Microarray dispensing with real-time verification and inspection

• US 6,558,623 B1
• Filed: 07/06/2000
• Issued: 05/06/2003
• Est. Priority Date: 07/06/2000
• Status: Expired due to Term

• Current Assignee: Agena Bioscience Inc. (Mesa Laboratories Inc.)
• Original Assignee: RoboDesign International, Inc. (Rigaku Corporation)
• Inventors: Mickley, Mandel W., Ganz, Brian L., Moulds, John Andrew, Brovold, Christopher T.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R
• Application Number:
  US09/611,256
• Time in Patent Office: 1,034 Days
• Field of Search: 422/100, 422/105, 422/63, 422/68.1, 738/630.1, 738/640.1, 738/641.1, 738/642.5, 141/119, 141/57, 141/61, 382/133, 382/134, 356/614, 356/237.1, 356/237.6
• US Class Current: 422/63
• 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 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00475 Sheets
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: C40B 60/14 : for creating libraries
• 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 1/312 : for samples mounted on planar substrates

Abstract

A microarrayer for spotting solution onto slides in an automated microarray dispensing device. Elements of the present invention include: at least one dispense head for spotting the slides, at least one light source capable of illuminating the slides, at least one camera operating in conjunction with the at least one light source. The at least one camera is capable of acquiring and transmitting slide image data to a computer. The computer is programmed to receive the slide image data and analyze it. The computer will then generate post analysis data based on the analysis of the slide image data. The post analysis data is available for improving the spotting of the solution onto the slides. In a preferred embodiment, the slide image data includes information relating to slide alignment, information relating to spot quality, and slide identification information. In a preferred embodiment, the analysis of the information relating to slide alignment enables the computer to make automatic adjustments to the relative positions of the at least one dispense head and the slides to increase the accuracy of the spotting. In a preferred embodiment, the analysis of the information relating to spot quality identifies a spot as pass or fail. An operator is then able to rework the spot. In a preferred embodiment, the analysis of the slide identification information enables the computer to track each slide.

Claims

1. A microarrayer for spotting solution onto slides, comprising:

A) at least one dispense head for spotting the slides,

B) at least one light source capable of illuminating the slides,

C) at least one camera operating in conjunction with said at least one light source, said at least one camera capable of acquiring and transmitting slide image data,

D) a computer programmed to;

1) receive said slide image data from said at least one camera,

2) analyze said slide image data, and

3) generate post analysis data based on said analysis of said slide image data, wherein said post analysis data comprises information relating to the success or failure of said microarrayer to successfully spot solution onto the slides and

E) an adjustment means for permitting adjustments to be made to said spotting of solution onto the slides, wherein said adjustments are based on said post analysis data.

2. The microarrayer as in claim 1, wherein said adjustment means is an automatic adjustment means for permitting said computer to automatically make said adjustments to said spotting of solution onto said slides.

3. The microarrayer as in claim 1, wherein said slide image data comprises information relating to slide alignment.

4. The microarrayer as in claim 1, wherein said slide image data comprises information relating to spot quality.

5. The microarrayer as in claim 4, wherein said post analysis data comprises information reporting the spot quality as pass or fail.

6. The microarrayer as in claim 5, wherein said adjustment means is a reworking means for permitting the microarrayer operator to rework a failed spot via the microarrayer based on said report of said post analysis data.

7. The microarrayer as in claim 5, wherein said adjustment means is a reworking means for permitting said computer to rework a failed spot via the microarrayer based on said report of said post analysis data.

8. The microarrayer as in claim 1, wherein said slide image data comprises slide identification information.

9. The microarrayer as in claim 8, wherein said slide identification information is contained in the slide'"'"'s 2D bar code.

10. The microarrayer as in claim 1, wherein said slide image data comprises:

A) information relating to slide alignment,

B) information relating to spot quality, and

C) slide identification information.

11. The microarrayer as in claim 1, further comprising a three axis robotic positioning stage for presentation of the slides and said at least one dispense head.

12. The microarrayer as in claim 11, wherein said three axis robotic positioning stage comprises three linear actuators.

13. The microarrayer as in claim 1, further comprising at least one cleaning station, comprising:

A) a sonic cleaner,

B) a rinsing fountain, and

C) a vacuum manifold.

14. The microarrayer as in claim 1, wherein said at least one dispense head is two dispense heads, wherein the first of said two dispense heads is a main dispense head, wherein the second of said two dispense heads is a rework dispense head.

15. The microarrayer as in claim 14, further comprising a dispense head assembly, comprising:

A) a mounting plate attached to the microarrayer via a linear actuator,

B) a pneumatic slide mounted to said mounting plate, wherein said main dispense head is mounted to said mounting plate and wherein said rework dispense head is mounted to said pneumatic slide enabling said rework dispense head to move above or below said main dispense head.

16. The microarrayer as in claim 1, wherein said camera is a CCD camera comprising a C-mount lens capable of providing the proper field of view and magnification for reading of the slides'"'"' 2D bar code and for acquiring said slide image data.

17. The microarrayer as in claim 1, further comprising a vibration isolated base pneumatically isolated from the microarrayer, wherein said vibration isolated base assists in absorbing the shock of external vibrations.

18. The microarrayer as in claim 1, wherein said computer comprises:

A) a PC based controller comprising VISUAL BASIC programming, and

B) a touch screen monitor for user interface.

19. The microarrayer as in claim 1, wherein said computer is capable of being connected to a computer network for remote monitoring and control.

20. The microarrayer as in claim 1, wherein further comprising at least one dispense tip attached to said at least one dispense head.

21. The microarrayer as in claim 1, wherein said at least one dispense tip is a quill type dispense tip.

22. The microarrayer as in claim 1, wherein said at least one dispense tip is a piezo type dispense tip.

23. The microarrayer as in claim 1, wherein said at least one light source is a strobe light.

24. The microarrayer as in claim 1, wherein said at least one light source is a fluorescence device.

25. A microarrayer for spotting solution onto slides, comprising:

A) a dispensing means for spotting the slides,

B) a light source means for illuminating the slides,

C) an image acquisition means for operating in conjunction with said light source means for acquiring and transmitting slide image data,

D) a computer programmed to;

1) receive said slide image data from said image acquisition means,

2) analyze said slide image data, and

3) generate post analysis data based on said analysis of said slide image data, wherein said post analysis data comprises information relating to the success or failure of said microarrayer to successfully spot solution onto the slides and

E) an adjustment means for permitting adjustments to be made to said spotting of solution onto the slides, wherein said adjustments are based on said post analysis data.