Non-alloying core shell nanoparticles

1. A method for making core/shell nanoparticle oligonucleotide conjugates comprising

(a) providing core/shell nanoparticles comprising magnetic cores and non-alloying gold shells surrounding the magnetic cores, the gold shells having a predetermined thickness and the core/shell nanoparticle having a mean diameter ranging from 5 to 150 nm, wherein the core/shell nanoparticles are prepared by treating the magnetic cores by simultaneous addition of a solution comprising a gold salt and a solution comprising a reducing agent so as to form a reaction mixture having a gold salt concentration of about 2 uM; and

(b) contacting the oligonucleotides with the core/shell nanoparticles in a first aqueous solution for a period of time sufficient to allow some of the oligonucleotides to bind to the nanoparticles;

(c) adding at least one salt to the aqueous solution to create a second aqueous solution; and

(d) contacting the oligonucleotides and nanoparticles in the second aqueous solution for an additional period of time to enable additional oligonucleotides to bind to the nanoparticles.

2. The method of claim 1 wherein the oligonucleotides include a moiety comprising a functional group which can bind to a nanoparticle.

3. The method of claim 1 wherein all of the salt is added to the water in a single addition.

4. The method of claim 1 wherein the salt is added gradually over time.

5. The method of claim 1 wherein the salt is selected from the group consisting of sodium chloride, magnesium chloride, potassium chloride, ammonium chloride, sodium acetate, ammonium acetate, a combination of two or more of these salts, one of these salts in a phosphate buffer, and a combination of two or more these salts in a phosphate buffer.

6. The method of claim 5 wherein the salt is sodium chloride in a phosphate buffer.

7. The method of claim 1 wherein nanoparticle-oligonucleotide conjugates are produced which have the oligonucleotides present on surface of the nanoparticles at a surface density of at least 10 picomoles/cm 2 .

8. The method of claim 7 wherein the oligonucleotides are present on surface of the nanoparticles at a surface density of at least 15 picomoles/cm 2 .

9. The method of claim 8 wherein the oligonucleotides are present on surface of the nanoparticles at a surface density of from about 15 picomoles/cm 2 to about 40 picomoles/cm 2 .

10. The method of claim 1 wherein the the magnetic cores comprise a metal oxide, Fe, Ni, Co, FePt or FeAu.

11. The method of claim 10 wherein the gold salt comprises HAuCl 4 , NaAuCl 4 , KAuCl 4 , or KAu(CN) 2 .

12. The method of claim 11 wherein the gold salt is HAuCl 4 .

13. The method of claim 10 wherein the reducing agent comprises NaBH 4 , ascorbic acid, NH 2 OH or N 2 H 4 .

14. The method of claim 13 wherein the reducing agent is NaBH 4 .

15. A method of detecting nucleic acid bound to a surface comprising:

(a) providing core/shell nanoparticle conjugates comprising:

(a) a core/shell nanoparticle comprising a magnetic core and a non-alloying gold shell surrounding the core, the gold shell having a predetermined shell thickness and the core/shell nanoparticle having a mean diameter ranging from 5 to 150 nm; and

(b) oligonucleotides attached to the gold shell, wherein the non-alloying gold shell is generated on a surface of the core by simultaneous addition of a solution comprising a gold salt and a solution comprising a reducing agent to a solution containing the metal-containing core;

(b) providing a surface having nucleic acid bound thereto;

(c) contacting the nucleic acid bound to the surface with the core/shell nanoparticle oligonucleotide conjugates under conditions effective to allow hybridization of oligonucleotides bound to the core/shell nanoparticle oligonucleotide conjugates with the nucleic acid bound to the substrate in the presence of an external magnetic field so as to accelerate movement of the core/shell nanoparticle oligonucleotide conjugate to the surface to promote hybridization between the nanoparticle conjugate and the nucleic acid;

(d) removing from the surface any unbound nanoparticle conjugates; and

(d) observing a detectable change brought about by hybridization of the nucleic acid with the nanoparticle conjugates

wherein the predetermined shell thickness is determined by the formula:

V core =4/3 ×Π×R 3 ;

V core/shell =4/3×Π×( R+A ) 3

 wherein A represents the desired shell thickness and R represents the core radius;

V shell =V core/shell −V core ; and

N shell =d shell ×V shell /FW shell

 wherein N shell represents the amount in moles of gold in the shell, d shell represents 19.3 g/ml, and FW shell represents 196.97 amu.