Lithium target with intermediate layer

Abstract

The present disclosure provides a neutron generating target that includes a neutron generating region, a highly thermally conductive base plate substrate, and an intermediate layer positioned between the neutron generating region and the substrate to facilitate heat transfer and / or avoid hydrogen deposition in the substrate. One example of the intermediate layer is highly oriented pyrolytic graphite. The present disclosure provides, among other things, a lithium-containing neutron generating target useful for generating a neutron beam for irradiating boron-containing compounds in boron neutron capture therapy ("BNCT") of cancer.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 413,608, filed October 5, 2022, and U.S. Provisional Patent Application No. 63 / 508,125, filed June 14, 2023, both of which are incorporated by reference herein in their entirety for all purposes.

[0002] The subject matter described herein generally relates to a neutron generating target that includes a neutron generating region (e.g., containing lithium), a base plate substrate (e.g., containing copper or graphite), and at least one intermediate layer (e.g., containing highly oriented graphite) positioned between the neutron generating region and the substrate. The at least one intermediate layer can facilitate heat transfer and / or avoid hydrogen accumulation in the substrate. [Background technology]

[0003] Cancer is one of the leading causes of death in modern society. The number of new cancer cases and deaths is increasing annually. Currently, the cancer incidence rate is nearly 450 cases per 100,000 people (men and women) per year, and the cancer mortality rate is nearly 71 cases per 100,000 people (men and women) per year. Locally invasive malignancies, such as brain cancer, head and neck cancer, and cutaneous and extracutaneous melanoma, are of particular concern because effective means for treating or inhibiting their growth are limited. For example, boron neutron capture therapy, or BNCT, uses an accelerator-based neutron source to generate short-lived alpha particles from boron-10 accumulated in a patient's tumor tissue. These alpha particles selectively kill tumor cells while avoiding damage to healthy organs and tissues. Summary of the Invention [Means for solving the problem]

[0004] The present disclosure provides lithium-containing neutron generating targets useful, among other things, for generating neutron beams for irradiating boron-containing compounds in boron neutron capture therapy ("BNCT") of cancer. In one example, the present disclosure provides a neutron generating target including a highly thermally conductive substrate, a neutron-generating lithium region on the substrate, and an intermediate layer positioned between the substrate and the lithium region. The present disclosure is based, at least in part, on the recognition that the inclusion of an intermediate layer, such as a graphite layer, within the target advantageously enables efficient transfer of heat generated during neutron production from the lithium region to the substrate, where the heat is further removed from the target by a coolant. The intermediate layer not only facilitates efficient heat removal and helps prevent melting of the lithium during operation, but also avoids undesirable interdiffusion of lithium into the material of the substrate, and vice versa. This advantageously minimizes the amount of lithium required to manufacture the target, allowing for significant reductions in target cost and overall operation. Additionally, and importantly here, the intermediate layer captures any remaining unreacted protons that leave the neutron-generating lithium region, thereby sequestering the hydrogen and preventing the formation of gaseous hydrogen in the substrate and blistering at the substrate-lithium interface. If the intermediate layer is porous, any hydrogen in the intermediate layer can be removed from the target by diffusing through the pores into the vacuum system containing the target.

[0005] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Methods and materials for use in this application are described herein; however, other suitable methods and materials known in the art can also be used. These materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patent applications, patents, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

[0006] Other systems, devices, methods, features, and advantages of the subject matter described herein will be, or will become, apparent to one with skill in the art upon examination of the following figures and detailed description. All such additional systems, methods, features, and advantages are intended to be included within this specification, be within the scope of the subject matter described herein, and be protected by the accompanying claims. Features of the exemplary embodiments should not be construed as limiting the scope of the appended claims unless there is an express recitation of those features in the claims.

[0007] Details of the subject matter described herein, both as to its structure and operation, may be apparent from consideration of the accompanying drawings, in which like reference numerals refer to like parts. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the subject matter. Moreover, all illustrations are intended to convey concepts, and relative size, shape, and other detailed attributes may be illustrated schematically, rather than literally or precisely. [Brief explanation of the drawings]

