NEGATIVE POISSON'S RATIO MATERIALS FOR THERMAL AND RADIATION THERAPY SEEDS

Abstract

A biocompatible seed for implantation in tissue of a patient includes an elongated body sized and shaped to be at least partially inserted into the tissue of the patient, in which the body includes a negative Poisson's ratio (NPR) material having a Poisson's ratio of between 0 and 1. The seed can be a thermal seed configured to generate heat responsive to exposure to a magnetic field. The seed can be a seed for brachytherapy that includes an inner layer including a radioactive material and an outer layer including the NPR material.

Claims

1. A method of treating a tumor with a brachytherapy treatment, the method comprising: implanting into the tumor one or more implantable seeds, each seed comprising an elongated body sized and shaped to be at least partially inserted into the tumor, in which the body comprises: an inner layer formed of a radioactive material, and an outer layer covering the inner layer, the outer layer comprising a negative Poisson's ratio (NPR) material having a Poisson's ratio of between 0 and 1; and allowing the implantable seeds to remain in the tumor for a predetermined amount of time to deliver radiation to the tumor.

2. The method of claim 1, in which the elongated body is a generally cylindrical body having an increasing diameter from a first end to a second end, the first end being configured to be inserted into the tumor.

3. The method of claim 1, in which the NPR material comprises a porous NPR metal material.

4. The method of claim 3, in which the porous NPR metal material comprises one or more of nickel, copper, palladium, or cobalt.

5. The method of claim 3, in which the porous NPR material comprises an NPR metal foam.

6. The method of claim 1, in which the NPR material has a Poisson's ratio of between 0 and 0.8.

7. The method of claim 1, in which the NPR material is composed of a cellular structure having a characteristic dimension of between 0.01 m and 3 mm.

8. The method of claim 1, in which the body comprises a composite material comprising the NPR material and a positive Poisson's ratio (PPR) material.

9. The method of claim 1, in which the body comprises alternating layers of the NPR material and a PPR material.

10. The method of claim 9, in which the alternating layers are oriented parallel to a longitudinal axis of the elongated body.

11. The method of claim 1, in which the inner layer comprises a PPR material.

Description

DESCRIPTION OF DRAWINGS

[0034] FIG. 1 is an illustration of thermal seeds.

[0035] FIG. 2 is an illustration of materials with negative and positive Poisson's ratios.

[0036] FIG. 3 is an illustration of thermal seeds.

[0037] FIG. 4 is an illustration of thermal seeds.

[0038] FIG. 5 is an illustration of radioactive seeds.

[0039] FIG. 6 is an illustration of seeds implanted in a patient.

[0040] FIG. 7 is a diagram of a method of making an NPR material.

DETAILED DESCRIPTION

[0041] We describe here implants used in thermal therapy (e.g., thermal seeds) or radiation therapy (e.g., brachytherapy seeds) that include materials having a negative Poissons ratio (NPR materials). NPR materials are lightweight, porous, and capable of being embedded in the surrounding tissue more securely than conventional implants due to their porosity and greater surface area in contact with tissue. Implants can be formed of NPR materials alone or in conjunction with materials having a positive Poisson's ratio (PPR materials). In some examples, some portions of the seeds are formed of NPR materials and other portions are formed of PPR materials. In some examples, composite materials that include both NPR materials and PPR materials are used for the seeds.

[0042] Referring to FIG. 1, a set of thermal seeds 100 is illustrated. The thermal seeds 100 have an elongated body that is sized and shaped to be at least partially inserted into a patient (e.g., a prostate of a patient). For instance, the elongated body of the thermal seeds 100 can be generally cylindrical, e.g., with a diameter of about 1 millimeters (mm) and a length of about 10 mm. Although the thermal seeds are illustrated in a generally cylindrical shape, the thermal seeds can be a variety of shapes that fill the prostate (e.g., hexagonal, octagonal, elliptical, etc.). Additionally, the thermal seeds can have a variable diameter from a proximal end 102 to a distal end 104.

[0043] In some examples, thermal seeds are formed of a biocompatible metal or metal alloy, such as Nickel (Ni), Copper (Cu), Palladium (Pd), Cobalt (Co), NiCu, PdCo, or other suitable materials. To use such thermal seeds in, e.g., treatment of BPH, the thermal seeds are inserted into the prostate of the patient. Once in the prostate, the thermal seeds can be heated through, e.g., magnetic induction. Magnetic induction is the creation of electromagnetic forces (e.g., inducing an electrical current) using an electrical conductor (e.g., the thermal seeds 100) and changing magnetic fields. The induced electrical current in the thermal seeds can create heat for application of thermal therapy to the tissue in which the seeds are implanted, e.g., to the prostate.

