Self-encoding sensor with microspheres

• US 9,157,113 B2
• Filed: 02/12/2014
• Issued: 10/13/2015
• Est. Priority Date: 10/06/1997
• Status: Expired due to Fees

• Current Assignee: Tufts University
• Original Assignee: Tufts University
• Inventors: Walt, David R., Dickinson, Todd A.
• Primary Examiner(s): Gabel, Gail R
• Application Number:
  US14/179,135
• Publication Number:
  US 20140179555A1
• Time in Patent Office: 608 Days
• US Class Current: 1/1
• 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 system for detecting an analyte comprising:

a substrate comprising a planar array comprising a population of sensor elements at a density of at least 20,000 sensor elements per 1 mm², the population of sensor elements comprising different subpopulations of redundant sensor elements, wherein analytes are bound to separate redundant sensor elements in at least one of the subpopulations of sensor elements;

a detector system configured to distinguish signals generated from individual sensor elements of the separate redundant sensor elements that are bound to the analytes; and

a data processor having instructions configured to combine each of the signals distinguished from the separate redundant sensor elements, wherein the signals indicate the presence of the analyte, and wherein the signals comprise optical signals, or non-optical signals generated by the separate redundant sensor elements.

2. The system of claim 1, wherein the data processor comprises instructions to convert the optical signals to data representations of optical signals.

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

4. The system of claim 1, wherein the data processor comprises instructions to convert the non-optical signals to data representations of non-optical signals.

5. The system of claim 1, wherein sensor elements in the population of sensor elements comprise wells.

6. The system of claim 5, wherein some but not all of the wells comprise beads.

7. The system of claim 1, wherein a sensor element in the population of sensor elements comprises a well that includes a bead.

8. The system of claim 7, wherein the well contains no more than one bead.

9. The system of claim 1, wherein the instructions configured to combine each of the signals distinguished from the separate redundant sensor elements comprise summing the signals detected at separate redundant sensor elements.

10. The system of claim 1, wherein the data processor comprises instructions to perform a statistical analysis on the signals detected at separate redundant sensor elements, thereby determining statistical validity of the signals.

11. The system of claim 1, wherein the data processor comprises instructions to determine outlier signals and exclude the outlier signals from the statistical analysis.

12. The system of claim 1, wherein the at least one subpopulation of redundant sensor elements comprises at least five-fold sensor redundancy.

13. The system of claim 1, wherein the redundant sensor elements comprise nucleic acids.

14. The system of claim 1, wherein the redundant sensor elements comprise antibodies.

15. The system of claim 1, wherein the redundant sensor elements comprise enzymes.

16. The system of claim 1, wherein the data processor comprises instructions to separately combine over time a signal detected at a separate redundant sensor element.

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

18. The system of claim 1, wherein the planar array comprises a pattern of charged groups.

19. The system of claim 1, wherein the signals comprise optical signals generated by the separate redundant sensor elements.

20. The system of claim 1, wherein the signals comprise non-optical signals generated by the separate redundant sensor elements.