CA2423806A1 - Modified carbocyanine dyes and their conjugates - Google Patents

Modified carbocyanine dyes and their conjugates Download PDF

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CA2423806A1
CA2423806A1 CA 2423806 CA2423806A CA2423806A1 CA 2423806 A1 CA2423806 A1 CA 2423806A1 CA 2423806 CA2423806 CA 2423806 CA 2423806 A CA2423806 A CA 2423806A CA 2423806 A1 CA2423806 A1 CA 2423806A1
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alkyl
sulfo
amino
independently
compound
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CA2423806C (en
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Wai-Yee Leung
Ching-Ying Cheung
Stephen Yue
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Molecular Probes Inc
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Molecular Probes, Inc.
Wai-Yee Leung
Ching-Ying Cheung
Stephen Yue
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Abstract

Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Claims (42)

1. A compound of the formula:
and its salts, wherein R3 is -L-R x; or -L-S c; and R4 is independently -L-R x; or -L-S c; or a C1-C22 alkyl or C7-C22 arylalkyl, each alkyl portion of which optionally incorporates up to six hetero atoms, selected from N, O and S, and each alkyl portion of which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-C6 alkylamino, or C2-C12 dialkylamino, or C3-C18 trialkylammonium; or R3 and R4 taken in combination complete a five- or six-membered saturated or unsaturated ring that is substituted by -L-R x; or -L-S c; and L is a single covalent bond, or a covalent linkage that is linear or branched, cyclic or heterocyclic, saturated or unsaturated, having 1-16 nonhydrogen atoms selected from the group consisting of C, N, P, O, and S, such that the linkage contains any combination of ether, thioether, amine, ester, amide bonds; or single, double, triple or aromatic carbon-carbon bonds; or phosphorus-oxygen, phosphorus-sulfur, nitrogen-nitrogen, nitrogen-oxygen, or nitrogen-platinum bonds; or aromatic or heteroaromatic bonds;
R x is a reactive group;
S c is a conjugated substance;

Y represents the atoms necessary to form one to two fused aromatic rings having 6 atoms in each ring, which atoms are selected from -CH, -C, -CR1, and -N(R2).beta., where each .beta. is 0 or 1, and each R1 is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
each R2, when present (where .alpha. or .beta. is 1), is independently -L-R x;
or -L-S c; or a C1-C22 alkyl or C7-C22 arylalkyl, each alkyl portion of which optionally incorporates up to six hetero atoms, selected from N, O and S, and each alkyl portion of which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, or C3-C18 trialkylammonium;
.alpha. is 0 or 1, and .alpha. + all .beta. = 1; and W represents the atoms necessary to form one to two fused aromatic rings having 6 atoms in each ring, which atoms are selected from -CH, -C, -CR1', and -N(R12).beta.', where each .beta.' is 0 or 1, and each R1' is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
each R12, when present (where .delta. or .beta.' is 1), is independently -L-R
x; or -L-S c; or is a C1-C22 alkyl or C7-C22 arylalkyl, each alkyl portion of which optionally incorporates up to six hetero atoms, selected from N, O and S, and each alkyl portion of which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-alkylamino, C2-C12 dialkylamino, or C3-C18 trialkylammonium;
.delta. is 0 or 1, and .delta. + all .beta.' = 1;
Z is O, S, or CR13R14;

R13 and R14 are independently -L-R x ; or -L-S c ; or a C1-C22 alkyl or C7-C22 arylalkyl, each alkyl portion of which optionally incorporates up to six hetero atoms, selected from N, O and S, and each alkyl portion of which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-C8 alkylamino, or C2-C12 dialkylamino, or C3-C18 trialkylammonium; or R13 and R14 taken in combination complete a five- or six-membered saturated or unsaturated ring that is optionally substituted by -L-R x; or -L-S c;
n is 1, 2 or 3; and each R21, R22, and R23 is independently H, F, Cl, C1-C6 alkyl, C1-C6 alkoxy, aryloxy, a nitrogen heterocycle, an iminium ion, -L-R x, or -L-S c; or any two adjacent substituents of R21, R22, R23, when taken in combination, forms a 4-, 5-, or 6-membered saturated or unsaturated hydrocarbon ring that is optionally substituted one or more times by C1-C6 alkyl, halogen, or a carbonyl oxygen; or R21 taken in combination with R4 forms a 6-membered ring that is optionally substituted by C1-C6 alkyl; or one of R23, whichever is adjacent to Z, taken in combination with one of R13 and R14 forms a 6-membered ring that is optionally substituted by C1-C6 alkyl.
2. A compound, as claimed in Claim 1, wherein the atoms of Y are selected from -CH, -C, and -CR1, where each R1 is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C8 alkyl, C1-C8 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
.alpha. is 1;
the atoms of W are selected from -CH, -C, -CR1', and -N(R12).beta.', where each .beta. is 0 or 1, and each R1' is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;

each R2 and R12 is independently -L-R x; or -L-S c; or a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, and is optionally substituted;
.delta. is 0 or 1, and .delta. + all .beta.'= 1; and .delta. is 1 only if W
does not contain any ring nitrogen atoms;
Z is CR13R14.
3. A compound, as claimed in Claim 2, wherein the atoms of W are selected from -CH, -C, -CR1', and -N(R12).beta.', where .beta.' is 1, but no more than one of the atoms in W is -N(R12).beta.', and each R1' is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
and .delta. is 0.
4. A compound, as claimed in Claim 2, wherein the atoms of W are selected from -CH, -C, and -CR1', and each R1' is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
.delta. is 1.
5. A compound, as claimed in Claim 2, wherein R3 is -L-R x; or -L-S c; and R4 is independently a C1-C6 alkyl, which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, or amino;
the atoms of Y are selected from -CH, -C, and -CR1, where each R1 is independently -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;

the atoms of W are selected from -CH, -C, -CR1', and -N(R12).beta.', where each .beta.' is 0 or 1, but no more than one of such atoms is -N(R12).beta.', and each R1' is independently -L-R x;
or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;

R2 and R12 are independently -L-R x; or -L-S c; or is a C1-C6 alkyl, which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, or amino;
one of R13 and R14 is a C1-C6 alkyl and the other of R13 and R14 is -L-R x; or -L-S c ; or a C1-C22 alkyl, which is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, alkoxy, C1-C6 alkylamino, or C2-C12 dialkylamino;

each of R21, R22, and R23 are H; or any two adjacent substituents of R21, R22, R23, when taken in combination, forms a 4-, 5-, or 6-membered saturated or unsaturated hydrocarbon ring that is optionally substituted one or more times by C1-C6 alkyl, halogen, or a carbonyl oxygen.
6. A compound, as claimed in Claim 1, wherein R3 is -L-R x; and R4 is independently a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, and is optionally substituted; or R3 and R4 taken in combination complete a five- or six-membered saturated or unsaturated ring that is substituted by -L-R x; and each R x is a reactive group that is independently an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl nitrile, an aldehyde, an alkyl halide, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine (including hydrazides), an imido ester, an isocyanate, an isothiocyanate, a maleimide, a phosphoramidite, a reactive platinum complex, a sulfonyl halide, a thiol group, or a photoactivatable group;

no more than one of the atoms within Y is -N(R2).beta., and each R1 is independently -L-R x;
or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy; and each S c is a conjugated substance that is an amino acid, peptide, polypeptide, protein, nucleotide, oligonucleotide, nucleic acid polymer, a sugar, a polysaccharide, an oligosaccharide, a fluorescent dye, or a microsphere;
.alpha. is only 1 when Y contains no ring nitrogen atoms, no more than one of the atoms within W is -N(R12).beta.', and each R1' is independently -L--R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
R2 and R12 are independently -L-R x; or -L-S c; or is a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, and is optionally substituted;
.delta. is 1 only if W does not contain any ring nitrogen atoms;
Z is CR13R14;
R13 and R14 are independently -L-R x ; or -L-S c; or a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, is optionally substituted;

