# US 12,182,084 B2 · Biosensors for biological or chemical analysis and systems and methods for same

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- Number: US 12,182,084 B2
- Document ID: US12182084B2
- Status: Granted
- Kind: B2
- Application number: 18/542,840
- Filed: 2023-12-18
- Published: 2024-04-11
- Granted: 2024-12-31
- Earliest claimed: 2012-04-16
- Assignees: Illumina, Inc.
- Applicants: Illumina, Inc.
- Inventors: Helmy A. Eltoukhy; Robert C. Kain; Wenyi Feng; Mark Pratt; Bernard Hirschbein; Poorya Sabounchi; Tarun Khurana
- Web page: https://patentgrep.com/patent/US12182084B2

## CPC

- G06F 16/214: {Database migration support}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- G01N 15/1404: Handling flow, e.g. hydrodynamic focusing
- G01N 15/1434: Optical arrangements
- G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)}
- G01N 33/6875: {Nucleoproteins}
- B01L 2300/0654: Lenses; Optical fibres
- B01L 2300/168: Specific optical properties, e.g. reflective coatings
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- 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)

## Abstract

A biosensor is provided including a detection device and a flow cell mounted to the detection device. The detection device has a detector surface with a plurality of reaction sites. The detection device also includes a filter layer. A method is providing including obtaining signal data from an array of light detectors; determining a crosstalk function for each of the light detectors of the array of light detectors; and determining characteristics of analytes of interest based on the signal data using the crosstalk functions.

## Claims

### Claim 1

A system comprising:
a biosensor comprising a detector surface and an array of light detectors in which each of the light detectors is associated with at least one reaction site of an array of reaction sites located on the detector surface;
a receptacle to receive and establish electrical and fluidic connections with a biosensor;
a fluidic control system for controlling a flow of fluid through the biosensor along the detector surface, where the fluidic control system includes an upstream conduit for providing the fluid to the biosensor and a downstream conduit for removing the fluid; and
an illumination system to direct excitation light toward the biosensor to illuminate the reaction sites; and
a system controller including an analysis module, where the analysis module obtains signal data from the light detectors, where the signal data includes light scores that are based on an amount of light detected by the light detectors during a plurality of imaging events.

### Claim 2 (depends on 1)

The system of claim 1, wherein the system controller is configured to analyze the light scores from a group of light detectors for each of the plurality of the imaging events.

### Claim 3 (depends on 2)

The system of claim 2, wherein the system controller is further configured to determine respective crosstalk functions of the light detectors in the group of light detectors.

### Claim 4 (depends on 3)

The system of claim 3, wherein each of the crosstalk functions for a corresponding light detector is based on the amount of light detected by other light detectors in the group.

### Claim 5 (depends on 3)

The system of claim 3, wherein the system controller is further configured to analyze the signal data for each of the imaging events using the crosstalk functions to determine at least one characteristic of the analytes-of-interest.

### Claim 6 (depends on 1)

The system of claim 1, wherein the signal data includes light scores that are based on an amount of light detected by the light detectors during the plurality of imaging events.

### Claim 7 (depends on 2)

The system of claim 2, wherein the analyzing the light scores comprises comparing the light scores of adjacent reaction sites to a predetermined score value to determine whether the adjacent reaction sites provided emission signals.

### Claim 8 (depends on 3)

The system of claim 3, wherein each of the crosstalk functions for a corresponding light detector is based on a number of adjacent reaction sites that provided emission signals and locations of the adjacent reaction sites that provided the emission signals.

### Claim 9 (depends on 8)

The system of claim 8, wherein the emission signals are provided in response to an excitation event.

### Claim 10 (depends on 1)

The system of claim 1, wherein the system controller controls operation of the fluidic control system and the illumination system according to a predetermined protocol to provide the imaging events.

### Claim 11 (depends on 10)

The system of claim 10, wherein the predetermined protocol is a sequencing-by-synthesis protocol.

### Claim 12 (depends on 1)

The system of claim 1, wherein at least some of the reaction sites have an analyte of interest immobilized thereon.

### Claim 13 (depends on 1)

The system of claim 1, wherein at least some of the reaction sites each comprise a colony of nucleic acids immobilized thereon.

### Claim 14 (depends on 1)

The system of claim 1, wherein at least some of the reaction sites each comprise a clonal colony of nucleic acids immobilized thereon, wherein each of the clonal colony of nucleic acids comprises nucleic acids having substantially the same sequence.

### Claim 15 (depends on 13)

The system of claim 13, where the colony of nucleic acids is a colony of single stranded nucleic acids.

### Claim 16 (depends on 13)

The system of claim 13, wherein at least some of the colonies of nucleic acids immobilized thereon of the at least some of the reaction sites comprise a labeled nucleotide having at least one fluorophore that produces an emission signal in response to incident excitation light.

### Claim 17 (depends on 14)

The system of claim 14, wherein at least some of the clonal colonies of nucleic acids immobilized thereon of the at least some of the reaction sites comprise a labeled nucleotide having at least one fluorophore that produces an emission signal in response to incident excitation light.
