeting agent is chosen such that wherein the at least one nanotube targets a desired at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or component thereof, and/or the like is targeted. In an embodiment, ester bonds are formed to functional groups via activation of carboxylic acids on the nanotube. The same chemistry works for making amide bonds to amines, e.g. terminal or side-chain amines on polypeptides, and for monoclonal antibodies. See Fullerene Pipes. 1998, 280, 1253-1256. [0059] In various embodiments, the targeting agent is added during functionalization. [0060] Various embodiments of the present invention comprise mediums of an in vitro and an in vivo character comprising at least one target. In an embodiment, the medium is an organism, such as, but not limited to an animal. In such an embodiment, the medium is a human. Generally, the medium can be any medium that comprises a target.

[0061] In various embodiments the target is an undesired constituent of the medium, such as, but not limited to, cancerous cells, atherosclerotic plaques, blood clots, and/or the like. In various other embodiments, the target comprises at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or components thereof, and/or the like.

[0062] In various embodiments of the present invention, a majority of the injectant is water. Sail concentrations of nanotubes is all that is required in solution to provide the treatment, hi an embodiment, the concentration of the nanotubes in the solution is about 0.1 mg/L to about 10 g/L. hi an alternate embodiment, the concentration of the nanotubes in the solution is about 1.0 mg/L to about 1.0 g/L. In an alternate embodiment, the concentration of the nanotubes in the solution is about 2.0 mg/L to about 500 mg/L. In an alternate embodiment, the concentration of the nanotubes in the solution is about 5.0 mg/L to about 100 mg/L. In an alternate embodiment, the concentration of the nanotubes in the solution is about 7.0 mg/L to about 50 mg/L. In general, any concentration is capable of working as long as agglomeration of the nanotubes is minimized.

[0063] hi various embodiment, agglomeration of nanotubes in solution is experienced at high RF radiation. However, lower RF radiation levels do not readily promote aggregation. R. Krupke et al, Science, Separation of Metallic from Semiconducting Single- Walled Carbon Nanotubes, 2003, 301, 344-347.

[0064] The step of injecting the at least one nanotube can be performed by any method common in the art. hi an embodiment, the at least one nanotube is ingested by a subject or patient in need of treatment, hi an alternate embodiment, the at least one nanotube is injected into a medium containing a target, hi an embodiment, the means for injection is selected from the group comprising a syringe, an IV, a hypodermic needle, a needle-less injector a solid, a pipette, and/or the like. Generally, any form and/or method of delivering a nanotube to or about a target can be used. [0065] In various embodiments, the at least one nanotube is delivered about the target. In an embodiment, about the target means delivery to a proximity wherein the treatment is effective. In another embodiment, about the target means within about 0.1 to about 1 cm. In an alternate embodiment, about the target means within about 1 nm to about 100 run. hi an alternate embodiment, about the target means within about 2 nm to about 50 nm. hi an alternate embodiment, about the target means within about 5 nm to about 25 nm. hi an alternate embodiment, about the target means within about 10 nm to about 15 nm. hi yet an alternate embodiment, about the target means within the cell, virus, fungus, bacteria, retrovirus, tissue, component thereof, and/or the like, hi yet an alternate embodiment, about the target means essentially adjacent the cell, virus, fungus, bacteria, retrovirus, tissue, component thereof, and/or the like.

[0066] hi various embodiments, the injected at least one nanotube is subjected to RF radiation to heat the nanotube in a controlled fashion. In an embodiment, the at least one nanotube is heated to at least 80 °C. In an alternate embodiment, the at least one nanotube is heated to at least 50 °C. hi an alternate embodiment, the at least one nanotube is heated to at least 120 °C. In an alternate embodiment, the at least one nanotube is heated to at least 70 °C. In an alternate embodiment, the at least one nanotube is heated to at least 100 ⁰C. It is known that a temperature of about 80°C is necessary to kill cells. However, the temperature chosen can be varied depending upon the desired application and/or effect.

[0067] The step of applying radio frequency (RF) radiation can be performed by any RF generator, hi various embodiments, the RF generator is selected from generators disclosed in US 6,180,976; US 5,895,948; US 5,162,258; US 5,708,559; and/or, the like, hi an embodiment, a large pulse of electromagnetic energy is generated, such as from a spark gap, and/or the like. The large pulse would be used to create a strong electric field that has a broad frequency spectrum. However, typically any RF generator can be used. Typical RF generators include, but are not limited to, plate type RF generators.