or R13 and R14 taken in combination complete a five- or six-membered saturated or unsaturated ring that is optionally substituted by -L-R x; or -L-S c; and R21, R22, and R23 are independently H, F, Cl, C1-C6 alkyl, C1-C6 alkoxy, aryloxy, a nitrogen heterocycle, an iminium ion, -L-R x, or -L-S c.
7. A compound, as claimed in Claim 1, wherein R3 is -L-S c; and R4 is independently a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, and is optionally substituted; or R3 and R4 taken in combination complete a five- or six-membered saturated or unsaturated ring that is substituted by -L-S c; and L is a single covalent bond, or a covalent linkage and S c is a conjugated substance that is an antibody, an amino acid, an angiostatin or endostatin, an avidin or streptavidin, a biotin, a blood component protein, a dextran, an enzyme, an enzyme inhibitor, a hormone, an IgG-binding protein, a fluorescent protein, a growth factor, a lectin, a lipopolysaccharide, a metal-binding protein, a microorganism or portion thereof, a neuropeptide, a non-biological microparticle, a nucleotide, an oligonucleotide, a peptide toxin, a phospholipid-binding protein, a small-molecule drug, a structural protein, or a tyramide;
no more than one of the atoms within Y is -N(R2).beta., and each R1 is independently -L-R x;
or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy; and -R x is a reactive group that is an activated ester of a carboxylic acid, an amine, a carboxylic acid, a halotriazine, a hydrazide, a maleimide, a reactive platinum complex; and a is only 1 when Y contains no ring nitrogen atoms, no more than one of the atoms within W is -N(R12).beta.', and each R1' is independently -L--R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
R2 and R12 are independently -L-R x; or -L-S c; or is a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, and is optionally substituted;
.delta. is 1 only if W does not contain any ring nitrogen atoms;
Z is CR13R14;
R13 and R14 are independently -L-R x; or -L-S c; or a C1-C22 alkyl, which optionally incorporates up to six hetero atoms, is optionally substituted;
or R13 and R14 taken in combination complete a five- or six-membered saturated or unsaturated ring that is optionally substituted by -L-R x; or -L-S c; and R21, R22, and R23, are independently H, F, Cl, C1-C6 alkyl, C1-C6 alkoxy, aryloxy, a nitrogen heterocycle, an iminium ion, -L-R x, or -L-S c.
8. A compound, as claimed in any of Claims 1-7, wherein L is a covalent linkage that is linear or branched, cyclic or heterocyclic, saturated or unsaturated, having 1-16 nonhydrogen atoms selected from the group consisting of C, N, P, O, and S, and incorporating the formula -(CH2)d(CONH(CH2)e)2'-, where d is 0-5, e is 1-5 and z' is 0 or 1, such that the linkage contains any combination of ether, thioether, amine, ester, amide bonds; or single, double, triple or aromatic carbon-carbon bonds; or phosphorus-oxygen, phosphorus-sulfur, nitrogen-nitrogen, nitrogen-oxygen, or nitrogen-platinum bonds; or aromatic or heteroaromatic bonds.
9. A compound, as claimed in any of Claims 1-8, wherein, R21, R22, and R23 are H.
10. A compound, as claimed in any of Claims 1-9, wherein S c is a conjugated substance that is an actin, an antibody or fragment thereof, an avidin or streptavidin, a biotin, a dextran, an enzyme, a fluorescent protein, a lectin, a lipopolysaccharide, a microorganism, a non-biological microparticle, a nucleotide, an oligonucleotide, a peptide toxin, a phosphotidylserine-binding protein, a protein A
or G, a small-molecule drug, or a tyramide.
11. A compound, as claimed in any of Claims 1-10, wherein the atoms of Y are selected from -CH, -C, and -CR1, where R1 is sulfo.
12. A compound, as claimed in any of Claims 1-3 and 5-11, wherein the atoms of W
are selected from -CH, -C, -CR1', and -N(R12).beta.', where each R1' is sulfo or Br.
13. A compound, as claimed in any of Claims 1-12, wherein R2 and R12 are independently a C1-C6 alkyl or C1-C6 alkyl substituted by sulfo.
14. A compound, as claimed in any of Claims 1-13, wherein, R13 and R14 are independently C1-C6 alkyl.
15. A compound of the formula and its salts, wherein R3 is -L-R x; or -L-S c; and R4 is a C1-C22 alkyl, and is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-C6 alkylamino, or C2-C12 dialkylamino, or C3-C18 trialkylammonium; or R3 and R4 taken in combination complete a five- or six-membered saturated or unsaturated ring that is substituted by -L-R x; or -L-S
c; and L is a single covalent bond, or a covalent linkage that is linear or branched, cyclic or heterocyclic, saturated or unsaturated, having 1-16 nonhydrogen atoms selected from the group consisting of C, N, P, O, and S, such that the linkage contains any combination of ether, thioether, amine, ester, amide bonds; or single, double, triple or aromatic carbon-carbon bonds; or phosphorus-oxygen, phosphorus-sulfur, nitrogen-nitrogen, nitrogen-oxygen, or nitrogen-platinum bonds; or aromatic or heteroaromatic bonds;
R x is a reactive group;
S c is a conjugated substance;
R6 through R9 and R16 through R18 are independently H, -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy; or any two adjacent substituents of R6 through R9 form a fused benzo ring that is optionally substituted one or more times by -L-R x; or by -L-S c; or by amino, sulfo, trifluoromethyl, or halogen; or by C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
R2 and R12 are independently a C1-C6 alkyl or C1-C6 alkyl substituted by sulfo;
R13 and R14 are independently a C1-C6 alkyl;
n is 1, 2 or 3.
16. A compound, as claimed in Claim 15, wherein R17 is H or Br, and R16 and R18 are H.
17. A compound of the formula and its salts, wherein R3 is -L-R x; or -L-S c; and R4 is a C1-C22 alkyl, and is optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxy, sulfo, phosphate, amino, sulfate, phosphonate, cyano, nitro, azido, C1-C6 alkoxy, C1-C6 alkylamino, or C2-C12 dialkylamino, or C3-C18 trialkylammonium; or R3 and R4 taken in combination complete a five- or six-membered saturated or unsaturated ring that is substituted by -L-R x; or -L-S
c; and L is a single covalent bond, or a covalent linkage that is linear or branched, cyclic or heterocyclic, saturated or unsaturated, having 1-16 nonhydrogen atoms selected from the group consisting of C, N, P, O, and S, such that the linkage contains any combination of ether, thioether, amine, ester, amide bonds; or single, double, triple or aromatic carbon-carbon bonds; or phosphorus-oxygen, phosphorus-sulfur, nitrogen-nitrogen, nitrogen-oxygen, or nitrogen-platinum bonds; or aromatic or heteroaromatic bonds;
R x is a reactive group;
S c is a conjugated substance;
R6 through R9 and R16 through R19 are independently H, -L-R x; or -L-S c; or amino, sulfo, trifluoromethyl, or halogen; or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy; or any two adjacent substituents of R6 through R9 and R16 through form a fused benzo ring that is optionally substituted one or more times by -L-R x; or by -L-S c; or by amino, sulfo, trifluoromethyl, or halogen; or by C1-C6 alkyl, alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy;
R2 and R12 are independently a C1-C6 alkyl or C1-C6 alkyl substituted by sulfo;
R13 and R14 are independently a C1-C6 alkyl;
n is 1, 2 or 3.
18. A compound, as claimed in Claim 17, wherein R17 is H, sulfo, or Br, and R16, R18, and R19 are H.
19. A compound, as claimed in any of Claims 15-18, wherein R7 is sulfo, and R6, R8, and R9 are H; or R6 and R7 combine to form a fused benzo ring that is substituted one or more times by sulfo, and R8 and R9 are H.
20. A compound, as claimed in any of Claims 1-19, wherein, L is a covalent linkage that incorporates the formula -(CH2)d(CONH(CH2)e)z,-, or -(CH2)d(CON(CH2)4NH(CH2)e)z,-, -(CH2)d(CONH(CH2)e NH2)z,-, -(CH2)d(CONH(CH2)e NHCO)-z,, where d is 0-5, e is 1-5 and z' is 0 or 1;
21. A compound, as claimed in any of Claims 1-20, wherein R4 is a C1-C6 alkyl.
22. A compound, as claimed in any of Claims 1-6 and 8-20, wherein there is only one R x on the compound and it is an activated ester of a carboxylic acid, an amine, a carboxylic acid, a halotriazine, a hydrazide, a maleimide, or a reactive platinum complex.
23. A compound, as claimed in any of Claims 1-22, where -L is -(CH2)d(CONH(CH2)e)z,-.
24. A compound, as claimed in any of Claims 1-23, wherein -Rx is a carboxylic acid, or a succinimidyl ester of a carboxylic acid, or a maleimide.
25. A compound, as claimed in any of Claims 1-4 and 6-21, wherein S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, an oligonucleotide, a small-molecule drug, or a tyramide.
26. A compound, as claimed in any of Claims 1-25, where n=1.
27. A compound, as claimed in any of Claims 1-25, where n=2.
28. A compound, as claimed in any of Claims 1-25, where n=3.
29. A compound of the formula and its salts, wherein R3 is -L-R x or -L-S c; and R4, R13, and R14 are methyl;
L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z,-, e is 1-5 and z' is 0 or 1;
Rx is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;
S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R2 and R12 are independently methyl or sulfopropyl;
R7 and R17 are sulfo, and R6, R8 , R9, R16, R18, and R19 are H; and n is 1.
30. A compound of the formula:

