The present invention relates to catalysis, sensors, and therapeutics.
Small metal aggregates show strong catalytic activity, unknown for bulk structures with identical chemical composition. The distinct absorption behavior of metal clusters provides a basis for various optical applications. The characteristic properties of matter in the atom-to-bulk transition range partly result from a strong size dependence of the electronic structure. The discrete energy levels of isolated atoms split and broaden to electron bands in larger aggregates. The band structure determines the propagation and mobility of electrons inside the crystal. In principle, control over the size-dependent electronic structure allows an adjustment of intrinsic material properties to the demands of a wide range of applications.
The high electron density and efficient screening in metals make the critical length scale for the atom-to-bulk-transition considerably smaller than for semiconductors. Gradual development of metallic behavior has been observed for ultra small clusters, either in the gas phase or on surfaces. The transition is characterized by the closure of gaps in the electronic states and the development of collective electronic excitations.
For example, as the metal particle size decreases, the core-level binding energy of metals such as Au, Ag, Pd, Ni and Cu increases sharply. This increase in the core-level binding energy in small particles occurs due to the poor screening of the core-hole and is a manifestation of the size-induced metal-nonmetal transition. Similarly, the interaction of oxygen with silver nanoclusters has shown the ability of the smaller nanocrystals to dissociate dioxygen to atomic oxygen species. Gold nanoclusters on titania are known to catalyze CO oxidation at a cluster size of around 3.5 nm, with the gold behaving more as a non-metal and smaller cluster sizes.
This change is because the average electronic energy spacing of successive quantum levels, δ, known as the Kubo gap is given by 4EF/3n, where EF is the Fermi energy of the bulk material and n is the total number of valence electrons in the nanocrystal. So for an individual silver nanoparticle of 3 nm diameter containing approximately 1000 silver atoms, the value of δ is 5-10 meV. Since the thermal energy at room temperature, kT˜25 meV, a 3 nm particle would be metallic. At lower temperatures, the level spacings become comparable to kT and rendering them non-metallic. Because of the presence of the Kubo gap in individual nanoparticles, properties such as electrical conductivity and magnetic susceptibility exhibit quantum size effects. The resultant discreteness of energy levels also brings about fundamental changes in the characteristic spectral features of the nanoparticles, especially those related to the valence band.
The use of nanoparticles as catalysts has been disclosed in the following: U.S. 20040132269, U.S. 20040028812, U.S. 20040025895, and U.S. 20040007241.
A number of applications have been described for the delivery of drugs to targets via the use of nanoparticles (see, for example, U.S. Pat. No. 5,962,566, U.S. 20040082521, U.S. 20030152636, U.S. 20030064965, and U.S. 20020034474).
In U.S. Pat. Nos. 6,281,514, 6,531,703 and 6,495,843 and WO9940628 a method is disclosed for promoting the passage of elementary particles at or through a potential barrier comprising providing a potential barrier having a geometrical shape for causing de Broglie interference between said elementary particles. In another embodiment, the invention provides an elementary particle-emitting surface having a series of indents. The depth of the indents is chosen so that the probability wave of the elementary particle reflected from the bottom of the indent interferes destructively with the probability wave of the elementary particle reflected from the surface. This results in the increase of tunneling through the potential barrier. When the elementary particle is an electron, then electrons tunnel through the potential barrier, thereby leading to a reduction in the effective work function of the surface. In further embodiments, the invention provides vacuum diode devices, including a vacuum diode heat pump, a thermionic converter and a photoelectric converter, in which either or both of the electrodes in these devices utilize said elementary particle-emitting surface. In yet further embodiments, the invention provides devices in which the separation of the surfaces in such devices is controlled by piezo-electric positioning elements. A further embodiment provides a method for making an elementary particle-emitting surface having a series of indents
In U.S. Pat. No. 6,117,344 and WO9947980 methods are described for fabricating nano-structured surfaces having geometries in which the passage of elementary particles through a potential barrier is enhanced. The methods use combinations of electron beam lithography, lift-off, and rolling, imprinting or stamping processes.
In U.S. Pat. No. 6,680,214 a method is disclosed for the induction of a suitable band gap and electron emissive properties into a substance, in which the substrate is provided with a surface structure corresponding to the interference of electron waves. Lithographic or similar techniques are used, either directly onto a metal mounted on the substrate, or onto a mold which then is used to impress the metal. In a preferred embodiment, a trench or series of nano-sized trenches are formed in the metal.