[0068] In various embodiments, the power and/or frequency of the RF generator is varied, hi an embodiment, about 1 watt to about 100000 watts is used, hi an alternate embodiment, about 5 watts to about 10000 watts is used, hi an alternate embodiment, about 50 watts to about 5000 watts is used. In an alternate embodiment, about 100 watts to about 1000 watts is used. In an alternate embodiment, about 250 watts to about 500 watts is used. [0069] Various frequencies are used in embodiments of the present invention. Typical ranges for use in various embodiments of the present invention are those below about infra-red (IR) radiation. In various embodiments, frequencies from TeraHertz all the way down to KiloHertz are used. In an embodiment, a frequency of about 400 KHz (induction heaters), 2.54 GHz (microwave and diathermy systems), 2 MHz, 13.56 MHz, 2x that and 3x that and 900 MHz (these are all approved ISM bands) Industrial, Scientific and Medical RF bands, is used. In general, any frequency can be used that is a RF frequency. Different frequencies require different exposure times, different power considerations, different shielding, different methods of delivery, and/or the like. Generally, a skilled clinician is capable of determining an appropriate treatment regimen to produce the desired effect.

[0070] In various embodiments, the time sufficient to treat the target varies from a few microseconds to days. In an embodiment, the time sufficient to treat the target is from about 0.1 second to about 1.0 days. In an alternate embodiment, the time sufficient to treat the target is from about 2 seconds to about 12 hours. In an alternate embodiment, the time sufficient to treat the target is from about 10 seconds to about 2 hours. In an alternate embodiment, the time sufficient to treat the target is from about 30 seconds to about 0.5 hours. In an alternate embodiment, the time sufficient to treat the target is from about 1.0 minute to about 10 minutes. In an alternate embodiment, the time sufficient to treat the target is from about 2.0 minutes to 5.0 minutes. In general, the time can be varied as needed to treat the target.

[0071] The above description is included to demonstrate particular embodiments of the present invention. It should be appreciated by those of skill in the art that the methods disclosed in the example that follows merely represent exemplary embodiments of the present invention. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments described and still obtain a like or similar result without departing from the spirit and scope of the present invention. Moreover, all patents and publication referenced herein are hereby incorporated by reference as if they were present herein in their entirety.

[0072] As such, various embodiments of the present invention comprise a method of treating a target tissue comprising the steps of dispersing at least one nanotube in a solution; injecting said solution into a medium containing a target; and, applying radio frequency (RF) radiation towards said at least one tube for a sufficient time to at least one of kill said target, ablate said target, modify said target, and/or the like.

[0073] Further embodiments comprise a system for the treatment of a target, said system comprising: at least one nanotube in solution; a means for injecting said nanotube into a medium; and, a means for generating radiofrequency (RP) radiation.

[0074] Yet further embodiments comprise a method for killing, ablating, and/or modifying a target in a medium, said target selected from at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, and/or the like, said method comprising the steps of solubilizing at least one nanotube in a solution; injecting said solution into a medium containing a target; and, applying radio frequency (RF) radiation towards said at least one tube for a sufficient time to at least one of kill said target, ablate said target, and/or modify said target. Further embodiments comprise the step of attaching an enzyme to said at least one nanotube; attaching at least one of a contrast agent, an anti-tumor agents, an anti-viral agents, an anti-retroviral agents, and inorganic matter to said nanotube. [0075] It will be understood that certain of the above-described structures, functions, and operations of the above-described embodiments are not necessary to practice the present invention and are included in the description simply for completeness of an exemplary embodiment or embodiments, hi addition, it will be understood that specific structures, functions, and operations set forth above can be practiced in conjunction with the present invention, but they are not essential to its practice. It is therefore to be understood that the invention may be practiced otherwise than as specifically described without actually departing from the spirit and scope of the present invention as defined by the appended claims. Further, all patents and publication referenced herein are hereby incorporated by reference as if they were presented in their entirety herein.

Examples:

[0076] Previous studies have shown that carpets (forests) of single- walled carbon nanotubes can be readily grown at atmospheric pressures with controlled mixtures containing various hydrocarbons and also in the presence of hydrogen and various hydrocarbons at sub- atmospheric pressures with activation of gas mixtures via plasma formation by microwave or RF discharges. Previous studies have also shown that hot filament activation of gas mixtures of hydrogen and hydrocarbons activates the growth of multi-walled carbon nanotubes in the presence of metal catalysts. Hata, et al., Science 2004, 306, 1362; Gyula, et al., J. Phys. Chem. B 2005, 109, 16684; Zhang, et al.,. PNAS 2005, 102, 16141; Iwasaki, et al., J. Phys. Chem. B 2005, 109, 19556; Zhong, et al, J. Appl. Phys, 2005, 44, 1558; Maruyama, et al., I 2005, 403, 320; Huang et al., J. AmChem. Soc. 2003, 125, 5636.

