System, method, and product for scanning of biological materials

• US 7,689,022 B2
• Filed: 03/14/2003
• Issued: 03/30/2010
• Est. Priority Date: 03/15/2002
• Status: Active Grant

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Katz, Joel, Schultz, Erik, Oleink-Ovod, Ksenia, Weiner, Nathan K., Miles, Christopher, Bukys, Albert, Bradbury, David, DiPaolo, Roger, Odoy, Patrick J., Stura, David A., Regan, Thomas P., Jones, Mark, McKenzie, Eric Earl, Deweerd, Herman, Overbeck, James, Woolaver, Tim
• Primary Examiner(s): Johns; Andrew W
• Application Number:
  US10/389,194
• Publication Number:
  US 20040012676A1
• Time in Patent Office: 2,573 Days
• Field of Search: 382/128, 382/133, 382/134, 382/255, 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 scanning system, comprising:

one or more optical elements constructed and arranged to direct a excitation beam at a probe array;

one or more detectors constructed and arranged to receive reflected intensity data responsive to the excitation beam, wherein the reflected intensity data is responsive, at least in part, to a focusing distance between an optical element and the probe array;

a transport frame constructed and arranged to adjust the focusing distance in a first direction with respect to the probe array;

an auto-focuser constructed and arranged to determine a best plane of focus based, at least in part, upon one or more characteristics of the reflected intensity data as received at two or more focusing distances, wherein the one or more characteristics includes a slope value, and the best plane of focus is based, at least in part, upon a maximum value of the slope value;

and wherein;

the one or more detectors are further constructed and arranged to receive a plurality of pixel intensity values based, at least in part, upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus; and

the system further comprises an image generator constructed and arranged to associate each of the pixel intensity values with one or more image pixel positions of a probe array based, at least in part, upon one or more position correction values.

2. A method, comprising the acts of:

directing an excitation beam at a probe array;

receiving reflected intensity data responsive to the excitation beam, wherein the intensity data is responsive, at least in part, to a focusing distance between an optical element and the probe array;

adjusting the focusing distance in a first direction with respect to the probe array;

repeating the steps of receiving and adjusting for a predetermined number of iterations, wherein the predetermined number of iterations is based, at least in part, on an anticipated error associated with the reflected intensity data; and

determining a best plane of focus based, at least in part, upon one or more characteristics of the reflected intensity data at the adjusted focusing distances.

3. The method of claim 2, wherein:

the first direction is away from or toward the probe array.

4. The method of claim 2, wherein:

the anticipated error associated with the reflected intensity data is inversely related to the predetermined number of iterations.

5. The method of claim 2, wherein:

the reflected intensity data are responsive to reflection of the excitation beam from one or more focus features.

6. The method of claim 5, wherein:

the reflected intensity data correspond to one or more reflection spots.

7. The method of claim 6, wherein:

the best plane of focus is based, at least in part, upon associating the one or more spots with one or more characteristics of a beam waist.

8. The method of claim 5, wherein:

the one or more focus features are positioned outside an active area and the one or more probe features are positioned inside the active area.

9. The method of claim 5, wherein:

the one or more focus features includes a chrome border.

10. The method of claim 2, wherein:

the one or more characteristics includes a slope value.

11. The method of claim 2, wherein:

the one or more characteristics includes a slope value, and the best plane of focus is based, at least in part, upon a maximum value of the slope value.

12. A scanning system, comprising:

one or more optical elements constructed and arranged to direct an excitation beam at a probe array;

one or more detectors constructed and arranged to receive reflected intensity data responsive to the excitation beam, wherein the intensity data is determined, at least in part, by a focusing distance between an optical element and the probe array;

an auto-focuser constructed and arranged to determine a best plane of focus based, at least in part, upon one or more characteristics of the reflected intensity data as received at two or more focusing distances, such that receipt of reflected intensity data and adjustment of the plane of focus occurs in a predetermined number of iterations, and wherein the predetermined number of iterations is based, at least in part, on an anticipated error associated with the reflected intensity data.

13. The scanning system of claim 12, wherein:

the first direction is away from or toward the probe array.

14. The scanning system of claim 12, wherein:

the anticipated error associated with the reflected intensity data is inversely related to the predetermined number of iterations.

15. The scanning system of claim 12, wherein:

the reflected intensity data are responsive to reflection of the excitation beam from one or more focus features.

16. The scanning system of claim 15, wherein:

the reflected intensity data correspond to one or more reflection spots.

17. The scanning system of claim 16, wherein:

the best plane of focus is based, at least in part, upon associating the one or more spots with one or more characteristics of a beam waist.

18. The scanning system of claim 15, wherein:

the one or more focus features are positioned outside an active area, and the one or more probe features are positioned inside the active area.

19. The scanning system of claim 15, wherein:

the one or more focus features includes a chrome border.

20. The scanning system of claim 12, wherein:

the one or more characteristics includes a slope value.

21. The scanning system of claim 12, wherein:

the one or more characteristics includes a slope value, and the best plane of focus is based, at least in part, upon a maximum value of the slope value.