Hybridization of polynucleotides conjugated with chromo-phores and fluorophores to generate donor-to-donor energy transfer system

• US 6,416,953 B1
• Filed: 11/28/2000
• Issued: 07/09/2002
• Est. Priority Date: 11/07/1991
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Heller, Michael J.
• Primary Examiner(s): FREDMAN, JEFFREY NORMAN
• Application Number:
  US09/724,753
• Time in Patent Office: 588 Days
• Field of Search: 435/6, 435/91.2, 536/23.1, 536/24.3
• US Class Current: 435/6.12
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2531/113 PCR
• CPC Class Codes: C12Q 2563/107 fluorescence
• CPC Class Codes: C12Q 2565/101 Interaction between at least two labels
• CPC Class Codes: G06N 3/123 DNA computing
• CPC Class Codes: G11B 2007/24624 fluorescent dyes
• CPC Class Codes: G11B 7/244 comprising organic materials only
• CPC Class Codes: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 comprising bio-molecules
• CPC Class Codes: G11C 13/04 using optical elements ; using other beam accessed elements, e.g. electron or ion beam
• CPC Class Codes: H01L 24/95 at chip-level, i.e. with connecting carried out on a plurality of singulated devices, i.e. on diced chips
• CPC Class Codes: H01L 25/50 : Multistep manufacturing processes of assemblies consisting of devices, each device being of a type provided for in group H01L27/00 or H01L29/00 H01L21/50 takes precedence
• CPC Class Codes: H01L 2924/00 : Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/01005 : Boron [B]
• CPC Class Codes: H01L 2924/01006 : Carbon [C]
• CPC Class Codes: H01L 2924/01011 : Sodium [Na]
• CPC Class Codes: H01L 2924/01012 : Magnesium [Mg]
• CPC Class Codes: H01L 2924/01013 : Aluminum [Al]
• CPC Class Codes: H01L 2924/01019 : Potassium [K]
• CPC Class Codes: H01L 2924/0102 : Calcium [Ca]
• CPC Class Codes: H01L 2924/01023 : Vanadium [V]
• CPC Class Codes: H01L 2924/01025 : Manganese [Mn]
• CPC Class Codes: H01L 2924/01032 : Germanium [Ge]
• CPC Class Codes: H01L 2924/01033 : Arsenic [As]
• CPC Class Codes: H01L 2924/01039 : Yttrium [Y]
• CPC Class Codes: H01L 2924/01043 : Technetium [Tc]
• CPC Class Codes: H01L 2924/01044 : Ruthenium [Ru]
• CPC Class Codes: H01L 2924/01054 : Xenon [Xe]
• CPC Class Codes: H01L 2924/0106 : Neodymium [Nd]
• CPC Class Codes: H01L 2924/01074 : Tungsten [W]
• CPC Class Codes: H01L 2924/01075 : Rhenium [Re]
• CPC Class Codes: H01L 2924/01076 : Osmium [Os]
• CPC Class Codes: H01L 2924/01077 : Iridium [Ir]
• CPC Class Codes: H01L 2924/01079 : Gold [Au]
• CPC Class Codes: H01L 2924/01082 : Lead [Pb]
• CPC Class Codes: H01L 2924/12042 : LASER
• CPC Class Codes: H01L 2924/12043 : Photo diode
• CPC Class Codes: H01L 2924/14 : Integrated circuits
• CPC Class Codes: Y10S 435/80 : Elimination or reduction of contamination by undersired ferments, e.g. aseptic cultivation
• CPC Class Codes: Y10S 436/80 : Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10T 436/13 : Tracers or tags

Abstract

The present invention contemplates chromophore-containing polynucleotides having at least two donor chromophores operatively linked to the polynucleotide by linker arms, such that the chromophores are positioned by linkage along the length of the polynucleotide at a donor-donor transfer distance, and at least one fluorescing acceptor chromophore operatively linked to the polynucleotide by a linker arm, such that the fluorescing acceptor chromophore is positioned by linkage at a donor-acceptor transfer distance from at least one of the donor chromophores, to form a photonic structure for collecting photonic energy and transferring the energy to an acceptor chromophore, and methods using the photonic structures.

