BACKGROUND

In technology and medicine, there is a wide field of application for nanoparticles having magnetic properties. They may be used as markers for specific properties, such as the vitality of cells, as contrast agents or as tracers for illustrating flow or vessels. The magnetic properties may be measured indirectly or directly.

One example for an indirect measurement method, for example, is magnetic resonance imaging (MRI), wherein substances containing iron or gadolinium are employed as contrast agents. Here, detection usually is by way of the changed relaxation properties of the surrounding protons. This allows for both determining the properties of the contrast agents and performing localization. There are a multitude of such particles and contrast agents having magnetic properties, including a number of functionalized particles. These are provided with special surface coatings and/or bonding sites in order to bond to special cells, for example. In the event of such bonds being effected, the particles both are located at the targets and may change their properties due to clustering, for example.

For the direct detection of magnetic particles, Gleich and Weizenecker, in Nature Vol 435/30 p. 1214ff, 2005, have presented a method for Magnetic Particle Imaging (MPI) capable of locating particles with a non-linear magnetization curve. This method is based on the fact that the magnetization of the particles has non-linearities only for small field strengths in an external alternating magnetic field, but reaches saturation for high field strengths, which then shows linear behavior. Across an additional field with a correspondingly great magnetic field formed so as to have a very small field or is field-free in a very small region, the field-free point (FFP), only the particles in this field-free point show non-linear magnetization behavior. Detection is done through measurement of the particles' magnetization. If higher harmonics of the frequency of the alternating field are found in the Fourier decomposition (spectrum), it can be gathered therefrom that particles are present in the field-free point, and an image can be calculated by scanning the sample with the field-free point. These higher harmonics are employed for evaluation.

SUMMARY

An implementation provides improved method and an improved apparatus for analyzing a sample volume comprising magnetic particles.

More particularly, one implementation provides a method and apparatus for analyzing a sample volume comprising magnetic particles in accordance with the main claims.

The approach described is suited as a detection method for magnetic particles. According to embodiments of the described approach, localization and additionally or alternatively measurement of the particle properties may be done by way of measuring the magnetic permeability. Advantageously, use of a single coil is sufficient here, which coil may be employed both to generate a magnetic excitation field acting on a sample volume and to obtain information on magnetic permeability of the sample volume. From the information on the magnetic permeability of the sample volume, for example, it can be gathered if at least one magnetic particle is present in the sample volume.

A method for analyzing a sample volume comprising magnetic particles comprises: applying an electric excitation signal to a measuring coil so as to generate a magnetic field acting on the sample volume using the measuring coil; sensing an electric measurement signal dependent on the inductance of the measuring coil; and analyzing magnetic permeability of the sample volume using the measurement signal.

Magnetic field lines of the magnetic field generated by the measuring coil may pass through the sample volume. The sample volume may be a region to be analyzed or a sample itself. For example, the sample volume may also include an area to be analyzed. According to different embodiments, the sample volume may be arranged inside the measuring coil, directly adjacent to the measuring coil or spaced from the measuring coil. Depending on the state of the sample volume, there may be no magnetic particles or at least one magnetic particle in the sample volume. A magnetic particle may be magnetic material, which may be introduced into the sample volume as a sample, for example. The measuring coil may comprise one coil winding or a plurality of coil windings. The coil may have a suitable shape, for example a cylindrical shape. The coil may be connected in a suitable circuit, for example a bridge circuit. The excitation signal may be applied to the measuring coil directly or via one or more elements. The excitation signal may be an alternating signal. Thus, the magnetic field may be an alternating field. For example, the excitation signal may be an alternating voltage or an alternating current. The measurement signal may represent an electric voltage. Such a measurement signal may be detected by way of voltage metering. For example, a voltage dropping over the coil may be sensed. The measurement signal may also represent an electric current. Such a measurement signal may be sensed by way of current measurement, for example by measuring the current flowing through the coil. The sensing the measurement signal and the applying the excitation signal may be executed simultaneously. The sensing and the applying may be executed over an extended period of time. If the excitation signal is an alternating signal, the measurement signal may be sensed while the excitation signal passes through one or more oscillation phases, for example. The inductance of the coil is dependent on the magnetic permeability of the sample volume. If the magnetic permeability of the sample volume changes, the inductance of the measuring coil changes. Thus, the measurement signal may indicate the magnetic permeability or a change in magnetic permeability of the sample volume. The analyzing the magnetic permeability of the sample volume may thus comprise evaluation of a quantity, a change and a temporal course of the measurement signal. Through evaluation of the measurement signal, information on the magnetic permeability of the sample volume may be obtained. Magnetic permeability of the sample volume may be the ratio of the magnetic flux density within the sample volume to the magnetic field strength within the sample volume. The information on the magnetic permeability may, in turn, be used to analyze a magnetic property of the matter within the sample volume, for example to detect at least one magnetic particle in the sample volume.