[0008] [Figure 1A] FIG. 1 is a schematic diagram of an exemplary embodiment of a neutron beam system. [Figure 1B] FIG. 2 is a schematic diagram of another exemplary embodiment of a neutron beam system. [Figure 2A] 2 is a cross-sectional view depicting an exemplary embodiment of a target assembly subsystem 200. FIG. [Figure 2B] 1 is a cross-sectional view depicting an example of an existing neutron generating target. [Figure 3A] 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100. FIG. [Figure 3B] FIG. 1 is a front perspective view depicting an exemplary embodiment of a neutron generating target 100. [Figure 3C] FIG. 1 is a rear perspective view depicting an exemplary embodiment of a neutron generating target 100. [Figure 3D]FIG. 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100 including a high thermal conductivity intermediate layer. [Figure 3E] FIG. 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100 including a high thermal conductivity intermediate layer. [Figure 3F] FIG. 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100 including a high thermal conductivity intermediate layer. [Figure 4A] 1A-1C are cross-sectional views depicting an exemplary embodiment of a neutron generating target 100, each including a braze layer, an adhesive layer, and a passivation region. [Figure 4B] 1A-1C are cross-sectional views depicting an exemplary embodiment of a neutron generating target 100, each including a braze layer, an adhesive layer, and a passivation region. [Figure 4C] 1A-1C are cross-sectional views depicting an exemplary embodiment of a neutron generating target 100, each including a braze layer, an adhesive layer, and a passivation region. [Figure 4D] FIG. 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100 including a substrate made from a highly thermally conductive material. [Figure 4E] FIG. 1 is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100 including a substrate made from highly oriented graphite. [Figure 5] 1 is a flowchart of an example process for treating cancer using a neutron-generating target 100. [Figure 6A] FIG. 2 is a cross-sectional view depicting another example of a neutron generating target. [Figure 6B] FIG. 10 is a cross-sectional view depicting yet another example of a neutron generating target. [Figure 6C] FIG. 10 is a cross-sectional view depicting a further example of a neutron generating target. [Figure 6D] FIG. 10 is a cross-sectional view depicting yet another example of a neutron generating target.

[0009] In the drawings, like reference numbers refer to like elements. DETAILED DESCRIPTION OF THE INVENTION

[0010] Before the present subject matter is described in detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such embodiments may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, as the scope of the present disclosure will be limited only by the appended claims.

[0011] The neutron generating targets and embodiments thereof described herein can be implemented in a variety of applications where neutron generation is desired. The targets can be used in both medical and non-medical applications. Suitable examples of non-medical applications include nuclear fusion reactors, scientific tools for nuclear physics research (e.g., Faraday cups for capturing charged particles in a vacuum), industrial manufacturing processes, beam systems for modifying material properties (e.g., surface treatment and deformation), beam systems for irradiating food, and non-medical imaging applications (e.g., cargo or container inspection). Suitable examples of medical applications include beam systems for pathogen destruction and medical sterilization, medical diagnostic systems, medical imaging systems, and radiation therapy systems (e.g., X-ray machines, cobalt-60 machines, linear accelerators, proton beam machines, and neutron beam machines). One example of a medical application of the neutron generating targets described herein is boron neutron capture therapy ("BNCT").

[0012] In general, boron neutron capture therapy ("BNCT") is a type of treatment for various types of cancer, including the most difficult types. Suitable examples of such cancers include liver cancer (including liver metastases), oral cancer, colon cancer, brain cancer such as glioblastoma, head and neck cancer, lung cancer, widespread squamous cell carcinoma, laryngeal cancer, and melanoma. BNCT is a technique that aims to selectively treat tumor cells while sparing normal cells using compounds containing the non-radioactive isotope boron-10, which has a high tendency to capture low-energy "thermal" or "epithermal" neutrons. In this technique, the boron-containing compound is administered to the patient (e.g., by injecting a parenteral composition into the patient's blood vessels), allowing the boron-10 to selectively concentrate in the tumor cells. Suitable examples of boron delivery agents that can be administered to cancer patients include boronated amino acids, boron nitride nanotubes, liposomes and immunoliposomes carrying boron particles, various boron-containing nanoparticles, boronated cyclic or acyclic peptides with affinity for cancer cells (e.g., boronated arginylglycylaspartic acid, "RGD," or cyclic versions thereof), boronated compounds with affinity for receptors overexpressed in cancer cells, boronated sugars, and boronic acids. Generally, these compounds can selectively accumulate in malignant tumors while sparing healthy tissue (e.g., at least about 85%, at least about 90%, at least about 95%, or at least about 99% by weight of the boron compound accumulates in tumor tissue, as opposed to healthy tissue). As used herein, the term "about" means "approximately" (e.g., plus or minus about 10% of the stated value). When a measurable value is provided in this disclosure, the value encompasses that value exactly and within 10% of that value. For example, when a boron carrier compound is administered, the tumor concentration of boron is approximately 20-50 μg 10 Boron-10 can be obtained in the range of 10 B / g of tumor. The tumor concentration of boron can be determined by any means commonly known to physicians for this purpose, such as imaging, calibration, and / or biopsy. Once a sufficient amount of boron-10 has collected in the tumor, the patient is subjected to radiation in the form of a neutron beam at or near the tumor site.

[0013] Typically, a neutron-generating material, such as lithium, is charged with neutrons of sufficient energy (e.g., 1.88 MeV Li) to produce a neutron beam. 7 →Be 7 The neutron-producing reaction can be described as follows, where p represents a proton and n represents a neutron: Li 7 (3p,4n)+p=Be 7 (4p,3n)+n (formula 1)

[0014] The resulting neutron beam is slowed down and focused on the patient, where the neutrons react with boron-10 in the tumor cells, producing short-range alpha particles (He 4 ) is generated. B 10 (5p,5n)+n=Li 7 (3p,4n)+He 4 (2p,2n) (Formula 2)

[0015] FIG. 1A includes a schematic diagram of an example neutron beam system 10 that can be used to generate neutrons for BNCT using a neutron generating target (target 100) of the present disclosure.