In WO03/083177, the use of electrodes having a modified shape and a method of etching a patterned indent onto the surface of a modified electrode, which increases the Fermi energy level inside the modified electrode, leading to a decrease in electron work function is disclosed. The method comprises creating an indented or protruded structure on the surface of a metal. The depth of the indents or height of protrusions is equal to a, and the thickness of the metal is Lx+a. The minimum value for a is chosen to be greater than the surface roughness of the metal. Preferably the value of a is chosen to be equal to or less than Lx/5. The width of the indentations or protrusions is chosen to be at least 2 times the value of a. Typically the depth of the indents is ≧λ/2, wherein λ is the de Broglie wavelength, and the depth is greater than the surface roughness of the metal surface. Typically the width of the indents is >>λ, wherein λ is the de Broglie wavelength. Typically the thickness of the is a multiple of the depth, preferably between 5 and 15 times said depth, and preferably in the range 15 to 75 nm.
In accordance with one embodiment of the present invention, there is provided a method for catalyzing a chemical reaction comprising contacting a reactant or reactants of said chemical reaction with a substantially plane slab of a material having on one surface one or more indents of a depth approximately 5 to 20 times a roughness of said surface and a width approximately 5 to 15 times said depth.
The present invention additionally provides a method for treating a human or animal subject having a disease comprising contacting said subject with a substantially plane slab of a material having on one surface one or more indents of a depth approximately 5 to 20 times a roughness of said surface and a width approximately 5 to 15 times said depth.
In a further embodiment said disease is caused by a virus, bacterium or fungus
The present invention additionally provides a method for killing a pest of an animal or plant comprising contacting said animal or plant with a substantially plane slab of a material having on one surface one or more indents of a depth approximately 5 to 20 times a roughness of said surface and a width approximately 5 to 15 times said depth.
The present invention additionally provides a method for killing a plant comprising contacting said plant with a substantially plane slab of a material having on one surface one or more indents of a depth approximately 5 to 20 times a roughness of said surface and a width approximately 5 to 15 times said depth.
In a further embodiment one or more additional agents are immobilized or adsorbed onto a surface opposite the indented surface. The agents may comprise one or more biocatalyst agents.
The present invention additionally provides a formulation of matter comprising: (a) a substantially plane slab of a material having on one surface one or more indents of a depth approximately 5 to 20 times a roughness of said surface and a width approximately 5 to 15 times said depth; (b) excipients, additives, stabilizers or other agents.
A technical advantage of the present invention is that it promotes the transfer of electrons across a potential barrier, and for a particular energy barrier that exists on the border between a solid body and a vacuum, provides a surface with a sharply defined geometric pattern that causes destructive interference between reflected electron probability waves (De Broglie waves). Another technical advantage of the present invention is that it allows for an increase in particle emission through a potential energy barrier. Another technical advantage of the present invention is that a surface has a sharply defined geometric pattern of a dimension that promotes destructive interference of the reflected elementary particle probability waves.
The present invention is concerned with the use of materials having nano-structured features as catalysts.
The present invention is concerned with the use of materials having nano-structured features as sensors.
The present invention is concerned with the use of materials having nano-structured features as agents to increase the biological activity of enzymes, antibodies, receptors, proteins and the like.
The present invention is concerned with the use of materials having nano-structured features as agents to reduce the biological activity of enzymes, antibodies, receptors, proteins and the like.
The present invention is concerned with the use of materials having nano-structured features, either alone or in conjunction with another agent, as biosensors.
The present invention is concerned with the use of materials having nano-structured features, either alone or in conjunction with another agent, as pesticides.
The present invention is concerned with the use of materials having nano-structured features, either alone or in conjunction with another agent, as herbicides.
The present invention is concerned with the use of materials having nano-structured features, either alone or in conjunction with another agent, as therapeutic agents for humans or animals.
For a more complete understanding of the present invention and the technical advantages thereof, reference is made to the following description taken with the accompanying drawings, in which:
The embodiments of the present invention and its technical advantages are best understood by referring to
Referring now to
The introduction of grooves into a surface as illustrated in
Referring now to
In a further embodiment the surface shown in
In a further embodiment the present invention is a sensor. Sensors detect the presence of a particular material by the perturbation in local conditions when a molecule to be sensed interacts with the sensor surface. The perturbation in local conditions may be an electrical change as a result of a redox reaction with a material coating the surface, or it may be a change in the surface plasmon resonance as a result of the interaction event. In the present invention, the sensor surface has the nano-structured surface described in the foregoing. The interaction of the material to be sensed with the sensor surface causes a change in the wave interference behavior of the electrons comprising the sensor surface. The change in the wave interference behavior of the sensor surface may be detected, for example, by measuring, directly or indirectly, a change in the work function of the material.
