Microarray dispensing with real-time verification and inspection

• US 7,025,933 B2
• Filed: 05/05/2003
• Issued: 04/11/2006
• 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: Ganz, Brian L., Moulds, John Andrew, Brovold, Christopher T., Mickley, Mandel W.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R.
• Application Number:
  US10/430,157
• Publication Number:
  US 20040062686A1
• Time in Patent Office: 1,072 Days
• Field of Search: 422/63, 422/65, 422/66, 422/68.1, 422/100, 422/105, 738/630.1, 738/640.1, 738/641.1, 738/642.5, 141/119, 141/57, 141/61, 382/133, 382/134, 356/237.1, 356/237.6, 356/614
• 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 2219/00576 fluorophore
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• 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: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 13/02 : for receptacle or instruments
• CPC Class Codes: B01L 3/0241 : Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• 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
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array

Abstract

A microarrayer for spotting solution onto a receiving surface in an automated microarray dispensing device. Elements of the present invention include: at least one dispense head for spotting the receiving surface, at least one light source capable of illuminating the receiving surface, 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 surface image data to a computer. The computer is programmed to receive the surface image data and analyze it. The computer will then generate post analysis data based on the analysis of the surface image data. The post analysis data is available for improving the spotting of the solution onto the receiving surface. In a preferred embodiment, the surface image data includes information relating to receiving surface alignment, information relating to spot quality, and receiving surface identification information. In a preferred embodiment, the analysis of the information relating to receiving surface alignment enables the computer to make automatic adjustments to the relative positions of the at least one dispense head and the receiving surface 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 receiving surface identification information enables the computer to track each receiving surface. In a preferred embodiment the receiving surface is a plurality of slides.

Claims

1. A microarrayer for spotting solution onto a receiving surface, comprising:

A. a receiving surface,

B. at least one dispense head for spotting said receiving surface,

C. at least one light source capable of illuminating said receiving surface,

D. at least one camera operating in conjunction with said at least one light source, said at least one camera capable of acquiring and transmitting surface image data,

E. a computer programmed to;

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

2) analyze said surface image data, and

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

F. an adjustment device for permitting adjustments to be made to said spotting of solution onto said receiving surface, wherein said adjustments are based on said post analysis data.

2. The microarrayer as in claim 1, wherein said receiving surface is a plurality of receiving surfaces.

3. The microarrayer as in claim 1, wherein said receiving surface is a plurality of slides.

4. The microarrayer as in claim 1, wherein said adjustment device is a reworking device for permitting the microarrayer operator to rework a spot via the microarrayer based on said post analysis data.

5. The microarrayer as in claim 1, wherein said adjustment device is a reworking device for permitting said computer to rework a spot via the microarrayer based on said post analysis data.

6. The microarrayer as in claim 1, wherein said microarrayer further comprises:

A. at least one dispense tip for immersion into said solution,

B. a pre-spot receiving surface, wherein said microarrayer removes excessive amounts of said solution by pressing said at least one dispense tip against said pre-spot receiving surface.

7. The microarrayer as in claim 1, wherein said microarrayer removes said solution from a plurality of microplates, wherein a robot automatically positions said microplates within accessible reach of said microarrayer.

8. The microarrayer as in claim 7, wherein said plurality of microplates are stored in storage racks at a storage location, wherein said robot is capable of retrieving said microplates from said storage racks and returning said microplates to said storage racks.

9. The microarrayer as in claim 8, wherein said storage location is an incubator.

10. The microarrayer as in claim 1, further comprising a flexible mapping device for allowing the microarrayer operator to customize the pattern in which said dispense head deposits solution onto said receiving surface.

11. The microarrayer as in claim 1, wherein said post analysis further comprises spot inspection data comprising information about the characteristics of individual spots.

12. The microarrayer as in claim 1, wherein said dispense head comprises a plurality of dispense tips, wherein said post analysis data further comprises spot inspection statistics comprising information about the performance of said dispense tips.

13. The microarrayer as in claim 1, wherein said microarrayer further comprises a calibration target for calibration of said camera.

14. The microarrayer as in claim 1, wherein said microarrayer further comprises:

A. at least two vacuum stations, and

B. at least two sonic cleaning stations.

15. The microarrayer as in claim 1, further comprising:

A. a plurality of dispense tips, and

B. a second adjustment device for allowing the microarrayer operator to adjust the manner in which solution is loaded onto said plurality of dispense tips and to adjust the manner in which solution is deposited onto said receiving surface.

16. A microarrayer for spotting solution onto a receiving surface, comprising:

A. a receiving surface means,

B. a dispensing means for spotting said receiving surface means,

C. a light source means capable of illuminating said receiving surface means,

D. a camera means operating in conjunction with said light source means, said camera means capable of acquiring and transmitting surface image data,

E. a computer means programmed to;

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

2) analyze said surface image data, and

3) generate post analysis data based on said analysis of said surface image data, wherein said post analysis data comprises information relating to the success or failure of said microarrayer to successfully spot solution onto said receiving surface means.

F. an adjustment means for permitting adjustments to be made to said spotting of solution onto said receiving surface means, wherein said adjustments are based on said post analysis data.

17. The microarrayer as in claim 16, wherein said receiving surface is a plurality of receiving surfaces.

18. The microarrayer as in claim 16, wherein said receiving surface is a plurality of slides.

19. The microarrayer as in claim 16, wherein said adjustment means is a reworking means for permitting the microarrayer operator to rework a spot via the microarrayer based on said post analysis data.

20. The microarrayer as in claim 16, wherein said adjustment means is a reworking means for permitting said computer to rework a spot via the microarrayer based on said post analysis data.

21. The microarrayer as in claim 16, wherein said microarrayer further comprises:

A. at least one dispense tip for immersion into said solution,

B. a pre-spot receiving surface means, wherein said microarrayer removes excessive amounts of said solution by pressing said at least one dispense tip against said pre-spot receiving surface means.

22. The microarrayer as in claim 16, wherein said microarrayer removes said solution from a plurality of microplates, wherein a robot means automatically positions said microplates within accessible reach of said microarrayer.

23. The microarrayer as in claim 22, wherein said plurality of microplates are stored in storage racks at a storage location, wherein said robot means is capable of retrieving said microplates from said storage racks and returning said microplates to said storage racks.

24. The microarrayer as in claim 23, wherein said storage location is an incubator.

25. The microarrayer as in claim 16, further comprising a flexible mapping means for allowing the microarrayer operator to customize the pattern in which said dispensing means deposits solution onto said receiving surface.

26. The microarrayer as in claim 16, wherein said post analysis date further comprises spot inspection data comprising information about the characteristics of individual spots.

27. The microarrayer as in claim 16, wherein said means comprises a plurality of dispense tips, wherein said post analysis data further comprises spot inspection statistics comprising information about the performance of said dispense tips.

28. The microarrayer as in claim 16, wherein said microarrayer further comprises a calibration target means for calibration of said camera.

29. The microarrayer as in claim 16, wherein said microarrayer further comprises:

A. at least two vacuum stations, and

B. at least two sonic cleaning stations.

30. The microarrayer as in claim 16, further comprising:

A. a plurality of dispense tips, and

B. a second adjustment means for allowing the microarrayer operator to adjust the manner in which solution is loaded onto said plurality of dispense tips and to adjust the manner in which solution is deposited onto said receiving surface means.