The acts of the method may be executed to measure the permeability of the sample volume. From the permeability curve of the sample volume resulting therefrom, the magnetization curve of the sample volume can be determined. In this way, both linear and non-linear magnetization curves can be determined.

The method may comprise comparing the measurement signal to a reference signal. The reference signal may be a reference voltage or a reference current, for example, as explained subsequently. Through the comparison, the magnetic permeability of the sample volume may be determined. The reference signal may represent a further electric measurement signal dependent on the inductance of the measuring coil while the measuring coil generates a magnetic field acting on a reference volume. The reference volume may comprise a reference sample, for example air. Thus, the measurement signal and the reference signal may be sensed at different times using the same measuring coil, once while the magnetic field acts on the sample volume (for determining the measurement signal) and once while the magnetic field acts on the reference volume (for determining the reference signal). At both times, the measuring coil may be excited by means of the same excitation signal. For example, the reference volume may be filled with a material of known magnetic properties, for example air. Thus, the sample volume may, for example, be a volume in which there is a sample, and the reference volume may be the same volume, but in which there is no sample. The reference signal may be sensed once and then stored. Thus, in the comparing, the measurement signal may be compared to a stored reference signal. The comparison may be performed by way of a suitable combination of the measurement signal and the reference signal. For example, the magnetic permeability may be determined on the basis of a difference between the measurement signal and the reference signal as well as a magnetic permeability associated with the reference signal. Thus, the magnetic permeability of the sample volume may be determined very easily.

According to one embodiment, a first contact of the measuring coil may be connected to a first terminal for applying the electric excitation signal via a first element, a second contact of the measuring coil may be connected to a second terminal for applying an electric balancing signal via a second element, and the second contact of the measuring coil may be connected to a measurement interface. The elements may, for example, be electric lines, resistors, capacitors or coils. An element may also represent a series connection and/or parallel connection of several elements. In the applying, the excitation signal may be applied to the first terminal and the balancing signal may be applied to the second terminal. In the sensing, the measurement signal may be sensed at the measurement interface. The balancing signal may represent a signal with which a reference voltage is present at the measurement interface if the magnetic field generated by the measuring coil acts on a reference volume. The reference voltage may have a certain voltage value, for example zero volts. A value or course of the balancing signal may have been determined during a reference measurement, wherein the magnetic field of the measuring coil acts on the aforementioned reference volume. This allows for using very simple circuits for providing the excitation signal and the balancing signal for analyzing the sample volume.

According to another embodiment, a first contact of the measuring coil may be connected to a first terminal for applying the electric excitation signal via a first element, a second contact of the measuring coil may be connected to a second terminal for applying an electric balancing signal via a second element, and the second contact of the measuring coil may be connected to a measurement interface. In the applying, the excitation signal may be applied to the first terminal and the balancing signal may be applied to the second terminal. In the sensing, the balancing signal may be sensed as the measurement signal. The balancing signal may be formed so as to set a certain reference voltage at the measurement interface depending on whether the magnetic field generated by the measuring coil acts on the sample volume or a reference volume. Thus, the balancing signal may be readjusted continuously so as to set the certain reference voltage. The reference voltage may be zero volts, for example. Advantageously, this way no reference measurement is necessary.

The method may comprise applying a further electric excitation signal to a further measuring coil so as to generate a further magnetic field acting on a further sample volume using the further measuring coil. Furthermore, the method may comprise sensing a further electric measurement signal dependent on the inductance of the further measuring coil. The further measurement signal may allow for analysis of the magnetic permeability of the further sample volume due to the dependence of the inductance of the further measuring coil on the magnetic permeability of the further sample volume. The two sample volumes may be identical, overlap each other at least partially or not overlap each other. In case the sample volumes overlap each other at least partially, a sample can be analyzed very accurately. For example, spatial distribution of the magnetic material within the sample can be analyzed.

