# US 10,871,436 B2 · Particles containing detectable elemental code

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- Number: US 10,871,436 B2
- Document ID: US10871436B2
- Status: Granted
- Kind: B2
- Application number: 15/253,060
- Filed: 2016-08-31
- Published: 2016-12-22
- Granted: 2020-12-22
- Earliest claimed: 2006-11-02
- Assignees: Fluidigm Canada Inc.
- Applicants: Fluidigm Canada Inc.
- Inventors: Mitchell A. Winnik; Cedric Van-Caeyzeele; Vladimir I. Baranov
- Web page: https://patentgrep.com/patent/US10871436B2

## CPC

- G01N 15/1012: {Calibrating particle analysers; References therefor}
- G01N 33/54313: {the carrier being characterised by its particulate form}
- G01N 33/54353: {with ligand attached to the carrier via a chemical coupling agent (coatings G01N33/54393)}
- G01N 33/553: Metal or metal coated
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- H01J 49/0009: {Calibration of the apparatus}
- Y10T 436/24: Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
- 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)
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The invention relates to a new type of element encoded particles suitable for the attachment of bio molecules to enable massively multiplex bio-analytical methods, and to calibrate and tune the elemental flow cytometer mass spectrometer (FC-MS).

## Claims

### Claim 1

A first element encoded particle for use in elemental analysis with a mass analyzer, the first element encoded particle comprising:
a unique combination of at least two staining elements, the at least two staining elements and the unique combination of the at least two staining elements selected such that, upon elemental analysis by the mass analyzer, a distinct signal is obtained from the combination of the at least two staining elements,
wherein the distinct signal obtained from the combination of the two staining elements serve as a signature of the first element encoded particle that distinguishes the first element encoded particle from element encoded particles stained with a different staining element,
wherein the at least two staining elements are each an isotope purified over other isotopes of a lanthanide element,
wherein the first element encoded particle is distinguishable based on its isotopic composition,
wherein an antibody is conjugated to the particle, and
wherein the particle is polymeric.

### Claim 2 (depends on 1)

The first element encoded particle of claim 1, wherein the at least two staining elements are contained in a seed particle.

### Claim 3 (depends on 2)

The first element encoded particle of claim 2, wherein the seed particle is produced by miniemulsion polymerization.

### Claim 4 (depends on 2)

The first element encoded particle of claim 2, further comprising a core shell encapsulating the seed particle.

### Claim 5 (depends on 4)

The first element encoded particle of claim 4, wherein the core shell is provided by using the seed particle in seeded emulsion polymerization.

### Claim 6 (depends on 5)

The first element encoded particle of claim 5, wherein the seeded emulsion polymerization involves acrylate.

### Claim 7 (depends on 4)

The first element encoded particle of claim 4, further comprising the antibody coupled with the core shell.

### Claim 8 (depends on 7)

The first element encoded particle of claim 7 wherein the antibody is tagged with an element.

### Claim 9 (depends on 4)

The first element encoded particle of claim 4, wherein the core shell is functionalized with a carboxylic group or an amine group.

### Claim 10 (depends on 1)

The first element encoded particle of claim 1, wherein the at least two staining elements comprise a first lanthanide staining complex and a second lanthanide staining complex.

### Claim 11 (depends on 10)

The first element encoded particle of claim 10, wherein the first lanthanide staining complex comprises a first lanthanide chelate and wherein the second lanthanide staining complex comprises a second lanthanide chelate.

### Claim 12 (depends on 1)

The first element encoded particle of claim 1, wherein the first element encoded particle is a bead, and wherein the antibody is coupled to the bead.

### Claim 13 (depends on 1)

The first element encoded particle of claim 1, wherein the unique combination of at least two staining elements comprises a different ratio of the at least two staining elements.

### Claim 14 (depends on 1)

The first element encoded particle of claim 1, wherein the isotope of the lanthanide element is Tb-159, Eu-153, La-139, Ho-165, or Pr-141.

### Claim 15 (depends on 1)

A plurality of element encoded particles for use in atomic composition analysis with a mass analyzer, the plurality of element encoded particles comprising:
the first element encoded particle of claim 1 and a second element encoded particle, the second element encoded particle having a unique combination of the at least two staining elements such that, upon elemental analysis by the mass analyzer, a distinct signal is obtained from the combination of the at least two staining elements, wherein the distinct signal obtained from the combination of the two staining elements serves as a signature of the second element encoded particle that distinguishes the second element encoded particle from the first element encoded particle, wherein the first and second element encoded particles are each covalently attached to a specific antibody that binds to a different antigen of interest, wherein the first and second element encoded particles are distinguishable by their isotopic composition but not otherwise distinguishable by their elemental composition.

### Claim 16 (depends on 15)

The plurality of element encoded particles of claim 15, wherein the at least two staining elements of the first element encoded particle are contained in a first seed particle and wherein the first seed particle is encapsulated in a first core shell, and wherein the at least two staining elements of the second element encoded particle are contained in a second seed particle and wherein the second seed particle is encapsulated in a second core shell.

### Claim 17 (depends on 15)

The plurality of element encoded particles of claim 15 and a plurality of reporter antibodies, wherein the reporter antibodies each bind to one of the different antigens of interest, and wherein the reporter antibodies are not the specific antibodies covalently attached to the first and second element encoded particles.

### Claim 18 (depends on 17)

The plurality of element encoded particles of claim 17, wherein the reporter antibodies are each labeled with an elemental tag.

### Claim 19 (depends on 18)

The plurality of element encoded particles of claim 18, wherein the reporter antibodies are each labeled with the same elemental tag.