and its salts, wherein R3 is -L-R x or -L-Sc; and R4, R13, and R14 are methyl;
L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z; , e is 1-5 and z' is 0 or 1;
R x is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;
S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R2 and Rl2 are independently methyl or sulfopropyl;
R7 and R17 are sulfo, and R6, R8 , R9, R16, R18, and R19 are H; and n is 2.
31. A compound of the formula:

and its salts, wherein R3 is -L-R I or -L-S c; and R4, R13, and R14 are methyl;
L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z'-, e is 1-5 and z' is 0 or 1;
R x is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;

S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R2 and R12 are independently methyl or sulfopropyl;
R7 and R17 are sulfo, and R6, R8 , R9, R16, R18, and R19 are H;
n is 3.
32. A compound of the formula:

and its salts, wherein R3 is -L-R x or -L-S c; and R4, R13 and R14 are methyl;
L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z'-, e is 1-5 and z' is 0 or 1;
Rx is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;

S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R6, R8, R9, R16, R17 and R18 are H; R7 is sulfopropyl;
R2 and R19 are independently methyl or sulfopropyl;
n is 2.
33. A compound of the formula:

and its salts, wherein R3 is -L-R x or -L-S c; and R4, R13 and R14 are methyl;
L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z'-, e is 1-5 and z' is 0 or 1;
R x is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;

Sc is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R6, R8, R9, R16, and R18 are H; R7 is sulfo; R17 is Br;
R2 and R12 are independently methyl or sulfopropyl;
n is 2.
34. A compound of the formula:

and its salts, wherein R3 is -L-R x or -L-S c; and R4, R13 and R14 are methyl;

L is a covalent linkage that is -(CH2)5(CONH(CH2)e)Z'-, e is 1-5 and z' is 0 or 1;
R X is a reactive group that is a carboxylic acid, a succinimidyl ester of a carboxylic acid or a maleimide;
S c is a conjugated substance that is an antibody or fragment thereof, a fluorescent protein, a lectin, a nucleotide, an oligonucleotide, a peptide, a small-molecule drug, or a tyramide;
R6 and R7 combine to form a fused benzo ring, which benzo ring is substituted meta and para to R7 attachment site by sulfo; R8, R9, R16, and R18 are H; R17 is Br;
R2 and R12 are independently methyl or sulfopropyl;
n is 2.
35. A method of staining a biological sample, comprising:
combining a dye solution comprising any of the dyes described in Claims l-34, with a biological sample in a concentration sufficient to yield a detectable optical response under the desired conditions.
36. A method, as claimed in Claim 43, wherein the sample comprises cells.
37. A method, as claimed in Claim 43, wherein the sample comprises proteins or nucleic acid polymers in a microarray.
38. A method, as claimed in Claim 43, wherein the sample comprises a ligand that is a member of a specific binding pair, for which S c is a complementary member.
39. A method, as claimed in any of Claims 35-38, wherein the sample is contained in or on a solid or semi-solid matrix that is a membrane, an electrophoretic gel, a silicon chip, a glass slide, a microwell plate, or a microfluidic chip.
40. A kit for fluorescent labeling of a biological sample, comprising a dye solution comprising any of the compound described in Claims 1-34, or its salts;
and a buffer suitable for use with such sample.
41. A compound of the formula:

and its salts, wherein R3 is C3-C7 carboxyalkyl; and R4 is a C1-C6 alkyl;
R2 is H or a C1-C6 alkyl or C1-C6 alkyl substituted by sulfo.

