Metallic nanoparticle synthesis with carbohydrate capping agent
The disclosure relates to metal nanoparticle compositions and their methods of formation and use, in particular gold nanoparticles (AuNP) and gold-coated magnetic nanoparticles. Compositions according to the disclosure include aqueous suspensions of metal nanoparticles that are stabilized with one or more carbohydrate capping agents and/or that are functionalized with one or more binding pair members for capture/detection of a target analyte. The nanoparticle suspensions are stable for extended periods and can be functionalized as desired at a later point in time, typically prior to use in an assay for the detection of a target biological analyte. The stable nanoparticle suspension can be formed by the aqueous reduction of oxidized metal precursors at non-acidic pH values in the presence of a carbohydrate-based capping agent such as dextrin or other oligosaccharides.
1. A method for forming reduced metal nanoparticles, the method comprising:
(a) providing an aqueous medium, the aqueous medium comprising (i) water and (ii) metal ions in solution in the water; and
(b) reducing the metal ions in the aqueous medium at a neutral or alkaline pH value in the presence of at least one of a linear and a branched carbohydrate capping agent for a time sufficient to form a plurality of reduced metal nanoparticles as a suspension stabilized in the aqueous medium with the carbohydrate capping agent adsorbed on outer surfaces of the reduced metal nanoparticles;
wherein the carbohydrate capping agent is present in the aqueous medium prior to reaction at a concentration ranging from 1 g/L to 100 g/L.
2. The method of claim 1 ,
wherein the plurality of reduced metal nanoparticles has an average particle size ranging from 5 nm to 50 nm.
3. The method of claim 2 , wherein the metal ions comprise gold ions and the plurality of reduced metal nanoparticles comprise gold nanoparticles.
4. The method of claim 2 , wherein the aqueous medium further comprises a counter ion in solution in the water from a dissolved metal ionic compound providing the metal ions.
5. The method of claim 2 , wherein the pH value of the aqueous medium in (b) ranges from 7 to 12.
6. The method of claim 2 , comprising performing (b) at a temperature ranging from 20° C. to 100° C.
7. The method of claim 2 , wherein the aqueous medium in (b) further comprises a combined reducing agent for reducing the metal ions and pH-adjusting agent for maintaining the neutral or alkaline pH value of the aqueous medium.
8. The method of claim 2 , wherein the carbohydrate capping agent comprises an oligosaccharide having 3 to 100 saccharide residues.
9. The method of claim 2 , wherein the carbohydrate capping agent comprises a plurality of oligosaccharides having a distribution of lengths with a number-average of saccharide residues ranging from 10 to 100.
10. The method of claim 2 , wherein the carbohydrate capping agent comprises one or more glucose residues.
11. The method of claim 2 , wherein the carbohydrate capping agent is in a substantially non-oxidized form.
12. The method of claim 2 , wherein the carbohydrate capping agent comprises dextrin.
13. The method of claim 2 , comprising performing the metal ion reduction in (b) in the presence of at least one of a monosaccharide and a disaccharide in addition to the carbohydrate capping agent.
14. The method of claim 2 , wherein:
(i) the carbohydrate capping agent comprises at least one of a monosaccharide and a disaccharide; and
(ii) (b) comprises performing the metal ion reduction in (b) in the presence of at least one non-carbohydrate capping agent in addition to the carbohydrate capping agent.
15. The method of claim 2 , wherein the carbohydrate capping agent has a concentration in the aqueous medium in (b) selected to control one or more size parameters of the plurality of metal nanoparticles.
16. The method of claim 2 , wherein the plurality of reduced metal nanoparticles has an average particle size ranging from 8 nm to 50 nm.
17. The method of claim 16 , wherein the plurality of reduced metal nanoparticles has a normal size distribution with a standard deviation of 25% or less relative to the average particle size of the distribution.
18. The method of claim 2 , wherein at least some of the carbohydrate capping agent is present as a layer on an outer surface of each reduced metal nanoparticle.
19. The method of claim 2 , wherein:
(i) the aqueous medium in (b) further comprises a binding pair member comprising (A) an immobilization moiety for immobilizing the binding pair member onto a reduced metal nanoparticle and (B) a binding moiety capable of binding to a target analyte or a second binding pair member; and
(ii) (b) is performed for a time sufficient in the presence of the binding pair member to additionally immobilize the binding pair member on an outer surface of a reduced metal nanoparticle via the immobilization moiety.
20. The method of claim 19 , wherein the immobilization moiety of the binding pair member comprises a carbohydrate moiety conjugated to the binding moiety.
21. The method of claim 2 , wherein the carbohydrate capping agent has at least 10 saccharide residues.
22. The method of claim 2 , wherein the reduced metal nanoparticles have a spherical shape, and the plurality of reduced metal nanoparticles has a number-average particle size ranging from 8 nm to 30 nm.
23. A method for forming reduced gold nanoparticles, the method comprising:
(a) providing an aqueous medium, the aqueous medium comprising (i) water and (ii) gold ions in solution in the water; and
(b) reducing the gold ions in the aqueous medium at a pH value ranging from 8 to 11 in the presence of at least one of a linear and a branched dextrin capping agent for a time sufficient to form a plurality of reduced gold nanoparticles as a suspension stabilized in the aqueous medium with the dextrin capping agent adsorbed on outer surfaces of the reduced gold nanoparticles;
wherein the plurality of reduced gold nanoparticles has an average particle size ranging from 5 nm to 15 nm,
the dextrin capping agent has at least 10 saccharide residues, and
the dextrin capping agent is present in the aqueous medium prior to reaction at a concentration ranging from 1 g/L to 100 g/L.
24. The method of claim 23 , further comprising performing the metal ion reduction in (b) in the presence of galactose in addition to the dextrin capping agent.
25. The method of claim 23 , wherein the dextrin capping agent comprises a plurality of oligosaccharides having a distribution of lengths with a number-average of saccharide residues ranging from 10 to 100.
26. The method of claim 23 , wherein the reduced gold nanoparticles have a spherical shape, and the plurality of reduced gold nanoparticles has a number-average particle size ranging from 8 nm to 15 nm.