[0016] 1A, beam system 10 includes an ion source 12, a low energy beam line ("LEBL") 14, an accelerator 16 coupled to LEBL 14, and a high energy beam line ("HEBL") 16 extending from accelerator 16 to a target 100. LEBL 14 is configured to transport a charged particle beam, e.g., a negative hydrogen ion beam, from ion source 12 to the input of accelerator 16, which is also configured to generate a proton beam by accelerating the hydrogen ion beam transported by LEBL 14. HEBL 18 transmits the proton beam from the output of accelerator 16 to target 100. Upon irradiation with sufficiently energetic protons, target 100 is configured to generate a neutron beam that is further directed to a tumor site (not shown) within a patient's body.

[0017] 1B is a schematic diagram illustrating another exemplary embodiment of a neutron beam system 10 for use in boron neutron capture therapy (BNCT), where the source 12 is an ion source and the accelerator 16 is a tandem accelerator. The neutron beam system 10 includes a pre-accelerator system 20 that functions as a charged particle beam injector, a high-voltage (HV) tandem accelerator 16 coupled to the pre-accelerator system 20, and a neutron beam emitting laser beam 18 that extends from the tandem accelerator 16 to a neutron target assembly 200 that houses a target 100 (not shown). The pre-accelerator system 20 is configured to transport a hydrogen ion beam from the ion source 12 to the input (e.g., input aperture) of the tandem accelerator 16 and thus also functions as the LEBL 14. The tandem accelerator 16 is powered by a high voltage power supply 42 coupled thereto and is capable of producing a proton beam having an energy approximately equal to twice the voltage applied to accelerating electrodes positioned within the accelerator 16. The energy level of the proton beam can be achieved by accelerating a beam of negative hydrogen ions from the input of the accelerator 16 to the innermost high potential electrode, stripping two electrons from each ion, and then accelerating the resulting protons downstream with the same applied voltage.

[0018] The HEBL 18 can deliver the proton beam from the output of the accelerator 16 to a target 100 in a neutron target assembly 200 positioned at the end of a beamline branch 70 that extends to a patient treatment room. The system 10 can be configured to direct the proton beam to any number of one or more targets and associated treatment areas. In this embodiment, the HEBL 18 includes three branches 70, 80, and 90 that can extend to three different patient treatment rooms, with each branch terminating in a target assembly 200 and a downstream beam shaping device (not shown). The HEBL 18 can include a pump chamber 51, quadrupole magnets 52 and 72 to prevent beam defocusing, dipole or bending magnets 56 and 58 to steer the beam into the treatment room, a beam corrector 53, diagnostic equipment such as current monitors 54 and 76, a high-speed beam position monitor 55 section, and a scanning magnet 74.

[0019] The design of the HEBL 18 depends on the configuration of the treatment facility (e.g., a single-level treatment facility configuration, a two-level treatment facility configuration, and the like). The proton beam can be delivered to a target assembly 200 (e.g., positioned near the treatment room) using a bending magnet 56. Quadrupole magnets 72 can then be included to focus the proton beam to a specific size on the target. The proton beam then passes through one or more scanning magnets 74, which provide lateral movement of the proton beam onto the target surface in a desired pattern (e.g., spiral, curved, row and column stepped, combinations thereof, and others). The lateral movement of the proton beam helps achieve a smooth, even time-averaged distribution of the proton beam on the lithium target 100, preventing overheating and ensuring neutron generation as uniform as possible within the lithium layer.

[0020] After entering the scanning magnet 74, the proton beam can be delivered to a current monitor 76, which measures the beam current. The target assembly 200 can be physically separated from the HEBL volume using a gate valve 77. The gate valve's primary function is to separate the vacuum volume of the beamline from the target while loading the target and / or replacing a used target with a new one. In an embodiment, the beam may not be bent 90 degrees by the bending magnet 56, but rather travels straight to the right in FIG. 1B and then enters the quadrupole magnet 52 located in the horizontal beamline. The beam can then be bent to the required angle by another bending magnet 58, depending on the building and room configuration. Otherwise, the bending magnet 58 can be replaced with a Y-shaped magnet to split the beamline into two directions for two different treatment rooms located on the same floor.

[0021] 2A is a cross-sectional view depicting an exemplary embodiment of a target assembly subsystem 200 of the neutron beam system 10 shown in FIG. 1B. In this embodiment, the neutron generating target 100 is enclosed between a cap 202 and the vacuum or near-vacuum interior region 210 of the HEBL 18. Arrow B indicates the direction of the charged particle beam, which initially strikes the face on the upstream side 112. Cooling of the target 100 can be achieved on the opposite downstream side 114 (where the neutron beam exits the target 100). The cap 202 can be bolted to the HEBL 18, thus providing both a vacuum-tight seal 206 between the target 100 and the vacuum region 210 of the HEBL 18, and a water-tight seal 205 between the target 100 and the coolant inlet 204 and outlet 208.

[0022] In one general aspect, the present disclosure provides targets useful for applications where various forms of radiation (e.g., neutron radiation) are required. One example of a target of the present disclosure is a neutron-generating target, such as target 100 in target assembly 200 (see FIGS. 1B and 2A), useful for generating a neutron beam for irradiating a boron-containing compound administered to a patient during BNCT.