R6 through R9 are independently H, amino, sulfo, trifluoromethyl, or halogen;
or C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy; or any two adjacent substituents of R6 through R9 form a fused benzo ring that is optionally substituted one or more times by amino, sulfo, trifluoromethyl, or halogen; or by C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C2-C12 dialkylamino, each of which is optionally further substituted by carboxy, sulfo, amino, or hydroxy.
42. A compound, as claimed in Claim 41, wherein R3 is C5-C6 carboxyalkyl; and R4 is methyl;
R2 is methyl or sulfopropyl;
R6 and R7 form a fused benzo ring that is optionally substituted one or more times by sulfo; or R7 is independently H or sulfo, and R6 is H; both R8 and R9 are H.
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US6133445A (en) 1997-12-17 2000-10-17 Carnegie Mellon University Rigidized trimethine cyanine dyes
US20030030797A1 (en) * 1999-09-24 2003-02-13 Henry Palladino Solid state fluorescence and absorption spectroscopy
DE10046215B4 (en) * 2000-09-19 2004-04-15 Institut für Chemo- und Biosensorik Münster e.V. i.Ins. Fluorochromes and their use
DE60126297T2 (en) * 2000-09-29 2007-11-15 Molecular Probes, Inc., Eugene MODIFIED CARBOCYANINE DYES AND THEIR CONJUGATES
US7129346B2 (en) * 2000-12-20 2006-10-31 Molecular Probes, Inc. Crown ether derivatives
US7579463B2 (en) * 2000-12-20 2009-08-25 Life Technologies Corporation Crown ether derivatives
JP4676654B2 (en) * 2001-07-19 2011-04-27 富士フイルム株式会社 Fluorescent nucleotide and labeling method using the same
US20050069962A1 (en) * 2001-10-12 2005-03-31 Archer Robert M Antibody complexes and methods for immunolabeling
US8323903B2 (en) * 2001-10-12 2012-12-04 Life Technologies Corporation Antibody complexes and methods for immunolabeling
US6972326B2 (en) * 2001-12-03 2005-12-06 Molecular Probes, Inc. Labeling of immobilized proteins using dipyrrometheneboron difluoride dyes
WO2003079015A1 (en) * 2002-03-11 2003-09-25 Visen Medical, Inc. Optical imaging probes
US7445894B2 (en) * 2002-05-03 2008-11-04 Molecular Probes, Inc. Compositions and methods for detection and isolation of phosphorylated molecules
US20040171034A1 (en) * 2002-05-03 2004-09-02 Brian Agnew Compositions and methods for detection and isolation of phosphorylated molecules
WO2004042347A2 (en) * 2002-05-03 2004-05-21 Molecular Probes, Inc. Compositions and methods for detection and isolation of phosphorylated molecules
US7615646B2 (en) 2002-05-10 2009-11-10 Carnegie Mellon University Chiral indole intermediates and their fluorescent cyanine dyes containing functional groups
US7785898B2 (en) 2002-05-31 2010-08-31 Genetic Technologies Limited Maternal antibodies as fetal cell markers to identify and enrich fetal cells from maternal blood
US7511155B2 (en) * 2002-07-08 2009-03-31 Ge Healthcare Uk Limited Reagents and a method for saturation labelling of proteins
AU2003270619A1 (en) 2002-09-12 2004-04-30 Molecular Probes, Inc. Site-specific labeling of affinity tags in fusion proteins
WO2004038038A2 (en) 2002-10-23 2004-05-06 University Of Utah Research Foundation Amplicon melting analysis with saturation dyes
US7005518B2 (en) * 2002-10-25 2006-02-28 Li-Cor, Inc. Phthalocyanine dyes
WO2004065491A1 (en) * 2003-01-24 2004-08-05 Schering Ag Hydrophilic, thiol-reactive cyanine dyes and conjugates thereof with biomolecules for fluorescence diagnosis
EP1599608A4 (en) 2003-03-05 2007-07-18 Genetic Technologies Ltd Identification of fetal dna and fetal cell markers in maternal plasma or serum
US7217649B2 (en) * 2003-03-14 2007-05-15 Lam Research Corporation System and method for stress free conductor removal
US7172907B2 (en) * 2003-03-21 2007-02-06 Ge Healthcare Bio-Sciences Corp. Cyanine dye labelling reagents with meso-substitution
JP4633716B2 (en) 2003-05-20 2011-02-16 インベスチゲン， インコーポレイテッド System for detecting polynucleotides
US7727969B2 (en) 2003-06-06 2010-06-01 Massachusetts Institute Of Technology Controlled release nanoparticle having bound oligonucleotide for targeted delivery
US7727752B2 (en) 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
US7271265B2 (en) * 2003-08-11 2007-09-18 Invitrogen Corporation Cyanine compounds and their application as quenching compounds
EP1658499B1 (en) * 2003-08-16 2007-10-03 Bayer HealthCare AG Determination of free fractions
WO2005050206A2 (en) 2003-09-17 2005-06-02 Molecular Probes, Inc. Competitive immunoassay
US20050095174A1 (en) * 2003-10-31 2005-05-05 Wolf David E. Semipermeable sensors for detecting analyte
ES2372395T3 (en) 2003-10-31 2012-01-19 Ge Healthcare Limited MARKING REAGENTS WITH CYANINE COLORS.
US20050214807A1 (en) * 2003-11-19 2005-09-29 Iain Johnson Environmental sensitive fluorogenic compounds and their application for singlet oxygen and protein detection
EP1689764B1 (en) * 2003-11-19 2013-01-02 AlleLogic Biosciences Corporation Oligonucleotides labeled with a plurality of fluorophores
US7776529B2 (en) 2003-12-05 2010-08-17 Life Technologies Corporation Methine-substituted cyanine dye compounds
EP2607431B1 (en) 2003-12-05 2016-08-24 Life Technologies Corporation Cyanine dye compounds
WO2005071096A2 (en) 2004-01-21 2005-08-04 Molecular Probes, Inc. Derivatives of cephalosporin and clavulanic acid for detecting beta-lacamase in a sample
US7387887B2 (en) 2004-04-20 2008-06-17 University Of Utah Research Foundation Nucleic acid melting analysis with saturation dyes
US9657347B2 (en) 2004-04-20 2017-05-23 University of Utah Research Foundation and BioFire Defense, LLC Nucleic acid melting analysis with saturation dyes
US8961407B2 (en) 2004-07-21 2015-02-24 Covidien Lp Surgical port assembly
WO2006023231A2 (en) 2004-07-27 2006-03-02 Molecular Probes, Inc. Fluorescent metal ion indicators with large stokes shift
US7524672B2 (en) * 2004-09-22 2009-04-28 Sandia Corporation Microfluidic microarray systems and methods thereof
US7592139B2 (en) 2004-09-24 2009-09-22 Sandia National Laboratories High temperature flow-through device for rapid solubilization and analysis
US7572640B2 (en) * 2004-09-28 2009-08-11 Singulex, Inc. Method for highly sensitive detection of single protein molecules labeled with fluorescent moieties
US9040305B2 (en) * 2004-09-28 2015-05-26 Singulex, Inc. Method of analysis for determining a specific protein in blood samples using fluorescence spectrometry
AU2005290314A1 (en) * 2004-09-28 2006-04-06 Singulex, Inc. System and method for spectroscopic analysis of single particles
