METHOD AND SYSTEM OF ARRAY IMAGING

• US 20100032547A1
• Filed: 09/25/2009
• Published: 02/11/2010
• Est. Priority Date: 08/22/2005
• Status: Abandoned Application

• Current Assignee: Tufts University
• Original Assignee: Tufts University
• Inventors: Walt, David R., Bencic-Nagale, Sandra
• Application Number:
  US12/567,618
• Publication Number:
  US 20100032547A1
• Time in Patent Office: Days
• US Class Current: 250/205
• CPC Class Codes: G01J 2001/0276 Protection
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/0213 using attenuators
• CPC Class Codes: G01J 3/0229 using masks, aperture plates, spatial light modulators or spatial filters, e.g. reflective filters
• CPC Class Codes: G01J 3/10 Arrangements of light sources specially adapted for spectrometry or colorimetry
• CPC Class Codes: G01J 3/2803 using photoelectric array detector
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6484 Optical fibres
• 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 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G01N 2201/088 Using a sensor fibre

Abstract

The present invention relates to a method and system of array imaging that extends or maximizes the longevity of the sensor array by minimizing the effects of photobleaching. The imaging system has a light source, a variable exposure aperture, and a variable filter system. The system extends the longevity of sensors by (1) using the variable exposure aperture to selectively expose sections of the sensor array containing representative numbers of each type of sensor, and/or (2) using the variable filter system to control the intensity of the excitation light, providing only the intensity required to induce the appropriate excitation and increasing that intensity over time as necessary to counteract the effects of photobleaching.

Claims

1. An array imaging system comprising:

(a) a light source;

(b) an array receiving component;

(b) a variable exposure aperture disposed between the light source and the array receiving component; and

(c) a variable filter system disposed between the light source and the array receiving component.

2. The array imaging system of claim 1, further comprising a magnification lens disposed between the light source and the array receiving component.

3. The array imaging system of claim 2, further comprising an array detector associated with the magnification lens.

4. The array imaging system of claim 1, wherein the variable filter system is programmable to decrease in optical density over time.

5. The array imaging system of claim 1, wherein the variable filter system comprises a set of filters disposed between the light source and the array receiving component, the set of filters being programmed to provide decreasing optical density.

6. The array imaging system of claim 5, wherein the set of filters comprises filters of varying optical densities.

7. The array imaging system of claim 5, wherein the set of filters comprises filters having optical densities ranging from about 0.2 to about 1.0.

8. The array imaging system of claim 5, wherein the set of filters provides optical density values ranging from about 1.0 to about 2.0.

9. The array imaging system of claim 1, wherein the variable exposure aperture is a positionable aperture configured to operate with the light source to control an area of exposure.

10. The array imaging system of claim 1, wherein the variable exposure aperture comprises a slit configured to allow light to pass through from the light source to the sensor array.

11. The array imaging system of claim 1, wherein the variable exposure aperture comprises a rectangular slit.

12. A method of determining a property of a target analyte in a sample comprising:

contacting said sample with a sensor array comprising a plurality of sensor element types and a plurality of sensor elements of each sensor element type;

illuminating a first section of said sensor array with a first intensity and collecting a first set of data;

illuminating said first section of said sensor array with a second intensity, wherein said second intensity exceeds said first intensity by an amount that compensates for the effect of photobleaching on said sensor elements, and collecting a second set of data; and

during at least one point during performance of the method, determining at least one property of said target analyte.

13. A method of imaging a sensor array that extends or maximizes the longevity of the sensor array by minimizing the effects of photobleaching, comprising:

A) providing a sensor array comprising a plurality of sensor elements of a plurality of sensor element types;

B) illuminating a first section of said sensor array with a first intensity;

C) illuminating said first section with a second intensity, wherein said second intensity exceeds said first intensity by an amount that compensates for the effects of photobleaching on said sensor elements from said section;

D) illuminating a second section of said sensor array with a third intensity, wherein said first section and said second section are different; and

E) illuminating said second section with a fourth intensity, wherein said fourth intensity exceeds said third intensity by an amount that compensates for the effects of photobleaching on said sensor elements from said section.

14. The method of claim 13, wherein said sensor array comprises a plurality of subsections collectively encompassing substantially the entire array area, and wherein steps B-E are repeated until each of said plurality of subsections has been illuminated at least once.

15. The method of claim 13, wherein step C is repeated a plurality of times, prior to performing step D.

16. The method of claim 13, wherein steps C and E are repeated a plurality of times.

17. The method of claim 14, wherein steps C and E are repeated a plurality of times until a plurality of said sensor elements of each of said plurality of subsections of said array has been substantially photobleached.

18. The method of claim 13, wherein the steps are completed in the order recited.

19. The method of claim 13, wherein steps B and D are performed prior to performing step C.

20. The method of claim 13, further comprising collecting a set of data in at least one of steps B, C, D, or E.

21. The method of claim 13, further comprising the step of determining at least one property of at least one analyte in a sample contacted with said sensor array.

22. The method of claim 13, wherein said first section and said second section are different.

23. The method of claim 13, wherein said first intensity and said third intensity are approximately equal.

25. The method of claim 22, wherein in the first illuminating step, each subsection is illuminated a plurality of times until a plurality of said sensor elements of each subsection of said array is substantially photobleached.

26. The method of claim 22, wherein the plurality of subsections defined in the defining step collectively encompass essentially the entirety of said sensor array and wherein each of the plurality of subsections is illuminated at least once.

24. A method of imaging a sensor array that extends or maximizes the longevity of the sensor array by minimizing the effects of photobleaching, comprising:

providing a sensor array comprising a plurality of sensor elements of a plurality of sensor element types;

defining a plurality of subsections of the array, wherein each subsection contains a distribution of each of the sensor elements of each sensor element type that is substantially the same as the overall distribution of each of the sensor elements of each sensor element type for the entire sensor array;

illuminating at least a portion of the subsections of the array with a first intensity; and

illuminating a previously illuminated subsection of the array with a second intensity, wherein said second intensity exceeds said first intensity by an amount that compensates for the effects of photobleaching on said sensor elements from said section.