System, method, and product for pixel clocking in scanning of biological materials

• US 6,650,411 B2
• Filed: 12/03/2001
• Issued: 11/18/2003
• Est. Priority Date: 04/26/2001
• Status: Active Grant

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Odoy, Patrick J., Woolaver, Timothy J.
• Primary Examiner(s): Evans, F. L.
• Assistant Examiner(s): GEISEL, KARA E
• Application Number:
  US09/683,217
• Publication Number:
  US 20020159057A1
• Time in Patent Office: 715 Days
• Field of Search: 356/318, 702/27, 250/458--46, 422/82-5-, 436/171-172
• US Class Current: 506/12
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 35/00 Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/0494 Detecting or compensating piositioning errors
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 27/44717 Arrangements for investigating the separated zones, e.g. localising zones
• CPC Class Codes: G01N 27/44721 by optical means
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression

Abstract

Systems and methods are described that may be applied to scanning biological materials in or on probe arrays. For example, a system is described that includes a scanner that has one or more excitation sources and an emission receiving element, such as an objective lens, that receives from locations of the probe array an emission signal responsive to the excitation sources. The scanner also has a radial position generator that generates radial positions of the emission receiving element. Also included in the system is a computer memory having stored therein a plurality of position data, each representing a radial position of the emission receiving element. Also stored in the computer memory unit is a set of comparator instructions that generate a clock signal based, at least in part, on comparing one or more of the plurality of radial positions with one or more of the plurality of position data.

Claims

1. A method for analyzing molecules, comprising the steps of:

(1) directing an excitation beam to a plurality of probe locations, each probe location including one or more probe molecules;

(2) receiving an emission signal responsive to the excitation beam exciting one or more probe locations;

(3) determining a plurality of radial positions of the excitation beam;

(4) comparing the plurality of radial positions to a plurality of position data;

(5) generating a clock signal based, at least in part, on comparing one or more of the plurality of radial positions with one or more of the plurality of position data; and

(6) analyzing molecules at one or more probe locations based, at least in part, on one or more values of the emission signal determined by the clock signal.

2. An apparatus, comprising:

an emission receiving element constructed and arranged to receive an emission signal from a plurality of locations of a probe array;

a radial position generator constructed and arranged to generate a plurality of radial positions of the emission receiving element;

a memory unit having stored therein a plurality of position data, each representing a radial position of the emission receiving element; and

a comparator constructed and arranged to generate a clock signal based, at least in part, on comparing one or more of the plurality of radial positions with one or more of the plurality of position data.

3. The apparatus of claim 2, further comprising:

a sampler constructed and arranged to sample the emission signal when enabled by the clock signal.

4. The apparatus of claim 2, further comprising:

an excitation-beam-delivering element constructed and arranged to deliver an excitation beam to the plurality of locations of the probe array, wherein the emission signal is responsive to the excitation beam.

5. The apparatus of claim 2, further comprising:

a scanning member constructed and arranged to scan the probe array, wherein the emission receiving element is moved with respect to the probe array by the scanning member.

6. The apparatus of claim 5, wherein:

the scanning member comprises a scanning arm having first and second ends, and wherein the emission receiving element includes an objective lens disposed in proximity to the first end.

7. The apparatus of claim 6, wherein:

the scanning arm is radially movable about an axis disposed in proximity to the second end.

8. The apparatus of claim 7, further comprising:

a moving member for moving the scanning arm.

9. The apparatus of claim 8, wherein:

the moving member moves the scanning arm in bi-directional arcs in a plane, wherein the axis is substantially perpendicular to the plane.

10. The apparatus of claim 8, wherein:

the moving member includes a galvanometer.

11. The apparatus of claim 10, wherein:

the radial position generator comprises a transducer responsive to movement of the galvanometer.

12. The apparatus of claim 11, wherein:

the transducer provides an electrical signal indicative of the radial position of the scanning arm, wherein the plurality of radial positions are derivable from the electrical signal.

13. The apparatus of claim 2, wherein:

the radial position generator generates an analog position signal, wherein the plurality of radial positions are derivable from the analog position signal.

14. The apparatus of claim 13, further comprising:

a converter constructed and arranged to convert the analog position signal into the plurality of radial positions, wherein the plurality of radial positions include digital values.

15. The apparatus of claim 3, wherein:

the clock signal includes a plurality of digital clock pulses.

16. The apparatus of claim 15, wherein:

the sampler includes an analog to digital converter.

17. The apparatus of claim 2, wherein:

the plurality of position data are determined so that a first linear distance between a first position of the emission receiving element corresponding to a first radial position and a second position of the emission receiving element corresponding to a second radial position is equal to a second linear distance between the second position of the emission receiving element and a third position of the emission receiving element corresponding to a third radial position.