In a further embodiment the present invention is a biosensor. Biosensors generally comprise one or more biological molecules or entities in electrical contact with a sensor surface. The biological molecule may, for example, be an enzyme, protein, receptor, antibody, hapten or nucleic acid molecule. The biological entity may be a cell or organelle. Biosensors detect the presence of a particular material by the perturbation in local conditions when a molecule to be sensed interacts with the biological molecule or entity. The perturbation in local conditions may be an electrical change as a result of a redox reaction, or it may be a change in the surface plasmon resonance as a result of the binding event. In the present invention, the sensor surface has the nano-structured surface described in the foregoing. The interaction of the material to be sensed with the one or more biological molecules causes a change in the wave interference behavior of the electrons comprising the sensor surface. The change in the wave interference behavior of the sensor surface may be detected, for example, by measuring, directly or indirectly, a change in the work function of the material. Alternatively, the movement of electrons from the nano-structured surface is connected to an electronic monitoring device that is sensitive to a long-term change in the electron flow from the nano-structured surface. It is likely that a stable interaction between a nano-structured surface and a biomolecule will induce such a long-term change in the electron flow from the nano-structured surface. The specificity of this interaction is achieved by construction of the nano-structured surface that is presenting an antibody or analogous binding partner for a specific biomolecule. Once constructed, the basic biosensor might then be implemented in several ways.
For example, the nano-structured surface biosensor is electrically connected to a drug delivery system. Such a sensor will be engineered to detect for example, the presence of a specific microbe; or in another example, a change in the chemical environment (e.g. the presence of hyperglycemic levels of glucose). Upon sensing the specific condition, the monitoring device would release specific amounts of a drug that is contained within the device. Upon drug distribution, there should be a signal broadcast that is detected by a receiver outside of the body. Depending on the scale of such a device, this application might be used for either single-shot emergency purposes, or for treatment of a chronic medical condition. If used on an ongoing basis, (not all stored drug is released simultaneously), a mechanism must be developed to reset or regulate the system. One limitation of this application would be the amount of drug required to be stored in such a device, and the need to refill the drug compartment. However, this might be reduced if the drug is associated with an nano-structured surface, thereby increasing its activity and lowering the required dose (see above).
A biosensor of the present invention may be applied to portable and stationary detectors of biological and chemical weapons. According to this embodiment a device that inputs an air sample over a series of biosensors that are each specific to a given agent. The required size of the device would vary with the volume of air/second that is required to be monitored. The smallest version of such a device would be portable and hand-held or easily installed into a standard car, allowing for wide distribution among police and other security personnel and enabling a timely response upon hazard detection. Such a device would also be useful on commercial aircraft, which are ideally suited for wide distribution of pathogens.
A biosensor of the present invention may be applied to water analysis. Strikingly, the current water safety measures are taken only after the water has been cultured for several hours and the microbe detected. A biosensor array of the present invention that is specific to the most common forms of bacterial contamination would decrease the length of time required for positive detection and public notification of contaminated water. The design of such a device would be very similar to that described above for biological weapons detection, with the exception that the detector composed of the nano-structured surface will be exposed to circulating water instead of air, and the specific adsorbed sensing molecules would correspond to the most common water contaminants. Another difference is that it is unlikely that the water being tested under certain circumstances is completely free from bacterial contamination. Therefore, the biosensor would have to be designed to distinguish between varying ranges of microbe titer, or at a minimum be able to distinguish between acceptable and unacceptable bacterial concentrations. As described, this device could also be utilized to guard against intentional water contamination, with the only limitation being the types of agents recognized by the nano-structured surface.
In one embodiment the present invention is a biocatalyst, in which the flat surface shown in
In one embodiment the present invention is a biological agent having modified properties, in which the flat surface shown in
Additionally, the binding molecule may be used to bring the nano-structured surface of the present invention into close proximity to a therapeutic target. Thus, where the therapeutic target is a cancer cell, an antibody, for example, may serve to effectively cover the surface of the cancer cell with the nano-particulate form of the surface of the invention. The properties of the surface of the invention are such as to result in the death of a cell so covered. Such an approach may be particularly useful for the treatment of cancers of the blood and lymphomas. It may also be useful in herbicides and pesticides, and as a antibacterial, antifungal or antiviral agent.
