# US 8,542,014 B2 · Magnetic resonance imaging of single domain nanoparticles

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- Number: US 8,542,014 B2
- Document ID: US8542014B2
- Status: Granted
- Kind: B2
- Application number: 13/617,502
- Filed: 2012-09-14
- Published: 2013-01-17
- Granted: 2013-09-24
- Earliest claimed: 2008-09-30
- Assignees: Imec
- Applicants: Stephanie Teughels; Peter Vaes
- Inventors: Stephanie Teughels; Peter Vaes
- Web page: https://patentgrep.com/patent/US8542014B2

## CPC

- G01N 24/10: by using electron paramagnetic resonance (G01N24/12 takes precedence)
- B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
- B82Y 25/00: Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
- G01R 33/60: using electron paramagnetic resonance (G01R33/24, G01R33/62 take precedence)
- G01R 33/281: {Means for the use of in vitro contrast agents (G01R33/282 takes precedence; involving use of a contrast agent in MR imaging G01R33/5601; in vivo contrast agents A61K49/0002)}
- G01R 33/445: {MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging}
- G01R 33/5601: {involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent}
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

A method and system are disclosed for gathering information about an object including single domain particles which have a diameter in the range of about 5 to 80 nm. In one aspect, a method includes generating a static magnetic field of less than about 0.1 Tesla on the object and generating an RF energy, pulsed or continuous wave, so as to generate electron paramagnetic resonance of the single domain particles. The method also includes detecting the electron paramagnetic resonance of the single domain particles in the form of an image of the object. The single domain particles may have a predetermined diameter and a predetermined saturation magnetization and the applied magnetic field may be such that the single domain particles reach a magnetization being at least about 10% of the saturation magnetization. The method may be used for detecting tags in an object and for activating tags.

## Claims

### Claim 1

A system for gathering information about an object, the object comprising single domain iron oxide particles having a diameter in the range of 5 nm to 80 nm, the system comprising:
a first field generator configured to generate a static magnetic field of less than 0.1 Tesla for the object;
a second field generator configured to generate radio frequency (RF) energy as a continuous wave for the object at a frequency to generate electron paramagnetic resonance (EPR) of the single domain iron oxide particles; and
a detection unit configured to detect the electron paramagnetic resonance of the single domain iron oxide particles, wherein the electron paramagnetic resonance is proportional to the magnetization of the single domain iron oxide particles, the magnetization inducing an RF field which is detected by the detection unit, wherein the detection unit comprises a receiver adapted for identifying a response to the generated RF energy and adapted for identifying a signature imposed on the response being indicative of the electron paramagnetic resonance exhibited by the single domain particles.

### Claim 2 (depends on 1)

The system according to claim 1, wherein the detection unit is adapted for detecting the electron paramagnetic resonance of the single domain particles in the form of a volumetric image of the object.

### Claim 3 (depends on 1)

The system according to claim 1, wherein the second field generator is adapted for generating the RF energy at an RF frequency below 1 GHz.

### Claim 4 (depends on 1)

The system according to claim 1, wherein the first field generator is adapted for generating a static magnetic field of less than 0.05 Tesla.

### Claim 5

A method of gathering information about an object, the object comprising single domain particles which comprises iron oxide, the particles having a diameter in the range of 5 nm to 80 nm, the method comprising:
generating a static magnetic field of less than 0.1 Tesla for the object;
generating radio frequency (RF) energy as a continuous wave for the object at a frequency to generate electron paramagnetic resonance (EPR) of the single domain particles in the object; and
detecting electron paramagnetic resonance (EPR) of the single domain particles upon interaction of the object with a static magnetic field of less than 0.1 Tesla and with the radio frequency (RF) energy as a continuous wave at a frequency to generate EPR of the single domain particles,
wherein the electron paramagnetic resonance is proportional to the magnetization of the single domain iron oxide particles, the magnetization inducing a RF field,
wherein detecting the electron paramagnetic resonance comprises identifying a response to the generated RF energy as a continuous wave and identifying a signature imposed on the response being indicative of electron paramagnetic resonance exhibited by the single domain particles.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the detecting comprises detecting in the form of a volumetric image of the object.

