System and method for scanning of probe arrays

• US 8,391,582 B2
• Filed: 05/25/2012
• Issued: 03/05/2013
• Est. Priority Date: 03/15/2002
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Weiner, Nathan K., Odoy, Patrick J., Schultz, Eric, Jones, Mark, DeWeerd, Herman, Stura, David A., Bukys, Albert K., Regan, Thomas P., Bradbury, David, McKenzie, Eric E., DiPaolo, Roger, Miles, Christopher, Katz, Joel M., Overbeck, James T., Woolaver, Tim J., Ksenia, Oleinik-Ovod
• Primary Examiner(s): Johns, Andrew W
• Application Number:
  US13/480,888
• Publication Number:
  US 20120235016A1
• Time in Patent Office: 284 Days
• Field of Search: 382/128, 382/133, 382/134, 382/135, 250/201.2, 250/201.3, 250/201.4, 250/201.7
• US Class Current: 382/133
• CPC Class Codes: G01N 2021/6471 Special filters, filter wheel
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

An embodiment of a scanning system is described including optical elements that direct an excitation beam at a probe array, detectors that receive reflected intensity data responsive to the excitation beam, where the reflected intensity data is responsive to a focusing distance between an optical element and the probe array, a transport frame that adjusts the focusing distance in a direction with respect to the probe array, an auto-focuser that determines a best plane of focus based upon characteristics of the reflected intensity data of at least two focusing distances where the detectors further receive pixel intensity values based upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus, and an image generator that associates each of the pixel intensity values with at least one image pixel position of a probe array based upon one or more position correction values.

Claims

1. A system for scanning a probe array, the system comprising:

one or more optical elements configured to direct an excitation beam at a substrate, wherein the substrate includes the probe array;

one or more detectors configured to receive reflections from the substrate generated by the excitation beam;

an auto-focuser configured to adjust a distance between the one or more optical elements and the probe array based on a determination of a best plane of focus, wherein the auto-focuser is configured to determine the best plane of focus based on the reflections, and wherein the best plane of focus comprises the distance at which the excitation beam produces a minimum spot size on the substrate.

2. The system of claim 1, wherein the auto-focuser comprises a computer software program.

3. The system of claim 1, wherein the one or more optical elements comprise at least one laser.

4. The system of claim 1, wherein the one or more optical elements comprise at least a first laser and a second laser, wherein at least one of the first laser and the second laser produces green light.

5. The system of claim 1, wherein the one or more detectors comprise at least one photomultiplier tube.

6. The system of claim 1, wherein the one or more detectors are selected from the group consisting of a silicon detector, a photodiode, a charge-coupled device, and a photomultiplier tube.

7. The system of claim 1, further comprising:

a filter wheel configured to adjust emitted spectral components of the excitation beam.

8. The system of claim 1, further comprising:

a barcode reader configured to read one or more barcodes associated with the probe array.

9. The system of claim 1, further comprising:

an auto-loader configured to transport the substrate within the system from a magazine to a location for scanning of the probe array.

10. A method for scanning a probe array, the method comprising:

illuminating a substrate with an excitation beam produced by one or more optical elements of a scanning system, wherein the substrate includes a probe array;

detecting reflections from the substrate generated by the excitation beam;

adjusting a distance between the one or more optical elements and the probe array based on a determination of a best plane of focus, wherein the best plane of focus is based on the reflections, and wherein the best plane of focus comprises the distance at which the excitation beam produces a minimum spot size on the substrate.

11. The method of claim 10, wherein the adjusting step is implemented, in part, by a computer software program.

12. The method of claim 10, wherein the one or more optical elements comprise a laser.

13. The method of claim 10, wherein the one or more optical elements comprise at least a first laser and a second laser, and wherein at least one of the first laser and the second laser produces green light.

14. The method of claim 10, wherein the one or more optical elements comprise at least one photomultiplier tube.

15. The method of claim 10, wherein the one or more optical elements comprise a silicon detector, a photodiode, a charge-coupled device, or a photomultiplier tube.

16. The method of claim 10, further comprising:

adjusting emitted spectral components of the excitation beam with a filter wheel.

17. The method of claim 10, further comprising:

reading one or more barcodes associated with the probe array with a barcode reader.

18. The method of claim 10, further comprising:

transporting the substrate within the system from a magazine to a location for scanning of the probe array.