Background

It is desirable to guide drugs to targeted locations within a patient’s body in order to increase a concentration of drugs where they are specifically required, without also increasing their concentration elsewhere. For example, targeted drug delivery may be used in the treatment of tumours.

Steering magnetic nanoparticles (MNPs) in a desired trajectory has been proposed for guiding magnetically labelled drugs to clinical targets. However, in order to steer MNPs to the targeted location, a strong magnetic field and field gradient are required. Furthermore, the strength and orientation of the desired magnetic field will vary in dependence on the specific targeted location. For example, the deeper the targeted location, the stronger the magnetic field and gradient required at the surface to produce the requisite trapping force at the targeted location. It is therefore desirable to provide a magnetic system suitable for producing a high field strength and gradient in a variety of configurations.

It is an object of embodiments of the invention to at least mitigate one or more of the problems of the prior art.

Summary of Invention

According to aspects of the present disclosure there is provided apparatus and methods as set forth in the appended claims.

According to aspects of the present disclosure there are provided a magnet array, an apparatus for affixing a magnet array proximal to a body, and a method of designing a magnet array for targeted drug delivery.

According to a first aspect, there is provided a magnet array for targeted drug delivery, comprising a plurality of permanent magnets, each magnet having a magnetic pole orientation; wherein the plurality of permanent magnets comprises at least one central magnet and a plurality of peripheral magnets distributed around the at least one central magnet in at least a first plane; wherein the magnetic pole orientation of the at least one central magnet is arranged in a first orientation; and wherein the magnetic pole orientation of each of the plurality of peripheral magnets is arranged to intersect the first orientation.

The array may further comprise a layer of ferromagnetic coupling material arranged on a first side of the plurality of permanent magnets in the first plane, wherein the ferromagnetic coupling material is mouldable and arranged to conform, in use, to a surface curvature of a body part.

Further optional aspects of the array are outlined in the appended claims.

According to another aspect, there is provided an apparatus for affixing a magnetic array proximal to a body part. The apparatus comprises a flexible body portion arranged to conform, in use, to the body part to secure the apparatus about the body part, the body portion having one or more securing means arranged there-about for releasably attaching to a retainer associated with a magnet array for securing the magnet array proximal to the body part at a selected one of a plurality of positions with respect to the body part. The apparatus comprises at least one retainer for attaching to the magnet array, wherein the retainer is releasably attachable to the securing means for locating the magnet array about the body part at the selected one of the plurality of positions.

Optionally, the flexible body portion comprises a mesh of straps arranged to conform, in use, to the body part. The securing means may comprise one or more of the straps, and the plurality of positions with respect to the body part may comprise locations along the length of the one or more of the straps.

The retainer optionally comprises a housing element for containing the magnet array, and a fastener for attaching the retainer to the securing means. The fastener may comprise clips suitable for attaching the retainer to the securing means.

Optionally, the retainer is arranged to attach to a magnet array as described above. The one or more securing means may be arranged to concurrently attach to a plurality of the retainers.

Optionally, the body part is the head of the body.

According to another aspect, there is provided a method of designing a magnet assembly for targeted drug delivery, comprising acquiring 3D data of a body part comprising a tumour; modelling a configuration of permanent magnets within the 3D data for guiding drugs to a location of the tumour; and optimising the configuration of permanent magnets to maximise a magnetic field strength at the location of the tumour.

Optionally, the 3D data is acquired by internal imaging of the body part. The internal imaging may among other options be Magnetic Resonance Imaging (MRI).

The modelled configuration of permanent magnets may comprise at least one magnet array as described above.

Optionally, optimising the configuration of permanent magnets comprises the steps of: calculating modelled magnetic field strength at the tumour location; amending the configuration of permanent magnets; and recalculating modelled magnetic field strength at the tumour location. Amending the configuration of permanent magnets may comprise at least one of: adding one or more magnets to the configuration; removing one or more magnets from the configuration; changing a pole orientation of at least one magnet in the configuration; and moving the location of at least one magnet in the configuration within the 3D data.