[0077] It is understood that carbon nanotubes are capable of carrying drugs in the organism because of their size, geometry, and physical attributes. Harutyunyan et al. Carbon nanotubes or Medical Applications, European Cells & Mat., 3:2002, pp. 84-87. Further, methods have been developed for attaching DNA and protein molecules to the inside and outside of various nanotubes, i.e., non-covalent functionalization, covalent-functionalization, π-stacking, endohedral functionalization, sidewall functionalization, and defect functionalization. [0078] Ashcroft et al. "Functionalization of individual ultra-short single-walled carbon nanotubes" Nanotechnology, 2006:17, 5033-5037 reported the functionalization of individual ultra-short (20-80 nm lengths) single-walled carbon nanotubes via in situ Bingel cyclopropanation. Upon chemical reduction of bundled nanotubes, the bundling forces were electrostatically overcome to yield single, negatively charged nanotubes in solution. These single tubes can then be functionalized with malonic acid bis-(3-tert- butoxycarbonylaminopropyl) ester using Bingel chemistry (CBr₄/DBU) to yield 4-5 adducts nm^" ¹ _J as determined by x-ray photoelectron spectroscopy (XPS).

[0079] Other methods of solubilizing nanotubes include wrapping the nanotubes in strands of soluble polymers, such as, but not limited to either DNA, polyethylene glycol (PEG), and/or the like.

[0080] It was reported further that the derivatized nanotubes remained as individuals after functionalization and charge quenching. Thermogravimetric analysis (TGA) and solid-state NMR spectroscopy confirmed covalent attachment of the adducts and indicated tight wrapping of the adduct arms about the nanotubes. The resulting debundled and derivatized nanotubes are capable of being used for a single-molecule-like 'capsule' for the containment and delivery of medically-useful payloads. See Id.

[0081] Various embodiments of the present invention are capable of being used to target at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, or components thereof, and/or the like. Nanotubes are capable of being functionalized with various ligands that recognize groups at the surface of cancer cells. In an embodiment, cells are made to express protein markers called folate receptors (FRs) on their surface by starving them of folic acids, then the FRs bind folic acid in order to redress the deficit, thereby labeling the tumor cells.

[0082] Various further embodiments of the present invention are capable of being used with attached enzymes to be used as enzymatic biosensors that could simultaneously detect and measure a variety of biological molecules. It has been reported by Jang et al. "Dual-

Functionalized Polymer Nanotubes as Substrates for Molecular-Probe and DNA-Carrier

Applications" Hyperstructured Organic Materials Research Center and School of Chemical and

Biological Engineering, Seoul National University, Shinlimdong 56-1, Seoul 151-742, Korea that bifunctionalized polymer nanotubes are applied as both a molecular probe and a DNA carrier by conjugating pyreneacetic acid with the amine groups and immobilizing DNA with the carboxylic acid groups on the surface.

[0083] Further, it has been reported that nanotubes loaded with metal, such as gadolinium, are capable of acting as a 'contrast agent' for magnetic resonance imaging (MRI), helping to improve disease detection by rendering structures in the body more visible. Sitharaman et al.

"Superparamagnetic gadonanotubes are high-performance MRI contrast agents" Chem. Commun.

3915-3917 (2005). MRI procedures very commonly use a contrast agent to enhance the image.

[0084] Nanotubes of the present invention are capable of being loaded with a wide variety of components, such as, but not limited to, anti-tumor agents, anti-viral agents, anti-retroviral agents, inorganic matter, and/or the like. Generally anything of a size sufficient to fit at least partially within the open end of the nanotube can be used. In various embodiments, at least one medicine and/or drug, at least one gene, and/or the like is placed at least partially within the nanotube.

[0085] In an embodiment, polymer-wound nanotubes are transported into a medium, such as a cell, by, for example, endocytosis, and the contents of the nanotube are released.

[0086] In an embodiment, the contents of the nanotube are released by heating the nanotube and disrupting the polymer, such as by RF radiation, IR radiation, and or the like. Generally any form of radiation can be used that will disrupt the polymer surrounding the nanotube.

