# US 9,157,113 B2 · Self-encoding sensor with microspheres

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- Number: US 9,157,113 B2
- Document ID: US9157113B2
- Status: Granted
- Kind: B2
- Application number: 14/179,135
- Filed: 2014-02-12
- Published: 2014-06-26
- Granted: 2015-10-13
- Earliest claimed: 1997-10-06
- Assignees: Trustees of Tufts College, Tufts University
- Applicants: Trustees of Tufts College, Tufts University
- Inventors: David R. Walt; Todd A. Dickinson
- Web page: https://patentgrep.com/patent/US9157113B2

## CPC

- C12Q 1/682: Signal amplification
- C12Q 1/6834: Enzymatic or biochemical coupling of nucleic acids to a solid phase
- 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)}
- G01N 21/6452: {Individual samples arranged in a regular 2D-array, e.g. multiwell plates}
- 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)}
- G01N 33/54313: {the carrier being characterised by its particulate form}
- B01J 2219/00317: Microwell devices, i.e. having large numbers of wells
- B01J 2219/0045: using optical fibres
- B01J 2219/00466: in a slurry
- B01J 2219/005: Beads
- B01J 2219/00524: in the shape of fiber bundles
- B01J 2219/00585: Parallel processes
- B01J 2219/00648: by the use of solid beads
- B01J 2219/00659: Two-dimensional arrays
- C40B 60/14: for creating libraries
- G01N 33/0031: {comprising two or more sensors, e.g. a sensor array}
- G01N 2201/0846: Fibre interface with sample, e.g. for spatial resolution
- Y10T 436/101666: Particle count or volume standard or control [e.g., platelet count standards, etc.]
- Y10T 436/109163: Inorganic standards or controls
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

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

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 5)

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

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 7)

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

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 1)

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

### Claim 15 (depends on 1)

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

### Claim 16 (depends on 1)

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.

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 1)

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

### Claim 19 (depends on 1)

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

### Claim 20 (depends on 1)

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