DNA capillary

• US 6,559,296 B2
• Filed: 02/21/2001
• Issued: 05/06/2003
• Est. Priority Date: 08/29/1997
• Status: Expired due to Fees

• Current Assignee: Olympus Optical Corporation Limited (Olympus Corporation)
• Original Assignee: Olympus Optical Corporation Limited (Olympus Corporation)
• Inventors: Suyama, Akira
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): Chakrabarti, Arun K.
• Application Number:
  US09/790,061
• Publication Number:
  US 20020013457A1
• Time in Patent Office: 804 Days
• Field of Search: 435/6, 435/46, 435/288.5, 435/45, 435/47, 536/22.1, 422/102, 422/103, 156/503
• US Class Current: 536/23.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0838 : Capillaries
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/087 : Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• CPC Class Codes: B01L 2300/16 : Surface properties and coatings
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10T 436/112499 : with sample on test slide

Abstract

The present invention relates to an apparatus for detecting nucleic acid molecules such as target DNA molecules and mRNA molecules by using a DNA probe, and provides a DNA capillary, comprising a fluid passageway formed of a cylindrical capillary made of glass, a plurality of independent probe regions formed in the inner wall of the fluid passageway, and DNA probes each immobilized in the probe region, the immobilized DNA probes differing from each other. For performing the measurement, a sample is introduced through an open portion into the capillary so as to perform reaction and, then, fluorimetry.

Claims

1. A DNA capillary comprising:

at least one tubular fluid passageway for a liquid defined by a wall for transmitting light in at least a part thereof, said tubular fluid passageway extending straight on the substrate in a longitudinal direction, the cross sectional area of said tubular fluid passageway along a plane perpendicular to a fluid flowing direction being constant over the entire length of a processing region of said tubular fluid passageway, the processing region of said tubular fluid passageway producing a capillary function, said tubular fluid passageway being bent and tapered at least partially to prevent bubble generation in the liquid; and

a plurality of different kinds of DNA probes formed in an inner wall of said tubular fluid passageway, said DNA probes being immobilized in a ring-like manner to make one complete rotation along the inner wall of said tubular fluid passageway in a predetermined amount for each kind of DNA probe and independently from each other depending on the kind of DNA probe.

2. The DNA capillary according to claim 1, wherein said capillary has a plurality of said tubular fluid passageways and said tubular fluid passageways are integrally arranged.

3. The DNA capillary according to claim 1, wherein said DNA probes are immobilized by a photochemical reaction, and wherein a capping agent which is subjected to photodecomposition under irradiation with light having a predetermined wavelength is coupled with all amino groups present on the surface of the inner wall of said tubular fluid passageway.

4. The DNA capillary according to claim 1, wherein said DNA capillary has a plurality of said tubular fluid passageways, said tubular fluid passageways are integrally arranged, and said DNA probe is immobilized by a photochemical reaction.

5. The DNA capillary according to claim 1, wherein said DNA capillary has a plurality of said tubular fluid passageways, said tubular fluid passageways are integrally arranged, and all of said tubular fluid passageways communicate with a combined fluid passageway in at least distal end portions on one side.

6. The DNA capillary according to claim 1, wherein said DNA probes comprise at least 20 base sequences before the DNA probes are immobilized, and the DNA probes are immobilized in said probe regions by a single photochemical reaction.

7. The DNA capillary according to claim 1, wherein said DNA probe comprises at least 20 bases.

8. The DNA capillary according to claim 1, wherein the cross sectional shape of the tubular fluid passageway includes a curved portion.

9. The DNA capillary according to claim 1, wherein the tubular fluid passageway has a rectangular cross sectional shape having roundish corner portions.

10. The DNA capillary according to claim 1, wherein the probe regions are arranged separately from each other along the tubular fluid passageway.

11. The DNA capillary according to claim 1, wherein said probe regions are arranged about 1 μ

m to 5 mm apart from each other.

12. The DNA capillary according to claim 1, wherein the DNA capillary has an inner diameter of about 0.1 mm to about 5 mm and a length of about 5 mm to about 100 mm.

13. The DNA capillary according to claim 12, wherein the DNA capillary has an inner diameter of 0.5 mm to 1 mm.

14. A DNA capillary comprising:

a plurality of tubular fluid passageways for a liquid defined by a wall for transmitting light in at least a part thereof, said tubular fluid passageway extending straight on the substrate in a longitudinal direction, the cross sectional area of said tubular fluid passageway along a plane perpendicular to a fluid flowing direction being constant over the entire length of a processing region of said tubular fluid passageway, the processing region of said tubular fluid passageway producing a capillary function, wherein adjacent open portions are arranged deviant from each other in the fluid flowing direction, and the processing regions of all the tubular fluid passageways are equal to each other in length in the fluid flowing direction and both ends of the processing regions are aligned; and

a plurality of different kinds of DNA probes formed in an inner wall of said tubular fluid passageway, said DNA probes being immobilized in a ring-like manner to make one complete rotation along the inner wall of said tubular fluid passageway in a predetermined amount for each kind of DNA probe and independently from each other depending on the kind of DNA probe.

15. The DNA capillary of claim 14, wherein said tubular fluid passageways are bent and tapered at least partially to prevent bubble generation in the liquid.

16. The DNA capillary according to claim 14, wherein said tubular fluid passageways are integrally arranged.

17. The DNA capillary according to claim 14, wherein said DNA probes are immobilized by a photochemical reaction, and wherein a capping agent which is subjected to photodecomposition under irradiation with light having a predetermined wavelength is coupled with all amino groups present on the surface of the inner wall of said tubular fluid passageways.

18. The DNA capillary according to claim 14, wherein said tubular fluid passageways are integrally arranged, and said DNA probe is immobilized by a photochemical reaction.

19. The DNA capillary according to claim 14, wherein said tubular fluid passageways are integrally arranged, and all of said tubular fluid passageways communicate with a combined fluid passageway in at least distal end portions on one side.

20. The DNA capillary according to claim 14, wherein said DNA probes comprise at least 20 base sequences before the DNA probes are immobilized, and the DNA probes are immobilized in said probe regions by a single photochemical reaction.

21. The DNA capillary according to claim 14, wherein said DNA probe comprises at least 20 bases.

22. The DNA capillary according to claim 14, wherein the cross sectional shape of the tubular fluid passageways includes a curved portion.

23. The DNA capillary according to claim 14, wherein the tubular fluid passageways have a rectangular cross sectional shape having roundish corner portions.

24. The DNA capillary according to claim 14, wherein the probe regions are arranged separately from each other along the tubular fluid passageways.

25. The DNA capillary according to claim 14, wherein said probe regions are arranged about 1 μ

m to 5 mm apart from each other.

26. The DNA capillary according to claim 14, wherein the DNA capillary has an inner diameter of about 0.1 mm to about 5 mm and a length of about 5 mm to about 100 mm.

27. The DNA capillary according to claim 26, wherein the DNA capillary has an inner diameter of 0.5 mm to 1 mm.