FLUORESCENT METHODS AND MATERIALS FOR DIRECTED BIOMARKER SIGNAL AMPLIFICATION

• US 20170115298A1
• Filed: 11/29/2016
• Published: 04/27/2017
• Est. Priority Date: 10/06/2006
• Status: Active Grant

• Current Assignee: Sirigen Ii Limited (Becton, Dickinson & Co)
• Original Assignee: Sirigen, Inc. (Becton, Dickinson & Co)
• Inventors: Gaylord, Brent S., Hong, Janice W., Fu, Tsu-Ju, Sun, ChengJun, Baldocchi, Russell A.
• Granted Patent: US 10,107,818 B2
• Time in Patent Office: Days
• CPC Class Codes: C08G 2261/3142 fluorene-based, e.g. fluorene, indenofluorene, or spirobifluorene
• CPC Class Codes: C08G 2261/3221 containing one or more nitrogen atoms as the only heteroatom, e.g. pyrrole, pyridine or triazole
• CPC Class Codes: C08G 2261/3241 containing one or more nitrogen atoms as the only heteroatom, e.g. carbazole
• CPC Class Codes: C08G 2261/3246 containing nitrogen and sulfur as heteroatoms
• CPC Class Codes: C08G 2261/522 fluorescent
• CPC Class Codes: C08G 2261/78 Complexation
• CPC Class Codes: C08G 2261/94 Applications in sensors, e.g. biosensors
• CPC Class Codes: C08G 61/02 Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes
• CPC Class Codes: C08G 61/12 Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: H10K 85/115 Polyfluorene; Derivatives thereof
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

Methods and compositions are provided that include a multichromophore and/or multichromophore complex for identifying a target biomolecule. A sensor biomolecule, for example, an antibody can be covalently linked to the multichromophore. Additionally, a signaling chromophore can be covalently linked to the multichromophore. The arrangement is such that the signaling chromophore is capable of receiving energy from the multichromophore upon excitation of the multichromophore. Since the sensor biomolecule is capable of interacting with the target biomolecule, the multichromophore and/or multichromophore complex can provide enhanced detection signals for a target biomolecule.

Claims

1-71. -71. (canceled)

72. A water soluble multichromophore, comprising the structure:

73. The multichromophore according to claim 72, wherein the aromatic repeat units are each independently a carbocyclic or heterocyclic aryl group comprising 1 to 5 fused aromatic rings.

74. The multichromophore according to claim 73, wherein the aromatic repeat units are each independently a carbocyclic or heterocyclic aryl group, wherein the aryl group is selected from benzene, naphthalene, anthracene, fluorene, thiophene, furan, pyridine, oxadiazole and substituted versions thereof.

75. The multichromophore according to claim 72, wherein the multichromophore is substituted with a plurality of charge neutral water-soluble groups.

76. The multichromophore according to claim 72, wherein CP₃ is present and comprises a bioconjugation site.

77. The multichromophore according to claim 72, wherein the multichromophore is further coupled to a signaling chromophore.

78. The multichromophore according to claim 72, wherein CP₁ and CP₂ are present and independently selected from a fluorene and a substituted fluorene comprising replacement of a carbon atom with a substituted heteroatom.

79. The multichromophore according to claim 78, wherein CP_i and CP₂ are substituted with one or more solubilizing groups selected from ethylene glycol oligomers, ethylene glycol polymers, ω

-ammonium alkoxy salts and ω

-sulfonate alkoxy salts.

80. The multichromophore according to claim 79, wherein CP₁, CP₂ and CP₃ are each substituted with —

R³—

C and —

R⁴-D wherein;

R³ and R⁴ are independently selected from C1-22 alkyl, C1-22 alkoxy and polyalkylene oxide having from 1 to about 22 carbon atoms and C and D are each H.

81. The multichromophore according to claim 79, wherein CP₁, CP₂ and CP₃ are each substituted with one or more groups selected from —

R³—

C and —

R⁴-D that are attached through a bridging functional group wherein;

R³ and R⁴ are independently selected from C1-22 alkyl, C1-22 alkoxy and polyalkylene oxide having from 1 to about 22 carbon atoms and C and D are each H; and

the bridging functional group is selected from —

O—

, —

S—

, —

C(O)—

, —

C(O)O—

, —

C(R)(R′

)—

, —

N(R′

)—

, and —

Si(R′

)(R″

)—

, wherein R, R′ and

R″

are selected from hydrogen, C1-12 alkyl and C1-12 alkoxy.

82. The multichromophore according to claim 81, wherein the bridging functional group is —

Si(R′

)(R″

)—

.