Patent Grant
11793596
This invention relates in general to the field of surgical guidance, more specifically to magnetic markers that aid in locating a lesion for surgical excision and to systems and methods for detecting such markers.
Markers are used to guide surgeons to a region of interest during a surgical procedure, where the site of interest is not physically visible or palpable, for example a small tumour that needs to be excised. Ideally, such a marker will be deployable through a narrow gauge needle e.g. 18 g to 14 g in order to reduce trauma to the patient. Typically, such markers are less than 10 mm in length so as to be unobtrusive and to minimise trauma. The marker may be placed during a biopsy or other surgical procedure at a site of interest in the body, for example a cancer lesion. The marker is placed under imaging guidance such as ultrasound or X-ray/mammography. During subsequent surgery, the marker is detected and localised using a handheld probe which provides audible, visual or other feedback to the surgeon to guide the surgery. Typically the marker is excised along with the surrounding tissue.
One such approach is to use a marker containing a radioisotope such as Iodine 90 which can be detected using a handheld gamma detection probe. However, use of radioactive materials is closely regulated, making it challenging to set up a radioactive seed programme in all but the largest academic hospital centres.
US 2017/252124 (Cianna Medical) discloses a localization system which uses a combination of radio frequency (RF) and infra red (IR) radiation to detect a marker in the form of an implantable radar antenna. However, this system is limited by the low tissue penetration depth of IR radiation, the need for intimate tissue contact for good IR propagation, and the lack of robustness often associated with an implantable device containing antennae and electronic circuits.
US 2015/264891 (Health Beacons) discloses a further system based on radio frequency identification (RFID) tags that have been used as identity markers for pets and livestock. The drawback with this approach is that the small RFID tag constitutes a dipole antenna which has ‘deadspots’ when approached perpendicular to the dipole axis. This could cause confusion for surgeons using the system to localize a lesion. Miniaturizing the RFID tag sufficiently for convenient clinical implantation is also challenging.
A further approach is discussed in the Applicant's earlier published patent applications (for example, WO 2011/067576, WO 2014/032235 and WO 2014/140567) and uses magnetic fields and a magnetic marker with high magnetic susceptibility. A handheld probe generates an alternating field which excites a magnetically responsive marker, and detects the responding magnetic field. This approach is effective for deeper sensing and avoids the drawbacks of RF approaches. However, these systems will detect any magnetically responsive material in the vicinity of the probe, such as a ferromagnetic surgical tool or other metallic implanted device. This means that for effective operation they need to be used with non-ferromagnetic surgical instruments and away from other metallic implantables. Additionally, such a probe may respond to iron oxide nanoparticle suspensions used for sentinel node detection in breast cancer.
It has therefore proved problematic to provide a marker and detection system that possesses all the properties required for localising lesions, namely: a marker of a small size (<10 mm long); ability to deliver the marker through a small needle (eg. 16 g-18 g); ability to detect the marker using a handheld probe; and robust for implantation and surgical removal, together with a detection system that is able to distinguish the lesion marker from other magnetically responsive materials.
Sulla (Utilizing Magnetic Microwires For Sensing In Biological Applications, Jnl. of Elec. Eng., VOL 66. NO 7/s, 2015, 161-163) describes the use of glass coated amorphous microwires exhibiting large Barkhausen jump behaviour for medical applications, in particular as an implant that can be detected magnetically by applying an external field using the bistable behaviour of the microwire. In this respect, ‘Large Barkhausen Jump’ (LBJ) materials, undergo a rapid reversal of their magnetic polarization when excited by an external magnetic field whose field strength opposing the instantaneous magnetic polarization of the wire exceeds a predetermined threshold value. Thus, the material exhibits bistable behaviour, reversing between two magnetic polarisation states. Each reversal of magnetisation generates a magnetic pulse with harmonic components. The profile and number of harmonics is measured (out to many tens of harmonics) to identify the marker from other materials. Sulla concludes that a piece of wire 40 mm in length is required for functional sensing, but a marker of this length would be unsuitable for lesion localisation as many lesions are only a few millimetres in size.