The properties of these nano-structured surfaces have the potential to accelerate and potentiate biochemistry. For example, it is possible that the activity of a therapeutic agent will be increased through its association with a nano-structured surface. In such a case, an increase in drug efficacy may allow for a marked reduction in required dosage and by extension, toxicity and deleterious side-effects. In another example, an ineffective candidate drug may become effective through an association with the nano-structured surface, thereby increasing the pool of candidates that may be biologically acceptable. Together, these scenarios suggest that these nano-structured surfaces might prove an indispensable addition to the drug development process from the earliest stages.
Use of these nano-structured surfaces in pharmaceutical applications requires the adsorption of the potential therapeutic agent to the nano-structured surface. Therefore, distribution of them for this application may be carried out in either an ‘off the shelf’ approach or by direct license of the patent. An ‘off the shelf’ nano-structured surface for drug applications would be a colloidal surface that is either ready for treatment with any given adsorption substrate, or comes pre-coated with adsorption substrate. The specific adsorption substrates to use would need to be determined through a combination of laboratory research to establish what is most useful, and through market research to determine which molecular anchors are most commonly used.
In a yet further embodiment of the present invention, the nano-structured surface itself, particularly in granulated form, may act as a herbicide or pesticide, or as a antibacterial, antifungal or antiviral agent. Coatings of other materials on the nano-structured surface may modify the raw properties of the nano-structured surface to make it more or less suitable for particular targets. In the case of bacteria, mold, and fungi, this may entail the association of an nano-structured surface with an electron donor that targets a cell membrane or cell wall receptor, introducing an unacceptable charge load in the cell. Another example of similar concept would be to associate an ion channel regulatory molecule with the nano-structured surface. The overstimulated activation/repression of the specific channel would shut down the cell, also leading to cell death. The great advantage of such a class of antimicrobials would be the ability to determine the specificity of action by the choice of the adsorbed bioactive molecule. Nano-structured surface antimicrobials could be used similarly to antibiotics, and will become increasingly important as microbial antibiotic resistance increases. In all cases, the nano-structured surface antimicrobial and pesticide should be in such a form that it can be sprayed onto fields with the same equipment currently used for standard chemical pesticides.
Although the above specification contains many specificities, these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention.
Indentations and protrusions to a basic surface are both described in the specification, and there is really little technical difference between the two, except in their production method. Where an indented surface is referred to, it should be read as also referring to a surface having protrusions, which, by definition, causes the surface to have an indented cross-section, having indents in the ‘spaces’ between the protrusions.
The method for enhancing passage of elementary particles through a potential barrier has many applications as disclosed in the foregoing.
Number | Date | Country | Kind |
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GB0417190.6 | Aug 2004 | GB | national |
This application claims the benefit of U.K. Provisional Application No. GB0417190.6, filed Aug. 2, 2004. This application is also a continuation-in-part application of application Ser. No. 10/508,914 filed Sep. 22, 2004, which is a U.S. national stage application of International Application PCT/US03/08907, filed Mar. 24, 2003, which international application was published on Oct. 9, 2003, as International Publication WO03083177 in the English language. The International Application claims the benefit of U.S. Provisional Application No. 60/366,563, filed Mar. 22, 2002, U.S. Provisional Application No. 60/366,564, filed Mar. 22, 2002, and U.S. Provisional Application No. 60/373,508, filed Apr. 17, 2002. This application is also a continuation-in-part application of application Ser. No. 10/760,697 filed Jan. 19, 2004 which is a divisional application of application Ser. No. 09/634,615, filed Aug. 5, 2000, now U.S. Pat. No. 6,680,214, which claims the benefit of U.S. Provisional Application No. 60/149,805, filed on Aug. 18, 1999, and is a continuation application of application Ser. No. 09/093,652, filed Jun. 8, 1998, now abandoned, and is related to application Ser. No. 09/020,654, filed Feb. 9, 1998, now U.S. Pat. No. 6,281,514. The above-mentioned patent applications are assigned to the assignee of the present application and are herein incorporated in their entirety by reference.
Number | Date | Country | |
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60366563 | Mar 2002 | US | |
60366564 | Mar 2002 | US | |
60373508 | Apr 2002 | US |
Number | Date | Country | |
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Parent | 10508914 | Sep 2004 | US |
Child | 11196365 | Aug 2005 | US |