[0044] The thermal seeds 100 described here can be at least partially formed of a biocompatible NPR material (also referred to as an auxetic material). In some examples, the thermal seeds 100 are formed completely of a biocompatible NPR material, such as a porous NPR material, e.g., a porous NPR metal material. In some examples, the porous material is an NPR foam material, e.g., an NPR metal foam. In some examples, the thermal seeds 100 are formed of a composite material that include both biocompatible NPR materials and biocompatible PPR materials, referred to as an NPR-PPR composite material. Forming the thermal seeds 100 from an NPR material can have advantages. For instance, NPR materials, such as porous NPR materials, e.g., NPR foam materials, have a low density, and seeds formed from NPR materials can be less obtrusive to a patient than comparable PPR seeds. In addition, porous NPR materials, such as NPR foam materials, thus present a large surface area to the tissue in which the NPR seed is implanted, facilitating good contact between the seed and the tissue. This good contact can help with positional stability of the seed. The large area of contact between the seed and the tissue also helps ensure efficient heat transfer from the seed to the tissue, contributing to therapeutic effectiveness.

[0045] An NPR material is a material that has a Poisson's ratio that is less than zero, such that when the material experiences a positive strain along one axis (e.g., when the material is stretched), the strain in the material along the two perpendicular axes is also positive (e.g., the material expands in cross-section). Conversely, when the material experiences a negative strain along one axis (e.g., when the material is compressed), the strain in the material along a perpendicular axis is also negative (e.g., the material compresses along the perpendicular axis). By contrast, a PPR material has a Poisson's ratio that is greater than zero. When a PPR material experiences a positive strain along one axis (e.g., when the material is stretched), the strain in the material along the two perpendicular axes is negative (e.g., the material compresses in cross-section), and vice versa.

[0046] Materials with negative and positive Poisson's ratios are illustrated in FIG. 2, which depicts a hypothetical two-dimensional block of material 200 with length 1 and width w.

[0047] If the hypothetical block of material 200 is a PPR material, when the block of material 200 is compressed along its width w, the material deforms into the shape shown as block 202. The width w1 of block 202 is less than the width w of block 200, and the length 11 of block 202 is greater than the length 1 of block 200: the material compresses along its width and expands along its length.

[0048] By contrast, if the hypothetical block of material 200 is an NPR material, when the block of material 200 is compressed along its width w, the material deforms into the shape shown as block 204. Both the width w2 and the length 12 of block 204 are less than the width w and length 1, respectively, of block 200: the material compresses along both its width and its length.

[0049] NPR materials for thermal seeds can be foams, such as polymeric foams, ceramic foams, metallic foams, or combinations thereof. A foam is a multi-phase composite material in which one phase is gaseous and the one or more other phases are solid (e.g., polymeric, ceramic, or metallic). Foams can be closed-cell foams, in which each gaseous cell is sealed by solid material; open-cell foams, in which the each cell communicates with the outside atmosphere; or mixed, in which some cells are closed and some cells are open.

[0050] An example of an NPR foam structure is a re-entrant structure, which is a foam in which the walls of the cells are concave, e.g., protruding inwards toward the interior of the cells. In a re-entrant foam, compression applied to opposing walls of a cell will cause the four other, inwardly directed walls of the cell to buckle inward further, causing the material in cross-section to compress, such that a compression occurs in all directions. Similarly, tension applied to opposing walls of a cell will cause the four other, inwardly directed walls of the cell to unfold, causing the material in cross-section to expand, such that expansion occurs in all directions. NPR foams can have a Poisson's ratio of between 1 and 0, e.g., between 0.8 and 0, e.g., 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1. NPR foams can have an isotropic Poisson's ratio (e.g., Poisson's ratio is the same in all directions) or an anisotropic Poisson's ratio (e.g., Poisson's ratio when the foam is strained in one direction differs from Poisson's ratio when the foam is strained in a different direction).

[0051] An NPR foam can be polydisperse (e.g., the cells of the foam are not all of the same size) and disordered (e.g., the cells of the foam are randomly arranged, as opposed to being arranged in a regular lattice). An NPR foam can have a characteristic dimension (e.g., the size of a representative cell, such as the width of the cell from one wall to the opposing wall) ranging from 0.01 m to about 3 mm, e.g., about 0.01 m, about 0.05 m, about 0.1 m, about 0.5 m, about 1 m, about 10 m, about 50 m, about 100 m, about 900 m, about 1 mm, about 2 mm, or about 3 mm.

[0052] Examples of polymeric foams for thermal seeds include thermoplastic polymer foams (e.g., polyester polyurethane or polyether polyurethane); viscoelastic elastomer foams; or thermosetting polymer foams such as silicone rubber. Examples of metallic foams include metallic foams based on Nickel (Ni), Copper (Cu), Palladium (Pd), Cobalt (Co), NiCu, PdCo, or other metals or alloys.

