Optical disk-based assay devices and methods

• US 20020106661A1
• Filed: 07/23/2001
• Published: 08/08/2002
• Est. Priority Date: 07/08/1996
• Status: Abandoned Application

• Current Assignee: Nagaoka & Co., Ltd.
• Original Assignee: Burstein Laboratories Incorporated
• Inventors: Virtanen, Jorma
• Application Number:
  US09/911,253
• Publication Number:
  US 20020106661A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00585 Parallel 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 2219/00619 using hydrophilic or hydrophobic regions
• 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 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• 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 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6834 : Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: C40B 80/00 : Linkers or spacers specially adapted for combinatorial chemistry or libraries, e.g. traceless linkers or safety-catch linkers
• CPC Class Codes: G01N 33/531 : Production of immunochemical test materials
• CPC Class Codes: G01N 33/54353 : with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/553 : Metal or metal coated
• CPC Class Codes: G01N 33/56988 : HIV or HTLV
• CPC Class Codes: G01N 33/5767 : non-A, non-B hepatitis
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk

Abstract

Optical disk-based assay devices and methods are described, in which analyte-specific signal elements are disposed on an optical disk substrate. In preferred embodiments, the analyte-specific signal elements are disposed readably with the disk'"'"'s tracking features. Also described are cleavable signal elements particularly suitable for use in the assay device and methods. Binding of the chosen analyte simultaneously to a first and a second analyte-specific side member of the cleavable signal element tethers the signal-responsive moiety to the signal element'"'"'s substrate-attaching end, despite subsequent cleavage at the cleavage site that lies intermediate the first and second side members. The signal responsive moiety reflects, absorbs, or refracts incident laser light. Described are nucleic acid hybridization assays, nucleic acid sequencing, immunoassays, cell counting assays, and chemical detection. Adaptation of the assay device substrate to function as an optical waveguide permits assay geometries suitable for continuous monitoring applications.

Claims

1. A cleavable signal element, comprising:

a cleavable spacer, said cleavable spacer having a substrate-attaching end, a signal-responsive end, and a cleavage site intermediate said substrate-attaching end and said signal responsive end;

a signal responsive moiety;

a first side member adapted to bind a first site on a chosen analyte; and

a second side member adapted to bind a second site of said chosen analyte;

wherein said signal responsive moiety is attached to said cleavable spacer at said signal responsive end, said first side member is attached to said cleavable spacer intermediate said signal responsive end and said cleavage site, and said second side member is attached to said cleavable spacer intermediate said cleavage site and said substrate attaching end.

2. The cleavable signal element of claim 1, wherein said signal responsive moiety is adapted to reflect or scatter incident light.

3. The cleavable signal element of claim 2, wherein said signal responsive moiety is a metal microsphere.

4. The cleavable signal element of claim 3, wherein said metal microsphere consists essentially of a metal selected from the group consisting of gold, silver, nickel, platinum, chromium and copper.

5. The cleavable signal element of claim 4, wherein said metal microsphere consists essentially of gold.

6. The cleavable signal element of claim 5, wherein said gold microsphere has a diameter between 1 nm-10 μ

m.

7. The cleavable signal element of claim 6, wherein said gold microsphere has a diameter between 0.5-5 μ

m.

8. The cleavable signal element of claim 7, wherein said gold microsphere has a diameter between 1-3 μ

m.

9. The cleavable signal element of claim 1, wherein said cleavage site is susceptible to chemical cleavage.

10. The cleavable signal element of claim 9, wherein said chemically susceptible cleavage site includes at least one siloxane group.

11. The cleavable signal element of claim 1, wherein said first side member and said second side member include oligonucleotides.

12. The cleavable signal element of claim 11, wherein said first and second side member oligonucleotides are 5 mers-20 mers.

13. The cleavable signal element of claim 12, wherein said first and second side member oligonucleotides are 8 mers-17 mers.

