Method and probe for detecting one or more magnetic particles in a measurement volume

Abstract

Magnetic particles can be viable for locating anatomical features, but conventional susceptibility devices lack sensitivity. A method for detecting one or more magnetic particles is provided, by applying an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f), measuring the one or more resulting energy signals 330 using at least two detection coils 300 in series but connected oppositely, analyzing the signal for a second harmonic (f2) of the fundamental excitation frequency 230 (f), and compensating inductive mismatching between the at least two detection coils using software and / or hardware. This provides a quantitative measure of the magnetic particles present, allowing for more precise analysis and greater sensitivity.

Description

[0001] METHOD AND PROBE FOR DETECTING ONE OR MORE MAGNETIC PARTICLES IN A MEASUREMENT VOLUME

[0002] The present disclosure relates generally to a method and probe for detecting one or more magnetic particles in a measurement volume, and more specifically to the technical field of detecting, measuring magnetic variables, and analyzing magnetic particles in various applications.

[0003] BACKGROUND ART

[0004] Sentinel lymph node biopsy (SLNB) is the standard of care for staging disease progression in patients found node-negative by clinical and radiological examinations for cancer types such as breast cancer or melanoma. In clinical practice since the late 1990s, SLNB is a minimally invasive surgery that replaces the more extensive procedure called completion axillary lymph node dissection (ALND), in which all axillary nodes were removed. Currently recommended for most cancer patients, SLNB followed by appropriate treatment provides similar outcomes to ALND, but with reduced morbidity.

[0005] Conventionally, radioactive tracers and / or blue dye are used to identify sentinel lymph nodes (SLNs) for biopsy. This so-called "combined technique" can be effective but suffers from drawbacks related to substantial regulation governing the use of radiotracers and the associated costs of handling and disposal, as well as related safety concerns. As a result, SLNB is limited to 66% of patients in the developed world and used very rarely in low resource countries. The use of radiation is governed by strict legislation, and nuclear medicine personnel are often required to administer injections. Medical personnel and patients are exposed to radiation and the radioactive waste generated during surgery requires temporary storage causing logistical challenges.

[0006] The patent document number US-20150338376A1 discloses a method and apparatus for measuring an amount of superparamagnetic material in an object by applying an alternating magnetic field with a first period to the object at a strength lower than saturation; measuring a first magnetic susceptibility with a detection coil; applying a static magnetic field for a second period equal or larger than the first period at a strength towards saturation; measuring a second magnetic susceptibility; and determining the amount of superparamagnetic material from a difference between the measured first and second susceptibility. This approach presents limitations.

[0007] PROBLEM STATEMENT

[0008] This disclosure addresses the problem of detecting one or more magnetic particles in a measurement volume, and in particular detection of one or more magnetic particles comprised in at least one cluster.

[0009] This disclosure provides a method and probe for detecting of one or more magnetic particles in a measurement volume by analyzing a contribution of the second harmonic of a fundamental excitation frequency. The method involves applying an alternating excitation magnetic field, measuring one or more resulting energy signals with one or more detection coils, such as measuring one or more voltages across one or more detection coils, and detecting one or more magnetic particles based on a contribution of the second harmonic. The probe includes excitation coils, detection coils, a detector, and an analyzer for performing the detection and analysis. Additionally, this disclosure discloses compensating one or more inductive mismatches (or a degree of inductive mismatching) between the at least two detection coils using software and / or hardware. Additionally or alternatively, this disclosure discloses the use of static offset magnetic fields, generated by permanent magnets, and compensation mechanisms for enhancing the accuracy of the detection process. In a specific development, this disclosure provides a method and probe for sentinel lymph node biopsy.

[0010] BRIEF DESCRIPTION OF DRAWINGS

[0011] Features and advantages of some embodiments of the present disclosure, and the manner in which the same are accomplished, will become more readily apparent upon consideration of the following detailed description of the disclosure taken in conjunction with the accompanying drawings, which illustrate preferred and exemplary embodiments, and which are not necessarily drawn to scale, wherein:

[0012] FIG. 1A to FIG. 1 C schematically show aspects of a method for detecting one or more magnetic particles in a measurement volume according to the present disclosure;

[0013] FIG. 2 schematically depicts a cross-section through a first embodiment of a probe according to the present disclosure; FIG. 3 schematically depicts a cross-section through a second embodiment of a probe according to the present disclosure; and

[0014] FIG. 4 schematically depicts a cross-section through a third embodiment of a probe according to the present disclosure.

[0015] In the figures, the same or similar features are referenced by the same reference numerals.

[0016] DEFINITIONS

[0017] The term "probe" is used herein to refer to a device suitable for detecting magnetic particles in a measurement volume. Optionally, it can be arranged to be held in a hand of a user.

[0018] An "excitation coil" designates an electrical coil that is suitable for applying an alternating and / or static electromagnetic field to a measurement volume.

[0019] "Fundamental excitation frequency" (f) refers to a center frequency in a spectrum at which an alternating electromagnetic energy field is generated.

[0020] A "detection coil" designates an electrical coil that is suitable for detecting alternating magnetic fields. For example, a voltage over a detection coil can be proportional to a rate of change of a magnetic flux.

[0021] "Static magnetic field" refers to a magnetic field arranged to have an approximately constant magnetic field strength over a significant period of time.

[0022] "Alternating magnetic field" refers to a magnetic field arranged to have a time-varying magnetic field strength.

[0023] "Compensation coil" designates an electrical coil that is suitable for applying an alternating and / or static electromagnetic field to compensate for one or more inductive mismatches between the two detection coils. "Target" designates a feature of interest proximate or comprising one or more magnetic particles to be detected. Optionally, the one or more magnetic particles can be comprised in at least one cluster.

[0024] "Magnetization curve M(H)" describes or depicts how a magnetization field (M) of a magnetic material varies as a function of an excitation field strength (H).

[0025] "Excitation strength" designates an amplitude of an excitation magnetic field.

[0026] "Nanoparticles" designates particles with a hydrodynamic diameter of less than approximately 700 nm. The particle diameter can be smaller, for example less than 100nm if the particle forms a core surrounded by one or more coatings and / or stabilizing shells.

[0027] A "variable transformer" designates a transformer which is capable of varying the mutual inductance between primary and secondary winding, for example by varying a ratio of the primary to secondary winding and / or by varying a flux leakage.

[0028] A "magnetic particle" designates a magnetic particle, which includes a magnetic nanoparticle, a paramagnetic particle, a paramagnetic nanoparticle, a superparamagnetic particle, a superparamagnetic nanoparticle, and any combinations thereof.