Brief Description of the Drawings

Embodiments of the invention will now be described by way of example only, with reference to the accompanying figures, in which:

Figure 1 shows a first example of a magnet array according to the present disclosure; Figure 2 shows the first example of the magnet array according to the present disclosure from a second orientation;

Figure 3 shows a second example of the magnet array according to the present disclosure;

Figure 4 shows a third example of the magnet array according to the present disclosure;

Figure 5 illustrates a fourth example of the magnet array according to the present disclosure;

Figure 6 illustrates a fifth example of the magnet array according to the present disclosure, and an illustration of an example of the magnetic field at varying distance from the magnet array;

Figure 7 illustrates a sixth example of the magnet array according to the present disclosure, and an illustration of an example of the magnetic field at varying distance from the magnet array;

Figure 8 illustrates an example apparatus for affixing a magnet array proximal to a body part according to present disclosure;

Figure 9 illustrates an example method 900 of designing a magnet assembly according to the present disclosure; and

Figure 10 shows a schematic illustration of a computer system on which method 900 may be executed.

Detailed Description

The present disclosure comprises a magnet array, an apparatus for affixing a magnet array proximal to a body part, and a method of designing a magnet assembly. There is provided a magnet array for suitable targeted drug delivery. Examples of the magnet array are illustrated in Figures 1 through 7 as will be explained. The magnet array comprises a plurality of permanent magnets, each magnet having a respective magnetic pole orientation indicative of an orientation of its resultant magnetic field. The plurality of permanent magnets comprise at least one central magnet, and a plurality of peripheral magnets distributed around the at least one central magnet. It will be appreciated that the magnet array may comprise any number of central magnets, and any number of peripheral magnets greater than one.

The magnetic pole orientation of the central magnet is arranged in a first orientation, and the magnetic pole orientation of each of the peripheral magnets is arranged to intersect the first orientation. For example, in an (x,y,z) co-ordinate system, the pole orientation of the central axis may lie along the z axis, and the pole orientation of each of the peripheral magnets distributed around the central magnet may intersect the z axis, for example arranged perpendicular to the z axis along the (x,y) plane. It will be appreciated that in other examples the pole orientation of at least some of the peripheral magnets may be oriented non-perpendicular to the z axis, though still intersect it.

The plurality of permanent magnets may be any shape and size. Particularly, they may each be a cuboid element of substantially uniform size. Each cuboid element may have sides of length between lmm and 20mm. The permanent magnets may be made of any magnetized material, for example Neodynium-iron-boron (FeNdB), Samarium Cobalt, or Ferrite.

Further features of the magnet array will be discussed in more detail with reference to example magnet arrays 100 to 700.

Figure 1 and Figure 2 show an example magnet array 100 from two different angles, as illustrated by the (x,y,z) reference grid in each Figure. The example magnet array 100 comprises one central magnet 110 and four peripheral magnets 120.

Figure 1 illustrates a cross section of the magnet array 100 in the (x,y) plane, which throughout the figures will be the plane perpendicular to the pole orientation of the central magnet. The pole orientation of the central magnet lies along the z axis. In example magnet array 100, the peripheral magnets 120 are distributed around the central magnet 110 in a cross shape in the (x,y) plane.

The pole orientation of each of the plurality of permanent magnets 110, 120 is illustrated in Figures 1 and 2 by an arrow. The central magnet 110 is arranged to have a pole orientation in a first orientation, which in Figure 1 is indicated as a cross, meaning the first orientation extends perpendicular to the plane of view along the z axis.

In example magnet array 100, the pole orientations of the peripheral magnets 120 are arranged oriented in the (x,y) plane pointing towards the central magnet 110, and a north pole of at least some of the peripheral magnets 120 is located proximal to the central magnet 110. This arrangement acts to focus the resultant magnetic field of example magnet array 100 towards the central magnet 110. The pole orientation of the central magnet 110 then acts to direct the resultant magnetic field preferentially towards one side of the (x,y) plane of magnet array 100, i.e. along the z axis. Advantageously, a substantially stronger magnetic field is produced on one side of the magnet array 100 than on the opposite side of the array.