[0023] Several targets 100 have previously been used for neutron generation, including BNCT. An example of such a target is shown in FIG. 2B. Generally, a target includes a neutron-generating layer 110, which is typically a planar layer composed primarily of lithium. The layer 110 is bonded to a substrate 120 made of a highly thermally conductive material, such as copper. A proton beam (e.g., a beam in direction B) impinges on the neutron-generating layer 110 of the target 100 at an upstream side 112. While shown incident in direction B, the proton beam can impinge on the target 100 at any angle. For example, the target 100 can be angled so that the proton beam impinges on the target at an angle between 0 and 90 degrees relative to the planar surface of the neutron-generating layer 110. The proton beam impinging on the neutron-generating layer 110 at the upstream side 112 and the neutron beam exiting the substrate 120 of the target 100 at the downstream side 114 generate a tremendous amount of heat. To remove this heat, the substrate 120 typically includes fluid flow channels, such as spiral channels 122, through which a coolant (e.g., water) flows constantly during operation to cool the substrate 120. The thickness of the lithium layer 110 is typically selected so that most protons react with Li atoms in the layer to produce Be (see Equation 1 above), or, if the protons do not have enough energy to initiate the reaction, are stopped and trapped within the lithium layer several micrometers or more away from the substrate 120. Over time, however, some protons penetrate the lithium layer and deposit on the substrate 120, where they accumulate and form bubbles of hydrogen gas 124, which can form blisters just below the interface of the lithium layer 110 and the substrate 120 and subsequently lead to delamination of a thin layer of the substrate 120. Blistering and delamination are highly undesirable because these processes present a significant obstacle to successful operation of the target. The blisters disrupt contact between the lithium layer 110 and the substrate 120 during operation and inhibit efficient heat removal from the substrate 120, which can result in melting and evaporation of the lithium layer 110, or alloying and diffusion of the molten lithium into the copper, or delamination of the lithium layer 110 in areas near the blisters.These processes result in a reduction in the purity or thickness of layer 110, resulting in a corresponding reduction in neutron output. Ultimately, hydrogen blisters can reduce the efficiency of neutron production by the target and disrupt the workflow of the neutron beam system 10. Existing solutions contribute little to the efficiency and effectiveness of target operation. One solution involves limiting target life by carefully monitoring the reduction in neutron production rate and replacing the target before or at the start of the blistering process. Another solution involves compensating for the reduced neutron production rate by extending the patient's exposure time. The former solution significantly increases operating costs, while the latter solution may not even achieve the desired therapeutic effect due to the reduced amount of boron at the tumor site over the course of extended exposure due to metabolic clearance of the boron-containing drug from the patient's body.

[0024] Thus, the present disclosure provides, among other things, a neutron generating target that advantageously reduces or avoids hydrogen accumulation within the substrate, thus reducing or avoiding blistering and related problems and promoting efficient operation of the neutron beam system 10. In one general aspect, the present disclosure provides a target including: (i) a substrate; (ii) a neutron generating region positioned on the substrate; and (iii) an intermediate layer positioned between the substrate and the neutron generating region. The intermediate layer of the target of the present disclosure is made of a material or mixture of materials that helps prevent or substantially avoid damage, blistering, and delamination of the neutron generating layer (e.g., a lithium layer) from the substrate. In one example, the intermediate layer advantageously sequester or adsorb hydrogen (e.g., protons used for neutron generation) that penetrates the neutron generating region, thereby avoiding any accumulation of hydrogen in the substrate. At the same time, the material of the intermediate layer is highly thermally conductive to facilitate efficient heat transfer from both the neutron generating region and the intermediate layer to the substrate during operation.

[0025] FIG. 3A is a cross-sectional view depicting an exemplary embodiment of a neutron generating target 100. FIGS. 3B and 3C are perspective views of the upstream side 112 and downstream side 114 of the target 100, respectively. Referring to FIG. 3A, the target 100 includes a neutron generating layer 110. Downstream of the proton beam propagating in direction B, the target 100 includes an intermediate layer 302 coupled to and supporting the neutron generating layer 110. The intermediate layer 302 is, in turn, supported by a high thermal conductivity substrate 120, which in some embodiments includes a spiral channel 122 through which a coolant flows to remove heat generated in the target 100 during operation. Several embodiments of the neutron generating region, intermediate layer, and substrate, as well as alternative embodiments of neutron generating targets, are described herein. Various embodiments of methods of fabricating targets and methods of using targets, for example in BNCT, are also described herein.

[0026] Example of Intermediate Layer Embodiments An intermediate layer, such as layer 302 with reference to FIGS. 3A-3C, may include any material or combination of materials configured to achieve a desired purpose, improve the properties, and extend the life of the target 100. As described herein, the material of the intermediate layer 302 does not react with, or has minimal chemical reactivity with, the material of the neutron-producing layer 110, such as lithium. The material of the intermediate layer 302 can be selected so that it does not substantially diffuse into, alloy with, or form a eutectic mixture with the material of the neutron-producing layer 110. Similarly, the material of the intermediate layer can be selected so that it does not excessively diffuse into, or alloy with, the material of the substrate 120. Additionally, the material of the intermediate layer 302 preferably has high thermal conductivity and the ability to sequester, flow, or diffuse hydrogen to prevent blistering of the substrate 120. As used herein, "high thermal conductivity" refers to a thermal conductivity of 300 watts per meter Kelvin (W×m -1 ×K -1 ) or more (for example, 400W x m -1 ×K -1The material of the intermediate layer 302 may also have a low likelihood of radiation activation under proton and neutron irradiation, facilitating the safety of personnel handling target replacement within the system 10.