### Claim 7 (depends on 5)

The method according to claim 5, wherein the single domain particles are monodisperse.

### Claim 8 (depends on 5)

The method according to claim 5, wherein the single domain particles are super-paramagnetic particles.

### Claim 9 (depends on 5)

The method according to claim 5, wherein the single domain particles comprise magnetite.

### Claim 10 (depends on 5)

The method according to claim 5, wherein generating RF energy comprises generating RF energy at a RF frequency below 1 GHz.

### Claim 11 (depends on 5)

The method according to claim 5, wherein generating a static magnetic field comprises generating a static magnetic field of less than 0.05 Tesla.

### Claim 12 (depends on 5)

The method according to of claim 5, wherein the single domain particles have a predetermined saturation magnetization and the static magnetic field is selected so that a magnetization of the single domain particles of at least 10% of the saturation magnetization is reached.

### Claim 13 (depends on 5)

A method of scanning an item tagged with a tag, the tag comprising single domain particles which comprises iron oxide, the particles having a diameter in the range of 5 nm to 80 nm, the method comprising gathering information about the tag by performing a method for gathering information about an object according to claim 5.

### Claim 14 (depends on 5)

A non-transitory computer-readable medium having stored therein a program which, when executed on a computer, performs the method according to claim 5.

### Claim 15

A method of gathering information about an object, the object comprising single domain particles which comprise iron oxide having a predetermined diameter and a predetermined saturation magnetization, the method comprising:
detecting electron paramagnetic resonance (EPR) of the single domain particles upon interaction of the object with a static magnetic field of less than 0.1 Tesla and with radio frequency (RF) energy transmitted as a continuous wave at a frequency to generate EPR of the single domain particles, wherein the static magnetic field is selected so that a magnetization of the single domain particles of at least 10% of the saturation magnetization is reached, wherein the electron paramagnetic resonance is proportional to the magnetization of the single domain iron oxide particles, the magnetization inducing an RF field, wherein detecting the electron paramagnetic resonance comprises identifying a response to the generated RF energy as a continuous wave and identifying a signature imposed on the response being indicative of electron paramagnetic resonance exhibited by the single domain particles.

### Claim 16 (depends on 15)

A method of scanning an item tagged with a tag, the method comprising gathering information about the tag by performing a method for gathering information about an object according to claim 15.

### Claim 17 (depends on 15)

A non-transitory computer-readable medium having stored therein a program which, when executed on a computer, performs the method according to claim 15.

### Claim 18

A method of gathering information about an object, the object comprising single domain particles which comprise iron oxide having at least a predetermined longitudinal relaxation time, the method comprising:
detecting electron paramagnetic resonance (EPR) of the single domain particles upon interaction of the object with a static magnetic field of less than 0.1 Tesla and with radio frequency (RF) energy transmitted as a continuous wave at a frequency to generate EPR of the single domain particles, wherein the electron paramagnetic resonance is proportional to the magnetization of the single domain iron oxide particles, the magnetization inducing an RF field, wherein detecting the electron paramagnetic resonance comprises identifying a response to the generated RF energy as a continuous wave and identifying a signature imposed on the response being indicative of electron paramagnetic resonance exhibited by the single domain particles.

### Claim 19

A receiver for detecting single domain particles comprising iron oxide, the single domain particles having a diameter in the range of 5 nm to 80 nm and having an electron paramagnetic response to an applied static magnetic field of less than 0.1 Tesla for the object and applied radio frequency (RF) energy transmitted as a continuous wave for the object at a frequency to generate electron paramagnetic resonance (EPR) of the single domain particles, the receiver comprising:
a detector configured to detect a response of the single domain particles comprising iron oxide in reply to the applied RF energy transmitted as a continuous wave to the applied RF energy and to identify a signature imposed on the response being indicative of electron paramagnetic resonance exhibited by the single domain particles; and
a discriminator configured to identify in the identified signature the electron paramagnetic response of the single domain particles,
wherein the electron paramagnetic resonance is proportional to the magnetization of the single domain iron oxide particles, the magnetization inducing an RF field.