The method may comprise determining a distribution of the magnetic particles in the sample volume and the further sample volume using the measurement signal, the further measurement signal and information on a position of the sample volume, a position of the further sample volume, information on a characteristic of the excitation signal and information on a characteristic of the further excitation signal. In this way, spatial distribution of the magnetic particles can be determined by way of suitable choice of the characteristics of the excitation signal is.

Additionally or alternatively, the method may comprise exposing the sample volume and the further sample volume to an additional magnetic field. Furthermore, the method may comprise determining a distribution of the magnetic particles in the sample volume and the further sample volume using the measurement signal, the further measurement signal and information on a characteristic of the additional magnetic field in the sample volume and the further sample volume. Thus, there is another way to determine the spatial distribution of the magnetic particles.

According to one embodiment, the method may comprise exposing the sample volume to an inhomogeneous additional magnetic field. In the analyzing, a distribution of the magnetic particles in the sample volume may be determined using the measurement signal and information on a spatial course of the additional magnetic field within the sample volume. The information on the spatial course may, for example, comprise information on a position of a portion of the additional magnetic field with low magnetic field strength.

The applying, sensing and the exposing may be executed multiple times, wherein the spatial course of the additional magnetic field may be changed in the repeated acts of exposing the sample volume. In the analyzing, the distribution of the magnetic particles may be determined using the measurement signal is sensed in the repeated acts of sensing and information on a change in the spatial course of the additional magnetic field during the repeated acts of exposing. Thus, for example, consecutive acts of sensing may be executed with a different spatial course of the additional magnetic field each. With the spatial course of the additional magnetic field during the sensing of the individual measurement signals being known, for example, a special distribution of the magnetic permeability or a spatial distribution of the magnetic particles within the sample volume can be determined.

An apparatus for analyzing a sample volume comprising magnetic particles comprises: a measuring coil formed to generate a magnetic field acting on the sample volume in response to application of an electric excitation signal to the measuring coil; and a measurement interface for sensing an electric measurement signal dependent on the inductance of the measuring coil, with the measurement signal allowing for analysis of the magnetic permeability of the sample volume due to the dependence of the inductance of the measuring coil on the magnetic permeability of the sample volume

Such an apparatus is suitable for executing the acts of the aforementioned method for analyzing a sample volume comprising magnetic particles.

In such an apparatus, the sample volume may be arranged inside the measuring coil. In this way, for example, a sample arranged in a test tube may be analyzed. As an alternative, the sample volume may be arranged outside the measuring coil.

The apparatus may comprise a coil core guided through the measuring coil. One end of the coil core may be formed as a tip for exposing the sample volume. The magnetic field of the measuring coil may be concentrated on the sample volume through the tip. Moreover, the coil core may be used to bridge a spatial distance between the coil and the sample volume.

The apparatus may comprise evaluation means. The evaluation means may be formed to determine the magnetic permeability of the sample volume using the measurement signal. The magnetic permeability of magnetic particles allows for analyzing both the particles themselves and their environment.

According to one embodiment, a first contact of the measuring coil may be connected to a first terminal for applying the electric excitation signal via a first element, a second contact of the measuring coil may be connected to a second terminal for applying an electric balancing signal via a second element, and the second contact of the measuring coil may be connected to the measurement interface. In this way, the measuring coil may be included in a suitable bridge circuit.

The first element may be a capacitor or an electric line. The second element may be a resistor, a coil or an electric line. By way of a suitable choice of the elements, metrological properties of the apparatus can be adjusted.

The apparatus may comprise a further measuring coil. The further measuring coil may be formed to generate a further magnetic field acting on a further sample volume in response to applying a further electric excitation signal to the further measuring coil. The apparatus may further comprise a further measurement interface for sensing a further electric measurement signal dependent on the inductance of the further measuring coil. The further measurement signal may allow for analyzing the magnetic permeability of the further sample volume due to the dependence of the inductance of the further measuring coil on the magnetic permeability of the further sample volume. The sample volume is may be different or at least partially identical. The sample volume and the further sample volume may thus overlap at least partially. Using the further measuring coil, for example, a sample volume can be analyzed more accurately, or a larger sample volume can be analyzed, as compared with using only one measuring coil. The apparatus may comprise two, three or more measuring coils.