US8685711B2 (en) 2004-09-28 2014-04-01 Singulex, Inc. Methods and compositions for highly sensitive detection of molecules
EP1794237A2 (en) 2004-09-30 2007-06-13 GE Healthcare UK Limited Fluorescent nucleotide analogues
WO2006047452A2 (en) * 2004-10-25 2006-05-04 Anaspec, Inc. Reactive 1,3’-crosslinked carbocyanines and their bioconjugates
WO2006099050A2 (en) * 2005-03-09 2006-09-21 Cepheid Polar dyes
US7456281B2 (en) 2005-04-20 2008-11-25 Idaho Technology, Inc. Nucleic acid melting analysis with saturation dyes
GB2425315B (en) * 2005-04-22 2009-10-07 Ge Healthcare Uk Ltd Water-soluble fluoro-substituted cyanine dyes as reactive fluorescence labelling reagents
US7598390B2 (en) * 2005-05-11 2009-10-06 Life Technologies Corporation Fluorescent chemical compounds having high selectivity for double stranded DNA, and methods for their use
US7737281B2 (en) * 2005-05-24 2010-06-15 Enzo Life Sciences, Inc. C/O Enzo Biochem, Inc. Purine based fluorescent dyes
US7569695B2 (en) * 2005-05-24 2009-08-04 Enzo Life Sciences, Inc. Dyes for the detection or quantification of desirable target molecules
US8227621B2 (en) * 2005-06-30 2012-07-24 Li-Cor, Inc. Cyanine dyes and methods of use
FR2889700B1 (en) * 2005-08-11 2012-11-23 Synthinnove Lab MARKERS, METHOD FOR PRODUCING THE SAME, AND APPLICATIONS THEREOF
US20070134685A1 (en) * 2005-09-06 2007-06-14 Invitrogen Corporation Control of chemical modification
PT1934607E (en) 2005-10-13 2013-11-13 Fundacao D Anna Sommer Champalimaud E Dr Carlos Montez Champalimaud Multiplex in situ immunohistochemical analysis
DE102006029454A1 (en) * 2005-12-05 2007-06-06 Dyomics Gmbh Hydrophilic markers based on diastereomeric
EP1792949B1 (en) * 2005-12-05 2010-09-08 Dyomics GmbH Hydrophilic marker on the basis of diastereomeric cyanines
US7521577B2 (en) 2006-01-12 2009-04-21 Molecular Probes, Inc. Heavy metal binding compounds and their method of use
US20070196860A1 (en) * 2006-01-18 2007-08-23 Invitrogen Corporation Methods for Measuring Real Time Kinase Activity
WO2007087582A1 (en) 2006-01-24 2007-08-02 Invitrogen Corporation Device and methods for quantifying analytes
WO2007090126A2 (en) * 2006-01-30 2007-08-09 Invitrogen Corporation Compositions and methods for detecting and quantifying toxic substances in disease states
US8114636B2 (en) 2006-02-10 2012-02-14 Life Technologies Corporation Labeling and detection of nucleic acids
EP2623986B1 (en) 2006-02-10 2017-06-14 Life Technologies Corporation Labeling and detection of post translationally modified proteins
US8562802B1 (en) 2006-02-13 2013-10-22 Life Technologies Corporation Transilluminator base and scanner for imaging fluorescent gels, charging devices and portable electrophoresis systems
US8021839B2 (en) * 2006-02-24 2011-09-20 Investigen, Inc. Methods and compositions for detecting polynucleotides
ATE515700T1 (en) 2006-03-23 2011-07-15 Absorber Ab BLOOD GROUP ANTIGENS OF DIFFERENT TYPES FOR DIAGNOSTIC AND THERAPEUTIC APPLICATIONS
JP4958461B2 (en) * 2006-03-30 2012-06-20 富士フイルム株式会社 Near-infrared absorbing dye-containing curable composition
ATE535525T1 (en) 2006-03-31 2011-12-15 Wako Pure Chem Ind Ltd CYANINE DYE OF PYRAZOLE TYPE
ES2550004T3 (en) 2006-04-04 2015-11-03 Singulex, Inc. High sensitivity system and troponin analysis methods
US7838250B1 (en) 2006-04-04 2010-11-23 Singulex, Inc. Highly sensitive system and methods for analysis of troponin
EP3156799B1 (en) 2006-04-04 2024-01-24 Novilux, LLC Analyzer and method for highly sensitive detection of analytes
US20070281363A1 (en) * 2006-04-13 2007-12-06 Ewald Terpetschnig Luminescent compounds
AU2007240316A1 (en) 2006-04-20 2007-11-01 Becton, Dickinson And Company Thermostable proteins and methods of making and using thereof
US20080076188A1 (en) * 2006-06-19 2008-03-27 Patsenker Leonid D Luminescent compounds
WO2008029085A2 (en) 2006-09-06 2008-03-13 Medical Research Council Polymerase
GB0619626D0 (en) * 2006-10-05 2006-11-15 Ge Healthcare Uk Ltd Fluoro-substituted benzoxazole polymethine dyes
WO2008076524A2 (en) 2006-10-27 2008-06-26 Life Technologies Corporation Fluorogenic ph sensitive dyes and their method of use
US7888506B2 (en) * 2007-01-26 2011-02-15 Duquesne University Of The Holy Spirit Composition, synthesis, and use of a new class of fluorophores
US8586743B2 (en) * 2007-01-30 2013-11-19 Life Technologies Corporation Labeling reagents and methods of their use
WO2008094637A2 (en) 2007-01-30 2008-08-07 Seta Biomedicals. Llc Luminescent compounds
JP5476989B2 (en) 2007-01-31 2014-04-23 和光純薬工業株式会社 Method for detecting amplification or deletion of genomic DNA fragment
US8221721B2 (en) * 2007-02-09 2012-07-17 Visen Medical, Inc. Polycyclo dyes and use thereof
US7771947B2 (en) 2007-02-23 2010-08-10 Investigen, Inc. Methods and compositions for rapid light-activated isolation and detection of analytes
EP2116577A4 (en) * 2007-02-28 2010-08-04 Mitsubishi Kagaku Media Co Ltd Cyanine dye and optical recording medium
FR2913424B1 (en) 2007-03-09 2009-07-24 Cis Bio Internat Sa CYANINE DERIVATIVES, FLUORESCENT CONJUGATES CONTAINING SAME AND USE THEREOF
EP2157088A4 (en) * 2007-04-11 2010-04-14 Uchrezhdenie Rossiiskoi Akadem Indicyanine dyes and the derivatives thereof for analysing biological micromolecules
WO2008151089A2 (en) * 2007-05-30 2008-12-11 Invitrogen Corporation Fluorescent phospholipase a2 indicators
US20090087860A1 (en) * 2007-08-24 2009-04-02 Todd John A Highly sensitive system and methods for analysis of prostate specific antigen (psa)
EP2223086B2 (en) * 2007-12-14 2016-06-01 Biotium Inc. Fluorescent compounds - labeling dyes
WO2009117033A2 (en) 2007-12-19 2009-09-24 Singulex, Inc. Scanning analyzer for single molecule detection and methods of use
EP2269064B1 (en) 2008-03-27 2016-11-30 Promega Corporation Protein labeling with cyanobenzothiazole conjugates
WO2009140541A2 (en) 2008-05-16 2009-11-19 Life Technologies Corporation Dual labeling methods for measuring cellular proliferation
US7951959B2 (en) 2008-09-17 2011-05-31 Thermo Fisher Scientific (Milwaukee) LLC Hydrophilic labels for biomolecules
CN102272106A (en) * 2008-11-07 2011-12-07 通用医疗公司 Monofunctional carbocyanine dyes for in vivo and in vitro imaging
JP2012509300A (en) * 2008-11-20 2012-04-19 ジーイー・ヘルスケア・アクスイェ・セルスカプ Dye conjugate imaging agent
JP5500875B2 (en) 2009-01-30 2014-05-21 キヤノン株式会社 Novel compound, probe using the novel compound, and contrast agent for fluorescence imaging using the novel compound or the probe
