Apparatus and method for using fiducial marks on a microarray substrate

• US 6,362,004 B1
• Filed: 11/09/1999
• Issued: 03/26/2002
• Est. Priority Date: 11/09/1999
• Status: Expired due to Term

• Current Assignee: Packard Instrument Co., Inc. (Revvity, Inc.)
• Original Assignee: Packard Biochip Technologies LLC
• Inventors: Noblett, David
• Primary Examiner(s): Drodge, Joseph W.
• Application Number:
  US09/436,974
• Time in Patent Office: 868 Days
• Field of Search: 422/63, 422/65, 422/82.05, 422/82.08, 422/99, 422/100, 422/102, 422/104, 436/43, 436/47, 436/56, 436/164, 436/165, 436/172, 436/174, 435/287.1, 435/287.3, 356/244, 356/246, 382/128, 382/129, 382/133, 382/134
• US Class Current: 436/43
• 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 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00542 Alphanumeric characters
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• 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: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

A microarray scanning system for conducting experiments on a planar substrate includes an apparatus for translating the secured substrate in two axes, the substrate having at least one fiducial mark on the planar substrate as a means for positioning and aligning the substrate for subsequent spot placement, analysis, or comparison procedures. The at least one fiducial mark is deposited at a predetermined position relative to the at least one location of a corresponding microarray of test spots or samples.

Claims

1. A microarray sample suitable for use in a microarray analyzer, said microarray sample comprising:

a planar substrate comprising a sample surface;

a plurality of target spots disposed on said sample surface at at least one location; and

a fiducial mark disposed on said sample surface, said fiducial mark located at a predetermined position relative to the at least one location of said plurality of target spots.

2. The microarray sample of claim 1 wherein said planar substrate comprises a microscope slide.

3. The microarray sample of claim 1 wherein said target spot comprises a genetic material.

4. The microarray sample of claim 1 wherein said fiducial mark comprises genetic material.

5. The microarray sample of claim 1 wherein said first fiducial mark comprises a geometric shape.

6. The microarray sample of claim 1 further comprising a second fiducial mark that is located a predetermined position relative to the location of said plurality of target spots.

7. The microarray sample of claim 6 wherein said second fiducial mark comprises at least one of the group consisting of an imprinted geometric shape, imprinted lettering, an etched region, and a predetermined mark discernible by an imaging system of the microarray analyzer.

8. The microarray sample of claim 1 wherein said fiducial mark comprises genetic material that responds to various materials used to test said target spots.

9. A microarray scanning system for conducting one or more sets of experiments on a planar substrate, said system comprising:

means for securing the substrate;

means for translating the substrate in two axes;

means for applying at least one fiducial mark onto the planar surface at a predetermined position relative to a location of an array of target spots; and

means for applying the array of target spots at said location on said substrate.

10. The microarray scanning system of claim 9 further comprising:

detection means for detecting said at least one fiducial mark; and

computational means for assigning coordinates to said at least one fiducial mark.

11. The microarray scanning system of claim 10 further including means for aligning multiple images of said samples using said fiducial marks.

12. The method of claim 11 wherein the step of aligning includes applying X- and Y-offsets and rotations to said images to minimize the distance between said respective fiducial marks.

13. A method for performing a series of measurements on a microarray of samples disposed on a substrate, said method comprising the steps of:

A. locating at least one fiducial mark on the substrate, said fiducial mark being at a predetermined position relative to a location of the samples;

B. aligning the microarray to a standard coordinate system using said at least one fiducial mark;

C. irradiating at least one of the samples with a source of optical excitation radiation so as to produce at least one fluorescent emission;

D. optically detecting said at least one fluorescence emission; and

E. storing said detection event in a retrievable storage medium.

14. The method of claim 13 further comprising the steps of:

irradiating said at least one sample with a second source of optical excitation radiation so as to produce at least a second fluorescent emission;

optically detecting said second fluorescence emission; and

storing said second detection event in said retrievable storage medium.

15. The method of claim 13 further including the steps of

performing steps A-E with one or more of a plurality of microarrays of samples;

and

aligning images of said microarrays based on the positions of said respective fiducial marks.

16. The method of claim 13 further including the steps of performing steps A-E with one or more of a plurality of microarrays of samples;

and

registering features in images of said microarrays based on the relative positions of said fiducial marks.

17. A microarray scanning system for conducting one or more sets of experiments on a planar substrate, said system comprising:

a positioning sub-system that positions the substrate by translating the substrate in two axes;

a spot placement sub-system that deposits material on the substrate, the spot placement sub-system depositing material comprising target spots deposited at at least one location and at least one fiducial mark, with the at least one fiducial mark located at at least one predetermined position relative to the at least one location of an array of the target spots.