SERS Nanotag Assays

• US 20100177306A1
• Filed: 04/18/2008
• Published: 07/15/2010
• Est. Priority Date: 04/18/2007
• Status: Active Grant

• Current Assignee: Sicpa Holding SA
• Original Assignee: Sicpa Holding SA
• Inventors: Natan, Michael J.
• Granted Patent: US 8,988,679 B2
• Time in Patent Office: Days
• US Class Current: 356/301
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 21/658 enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G01N 2201/06193 Secundary in-situ sources, e.g. fluorescent particles
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less

Abstract

A method of producing a surface enhanced Raman scattering spectrum which is useful for certain types of assays, in particular proximity assays. The method includes providing two SERS-active nanoparticles. The first SERS-active nanoparticle will absorb a photon at a first wavelength and emit a Raman-shifted photon at a second wavelength. The second SERS-active nanoparticle will absorb a photon at the second wavelength and emit a Raman-shifted photon at a third wavelength. Accordingly, when the first and second SERS-active nanoparticles are proximate to one another and the first SERS-active nanoparticle is illuminated at the first wavelength a Raman-shifted photon at the second wavelength may be emitted. This photon can be absorbed by the second SERS-active nanoparticle causing detectable emission of a second Raman-shifted photon at the third wavelength. Various assays may be designed based upon the above. Proximity assays using two SERS-active nanoparticles will have advantageous background signal characteristics.

Claims

1. A method of producing a surface enhanced Raman scattering (SERS) spectrum comprising:

providing a first SERS active nanoparticle which will absorb a photon at a first wavelength and emit a Raman shifted photon at a second wavelength;

providing a second SERS active nanoparticle which will absorb a photon at the second wavelength and emit a Raman shifted photon at a third wavelength;

bringing the first and second SERS active nanoparticles proximate to one another; and

illuminating the first SERS active nanoparticle at the first wavelength causing the first SERS active nanoparticle to emit a Raman shifted photon at the second wavelength which is absorbed by the second SERS active nanoparticle causing emission of a second Raman shifted photon at the third wavelength.

2. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 1 wherein the first SERS active nanoparticle and the second SERS active nanoparticle have different shapes.

3. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 2 wherein the first SERS active nanoparticle is spherical and the second SERS active nanoparticle is non-spherical.

4. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 2 wherein the first SERS active nanoparticle is solid and the second SERS active nanoparticle is hollow.

5. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 2 wherein the first SERS active nanoparticle is of uniform composition and the second SERS active nanoparticle has different compositions in a core and shell.

6. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 2 wherein the first SERS active nanoparticle comprises a single metal and the second SERS active nanoparticle comprises a mixture or alloy of two metals.

7. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 6 wherein the second SERS active nanoparticle comprises a mixture or alloy of Au and Ag.

8. The method of producing a surface enhanced Raman scattering (SERS) spectrum of claim 1 wherein an absorbance maximum of the first SERS active nanoparticle is separated from an absorbance maximum of the second. SERS active nanoparticle by between 200 cm⁻

1 and 3500 cm<sup>−

1</sup>.

9. A proximity assay comprising:

a first SERS active nanoparticle which will absorb a photon at a first wavelength and emit a Raman shifted photon at a second wavelength;

a second SERS active nanoparticle which will absorb a photon at the second wavelength and emit a Raman shifted photon at a third wavelength; and

a light source configured to emit light at the first wavelength; and

a detector configured to detect light at the third wavelength.

10. The proximity assay of claim 9 wherein the first SERS active nanoparticle and the second SERS active nanoparticle have different shapes.

11. The proximity assay of claim 10 wherein the first SERS active nanoparticle is spherical and the second SERS active nanoparticle is non-spherical.

12. The proximity assay of claim 10 wherein the first SERS active nanoparticle is solid and the second SERS active nanoparticle is hollow.

13. The proximity assay of claim 10 wherein the first SERS active nanoparticle is of uniform composition and the second SERS active nanoparticle has different compositions in a core and shell.

14. The proximity assay of claim 10 wherein the first SERS active nanoparticle comprises a single metal and the second SERS active nanoparticle comprises a mixture or alloy of two metals.

15. The proximity assay of claim 14 wherein the second SERS active nanoparticle comprises a mixture or alloy of Au and Ag.

16. The proximity assay of claim 9 wherein an absorbance maximum of the first SERS active nanoparticle is separated from an absorbance maximum of the second SERS active nanoparticle by between 200 cm⁻

1 and 3500 cm<sup>−

1</sup>.

17. A method of detecting an analyte of interest comprising:

associating the analyte of interest with a Raman reporter having a SERS active vibrational peak at energy v1;

illuminating the Raman reporter with light having a frequency of L; and

detecting emitted light at a frequency of L-(2v1).