14. The cleavable signal element of claim 12, wherein said first and second side member oligonucleotides are 8 mers-12 mers.

15. The cleavable signal element of claim 1, wherein

said first side member includes a first member of a first specific binding pair,

said second side member includes a first member of a second specific binding pair, and

said second member of said first specific binding pair and said second member of said second specific binding pair are each present on the surface of a single analyte.

16. The cleavable signal element of claim 15, wherein said first member of said first specific binding pair includes a first antibody, antibody fragment, or antibody derivative, and said first member of said second specific binding pair includes a second antibody, antibody fragment, or antibody derivative.

17. The cleavable signal element of claim 15, wherein

said first side member includes a first side member oligonucleotide,

said second side member includes a second side member oligonucleotide,

said first member of said first specific binding pair includes a first binding pair oligonucleotide,

said first member of said second specific binding pair includes a second binding pair oligonucleotide, and

said first side member oligonucleotide includes sequence complementary to sequence included in said first binding pair oligonucleotide, said second side member oligonucleotide includes sequence complementary to sequence included in said second binding pair oligonucleotide, and said complementary sequences are noncovalently associated.

19. The assay device of claim 18, wherein said analyte-specific signal elements are cleavable.

20. An assay device for detecting analyte, comprising:

an optical disk having analyte-specific signal elements disposed readably thereon, wherein said analyte-specific signal elements are cleavable signal elements according to any one of claims 1-17.

21. A method of assaying for analyte, comprising the steps of:

contacting the assay device of claim 18 with a sample, and then

detecting, using an optical disk reader, analyte-specific signals therefrom.

22. A method of assaying for analyte, comprising the steps of:

contacting the assay device of claim 19 with a sample;

cleaving said cleavable signal elements; and

then

detecting the signal responsive moiety of analyte-restrained cleaved signal elements.

24. A method of using an optical disk reader to assay for analyte, comprising the step of detecting, from the assay device of claim 18, analyte-specific signals.

25. A method of using an optical disk reader to assay for analyte, comprising the step of detecting, from the assay device of claim 19, analyte-specific signals.

27. The method of claim 26, wherein said analyte-specific signal elements are cleavable signal elements.

29. The monitoring device of claim 28, wherein said analyte-specific signal elements are disposed readably with said disk'"'"'s tracking features.

30. The monitoring device of claim 28, wherein said analyte-specific signal elements are cleavable signal elements.

31. A monitoring device, comprising:

an optical disk having a plurality of analyte-specific signal elements, wherein said optical disk is adapted to function as an optical waveguide and said analyte-specific signal elements are so disposed that specific binding of analyte detectably alters the light-transmitting properties of said optical waveguide, wherein said analyte-specific signal elements are cleavable signal elements according to claim 1.

32. A method of monitoring for presence of analyte, comprising:

contacting the monitoring device of claim 28 with a sample, and then detecting alterations in the light-transmitting properties of said monitoring device'"'"'s optical waveguide.

33. A method of monitoring for presence of analyte, comprising:

contacting the monitoring device of claim 30 with a sample;

detecting alterations in the light-transmitting properties of said monitoring device'"'"'s optical waveguide;

cleaving said signal elements; and

then

detecting the signal responsive moiety of analyte-restrained cleaved signal elements.

18. An assay device for detecting analyte, comprising:

an optical disk having analyte-specific signal elements disposed readably thereon.

23. A method of using an optical disk reader to assay for analyte, comprising the step of detecting, from an optical disk, analyte-specific signal elements disposed readably with said disk'"'"'s tracking features.

26. A method of making an assay device for detecting analyte, comprising:

disposing analyte-specific signal elements on an optical disk readably with said disk'"'"'s tracking features.

28. A monitoring device, comprising:

an optical disk having a plurality of analyte-specific signal elements, wherein said optical disk is adapted to function as an optical waveguide and said analyte-specific signal elements are so disposed that specific binding of analyte detectably alters the light-transmitting properties of said optical waveguide.