[0027] The thickness of the intermediate layer 302 depends on the particular application of the target, which can vary as described herein. For example, the thickness of the intermediate layer measured along the axis B of the proton beam can be in the range of about 10 micrometers (μm) to about 5 millimeters (mm), about 10 μm to about 2 mm, about 10 μm to about 1 mm, about 20 μm to about 1 mm, about 50 μm to about 5 mm, about 50 μm to about 1 mm, about 50 μm to about 750 μm, about 50 μm to about 500 μm, about 50 μm to about 250 μm, or about 50 μm to about 200 μm, as referenced in numeral 303 of FIG. 3A and throughout. In some embodiments, the thickness 303 is about 20 μm, about 50 μm, about 100 μm, about 200 μm, about 250 μm, about 400 μm, about 500 μm, about 750 μm, about 1 mm, or about 2 mm. The thickness can be selected to ensure that all protons leaving the neutron-generating layer 110 are slowed below 1 eV and do not reach the substrate 120, and that the total accumulation of hydrogen is below the ability of the intermediate layer 302 to sequester all hydrogen supplied to the target, such that the thermal conductivity of the intermediate layer is sufficient to allow efficient removal of heat from the target 100 during proton irradiation. In some embodiments, the thickness of the intermediate layer can be selected to allow only a portion of the incident protons to be slowed below 1 eV and accumulate within the substrate. In this embodiment, the total proton dose is maintained below the blistering threshold of the substrate material, where the accumulated protons form gaseous hydrogen within the substrate material. In some embodiments, hydrogen sequestration has a limit set by either the ability of the interlayer to react with or be sandwiched between layers. An example of an acceptable limit for cross-referencing is 4.5 wt.% hydrogen in graphite. For the example of a dense graphite piece without a porous structure, this limit can correspond to a graphite layer at least 45 μm thick per ampere-hour of protons deposited on the graphite interlayer over a circular area 100 mm in diameter. Other materials are similarly limited in their ability to sequester hydrogen based on their individual capacities and internal reactions.Porous graphite, with its ability to allow hydrogen to escape through channels and porosity, can accommodate more than 4.5% hydrogen by weight, made possible by its ability to allow hydrogen to constantly and continuously diffuse from the material itself into the pores and be removed via a vacuum pump. Other materials are similarly enhanced by porous structures that allow for the capture and release of hydrogen beyond the containment limit for each material. In some embodiments, the material of the intermediate layer 302 has a high thermal conductivity. In some embodiments, the intermediate layer may be a composite material. One component of the composite will be responsible for providing mechanical stability and thermal conductivity, while the other component may be able to dissolve hydrogen or have a high diffusion constant for hydrogen. In some embodiments, the thermal conductivity of the intermediate layer 302 is approximately equal to or exceeds the thermal conductivity of the material of the substrate 120. For example, the thermal conductivity of the intermediate layer 302 may be 300 watts per meter Kelvin (W×m). -1 ×K -1 )~Approx. 2,500W×m -1 ×K -1 In some examples, the thermal conductivity of the intermediate layer 302 may be in the range of about 400 W×m -1 ×K -1 , about 500W×m -1 ×K -1 , about 750W×m -1 ×K -1 , approx. 1,000W×m -1 ×K -1 , approx. 1,500W×m -1 ×K -1 , approx. 1,700W×m -1 ×K -1 , approx. 2,000W×m -1 ×K -1 , approx. 2,200W×m -1 ×K -1 , or approximately 2,500W x m -1 ×K -1 is.