[0029] The term “first harmonic” (f1 ) is an alternating signal with a center frequency that is approximately the same (1x) as a “fundamental frequency” (f). The term "second harmonic" (f2) refers to an alternating signal with a center frequency that is approximately two-times (2x) a fundamental frequency (f). If there are multiple peaks in a spectrum, a 'fundamental frequency' (f) is the frequency of a peak at the lowest frequency in the spectrum.

[0030] In the figures, a first axis 910, a second axis 920, and a third axis 930 are depicted. The first axis 910 is perpendicular to the second axis 920, and the third axis 930 is perpendicular to both the first axis 910 and the second axis 920. In the examples described, the first axis 910 is assumed to direct in an X direction, the second axis 920 is assumed to direct in a Y direction, and the third axis 930 is assumed to direct in a Z direction. Conventionally, in the description, the axes in the corresponding directions are therefore named as X-axis 910, Y-axis 920, and Z-axis 930. Functionally, the X-axis 910 and Y-axis 920 can be interchanged. The probe described in this disclosure can be arranged by a skilled person to be used at different deviations from the conventional orientations and nominal co-ordinate axes.

[0031] FIG. 1 A to 1 C schematically show aspects of a method for detecting one or more magnetic particles in a measurement volume 690 according to the present disclosure. In particular detection, the method is advantageous for detecting one or more magnetic particles comprised in at least one cluster 650.

[0032] The one or more magnetic particles can comprise one or more metals with a relatively high susceptibility, such as iron (Fe), cobalt (Co), manganese (Mn). nickel (Ni), or any combination thereof. For example, one or more magnetic particles comprising an iron oxide, such as magnetite (Fe3O4), maghemite (Fe2O3 or y- Fe2O3), or any combination thereof.

[0033] Advantageously, the one or more magnetic particles can comprise one or more substances suitable for forming nanoparticles, such as an oxide, an iron oxide, iron (Fe), cobalt (Co), manganese (Mn), nickel (Ni), platinum (Pt), or any combination thereof. For example, a cluster 650 can comprise one or more magnetic nanoparticles.

[0034] For example, at least one cluster 650 is comprised in a human or animal body, such as comprised in an anatomical feature.

[0035] For example, at least one cluster 650 is comprised in a lymph node, such as a sentinel lymph node. For example, a lymph node can have an approximate spherical diameter of 1 cm, a smaller diameter or a larger diameter.

[0036] FIG. 1A schematically depicts a cross-section through a probe 100 according to the present disclosure which is suitable for performing one or more methods described in this disclosure. The probe 100 is suitable for detecting one or more magnetic particles in a measurement volume 690. One or more dimensions of the measurement volume 690 are arranged to define a search volume in which the target 650 is expected to be found. In general, the probe 100 comprises one or more excitation coils 200 and at least two detection coils 300. For example, the excitation coils 200 and the detection coils 300 can be made with 10's to 1000's of turns comprising wire with an average diameter of wire in the range 0.1 mm -1 mm. The probe 100 further comprises a detector 880 and an analyzer 870, which are described in more details with reference to FIG. 2 to FIG. 4. Although described herein as separate functions, these functions can be at least partially integrated, and they can be implemented using one or more common components.

[0037] The one or more excitation coils 200 are arranged to apply an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f) to the measurement volume 690. The at least two detection coils 300 are arranged to measure one or more resulting energy signals 330. The at least two detection coils 300 are arranged in series, but connected oppositely as described in more details with reference to FIG. 2 to FIG. 4. The detector 870 is arranged for measuring a contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300. The analyzer 880 is arranged for determining a presence of one or more magnetic particles in the measurement volume 690 by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0038] For example, the method can be arranged to detect one or more magnetic particles at a predetermined distance, such as 20cm, 10cm, or 5cm, by setting or modifying one or more parameters which are suitable to increase or to decrease a degree of influence of the one or more magnetic particles on the one or more resulting energy signals 330.

[0039] FIG. 2 depicts a schematic cross-section through a first embodiment of a probe 100 (a first probe 101 ) showing magnetic-field related parts. Exterior parts and / or housing parts are not shown. As depicted in FIG. 1 A, the target 600, disposed in a measurement volume 690, comprises at least one cluster 650 comprising one or more magnetic particles. One or more dimensions of the measurement volume 690 are arranged to define a search volume in which the target 650 is expected to be found.

[0040] In the example depicted in FIG. 2, the first probe 101 comprises: one or more excitation coils 200, at least two detection coils 300, and optionally one or more permanent magnets 400. The at least two detection coils 300 are arranged with respect to the one or more excitation coils 200 such that during application of the alternating excitation magnetic field 270, a measurement by the at least two detection coils 300 without a target 600 is approximately zero. For example, the at least two detection coils 300 can be arranged such that during application of the alternating excitation magnetic field 270, a measured voltage across the at least two detection coils 300 without the target 600 is approximately 0 volts. Alternatively, the target 600 can be present in the measurement volume 690, but appear functionally absent if the one or more resulting energy signals 330 are too weak for measurement by the at least two detection coils 300. For example, if too few magnetic particles are comprised in the target 600 and / or if the magnetic particles comprised in the target 600 have a too low susceptibility.

[0041] In the example depicted in FIG. 2, the at least two detection coils 300 comprise a first detection coil 301 and a second detection coil 302, connected electrically in anti-series. Anti-series means connecting the first detection coil 301 and the second detection in series, but swapping the terminals of one of the coils such that the coils are connected in series with opposite winding directions.

[0042] It can be advantageous to functionally arrange the coils 300 such that a mutual inductance between the first detection coil 301 and the one or more excitation coils 200 is approximately equal to a corresponding mutual inductance between the second detection coils 302 and the one or more excitation coils 200. Thereby, the at least two detection coils 300 are arranged to provide a high degree of cancellation of the excitation magnetic field 270. Additionally or alternatively, the at least two detection coils 300 can be arranged to provide a high degree of cancellation of any external homogeneous magnetic field, such as the earth’s magnetic field.

[0043] As depicted in the example of FIG. 2, the first detection coil 301 and second detection coil 302 can be optionally arranged along a common axis of the first probe 101 .

[0044] As depicted in the example of FIG. 2, the first detection coil 301 and second detection coil 302 can be optionally separated along the common axis of the first probe 101 by the one or more excitation coils 200. However, the first detection coil 301 and the second detection coil 302 can optionally be wound at least partially together with the one or more excitation coils 200. Therefore, a significant physical separation along a common axis of the first probe 101 is not required.

