Hybrid random bead/chip based microarray

• US 7,164,533 B2
• Filed: 01/22/2004
• Issued: 01/16/2007
• Est. Priority Date: 01/22/2003
• Status: Expired due to Term

• Current Assignee: Illumina Incorporated
• Original Assignee: CyVera Corporation (Illumina Incorporated)
• Inventors: Kersey, Alan D., Li, Tuo, Putnam, Martin A., Moon, John
• Primary Examiner(s): Lavarias; Arnel C.
• Application Number:
  US10/763,995
• Publication Number:
  US 20040263923A1
• Time in Patent Office: 1,090 Days
• Field of Search: 359/2, 359/566, 359/569, 359/558, 359/571, 359/572, 359/72, 356/72, 356/73.1, 385/12, 385/128, 385/37, 250/559.04, 250/559.11, 250/559.4, 250/227.14, 250/227.29, 250/566, 250/568, 235/473, 435/4, 435/6, 435/228.7, 436/518, 436/524, 436/525, 436/526, 436/527, 436/528, 436/531
• US Class Current: 359/569
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/54306 Solid-phase reaction mechanisms
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/552 Glass or silica
• CPC Class Codes: G03H 1/0005 Adaptation of holography to specific applications holographic optical element G02B5/32; holographic scanner G02B26/106; recognition using holographic mask G06V10/88; holographic memories G11B7/0065, G11C13/042
• CPC Class Codes: G03H 1/02 Details of features involved during the holographic process; Replication of holograms without interference recording
• CPC Class Codes: G03H 1/0236 Form or shape of the hologram when not registered to the substrate, e.g. trimming the hologram to alphanumerical shape substrates bearing a hologram G03H1/0272
• CPC Class Codes: G03H 1/26 Processes or apparatus specially adapted to produce multiple sub- holograms or to obtain images from them, e.g. multicolour technique
• CPC Class Codes: G03H 2001/0033 in hologrammetry for measuring or analysing
• CPC Class Codes: G03H 2001/0044 holographic fringes deformations; holographic sensors holographic rain sensor in vehicles B60S1/084
• CPC Class Codes: G03H 2210/53 Coded object not directly interpretable, e.g. encrypted object, barcode
• CPC Class Codes: G03H 2210/63 Environment affecting the recording, e.g. underwater G03H2001/0432 takes precedence
• CPC Class Codes: G03H 2230/10 Microhologram not registered to the substrate
• CPC Class Codes: G03H 2250/12 Special arrangement of layers
• CPC Class Codes: G06K 19/04 : characterised by the shape
• CPC Class Codes: G06K 19/06009 : with optically detectable marking G06K19/063, G06K19/08 take precedence

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

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.