In some examples, the magnet array 100 is at least partially deformable. The plurality of permanent magnets 110, 120 may be rearrangeable in a different configuration. In this way, the same plurality of permanent magnets may be rearranged to form a different arrangement or configuration of the magnet array. Furthermore, the magnet array 100 may be at least partially deformable to conform to a surface of a body part of a patient, by allowing at least a portion of the adjacent surfaces of two or more permanent magnets 110, 120 to be separated by a distance, which may vary along the surface of the two magnets 110, 120.

Figure 3 illustrates a second example magnet array 300 according to the present invention, comprising one central magnet 310 and eight peripheral magnets 320. In particular, example magnet array 300 illustrates peripheral magnets 320 with a pole orientation non-parallel to the sides of any of the cuboid elements.

Figure 4 illustrates a third example magnet array 400 according to the present invention, comprising four central magnets 410 and eight peripheral magnets 420 as have been described. Magnet array 400 illustrates an example array comprising a plurality of central magnets 410, wherein each of the central magnets 410 are arranged with parallel pole orientation. However, in further examples at least some of the plurality of central magnets 410 may have non-parallel pole orientations.

Example magnet arrays 100, 300 and 400 all comprise one or a plurality of central magnets 110, 310, 410 with pole orientations perpendicular to their respective peripheral magnets 120, 320, 420. However, in other examples some or all of the peripheral magnets 420 may have pole orientations at a number of intermediate angles between 0 and 90 degrees of the orientation of the at least one central magnet 410. For example, the magnet array may comprise one or more peripheral magnets 420 with a pole orientation at 45 degrees to that of the respective central magnets 410.

In some examples, as in magnet arrays 100, 300 and 400, the magnet array 400 is arranged as a single planar layer of permanent magnets 410, 420. Each of the permanent magnets 410, 420 are arranged to be adjacent in the (x,y) plane. In further examples, the permanent magnets may be arranged in a plurality of layers, and consequently the magnet array may comprise permanent magnets 410, 420 adjacent along the z axis.

Figure 5 illustrates an example magnet array 500 comprising a plurality of magnet layers 501, 502. Magnet array 500 is illustrated in a cross-sectional view in the (x,z) plane, and comprises two of the example magnet arrays 400 arranged stacked along the z axis. Magnet array 500 comprises a plurality of central magnets 510 and peripheral magnets 520, although only a selection are illustrated in the (x,z) plane, for example those permanent magnets falling along line A in Figure 4.

The example magnet array 500 comprises two planar layers 501, 502 of magnets. In further examples, the magnet array 500 may comprise any number of layers 501, 502 along the z axis. Each layer 501, 502 may comprise any configuration of planar magnet array according to the present disclosure and is not limited to be identical to any other layer.

In some examples, the magnet array may comprise magnetically neutral material in at least one portion of the array. For instance, this magnetically neutral material may be placed adjacent to one or more of the plurality of permanent magnets, including in a gap in the array corresponding to the shape of one of the permanent magnets. For example, magnet array 400 comprises gaps 430 corresponding to a lack of peripheral magnets 420. The magnet array may comprise magnetically neutral material in one or more of the gaps 430 adjacent to the peripheral magnets 420.

Advantageously, magnet arrays according to examples of the present invention are arranged to produce a strong magnetic field in the range 0.5T to 1.2T which allows the array to steer MNPs more successfully to targets within a patient’s body. Figure 6 illustrates a further example magnet array 600 according to the invention. Example magnet array 600 is illustrated in both the (x,y) and (x,z) planes and comprises three planar layers 601, 602, 603 of permanent magnets. Figure 6 further illustrates a graphical representation 650 of experimental magnetic field data indicative of the strength of the magnetic field at a variety of distances from the assembled example magnet array 600.