[0045] As depicted in the example of FIG. 2, the first detection coil 301 can optionally be arranged proximate a first end of the one or more excitation coils 200, and the second detection coil 302 can optionally be arranged proximate a second end of the one or more excitation coils 200.

[0046] As depicted in the example of FIG. 2, the first detection coil 301 can be optionally arranged proximate a first end of the first probe 101 , wherein the first end of the first probe 101 is arranged to emit an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f),

[0047] As depicted in the example of FIG. 2, the first probe 101 comprises an energy source 810, arranged to provide one or more excitation coils 200 with a suitable excitation input signal such that the one or more excitation coils 200 generate a suitable alternating excitation magnetic field 270. For example, a suitable excitation input signal can comprise an excitation frequency approximately equal to a fundamental excitation frequency 230 (f). For example, a suitable excitation input signal can be a sine wave. For example, a suitable excitation input signal can comprise a sine wave at a fundamental excitation frequency 230(f).

[0048] The one or more excitation coils 200 are arranged to apply the alternating excitation magnetic field 270 with the fundamental excitation frequency 230 (f) to the measurement volume 690. For example, the first probe 101 can be arranged to generate an alternating excitation magnetic field 270 with a flux density (B) in the measurement volume 690 in the range 0.1 to 10 mT.

[0049] Optionally, the first probe 101 can comprise at least a partial housing (not depicted).

[0050] Suitable electronics, photonics and / or software are provided, and arranged to drive the first probe 101 , acquire data, interpret signals, and / or perform the methods as described herein, Suitable electronics and / or photonics can be comprised in the first probe 101 , in a suitable base unit (not depicted) connected to the first probe 101 , or any combination thereof. Suitable electronics, and / or photonics can include components, such as one or more amplifiers, one or more low-noise pre-amplifiers, one or more filters, one or more temperature sensors, one or more power supplies, or any combination thereof. The first probe 101 and any optional base unit can be connected together using one or more electrical, optical, and / or wireless connections. Optionally, the electronics, photonics and / or software can be arranged to generate one or more audio signals and / or one or more user indications. The first probe 101 and / or optional base unit can comprise one or more user interfaces.

[0051] For example, suitable electronics can be comprised in one or more excitation circuits, arranged to provide energy to the one or more excitation coils 200 comprising an excitation frequency equal to the fundamental excitation frequency 230 (f). For example, one or more excitation amplifiers can be used to increase an amplitude of the excitation frequency. For example, suitable electronics can be comprised in one or more excitation coil drivers 210, arranged to provide energy to the one or more excitation coils 200 comprising an excitation frequency equal to the fundamental excitation frequency 230 (f).

[0052] As depicted in the example of FIG. 5A, the energy source 810 can comprise one or more excitation coil drivers 210. The one or more excitation coil drivers 210 can comprise one or more excitation resonance circuits 215 wherein a suitable excitation frequency source 216 is connected in series with an excitation capacitor 217 having a capacitance C. In the example depicted, the one or more excitation coils 200 have an inductance L, and are connected across the combination of the excitation frequency source 216 and the excitation capacitor 217. For this example, the resonance frequency can be configured using: f = 1 / (2pi*sqrt(LC)).

[0053] For example, if the fundamental excitation frequency 230 (f) is approx. 10kHz, and the inductance (L) of the one or more detection coils 200 is approximately 630uH, then the capacitance of the excitation capacitor 217 should be approximately 402nF.

[0054] Using one or more excitation resonance circuits 215 can yield an improved signal-to-THD (Total Harmonic Distortion) ratio and / or signal-to-noise ratio of the alternating excitation magnetic field 270, compared to the alternative use of one or more excitation amplifiers.

[0055] For example, suitable electronics can be comprised in one or more detection circuits, arranged for measuring a contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300.

[0056] For example, suitable electronics can be comprised in one or more detectors 870, arranged for measuring a contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300.

[0057] As depicted in the example of FIG. 5B, one or more detectors 870), can comprise one or more detection resonance circuits 871 , wherein a first detection coil 301 and a second detection coil 302 are connected electrically in anti-series, with the terminals of the second detection coil 302 switched such that the detection coils 310, 302 are connected in series with opposite winding directions. The one or more detection resonance circuits 871 comprise the at least two detection coils 300, with an inductance L, connected across a detection capacitor 878 with a capacitance C. For this example circuit, the resonance frequency can be configured using: f1 = 2f0 = 1 / (2pi*sqrt(LC)).

[0058] For example, if the detection frequency (f1 ) is approx. 20kHz, and the inductance (L) of the at least two detection coils 300 is approximately 2.5mH, then the capacitance of the detection capacitor 878 should be approximately 12.8nF.

[0059] Using one or more detection resonance circuits 871 can yield an improved signal-to- excitation signal and / or signal-to-noise ratio because a degree of unwanted energy detected due to any significant inductive mismatch between the first detection coil 301 and the second detection coil 302 can be reduced.

[0060] Advantageously, the first probe 101 can be arranged to at least partially take into account one or more of the following problems to optimize detection depth. Signal levels from the at least two detection coils 300 can be relatively low if, for example, the target 600 only comprises a relatively small amount of paramagnetic material and / or there is a relatively large distance between the paramagnetic material and one or more detection coils 300.

[0061] A signal-to-noise ratio can be increased by arranging the first probe 101 to operate under one or more of the following conditions a1 ) to a6): a1 ) increasing energy and / or power in one or more excitation circuits can provide higher amplitudes in an excitation magnetic field 270. This can cause an undesired increase in an operating temperature of the first probe 101 , which can be reduced by providing suitable cooling and / or heat transfer measures, and / or duty cycling. a2) Increasing one or more coil diameters can provide higher amplitudes in an excitation magnetic field 270, but this can increase one or more diameters of the first probe 101 . a3) Increasing a fundamental excitation frequency 230 (f) can result in a larger amplitude of one or more resulting energy signals 330, but this can increase a degree of loss in one or more excitation coils 200, for example due to an increased skin effect. The fundamental excitation frequency 230 (f) should not exceed a critical frequency of one or more magnetic particles which can reduce a degree of response to excitation. The critical frequency is related to one or more physical and / or magnetic properties of the one or more magnetic particles. a4) A strength of a magnetic field (B-field) applied by one or more excitation coils 200 can be influenced by one or more parameters, such as one or more dimensions of the one or more excitation coils 200 and the number of current-turns (amp-turns). Decreasing a wire diameter can mean that less current is required, whereby losses due to a skin effect and / or a proximity effect can decrease. But more voltage can be required, which can require more coil insulation, thereby increasing a contribution of insulation to the coil volume, and thus decreasing an amount of copper and increasing ohmic losses. A degree of thermal noise can also increase if a resistance of the one or more excitation coils 200 increase. a5) A strength of a magnetic field (B-field) detected by one or more detection coils 300 can be influenced by one or more parameters, such as one or more dimensions of the one or more detection coils 300. Decreasing a wire diameter can mean that an amplitude measured with the one or more detection 300 coils, such as a detected voltage, increases, but a degree of thermal noise can also increase. a6) One or more thermally-conductive materials can be used, such as one or more metals and / or one or more ceramics, to provide a degree of improvement to one or more thermal paths between one or more coils and an environment, for example one or more thermal paths to a different side of the first probe 101 . But using one or more metals can cause one or more currents to be induced which can cause an undesirable degree of asymmetry in one or more measurements, such as one or more detected voltages, between the first detection coil 301 and the second detection coil 302.

