Non-alloying core shell nanoparticles

Abstract

The present invention relates composite core/shell nanoparticles and a two-step method for their preparation. The present invention further relates to biomolecule-core/shell nanoparticle conjugates and methods for their preparation. The invention also relates to methods of detection of biomolecules comprising the biomolecule-core/shell nanoparticle conjugates.

1 . An core/shell nanoparticle comprising: 
 (a) an inner metal-containing nanoparticle core; and    (b) an outer non-alloying gold shell surrounding the nanoparticle core.    
     
     
         2 . A core/shell nanoparticle oligonucleotide conjugate comprising: 
 (a) an inner metal-containing nanoparticle core;    (b) an outer non-alloying gold shell surrounding the nanoparticle core; and    (c) oligonucleotides attached to the gold shell.    
     
     
         3 . The core/shell nanoparticle of  claim 2  wherein the oligonucleotides have a sequence complementary to a portion of a sequence of a target nucleic acid.  
     
     
         4 . The core/shell nanoparticle of claims  1  or  2 , wherein the inner metal containing nanoparticle core comprises silver, Pt, Fe, Co, or Ni.  
     
     
         5 . The core/shell nanoparticle of claims  1  or  2 , wherein the inner metallic nanoparticle core comprises an alloy metal comprising FePt or FeAu.  
     
     
         6 . The core/shell nanoparticle of claims  1  or  2  wherein the inner metal-containing nanoparticle core comprises a metal oxide.  
     
     
         7 . The core/shell nanoparticle of claims  1  or  2 , wherein the inner metal-containing nanoparticle core is magnetic.  
     
     
         8 . The core/shell nanoparticle of  claim 6  wherein the inner metal-containing nanoparticle core comprises Fe 3 O 4  or CO 3 O 4 .  
     
     
         9 . The core/shell nanoparticle of claims  1  or  2 , wherein the inner metal-containing nanoparticle core comprises a semiconductor.  
     
     
         10 . The core/shell nanoparticle of  claim 9 , wherein the inner metal-containing nanoparticle core comprises CdSe or CdS.  
     
     
         11 . The core/shell nanoparticle of claims  1  or  2 , wherein the gold shell ranges from about 0.5 to about 2 monolayers in thickness.  
     
     
         12 . The core/shell nanoparticle of  claim 2  wherein the oligonucleotides are attached to the nanoparticles in a stepwise ageing process comprising (i) contacting the oligonucleotides with the nanoparticles in a first aqueous solution for a period of time sufficient to allow some of the oligonucleotides to bind to the nanoparticles; (ii) adding at least one salt to the aqueous solution to create a second aqueous solution; and (iii) 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;  
     
     
         13 . The core/shell nanoparticle of  claim 12  wherein the oligonucleotides include a moiety comprising a functional group which can bind to a nanoparticle.  
     
     
         14 . The core/shell nanoparticle of  claim 12  wherein all of the salt is added to the water in a single addition.  
     
     
         15 . The core/shell nanoparticle of  claim 12  wherein the salt is added gradually over time.  
     
     
         16 . The core/shell nanoparticle of  claim 12  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.  
     
     
         17 . The core/shell nanoparticle of  claim 16  wherein the salt is sodium chloride in a phosphate buffer.  
     
     
         18 . The core/shell nanoparticle of  claim 12  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 .  
     
     
         19 . The core/shell nanoparticle of  claim 18  wherein the oligonucleotides are present on surface of the nanoparticles at a surface density of at least 15 picomoles/cm 2 .  
     
     
         20 . The core/shell nanoparticle of  claim 19  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 .  
     
     
         21 . A nanostructure comprising the core/shell nanoparticles of claims  1  or  2 .  
     
     
         22 . A silver/gold core/shell nanoparticle comprising: 
 (a) an inner silver nanoparticle core; and    (b) an outer non-alloying gold shell surrounding the nanoparticle core.    
     
     
         23 . A magnetic core/shell nanoparticle comprising: 
 (a) an inner Fe 3 O 4  nanoparticle core; and    (b) an outer non-alloying gold shell surrounding the nanoparticle core.    
     
     
         24 . A semiconductor core/shell nanoparticle comprising: 
 (a) an inner semiconductor nanoparticle core; and    (b) an outer non-alloying gold shell surrounding the nanoparticle core.    
     
     
         25 . The semiconductor core/shell nanoparticle of  claim 24 , wherein the inner nanoparticle core comprises CdSe or CdS.  
     
     
         26 . The core/shell nanoparticle oligonucleotide conjugate of any of claims  1 ,  2  or  22  wherein the surface plasmon absorption peak is at about 500 to 530 nm.  
     
     
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