18. The apparatus of claim 2, wherein:

the probe array includes a synthesized probe array.

19. The apparatus of claim 2, wherein:

the probe array includes a spotted probe array.

20. A method, comprising the steps of:

(1) detecting a signal from a plurality of locations of a probe array;

(2) generating a plurality of radial positions corresponding with two or more of the plurality of locations of the probe array; and

(3) comparing one or more of the plurality of radial positions with one or more of a plurality of position data.

21. The method of claim 20, further comprising the steps of:

(4) generating a clock signal responsive to step (3); and

(5) sampling the signal when enabled by the clock signal.

22. The method of claim 20, further comprising the step of:

(4) delivering an excitation beam to the plurality of locations of the probe array, wherein the signal is responsive to the excitation beam.

23. The method of claim 20, wherein:

step (1) includes scanning the probe array in arcs.

24. The method of claim 23, wherein:

the arcs include bi-directional arcs.

25. The method of claim 23, wherein:

step (1) includes scanning the probe array in a first arcuate scan line two or more times before scanning the probe array in a second arcuate scan line.

26. The method of claim 20, wherein:

the plurality of position data include, or are based at least in part, on predetermined data.

27. The method of claim 26, wherein:

the plurality of position data are determined so that a first linear distance between a first position of an emission receiving element corresponding to a first radial position and a second position of the emission receiving element corresponding to a second radial position is equal to a second linear distance between the second position of the emission receiving element and a third position of the emission receiving element corresponding to a third radial position.

28. The method of claim 20, wherein:

the probe array includes a synthesized probe array.

29. The method of claim 20, wherein:

the probe array includes a spotted probe array.

30. An apparatus, comprising:

an emission receiving element constructed and arranged to receive an emission signal from a plurality of locations of a probe array; and

a clock signal generator constructed and arranged to generate a clock signal based, at least in part, on radial position data.

31. The apparatus of claim 30, further comprising:

a sampler constructed and arranged to sample the emission signal when enabled by the clock signal.

32. A method, comprising the steps of:

receiving an emission signal from a plurality of locations of a probe array; and

generating a clock signal based, at least in part, on radial position data.

33. The method of claim 32, further comprising the step of:

sampling the emission signal when enabled by the clock signal.

34. A position-based pixel clock sampling apparatus for enabling the sampling of an emission signal detected using a scanner having a scanning arm, comprising:

a transducer constructed and arranged to provide an analog position signal representing a plurality of radial positions of the scanning arm;

a memory unit having stored therein a set of digital position data, each representing a radial position of the scanning arm;

a comparator constructed and arranged to generate a plurality of clock pulses based, at least in part, on a comparison of the position signal with the position data; and

an analog to digital converter constructed and arranged to sample the emission signal when enabled by the plurality of clock pulses.

35. The apparatus of claim 34, wherein:

the radial positions are spaced in accordance with constant linear distances.

36. A method for sampling an emission signal detected using a scanner having a scanning arm, comprising the steps of:

providing an analog position signal representing a plurality of radial positions of the scanning arm;

providing a set of digital position data, each representing a radial position of the scanning arm;

generating a plurality of clock pulses based, at least in part, on a comparison of the position signal with the position data; and

sampling the emission signal when enabled by the plurality of clock pulses.

37. A scanning system, comprising:

(1) a scanner including

(a) one or more excitation sources constructed and arranged to generate one or more excitation beams,

(b) an emission receiving element constructed and arranged to receive an emission signal, responsive to the excitation beams, from a plurality of locations of a probe array, and

(c) a radial position generator constructed and arranged to generate a plurality of radial positions of the emission receiving element; and

(2) a computer including

(a) a processor, and

(b) a memory unit having stored therein (i) a plurality of position data, each representing a radial position of the emission receiving element, and (ii) a set of comparator instructions constructed and arranged to generate, in cooperation with the processor, a clock signal based, at least in part, on comparing one or more of the plurality of radial positions with one or more of the plurality of position data.

38. A computer program product for use with a computer having a processor and a memory unit, comprising:

a set of comparator instructions stored in the memory unit and executed in cooperation with the processor, constructed and arranged to generate a clock signal based, at least in part, on comparing one or more of a plurality of radial positions with one or more of a plurality of position data, wherein the plurality of radial positions are generated by a radial position generator of a scanning apparatus based on radial positions of an emission receiving element.

39. The computer program product of claim 38, wherein:

the plurality of position data are stored in the memory unit.

40. The computer program product of claim 38, wherein:

the plurality of position data are determined so that a first linear distance between a first position of the emission receiving element corresponding to a first radial position and a second position of the emission receiving element corresponding to a second radial position is equal to a second linear distance between the second position of the emission receiving element and a third position of the emission receiving element corresponding to a third radial position.