WO2018049518A1

WO2018049518A1 - Method for manufacturing biocompatible coated magnetic seed markers

Info

Publication number: WO2018049518A1
Application number: PCT/CA2017/051075
Authority: WO
Inventors: Ananth RAVI; John Dillon
Original assignee: Sunnybrook Research Institute
Priority date: 2016-09-14
Filing date: 2017-09-13
Publication date: 2018-03-22

Abstract

A method for manufacturing magnetic seed markers for implantation in a subject is provided. Previously magnetized magnetic cores are arranged in a jig assembly and the exposed surface of the magnetic cores are coated with one or more coating layers. The partially coated seed markers are removed from the jig assembly and the uncoated surfaces are coated with one or more coating layers.

Description

METHOD FOR MANUFACTURING BIOCOMPATIBLE COATED MAGNETIC SEED

MARKERS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application

Serial No. 62/394,539, filed on September 14, 2016, and entitled "METHOD FOR MANUFACTURING BIOCOMPATIBLE COATED MAGNETIC SEED MARKERS," which is herein incorporated by reference in its entirety.

BACKGROUND

[0002] It would be desirable to provide a method for manufacturing magnetic seed markers that can be safely implanted in a living subject to localize the boundary of an anatomical region-of-interest, such as a tumor or other lesion. Such magnetic seed markers would thus need to be biocompatible.

[0003] Existing techniques for manufacturing magnetic seeds would magnetize the seeds before any biocompatible coatings have been applied. With these techniques, traditional coating processes, such as barrel plating methods, cannot be reliably used because the magnetized seeds would aggregate together, prohibiting uniform coating of their surfaces. But, magnetizing the magnetic seeds after they have been coated would result in a larger variance in seed composition and magnetic field strength, which would adversely affect their performance in clinical use.

[0004] Thus, there remains a need to provide a method for manufacturing large batches of biocompatible magnetic seeds with low inter-seed variability in composition and magnetic field strength.

SUMMARY OF THE DISCLOSURE

[0005] The present disclosure overcomes the aforementioned drawbacks by providing a method for manufacturing a magnetic seed marker. A magnetic core is arranged in an aperture formed in a first plate, wherein the first plate is composed of a non-magnetic material. A coating layer is deposited on an exposed surface of the magnetic core, and a second plate is positioned proximate the first plate. The second plate is composed of a magnetic material such that when the second plate is positioned proximate the first plate the magnetic core becomes magnetically coupled to the second plate. The first plate is removed so as to expose an uncoated surface of the magnetic core, which is still magnetically coupled to the second plate. A coating layer is then deposited on the uncoated surface of the magnetic core, resulting in a fully coated, already magnetized magnetic seed marker.

[0006] In some aspects of the present disclosure, more than one coating layer can be applied to magnetic core. In these examples, the multiple coating layers can be sequentially applied to the exposed surface of the magnetic core before the same coating layers are applied to the uncoated surface of the magnetic core.

[0007] The foregoing and other aspects and advantages of the invention will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration a preferred embodiment of the invention. Such embodiment does not necessarily represent the full scope of the invention, however, and reference is made therefore to the claims and herein for interpreting the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is an example of a magnetic seed marker.

[0009] FIG. 2A is a cross-sectional view of an example magnetic seed marker having a single biocompatible coating layer. [0010] FIG. 2B is a cross-sectional view of an example magnetic seed marker having multiple coating layers including at least an outer coating layer that is biocompatible.

[0011] FIG. 3 is an example jig assembly for arranging already magnetized magnetic cores to be partially coated with one or more coating layers.

[0012] FIG. 4 is a cross-sectional view of an example jig assembly.

[0013] FIG. 5 shows a cutaway view of a magnetic core arranged in an aperture of the jig assembly of FIG. 4.

[0014] FIG. 6 shows a cutaway view of the magnetic core of FIG. 5 arranged in an aperture of the jig assembly of FIG. 4 after a coating layer has been applied to the exposed surface of the magnetic core.

[0015] FIG. 7 A is an example of a partially coated magnetic seed core having a single partial coating layer.

[0016] FIG. 7B is an example of a partially coated magnetic seed core having multiple partial coating layers.

[0017] FIGS. 8A-8D illustrate the general steps for removing partially coated magnetic seed cores from a jig assembly and preparing the uncoated surfaces of the partially coated magnetic seed cores for coating.

[0018] FIG. 9 is a cutaway view of a partially coated magnetic seed core that is magnetically coupled to a surface of a ferromagnetic plate.

[0019] FIG. 10A is an example of a fully coated magnetic seed marker having a single coating layer.

[0020] FIG. 10B is another example of a fully coated magnetic seed marker having a single coating layer.