[0053] NPR-PPR composite materials are composites that include both regions of NPR material and regions of PPR material. NPR-PPR composite materials can be laminar composites, matrix composites (e.g., metal matrix composites, polymer matrix composites, or ceramic matrix composites), particulate reinforced composites, fiber reinforced composites, or other types of composite materials. In some examples, the NPR material is the matrix phase of the composite and the PPR material is the reinforcement phase, e.g., the particulate phase or fiber phase. In some examples, the PPR material is the matrix phase of the composite and the NPR material is the reinforcement phase.

[0054] In some examples, thermal seeds can be multilayer structures. With reference to FIG. 3, thermal seeds 300 have an inner layer 302 and an outer layer 304. The inner layer 302 can have a diameter of, e.g., about 0.01 millimeters to about 14.9 millimeters, and the outer layer 304 can have a thickness of, e.g., about 0.01 millimeters to about 14.9 millimeters.

[0055] The inner layer 302 and the outer layer 304 are formed of different materials. The different composition of the inner layer 302 and outer layer 304 can allow for desired performance characteristics to be achieved. For instance, the inner layer 302 can be formed of a material with a high thermal capacity or thermal conductivity to facilitate effective thermal therapy, and the outer layer 304 can be formed of a biocompatible NPR material to provide a porous exterior that gives a large surface area in contact with the surrounding tissue. In some examples, the outer layer 304 is a non-porous material that acts as a barrier layer to prevent contact between the inner layer 302 and the surrounding tissue. In some examples, the outer layer 304 makes the thermal seeds comfortable for the patient, e.g., the outer layer is formed of a low friction material (e.g., the outer layer has a lower coefficient of friction than the inner layer with respect to the patient's prostate), a softer material that conforms better to a patient's prostate than the material of the inner layer, or a moldable material. In an example, the outer layer 302 is formed of an NPR material, such as a porous NPR material, e.g., an NPR polymer foam or an NPR metal foam, or an NPR-PPR composite material; and the inner layer is formed of a PPR material, such as a metal or metal alloy, e.g., Nickel (Ni), Copper (Cu), Palladium (Pd), Cobalt (Co), NiCu, PdCo, or another suitable material; or vice versa. An outer layer composed of an NPR material can be advantageous because the seeds can be embedded in the surrounding tissue, e.g., prostate, more securely due to the porosity and increased surface area in contact with the tissue.

[0056] In some examples, thermal seeds have more than two layers (e.g., 3 layers, 4 layers, etc.). In implementations with more than two layers, each layer can be formed of a different material, or multiple layers can be formed of the same material.

[0057] In some embodiments, thermal seeds can be composed of multiple layers of PPR and NPR materials. For example, with reference to FIG. 4, thermal seeds 400 have PPR layers 402 and NPR layers 404 that extend longitudinally along the thermal seeds 400, e.g., along an axis aligned with the elongated length of the thermal seeds 400. In the illustrated example, the thermal seeds 400 have three PPR layers 402 and four NPR layers 404, however in other embodiments the thermal seeds can have more or fewer layers. The PPR layers 402 and the NPR layers 404 are of even width, although in other embodiments the widths of the layers can be irregular. In some embodiments, the multiple layers of PPR and NPR materials can be arranged laterally rather than longitudinally, e.g., perpendicular to the longitudinal axis of the thermal seeds. In other embodiments, the multiple layers of PPR and NPR materials can be arranged obliquely to the thermal seeds, e.g., neither parallel to nor perpendicular to the longitudinal axis of the thermal seeds.

[0058] Other types of therapy, such as radiation therapy (e.g., brachytherapy) can utilize seeds formed of an NPR material. With reference to FIG. 5, seeds 500 include an outer layer 504 formed of an NPR material or an NPR-PPR composite material and an inner layer 502 formed of a radioactive material (e.g., radium, cesium, iridium, iodine, phosphorus, palladium). The inner layer 502 is partially or completely encapsulated within the outer layer 502. The outer layer 504 can be an NPR foam material, such as a porous NPR material, e.g., an NPR polymer foam, an NPR ceramic foam, or an NPR metal foam. An outer layer composed of an NPR material, such as a porous NPR material, e.g., an NPR foam material, can be advantageous because the seeds can be embedded in the surrounding tissue, e.g., prostate, more securely due to the porosity and increased surface area in contact with the tissue. Some porous NPR materials, e.g., NPR foam materials, are relatively soft, moldable, or both, allowing the seeds to conform well to the surrounding tissue, which helps ensure positional stability. In some examples, the porous NPR material, e.g., NPR foam material, of the outer layer 504 can be low friction material (e.g., the outer layer has a lower coefficient of friction than the inner layer with respect to the patient's prostate), which can help make the insertion of the seeds 500 less irritating to the patient's tissue. In some embodiments, the NPR and PPR layers can be arranged similarly to the arrangement of multiple NPR and PPR layers of FIG. 4.