[0028] In some examples, the intermediate layer 302 includes a metal or a metal compound. Suitable examples of metals useful in the intermediate layer 302 include platinum (Pt), tantalum (Ta), titanium (Ti), aluminum (Al), tin (Sn), zirconium (Zr), hafnium (Hf), vanadium (V), niobium (Nb), holmium (Ho), nickel (Ni), palladium (Pd), zinc (Zn), or a combination thereof. The metal combination in the intermediate layer 302 may include a magnesium-nickel alloy (e.g., MgNi), a magnesium-iron alloy (e.g., MgFe), or a similar alloy. Suitable examples of metal compounds include salts, oxides, silicides, nitrides, and carbides of the aforementioned metals. In some embodiments, the intermediate layer 302 includes (e.g., consists entirely of) a metal compound selected from tantalum nitride (TaN), titanium nitride (TiN), tantalum silicide (TaSi), and tantalum silicon nitride (TaSiN). Other nitrides, such as tungsten nitride (WN), niobium nitride (NbN), molybdenum nitride (MoN), chromium nitride (CrN), vanadium nitride (VN), zirconium nitride (ZrN), and hafnium nitride (HfN), are also possible. Mixed nitrides, such as titanium tungsten nitride (TiWN), can also be used. In some embodiments, the intermediate layer 302 includes pure aluminum (e.g., 99% or 99.5% aluminum by weight). In some embodiments, the intermediate layer 302 includes pure platinum (e.g., 99% or 99.5% platinum by weight). In some embodiments, the intermediate layer 302 comprises pure titanium (e.g., 99% or 99.5% by weight titanium). In some embodiments, the intermediate layer 302 comprises pure tin (Sn) (e.g., 99% or 99.5% by weight tin (Sn)). In some embodiments, the intermediate layer 302 comprises pure titanium nitride (TiN) (e.g., 99% or 99.5% by weight TiN). In some embodiments, the material of the intermediate layer is an alloy of aluminum and platinum (Al / Pt). In some embodiments, the Al / Pt alloy comprises about 30%, about 50%, about 60%, about 70%, about 80%, or about 90% aluminum by weight.In some embodiments, the material of the intermediate layer is an alloy of aluminum and titanium (Al / Ti). In some embodiments, the Al / Ti alloy includes about 30% by weight, about 50% by weight, about 60% by weight, about 70% by weight, about 80% by weight, or about 90% by weight of aluminum. In some embodiments, the material of the intermediate layer is an alloy of platinum and titanium (Pt / Ti). In some embodiments, the Pt / Ti alloy includes about 30% by weight, about 50% by weight, about 60% by weight, about 70% by weight, about 80% by weight, or about 90% by weight of titanium. Without being bound by any particular theory or speculation, it is believed that the metal or metal compound in the intermediate layer 302 may chemically react with the neutron-producing layer 110 and form a metal hydride, thereby sequestering hydrogen (e.g., protons) that penetrate the neutron-producing layer 110 in direction B. In some embodiments, the thermal conductivity of the intermediate layer 302 modified by a hydride reaction is greater than or equal to about 90%, about 80%, or about 75% of the thermal conductivity of the intermediate layer 302 in the absence of any hydride.

[0029] In some embodiments, the intermediate layer 302 comprises a non-metal or its derivative. Examples of such materials include nitrogen (N), carbon (C), germanium (Ge), silicon (Si), silicon oxides (e.g., SiO, SiO), silicon nitrides (e.g., SiN), carbon nitrides (e.g., CN), and other similar silicon-, germanium-, and carbon-based materials. In some embodiments, the intermediate layer 302 comprises pure silicon (e.g., 99% or 99.5% silicon by weight). In some embodiments, the intermediate layer 302 comprises pure germanium (e.g., 99% or 99.5% germanium by weight). In some embodiments, the intermediate layer 302 comprises pure carbon (e.g., 99% or 99.5% carbon by weight). In some embodiments, the intermediate layer 302 comprises pure nitrogen (e.g., 99% or 99.5% nitrogen by weight). In some embodiments, the intermediate layer 302 comprises a nitrogen compound.

[0030] In some embodiments, intermediate layer 302 comprises graphite. Suitable examples of graphite include highly oriented solid, unoriented solid, fibrous graphite, carbon fiber reinforced carbon, porous graphite, carbon nanotubes, and graphene (single sheet planar graphite). In some embodiments, the graphite in intermediate layer 302 is highly oriented solid carbon fiber reinforced carbon having well-oriented fibers, well-oriented filler graphite, well-oriented fiber bundles, well-oriented nanotube bundles, and porous graphite with high thermal conductivity. In some embodiments, intermediate layer 302 comprises pure graphite (e.g., 99% or 99.5% graphite by weight). In some embodiments, the graphite in intermediate layer 302 has high thermal conductivity.

[0031] In some embodiments, the intermediate layer 302 comprises oriented pyrolytic graphite. Figure 3D is a cross-sectional view of an exemplary embodiment of a target 100 including an intermediate layer 302 comprising oriented pyrolytic graphite. In some embodiments, the oriented pyrolytic graphite comprises carbon sheets or fibers that are uniformly oriented (e.g., aligned) and extend in a direction perpendicular to the planar surface of the target (e.g., parallel to the axis of the proton beam incident on the target 100 in direction B, as shown in Figure 3D). For example, the intermediate layer 302 may comprise concentric tubes of graphite material, with the tubes with smaller radii positioned closer to the center of the target 100 and the tubes with larger radii positioned closer to the edges of the target 100. Each tube between the centermost and outermost tubes may be substantially equidistant from the adjacent inner and outer concentric tubes.