[0021] FIG. IOC is an example of a fully coated magnetic seed marker having multiple coating layers.

[0022] FIG. 11 is a flowchart setting forth the steps of an example method for manufacturing coated magnetic seed markers in accordance with the present disclosure.

DETAILED DESCRIPTION

[0023] Described here are systems and methods for manufacturing magnetic seeds for implantation in a subject. Producing magnetic seeds with strong magnetic fields, with low inter-seed variability, and such that the magnetic seeds are safe for implantation into a living subject is a challenging process. The systems and methods of the present disclosure provide solutions to these challenges.

[0024] FIGS. 1, 2A, and 2B illustrate an example of a magnetic seed 10 manufactured according to an example of the present disclosure. The magnetic seed 10 generally includes a magnetic core 12 composed of an alloy containing a rare-earth element and coated with a coating layer 14. As one example, the magnetic core 12 can be a neodymium magnet composed of an NdFeB ("NIB"] alloy or other alloys containing neodymium or other rare-earth elements. The magnetic core 12 can have any suitable shape, including spherical, cylindrical, ellipsoidal, rectangular, and so on. Generally, the magnetic cores 12 are sized and shaped to be received by a needle for implantation into a living subject. As one non-limiting example, the magnetic cores 12 can be cylindrical in shape with a diameter of 1.6 mm and a length of 3.2 mm. In some embodiments, the magnetic core 12 can be constructed such that the magnetic seed 10 will generate an anisotropic magnetic field.

[0025] The coating layer 14 can include a single layer, as shown in FIG. 2A, or can include multiple different layered coatings (14a, 14b, 14c, 14d], as shown in FIG. 2B. The coating layer 14 generally provides a biocompatible layer so the magnetic seed 10 can be safely implanted in a living subject. As one example, the biocompatible layer can include a metal layer containing gold, silver, nickel, copper, or alloys containing those metals. As another example, the biocompatible layer can include a biocompatible polymer layer, such as parylene.

[0026] The magnetic core 12 is manufactured using a sintering process during which a magnetic field is induced on the material being sintered to magnetize the magnetic core 12 during the sintering process. By magnetizing the magnetic core 12 during the sintering process— and before applying the coating layer 14— a better crystal structure can be obtained in the magnetic core 12 than if the magnetic core 12 was magnetized after the sintering process or after the coating layer 14 was applied. As such, more consistent magnetic fields can be attained in magnetic cores 12 that are magnetized while being sintered.

[0027] Because the magnetic core 12 is magnetized before applying the coating layer 14, attempts to coat the magnetic cores 12 with one or more coatings is challenging using standard loose barrel coating techniques commonly utilized for small life sciences components. For instance, the magnetized nature of the magnetic cores 12 would result in the magnetic cores 12 aggregating within the drum used for loose barrel coating techniques, which would result in an incomplete coating of the magnetic cores 12.

[0028] To address this problem, a jig assembly and coating processes are implemented to isolate each magnetic core 12 in an array and to coat one side of the magnetic core 12 before turning the magnetic core 12 over and to coat the other side.

[0029] FIGS. 3 and 4 illustrate an example jig assembly 20 that can be used to facilitate even coating of already magnetized magnetic cores 12. The jig assembly 20 generally includes a plate 22 composed of a non-magnetic material (e.g., a plastic or resin] in which multiple apertures 24 are formed. The apertures 24 are arrayed and spaced apart a sufficient distance such that when each aperture 24 is filled with a magnetic core 12, the magnetic fields of adjacent magnetic cores 12 will not interfere with the positioning of those magnetic cores 12 in the plate 22.

[0030] The diameter of each aperture 24 is sized to receive a magnetic core 12, and the depth of each aperture 24 below the top surface 26 of the plate 22 is such that when a magnetic core 12 is positioned within the aperture 24 the surface of the magnetic core 12 is partially exposed. As shown in FIGS. 5 and 6, the exposed surface 28 of the magnetic core 12 is free to be coated with one or more partial coating layers 30.

[0031] Examples of partially coated magnetic cores 12 are illustrated in FIGS. 7 A and 7B. In FIG. 7 A, a single partial coating layer 30 has been applied to the magnetic core 12, and in FIG. 7B, three partial coating layers 30a, 30b, 30c have been applied to the magnetic core 12. In this latter example, the partial coating layers 30a, 30b, 30c can be applied sequentially before removing the magnetic cores 12 from the jig assembly 20. It will be appreciated that although FIGS. 7A and 7B show one and three partial coating layers, respectively, that any suitable number of coating layers can be applied using one or more different coating materials. FIGS. 7A and 7B also show the uncoated surface 32 of the magnetic core 12 that remains after the magnetic cores 12 are removed from the jig assembly 20.