[0062] Advantageously, the first probe 101 can be arranged to at least partially take into account one or more of the following problems to provide a degree of optimization in a signal-to- noise ratio. An acceptable functioning of a compensation mechanism can require a lower degree of a harmonic distortion in one or more excitation signals for one or more excitation magnetic fields and / or a reasonably stable degree of a harmonic distortion over time. But a degree of harmonic distortion can be decreased by arranging the first probe 101 to operate under one or more of the following conditions b1 ) to b5): b1 ) Reducing one or more distortions in one or more active electronic components, such as in one or more amplifiers. b2) Compensating for a degree of a non-linear behavior of one or more passive and / or active electronic components, such as one or more resistances and / or capacitors wherein a temperature can vary harmonically in time due to one or more harmonic currents through it, thereby modulating a resistance / capacitance and causing a non-linear effect. It can therefore be advantageous to select one or more components with a smaller degree of temperature dependency. b3) Reducing a degree of a mechanical deformation of one or more coils due to, for example, one or more Lorentz forces. For example, if one or more coils are not sufficiently potted wherein one or more turns are not properly fixed within the one or more coils. Whatever the cause, a degree of a mechanical deformation can result in higher harmonics. In some cases, one or more mechanical resonance modes of one or more components of the first probe 101 can be excited, further increasing one or more mechanical deformations. It can therefore be advantageous to use one or more materials for coil potting with a higher elasticity modulus and / or providing a one or more aspects of a construction of the first probe 101 with a higher degree of stiffness. b-4) Reducing a degree of a cross-talk between one or more electronic components, which can cause a degree of unwanted modulation of one or more signals. It can therefore be advantageous to shield one or more components, for example by using one or more twisted pairs and / or use one or more balanced lines. b5) Reducing a degree of disturbance in one or more properties of one or more electronic components due to a degree of exposure to one or more alternating and / or static magnetic fields (B-fields). For example, due to a magnetoresistance, a Hall effect, or a similar effect. It can therefore be advantageous to shield one or more of these components from one or more magnetic field (B-field).

[0063] If one or more detection methods as described herein are to be used to detect and / or locate an anatomical feature in a human or animal body, suitable magnetic particles should first be administered to the body such that at least one cluster 650 comprising one or more magnetic particles forms in the anatomical feature of interest. For example, one or more magnetic particles can be injected into tissue. For example, one or more injections can be arranged to allow at least one cluster 650, comprising one or more magnetic particles, to form in a lymph node into which a solution comprising the particles drains, which is also called a "sentinel lymph node".

[0064] Detection of at least one cluster 650 comprising one or more magnetic particles can be achieved by using a method 700 for detecting one or more magnetic particles in a measurement volume 690 as depicted schematically in FIG. 1 A. In particular, the method depicted is suitable for detecting at least one cluster 650 comprising one or more magnetic particles. For example, the method depicted is suitable for detecting one or more magnetic particles comprising one or more superparamagnetic materials and / or one or more paramagnetic materials. For example, the method depicted is suitable for detecting one or more magnetic particles comprised in an anatomical feature, such as a lymph node or sentinel lymph node.

[0065] Paramagnetic describes any material that gets magnetized by an externally applied magnetic field, whereby the magnetization is in the same direction as the external magnetic field.

[0066] Preferably, at least one cluster 650 comprising one or more magnetic particles has a magnetic susceptibility (x) that is significantly different from that of the surrounding material in the measurement volume 690, whereby detection becomes possible using the first probe 101 as described herein.

[0067] FIG. 1 B depicts an example of a suitable magnetic susceptibility 630 (x), showing a relationship (or magnetization curve) between a particle magnetization 632 (M) and an excitation strength 634 (H) of an excitation magnetic field 270. The example of depicted FIG. 1 B is suitable for use in the detection method 700 depicted at least partially in FIG.

[0068] IA, and suitable for use in the probe 100 depicted in FIG. 1A and the first probe 101 depicted in FIG. 2.

[0069] The at least one cluster 650 comprises one or more magnetic particles, whereby the at least one cluster 650 has the magnetic susceptibility 630 (x) relationship depicted in FIG.

[0070] I B. The first probe 101 is arranged to apply an excitation magnetic field 270 with an excitation strength 634 such that the one or more magnetic particles are at least partially magnetized. One or more field strengths of the alternating excitation magnetic field 270 can therefore be arranged to influence at least one region of use of the magnetic susceptibility 630 relationship, thereby determining a degree of particle magnetization 632 due to the excitation strength 634 of the excitation magnetic field 270.

[0071] The excitation magnetic field 270 is preferably arranged such that the excitation strength 634 is not so strong as to drive a significant amount of the magnetic material comprised in the cluster 650 into saturation.

[0072] The excitation magnetic field 270 is preferably arranged such that the excitation strength 634 is strong enough to avoid a linear response . The excitation magnetic field 270 is preferably arranged such that the excitation strength 634 is at least partially using at least one region of the magnetic susceptibility 630 relationship with a significant degree of curvature of M(H). that is, a significant value of: d2M dx - or — dH2dH

[0073] For example, an excitation strength 634 (H) in the range 100 to 10000 A / m can be suitable for detecting at least one cluster 650 comprising one or more magnetic particles comprising an iron oxide.

[0074] FIG. 1 C depicts an example of a suitable excitation magnetic field 270, having a degree of alternation during an excitation period 280 (of time). The excitation magnetic field 270 has a fundamental excitation frequency 230 (f). The example of FIG. 1 C is suitable for use in the detection method 700 depicted at least partially in FIG. 1 A, and suitable for use in the probe 100 depicted in FIG. 1A and the first probe 101 depicted in FIG. 2.