[0087] In further embodiment, a target is treated by application of RF radiation for a sufficient time to heat the target and/or an area about the target. [0088] The step of applying radio frequency (RF) radiation can be performed by any RF generator. In various embodiments, the RF generator is selected from generators disclosed in US 6,180,976; US 5,895,948; US 5,162,258; US 5,708,559; and/or, the like. Typically any RF generator can be used.

[0089] Various embodiments of the present invention are useful for treating conditions associated with undesired targets. In particular, embodiments of the present invention are beneficial in treating cancers using minimally invasive procedures.

[0090] Various elements of the art are found within the following publications and are hereby incorporated by reference J. Jiao et al, Mat. Res. Soc. Symp. Proc, Fabrication and Characterization of Carbon Nanotube Field Emitters, 2002, 706, Z5.3.1-Z5.3.6; S. Li et al, Chin. Phys. Soc, Electron Field Emission From Single- Walled Carbon Nanotube Nonwoven, 2006, 15(2), 422-427; R.F. Wuerker et al, Annales Geophysicae, Pulsed Energy Storage Antennas For Ionospheric Modification, 2005, 23, 101-107; A. Fiori et al, Dipartimento di Scienze e Technologie Chimiche, Universitά di Roma Tor Vergata, via della Ricerca Scientifica, 00133 Roma; A. Di Carlo et al., Dipartimento di Ingegneria Elettronica, Universitά di Roma Tor Vergata, via del Politecnico, 00133 Roma; A. Ciorba et al., Dipartimento di Energetica, Universitά di Roma La Sapienza via Scarpa 16, 00162 Roma, Field Emission Properties of Selected Single Wall Carbon Nanotube Samples; F. Olsson et al, BAE Systems Bofors, Experiments and Simulations of a Compact UWB Pulse Generator Coupled to Different Antenna Structures.SE-691 80 KARLSKOGA, Sweden; R. Krupke et al, Science, Separation of Metallic from Semiconducting Single- Walled Carbon Nanotubes. 2003, 301, 344-347; Z. Chan et al, J. Dispersion Sd. and Tech., Influence of AC Electric Field on Dispersion of Carbon Nanotubes in Liquids. 2006, 27, 935-940; CA. Grimes et al, Chem. Phys. Lett, The 500 MHz to 5.50 GHz Complex Permittivity Spectra of Single- Wall Carbon NAnotube-Loaded Polymer Composites, 2000, 319, 460-464; J. Liu et al, Science, Fullerene Pipes, 1998, 280, 1253-1256; M. Zhang et al, Appl. Phys. Lett., Radio-Frequency Characterization for the Single-Walled Carbon Nanotubes. 2006, 88, 163109-1-163109-3; J. Han et al, Phys. Lett., The Conductivity of Single Walled Nanotube Films in Terahertz Region. 2003, 310, 457-459; A. Wadhawan et al, Appl Phys. Lett., Nanoparticle-Assisted Microwave Absorption By Single- Wall Carbon Nanotubes, 2003, 83(13), 2683-2685; C. Highstrete et al, Appl Phys. Lett., Microwave Dissipation in Arrays of Single-Wall Carbon Nanotubes, 2006, 89, 173105-1-173105-3; B. Kim et al, J. Appl. Phys., Electrical Properties of Single- Wall Carbon Nanotube and Epoxy Composites, 2003, 94(10), 6724-6728; T. Imholt et al, Chem. Mater., Nanotubes in Microwave Fields: Light Emission., Intense Heat, Outgassing. and Reconstruction, 2003, 15, 3969-3970; J. Vaillancourt et al, Electronics Lett, High-Speed Thin-Film Transistor on Flexible Substrate Fabricated at Room Temperature, 2006, 42(23); T. Kempa et al, J. Appl. Phys., Dielectric Media Based on Isolated Metallic Nanostructures, 2005, 98, 034310-1-034310-4; W. Shi et al, Can. J. Phys./Rev. Can. Phys., Investigation on Dielectric Properties of the Polyetherketone Nanocomposite with Lead Titanate Ultrafines. 2001, 79(5), 847-855; L. Trakhtenberg et al, J. Non-Crystalline Solids, New Nano-Composite Metal-Polymer Materials: Dielectric Behaviour, 2002, 305, 190-196; Z. Dang et al, Mater. Res. Bulletin, Dielectric Properties and Morphologies of Composites Filled With Whisker and Nanosized Zinc Oxide, 2003, 38, 499-507; R. Che et al, Adv. Mater., Microwave Absorption Enhancement and Complex Permittivity and Permeability of Fe Encapsulated Within Carbon Nanotubes, 2004, 16(5), 401-405; L. Valentini et al, J. Diamond and Related Mater., AC Conductivity of Conjugated Polymer onto Self-Assembled Aligned Carbon Nanotubes, 2004, 13, 250-255; P. Pδtschke et al, Polymer, Dielectric Spectroscopy on Melt Processed Polycarbonate - Multiwalled Carbon Nanotube Composites. 2003, 44, 5023-5030; P.C.P. Watts et al, Chem. Phys. Lett., The Complex Permittivity of Multi-Walled Carbon Nanotube- Polvstyrene Composite Films in X-band, 2003, 378, 609-614; A.N. Lagarkov et al, Physical Rev., Electromagnetic Properties of Composites Containing Elongated Conducting Inclusions, 1996, 53(10), 6318-6336; K. Kempa, Physical Rev., Dielectric Function of Media Based on Conductive Particles. 2006, 74, 033411-1-033411-3; R.M. Hill et al, J. Phys. C: Solid State Phys., Bebve and Non-Debve Relaxation, 1985, 18, 3829-3836; C. Li et al, Physical Rev., Single- Walled Carbon Nanotubes as Ultrahigh Frequency Nanomechanical Resonators, 2003, 68, 073405-1-073405-3; H. Kim et al, Appl Phys. Lett., Electrical Conductivity and Electromagnetic Interference Shielding of Multiwalled Carbon Nanotube Composites Containing Fe Catalyst, 2004, 84(4), 589-591.

