Automated information processing in randomly ordered arrays

• US 20020150909A1
• Filed: 08/09/2001
• Published: 10/17/2002
• Est. Priority Date: 02/09/1999
• Status: Abandoned Application

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Haas, Juergen, Chee, Mark S., Stuelpnagel, John R., Dickinson, Todd A., Kermani, Bahram G.
• Application Number:
  US09/925,941
• Publication Number:
  US 20020150909A1
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00572 Chemical means
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• 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 2219/00689 using computers
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• 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: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6484 : Optical fibres
• 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 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/7703 : using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G06T 2207/10056 : Microscopic image
• CPC Class Codes: G06T 2207/30072 : Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 7/254 : involving subtraction of images
• CPC Class Codes: G06T 7/74 : involving reference images or patches

Abstract

The invention relates to the use of a computer system to compare images generated from a randomly ordered array. This system preserves the relative position of each site within the array so that the same site can be compared in different images.

Claims

1. A method of determining the presence of a target analyte in a sample comprising:

a) acquiring a first data image of a random array composition comprising;

i) a substrate with a surface comprising discrete sites; and

ii) a population of microspheres comprising at least a first and a second subpopulation each comprising a bioactive agent;

wherein said microspheres are distributed on said surface such that each of said discrete sites contain no more than 1 microsphere;

b) mapping a grid onto said first data image to create a registered first data image;

c) contacting said random array composition with said sample;

d) acquiring a second data image from said array with said sample;

e) mapping a grid onto said second data image to create a registered second data image; and

f) comparing said first and said second registered data images to determine the presence or absence of said target analyte.

2. A method according to claim 2 wherein said discrete sites are wells.

3. A method according to claim 38 wherein said bioactive agents are proteins.

4. A method according to claim 38 wherein said bioactive agents are nucleic acids.

5. A method of signal pre-processing comprising:

a) acquiring a first data image of a random array composition comprising;

i) a substrate with a surface comprising discrete sites; and

ii) a population of microspheres comprising at least a first and a second subpopulation each comprising a bioactive agent;

wherein said microspheres are distributed on said surface such that said discrete sites contain microspheres;

b) determining the similarity of a first signal from at least one discrete site to at least one reference signal, wherein when said first signal is similar to at least one of said reference signals, said at least one discrete site contains a bead.

6. A method according to claim 5, wherein said determining comprises obtaining said first signal from said at least one discrete site and comparing said first signal to a threshold similarity measure obtained by comparing a reference signal to a theoretical signal, wherein when said first signal is within said threshold similarity measure, said first discrete site contains a bead.

7. A method according to claim 6 wherein when said first signal is not within said threshold similarity measure, said first discrete site does not contain a bead.

8. A method according to claim 7 wherein when said first signal is not within said threshold similarity measure, said first discrete site contains a defective bead.

9. A method according to claim 7 or 8 further comprising disregarding said discrete site wherein said first signal is not within said threshold similarity measure.

10. A method according to claim 5 wherein when said first signal is within said threshold similarity measure, said first discrete site contains a bead that comprises an optical signature that is similar to said reference signal.