CN102459469A (en) * 2009-04-17 2012-05-16 利康股份有限公司 Fluorescent imaging with substituted cyanine dyes
EP2421955A4 (en) 2009-04-21 2012-10-10 Genetic Technologies Ltd Methods for obtaining fetal genetic material
WO2010138738A1 (en) 2009-05-27 2010-12-02 Lumicell Diagnostics, Inc. Methods and systems for spatially identifying abnormal cells
US9155471B2 (en) 2009-05-27 2015-10-13 Lumicell, Inc'. Methods and systems for spatially identifying abnormal cells
AU2010259022B2 (en) 2009-06-08 2016-05-12 Singulex, Inc. Highly sensitive biomarker panels
US8309059B2 (en) 2009-08-31 2012-11-13 Promega Corporation Reactive cyanine compounds
US8652441B2 (en) * 2009-10-05 2014-02-18 Canon Kabushiki Kaisha Contrast agent for photoacoustic imaging and photoacoustic imaging method
US8658434B2 (en) * 2009-10-28 2014-02-25 Biotium, Inc. Fluorescent pyrene compounds
US9579402B2 (en) * 2009-12-04 2017-02-28 Biotium, Inc. Heterocycle-substituted xanthene dyes
US8974651B2 (en) 2010-04-17 2015-03-10 C.C. Imex Illuminator for visualization of fluorophores
WO2011140484A1 (en) 2010-05-06 2011-11-10 Singulex, Inc Methods for diagnosing, staging, predicting risk for developing and identifying treatment responders for rheumatoid arthritis
CN103052690A (en) * 2010-06-29 2013-04-17 通用电气医疗集团股份有限公司 Dye compositions and dye syntheses
GB201010878D0 (en) * 2010-06-29 2010-08-11 Ge Healthcare As Dye compositiion and dye syntheses
US8623324B2 (en) 2010-07-21 2014-01-07 Aat Bioquest Inc. Luminescent dyes with a water-soluble intramolecular bridge and their biological conjugates
WO2012022734A2 (en) 2010-08-16 2012-02-23 Medimmune Limited Anti-icam-1 antibodies and methods of use
WO2012054749A1 (en) 2010-10-20 2012-04-26 Li-Cor, Inc. Cyanine dyes and their conjugates
US20130287689A1 (en) * 2010-11-02 2013-10-31 Life Technologies Corporation Modified Hydrocyanine Dyes for the Detection of Reactive Oxygen Species
US9314304B2 (en) 2010-12-08 2016-04-19 Lumicell, Inc. Methods and system for image guided cell ablation with microscopic resolution
EP3029027B1 (en) 2010-12-21 2018-06-27 Pierce Biotechnology, Inc. Fluorescent compounds
US8889884B1 (en) 2011-07-14 2014-11-18 Pierce Biotechnology, Inc. Phosphine derivatives of fluorescent compounds
US9249307B2 (en) 2011-08-16 2016-02-02 Pierce Biotechnology, Inc. Benzocyanine compounds
WO2013039883A1 (en) 2011-09-12 2013-03-21 Abbvie Biotherapeutics Inc. Artificial nk cells and uses thereof
EP2758475B1 (en) 2011-09-23 2017-04-26 Illumina Cambridge Limited Dyes for labelling molecular ligands
CZ304094B6 (en) * 2011-12-01 2013-10-16 Vysoká skola chemicko-technologická v Praze Use of polymethine salts as mitochondrial probes
NL2008241C2 (en) * 2012-02-06 2013-08-08 Hq Medical Netherlands B V Cell death probe.
US9751868B2 (en) 2012-02-28 2017-09-05 Pierce Biotechnology, Inc. Benzocyanine compounds
US20140072515A9 (en) 2012-03-02 2014-03-13 Greg Hermanson Cyanine compounds
CA2867144C (en) 2012-03-27 2019-07-02 Ventana Medical Systems, Inc. Signaling conjugates and methods of use
WO2013181506A1 (en) 2012-05-31 2013-12-05 The University Of North Carolina At Chapel Hill Dissolution guided wetting of structured surfaces
CN104540819B (en) 2012-08-28 2019-04-19 皮尔斯生物科技有限公司 Benzopyran compounds
BR112015003160A2 (en) * 2012-10-24 2017-07-04 Becton Dickinson Co hydroxamate-substituted bioconjugated azaindoline - cyanine dyes thereof
EP2912459A2 (en) 2012-10-25 2015-09-02 Life Technologies Corporation Methods and compositions for enzyme-mediated site-specific radiolabeling of glycoproteins
US20160010145A1 (en) * 2012-12-07 2016-01-14 Life Technologies Corporation Detection of rna with substituted unsymmetrical cyanine dyes
DK2964624T3 (en) 2013-03-08 2017-04-03 Illumina Cambridge Ltd RHODAMINE COMPOUNDS AND USE AS FLUORESCING LABELS
AU2013380645B2 (en) 2013-03-08 2018-03-15 Illumina Cambridge Ltd Polymethine compounds and their use as fluorescent labels
KR20160037834A (en) 2013-03-14 2016-04-06 루미셀, 아이엔씨. Medical imaging device and methods of use
EP2970674B1 (en) 2013-03-15 2018-12-12 VisEn Medical, Inc. 4,4-disubstituted cyclohexyl bridged heptamethine cyanine dyes and uses thereof
CA2901379C (en) 2013-03-15 2023-05-16 Visen Medical, Inc. Substituted silaxanthenium red to near-infrared fluorochromes for in vitro and in vivo imaging and detection
US10024863B2 (en) 2013-03-15 2018-07-17 Life Technologies Corporation Methods for dye selection for protein melt temperature determinations
WO2015050959A1 (en) 2013-10-01 2015-04-09 Yale University Anti-kit antibodies and methods of use thereof
BR112016006999B1 (en) 2013-10-02 2023-11-14 Medimmune, Llc ANTI-INFLUENZA NEUTRALIZING ANTIBODIES AND THEIR USES, THEIR PRODUCTION METHOD, COMPOSITION THAT COMPRISES THEM, NUCLEIC ACID AND VECTOR
US9636034B2 (en) 2013-10-23 2017-05-02 Verily Life Sciences Llc Non-invasive analyte detection system with modulation source
US10542918B2 (en) 2013-10-23 2020-01-28 Verily Life Sciences Llc Modulation of a response signal to distinguish between analyte and background signals
US9835587B2 (en) 2014-04-01 2017-12-05 C.C. Imex Electrophoresis running tank assembly
GB201408077D0 (en) 2014-05-07 2014-06-18 Illumina Cambridge Ltd Polymethine compounds and their use as fluorescent labels
EP2944326B1 (en) * 2014-05-16 2018-11-21 Cyanagen Srl Tricarbocyanine-cyclodextrin-conjugates and their use for the diagnosis of kidney diseases
US10357510B2 (en) * 2014-08-07 2019-07-23 The Regents Of The University Of Michigan Metal nanoclusters and uses thereof
UA109751C2 (en) 2014-09-26 2015-09-25 METHOD OF DETERMINATION OF HYDROGEL IN BIOLOGICAL FABRICS
SG10202012249YA (en) 2014-12-08 2021-01-28 Berg Llc Use of markers including filamin a in the diagnosis and treatment of prostate cancer
US9861710B1 (en) 2015-01-16 2018-01-09 Verily Life Sciences Llc Composite particles, methods, and in vivo diagnostic system
JP6552236B2 (en) * 2015-03-23 2019-07-31 キヤノン株式会社 Near-infrared dye-bound transferrin, contrast agent for photoacoustic imaging comprising the near-infrared dye-bound transferrin
US10028659B2 (en) 2015-03-26 2018-07-24 Verily Life Sciences Llc Aptamer-based sensors, implantable devices and detection system
GB201508858D0 (en) 2015-05-22 2015-07-01 Illumina Cambridge Ltd Polymethine compounds with long stokes shifts and their use as fluorescent labels
EP3098269B1 (en) 2015-05-28 2022-04-06 Miltenyi Biotec B.V. & Co. KG Bright fluorochromes based on multimerization of fluorescent dyes on branched polyether scaffolds