[0075] The detection method 700 for detecting one or more magnetic particles therefore comprises one or more of steps a) to d): a) applying an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f) to a measurement volume 690 comprising the target 600 during an excitation period 280. For example, the fundamental excitation frequency 230 (f) of the excitation magnetic field 270 can be between 2.5 kHz and 40 kHz. b) Measuring one or more resulting energy signals 330 with at least two detection coils 300 connected in series but connected oppositely (connected in anti-series) For example, by measuring one or more voltages, one or more currents, one or more powers, or any combination thereof, with one or more detection coils 300.

[0076] The one or more resulting energy signals 330 are influenced by one or more physical and / or magnetic parameters of the one or more magnetic particles comprised in the target 600. A degree of influence can depend on one or more parameters such as: an amount of magnetic material comprised in the target 600, a magnetic property of one or more magnetic particles, a volume of one or more magnetic particles, a dimension of one or more magnetic particles, a distance between one or more magnetic particles and one or more detection coils 300, a separation distance between two or more magnetic particles, an amount of magnetic particles comprised in at least one cluster 650, an amount of clusters 650 in the target 600, an amount of clusters in the measurement volume 690, a volume of at least one cluster 650, a dimension of at least one cluster 650, a distance between at least one cluster 650 and one or more detection coils 300, a distance between two or more clusters 650, a distance between two or more clusters 650, or any combination thereof.

[0077] For example, a voltage measured over a detection coil can be proportional to a rate of change of a magnetic flux. For example, a voltage measured over a detection coil can be in a range from 0.1 nV to 10 pV (microvolts). c) Measuring a contribution of a second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300. For example:

[0078] For example, a second harmonic (f2) can be extracted via a Fourier transform of a measurement using the at least two detection coils 300.

[0079] As depicted in the example of FIG. 2, a detector 870 can be provided using hardware and / or software, wherein the detector 870 is arranged to extract a second harmonic (f2) from measurements made using the at least two detection coils 300 connected in antiseries.

[0080] As depicted in the example of FIG. 2, a detector 870 can comprise one or more analog- to-digital converters (ADC) 872, arranged to measure one or more voltages across the first detection coil 301 and the second detection coil 302 in anti-series. The detector 870 can further comprise a Fourier transformer 875, arranged to receive a digital signal from the one or more analog-to-digital converters (ADC) 872,

[0081] The Fourier transformer 875 is arranged to extract a second harmonic (f2), for example by applying a Fourier transform to a digital signal from the one or more analog-to-digital- converters (ADC) 872 within a predefined time-window, and being arranged to provide one or more peak amplitude values at a second harmonic (f2) frequency as an output. The time-span of the predefined window is arranged to determine a rate at which measurements are carried out. For example, it can be advantageous for the rate to be less than or equal to approximately 0.1 second so that a probe 100 or first probe 101 arranged to carry out the method is sufficiently responsive. For example, the detector 870 can comprise one or more band-pass filters with a bandwidth of approximately 10 Hz around the second harmonic (f2). Additionally or alternatively, the detector 870 can comprise one or more electronic filters and / or one or more amplifiers between the one or more detection coils 300 and one or more analog-digital converters 872. d) Determining a presence of one or more magnetic particles in the measurement volume 690 by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0082] One or more magnetic particles can be considered detected if one or more characteristics of the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f) sufficiently correspond to one or more predetermined criteria for detection. One or more suitable criteria for detection can be determined by estimation, scanning, simulation and / or measurement.

[0083] For example, for an expected dimension of a magnetic material at an expected distance from a detection coil 300, detection can be considered as positive if an expected amplitude of a resulting energy signal is exceeded. Additionally or alternatively, one or more expected parameters can be at least partially determined by estimation, simulation, scanning and / or measurement. Additionally or alternatively, one or more expected parameter can be at least partially selected or provided by a user. For example, an expected distance of an anatomical target from a detection coil 300 can be at least partially estimated from anatomical tables and charts, and / or from other medical scans. As depicted in the example of FIG. 2, an analyzer 880 can be provided using hardware and / or software, wherein the analyzer 880 is arranged to receive the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f). The analyzer 880 is further arranged to determine a presence of one or more magnetic particles in the measurement volume 690 by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0084] Optionally, the probe 100 or the first probe 101 can be arranged to provide one or more static offset magnetic fields (not depicted), wherein a field strength of the one or more static offset magnetic fields can be arranged to influence at least one region of use of the magnetic susceptibility 630 relationship. This can increase a detection depth. For example, one or more optional static offset magnetic fields can be generated using one or more direct-current coils, one or more permanent magnets (as depicted with 400 in FIG. 2), or any combination thereof. Compared to a direct-current coil producing approximately the same magnetic field strength, a permanent magnet 400 can be more compact, with a less complex arrangement and a lower dissipation. For example, the probe 100 or the first probe 101 can be arranged to apply one or more static offset magnetic fields to the measurement volume 690 in a range of 0.1 to 10 mT. It can be advantageous to arrange the one or more static offset magnetic fields in the measurement volume 690 such that an average static field strength is approximately homogeneous. For example, a larger permanent magnet can be used further away from the measurement volume 690 to provide a lower degree of a variation in an average static field strength in the measurement volume 690.

[0085] As described above in step b), one or more resulting energy signals 330 are measured using the at least two detection coils 300 whereby one or more contributions of one or more harmonics of the fundamental excitation frequency 230 (f) can be measured (or determined) in the one or more resulting energy signals 330. The one or more harmonics measured can be a first harmonic (f1 ), a second harmonic (f2), a higher harmonic (fx), or any combination thereof. The one or more contributions of one or more harmonics can be measured (or determined) from measurements using one or more detection coils 300, such a one or more voltages, one or more currents, one or more powers, or any combination thereof. As described above in step c), it can be particularly advantageous to measure (or determine) a contribution of a second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0086] The coils are functionally arranged such that a mutual inductance between the first detection coil 301 and the one or more excitation coils 200 is approximately equal to a corresponding mutual inductance between the second detection coils 302 and the one or more excitation coils 200. In general, such a higher degree of matching between the first detection coil 301 and the second detection coil 302 can improve a discrimination ratio between one or more unwanted signals and a wanted signal, such as a contribution of a second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0087] In general, a degree of inductive mismatch between the first detection coil 301 and the second detection coil 302 can be determined by measuring (or determining) a contribution of a first harmonic (f1 ) of the fundamental excitation frequency 230 (f) in the one or more energy signals 330. A signal strength at a first harmonic (f1 ) of the fundamental excitation frequency 230 (f) can be used to determine a degree of inductive mismatch. It can therefore be advantageous for the probe 100 or first probe 101 to comprise one or more optional mismatch compensators (not depicted), and arrange the probe 100 or first probe 101 to determine an effectiveness of the one or more mismatch compensators by measuring (or determining) a contribution of a first harmonic (f1 ) in the one or more energy signals 330. It can therefore be advantageous to arrange one or more mismatch compensators to reduce a contribution of a first harmonic (f1 ) to approximately 0, or to substantially 0.