These conditions suggest that this large Barkhausen jump behaviour described in the prior art is unsuitable for use as a lesion localisation marker for the following reasons:
A further drawback of this type of system is the large anisotropy of the response from the marker wires, meaning that the response in the axial direction is much greater than the response in the transverse direction. In the EAS application, this does not present a problem because the system only needs to sense the presence of the marker, not its distance from the detector, and so large coils and high field strengths enable satisfactory EAS detection. However, in surgical guidance with a handheld probe, a response that varies depending on the direction of approach will be confusing to the user because the marker will appear to be a varying distance from the probe depending on the orientation of approach.
The Applicant's co-pending Application No GB1801224.5, the contents of which are incorporated herein by reference, describes an implantable magnetic marker comprising at least one piece of magnetic material that exhibits a large Barkhausen jump (LBJ) in its magnetisation curve, but where the marker is excited below the switching field required to initiate bistable switching behaviour of the LBJ material of the marker. The marker may also be below the critical length required to initiate bistable switching behaviour of the LBJ material. The concepts of ‘critical length’ and ‘switching field’ for LBJ wires are known from for example Vazquez (A soft magnetic wire for sensor applications, J. Phys. D: Appl. Phys. 29 (1996) 939-949). The marker in GB1801224.5 GB utilises a newly recognised “sub-bistable” mode of excitation for its LBJ material that causes a measurable harmonic response to be sensed even when the excitation field is below that of the ‘switching field’, traditionally considered necessary to initiate the classic bistable switching behaviour and a harmonic response.
Markers in the art all use straight pieces of LBJ wire. This is because the classic switching behaviour occurs through a cascade or domino effect in which the magnetic domains in the LBJ wires all flip at one time, and thus alignment of all the domains with the driving magnetic field is key. Domains not substantially aligned with the field will not flip or switch, meaning that the bistable behaviour of the magnetic response in which all the domains undergo a rapid reversal of magnetisation could not be realised thus resulting in the use of straight wires for detection. The use of any other configuration would be counter-intuitive based on the prior art literature.
However, when a straight piece of LBJ wire is excited, the magnetic response it gives is directional, that is there is a greater response along the axis of the wire and a much lower response in a direction perpendicular to the wire. For this reason, the inventors in co-pending Patent Application No. GB1801224.5, which uses their newly recognised “sub-bistable” mode of excitation for a marker comprising a LBJ material, describe how the dipole length of the LBJ material in the direction of the drive field is an important parameter for enabling harmonic response and detection. The inventors therefore teach providing a number of wires, for example in a tripod arrangement, such that the dipole length in any given direction is substantially similar. This enables a more uniform response to be achieved and provides one with the ability to measure the distance from the marker to a detection probe.
However, the provision of a satisfactory marker having the required uniform response with the same dipole length in each direction, does encounter a number a problems. In this respect, an implantable marker for locating a lesion is generally inserted through a small diameter deployment device requiring the marker to be able to reconfigure from <2 mm diameter to its final shape with the same dipole length in each direction. The tripod arrangement of the material or other 3D shape with similar dipole length in each direction results in a marker that has thin sections making it fragile or vulnerable to movement. If the marker fails to deploy correctly, then the response will be non-uniform and inaccurate.
Therefore, there is a need for a marker which is more robust and preferably does not need to make a reconfiguration on deployment.
The present invention aims to address this need.
According to a first aspect of the present invention there is provided a magnetic marker comprising:
In a preferred embodiment, the marker comprises at least one piece of LBJ material having at least two full convolutions, preferably more, to form a coil or helix.
Surprisingly, the inventors have found that a coil of LBJ wire produces a measurable harmonic response in addition to a straight LBJ wire. At higher fields and larger diameter coils, this is a switching response similar qualitatively to the classic bistable switching described in the prior art. However, at lower fields and with smaller diameter coils, the response is ‘sub-bistable’ as described in the Applicant's co-pending Patent Application No. GB1801224.5.
Furthermore, while a single straight LBJ wire provides an axial response that is much greater than the transverse (perpendicular to the axis) response, more surprisingly the inventors have found that a coil of LBJ wire when excited in either the bistable or sub-bistable mode, has a larger transverse response than axial response, even when its length is several times its diameter.
The marker according to the invention may comprise a coil or helix of LBJ material having any number of complete turns or convolutions. The diameter and/or the pitch of the coils may be varied to adjust the response, including the ratio of the transverse to axial response in order to provide a more uniform response. For example, the marker may be formed of convolutions of an identical pitch or the convolutions may have a varying pitch along the longitudinal axis or length of the marker. Similarly, the marker may be formed of convolutions of an identical diameter or the convolutions may vary in diameter along the length of the marker, for example to provide a marker that is conical-shaped, barrel-shaped or hour glass shaped.
