Method, chip, device and system for effecting and monitoring nucleic acid accumulation

• US 6,465,241 B2
• Filed: 12/14/2000
• Issued: 10/15/2002
• Est. Priority Date: 09/21/1998
• Status: Expired due to Fees

• Current Assignee: Ramot University Authority For Applied Research and Industrial Development Limited
• Original Assignee: Ramot University Authority For Applied Research and Industrial Development Limited
• Inventors: Haronian, Dan, Nathan, Menachem, Gershoni, Jonathan M., Yaron, Arieh
• Primary Examiner(s): Whisenant, Ethan C.
• Assistant Examiner(s): LU, FRANK WEI MIN
• Application Number:
  US09/735,799
• Publication Number:
  US 20020061519A1
• Time in Patent Office: 670 Days
• Field of Search: 435/6, 435/91.1, 435/183, 435/283.1, 435/287.1, 435/287.2, 436/94, 536/23.1, 536/24.3, 536/24.33, 536/25.3, 536/25.32, 422/50, 422/55, 422/68.1, 422/82.05, 422/82.09, 422/82.11
• US Class Current: 435/287.2
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: G01N 21/25 Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B

Abstract

A nucleic acid accumulation analyzing chip comprising an optical waveguide having a radiation input port and a radiation output port, the optical waveguide being formed with at least one optical microcavity along its optical path, at least one oligonucleotide being immobilized to the optical waveguide in the microcavity, such that when the at least one oligonucleotide is contacted with reaction reagents under conditions allowing a nucleic acid accumulation reaction to take place, accumulated nucleic acid is detectable by providing radiation at the radiation input port of the optical waveguide and monitoring radiation signal modulation at the radiation output port of the optical waveguide.

Claims

1. A nucleic acid accumulation analyzing chip comprising:

i. an first optical waveguide having a radiation input port and a radiation output port;

ii. at least one optical microcavity having a bottom face, said at least one optical microcavity placed in said first optical waveguide along its optical path; and

iii. at least one oligonucleotide being immobilized to said bottom face of said optical microcavity, such that when said at least one oligonucleotide is contacted with reaction reagents under conditions allowing a nucleic acid accumulation reaction to take place, accumulated nucleic acid is detectable by providing radiation at said radiation input port of said optical waveguide and monitoring radiation signal modulation at said radiation output port of said first optical waveguide.

2. The nucleic acid accumulation analyzing chip of claim 1, wherein said first optical waveguide is of Si₃N₄.

3. The nucleic acid accumulation analyzing chip of claim 2, further comprising a support layer supporting said first optical waveguide, said support layer effecting said bottom face of said optical microcavity.

4. The nucleic acid accumulation analyzing chip of claim 3, wherein said support layer is of SiO₂.

5. The nucleic acid accumulation analyzing chip of claim 3, further comprising a foundation layer supporting said support layer, said foundation layer capable of serving as a resistor layer deployed in heat transfer relation with said optical microcavity, said resistor layer being for providing said optical microcavity with heat for generating said conditions allowing said nucleic acid accumulation reaction to take place.

6. The nucleic acid accumulation analyzing chip of claim 5, wherein said foundation layer includes a material selected from the group consisting of doped silicon, chromium, titanium-tungsten and tungsten.

7. The nucleic acid accumulation analyzing chip of claim 5, further comprising a base layer supporting said foundation layer.

8. The nucleic acid accumulation analyzing chip of claim 5, wherein said base layer includes a material selected from the group consisting of silicon and glass.

9. The nucleic acid accumulation analyzing chip of claim 1, wherein said optical microcavity has a volume in a range of about 1 to about 10 cubic micrometers.

10. The nucleic acid accumulation analyzing chip of claim 1, wherein said at least one oligonucleotide is immobilized to said bottom face of said optical microcavity in a surface density of between about 10³ oligonucleotide molecules per square micrometer and about 10⁶ oligonucleotide molecules per square micrometer.

11. The nucleic acid accumulation analyzing chip of claim 1, wherein said nucleic acid accumulation reaction is selected from the group consisting of polymerase chain reaction, ligase chain reaction, nucleic acid sequence based amplification and nucleic acid hybridization.

12. The nucleic acid accumulation analyzing chip of claim 1, further comprising a second optical waveguide aligned with said first optical waveguide in a Mach-Zender configuration, wherein said nucleic acid accumulation takes place only in said optical microcavity of said first optical waveguide, and wherein said second optical waveguide serves as reference.