[0088] The alternating excitation magnetic field 270 can comprise one or more harmonic distortions which can also be detected or measured using the one or more detection coils 300. Such one or more harmonic distortions are considered unwanted, but such unwanted harmonic distortions are expected to reduce proportionally with an amplitude of a first 1 st harmonic (f1 ) amplitude in the one or more resulting energy signals 330. It can be advantageous to arrange such unwanted harmonic distortions in the one or more resulting energy signals 330 to have a smaller amplitude than a corresponding amplitude of a second harmonic (f2) due to the presence of a target 600.

[0089] It can also be advantageous to arrange such unwanted harmonic distortions to have a high degree of stability and reproducibility, thereby allowing the unwanted harmonic distortions to be subtracted in hardware and / or software.

[0090] FIG. 3 depicts a schematic cross-section through a second embodiment of a probe 100 (a second probe 102) showing magnetic-field related parts. Exterior parts and / or housing parts are not shown. The second probe 102 depicted in FIG. 3 is the same as the first probe 101 depicted in FIG. 2, except for the second probe 102 comprising one or more mismatch compensators. The one or more detectors 870, the one or more analyzers 880, and the electrical connections to the two detection coils 300 shown in FIG. 2 have not been depicted in FIG. 3, but a skilled person realizes that one or more of these aspects can be used with the second probe 102.

[0091] In the example depicted in FIG. 3, the one or more mismatch compensators comprise one or more compensation coils 500, arranged to reduce a degree of inductive mismatch between the first detection coil 301 and the second detection coil 302.

[0092] It can be advantageous to functionally arrange the coils such that the one or more compensation coils 500 has a relatively-large mutual inductance with one of the detection coils 301 , 302, and a relatively-small mutual inductance with the other detection coil 301 , 302. For example, the one or more compensation coils 500 can be arranged proximate to one of the detection coils 301 , 302 and distant from the other detection coil 301 , 302.

[0093] As depicted in the example of FIG. 3, the one or more compensation coils 500 can optionally be arranged along a common axis of the second probe 102.

[0094] As depicted in the example of FIG. 3, the first detection coil 301 can optionally be arranged proximate a first end of the one or more excitation coils 200, and the second detection coil 302 can optionally be arranged proximate a second end of the one or more excitation coils 200. In the example depicted in FIG. 3, the one or more compensation coils 500 are arranged proximate the second detection coil 302. In the example depicted in FIG. 3, the one or more compensation coils 500 are arranged in a separation along the common axis of the second probe 102 between the second detection coil 302 and the optional one or more permanent magnets 400. For example, a cross-section area (or number of turns) of the one or more compensation coils 500 can be similar to a corresponding cross-section area (or number of turns) of one or more excitation coils 200. Alternatively, a cross-section area (or number of turns) of the one or more compensation coils 500 can be approximately 10 to 100 times smaller than a corresponding crosssection area (or number of turns) of one or more excitation coils 200.

[0095] The second probe 102 is arranged to determine an effectiveness of the one or more mismatch compensation coils 500. For example, the second probe 102 can be arranged to measure (or determine) a contribution of a first harmonic (f1 ) in the one or more energy signals 330.

[0096] The second probe 102 is arranged to provide one or more compensation excitation signals to the one or more compensation coils 500, whereby the one or more compensation excitation signals are arranged to reduce a degree of inductive mismatch between the first detection coil 301 and the second detection coil 302. For example, the one or more compensation excitation signals can be arranged to correspond to a high degree to one or more excitation signals for the one or more excitation coils 200. Hereby, one or more harmonic distortions in the one or more excitation signals for the one or more excitation coils 200 are also present in the one or more compensation excitation signals. The one or more compensation excitation signals are thus arranged such that they comprise substantially the same harmonic distortion as the one or more excitation signals. The second probe 102 is further arranged to adapt a magnitude of the one or more compensation excitation signals such that a contribution of a first harmonic (f1 ) contribution in the one or more energy signals 330 is reduced, is reduced to be close to 0, is reduced to be approximately 0, or is reduced to be substantially 0. This can be advantageous because one or more harmonic distortions in the one or more excitation signals for the one or more excitation coils 200 are compensated and / or cancelled by the one or more compensation excitation signals.

[0097] As described above, a higher degree of stability and reproducibility allows a contribution to a second harmonic (f2) to be predicted, and therefore to be used for one or more optional compensation arrangements. Additionally or alternatively, a degree of one or more harmonic disturbance can be decreased by arranging the first probe 101 to operate under one or more of the following conditions (c1 to c3): c1 ) Compensating by subtracting a first harmonic (f1 ) offset from a measured second harmonic (f2) signal using one or more hardware components, such as one or more differential amplifiers. For example, a first harmonic (f1 ) offset signal can be subtracted from the measured second harmonic (f2) signal.

[0098] Fig. 5C depicts a schematic representation of a signal processor comprised in a detector 870, and arranged to provide a degree of compensation. The detector 870 is arranged to receive and process at least one analog signal from the at least two detection coils 300, wherein the at least one analog signal comprises information of interest. Optionally, the detector 870 can be arranged to provide a degree of amplification and / or a degree of conditioning of the at least one analog signal to make it more suitable for signal processing. The at least one analog signal is received by one or more analog-to-digital converters (ADCs) 877, arranged to convert converts the at least one analog signal to at least one digital signal to allow processing in one or more digital domains.

[0099] The at least one digital signal from the one or more ADCs 877 are received by one or more Fourier transformers 875, arranged to output one or more frequency components of the at least one digital signal. In the example depicted in FIG. 5C, a first harmonic (f1 ) component is outputted and passed to one or more compensation controllers 520. In the example depicted in FIG. 5C, a second harmonic (f2) component is outputted and passed to an analyzer 880, arranged to determine a presence of one or more magnetic particles in the measurement volume 690 by analyzing the second harmonic (f2) component.

[0100] The one or more compensation controllers 520 are arranged to determine one or more compensation scaling factors (V) to be applied to the second harmonic (f2) component, whereby one or more digital compensation signals (V.f2) are outputted by the one or more compensation controllers 520. The one or more compensation scaling factors (V) can be arranged to provide a suitable increase or decrease in the second harmonic (f2) component. For example, one or more compensation scaling factors (V) can be at least partially determined when no target 600 is present in a measurement volume 690, which is a reference situation that can have a high degree of reproducibility and / or a high degree of stability over a period of time. Any suitable parameter corresponding to a size of a frequency peak can be used as a measure of a harmonic component, such as an amplitude and / or a complex amplitude.