As illustrated in graph 650, example magnet array 600 produces a maximum magnetic field strength of 1.17T, with a field gradient of 37.8T/m and a magnetic force of 43.6T ² /m at 3cm from the magnet array 600. The magnetic field strength decreases with increasing depth penetration, with a field strength of 0.012T at 5cm from the magnet array 600 and 0.001T at l4cm from the magnet array 600. The total magnetic force of magnet array 600 is 8.3T ² /m up to l4cm from the magnet array 600. Advantageously, the strong field and large field gradient is unilateral along the z axis of the array, producing a strong field on only one side of the (x,y) plane of the array 600. Thereby unnecessary strong magnetic fields are minimised elsewhere and the magnet array 600 is enabled to focus the field at the region of interest within the patient’s body. Such benefits are also conferred by example magnet arrays 100 to 500.

Some example magnet arrays comprise a layer of mouldable ferromagnetic coupling material. By mouldable it is meant that the layer is arranged to flexibly conform to differently shaped surfaces. In this way the layer is adaptable and may be adjusted to conform successively to different surfaces by moulding. The layer may have a degree of resilience, such that it naturally retains a deformed shape i.e. when removed from a surface to which it has been moulded it naturally retains the shape of the surface to aid being remounted on the same surface. However, further force may be applied, beyond a deformation force, to cause the mouldable layer to form conform to another surface of different shape.

Figure 7 illustrates a cross section of an example magnet array 700 according to the present invention comprising a layer of mouldable ferromagnetic coupling material 740. Magnet array 700 comprises a plurality of permanent magnets arranged in three planar layers 701, 702, 703 of four central magnets 710 and a plurality of peripheral magnets 720. The ferromagnetic coupling material 740 may form a layer on at least one side of the magnet array 700. For example, a first face of the ferromagnetic coupling material 740 may abut one side of the magnet array 700 in the first plane. The layer of ferromagnetic coupling material 740 may be substantially continuous over the side of the magnet array 700. The layer of coupling material may comprise an opposing face 741 which is mouldable and may be formed to correspond to the surface curvature of a body part or other surface, particularly an irregular or curved surface. For such a surface, ordinarily the array 700 would not be easily arranged to provide substantially continuous contact with the irregular surface. By providing a layer of mouldable coupling material 740, the array 700 will be adaptable to provide substantially continuous contact with surfaces in different circumstances. For example, the face 741 may correspond to the curvature of a head, or arm of the body. As discussed, the face 741 is mouldable and so may be successively adapted to conform to each surface in turn.

The ferromagnetic coupling material 740 may be any mouldable ferromagnetic material, and particularly may be one of iron loaded epoxy resin, magnetic putty, or malleable steel plates. The ferromagnetic coupling material 740 acts to focus the magnetic strength of the array 700, in addition to in some examples utilising space between a body part and the array. Furthermore, the ferromagnetic coupling material 740 may also be used to shape the magnetic field of the array 700 and may be used to spatially shift the peak of the magnetic field further from the array 700. One such example effect is illustrated in Figure 7 in graph 750. Graph 750 illustrates modelled magnetic field strength against distance from the array, for a modelled magnet array 700 including the layer of ferromagnetic coupling material 740. Unlike analogous graph 650, graph 750 indicates the peak of the magnetic field has been shifted spatially further away from the array 700 due to the presence of layer 740. Advantageously, if the magnet array is utilised to guide magnetic particles within the body, shifting the peak of the magnetic field will shift the location within the body at which the particles will concentrate.

Further aspects of the present disclosure comprise an apparatus for affixing a magnetic array proximal to a body part. It may be desired to secure one or more magnet arrays proximal to a desired location within a body part. For example, to guide magnetically labelled drugs to a desired treatment area within the body part one or more arrays may need to be secured at specific locations with respect to the treatment area in order to produce a magnetic field suitable for guiding the drugs to the correct location.

