Method and apparatus for automatic pin detection in microarray spotting instruments

• US 6,878,554 B1
• Filed: 03/20/2000
• Issued: 04/12/2005
• Est. Priority Date: 03/20/2000
• Status: Expired due to Term

• Current Assignee: PerkinElmer LAS, Inc. (Perkinelmer Incorporated)
• Original Assignee: PerkinElmer LAS, Inc. (Perkinelmer Incorporated)
• Inventors: Schermer, Mack J., Candiloro, C. Brian
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US09/527,892
• Time in Patent Office: 1,849 Days
• Field of Search: 436/180
• US Class Current: 436/180
• 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 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00527 Sheets
• 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 2219/00612 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00693 Means for quality control
• 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: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method and apparatus are provided for automatically sensing the presence (or absence) of spot dispensers such as pins in various possible mounting locations in the printhead of a microarray spotting instrument. Pin-location data obtained by the method and apparatus is provided to the computer controller of the instrument, which uses the data to control the motion of the printhead during operation of the instrument. A pin detection apparatus includes one or more sensor elements that automatically sense possible pin locations in the printhead for the presence of pins. The sensor elements are preferably arranged in an array corresponding to the array of pin locations in the printhead so that pin detection at each pin location can be performed simultaneously. Various types of sensor elements can be used to locate pins in a printhead. For example, sensors can be used that are remote from or attached to a printhead. Pin sensors can be used that sense pin locations from various positions relative to the printhead including above or below the printhead. Also, pin sensing can be by contact or non-contact mechanisms. The method and apparatus allow pin positions in a printhead to be quickly and accurately determined, and without significant risk of damaging the pins, which are fragile.

Claims

1. A method of determining which pin locations in a printhead of a microarray spotting instrument are occupied by fluid dispensing pins, comprising:

providing a printhead of a microarray spotting instrument, said printhead including a plurality of pin locations, at each of which a fluid dispensing pin is releasably or movably positionable;

providing a pin detection apparatus; and

for each pin location, using the pin detection apparatus to automatically detect whether a pin is present at said pin locations.

2. The method of claim 1 wherein said pin detection apparatus comprises a sensor to sense whether a pin is present in a given pin location.

3. The method of claim 2 wherein said sensor comprises a contact and circuitry for detecting electrical conduction between said contact and said pin.

4. The method of claim 3 wherein said contact comprises a probe hole in a printed circuit board.

5. The method of claim 3 wherein said contact is compliant.

6. The method of claim 5 wherein said contact is spring-mounted.

7. The method of claim 5 wherein said contact comprises a conductive rubber pad.

8. The method of claim 2 wherein said sensor senses the presence of the pinhead of the pin.

9. The method of claim 2 wherein said sensor senses the presence of a tip of the pin.

10. The method of claim 2 wherein said sensor comprises a strain gage sensor.

11. The method of claim 2 wherein said sensor comprises a piezoelectric sensor element.

12. The method of claim 2 wherein said sensor comprises a micro-switch.

13. The method of claim 2 wherein said sensor comprises a capacitive sensor.

14. The method of claim 2 wherein said sensor comprises an inductive sensor.

15. The method of claim 14 wherein said inductive sensor comprises an air-core coil inductor including a hole for receiving at least a portion of a pin.

16. The method of claim 14 wherein said inductive sensor comprises a pair of spaced apart, but proximate coils each adapted for receiving a portion of a pin.

17. The method of claim 2 wherein said sensor comprises an optical sensor.

18. The method of claim 1 wherein said pin detection apparatus comprises a plate with a hole, and wherein using said pin detection apparatus comprises:

applying a vacuum to said hole;

positioning said printhead relative to said plate such that if a pin were located in a given pin location of said printhead, said pin would be inserted in said hole; and

sensing any pressure changes in said hole.

19. The method of claim 1 wherein said pin detection apparatus comprises a surface with a step, and wherein using said apparatus comprises:

positioning said printhead relative to said step such that a given pin location is positioned above said step and if a pin were located in said given pin location, said pin would be supported by said step and a pinhead of said pin would be raised relative to the printhead; and

sensing any pinhead raised relative to said printhead.

20. The method of claim 1 wherein said pin detection apparatus includes an array of sensor elements corresponding in arrangement to said pin locations in said printhead for simultaneously detecting the presence of pins in each pin location.

21. The method of claim 1 wherein said pins comprise solid pins.

22. The method of claim 1 wherein said pins comprise split pins.

23. The method of claim 1 wherein said pins comprise tubular pins.

24. The method of claim 1 further comprising using the pin detection apparatus to automatically detect whether a pin is stuck in a raised position in the printhead.

25. In a microarray spotting instrument, an apparatus for determining which pin locations in a printhead of the microarray spotting instrument are occupied by releasably or movably mounted fluid dispensing pins, comprising at least one sensor element to automatically detect whether a fluid dispensing pin is present or absent in each said pin location for determining the arrangement of a plurality of fluid dispensing pins loaded in said printhead.

26. In a microarray spotting instrument, a method of providing to a controller operating the instrument information on which pin locations in a printhead in the instrument are occupied by fluid dispensing pins, comprising:

providing a printhead having a plurality of pin locations at which fluid dispensing pins are movably or releasably positionable;

automatically sensing whether a pin is present in a pin location and generating a signal indicative thereof; and

transmitting the signal to the controller.

27. A method of printing on a substrate and determining whether a pin in a printhead of a microarray spotting instrument is stuck in a raised position, comprising:

dipping tips of pins mounted in the pinhead into a reservoir of target material;

positioning the printhead over a microarray substrate to be spotted;

lowering the printhead to bring the tips of the pins into contact with the substrate to print spots on the substrate and, in the process, moving the pins in the printhead into raised positions relative to the printhead;

raising the printhead to separate the pins from the substrate; and

using a pin detection apparatus to automatically detect whether a pin in the printhead is stuck in a raised position.

28. The method of claim 27 further comprising stopping operation of the spotting instrument when a pin is detected to be stuck in a raised position.

29. The method of claim 27 further comprising issuing an alert when a pin is detected to be stuck in a raised position.

30. The method of claim 27 further comprising reconfiguring an instrument control sequence to avoid using a pin detected to be stuck in a raised position.