Plasmon resonant particles, methods and apparatus

• US 6,180,415 B1
• Filed: 02/20/1998
• Issued: 01/30/2001
• Est. Priority Date: 02/20/1997
• Status: Expired due to Term

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Schultz, David A., Smith, David R., Mock, Jack J., Schultz, Sheldon, Silva, Thomas J.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/027,048
• Time in Patent Office: 1,075 Days
• Field of Search: 436/164, 436/171, 436/518, 436/524, 436/525, 436/805, 356/301, 356/307, 356/317, 356/318, 356/337
• US Class Current: 436/518
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 21/554 detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G06K 19/06084 the marking being based on nanoparticles or microbeads
• CPC Class Codes: G06K 7/1408 the method being specifically adapted for the type of code
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

A method and apparatus for interrogating a target having a plurality of plasmon resonant particles (PREs) distributed in the target are disclosed. In the method, a field containing the target is illuminated, and one or more spectral emission characteristics of the light-scattering particles in the field are detected. From this data, an image of positions and spectral characteristic values in the field is constructed, allowing PREs with a selected spectral signature to be discriminated from other light-scattering entities, to provide information about the field. Also disclosed are a novel PRE composition for use in practicing the method, and a variety of diagnostic applications of the method.

Claims

1. A method of interrogating a field having a plurality of plasmon or resonant entities (PREs) distributed therein, comprising;

illuminating the field with an optical light source,

detecting a spectral emission characteristic of individual PREs and other light scattering entities in the field,

constructing a computer image of the positions and values of the emission spectral characteristic of individual PREs and other light-scattering entities present in the field, and

discriminating PREs with a selected spectral signature from other light-scattering entities based on detected spectral characteristic values unique to the selected-signature PREs, to provide information about the field.

2. The method of claim 1, wherein said detecting includes simultaneously detecting the spectral emission characteristic of the light-scattering entities in the field.

3. The method of claim 2, wherein said detecting further includes detecting the spectral emission characteristic of the light scattering entities in the field simultaneously at a plurality of defined spectral frequencies.

4. The method of claim 1, wherein said illuminating and detecting steps include:

illuminating said PREs with incident light predominantly in a first frequency band;

detecting the spectral emission characteristics of individual PREs and other light scattering entities in the field under illumination at the first frequency band;

illuminating said PREs with incident light predominantly in a second frequency band; and

detecting the spectral emission characteristics of individual PREs and other light scattering entities in the field under illumination at the second frequency band.

5. The method of claim 1, wherein said detecting includes sequentially detecting the spectral emission characteristic of individual PREs and other light scattering entities in the field at a plurality of defined spectral bands.

6. The method of claim 1, wherein said illuminating includes exposing the field to a plurality of narrowband pulses of light which vary in duration, and said detecting includes detecting variations in emitted light intensity produced by variations in duration.

7. The method of claim 1, wherein at least some of the PREs are non spherical, said illuminating includes exposing the field to polarized light at different orientations and/or different angles of incident, and said discriminating includes detecting changes in a spectral emission characteristic as a function of incident light polarization orientation or angle.

8. The method of claim 1, wherein said PREs are formed in the field by a step selected from the group consisting of:

(i) binding nucleation centers to a field, metal enhancing said nucleation centers, observing enhancement of said nucleation center during said metal enhancing process, and terminating enhancement when a PRE of a desired spectral characteristic has been formed;

(ii) adding pre-formed PREs to a target in the field,

(iii) making PREs at target sites in the field.

9. The method of claim 1, wherein discriminating PREs with a selected spectral signature from other light-scattering entities in the field includes discriminating a selected type of PRE from all other light-scattering entities in the field, based on detected values, for each light-scattering entity in the field, of peak position, peak intensity, or peak width at half intensity of the spectral emission curve, peak halfwidth in the image plane, and polarization or angle of incidence response.

10. The method of claim 9, wherein said discriminating is effective to discriminate, for a selected type of PREs, those selected PREs which are interacting with one another and those which are not.

11. The method of claim 9, wherein said discriminating is effective to discriminate a selected type of PRE from another selected type of PRE in the field.

12. The method of claim 1, wherein the PREs have surface-localized fluorescent molecules or Raman-active molecular entities, and said detecting includes detecting plasmon-resonance induced fluorescent emission or Raman spectroscopy emission from one or more of said molecules or entities, respectively.

13. The method of claim 1, for use in determining the total number of PREs of a selected type in a field, wherein said discriminating includes counting the number of PREs having a selected range of values of a selected spectral emission characteristic in the constructed computer image.

14. The method of claim 1, for use in determining a spatial pattern of PREs having a selected range of values of a selected spectral characteristic in the field, wherein discriminating includes constructing an image of the relative locations of PREs with those spectral-characteristic values.

15. The method of claim 14, wherein the location between two adjacent PREs is less than the Rayleigh resolution distance, and said detecting includes exposing the field with light of one wavelength, to obtain a diffraction image of PREs in the field, exposing the field with light of a second wavelength to obtain a second diffraction image of PREs in the field, and comparing the distance between peaks in the two diffraction patterns.

16. The method of claim 1, for use in interrogating a change in the environment of the field, wherein said discriminating includes comparing the values of the detected spectral characteristic of a PRE in the field before and after said change.

17. The method of claim 16, wherein the field is interrogated for changes in the dielectric constant of environment.

18. The method of claim 1, for use in detecting motion of PREs in the field, wherein said illuminating is effective to generate, for each PRE, a diffraction pattern having a center peak and said detecting includes detecting the center peaks of the diffraction patterns of the PRE'"'"'s in the image plane, as a function of time.