[0101] The one or more digital compensation signals (V.f2) can be used for various purposes, such as a feedback control and / or interfacing with other digital electronics. In the example depicted in FIG. 5C, the one or more digital compensation signals (V.f2) are passed to one or more digital-to-analog converters (DACs) 872, arranged to convert the one or more digital compensation signals (V.f2) to one or more analog compensation signals.

[0102] The one or more analog compensation signals can be used for various purposes, such as a feedback control and / or interfacing with other analog electronics. In the example depicted in FIG. 5C, the one or more analog compensation signals are passed to one or more subtractors, arranged to subtract the one or more analog compensation signals from the at least one analog signal from the at least two detection coils 300.

[0103] One or more compensation scaling factors (V) can be at least partially simulated, measured, calibrated, and / or estimated such that a significant degree of first harmonic (f1 ) distortion is reduced in the at least one analog signal from the at least two detection coils 300. c2) Compensating by subtracting a first harmonic (f1 ) offset in software. For example, a first harmonic (f1 ) offset value can be subtracted from the measured second harmonic (f2) value.

[0104] For example, a detector can be arranged to output a first harmonic (f1 ) component and to pass the first harmonic (f1 ) component to an analyzer. The detector can be further arranged to output a second harmonic (f2) component and to pass a second harmonic (f2) component to the analyzer. For example, the analyzer can be arranged to determine one or more first harmonic (f1 ) offset values, and further arranged to subtract the one or more first harmonic (f1 ) offset values from second harmonic (f2) component. c3) Arranging the second probe 102 to generate a phase-controlled sine wave with a frequency approximately equal to a second harmonic (f2) of the fundamental excitation frequency 230 (f), and further arranged to at least partially mix the second-harmonic (f2) sine wave with one or more analog signals from one or more detection coils 300.

[0105] Optionally, the second probe 102 can further comprise one or more low pass filters arranged to remove a significant degree of a first harmonic (f1 ) contribution, and arranged to provide an approximately-DC output that is approximately proportional to a second harmonic (f2) contribution in one or more analog signals from one or more detection coils. This arrangement can be advantageous because the second probe 102 comprises a low- pass filter, whereby a signal-to-noise ratio can be increased. Additionally or alternatively, this arrangement can be advantageous because it can reduce a degree of clipping in one or more analog-to-digital converters. The first harmonic (f1 ) contribution can be at least partially suppressed, reducing a degree of risk of clipping, whereby a larger proportion of an input range of one or more analog-to-digital converters can be adapted for an expected second harmonic (f2) contribution, wherein the second harmonic (f2) contribution is approximately DC due to the mixing.

[0106] FIG. 4 depicts a schematic cross-section through a third embodiment of a probe 100 (a third probe 103) showing magnetic-field related parts. Exterior parts and / or housing parts are not shown. The third probe 103 depicted in FIG. 4 is the same as the first probe 101 depicted in FIG. 2, except for the third probe 103 comprising one or more variable transformers 840, and the energy source 810 being directly connected to the one or more variable transformers 840 instead of being connected directly to the one or more detection coils 200. A further difference in the example depicted in FIG. 4, is that the one or more excitation coils 200 comprise a first excitation coil 201 and a second excitation coil 202 arranged adjacently to each other.

[0107] The one or more detectors 870, the one or more analyzers 880, and the electrical connections to the two detection coils 300 shown in FIG. 2 have not been depicted in FIG. 4, but a skilled person realizes that one or more of these aspects can be used with the third probe 103.

[0108] As depicted in the example of FIG. 4, the one or more excitation coils 200 can optionally be arranged along a common axis of the third probe 103. Optionally, the first excitation coil 201 and the second excitation coil 202 can be arranged adjacently to each other along the common axis of the third probe 103.

[0109] In the example depicted in FIG. 4, the one or more variable transformers 840 comprise at least one primary winding 841 connected to the energy source 810, a first secondary winding 845 connected to the first excitation coil 201 , and a second secondary winding 846 connected to the second excitation coil 202. This can be advantageous because it allows two or more alternating signals to be provided using one energy source 810, whereby the two or more alternating signals have very similar frequency components and can have very similar harmonic distortions. In the example depicted in FIG. 4, differences in one or more physical or magnetic properties between the first secondary winding 845 and second secondary winding 846 can be modified to provide a higher degree of performance matching between the first excitation coil 201 and the second excitation coil 602. adapted to the one or more excitation coils 200.

[0110] Optionally, one or more compensation coils depicted in FIG. 3 can be suitably adapted, and comprised in the third probe 103. Additionally or alternatively, one or more variable transformers 840 can be used to provide one or more compensation signals to one or more compensation coils that have very similar frequency components and very similar harmonic distortions compared to one or more excitation signals.

[0111] Optionally, the probe 100, first probe 101 , second probe 102 and third probe 103 can be arranged to provide a degree of adjustment in one or more positions of one or more detection coils 300, one or more excitation coils 200, one or more compensation coils 500, one or more permanent magnets 500, one or more windings of a variable transformer 840, or any combination thereof.

[0112] It can also be advantageous to provide one or more actuators, such as one or more piezo actuators, and one or more controllers to actively control the one or more positions, for example one or more changes in position of approximately 0.1 mm or less. This can be advantageous because one or more harmonic distortions in one or more excitation signals for the one or more excitation coils 200 can be compensated and / or cancelled by one or more adjustments and / or one or more actuations.

[0113] Optionally, one or more positions of one or more permanent magnets 400 can be arranged to be actively adjustable by several millimeters, such as using one or more piezo actuators and one or more controllers to actively control the one or more positions. It can be advantageous to actively adjust one or more positions of the one or more permanent magnets 400 at the first harmonic (f1 ) frequency of the fundamental excitation frequency (f), thereby generating an alternating excitation magnetic field replacing one or more excitation coils 200. It can be advantageous to replace all of the excitation coils.

[0114] Advantageous embodiments are disclosed herein, including M1 to M4, P1 to P4.

[0115] M1. A method for detecting one or more magnetic particles in a measurement volume 690, comprising: applying an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f) to the measurement volume 690; measuring one or more resulting energy signals 330 with at least two detection coils 300 in series, but connected oppositely; measuring a contribution of a second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300; and determining a presence of one or more magnetic particles in the measurement volume 690 by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0116] M2. The method of M1 , further comprising applying one or more static offset magnetic fields to the measurement volume 690.