Claims

What is claimed is:

1. A method of treating a target tissue comprising the steps of: a. dispersing at least one nanotube in a solution; b. injecting said solution into a medium containing a target; and, c. applying radio frequency (RF) radiation towards said at least one tube for a sufficient time to at least one of kill said target, ablate said target, modify said target, and/or the like.

2. The method of claim 1, wherein said step of dispersing said at least one nanotube further comprises functionalizing said at least one nanotube.

3. The method of claim 1, wherein said step of dispersing said at least one nanotube further comprises adding a surfactant to said solution.

4. The method of claim 1 , wherein said step of dispersing said at least one nanotube further comprises adding at least one moiety to generate a covalent sheath around said at least one nanotube.

5. The method of claim 1, further comprising the step of attaching a targeting agent to said at least one nanotube.

6. The method of claim 1, further comprising the step of sonicating said solution to remove bundled nanotubes from said solution.

7. The method of claim 1 , wherein said target is a surgically nonresectable pathology.

8. The method of claim 1 , wherein said solution comprises a surfactant.

9. A system for the treatment of a target, said system comprising: at least one nanotube in solution; a means for injecting said nanotube into a medium; and, a means for generating radiofrequency (RF) radiation.

10. The system of claim 9, wherein said at least one nanotube in solution is functionalized.

11. The system of claim 9, wherein said at least one nanotube in solution comprises a targeting agent for targeting said target.

12. A method for killing, ablating, and/or modifying a target in a medium, said target selected from at least one virus, at least one cell, at least one tissue, at least one retrovirus, at least one bacteria, at least one fungus, and/or the like, said method comprising the steps of: a. solubilizing at least one nanotube in a solution; b. injecting said solution into a medium containing a target; and, c. applying radio frequency (RF) radiation towards said at least one tube for a sufficient time to at least one of kill said target, ablate said target, and/or modify said target.

13. The method of claim 12, wherein said nanotube comprises an agent for killing, ablating, and/or modifying said target.

14. The method of claim 12, wherein said RF radiation is a short pulse.

15. The method of claim 12, further comprising the step of attaching an enzyme to said at least one nanotube.

16. The method of claim 15, wherein said nanotube is an enzymatic biosensorΛ

17. The method of claim 12, further comprising the step of attaching at least one of a contrast agent, an anti-tumor agents, an anti-viral agents, an anti-retroviral agents, and inorganic matter to said nanotube.

18. The method of claim 17, further comprising the step of introducing said at least one nanotube to at least one cell.

19. The method of claim 18, wherein said nanotube is a polymer- wound nanotube.

20. The method of claim 19, wherein said nanotube is introduced to said at least one cell by endocytosis.

21. The method of claim 20, further comprising releasing said at least one of a contrast agent, an anti-tumor agents, an anti-viral agents, an anti-retroviral agents, and inorganic matter to said nanotube.