US9670318B2 (en) 2015-05-28 2017-06-06 Miltenyi Biotec Gmbh Bright fluorochromes based on multimerization of fluorescent dyes
GB201516987D0 (en) 2015-09-25 2015-11-11 Illumina Cambridge Ltd Polymethine compounds and their use as fluorescent labels
CN112274649A (en) * 2015-12-10 2021-01-29 希望之城 Cell penetrating cyanine conjugated antibodies
US9862682B2 (en) 2016-01-08 2018-01-09 BroadPharm Functionalized pegylated cyanine compounds, pharmaceutical compositions, and methods of use thereof
ES2936226T3 (en) 2016-04-15 2023-03-15 Beckman Coulter Inc Photoactive macromolecules and their uses
US20190120845A1 (en) 2016-04-15 2019-04-25 Icahn School Of Medicine At Mount Sinai Tissue profiling using multiplexed immunohistochemical consecutive staining
US10294204B2 (en) * 2016-04-27 2019-05-21 Bioacts Co., Ltd. Fluorescence compounds and preparation method thereof
KR101944912B1 (en) * 2016-04-27 2019-02-07 (주)바이오액츠 Fluorescence Compounds and Preparation Method Therof
US9796854B1 (en) 2016-07-07 2017-10-24 Intuitive Surgical Operations, Inc. Method of synthesizing near IR, closed chain sulfo-cyanine dyes
CN110546273A (en) 2017-03-30 2019-12-06 生命技术公司 quantification of NGS DNA by adaptor sequences
GB201711219D0 (en) 2017-07-12 2017-08-23 Illumina Cambridge Ltd Short pendant arm linkers for nucleotides in sequencing applications
CN107290198B (en) * 2017-07-25 2019-07-16 中国科学院微生物研究所 A method of biomaterial is dyed using PIP
US11091646B2 (en) 2017-08-14 2021-08-17 Seta Biomedicals, Llc Luminescent squaraine rotaxane compounds
GB201716931D0 (en) 2017-10-16 2017-11-29 Illumina Cambridge Ltd New fluorescent compounds and their use as biomarkers
WO2019204432A2 (en) * 2018-04-17 2019-10-24 Cornell University Fluorine-18 labeled compositions and their use in imaging of biological tissue
CN108752406A (en) * 2018-05-29 2018-11-06 苏州百源基因技术有限公司 A kind of nucleotide of fluorescent marker and its preparation method and application
US11408840B2 (en) 2018-06-28 2022-08-09 Just-Evotec Biologics, Inc. High throughput interrogation of physiochemical properties of a protein
BR102019025989A2 (en) 2018-12-14 2020-06-23 Beckman Coulter, Inc. MODIFICATION OF POLYMERIC DYES AND APPLICATIONS
BR112020026669A2 (en) 2019-03-01 2021-09-08 Illumina Cambridge Limited COUMARIN COMPOUND SUBSTITUTED WITH TERTIARY AMINE, NUCLEOTIDES OR OLIGONUCLEOTIDES, KIT, USE THEREOF, SEQUENCING METHOD AND METHOD TO SYNTHESIS A COMPOUND
CA3103900A1 (en) 2019-03-01 2020-09-10 Illumina Cambridge Limited Exocyclic amine substituted coumarin compounds and their uses as fluorescent labels
WO2020178231A1 (en) 2019-03-01 2020-09-10 Illumina, Inc. Multiplexed fluorescent detection of analytes
NL2023327B1 (en) 2019-03-01 2020-09-17 Illumina Inc Multiplexed fluorescent detection of analytes
KR20220015394A (en) 2019-04-30 2022-02-08 라리마 테라퓨틱스, 인코포레이티드 Frataxin sensitivity markers for determining the efficacy of prataxin replacement therapy
WO2021096971A1 (en) * 2019-11-11 2021-05-20 The Trustees Of Dartmouth College Composition and method for in vivo assay of opioid receptors
CN111393872B (en) * 2020-03-18 2022-05-17 宝天生物科技（上海）有限公司 Ultraviolet light excited fluorescent dye and application thereof
CN115397923A (en) * 2020-04-24 2022-11-25 富士胶片株式会社 Compound and labeled biological substance using same
KR20230034333A (en) 2020-07-02 2023-03-09 라이프 테크놀로지스 코포레이션 Trinucleotide Cap Analogues, Preparation and Uses Thereof
CN116323965A (en) 2020-07-23 2023-06-23 生命技术公司 Compositions, systems and methods for bioassays using dyes
CN116075597A (en) 2020-07-23 2023-05-05 生命技术公司 Energy transfer dye conjugates for use in bioassays
US20220033900A1 (en) 2020-07-28 2022-02-03 Illumina Cambridge Limited Substituted coumarin dyes and uses as fluorescent labels
EP4190795A1 (en) 2020-07-30 2023-06-07 FUJIFILM Corporation Compound, and labeled biological substance in which same is used
WO2022047359A1 (en) 2020-08-31 2022-03-03 Berg Llc Protein biomarkers for pancreatic cancer
CN117015711A (en) 2021-02-05 2023-11-07 贝克曼库尔特有限公司 Compositions and methods for preventing non-specific interactions between polymer dye-antibody conjugates
US20230059578A1 (en) 2021-04-06 2023-02-23 Berg Llc Protein markers for estrogen receptor (er)-positive-like and estrogen receptor (er)-negative-like breast cancer
EP4320440A1 (en) 2021-04-06 2024-02-14 BPGbio, Inc. Protein markers for estrogen receptor (er)-positive luminal a(la)-like and luminal b1 (lb1)-like breast cancer
CA3214833A1 (en) 2021-04-06 2022-10-13 Bpgbio, Inc. Protein markers for the prognosis of breast cancer progression
WO2022265043A1 (en) 2021-06-18 2022-12-22 富士フイルム株式会社 Compound and labeled biomaterial using same
CN117529529A (en) * 2021-07-21 2024-02-06 生命技术公司 Azaindole cyanine dye, application and preparation method
WO2023004400A1 (en) 2021-07-21 2023-01-26 Life Technologies Corporation Dibenzoxanthene quenchers, uses, and methods of preparation
CN117460790A (en) 2021-08-18 2024-01-26 富士胶片株式会社 Fluorescent compound and fluorescent-labeled biological material using same
WO2023032994A1 (en) 2021-08-31 2023-03-09 富士フイルム株式会社 Compound and labeled biomaterial using same
WO2023032996A1 (en) 2021-08-31 2023-03-09 富士フイルム株式会社 Compound and labeled biomaterial using same
WO2023032995A1 (en) 2021-08-31 2023-03-09 富士フイルム株式会社 Compound and labeled biomaterial using same
WO2023056460A1 (en) 2021-09-30 2023-04-06 Beckman Coulter, Inc. Water-soluble tetrahydropyrene based fluorescent polymers
WO2023086103A1 (en) 2021-11-12 2023-05-19 Beckman Coulter, Inc. Novel formulation for drying of polymer dye conjugated antibodies
KR102414574B1 (en) * 2022-02-27 2022-06-30 (주)바이오액츠 Fluorescent compound for detecting biological materials and the preparation method thereof
US20230357851A1 (en) 2022-04-06 2023-11-09 Larimar Therapeutics, Inc. Frataxin-sensitive markers for monitoring frataxin-replacement therapy
WO2023240201A1 (en) 2022-06-08 2023-12-14 Larimar Therapeutics, Inc. Frataxin-sensitive markers for monitoring progression and treatment of leigh syndrome
WO2024007016A2 (en) 2022-07-01 2024-01-04 Beckman Coulter, Inc. Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives
WO2024044327A1 (en) 2022-08-26 2024-02-29 Beckman Coulter, Inc. Dhnt monomers and polymer dyes with modified photophysical properties
CN115772390B (en) * 2022-12-02 2023-09-08 湖北龙海化工有限公司 Low-fluorescence blocking anti-collapse asphalt for drilling fluid

