Dhnt monomers and polymer dyes with modified photophysical properties
AssigneeBeckman Coulter, Inc.
InventorsMassimiliano TOMASULO, Arunkumar EASWARAN, Sergei GULNIK
Life of this patent
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Abstract
The present disclosure relates to dihydronaphthothiophene (DHNT), dihydrobenzo dithiophene (DHBDT), and dihydronapthothienothiophene (DHNTT) monomer units and fluorescent polymers and co-polymers thereof. DHNT, DHNTT, and/or DHBDT containing water-soluble fluorescent co-polymers, water-soluble tandem fluorescent co-polymers, water-soluble fluorescent co-polymer complexes, water-soluble tandem fluorescent co-polymer complexes, and their use in methods for detecting analytes in a biological sample are also provided.
Claims20
A water-soluble polymer dye comprising at least one co-monomer M1 having a structure according to Formula (Ia):
- wherein
- Ar1 and Ar2 are each independently substituted or unsubstituted aryl or heteroaryl groups and at least one of Ar1 and Ar2 comprises at least one fused thienyl ring;
- each X is independently selected from the group consisting of C and Si;
- each Y is independently selected from the group consisting of a bond, CR1R2, CHR1, CHR2, SiHR2, SiHR1, and SiR1R2, and when Y is a bond X is directly bonded to both rings, and when Y is a bond, Ar1 and Ar2 are not both thienyl;
- each R1 is independently selected from the group consisting of a water-solubilizing moiety, a linker moiety, alkyl, alkene, alkyne, cycloalkyl, hydroxy, haloalkyl, (hetero)aryloxy, (hetero)arylamino, aryl, heteroaryl, a polyethylene glycol (PEG) group, carboxylic acid, ammonium alkyl salt, ammonium alkyloxy salt, ammonium oligoether salt, sulfonate alkyl salt, sulfonate alkoxy salt, sulfonamido oligoether, sulfonamide, sulfinamide, phosphonamidate, phosphinamide, phosphonate,
- each R2 is independently selected from the group consisting of a water-solubilizing moiety, a linker moiety, H, alkyl, alkene, alkyne, cycloalkyl, halogen, haloalkyl, alkoxy, (hetero)aryloxy, aryl, heteroaryl, (hetero)arylamino, a PEG group, sulfonamide-PEG, phosphoramide-PEG, ammonium alkyl salt, ammonium alkyloxy salt, ammonium oligoether salt, sulfonate alkyl salt, sulfonate alkoxy salt, sulfonate oligoether salt, sulfonamido oligoether, sulfonamide, sulfinamide, phosphonamidate, phosphinamide, phosphonate,
- each R3 is independently selected from the group consisting of H, alkyl, alkene, alkyne, cycloalkyl, haloalkyl, alkoxy, (hetero)aryloxy, aryl, (hetero)arylamino, a water-solubilizing moiety, a chromophore, and a PEG group;
- each Z is independently selected from the group consisting of CH2, CHR4, O, NR4, and NH;
- each Q is independently selected from the group consisting of a bond, NH, NR4, C1-C12 alkylene, CHR4, and CH2;
- each R4 is independently selected the group consisting of H, a PEG group, a water-solubilizing moiety, a linker moiety, a chromophore, a linked chromophore, a functional group, a linked functional group, a substrate, a linked substrate, a binding partner, a linked binding partner, a quenching moiety, L2-E, halogen, an amine, hydroxyl, alkylamino, substituted or unsubstituted C1-C12 alkyl, C2-C12 alkene, C2-C12 alkyne, C3-C12 cycloalkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C2-C18 (hetero)aryloxy, C2-C18 (hetero)arylamino, (CH2)x′(OCH2—CH2)y′OR9, wherein each R9 is C1-C8 alkyl, x′ is independently an integer from 0-20 and each y′ is independently an integer from 0-50, Z—(CH2)n—SO2-Q-R3, a C2-C18 (hetero)aryl group, amide, amine, carbamate, carboxylic acid, carboxylate ester, maleimide, activated ester, N-hydroxysuccinimidyl, hydrazine, hydrazone, azide, aldehyde, thiol, and protected groups thereof;
- each W1 is independently a water-solubilizing moiety;
- L1, L2, and L3 are each independently selected linker moieties;
- each E is independently selected from the group consisting of a chromophore, a functional moiety, a substrate, and a binding partner;
- each R7 is independently selected from the group consisting of H, hydroxyl, C1-C12 alkyl, C2-C12 alkene, C2-C12 alkyne, C3-C12 cycloalkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C2-C18 (hetero)aryloxy, C2-C18 (hetero)arylamino, C2-C12 carboxylic acid, C2-C12 carboxylate ester and —OC1-C12 hydroxy;
- at least one of R1, R2, R3, or R4 comprises a water-solubilizing moiety;
- each h is independently an integer from 0 to 50;
- each n is independently an integer from 1 to 20;
- each s is independently 1 or 2;
- and
- each t is independently 0, 1, 2, or 3.
A method for detecting a target analyte in a sample comprising:
- providing a sample that is suspected of containing the target analyte;
- and
- contacting the sample with a labeled specific binding partner according to claim to form a fluorescent polymer dye conjugate complex with the target analyte if the target analyte is present;
- applying a light source to the sample that can excite the at least one fluorescent polymer dye conjugate complex;
- and
- detecting light emitted from the fluorescent polymer dye conjugate complex, optionally
- wherein the sample is a biological sample selected from the group consisting of blood, bone marrow, spleen cells, lymph cells, bone marrow aspirates, urine, serum, saliva, cerebral spinal fluid, urine, amniotic fluid, interstitial fluid, feces, mucus, tissue, or is from a cell culture.
Dependencies are inferred from the claim text.