Signal amplified biological detection with conjugated polymers

• US 8,969,509 B2
• Filed: 06/25/2010
• Issued: 03/03/2015
• Est. Priority Date: 06/26/2009
• Status: Active Grant

• Current Assignee: Sirigen, Inc. (Becton, Dickinson & Co), National University of Singapore
• Original Assignee: Sirigen, Inc. (Becton, Dickinson & Co)
• Inventors: Liu, Bin, Wang, Chun, Zhan, Ruoyu, Bartholomew, Glenn P., Hong, Janice W., Wheeler, Jean M., Gaylord, Brent S.
• Primary Examiner(s): Truong, Duc
• Application Number:
  US13/378,989
• Publication Number:
  US 20120252986A1
• Time in Patent Office: 1,712 Days
• Field of Search: 528/392, 528/425
• US Class Current: 528/392
• CPC Class Codes: C08G 2261/3142 fluorene-based, e.g. fluorene, indenofluorene, or spirobifluorene
• CPC Class Codes: C08G 2261/3422 conjugated, e.g. PPV-type
• CPC Class Codes: C08G 2261/5222 electrofluorescent
• CPC Class Codes: C08G 61/02 Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes

Abstract

The devices and method are provided for detecting labeled and label-free analytes, such as nucleic acids and proteins, employing conjugated cationic, anionic and neutral polymers. The analytes can be immobilized on a solid support material. The solid support material can be disposed in the pre-fabricated patterns on a substrate. The chemical structures of the polymers employed by the various embodiments of the present invention are described herein.

Claims

1. A polymer represented by the following formula:

2. The polymer of claim 1, comprising a repeat unit represented by the following formula:

3. The polymer of claim 2, wherein G¹ and G^1′

, are each independently, —

SHR⁺, SR₂⁺, —

NH₃⁺, —

NH₂R⁺, —

NHR₂⁺ or —

NR₃⁺ with an associated counterion.

4. The polymer of claim 3, wherein each R⁶ and each R⁷ is hydrogen.

5. The polymer of claim 4, wherein each R⁵ is hydrogen.

6. The polymer of claim 3, wherein L¹ and L^1′

, are each independently, a C1-C12 alkylene or —

Y₁-[O—

Y₂]_p—

.

7. The polymer of claim 6, wherein L¹ and L^1′

, are each independently —

Y₁-[O—

Y₂]_p—

, and Y₁ and Y₂ are each independently, a C1-C12 alkylene.

8. The polymer of claim 6, wherein L¹ and L^1′

, are each independently a C1-C12 alkylene.

9. The polymer of claim 8, wherein G¹ and G^1′

, are each independently —

NH₃⁺, —

NH₂R⁺, —

NHR₂⁺ or —

NR₃⁺.

10. The polymer of claim 1, comprising a repeat unit represented by the following formula:

11. The polymer of claim 1, comprising a repeat unit represented by the following formula:

12. The polymer of claim 1, comprising a repeat unit represented by the following formula:

13. The polymer of claim 1, wherein E, for each occurrence, is independently represented by formula (VI):

14. The polymer of claim 1, wherein E, for each occurrence, is independently selected from the group consisting of a-h having the structure

19. The polymer of claim 1, wherein A, for each occurrence, is independently represented by:

20. The polymer of claim 1, wherein the polymer is further covalently attached to a dye, antibody, nucleic acid, substrate or biomolecule or combination thereof.

21. The polymer of claim 1, wherein E, for each occurrence, is independently an aryl group optionally substituted with a reactive group or a pendent reactive group capable of undergoing chain extension, conjugation, or crosslinking.

15. A method of preparing a polymer represented by formula (I), comprising reacting a compound of formula (II)

Br-{circle around (A)}-Br 

 

(II),

with a compound of formula (III)

16. The method of claim 15, wherein:

the compound of formula (II) is represented by the following formula

17. The method of claim 15, wherein E, for each occurrence, is independently represented by formula (VI):

18. The method of claim 15, wherein E, for each occurrence, is independently selected from the group consisting of a-k having the structure