It is preferable to provide at least one axial member comprising at least one piece of LBJ material extending at least partially through the centre of the coiled marker to adjust the ratio of the transverse to axial response of the marker in order to provide a more uniform response. The at least one axial member may be in the form of a separate piece of material inserted through the coil or may be formed continuously with the coil at one or both ends of the marker.
The marker according to the invention may also comprise multiple coils. The multiple coils may be interwoven together or may comprise a coil having convolutions of a smaller diameter contained within a coil having convolutions of a larger diameter. The pitch may differ in the different coils but it is preferably similar to enable close meshing of multiple coils.
The marker may also be provided with at least one tissue engagement member to aid securement of the marker to tissue at a lesion site. For example, one or both ends of the coiled marker may be provided with a hook or prong, preferably being formed integrally with the marker.
Preferably, the marker comprises less than 5 mg of LBJ material. The material may be provided in the form of a wire that is wound into a coil of the required pitch and diameter. Examples of such materials include, but are not limited to, iron-, cobalt- and nickel-rich glass-coated amorphous microwires, iron-silicon-boron based amorphous microwires, iron-cobalt based amorphous microwires, and/or bulk metallic glass wires.
Preferably, the marker is deployable from a needle having an inner diameter of less than 2 mm. More preferably, the aspect ratio of the marker prior to deployment is >3. It is preferable for the coiled marker to be deployable in its final form without the need for a shape transition, thereby reducing the likelihood of the marker failing to deploy correctly which may affect the accuracy and uniformity of any detected response from the marker.
The wires may be coated or provided within a housing. Preferably, the LBJ wire is coated or provided within a tube of non-magnetic material to provide composite properties such as strength, stiffness, flexibility and biocompatibility. For example, the wire may be coated with a polymer coating such as FEP, Parylene, PTFE, ETFE, PE, PET, PVC, or silicone or an epoxy-based encapsulant. Alternatively, the wire may be encased in a tube prior to being formed into the required coiled marker shape. Suitable materials for the tube include Nitinol, titanium, stainless steels and other biocompatible alloys. Preferably the material is non-magnetic and has a relatively low conductivity. More preferably, the housing is formed from a material having a resistivity greater than 2×10−7 Ωm. The resistivity may also be increased through selective cutting of the tube such as with an interrupted laser cut spiral. This may also aid in winding of the tube.
The tube, especially if selectively cut, may be further coated or housed within a biocompatible sheath prior to coiling and/or the coiled marker may be housed or coated in a similar sheath. Preferably this sheath is also an insulating layer.
The marker housing may be formed from a moulded or extruded material. For example, a polymer may be extruded around the magnetic wire to form a coated wire that can then be formed into a loop. Suitable materials for the coating or overmoulding include PEEK, PEKK, polyethylene, polypropylene, polyester, polyurethane, polyimide, polyether block amide, polyamide, PTFE, FEP and silicones.
In one embodiment, a marker according to the present invention includes a housing comprising one or more strands of material which are wound around the magnetic material, for example in the form of a helix, to form a more robust construction prior to forming into the final marker shape. Preferably the surrounding material completely encloses the magnetic marker material. The strands of the surrounding material could be formed from one material or from more than one type of material to obtain a different profile of material properties such as strength, stiffness, resistivity, or echogenicity. The surrounding material could be wound in a single layer or in multiple layers within the scope of the invention. Similarly, the layers could be wound in alternate senses or directions, and could comprise different materials or cross sections and may be further coated or housed within a biocompatible sheath prior to coiling and/or the coiled marker may be housed or coated in a similar sheath.
Thus, the marker is formed of a coil that can be deployed from a needle in its final form without the need for a shape transition. However, in an alternative embodiment, the marker can comprise a resiliently deformable tube containing the LBJ wire such that the coil expands on deployment to a larger size.
It is to be appreciated that the cross section of the marker is not limited to a particular shape. For example, the marker may be round, rectangular or triangular in cross-section. It may be preferable to provide a marker having a section in which there is a substantially straight side, for example rectangular or triangular in order to provide angles at which there is an increased magnetic response relative to other angles, e.g. when a straight section is aligned with the excitation field.
