Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and methods of use
View Patent ↗The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.
1. A conjugate comprising
(i) a water-soluble luminescent semiconductor quantum dot, which comprises a core, a cap and a hydrophilic attachment group, wherein said hydrophilic attachment group is an organic group comprising a sulfur atom and at least one hydrophulic substituent selected from the group consisting of a sulfonic acid or salt thereof, a sulfanic acid or salt thereof, a quaternary ammnonium salt, and a hydroxy, and
(ii) a biomolecule, wherein the biomolecule is attached to the quantum dot via the hydrophilic attachment group.
2. The conjugate of claim 1 , wherein the biomolecule is a protein or a fragment thereof.
3. The conjugate of claim 1 , wherein the protein or fragment thereof is an antibody or an antigenically reactive fragment thereof.
4. The conjugate of claim 1 , wherein the biomolecule is a nucleic acid.
5. The conjugate of claim 1 , wherein the biomolecule is attached to the hydrophilic attachment group via a linker.
6. The conjugate of claim 5 , wherein the linker is a primary amine.
7. The conjugate of claim 5 , wherein the linker is streptavidin, neutravidin or biotin.
8. The conjugate of claim 5 , wherein the linker is a thiol group.
9. The conjugate of claim 5 , wherein said biomolecule is a single-stranded oligomicleotide comprising a stem and loop structure and wherein said hydrophilic attachment group is attached to one end of the single-stranded oligonucleotide and a quenching moiety is attached to the other end of the single-stranded oligonucteotide and said quenching moiety quenches said luminescent semiconductor quantum dot.
10. A composition comprising the conjugate of claim 1 and an aqueous carrier.
11. A conjugate comprising a water-soluble luminescent semiconductor quantum dot, which comprises a CdSe core, a ZnS cap and a mercaptoacetic acid attachment group, and a biomolecule.
12. The conjugate of claim 11 , wherein the CdSe core is about 4.2 nm and the ZnS coating is about 1 nm.
13. A composition comprising the conjugate of claim 12 and an aqueous carrier.
14. A composition comprising the conjugate of claim 11 and an aqueous carrier.
15. A conjugate comprising
(i) a water-soluble luminescent semiconductor quantum dot, which comprises a core, a cap and a hydrophilic attachment group, wherein said hydrophilic attachment group is an organic group comprising a sultur atom and at least one hydrophilic substituent comprising a C 1 –C 6 alkyl carboxylic acid or salt thereof, and
(ii) a biomolecule, wherein the biomolecule is attached to the quantum dot via the hydrophilic attachment group.
16. The conjugate of claim 15 , wherein the biomolecule is a protein or a fragment thereof.
17. The conjugate of claim 15 , wherein the protein or fragment thereof is an antibody or an antigenically reactive fragment thereof.
18. The conjugate of claim 15 , wherein the biomolecule is a nucleic acid.
19. The conjugate of claim 15 , wherein the biomolecule is attached to the hydrophilic attachment group via a linker.
20. The conjugate of claim 19 , wherein the Linker is a primary amine.
21. The conjugate of claim 19 , wherein the linker is streptavidin, neutravidin or biotin.
22. The conjugate of claim 19 , wherein the linker is a thiol group.
23. The conjugate of claim 19 , wherein said biomolecule is a single-stranded oligonucleotide comprising a stem and loop structure and wherein said hydrophilic attachment group is attached to one end of the single-stranded oligonucleotide and a quenching moiety is attached to the other end of the single-stranded oligonucleotide and said quenching moiety quenches said luminescent semiconductor quantum dot.
24. A composition comprising the conjugate of claim 15 and an aqueous carrier.