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05/14/09 - USPTO Class 252 |  24 views | #20090121193 | Prev - Next | About this Page  252 rss/xml feed  monitor keywords

Surface enhanced spectroscopy-active composite nanoparticles

USPTO Application #: 20090121193
Title: Surface enhanced spectroscopy-active composite nanoparticles
Abstract: Metal nanoparticles associated with a spectroscopy-active (e.g., Raman-active) analyte and surrounded by an encapsulant are useful as sensitive optical tags detectable by surface-enhanced spectroscopy (e.g., surface-enhanced Raman spectroscopy). (end of abstract)



Agent: Swanson & Bratschun, L.L.C. - Littleton, CO, US
Inventor: Michael J. Natan
USPTO Applicaton #: 20090121193 - Class: 2524081 (USPTO)

Surface enhanced spectroscopy-active composite nanoparticles description/claims


The Patent Description & Claims data below is from USPTO Patent Application 20090121193, Surface enhanced spectroscopy-active composite nanoparticles.

Brief Patent Description - Full Patent Description - Patent Application Claims
  monitor keywords CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 11/132,471, filed May 18, 2005, entitled “Surface Enhanced Spectroscopy-Active Composite Nanoparticles.” U.S. patent application Ser. No. 11/132,471 is a continuation of U.S. patent application Ser. No. 10/345,821, filed Jan. 16, 2003, entitled “Surface Enhanced Spectroscopy-Active Composite Nanoparticles,” and now U.S. Pat. No. 7,192,778, which is a continuation-in-part of U.S. patent application Ser. No. 09/680,782, filed Oct. 6, 2000, entitled “Surface Enhanced Spectroscopy-Active Composite Nanoparticles,” now U.S. Pat. No. 6,514,767, issued Feb. 4, 2003, which claims priority to U.S. Provisional Application No. 60/157,931, filed Oct. 6, 1999, entitled “Glass Coated Surface Enhanced Raman Scattering Tags,” and U.S. Provisional Application No. 60/190,395, filed Mar. 17, 2000, entitled “GANS Particles.” Each of the foregoing applications is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

This invention relates generally to submicron-sized tags or labels that can be covalently or non-covalently affixed to entities of interest for the purpose of quantification, location, identification, or tracking. More particularly, it relates to surface enhanced spectroscopy-active composite nanoparticles, methods of manufacture of the particles, and uses of the particles.

BACKGROUND OF THE INVENTION

When light is directed onto a molecule, the vast majority of the incident photons are elastically scattered without a change in frequency. This is termed Rayleigh scattering. However, the energy of some of the incident photons (approximately 1 in every 107 incident photons) is coupled into distinct vibrational modes of the molecule\'s bonds. Such coupling causes some of the incident light to be inelastically scattered by the molecule with a range of frequencies that differ from the range of the incident light. This is termed the Raman effect. By plotting the frequency of such inelastically scattered light against its intensity, the unique Raman spectrum of the molecule under observation is obtained. Analysis of the Raman spectrum of an unknown sample can yield information about the sample\'s molecular composition.

The incident illumination for Raman spectroscopy, usually provided by a laser, can be concentrated to a small spot if the spectroscope is built with the configuration of a microscope. Since the Raman signal scales linearly with laser power, light intensity at the sample can be very high in order to optimize sensitivity of the instrument. Moreover, because the Raman response of a molecule occurs essentially instantaneously (without any long-lived highly energetic intermediate states), photobleaching of the Raman-active molecule-even by this high intensity light-is impossible. This places Raman spectroscopy in stark contrast to fluorescence spectroscopy, in which photobleaching dramatically limits many applications.

The Raman effect can be significantly enhanced by bringing the Raman-active molecule(s) close (≦50 Å) to a structured metal surface; this field decays exponentially away from the surface. Bringing molecules in close proximity to metal surfaces is typically achieved through adsorption of the Raman-active molecule onto suitably roughened gold, silver or copper or other free electron metals. Surface enhancement of the Raman activity is observed with metal colloidal particles, metal films on dielectric substrates, and with metal particle arrays. The mechanism by which this surface-enhanced Raman scattering (SERS) occurs is not well understood, but is thought to result from a combination of (i) surface plasmon resonances in the metal that enhance the local intensity of the light, and; (ii) formation and subsequent transitions of charge-transfer complexes between the metal surface and the Raman-active molecule.