The marker for use in the present invention is preferably configured such that when implanted into the body the magnitude of a harmonic response from the marker when interrogated by an alternating magnetic field is substantially the same when measured from any direction relative to the marker, and allows the distance between the probe and the marker to be determined.
According to a second aspect of the present invention, there is provided a detection system for locating a marker, the system comprising:
Depending upon the size and configuration of the marker, the drive coil may excite the marker above a threshold that initiates bistable switching behaviour of the LBJ material. Alternatively, and more preferably, the at least one drive coil excites the marker below the switching field required to initiate bistable switching behaviour of the LBJ material of the marker.
Preferably, a harmonic response is used to determine location/distance/proximity of the marker from a probe. More preferably, the ratio of maximum to minimum harmonic response with direction is <3.
In a preferred embodiment of this aspect of the invention, both the drive and sense coils are provided in a handheld probe. Alternatively, only the sense coil may be provided in a handheld probe. In this embodiment, a larger drive coil may be provided external to the probe to enable an increased magnetic field to be generated at the marker site. For example, the drive coil may be provided within a pad for placement near or beneath a patient.
The detection system preferably comprises an output module for processing the received harmonic signal and providing at least one indicator to the user relating to a location of the marker relative to the sense coil, for example an indication of the proximity, distance, direction and/or orientation of the marker with respect to the sense coil.
More preferably, the system processes one or more aspects of the harmonic response of the marker, such as the magnitude of one or more odd harmonics (e.g. 3rd and 5th), even harmonics (e.g. 2nd, 4th and 6th) or a combination of both or the ratios of these harmonics to each other or to the fundamental frequency. Appropriate filters may be provided to enhance the drive and sensed signals.
The output module may include a visual display or sound generator.
According to a third aspect of the present invention there is provided a method of detecting an implantable marker, the implantable marker comprising at least one piece of magnetic material that exhibits a large Barkhausen jump (LBJ) in its magnetisation curve, wherein the LBJ material comprises at least one overlapping loop maintained in the marker during detection thereof, the method comprising applying an alternating magnetic field to the marker to excite the marker to initiate bistable or sub-bistable switching behaviour of the LBJ material of the marker; and detecting one or more harmonics of the drive frequency of a signal received from the excited marker caused by a change in magnetization of the marker.
Preferably, the marker is excited below the switching field required to initiate bistable switching, wherein the application of the alternating magnetic field to excite the marker below the switching field results in a sub-bistable response being detected for the marker.
Preferably, the drive frequency is above 1 kHz, preferably being in the range 1-100 kHz, especially 10-40 kHz.
The method preferably includes measuring an aspect of the harmonic response of the marker to provide an output relating to the location of the marker. For example, this may be the amplitude of one or more odd harmonics, even harmonics or a combination of both, the ratios of these harmonics to each other or to the fundamental frequency. Appropriate filtering and processing of the signals may be provided to enhance the output provided by the method.
For a better understanding of the present invention and to show more clearly how it may be carried into effect, reference will now be made by way of example only, to the accompanying drawings, in which:
The present invention relates to a magnetic marker that can be implanted for marking a site in the body, for example the site of a lesion and subsequently be detected and localised using a handheld probe. The invention also describes a detection system and method for locating the position of the implanted marker in the body.
It is desirable to provide improved markers for enhanced localisation by the probe. The Applicant's co-pending Application No. GB1801224.5 describes one such marker. The marker comprises at least one piece of magnetic marker material having a large Barkhausen discontinuity in its magnetisation curve, also known as a large Barkhausen jump material (or a LBJ material). When the LBJ material is exposed to an external magnetic field whose field strength opposing the instantaneous magnetic polarization of said length of material exceeds a predetermined threshold value, the switching field HSW, its magnetic polarization undergoes a rapid reversal. This reversal of magnetisation generates a magnetic pulse with rich harmonic components. Conventionally, the markers are sized to be above the so-called ‘critical length’, that is the length at which the magnetization can undergo the full bistable transition or ‘flipping’ behaviour which is required to generate a significant harmonic response. However, the inventors found that a harmonic response can be obtained from markers significantly below their critical length and/or below the switching field HSW in a newly recognized “sub-bistable” mode and that this is advantageous for use for localization of the implantable marker.