[0032] In some embodiments, the oriented pyrolytic graphite is highly oriented. In one example of highly oriented pyrolytic graphite, more than 50%, 75%, 90%, or 99% of the material components (e.g., sheets, fibers, etc.) are substantially equidistant from one another. For example, the variation in distance 304 between any two adjacent carbon sheets 305 can be about 0.1%, about 0.5%, about 1%, about 2%, about 5%, or about 10%. In this example, the components of the highly oriented graphite can be aligned or substantially aligned (parallel to one another), and for multiple substantially aligned components, the variation in alignment can be about 0.1%, about 0.5%, about 1%, about 2%, about 5%, or about 10%. Also, in this example, the multiple aligned or substantially aligned components (e.g., sheets of carbon atoms) of the highly oriented graphite can be parallel or substantially parallel to direction B, which in some examples is the direction in which the proton beam is incident on the target. The substantially parallel component can be within about 1 degree (°), about 2 degrees, about 5 degrees, about 10 degrees, about 15 degrees, or about 30 degrees relative to direction B. In some examples, the aligned or substantially aligned components (e.g., sheets of carbon atoms) of highly oriented graphite can be perpendicular or substantially perpendicular to a vector in the plane of the surface of target 100, shown as direction A in FIG. 3D . The substantially parallel component can be within about 1 degree (°), about 2 degrees, about 5 degrees, about 10 degrees, about 15 degrees, or about 30 degrees relative to the normal of direction A.

[0033] In some embodiments, the oriented pyrolytic graphite is highly oriented. Referring to FIG. 3D, the intermediate layer includes carbon sheets (flat layers of carbon atoms) 305 that are single-atom or nearly single-atom thick. Any two adjacent carbon sheets 305 are positioned at a distance of about 0.1 nm to about 0.5 nm (see numerals 304 in FIG. 3D) and are bonded by van der Waals forces. In one example, about 50%, about 75%, about 90%, about 95%, or about 99% of the carbon sheets 305 in the intermediate layer 302 are substantially equally spaced from one another, aligned, or substantially aligned, and parallel or substantially parallel to the axis of the incident beam in direction B. In some embodiments, the carbon sheets 305 in the intermediate layer 302 are substantially equally spaced from one another (e.g., the variation in the distance 304 between any two adjacent carbon sheets 305 can be about 0.1%, about 0.5%, about 1%, about 2%, about 5%, or about 10%). In some embodiments, the carbon sheets 305 in the intermediate layer 302 are substantially aligned. In some embodiments, the aligned or substantially aligned sheets 305 are substantially parallel to the axis of the incident beam in direction B.

[0034] Without being bound by any theory, it is believed that hydrogen (protons) leaving the neutron-generating layer 110 are sequestered in the oriented graphite intermediate layer 302 by being sandwiched in the spaces 306 between any two adjacent carbon sheets 305 without reacting with graphite, thereby preserving the chemical composition and thermal conductivity of the graphite layer. Without being bound by any theory or speculation, it is also believed that the thermal conductivity of the intermediate layer 302 comprising highly oriented pyrolytic graphite in direction B is about 300 times, about 250 times, about 200 times, about 150 times, or about 100 times greater than the thermal conductivity in direction A (see FIG. 3D ), which is parallel to the surface of the substrate 120 and perpendicular to direction B. In some embodiments, the thermal conductivity of the intermediate layer 302 in direction B is approximately equal to or exceeds the thermal conductivity of the material of the substrate 120. For example, the thermal conductivity of the oriented graphite layer 302 in direction B is 300 W×m -1 ×K-1 or more than 400W×m -1 ×K -1 or more than 500W×m -1 ×K -1 or above 1300W×m -1 ×K -1 or above 1400W×m -1 ×K -1 or about 400W x m -1 ×K -1 ~Approx. 2000W×m -1 ×K -1 At the same time, the thermal conductivity of the oriented graphite layer 302 in direction A is about 5 W×m -1 ×K -1 , about 7W×m -1 ×K -1 , or approximately 10W x m -1 ×K -1 is.

[0035] In some embodiments, intermediate layer 302 comprises porous graphite (e.g., porous graphite with high thermal conductivity). FIG. 3E is a cross-sectional view of an exemplary embodiment of target 100 including intermediate layer 302 comprising porous graphite. Referring to FIG. 3E, graphite layer 302 comprises a plurality of pores 307. In some embodiments, pores 307 have an average, number-average, or volume-average pore size of about 0.1 nm to about 200 nm, about 0.2 nm to about 150 nm, about 1 nm to about 100 nm, about 5 nm to about 75 nm, about 10 nm to about 50 nm, or about 15 nm to about 25 nm. In some embodiments, the density of the porous graphite in intermediate layer 302 is about 1.5 grams per cubic centimeter (g / cm 3 ) ~ approx. 3g / cm 3 , about 1.75g / cm 3 , about 2g / cm 3 , about 2.1g / cm 3 , about 2.2g / cm 3 , 2.25g / cm 3 , about 2.3g / cm 3 , or about 2.5 g / cm 3In some embodiments, the porous graphite of layer 302 can be low, medium, or high porosity. As used herein, the term "porosity" refers to the percentage ratio of void space (total volume of pores) to the total volume of the graphite material. In some embodiments, the intermediate layer comprises a porous graphite material having a porosity of about 0.5 percent (%) to about 40%, about 1% to about 35%, about 5% to about 30%, or about 5% to about 20%. In some embodiments, the porosity of the porous graphite is about 5%, about 8%, about 10%, about 12%, about 13%, about 15%, about 16%, about 18%, or about 20%. In some embodiments, the porous graphite has a low, medium, or high gas permeability. In some embodiments, the average permeability of the porous graphite is about 1×10 -15 Square meters (m 2 ) ~ approx. 6×10 -14 m 2 In some embodiments, the average permeability of the porous graphite is about 1×10 -15 Square meters (m 2 ) ~ approx. 1×10 -11 m 2 Without being bound by any particular theory of conjecture, it is believed that protons entering the intermediate layer 302 downstream of the neutron-producing layer 110 accumulate and form hydrogen gas, which fills the pores of the porous material of layer 302 and diffuses from the target into the vacuum system in directions A and C. The hydrogen may also diffuse toward the lithium layer and react with small amounts of lithium on its surface to form, for example, lithium hydride (LiH). Without being bound by theory, it is believed that reaction with small amounts of lithium in the neutron-producing layer 110 does not substantially reduce neutron production.