Family Cites Families (97)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB870753A (en) 1957-07-04 1961-06-21 Ilford Ltd Improvements in or relating to methine dyes
US2993791A (en) 1957-10-31 1961-07-25 Gen Aniline & Film Corp Color couplers containing long chain alkylaminoisophthalicester groups
US3723419A (en) 1967-05-17 1973-03-27 Eastman Kodak Co Preparation of formylmethylene compounds and corresponding photographic dyestuffs
US3864644A (en) 1971-03-22 1975-02-04 Eastman Kodak Co Dye lasers including rigidized carbocyanine dyes
US4011086A (en) 1975-10-14 1977-03-08 Eastman Kodak Company Photographic emulsions and elements containing rigidized carbocyanine dyes
US4273862A (en) 1977-06-11 1981-06-16 Mitsubishi Paper Mills, Ltd. Direct-positive silver halide photographic sensitive materials
US4711955A (en) 1981-04-17 1987-12-08 Yale University Modified nucleotides and methods of preparing and using same
US5171534A (en) 1984-01-16 1992-12-15 California Institute Of Technology Automated DNA sequencing technique
US6086737A (en) 1984-03-29 2000-07-11 Li-Cor, Inc. Sequencing near infrared and infrared fluorescence labeled DNA for detecting using laser diodes and suitable labels therefor
US5366603A (en) 1984-03-29 1994-11-22 Li-Cor, Inc. Sequencing near infrared and infrared fluorescence labeled DNA for detecting useing laser diodes
JPS62123454A (en) † 1985-08-08 1987-06-04 Fuji Photo Film Co Ltd Silver halide photographic sensitive material
US5627027A (en) 1986-04-18 1997-05-06 Carnegie Mellon University Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods
US6048982A (en) * 1986-04-18 2000-04-11 Carnegie Mellon University Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods
US5268486A (en) * 1986-04-18 1993-12-07 Carnegie-Mellon Unversity Method for labeling and detecting materials employing arylsulfonate cyanine dyes
US6225050B1 (en) * 1986-04-18 2001-05-01 Carnegie Mellon University Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods
US5569587A (en) 1986-04-18 1996-10-29 Carnegie Mellon University Method for labeling and detecting materials employing luminescent arysulfonate cyanine dyes
US5047519A (en) 1986-07-02 1991-09-10 E. I. Du Pont De Nemours And Company Alkynylamino-nucleotides
CA1340806C (en) 1986-07-02 1999-11-02 James Merrill Prober Method, system and reagents for dna sequencing
US5049673A (en) 1987-10-30 1991-09-17 The Regents Of The University Of California Fluorescent indicator dyes for calcium working at long wavelengths
JPH0672706B2 (en) 1988-05-31 1994-09-14 清水建設株式会社 Scent supply method and scent supply device
US4997928A (en) 1988-09-15 1991-03-05 E. I. Du Pont De Nemours And Company Fluorescent reagents for the preparation of 5'-tagged oligonucleotides
US5196306A (en) 1989-03-29 1993-03-23 E. I. Du Pont De Nemours And Company Method for the detection or quantitation of an analyte using an analyte dependent enzyme activation system
US5137810A (en) 1989-04-26 1992-08-11 The University Of North Carolina Method of determining the gram sign of bacteria
US4981977A (en) 1989-06-09 1991-01-01 Carnegie-Mellon University Intermediate for and fluorescent cyanine dyes containing carboxylic acid groups
JPH0614984Y2 (en) 1989-11-29 1994-04-20 西川化成株式会社 Parts mounting structure to resin molding
US5405975A (en) 1993-03-29 1995-04-11 Molecular Probes, Inc. Fluorescent ion-selective diaryldiaza crown ether conjugates
US5648270A (en) 1995-02-06 1997-07-15 Molecular Probes, Inc. Methods of sensing with fluorescent conjugates of metal-chelating nitrogen heterocycles
US5453517A (en) 1992-02-25 1995-09-26 Molecular Probes, Inc. Reactive derivatives of bapta used to make ion-selective chelators
US5567588A (en) 1990-06-11 1996-10-22 University Research Corporation Systematic evolution of ligands by exponential enrichment: Solution SELEX
FR2664760B1 (en) * 1990-07-13 1996-09-27 Sgs Thomson Microelectronics DEVICE FOR PROTECTION AGAINST OVERVOLTAGES AND ITS MONOLITHIC IMPLEMENTATION.
NL9001639A (en) 1990-07-19 1992-02-17 Amc Amsterdam PT-CONTAINING COMPOUND, METHOD FOR PREPARING IT, AND USE OF SUCH COMPOUNDS.
US5714327A (en) 1990-07-19 1998-02-03 Kreatech Diagnostics Platinum-containing compounds, methods for their preparation and applications thereof
US5208148A (en) 1990-12-07 1993-05-04 Molecular Probes, Inc. Lipophilic fluorescent glycosidase substrates
YU187991A (en) 1990-12-11 1994-09-09 Hoechst Aktiengesellschaft 3- (2) -AMINO-ALI THIOL-MODIFIED, FLUORESCENT-DYED NUCLEOSIDES, NUCLEOTIDS AND OLIGONUCLEOTIDES, PROCESS FOR THEIR OBTAINING AND THEIR USE
JPH08168B2 (en) 1991-02-12 1996-01-10 マルチネツ ムジカ デー．フェルナンド Filtration device for machine tools
JP3084454B2 (en) 1991-04-23 2000-09-04 コニカ株式会社 Silver halide photographic material
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
SE9200917D0 (en) * 1991-08-20 1992-03-25 Pharmacia Biosensor Ab ASSAY METHOD
US5831098A (en) 1992-03-16 1998-11-03 Minnesota Mining And Manufacturing Company 2-methyl-4,4a-dihydro-3H-carbazolium salts and dyes derived therefrom
JPH05313304A (en) † 1992-05-11 1993-11-26 Fuji Photo Film Co Ltd Silver halide photographic sensitive material
JPH0614984A (en) 1992-07-01 1994-01-25 Yamatake Honeywell Co Ltd Scent generating device
EP0658167B1 (en) 1992-09-03 1999-04-14 The Perkin-Elmer Corporation 4,7-dichlorofluorescein dyes as molecular probes
US5808044A (en) 1993-01-22 1998-09-15 Pharmacia Biotech Inc. Indocarbocyanine and benzindocarbocyanine phosphoramidites
US5556959A (en) 1993-01-22 1996-09-17 Pharmacia P-L Biochemicals Inc. Indocarbocyanine-linked phosphoramidites
US5436134A (en) 1993-04-13 1995-07-25 Molecular Probes, Inc. Cyclic-substituted unsymmetrical cyanine dyes
US5496700A (en) * 1993-08-06 1996-03-05 The United States Of America As Represented By The Secretary Of The Navy Optical immunoassay for microbial analytes using non-specific dyes
US5516911A (en) 1993-12-30 1996-05-14 The United States Of America As Represented By The Department Of Health And Human Services Fluorescent intracellular calcium indicators
US5453505A (en) 1994-06-30 1995-09-26 Biometric Imaging, Inc. N-heteroaromatic ion and iminium ion substituted cyanine dyes for use as fluorescence labels
US5487502A (en) 1994-07-25 1996-01-30 Liao; Ming-Kang Decorative means for emitting odor and generating sound
DE69526617T2 (en) * 1994-09-22 2002-08-29 Fuji Photo Film Co Ltd Infrared absorbing dye Silver halide photographic material
US5547588A (en) * 1994-10-25 1996-08-20 Gas Research Institute Enhanced ettringite formation for the treatment of hazardous liquid waste
US6150510A (en) 1995-11-06 2000-11-21 Aventis Pharma Deutschland Gmbh Modified oligonucleotides, their preparation and their use
DE4445065A1 (en) 1994-12-07 1996-06-13 Diagnostikforschung Inst Methods for in-vivo diagnostics using NIR radiation
US6127134A (en) 1995-04-20 2000-10-03 Carnegie Mellon University Difference gel electrophoresis using matched multiple dyes
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
US6008373A (en) 1995-06-07 1999-12-28 Carnegie Mellon University Fluorescent labeling complexes with large stokes shift formed by coupling together cyanine and other fluorochromes capable of resonance energy transfer
JP3292007B2 (en) * 1995-11-09 2002-06-17 松下電器産業株式会社 Dye-labeled protein complex and method for producing the same
US6004536A (en) 1995-11-14 1999-12-21 Molecular Probes, Inc. Lipophilic cyanine dyes with enchanced aqueous solubilty
US5668268A (en) 1995-11-27 1997-09-16 Hybridon, Inc. Passivated polymer supports for nucleic acid synthesis
US6165734A (en) * 1995-12-12 2000-12-26 Applied Spectral Imaging Ltd. In-situ method of analyzing cells
US5714386A (en) 1996-01-11 1998-02-03 Board Of Trustees Of The Leland Stanford Junior University Cy7-allophycocyanin conjugates for use in multiplex fluorescence detection assays
US5922618A (en) * 1996-03-04 1999-07-13 Matsushita Electric Industrial Co., Ltd. Dye-labeled antibody conjugate and preparation method thereof
DE69706417T2 (en) 1996-04-19 2002-06-27 Amersham Pharm Biotech Uk Ltd SQUARE DYES AND THEIR USE IN A FLUORESCENCE SEQUENCING PROCESS
US6245499B1 (en) * 1996-04-30 2001-06-12 Fuji Photo Film Co., Ltd. Photothermographic material
JP3537267B2 (en) * 1996-06-06 2004-06-14 松下電器産業株式会社 Equipment operation method
US5688966A (en) 1996-07-26 1997-11-18 E. I. Du Pont De Nemours And Company Compounds and method for synthesizing sulfoindocyanine dyes
US6303758B1 (en) * 1996-11-08 2001-10-16 Matsushita Electric Industrial Co., Ltd. Dye-labeled and polymerized antibody and method for preparing the same
US6303759B1 (en) * 1996-11-08 2001-10-16 Matsushita Electric Industrial Co., Ltd. Dye-labeled and polymerized antibody and method for preparing the same
US6027709A (en) 1997-01-10 2000-02-22 Li-Cor Inc. Fluorescent cyanine dyes
US5877310A (en) 1997-04-25 1999-03-02 Carnegie Mellon University Glycoconjugated fluorescent labeling reagents
AU7221398A (en) † 1997-04-29 1998-11-24 Nycomed Imaging As Method of demarcating tissue
US5986086A (en) 1997-06-20 1999-11-16 Amersham Pharmacia Biotech Inc. Non-sulfonated cyanine dyes for labeling nucleosides and nucleotides
US6133445A (en) 1997-12-17 2000-10-17 Carnegie Mellon University Rigidized trimethine cyanine dyes
US7250517B2 (en) * 1998-04-08 2007-07-31 Ewald A. Terpetschnig Luminescent compounds
US6538129B1 (en) * 1999-04-07 2003-03-25 Ewald A. Terpetschnig Luminescent compounds
WO1999051702A1 (en) 1998-04-08 1999-10-14 Terpetschnig Ewald A Luminescent compounds
US6002003A (en) 1998-04-14 1999-12-14 Beckman Instruments, Inc. Cyanine dye activating group with improved coupling selectivity
GB9812596D0 (en) 1998-06-11 1998-08-12 Amersham Pharm Biotech Uk Ltd Energy transfer assay method
US6114350A (en) 1999-04-19 2000-09-05 Nen Life Science Products, Inc. Cyanine dyes and synthesis methods thereof
US6664047B1 (en) 1999-04-30 2003-12-16 Molecular Probes, Inc. Aza-benzazolium containing cyanine dyes
EP1212375A2 (en) * 1999-06-09 2002-06-12 Carnegie-Mellon University Ph sensitive cyanine dyes as reactive fluorescent reagents
ATE435262T1 (en) 1999-07-02 2009-07-15 Visen Medical Inc FLUORESCENT CYANINE LABELS WITH A SULPHAMIDO BRIDGE
WO2001002374A1 (en) 1999-07-06 2001-01-11 Surromed, Inc. Bridged fluorescent dyes, their preparation and their use in assays
DE19937024A1 (en) 1999-08-05 2001-02-08 Bayer Ag Use of acylsulfonamido substituted polymethine dyes as fluorescent dyes and / or markers
ATE296828T1 (en) 1999-09-20 2005-06-15 Fuji Photo Film Co Ltd COMPOUNDS FOR FLUORESCENCE LABELING
DE19957320A1 (en) * 1999-11-29 2001-05-31 Febit Ferrarius Biotech Gmbh Dynamic sequencing of nucleic acid by hybridization, useful e.g. for research or detecting mutations, includes several hybridization cycles using progressively longer probes
US6977306B2 (en) * 2000-05-02 2005-12-20 Sumitomo Chemical Company, Limited Citalopram hydrobromide crystal and method for crystallization thereof
US6342326B1 (en) * 2000-05-10 2002-01-29 Beckman Coulter, Inc. Synthesis and use of acyl fluorides of cyanine dyes
DE10046215B4 (en) 2000-09-19 2004-04-15 Institut für Chemo- und Biosensorik Münster e.V. i.Ins. Fluorochromes and their use
WO2002026980A2 (en) 2000-09-27 2002-04-04 Lexicon Genetics Incorporated Human ion-exchanger proteins and polynucleotides encoding t he same
DE60126297T2 (en) 2000-09-29 2007-11-15 Molecular Probes, Inc., Eugene MODIFIED CARBOCYANINE DYES AND THEIR CONJUGATES
EP1209205A1 (en) * 2000-11-28 2002-05-29 Innosense S.r.l. Improved process and method for the preparation of asymetric monofunctionalised indocyanine labelling reagents and obtained compounds
US6962992B2 (en) 2000-12-20 2005-11-08 Molecullar Probes, Inc. Crown ether derivatives
US6972326B2 (en) 2001-12-03 2005-12-06 Molecular Probes, Inc. Labeling of immobilized proteins using dipyrrometheneboron difluoride dyes
US7615646B2 (en) 2002-05-10 2009-11-10 Carnegie Mellon University Chiral indole intermediates and their fluorescent cyanine dyes containing functional groups
WO2004104185A1 (en) 2003-05-08 2004-12-02 Xcyte Therapies, Inc. Generation and isolation of antigen-specific t cells
EP2223086B2 (en) * 2007-12-14 2016-06-01 Biotium Inc. Fluorescent compounds - labeling dyes

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