SELF-ENCODING SENSOR WITH MICROSPHERES

• US 20120004120A1
• Filed: 08/23/2011
• Published: 01/05/2012
• Est. Priority Date: 10/06/1997
• Status: Active Grant

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Walt, David R., Dickinson, Todd A.
• Granted Patent: US 8,426,217 B2
• Time in Patent Office: Days
• US Class Current: 506/7
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/0045 using optical fibres
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: C12Q 1/682 Signal amplification
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C40B 60/14 for creating libraries
• 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
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 2201/0846 Fibre interface with sample, e.g. for spatial resolution
• CPC Class Codes: G01N 33/0031 comprising two or more sensors, e.g. a sensor array
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: Y10T 436/101666 Particle count or volume standard or control [e.g., platelet count standards, etc.]
• CPC Class Codes: Y10T 436/109163 Inorganic standards or controls

Abstract

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

Claims

1. A method of detecting an analyte, said method comprising:

(a) providing an array comprising a population of sensor elements at a density of at least 20,000 sensor elements per 1 mm², said population of sensor elements comprising different subpopulations of redundant sensor elements;

(b) providing said array with an analyte under conditions wherein said analyte binds to redundant sensor elements in at least one subpopulation of sensor elements, thereby producing signals at separate redundant sensor elements;

(c) detecting said signals from separate redundant sensor elements in said at least one subpopulation of redundant sensor elements; and

(d) combining signals detected from said separate redundant sensor elements wherein said signals are indicative of said analyte, and wherein said signals comprise like signals selected from the group consisting of optical signals, data representations of optical signals, non-optical signals and data representations of non-optical signals.

2. The method of claim 1, wherein said signals comprise data representations of optical signals.

3. The method of claim 1, wherein said non-optical signals comprise like signals selected from the group consisting of spectroscopic signals, resonance signals and radioactive signals.

4. The method of claim 1, wherein said signals comprise data representations of a non-optical signals.

5. The method of claim 1, wherein at least one subpopulation of redundant sensor elements comprises target redundancy.

6. The method of claim 1, wherein sensor elements in said population of sensor elements comprise wells.

7. The method of claim 6, wherein some but not all wells comprise beads.

8. The method of claim 1, wherein a sensor element in said population of sensor elements comprises a well that includes a bead.

9. The method of claim 8, wherein said well is adapted to include not more than one bead.

10. The method of claim 9, wherein said bead comprises a nucleic acid.

11. The method of claim 1, wherein said combining comprises summing said signals detected at separate redundant sensor elements.

12. The method of claim 1 further comprising performing a statistical analysis on said signals detected at separate redundant sensor elements, thereby determining statistical validity of said signals.

13. The method of claim 12 further comprising determining outlier signals and excluding said outlier signals from said statistical analysis.

14. The method of claim 1, wherein said at least one subpopulation of redundant sensor elements comprises at least five-fold sensor redundancy.

15. The method of claim 1, wherein said redundant sensor elements comprise nucleic acids.

16. The method of claim 1 further comprising separately combining over time a signal detected at a separate redundant sensor element.

17. The method of claim 1, wherein said array comprises a population of sensor elements at a density of at least 50,000 sensor elements per 1 mm².

18. A method of detecting signals produced at sensor elements of an array, said method comprising:

(a) providing an array comprising a population of sensor elements at a density of at least 20,000 sensor elements per 1 mm², said population of sensor elements comprising different subpopulations of redundant sensor elements, each of said redundant sensor elements comprising a well that includes not more than one bead having nucleic acids attached thereto;

(b) providing an analyte to the array so as to produce signals at separate redundant sensor elements in at least one subpopulation of sensor elements;

(c) detecting said signals from separate redundant sensor elements in at least one subpopulation of redundant sensor elements; and

(d) combining signals detected from said separate redundant sensor elements wherein said signals comprise like signals selected from the group consisting of optical signals, data representations of optical signals, non-optical signals and data representations of non-optical signals.

19. The method of claim 18, wherein said signals comprise data representations of optical signals.

20. The method of claim 18, wherein said non-optical signals comprise like signals selected from the group consisting of spectroscopic signals, resonance signals and radioactive signals.

21. The method of claim 18, wherein said signals comprise data representations of a non-optical signals.

22. The method of claim 18, wherein at least one subpopulation of redundant sensor elements comprises target redundancy.

23. The method of claim 22, wherein said combining comprises summing said signals detected at separate redundant sensor elements.

24. The method of claim 23 further comprising performing a statistical analysis on said signals detected at separate redundant sensor elements, thereby determining statistical validity of said signals.

25. The method of claim 24, wherein said redundant sensor elements comprise nucleic acids.

26. The method of claim 25 further comprising separately combining over time a signal detected at a separate redundant sensor element.

27. The method of claim 26, wherein said array comprises a population of sensor elements at a density of at least 50,000 sensor elements per 1 mm².

28. The method of claim 27, wherein said at least one subpopulation of redundant sensor elements comprises at least five-fold sensor redundancy.