IP Library Granted Patent US 7,164,533
Granted Patent B2
US 7,164,533 · App. 10/763,995 · Granted Jan 16, 2007

Hybrid random bead/chip based microarray

Assignee: CyVera Corporation
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Quick Facts
Patent No.
US 7,164,533
App. No.
10/763,995
Granted
Jan 16, 2007
Kind
B2
Abstract

A method and apparatus f or performing an assay process, featuring providing microbeads in a solution; placing the microbeads on an alignment substrate; reading codes of the microbeads and the position thereof on the alignment substrate; reading the fluorescence on each microbead and the position order thereof on the alignment substrate; and determining an assay result based on bead position order and bead code of the earlier reading steps, where the microbead is an encoded particle having a particle substrate; a portion of the substrate being made of a substantially single material and having at least one diffraction grating embedded therein, the grating having a resultant refractive index variation within the single material at a grating location; and the grating providing an optical output signal indicative of a code when illuminated by an incident light signal propagating from outside said substrate, the optical output signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light signal.

Claims (38)

1. Apparatus for reading microbeads that form part of an assay process, comprising:

an alignment substrate for receiving the microbeads thereon; and

a bead mapper for reading codes of the microbeads and the position order thereof on the alignment substrate,

wherein the microbead is an encoded particle and comprises:

a particle substrate;

at least a portion of said substrate being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within said single material at a grating location; and

said grating providing an optical output signal indicative of a code when illuminated by an incident light signal propagating from outside said substrate, said optical output signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light signal.

2. The apparatus of claim 1 , wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

3. The apparatus of claim 1 , wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

4. The apparatus of claim 1 , wherein said substrate is made of a material selected from the group: glass, silica, plastic, rubber, and polymer.

5. The apparatus of claim 1 , wherein said code comprises at least a predetermined number of digital bits, said number being: 3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

6. The apparatus of claim 1 , wherein said code comprises a plurality of bits, each bit having a corresponding spatial location in said optical output signal and each bit in said code having a value related to the intensity of said output optical signal at the spatial location of each bit.

7. The apparatus of claim 1 , wherein said substrate has a length that is less than a predetermined value, said value being about 30, 65, 80, 125, 250, 500, 750 or 1000 microns.

8. The apparatus of claim 1 , wherein said substrate has a diameter that is less than a predetermined value, said value being about 30, 65, 80, 125, 250, 500, 750 or 1000 microns.

9. The apparatus of claim 1 , wherein at least a portion of said substrate has a 3-D shape selected from the group: a cylinder, a sphere, a cube, and a pyramid.

10. A method of performing an assay process, comprising the steps of:

providing microbeads in a solution;

placing the microbeads on an alignment substrate;

reading codes of the microbeads and the position thereof on the alignment substrate;

reading the fluorescence on each microbead and the position order thereof on the alignment substrate; and

determining an assay result based on bead position order and bead code of the earlier reading steps;

wherein the microbead is an encoded particle and comprises:

a particle substrate;

at least a portion of said substrate being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within said single material at a grating location; and

said grating providing an optical output signal indicative of a code when illuminated by an incident light signal propagating from outside said substrate, said optical output signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light signal.

11. The method of claim 10 , wherein the fluorescence reading step is performed before the code reading step.

12. The method of claim 10 , wherein the method comprises hybridizing the microbeads with a sample in the solution.

13. The method of claim 12 , wherein the hybridizing step is performed, between the providing step and placing step.

14. The method of claim 12 , wherein the hybridizing step is performed between the placing step and the reading codes step.

15. The method of claim 12 wherein the hybridization step is performed between the reading codes step and reading fluorescence step.

16. The method of claim 10 , wherein the refractive index variation comprises at least one refractive index pitch superimposed at a grating location.

17. The method of claim 10 , wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

18. The method of claim 10 , wherein said substrate is made of a material selected from the group: glass, silica, plastic, rubber, and polymer.

19. The method of claim 10 , wherein said code comprises at least a predetermined number of digital bits, said number being: 3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

20. The method of claim 10 , wherein said code comprises a plurality of bits, each bit having a corresponding spatial location in said optical output signal and each bit in said code having a value related to the intensity of said output optical signal at the spatial location of each bit.

21. The method of claim 10 , wherein said substrate has a length that is less than a predetermined value, said value being about 30, 65, 80, 125, 250, 500, 750 or 1000 microns.

22. The method of claim 10 , wherein said substrate has a diameter that is less than a predetermined value, said value being about 30, 65, 80, 125, 250, 500, 750 or 1000 microns.

23. The apparatus of claim 10 , wherein at least a portion of said substrate has a 3-D shape selected from the group: a cylinder, a sphere, a cube, and a pyramid.

Assignments (4)
MERGER Recorded Aug 25, 2010
From: CYVERA CORPORATION
To: ILLUMINA, INC.
Reel/Frame 024879/0384 →
CORRECTING CONFIRMATION OF UNDERSTANDING ASSIGNOR/ASSIGNEE PREVIOUSLY RECORDED AT REEL/FRAME 016660/0237. Recorded Oct 13, 2006
From: ILLUMINA, INC.
To: CYVERA CORPORATION
Reel/Frame 018430/0465 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 19, 2005
From: CYVERA CORPORATION
To: ILLUMINA, INC.
Reel/Frame 016660/0237 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 23, 2004
From: MOON, JOHN; KERSEY, ALAN D.; PUTNAM, MARTIN; LI, TUO
To: CYVERA CORPORATION
Reel/Frame 015714/0618 →
Continuity (6)
Continuation In Part 1066123400 · Sep 12, 2003
Continuation In Part 1066103100 · Sep 12, 2003
Continuation In Part 1066183600 · Sep 12, 2003
Provisional Application 6051993200 · Nov 14, 2003
Provisional Application 6044167800 · Jan 22, 2003
Related Publication 20040263923A1 · Dec 30, 2004