[0059] Using radioactive seeds in a brachytherapy procedure can allow a higher dose of radiation to be delivered to a limited area than conventional, external beam radiation treatments. Radioactive seeds can be more effective at destroying cancer cells than conventional radiation treatments while minimizing damage to surrounding normal tissue. The radiation emitted from the inner layer 502 can kill damaging tumors or cells (e.g., cancer cells). The outer layer 504 is formed of a material that does not interfere with the radiation emitted from the inner layer 502.

[0060] FIG. 6 illustrates thermal seeds 604 implanted in a patient 600. For example, the seeds 604 are implanted in a prostate 602 of the patient 600. A magnetic field source 606 applies a magnetic field 608 to the seeds, inducing electromagnetic forces in the seeds 604 through magnetic induction. As described above, magnetic induction is the creation of electromagnetic forces (e.g., inducing an electrical current) using an electrical conductor (i.e., thermal seeds) and changing magnetic fields. The induced electrical current in the seeds creates heat for thermal therapy of the surrounding tissue, e.g., the prostate 602.

[0061] In the case of brachytherapy, the implanted seeds are radioactive and emit radiation, and the magnetic field source 606 is not necessary. The seeds are implanted in the tissue, e.g., in a tumor, and allowed to remain in the tumor for a predetermined amount of time sufficient to deliver a clinically meaningful amount of radiation to the tumor.

[0062] In some examples, porous NPR materials, such as NPR foams, are produced by transformation of PPR foams to change the structure of the foam into a structure that exhibits a negative Poisson's ratio. In some examples, porous NPR materials, such as NPR foams, are produced by transformation of nanostructured or microstructured PPR materials, such as nanospheres, microspheres, nanotubes, microtubes, or other nano- or micro-structured materials, into a foam structure that exhibits a negative Poisson's ratio. The transformation of a PPR foam or a nanostructured or microstructured material into an NPR foam can involve thermal treatment (e.g., heating, cooling, or both), application of pressure, or a combination thereof. In some examples, PPR materials, such as PPR foams or nanostructured or microstructured PPR materials, are transformed into NPR materials by chemical processes, e.g., by using glue. In some examples, NPR materials are fabricated using micromachining or lithographic techniques, e.g., by laser micromachining or lithographic patterning of thin layers of material. In some examples, NPR materials are fabricated by additive manufacturing (e.g., three-dimensional (3D) printing) techniques, such as stereolithography, selective laser sintering, or other appropriate additive manufacturing technique.

[0063] In an example, a PPR thermoplastic foam, such as an elastomeric silicone film, can be transformed into an NPR foam by compressing the PPR foam, heating the compressed foam to a temperature above its softening point, and cooling the compressed foam. In an example, a PPR foam composed of a ductile metal can be transformed into an NPR foam by uniaxially compressing the PPR foam until the foam yields, followed by uniaxially compression in other directions.

[0064] FIG. 7 illustrates an example method of making a multi-layer thermal seed in which an inner layer is formed of an NPR material. A granular or powdered material, such as a polymer material (e.g., a rubber) is mixed with a foaming agent to form a porous material 50. The porous material 50 is placed into a mold 52. Pressure is applied to compress the material 50 and the compressed material is heated to a temperature above its softening point. The material is then allowed to cool, resulting in a porous NPR material 54. The porous NPR material 54 is covered with an outer layer 56, such as a polymer layer, and heat and pressure can be applied again to cure the final material into a thermal seed 58.

[0065] In some examples, such as for brachytherapy seeds, the outer layer of the seed is formed of an NPR material. A granular or powdered material, such as a polymer material (e.g., a rubber) is mixed with a foaming agent to form a porous material. The porous material is placed into a mold surrounding an inner layer (e.g., a radioactive layer). Pressure is applied to compress the material and the compressed material is heated to a temperature above its softening point. The material is then allowed to cool, resulting in a porous NPR outer layer.

[0066] Other methods can also be used to fabricate thermal seeds or brachytherapy seeds formed of an NPR material or an NPR-PPR composite material. For example, various additive manufacturing (e.g., 3D printing) techniques, such as stereolithography, selective laser sintering, or other appropriate additive manufacturing technique, can be implemented to fabricate an thermal seed formed of an NPR material or an NPR-PPR composite. In some examples, different components of the thermal seed are made by different techniques. For example, the inner layer may be 3D printed while the outer layer is not, or vice versa. Additive manufacturing techniques can enable seams to be eliminated.

[0067] Particular embodiments of the subject matter have been described. Other embodiments are within the scope of the following claims.