Hybrid random bead/chip based microarray

• US 7,659,983 B2
• Filed: 11/30/2006
• Issued: 02/09/2010
• Est. Priority Date: 01/22/2003
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Electronics and Telecommunications Research Institute
• Inventors: Kersey, Alan D., Li, Tuo, Putnam, Martin A., Moon, John A.
• Primary Examiner(s): Geisel; Kara E
• Application Number:
  US11/607,837
• Publication Number:
  US 20080129990A1
• Time in Patent Office: 1,167 Days
• Field of Search: 356/317, 356/246, 356/417, 356/244
• US Class Current: 356/417
• 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
• 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 for performing an assay process, featuring providing microbeads in a solution, each microbead having a particle substrate with a grating with a superposition of different predetermined regular periodic variations of the index of refraction disposed in the particle along a grating axis and indicative of a code; 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.

Claims

1. A method of identifying an analyte, the method comprising:

providing a plurality of microparticles, the microparticles having elongated bodies with optically detectable codes extending along the bodies of the corresponding microparticle, the microparticles having chemical probes attached thereto, each of the chemical probes being associated with a corresponding one of the codes;

exposing the microparticles to a target analyte that selectively binds to a chemical probe on at least one of the microparticles, wherein an optically detectable label on the at least one microparticle indicates that the target analyte binds to the chemical probe;

providing the microparticles in a random manner on a substrate;

determining the codes for the microparticles provided on the substrate and code positions of the codes on the substrate;

detecting the label on the at least one microparticle and a label position of the label on the substrate; and

using the code positions and the label positions to analyze the target analyte.

2. The method in accordance with claim 1 wherein the code determining and label detecting operations are conducted in an automated manner.

3. The method in accordance with claim 1 wherein the label is a fluorescent label and the detecting operation includes capturing at least one image of fluorescent optical output emanating from the microparticles on the substrate.

4. The method of claim 1 wherein the determining operation includes capturing at least one image of an optical output indicative of the codes for the microparticles.

5. The method of claim 1, wherein the determining operation includes capturing at least one image having illuminated strips indicative of digital patterns associated with the codes for the microparticles.

6. The method in accordance with claim 1 wherein providing the microparticles on the substrate includes flowing the microparticles onto the substrate within a solution, the microparticles falling onto the substrate in a random distribution.

7. The method in accordance with claim 1 further comprising holding the microparticles on a flat surface of the substrate.

8. The method in accordance with claim 1 wherein the substrate includes a plurality of grooves, the method further comprising orienting the elongated bodies of the microparticles within the grooves, the microparticles being randomly distributed within the grooves.

9. The method in accordance with claim 1 wherein the microparticles are rectangular and have a substantially square cross-sectional shape.

10. The method in accordance with claim 1 wherein the microparticles have an inner region and an outer region that surrounds the inner region, the inner region extending along a longitudinal axis of the microparticles and being located at a center of the microparticle, the code being within the inner region.

11. The method in accordance with claim 1 wherein the code is completely surrounded by a transparent material and extends along a longitudinal axis of the microparticle such that the code is determinable from any direction about the longitudinal axis.

12. The method in accordance with claim 1 wherein the code comprises at least one grating, wherein the grating is one of written, impressed, embedded, imprinted, etched, grown, and deposited within the microparticle.

13. The method in accordance with claim 9 wherein the code comprises a digital code formed from a series of bits arranged proximate to one another along a longitudinal axis of the microparticle, the determining operation includes reading the series of bits.

14. The method in accordance with claim 1 wherein the label is a fluorescent label.

15. An apparatus for identifying an analyte, the apparatus comprising:

a substrate configured to randomly receive a plurality of microparticles, the microparticles having elongated bodies with optically detectable codes extending along the bodies of the corresponding microparticle, the microparticles having chemical probes attached thereto, each of the chemical probes being associated with a corresponding one of the codes, at least one of the microparticles comprising an optically detectable label indicating that a target analyte selectively binds to the chemical probe attached to the microparticle;

a code mapper to determine the codes for the microparticles provided on the substrate, the code mapper determining code positions for each of the codes on the substrate;

a scanner to detect the label on the at least one microparticle, the scanner detecting a label position of the label on the substrate; and

an assay analysis module to use the code positions and the label positions to analyze the target analyte.

16. The apparatus of claim 15, further comprising memory storing a code table that correlates the codes to corresponding chemical probes, the code mapper determining which chemical probes are attached to the microparticles based on the correlation stored in the code table.

17. The apparatus of claim 15, further comprising memory storing a label table that correlates multiple labels to corresponding target analytes, the scanner determining information about the target analyte based on the label table.

18. The apparatus of claim 15, wherein the label is a fluorescent label and the apparatus further comprises an optical excitation source that directs an optical excitation signal onto the microparticles to cause fluorescent optical outputs to emanate from the at least one microparticle having the target analyte bound thereto.

19. The apparatus of claim 15, wherein the label is a fluorescent label and the scanner includes a detector that captures at least one image of fluorescent optical output emanating from the microparticles on the substrate.

20. The apparatus of claim 15, wherein the code mapper includes a detector to capture at least one image of an optical output indicative of the codes for the microparticles.

21. The apparatus of claim 15, wherein the substrate constitutes at least one of a plate, chip, tray and slide.

22. The apparatus of claim 15, wherein the substrate holds the microparticles on a flat surface.

23. The apparatus of claim 15, wherein the substrate includes a plurality of grooves that receive the microparticles to orient the elongated bodies of the microparticles within the grooves, the microparticles being randomly distributed within the grooves.

24. The apparatus of claim 15, wherein the substrate includes a plurality of grooves that are arranged parallel with respect to one another.

25. The apparatus of claim 15, further comprising an agitating assembly to agitate the substrate to align the microparticles in a desired orientation.

26. The apparatus of claim 15, wherein the substrate includes multiple grooves, the grooves having at least one of a square shape, a rectangular shape, a V-shape and a semi-circular shape.

27. The apparatus of claim 15, further comprising a sonic transducer, a mechanical wipe or a shaking device to agitate the substrate.

28. The apparatus of claim 15 further comprising a source light configured to illuminate the microparticles, the microparticles providing an optical output for determining the code and code positions and the at least one microparticle providing an optical output for detecting the label and label position.

29. The apparatus of claim 28 further comprising at least one detector, wherein the source light includes first and second optical excitation sources and the at least one detector receives the optical outputs.

30. The apparatus of claim 28 further comprising first and second detectors, the source light including at least one optical excitation source for illuminating the microparticles, the first and second detectors receiving the optical outputs.

31. The apparatus of claim 28, wherein the source light includes an optical excitation source for determining the code and code positions and an optical excitation source for detecting the label and label position.