The alternating magnetic field excites the marker 6 and the magnetisation of the marker leads to the generation of harmonic components in the field. Depending on the arrangement of the marker, the harmonics may be odd harmonics, (3rd, 5th, 7th etc.) or even harmonics (2nd, 4th, 6th etc.) or a combination of both odd and even harmonics. The marker is detected by measuring the magnitude of one or more of the harmonic frequencies directly or by measuring the ratio of the magnitude of one or more harmonics to others or to the magnitude of the fundamental frequency.
The response from the marker is detected by one of more sense coils 10 to generate a sense voltage or current. The sense coils may be in a handheld or robotic probe. A high-pass or notch filter 14 may be arranged to filter out or attenuate at least components of the sense signal at the drive frequency so that the resulting signal has minimal content at the drive frequency and comprises higher harmonic components of the signal, for example the second, third, fourth, fifth or seventh order harmonics or combinations of these. The filter may take the form of a passive LCR type filter comprising a known arrangement of for example capacitors, inductors and resistors or an active filter comprising a known arrangement for example based on one or more op-amps.
The filtered signal may be fed to a harmonic detection circuit 16 which amplifies one or more harmonic components of the signal and converts the signal 18 to a measure of distance from the probe to the marker. A user display and sound generator 20 provides a visual and audio output to the user indicating for example, the proximity of the marker or the magnitude of the magnetic signal. The system may indicate the proximity, size, distance to, direction or orientation of the marker, or combinations of these.
When a straight piece of LBJ wire is excited, the magnetic response it gives is directional, that is there is a greater response along the axis of the wire and a much lower response in a direction perpendicular to the wire. For this reason, the inventors co-pending Application GB1801224.5 describes how the dipole length of the LBJ material in the direction of the drive field is an important parameter for enabling harmonic response and detection and discloses the use of a number of wires, for example in a tripod arrangement, such that the dipole length in any given direction is substantially similar. However, such markers have thin sections making them fragile or vulnerable to movement. This can make satisfactory deployment of the marker difficult.
It is critical that the marker 6 deploys correctly from the needle because otherwise the similarity or identity of the dipole length in each direction will be affected, leading to a non-uniform and inaccurate response.
The present invention provides improved markers that contain LBJ material which may be detected using their conventional bistable behaviour or using the recently identified “sub-bistable” mode. The inventors have surprisingly found that markers that have a LBJ material formed into a coil or loop produce a measurable harmonic response. This was not to be expected because classic switching behaviour occurs through a cascade or domino effect in which the magnetic domains in the LBJ wires all flip at one time, and thus alignment of all the domains with the driving magnetic field is key. Domains not substantially aligned with the field will not flip or switch, thus resulting in the use of straight wires for detection. Thus, the skilled person would consider the use of any other configuration to be counter-intuitive based on the prior art literature. The coiled markers according to the invention demonstrate switching response similar qualitatively to the classic bistable switching described in the prior art at higher fields and larger diameter coils, while at lower fields and with smaller diameter coils, the response is ‘sub-bistable’ as described in GB1801224.5.
Furthermore, while a single straight LBJ wire provides an axial response that is much greater than the transverse (perpendicular to the axis) response, more surprisingly, the inventors have found that a coil of LBJ wire when excited in the sub-bistable mode (and indeed the bistable mode), has a larger transverse response than axial response, even when its length is several times its diameter.
Further embodiments of a marker according to the present invention are shown in
The LBJ magnetic material that is wound into coil as herein described may be combined with other materials to improve the marker. For example, the marker may be packaged within other materials. In this respect, markers for implantation need to be both biocompatible to prevent a reaction with body tissue, and robust. Some preferred magnetic materials are thin (wires below 0.15 mm in diameter), and contain non-biocompatible materials. Therefore, to improve the biocompatibility and robustness of the marker, it is preferable to provide a housing or coating for the magnetic material.
In a preferred embodiment a biocompatible and insulating coating or sheath such as FEP, Parylene, PTFE, ETFE, PE, PET, PVC or silicone further surrounds the tube 24. This insulating layer stops conduction between the turns within the coils further reducing the effects of Eddy current on the magnetic response of the marker.