[0032] As shown in FIGS. 8A-8D, the partially coated magnetic cores 12 are removed from the jig assembly 20 such that the uncoated surface 32 of each magnetic core 12 can be coated with one or more coating layers. The partially coated magnetic cores 12 can be removed from the jig assembly 20 by arranging a ferromagnetic plate 34 proximate the jig assembly 20 (FIG. 8A] such that the partially coated magnetic cores 12 positioned within the jig assembly 20 adhere to the ferromagnetic plate 34 (FIG. 8B]. As one example, the ferromagnetic plate can be composed of steel or an alloy thereof; however, any suitable ferromagnetic material can be used. The ferromagnetic plate 34 and jig assembly 20 are then separated (FIG. 8C], which removes the partially coated magnetic cores 12 from the apertures 24 in the jig assembly 20, thereby exposing the uncoated surface 32 of each partially coated magnetic core 12. Because the partially coated magnetic cores 12 were magnetized during the sintering process, the partially coated magnetic cores 12 will remain adhered to the ferromagnetic plate 34 when the ferromagnetic plate 34 and jig assembly 20 are separated. The ferromagnetic plate 34 can then be flipped or otherwise rotated (FIG. 8D] to ready the uncoated surfaces 32 of the partially coated magnetic cores 12 to have one or more coating layers applied thereto.

[0033] FIG. 9 shows a partially coated magnetic core 12 positioned on the ferromagnetic plate 34 with the uncoated surface 32 exposed for coating. A coating layer 36 is then applied to the uncoated surface 32 of the partially coated magnetic core 12. As shown in FIG. 10A, the coating layer 36 can be applied such that the coating layer 36 is only provided to the uncoated surface 32 of the magnetic core 12, or as shown in FIG. 10B, the coating layer 36 can be applied such that is covers both the uncoated surface 32 and the coated surface 30 of the partially coated magnetic core 12. Preferably, the coating layer 36 is applied such that the coating layer 36 is only provided to the uncoated surface 32 of the magnetic core 12 to maintain a more uniform construction of the magnetic seed 10.

[0034] FIG. IOC illustrates an example of a magnetic seed 10 in which a first coating layer 14a and a second coating layer 14b. The first coating layer 14a is composed of coated surface 30a and a coating layer 36a applied to the uncoated surface 32 of the partially coated magnetic core 12, and coating layer 14b is composed of coated surface 30b and the coating layer 36b applied after the coating layer 36a is applied to the uncoated surface 32 of the partially coated magnetic core 12.

[0035] Referring now to FIG. 11, a flowchart is illustrated as setting forth the steps of an example method for manufacturing a magnetic seed. As described above and indicated at step 102, magnetic seed cores are formed using a sintering process during which a magnetic field is applied to the material being sintered so as to magnetize the magnetic seed cores as they are being sintered. The magnetic seed cores can be composed of an alloy containing a rare-earth element, such as an alloy containing neodymium. As one example, the magnetic seed cores can be composed of an NIB alloy.

[0036] The magnetized seed cores are then arranged in a jig assembly, such as the jig assembly described above, as indicated at step 104. For instance, the magnetized seed cores are positioned in the apertures formed in the jig assembly, such that the surface of the magnetized seeds is partially exposed. A coating layer is then applied to the exposed surface of the magnetized seeds, as indicated at step 106. The material applied to form the coating layer is preferably a biocompatible material, but can also include a non-biocompatible material if additional, biocompatible coating layers will be applied on top of the non-biocompatible layer. Examples of materials that can be applied in coating layers include polymers, such as parylene or other biocompatible polymers, and metals such as nickel, copper, silver, and gold, and alloys containing such metals. As an example, the coating material can be applied to the exposed surface of the magnetic cores using any suitable plating or deposition method, including electroplating, electroless plating, vapor deposition, and sputter deposition

[0037] A determination is made at decision block 108 whether additional coating layers should be applied. If additional coating layers are to be applied, then those layers are applied as indicated at step 106, and this loop repeats until the desired number of coating layers has been applied to the magnetized seed. When all of the coating layers have been applied, the partially coated seeds are separated from the jig assembly, as indicated at step 110. The partially coated seeds can be removed from the jig by positioning a ferromagnetic plate proximate the jig assembly, such that the partially coated seeds become magnetically coupled to the ferromagnetic plate. When the ferromagnetic plate is retracted from the surface of the jig assembly, the partially coated seeds will remain adhered to the ferromagnetic plate and will thus be removed from the apertures in the jig assembly. As a result, the uncoated surface of the partially coated seeds become exposed such that one or more coating layers can be applied to the uncoated surfaces. The jig assembly can then be cleaned or treated as necessary for its next use.