[0117] M3. The method of M2, wherein the one or more static offset magnetic fields are generated by one or more permanent magnets 400.

[0118] M4. The method of any one of M1 , M2, or M3, comprising compensating one or more inductive mismatches between the at least two detection coils 300 using software and / or hardware.

[0119] P1 . A probe 100 for detecting one or more magnetic particles in a measurement volume 690, comprising: one or more excitation coils 200 for applying an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f) to the measurement volume 690; at least two detection coils 300 in series, but connected oppositely, for measuring one or more resulting energy signals 330; a detector 870 for measuring a contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f) in the one or more resulting energy signals 330 using the at least two detection coils 300; and an analyzer 880 for determining a presence of one or more magnetic particles in the measurement volume 690 by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency 230 (f).

[0120] P2. The probe 100 of P1 , wherein the probe 100 is further arranged to apply one or more static offset magnetic fields to the measurement volume 690. P3. The probe 100 of P2, wherein the one or more static offset magnetic fields are generated by one or more permanent magnets 400.

[0121] P4. The probe of any one of P1 , P2 or P3, comprising one or more mismatch compensators for compensating one or more inductive mismatches between the at least two detection coils 300 using hardware and / or software.

[0122] In summary, radioactive tracers are conventionally used to locate anatomical features, but regulation makes them difficult to use. Magnetic particles can be a viable alternative, but conventional susceptibility devices suffer from lack of sensitivity. A method for detecting one or more magnetic particles lying an alternating excitation magnetic field 270 with a fundamental excitation frequency 230 (f), measuring one or more resulting energy signals 330 with at least two detection coils 300 in series but connected oppositely, and analyzing the signal for a second harmonic (f2) of the fundamental excitation frequency 230 (f). This provides a quantitative measure of detectable magnetic particles, allowing for more precise analysis and greater sensitivity. Performance can be further improved by compensating a degree of inductive mismatching between the at least two detection coils 300 using software and / or hardware.

[0123] REFERENCE NUMERAL LIST

[0124] 100 probe

[0125] 101 first probe

[0126] 102 second probe

[0127] 103 third probe

[0128] 200 excitation coil

[0129] 201 first excitation coil

[0130] 202 second excitation coil 210 excitation coil driver

[0131] 215 excitation resonance circuit

[0132] 216 excitation frequency source

[0133] 217 excitation capacitor230 fundamental excitation frequency (f) 270 excitation magnetic field

[0134] 280 excitation period of time

[0135] 300 detection coil

[0136] 301 first detection coil second detection coil energy signal permanent magnet compensation coil compensation controller target magnetic susceptibility particle magnetization excitation strength cluster comprising magnetic particles measurement volume detection method energy source variable transformer primary winding first secondary winding second secondary winding detector detection resonance circuit digital-to-analog converter (DAC) Fourier transformer analog-to-digital converter (ADC) detection capacitor analyzer first axis or X-axis second axis or Y-axis third axis or Z-axis

Claims

CLAIMS1 . A method for detecting one or more magnetic particles in a measurement volume (690), comprising: applying an alternating excitation magnetic field (270) with a fundamental excitation frequency (230) (f) to the measurement volume (690); measuring one or more resulting energy signals (330) with at least two detection coils (300) in series, but connected oppositely; measuring a contribution of a second harmonic (f2) of the fundamental excitation frequency (230) (f) in the one or more resulting energy signals (330) using the at least two detection coils (300); determining a presence of one or more magnetic particles in the measurement volume (690) by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency (230) (f); and compensating a degree of inductive mismatching between the at least two detection coils (300) using software and / or hardware.

2. The method of claim 1 , wherein the compensation is achieved by subtracting one or more compensation signals from one or more measurement signals, wherein the one or more measurement signals are provided by the at least two detection coils (300).

3. The method of any preceding claim, wherein the compensation is achieved by providing one or more compensation signals to the at least two detection coils (300).

4. The method of any preceding claim, wherein the compensation is achieved with one or more compensation coils (500).

5. The method of any preceding claim, wherein the degree of inductive mismatching is determined by a contribution of a first harmonic (f1 ) of the fundamental excitation frequency (230) (f) in the one or more energy signals (330).

6. The method of any preceding claim, further comprising applying one or more static offset magnetic fields to the measurement volume (690).

7. The method of claim 6, wherein the one or more static offset magnetic fields are generated by one or more permanent magnets (400).

8. The method of any preceding claim, wherein the one or more magnetic particles are comprised in at least one cluster (650).

9. The method of any preceding claim, wherein the one or more magnetic particles are comprised in a lymph node.

10. The method of any preceding claim, wherein the one or more magnetic particles comprise one or more magnetic nanoparticles.11 . A probe for detecting one or more magnetic particles in a measurement volume (690), comprising: one or more excitation coils (200) for applying an alternating excitation magnetic field (270) with a fundamental excitation frequency (230) (f) to the measurement volume (690); at least two detection coils (300) in series, but connected oppositely, for measuring one or more resulting energy signals (330); a detector (870) for measuring a contribution of the second harmonic (f2) of the fundamental excitation frequency (230) (f) in the one or more resulting energy signals (330) using the at least two detection coils (300); an analyzer (880) for determining a presence of one or more magnetic particles in the measurement volume (690) by analyzing the contribution of the second harmonic (f2) of the fundamental excitation frequency (230) (f); and one or more mismatch compensators for compensating a degree of inductive mismatching between the at least two detection coils (300) using hardware and / or software.

12. The probe of claim 11 , wherein the one or more mismatch compensators are arranged to subtract one or more compensation signals from one or more measurement signals, wherein the one or more measurement signals are provided by the at least two detection coils (300).

13. The probe of claim 11 or 12, wherein the one or more compensators are arranged to provide one or more compensation signals to the at least two detection coils (300).

14. The probe of any one of claims 11 to 13, wherein the one or more compensators comprise one or more compensation coils (500).

15. The probe of any one of claims 11 to 14, wherein the degree of inductive mismatching is determined by a contribution of a first harmonic (f1 ) of the fundamental excitation frequency (230) (f) in the one or more energy signals (330).

16. The probe of any one of claims 11 to 15, wherein the probe (100) is further arranged to apply one or more static offset magnetic fields to the measurement volume (690).

17. The probe of claim 16, wherein the one or more static offset magnetic fields are generated by one or more permanent magnets (400).

18. A magnetic detection system for sentinel lymph node biopsy, comprising the probe (100) of any one of claims 11 to 17.

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