Figure 8 illustrates an example securing apparatus 800 suitable for affixing one or more magnet arrays proximal to a body part as discussed. Securing apparatus 800 comprises a flexible body portion 810 arranged to conform in use to the body part. For example, the flexible body portion 810 may comprise fabric or other flexible material which in use may conform to the shape of the body part. Body portion 810 may in further examples comprise a rigid material, for example a plastic, pre-moulded specifically to the shape of the body part. In some examples, the body portion 810 may comprise a mesh of straps arranged to conform to the body part in use. Body portion 810 is arranged to secure the securing apparatus 800 about the body part and may comprise a fastener 860 that, when fastened, secures the apparatus about the body part. For example, fastener 860 may be a buckle or other strap fastening apparatus. The body part may be a patient’s head as illustrated in Figure 8. The body part may in further examples a different part of the body, for instance an arm, leg or torso.

The body portion 810 attaches to one or more securing means 820 for releasably attaching to a retainer 830 of a magnet array. In other examples, the securing means 820 may be integrated with the body portion 810. For example, the securing means 820 may be one or more of the straps of the body portion 810. The securing means 820 are arranged for securing the magnet array proximal to the body part at a selected one of a plurality of positions with respect to the body part. For example, the plurality of positions may comprise a plurality of locations along the length of the one or more of the straps. In these examples, the retainer 830 may be arranged to be releasably attachable at locations along the length of the straps.

In some examples, the securing means may be separate to the body portion 810. For example, securing means 820 may comprise a plurality of individual fasteners. For example, the fasteners may be releasable fastening material such as hook-and-loop fastening. In other examples, the fasteners may be mechanical fasteners such as clips arranged at a plurality of positions about the body portion 810.

The example apparatus 800 comprises at least one retainer 830 for attaching to the magnet array 100 to 700. The retainer 830, as mentioned, is releasably attachable to the securing means 820. In use, attaching the retainer 830 to the securing means 820 causes the magnet array to be located about the body part at the selected one of the plurality of positions, as has been mentioned.

The retainer 830 may comprise a housing element 840 for securing the retainer 830 to the magnet array. The housing element 840 may be shaped to securely engage with at least part of the magnet array. For example, the housing element 840 may allow at least a part of the magnet array to be received snugly into the housing element 840. Alternately, the housing element 840 may be arranged to securely engage with the magnet array in other ways, for example with adhesive material or a releasable fastening material.

The retainer 830 may comprise at least one fastener 850 for releasably attaching the retainer 830 to the securing means 820. For example, the fastener 850 may comprise a releasable fastening material compatible with that of the securing means 820, for example hook-and-loop fastening. In other examples, as in Figure 8, the fastener 850 may comprise one or more clips suitable for attaching the retainer 830 to the securing means 820. For example, if the securing means 820 are straps, the fastener 850 may comprise compatible clips arranged to attach the retainer 830 to locations along the length of the straps.

Advantageously, in some examples a plurality of retainers 830 may simultaneously attach to the securing means 820 at a plurality of the positions about the body portion 810. A plurality of magnet arrays may therefore be affixed proximal to a plurality of locations on the body part simultaneously. The securing means 820 therefore enables a configurable spatial assembly of magnet arrays to be affixed proximal to the body part, enabling a configurable magnetic field to be produced to target a specific location within the body part.

Figure 9 illustrates a computer-implemented method 900 of designing a magnet assembly suitable for guiding drugs to a target area within the body. The magnet assembly may be designed suitable to be affixed proximal to a body part by securing apparatus 800.

Some or all parts of method 900 may be implemented by a computer system 1000 as illustrated schematically in Figure 10. Computing system 1000 comprises a memory 1020, and a processor 1010 configured to execute software on memory 1020. Computing system 1000 may be networked and configured to be communicable with other computing systems via a wireless or wired network. Computing system 1000 may further comprise one or both of a display device 1030 for outputting data to a user and an input device 1040 for receiving information input by a user. For example, display device 1030 may be a screen and input device 1040 may be a keyboard, mouse or touch sensitive device. Display device 1030 and input device 1040 may be integrated.