Claims

1. A biosensor for detecting the presence of an analyte in solution, said analyte comprising a target DNA sequence, said biosensor comprising:

an excitation source for delivering emitting photonic energy;

a donor sequence comprising a first polynucleotide having a terminal donor chromophore and at least one intermediate donor chromophore linked to said first polynucleotide by linker arms, wherein said first polynucleotide is complementary to a first region of said target DNA sequence;

an acceptor sequence comprising a second polynucleotide having at least one acceptor chromophore linked to said second polynucleotide by linker arms, wherein said second polynucleotide is complementary to a second region of said target DNA sequence;

wherein the distance between one said donor chromophore and one said acceptor chromophore is such that they are in an energy transfer relationship; and

an associated photon sensing means to detect photonic energy emitted from said acceptor.

2. The biosensor of claim 1, wherein said analyte, upon hybridization, is sufficiently close to permit detection by said photon sensing means.

3. The biosensor of claim 1, wherein at least one of said first polynucleotide, said second polynucleotide, and said target DNA sequence is bound to a solid support or matrix that is insoluble in the analyte solution.

4. The biosensor of claim 3, wherein said solid support or matrix is selected from the group consisting of glass, metals, silicon, organic polymers, membranes, and bio-polymers.

5. The biosensor of claim 1, wherein said associated photon sensor means is selected from the group consisting of a photodiode, photodiode array, photomultiplier tube, and a fiber optic detection system.

24. The biosensor of claim 1, wherein said first polynucleotide and said second polynucleotide are incorporated into a single polynucleotide strand.

25. The biosensor of claim 1, wherein said first polynucleotide and said second polynucleotide are separate polynucleotide strands.

6. An electronic device comprising:

an extended energy transfer system comprising a polynucleotide having a terminal donor chromophore, at least one intermediate donor chromophore, and at least one acceptor chromophore linked to said polynucleotide by linker arms, wherein the distance between said terminal donor chromophore and one said acceptor chromophore is such that the donor chromophore and the acceptor chromophore are in an energy transfer relationship, and there is at least one said intermediate donor chromophore; and

wherein said polynucleotide is linked to a solid support.

7. The electronic device of claim 6, wherein the solid support is selected from the group consisting of glass, metals, silicon, organic polymers, membranes, and bio-polymers.

8. The electronic device of claim 6, wherein said device is a photonic energy collector.

9. The electronic device of claim 6, wherein said device is a light amplifier.

10. The electronic device of claim 6, wherein said device is an energy transfer conduit.

11. The electronic device of claim 6, wherein the solid support is adapted to provide a complimentary function.

12. The electronic device of claim 11, wherein the function is to donate energy to the extended energy transfer system.

13. The electronic device of claim 11, wherein the function is to detect emitted photonic energy.

14. The electronic device of claim 11, wherein the function is to receive emitted photonic energy.

15. The electronic device of claim 11, wherein the function is to convert emitted photonic energy.

16. The electronic device of claim 11, wherein the function is to transmit emitted photonic energy to a second circuit.

17. The electronic device of claim 11, wherein the function is to translate emitted photonic energy.

18. The electronic device of claim 16, wherein the second circuit is a photosensor.

19. The electronic device of claim 16, wherein the second circuit is a photovoltaic cell.

20. An extended photonic energy transfer system able to communicate with an electronic circuit, said transfer system comprising:

a polynucleotide having a terminal donor chromophore, at least one intermediate donor chromophore, and at least one acceptor chromophore linked to said polynucleotide by linker arms;

wherein the distance between said terminal donor chromophore and one said acceptor chromophore is such that the donor chromophore and the acceptor chromophore are in an energy transfer relationship, and there is at least one said intermediate donor chromophore; and

wherein at least one said chromophore is adapted to convert electronic energy to photonic energy.

21. The transfer system of claim 20, wherein the chromophore adapted to convert electronic energy to photonic energy is selected from the group consisting of luminescent compounds, ruthenium complexes, and photovoltaic cells.

22. An extended photonic energy transfer system able to communicate with an electronic circuit, said transfer system comprising:

a polynucleotide having a terminal donor chromophore, at least one intermediate donor chromophore, and at least one acceptor chromophore linked to said polynucleotide by linker arms;

wherein the distance between said terminal donor chromophore and one said acceptor chromophore is such that the donor chromophore and the acceptor chromophore are in an energy transfer relationship, and there is at least one said intermediate donor chromophore; and

wherein at least one said chromophore is adapted to convert photonic energy to electronic energy.

23. The transfer system of claim 22, wherein the chromophore adapted to convert photonic energy to electronic energy is selected from the group consisting of luminescent compounds, ruthenium complexes, and photovoltaic cells.