Metal nanoshells for biosensing applications

Abstract

The present invention provides nanoshell particles (“nanoshells”) for use in biosensing applications, along with their manner of making and methods of using the nanoshells for in vitro and in vivo detection of chemical and biological analytes, preferably by surface enhanced Raman light scattering. The preferred particles have a non-conducting core and a metal shell surrounding the core. For given core and shell materials, the ratio of the thickness (i.e., radius) of the core to the thickness of the metal shell is determinative of the wavelength of maximum absorbance of the particle. By controlling the relative core and shell thicknesses, biosensing metal nanoshells are fabricated which absorb light at any desired wavelength across the ultraviolet to infrared range of the electromagnetic spectrum. The surface of the particles are capable of inducing an enhanced SERS signal that is characteristic of an analyte of interest. In certain embodiments a biomolecule is conjugated to the metal shell and the SERS signal of a conformational change or a reaction product is detected.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional application of U.S. Patent Application No. 09,616,154 filed Jul. 14, 2000 entitled “Metal Nanoshells for Biosensing Applications” which is a continuation-in-part of co-pending U.S. patent application Ser. No. 09 / 038,377 filed Mar. 11, 1998, and also claims the benefit of U.S. Provisional Application No. 60 / 144,136 filed Jul. 16, 1999. The disclosures of those applications are incorporated herein by reference.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] This invention was made with government support under Grant No. N00014-97-1-0217 awarded by the Office of Naval Research and under Grant No. ECS-9258118 awarded by the National Science Foundation. The United States government has certain rights in the invention.BACKGROUND OF THE INVENTION [0003] 1. Field of the Invention [0004] The present invention generally relates to particles composed of a nonconducting core coated with a very...

AI Technical Summary

Benefits of technology

[0015] According to certain embodiments, the in vitro assay method includes selecting one or more optically tuned nanoshells with an absorption or scattering maximum wavelength that substantially matches the wavelength of a desired source of electromagnetic radiation. In some embodiments the chosen nanoshells include one or more conjugated biomolecules. The method also includes associating the nanoshells with one or more molecules of the desired analyte contained in the sample such that an analyte/nanoshell complex is formed. In certain embodiments the method includes associating the nanoshells with a reporter molecule, in which case a reporter/analyte/nanoshell complex is formed. Either complex is capable of producing a Raman signal upon irradiation by the selected source. Preferably the source is in the near-IR range of the electromagnetic spectrum. The method further includes irradiat...

Problems solved by technology

Although infrared excitation eliminates sample fluorescence, it also results in marked decrease in sensitivity, further motivating the need for a sensitization method.

Current methods being used for SERS enhancement of near infrared FT-Raman spectroscopy are frequently plagued by difficult substrate preparation, poor reproducibility, sensitivity to contamination, or limited suitability for in vivo use.

J. Biol. Chem. 227:285-299 (1957)), however, which significantly restricts the use of visible excitation Raman spectroscopy on biological systems.

Although that method was used in a successful sandwich immunoassay, the use of a microscopic silver substrate and the necessity for conjugation of the biomolecules with specific (carcinogenic) chromophores for resonance Raman detection severely limits the adaptability of that approach.

Since near infrared excitation results in a dramatic decrease in sensitivity relative to visible Raman excitation, the most outstanding current limitation to Raman-based glucose monitoring is the lack of sensitivity.

Images