SERS allows detection of molecules attached to the surface of a single gold or silver nanoparticle. A Raman enhancing metal nanoparticle that has associated or bound to it a Raman-active molecule(s) can have utility as an optical tag. For example, the tag can be used in immunoassays when conjugated to an antibody against a target molecule of interest. If the target of interest is immobilized on a solid support, then the interaction between a single target molecule and a single nanoparticle-bound antibody can be detected by searching for the Raman-active molecule\'s unique Raman spectrum. Furthermore, because a single Raman spectrum (from 100 to 3500 cm−1) can detect many different Raman-active molecules, SERS-active nanoparticles may be used in multiplexed assay formats.

SERS-active nanoparticles with adsorbed Raman-active molecules offer the potential for unprecedented sensitivity, stability, and multiplexing functionality when used as optical tags in chemical assays. However, metal nanoparticles present formidable practical problems when used in such assays. They are exceedingly sensitive to aggregation in aqueous solution; once aggregated, it is not possible to re-disperse them. In addition, the chemical compositions of some Raman-active molecules are incompatible with the chemistries used to attach other molecules (such as proteins) to metal nanoparticles. This restricts the choices of Raman-active molecules, attachment chemistries, and other molecules to be attached to the metal nanoparticle.

SUMMARY OF THE INVENTION

One embodiment of the present invention provides surface-enhanced spectroscopy (SES)-active composite nanoparticles, such as SERS-active composite nanoparticles (SACNs). Such nanoparticles each contain a SES-active metal nanoparticle; a submonolayer, monolayer, or multilayer of spectroscopy-active species associated with or in close proximity (e.g., adsorbed) to the metal surface; and an encapsulating shell made of a polymer, glass, or any other dielectric material. This places the spectroscopy-active molecule (alternately referred to herein as the “analyte,” not to be confused with the species in solution that is ultimately being quantified) at the interface between the metal nanoparticle and the encapsulant.

In some embodiments, the encapsulant is glass. The resulting glass-coated analyte-loaded nanoparticles (GANs) retain the activity of the spectroscopy-active analyte, but tightly sequester this activity from the exterior surface of the nanoparticle. Thus, in the case of surface-enhanced Raman scattering (SERS), the resulting GAN exhibits SERS activity, but the Raman-active analyte is located at the interface between the metal nanoparticle and the encapsulant.

The analyte molecule can be chosen to exhibit extremely simple Raman spectra, because there is no need for the species to absorb visible light. This, in turn, allows multiple composite nanoparticles, each with different analyte molecules, to be fabricated such that the Raman spectrum of each analyte can be distinguished in a mixture of different types of particles.

Surface-enhanced spectroscopy (SES)-active composite nanoparticles are easily handled and stored. They are also aggregation resistant, stabilized against decomposition of the analyte in solvent and air, chemically inert, and can be centrifuged and redispersed without loss of SERS activity. SACNs may be provided as a dispersion in suitable solvent for storage or association with an object or molecule.

In one embodiment, the encapsulant may be readily derivatized by standard techniques. This allows the particles to be conjugated to molecules (including biomolecules such as proteins and nucleic acids) or to solid supports without interfering with the Raman activity of the particles. Unlike metal nanoparticles, SACNs can be evaporated to dryness and then completely redispersed in solvent. Using the techniques provided herein, it is possible to fabricate particles that are individually detectable using SERS.

In an alternative embodiment, SACNs are attached to, mixed with, or otherwise associated with objects for tracking, identification, or authentication purposes. Each type of particle or group of particle types, as defined by the Raman spectrum of the encapsulated analyte, represents a particular piece of information. Tagged objects are verified by acquiring their Raman spectrum. Any liquid, solid, or granular material can be tagged with a SACN. By associating an object with more than one different SACN type, a large number of distinct SACN groups can be obtained.

BRIEF DESCRIPTION OF THE FIGURES

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