Capped and conjugated quantum dots
One or more aqueous, near infrared emitting, high yield, highly photoluminescent, stable quantum dots conjugated to one or more biomarkers specific moieties. The conjugated quantum dots have an enhanced detection sensitivity and selectivity and may be formed using a novel and efficient method for conjugating one or more biomarker specific moieties to the quantum dots. The invention is further directed to a method for using the conjugated quantum dots for cancer detection in the margin of excised tissue.
1. A quantum dot having a core selected from the group consisting of CdSe, CdTe, CdPbS, and ZnSnS and which are capped with a mercaptocarboxylic acid capping agent and at least part of said mercaptocarboxylic acid capping agent is replaced with mercaptosilane capping agent to provide a molar ratio of mercaptosilane capping agent to the moles of quantum dots is from about 0.5 to about 4, and wherein the ratio of capping agent:metal:Se, Te or S is from about 2:1:1 to about 16:8:1.
2. The quantum dot as claimed in claim 1 wherein the mercaptosilane comprises 3-mercaptopropyltrimethoxysilane.
3. The quantum dot as claimed in claim 2 , wherein the mercaptocarboxylic acid is selected from the group consisting of mercaptoacetic acid, mercaptopropionic acid, mercaptosuccinic acid, mercaptobenzoic acid, and mercaptoundecanoic acid.
4. The quantum dot as claimed in claim 3 , wherein the mercaptocarboxylic acid is mercaptopropionic acid.
5. The quantum dot as claimed in claim 1 , wherein the ratio of mercaptocarboxylic acid and mercaptosilane capping agent:metal:Se, Te or S is about 4:3:1 to about 8:5:1.
6. The quantum dot of claim 1 , wherein the core is selected from the group consisting of CdPbS, and ZnSnS.
7. A conjugated quantum dot comprising the quantum dot as claimed in claim 1 and a biomarker specific antibody selected from the group consisting of, anti-Tn antigen antibody, anti-T antigen antibodies, anti-sial-T antigen antibodies, anti-sial-Tn antigen antibodies, anti-HER2 antibodies, and anti-IGFR antibodies conjugated to the quantum dot.
8. The conjugated quantum dot of claim 7 , further comprising a conjugation linker selected from the group consisting of sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate, succinimidyl-([N-maleimidopropionamido]-n-ethyleneglycol) ester, SM(PEG) n with n=2, 4, 6, 8, 12, 24, 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride-N hydroxysulfosuccinimide and streptavidin.
9. The conjugated quantum dot of claim 8 , comprising two conjugation linkers.
10. The quantum dot as claimed in claim 7 wherein the mercaptosilane comprises 3-mercaptopropyltrimethoxysilane.
11. The quantum dot as claimed in claim 10 , wherein the mercaptocarboxylic acid is selected from the group consisting of mercaptoacetic acid, mercaptopropionic acid, mercaptosuccinic acid, mercaptobenzoic acid, and mercaptoundecanoic acid.
12. The quantum dot as claimed in claim 11 , wherein the mercaptocarboxylic acid is mercaptopropionic acid.
13. The quantum dot as claimed in claim 7 , wherein the ratio of capping agent:metal:Se, Te or S is about 4:3:1 to about 8:5:1.