Method and system of array imaging

• US 7,595,473 B2
• Filed: 08/22/2005
• Issued: 09/29/2009
• Est. Priority Date: 08/22/2005
• Status: Active Grant

• Current Assignee: Tufts University
• Original Assignee: Tufts University
• Inventors: Walt, David R., Bencic-Nagale, Sandra
• Primary Examiner(s): Epps; Georgia Y
• Application Number:
  US11/209,432
• Publication Number:
  US 20070040095A1
• Time in Patent Office: 1,499 Days
• Field of Search: 250/237.R, 250/216, 250/205, 356/317, 356/318, 436/172, 422/82.05, 422/91
• 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. A method of detecting the presence of at least one target analyte in at least a first and a second sample comprising:

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

defining a first section of said sensor array and a second section of said sensor array which is non-overlapping with said first section, wherein each of said first and second sections contains a distribution of sensor elements of each sensor element type that is substantially the same as an overall distribution of the sensor elements of each sensor element type for the entire sensor array;

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

contacting said second sample with said sensor array and with at least a portion of said sensor elements;

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

during at least one point during performance of the method, determining the presence or absence of said target analyte.

2. The method of claim 1, further comprising a step of purging said first sample from said sensor array before contacting said second sample with said sensor array.

3. The method of claim 1, wherein the second intensity is greater than the first intensity.

4. The method of claim 1, wherein the illuminating the sensor array comprises illuminating the sensor array through a variable exposure aperture.

5. The method of claim 4, wherein the variable exposure aperture is positionable.

6. The method of claim 4, wherein the variable exposure aperture is a slit.

7. The method of claim 6, wherein the slit is a rectangular-shaped slit.

8. The method of claim 1, wherein a determining step is performed after each illuminating step.

9. The method of claim 1, wherein the illuminating steps comprise illuminating the sensor array through a variable excitation filter system.

10. The method of claim 1, wherein the sensor array comprises between about 10,000 and about 100,000 sensor elements.

11. The method of claim 1, wherein the sensor array comprises between about 100,000 and about 1,000,000 sensor elements.

12. The method of claim 1, wherein the first section of the sensor array is illuminated at least about 300 times.

13. A method of determining the amount of at least one target analyte present in at least a first and a second sample comprising:

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

defining a first section of said sensor array and a second section of said sensor array which is non-overlapping with said first section, wherein each of said first and second sections contains a distribution of sensor elements of each sensor element type that is substantially the same as an overall distribution of the sensor elements of each sensor element type for the entire sensor array;

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

contacting said second sample with said sensor array comprising at least a portion of said sensor elements;

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

during at least one point during performance of the method, determining an amount of said target analyte present.

14. The method of claim 13, wherein a determining step is performed after each illuminating step.

15. The method of claim 13, wherein the illuminating steps comprise illuminating the sensor array through a variable excitation filter system.

16. The method of claim 13, wherein the sensor array comprises between about 10,000 and about 100,000 sensor elements.

17. The method of claim 13, wherein the sensor array comprises between about 100,000 and about 1,000,000 sensor elements.

18. 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;

defining a first section of said sensor array, said first section comprising a first plurality of sensor elements, and a second section of said sensor array which is non-overlapping with said first section, said second section comprising a second plurality of sensor elements;

illuminating said first section of said sensor array and said first plurality of sensor elements a plurality of times and collecting at least one first set of data;

illuminating said second section of said sensor array and said second plurality of sensor elements a plurality of times and collecting at least one second set of data; and

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

19. The method of claim 18, wherein said first and second sample comprises a vapor.

20. The method of claim 18, wherein said first and second sample comprises a liquid.

21. The method of claim 18, wherein the first section of the sensor array is illuminated at least about 300 times.

22. The method of claim 18, wherein the second section of the sensor array is illuminated at least about 300 times.