[0038] The ferromagnetic plate is then prepared for the next stage of the coating process, as indicated at step 112. For instance, the ferromagnetic plate can be flipped or otherwise rotated to orient the partially coated magnetic seeds for the next stage of coating. A coating layer is then applied to the uncoated surface of the magnetized seeds, as indicated at step 114. In some embodiments, the coating layer may also be applied to the previously coated portion of the partially coated seeds. Preferably, the same coating material is applied in this step as was applied in step 106. A determination is made at decision block 116 whether additional coating layers should be applied. If additional coating layers are to be applied, then those layers are applied as indicated at step 114, and this loop repeats until the desired number of coating layers has been applied to the magnetized seed. Preferably, the same coating materials are applied in step 114, and in the same order, as was applied in any loop of step 106. When all of the coating layers have been applied, the now fully coated seeds are separated from the ferromagnetic plate, as indicated at step 118. For example, the fully coated magnetic seeds can be manually removed from the ferromagnetic plate, or can be mechanically removed from the ferromagnetic plate, such as by scraping the ferromagnetic plate against a straight edge to dislodge the seeds or by vibrating the seeds free.

[0039] One, non-limiting example of a coating schedule that can be used for coating the magnetic seeds is as follows. First, a layer of nickel is deposited on the exposed surfaces of the magnetic cores. This first layer can be deposited using any suitable plating or deposition method, including electroplating, electroless plating, vapor deposition, and sputter deposition. Preferably, the first layer of nickel is only a few micrometers thick. As one example, the first layer of nickel can be between 5 and 6 micrometers thick. Next, a layer of copper is deposited on the exposed, nickel-coated surfaces of the magnetic cores. This second layer can be deposited using any suitable plating or deposition method, including electroplating, electroless plating, vapor deposition, and sputter deposition. Preferably, the layer of copper is only a few micrometers thick. As one example, the layer of copper can be between 7 and 8 micrometers thick. Next, a second layer of nickel is deposited on the exposed, copper- coated surfaces of the magnetic cores. This third layer can be deposited using any suitable plating or deposition method, including electroplating, electroless plating, vapor deposition, and sputter deposition. Preferably, the second layer of nickel is only a few micrometers thick. As one example, the second layer of nickel can be between 5 and 6 micrometers thick. Lastly, a layer of parylene is deposited on the exposed, nickel- coated surfaces of the magnetic cores. This fourth layer can be deposited using any suitable deposition method, including vapor deposition. Preferably, the layer of parylene is only a few micrometers thick. As one example, the layer of parylene can be between 2 and 4 micrometers thick. [0040] The present invention has been described in terms of one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

Claims

1. A method for manufacturing a magnetic seed marker, the steps of the method comprising:

(a] arranging a magnetic core in an aperture formed in a first plate, wherein the first plate is composed of a non-magnetic material and the aperture is sized such that a portion of a surface of the magnetic core remains exposed as an exposed surface;

(b] depositing a coating layer on an exposed surface of the magnetic core;

(c] positioning a second plate proximate the first plate, wherein the second plate is composed of a ferromagnetic material and wherein positioning the second plate proximate the first plate causes the magnetic core to magnetically coupled to the second plate;

(d] removing the first plate so as to expose an uncoated surface of the

magnetic core that is magnetically coupled to the second plate; and

(e] depositing a coating layer on the uncoated surface of the magnetic core.

2. The method as recited in claim 1, further comprising forming the magnetic core by sintering an alloy containing a rare-earth element while applying a magnetic field on the alloy such that the magnetic core is magnetized while the alloy is being sintered.

3. The method as recited in claim 1, wherein step (b] further comprises depositing at least one additional coating layer on the exposed surface of the magnetic core, and step (e] further comprises depositing at least one additional coating layer on the uncoated surface of the magnetic core.

4. The method as recited in claim 1, wherein the coating layer is deposited on the exposed surface of the magnetic core using a plating process.

5. The method as recited in claim 4, wherein the plating process includes at least one of electroplating, eletroless plating, vapor deposition, or sputtering deposition.

6. The method as recited in claim 1, wherein the coating layer is deposited on the uncoated surface of the magnetic core using a plating process.

7. The method as recited in claim 6, wherein the plating process includes at least one of electroplating, eletroless plating, vapor deposition, or sputtering deposition.

8. The method as recited in claim 1, further comprising removing the magnetic core from the second plate using at least one of a mechanical or manual collection.

9. The method as recited in claim 1, wherein:

step (a] includes arranging a plurality of magnetic cores in a respective plurality of apertures formed in the first plate;

step (b] includes depositing the coating layer on the exposed surface of each magnetic core;

step (d] includes removing the first plate so as to expose the uncoated surface of each magnetic core; and

step (e] includes depositing the coating layer on the uncoated surface of each magnetic core.