# US 2014/0193851 A1 · Detecting Individual Analytes by Means of Magnetic Flow Measurement

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- Number: US 2014/0193851 A1
- Document ID: US20140193851A1
- Status: Published application
- Kind: A1
- Application number: 14/239,077
- Filed: 2012-08-01
- Published: 2014-07-10
- Earliest claimed: 2011-08-15
- Assignees: Siemens Aktiengesellschaft
- Applicants: Siemens Aktiengesellschaft
- Inventors: Oliver Hayden; Michael Johannes Helou; Mathias Reisbeck; Sandro Francesco Tedde
- Web page: https://patentgrep.com/patent/US20140193851A1

## CPC

- C12Q 1/02: involving viable microorganisms
- B03C 1/01: by addition of magnetic adjuvants
- B03C 1/288: {disposed at the outer circumference of a recipient}
- G01N 15/1031: by measuring electrical or magnetic effects
- G01N 33/585: {with a particulate label, e.g. coloured latex}
- G01N 33/587: {Nanoparticles}
- G01R 33/09: Magnetoresistive devices
- B03C 2201/18: Magnetic separation whereby the particles are suspended in a liquid
- B03C 2201/24: for measuring or calculating of parameters, e.g. efficiency
- 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
- B03C: MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS (separating isotopes B01D59/00; combinations of magnetic or electrostatic separation with separation of solids by other means B03B, B07B)
- 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)
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

In a magnetic flow measurement, such as flow cytometry, individual analytes are detected in the through-flow. The analytes (e.g., cells) are marked with magnetic labels directly in the medium surrounding the analytes. The analytes are transported through the flow channel of a measuring device including at least one magnetic sensor. Using the magnetic marking of the analytes, the magnetic analyte diameter (rmag) is detected rather than the optical or hydrodynamic size (ropt) of the analytes. The analyte diameter is determined by the stray field maximum. The analyte diameter is smaller than the analyte size, such that individual analytes may be detected at high analyte concentrations.

## Claims

### Claim 1

A method for magnetic flow measurement of an analyte, the method comprising:
magnetic marking of analytes in a sample;
generating a flow of the analytes over a sensor arrangement, the flow of the analytes being guided at least over a magnetoresistive component;
generating a gradient magnetic field to enrich the marked analytes over the magnetoresistive component, and a homogeneous magnetic field, the homogeneous magnetic field and the magnetoresistive component being arranged with respect to one another such that the homogeneous magnetic field is not detected by the magnetoresistive component; and
detecting the marked analytes individually;
wherein the magnetic marking is implemented such that each marked analyte of the analytes has a stray magnetic field with a maxima detectable by the magnetoresistive component and disposed at a distance from a center of the analyte less than a hydrodynamic radius of the analyte.

### Claim 2 (depends on 1)

The method of claim 1, wherein the magnetic marking is implemented with magnetic nanobeads.

### Claim 3 (depends on 1)

The method of claim 1, wherein the magnetic marking is implemented with nanobeads having a hydrodynamic diameter between 10 nm and 500 nm.

### Claim 4 (depends on 1)

The method of claim 1, wherein the magnetic marking is implemented with nanobeads comprising magnetite or maghemite.

### Claim 5 (depends on 1)

The method as of claim 1, wherein the magnetic marking is implemented with nanobeads having a magnetization of between 10 and 60 (A·m2)/kg.

### Claim 6 (depends on 1)

The method of claim 1, further comprising enriching the marked analytes over the magnetoresistive component via the gradient magnetic field, such that the marked analytes are locally present in a concentration increased from sample concentrations by a factor of between 100 and 10,000.

### Claim 7 (depends on 1)

The method of claim 1, wherein the marked analytes are in direct contact with one another when flowing over the magnetoresistive component.

### Claim 8 (depends on 1)

The method of claim 1, further comprising adjusting a speed of the flow such that the analytes are guided over the magnetoresistive component with a constant speed.

### Claim 9 (depends on 1)

The method of claim 1, wherein the magnetic marking is implemented with superparamagnetic nanobeads.

### Claim 10 (depends on 9)

The method of claim 9, wherein the superparamagnetic nanobeads have a hydrodynamic diameter between 10 nm and 500 nm.

### Claim 11 (depends on 9)

The method of claim 9, wherein the superparamagnetic nanobeads comprise magnetite or maghemite.

### Claim 12 (depends on 9)

The method of claim 9, wherein the superparamagnetic nanobeads have a magnetization of between 10 and 60 (A·m2)/kg.

### Claim 13 (depends on 1)

The method of claim 1, further comprising enriching the marked analytes over the magnetoresistive component via the gradient magnetic field, such that the marked analytes are locally present in a concentration increased from sample concentrations of 0.1 to 104 analytes per microliter by a factor of between 100 and 10,000.

### Claim 14 (depends on 1)

The method of claim 1, further comprising adjusting a speed of the flow such that the analytes roll over the magnetoresistive component with a constant speed.

### Claim 15

A method for magnetic flow measurement of an analyte comprising:
magnetic marking of analytes in a sample with magnetic nanobeads;
generating a flow of the analytes over a sensor arrangement, the flow of the analytes being guided at least over a magnetoresistive component;
enriching the marked analytes over the magnetoresistive component with a gradient magnetic field;
generating a homogeneous magnetic field, the homogeneous magnetic field and the magnetoresistive component being arranged with respect to one another such that the homogeneous magnetic field is not detected by the magnetoresistive component; and
detecting the marked analytes individually;
wherein the magnetic marking is implemented such that each marked analyte of the analytes has a stray magnetic field with a maxima detectable by the magnetoresistive component and disposed at a distance from a center of the analyte less than a hydrodynamic radius of the analyte.

### Claim 16 (depends on 15)

The method of claim 15, further comprising enriching the marked analytes over the magnetoresistive component via the gradient magnetic field, such that the marked analytes are locally present in a concentration increased by a factor of between 100 and 10,000.

### Claim 17 (depends on 15)

The method of claim 15, further comprising enriching the marked analytes over the magnetoresistive component via the gradient magnetic field, such that the marked analytes are locally present in a concentration increased from sample concentrations of 0.1 to 104 analytes per microliter by a factor of between 100 and 10,000.

### Claim 18 (depends on 15)

The method of claim 15, wherein the marked analytes are in direct contact with one another when flowing over the magnetoresistive component.

### Claim 19 (depends on 15)

The method of claim 15, further comprising adjusting a speed of the flow such that the analytes are guided over the magnetoresistive component with a constant speed.

### Claim 20 (depends on 15)

The method of claim 15, further comprising adjusting a speed of the flow such that the analytes roll over the magnetoresistive component with a constant speed.