Table 2 below shows the influence of the conductivity of the tube material on the harmonic response for straight lengths of an LJB wire in different tube materials. The signal from the LBJ wire in the copper tube with a material resistivity of 0.17×10−7 Ωm is at least 16 times lower than the signal from similar wires in tubes made with other materials with a higher resistivity of greater than 2×10−7 Ωm. The use of selective cutting of the tube such as with an interrupted laser cut spiral, which also supplies flexibility for coiling, may also be used to increase resistance and reduce the production of Eddy currents. The polymer coating may be applied before or after the material or tube is formed into a coil.
In a preferred embodiment, the marker housing could be formed from a moulded or extruded material. For example, a polymer may be extruded around the magnetic wire to form a coated wire that can then be formed into a loop or coil. Any of the embodiments above could also be overmoulded with a polymer to form a marker. The advantage of such an embodiment is that the polymer could provide biocompatibility and also make the manufacturing process simpler and less costly. The use of polymers also minimises any Eddy current effects seen with metal coatings or housings that could affect the magnetic response. Suitable materials for the coating or overmoulding include PEEK, PEKK, polyethylene, polypropylene, polyester, polyurethane, polyimide, polyether block amide, polyamide, PTFE, FEP, PET and silicones.
In another preferred embodiment, a marker according to the present invention includes a housing comprising one or more strands of material 26 which are wound around the magnetic material to form a more robust construction prior to forming into the final marker shape.
In any of the above embodiments, the marker may comprise a resiliently deformable member (tube, wire strands or coating) containing the LBJ wire such that the coil expands on deployment to a larger size. The expansion may be driven elastically by a resiliently deformable material or by a shape memory transition material such as nitinol.
In a further embodiment, the cross section of the marker may take a number of forms including round, rectangular or triangular, as shown in
Table 1 below illustrates characteristics of markers according to the invention and their H3 magnetic response. Embodiments shown in
Table 2 below illustrates the effect of the housing material of the marker on the magnitude of H3 response at a distance of 20 mm for a probe of a straight length of Co—Fe LBJ material of 4 mm.
Table 3 below shows how the magnitude of H3 response varies with diameter at a distance of 20 mm for a marker with similar coil pitches for coils in both 304ss and PET as well as demonstrating the increased response from coils in a material where there is less opposing eddy currents e.g. coils (PET), showing the increase in relative response per turn for the single coils with diameter. It also demonstrates the increased signal from a coil of smaller diameter inside a coil of larger diameter (
The inventors have found that such markers can be combined to create a marker with a more optimal or preferred harmonic response profile. Specifically, it is preferable if the harmonic response at a given distance from the marker is substantially uniform.
Thus for example, the prior art single straight wire can be combined with the coil of
It is demonstrated in
In the context of this disclosure, a uniform response means that the ratio of the maximum to minimum magnitude of the response being measured (be it H3, or other magnetic response) is less than 3 and preferably less than 2. Because the magnetic response when being detected with an arrangement similar to that in
The uniformity of response can also be varied by adjusting the pitch, number of turns/convolutions, length, diameter, shape, cross section and end configuration of the coil, and by varying the diameter or pitch of the turns at different points along the length of the coil.
By increasing the pitch compared with the marker of
If the pitch is increased to improve the uniformity of the response, the length of the marker for a given magnitude of response will increase, or the number of convolutions in a given length of marker will be reduced. The inventors have found that in this case, more than one coil can be combined in the form of a multi-start helix to increase the response while maintaining the small size of the marker.
The present invention provides a new and improved magnetic marker that may be used in a system and method for detecting the marker, thereby enabling a lesion for surgical excision to be located. The marker contains at least a piece of LBJ magnetic material that is wound into a coil having at least one, preferably more, convolutions. The marker may be excited at the switching field (bistable mode) or at a field lower than the bistable switching field (sub-bistable mode) and the generated harmonics measured from any direction to determine the position and orientation of the marker. In embodiments, the marker may also be provided below the critical length of the LBJ material required to enable bistable switching behaviour.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1804683 | Mar 2018 | GB | national |
This application is a continuation application of U.S. patent application Ser. No. 16/981,860 filed on Sep. 17, 2020, which is the national phase under 35 U.S.C. § 371 of International Application No. PCT/IB2019/052170 filed on Mar. 18, 2019, which claims priority to and the benefit of United Kingdom Patent Application No. 1804683.9 filed on Mar. 23, 2018, the entire disclosures of each of which are incorporated by reference herein.
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| Number | Date | Country | |
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| 20220054224 A1 | Feb 2022 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16981860 | US | |
| Child | 17518104 | US |