Method 900 comprises a step 910 of receiving body data indicative of a three- dimensional (3D) structure of a body part including a target area, which for example may be a tumour. The 3D data may be acquired by internal imaging of the body part. For example, the 3D data may be acquired using a Magnetic Resonance Imaging (MRI) system. Said MRI system may comprise a homogeneous magnet and a set of gradient coils suitable for creating a secondary magnetic field when a current is passed through the coils. The secondary magnetic field is suitable for distorting the field of the homogeneous magnet in a predictable spatial pattern. Said MRI system may comprise applying said fields to a patient’s body and receiving a radio signal indicative of 3D body structure, which may be processed by the MRI system. The MRI system may then output body data indicative of the 3D body structure. Step 910 may then comprise receiving the body data from the MRI system and storing the body data in memory 1020 or receiving the body data via a network to which computing system 1000 is communicable.

Method 900 comprises a step 920 of modelling a magnet configuration in dependence on the received 3D body data. Step 920 may comprise selecting at least one location within the 3D body data and modelling the effect of at least one permanent magnet at the at least one location. For example, the magnet configuration may be modelled using Finite Element Method Magnetics (FEMM) software run on the processor 1010, or any other software suitable for modelling magnetic fields. The selection of the at least one location may be subject to a number of restrictions. For example, the at least one location may be restricted to one or more of: locations outside the body part, locations on the surface of the body part, or a predetermined set of locations on the body part suitable for affixing magnet arrays using securing apparatus 800. The restrictions may be predetermined and stored on memory 1020. The at least one permanent magnet may be at least one magnet array 100 to 700.

Method 900 may comprise a step 930 of calculating the magnetic field. The resultant magnetic field of the modelled magnet configuration from step 920 may be calculated at a number of points within the 3D data, including the target area, and stored in the memory 1020. Step 930 may also comprise calculating and storing the field gradient and/or magnetic force. Step 930 may comprise outputting an indication to the user of one or more of the magnetic field strength, field gradient and magnetic force at at least one location in the 3D data, for example the target area. The indication may be provided through display device 1030.

Method 900 comprises a step 940 of determining if the configuration of permanent magnets is optimised. This may comprise determining if one or more conditions of the magnetic field strength, field gradient or magnetic force are met. For example, the condition may be that the field strength is maximised at the target area or minimised at another area.

If it is determined at step 940 that the configuration is not optimised, method 900 comprises a step 950 of amending the magnet configuration. Step 950 may comprise adding one or more magnets to the configuration, removing one or more magnets to the configuration, changing the pole orientation of one or more magnets within the configuration, or moving the location of at least one magnet in the configuration within the 3D data. These amendments may remain subject to the restrictions outlined in step 920. This may be achieved by adding, removing or moving whole magnet arrays 100 to 700 from the configuration, or by amending individual permanent magnets.

After step 950, method 900 may return to step 950 to recalculate the field parameters as previously described. This method may be iterative and repeat a number of times before it is determined that the configuration is optimised in step 940.

If it is determined that the array is optimised, method 900 may then comprise a step 960 of outputting the configuration. Step 960 may comprise one or more of storing the optimal configuration in memory 1020, sending the optimal configuration to a device with which computing system 1000 is communicable, and outputting the optimal configuration to the user via display device 1030. For example, the optimal configuration may be displayed to the user superimposed on a representation of securing apparatus 800 for implementation.

It will be appreciated that embodiments of the present invention can be realised in the form of hardware, software or a combination of hardware and software. Any such software may be stored in the form of volatile or non-volatile storage such as, for example, a storage device like a ROM, whether erasable or rewritable or not, or in the form of memory such as, for example, RAM, memory chips, device or integrated circuits or on an optically or magnetically readable medium such as, for example, a CD, DVD, magnetic disk or magnetic tape. It will be appreciated that the storage devices and storage media are embodiments of machine-readable storage that are suitable for storing a program or programs that, when executed, implement embodiments of the present invention. Accordingly, embodiments provide a program comprising code for implementing a system or method as claimed in any preceding claim and a machine readable storage storing such a program. Still further, embodiments of the present invention may be conveyed electronically via any medium such as a communication signal carried over a wired or wireless connection and embodiments suitably encompass the same. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The claims should not be construed to cover merely the foregoing embodiments, but also any embodiments which fall within the scope of the claims.