[0036] In some embodiments, a suitable combination (e.g., layering) of materials can be used as the intermediate layer 302. For example, the intermediate layer 302 can include multiple layers in the form of sublayers, such as a combination of first and second metal sublayers, a metal first sublayer with a metal compound second sublayer, a metal compound first sublayer with a metal compound second sublayer, a metal or metal compound first sublayer with a non-metallic second sublayer, a non-metal or non-metal compound first sublayer with a non-metal or non-metal compound second sublayer, or others described herein. FIG. 3F is a cross-sectional view of an exemplary embodiment of a target 100 including an intermediate layer 302 comprising a combination of materials. Referring to FIG. 3F, the intermediate layer 302 includes a first sublayer 308 adjacent to and supported by the substrate 120 and a second sublayer 309 positioned between the first sublayer 308 and the neutron-generating layer 110. The first sublayer 308 and the second sublayer 309 can be similar or dissimilar materials bonded to each other by covalent, ionic, metallic, electrostatic, or van der Waals bonds and interactions. For example, the first sublayer 308 can contain a metal or metal compound, such as platinum (Pt), titanium (Ti), tantalum (Ta), tantalum nitride (TaN), or titanium nitride (TiN), or a combination thereof, and the second sublayer 309 can contain a non-metal compound, such as silicon, germanium, or carbon, or a combination thereof. In another example, the first sublayer 308 can contain a non-metal, and the second sublayer 309 can contain a metal or metal compound. Suitable examples of intermediate layer 302 containing a combination of materials include a titanium and silicon sublayer, a titanium and graphite sublayer, a titanium and germanium sublayer, a platinum and silicon sublayer, a platinum and graphite sublayer, and a platinum and germanium sublayer. The ratio of the thickness of first sublayer 308 (see numeral 311 in FIG. 3F) to the thickness of second sublayer 309 (see numeral 310 in FIG. 3F) can be in the range of about 1 / 100 to about 100 / 1 (e.g., about 1 / 20, about 1 / 10, about 1 / 2, about 1 / 1, about 2 / 1, about 10 / 1, or about 20 / 1).

[0037] In some embodiments, the target 100 may include a layer that facilitates attachment of the intermediate layer 302 to the underlying substrate 120. FIG. 4A is a cross-sectional view of an exemplary embodiment of the target 100 including a sub-intermediate layer 312 positioned between the substrate 120 and the intermediate layer 302. For ease of explanation, this sub-intermediate layer 312 is referred to herein as a braze layer, although the layer 312 can function to enable and / or facilitate attachment of the layer 302 to the substrate 120 through the materials and / or attributes of the layer 312 described herein without being such a braze layer. Furthermore, although permitted to be implemented, the use of the term “brazing” herein does not require a particular manufacturing method for the brazing layer (such as flowing liquid metal into the gap between the intermediate layer and the substrate). Furthermore, although permitted to be present, the use of the term “brazing” herein does not require the presence of materials (such as copper and zinc) in the brazing layer.

[0038] Without being bound by theory, it is believed that the braze layer can be a metal or an alloy of several metals that bonds the substrate with the material of the intermediate layer 302. In some examples, the braze layer includes a mixture of copper and an additive material, such as indium, gallium, or magnesium. The additive material can be any material that has a favorable eutectic temperature alloy with copper (e.g., a eutectic temperature of approximately 1000°C or less, 950°C or less, 900°C or less, or 850°C or less). In some examples, the additive material is a material that has a favorable eutectic temperature alloy with copper when the alloy includes 50 atomic percent or less (e.g., 30 atomic percent or less, 20 atomic percent or less, 10 atomic percent or less) of the additive material relative to the amount of copper. Such an alloy can include 50 atomic percent or more (e.g., 70 atomic percent or more, 80 atomic percent or more, 90 atomic percent or more) of copper relative to the amount of the additive material. In some examples, the mixture includes titanium hydride combined with copper and the additive material.

[0039] An exemplary material included in the braze layer can include a copper titanium alloy, which can further include one or more other elements, such as metals including, but not limited to, gallium (e.g., Cu-Ga-Ti alloy), indium (e.g., Cu-In-Ti alloy), or magnesium (e.g., Cu-Mg-Ti alloy). In some examples, the material included in the braze layer includes a copper titanium hydride alloy, which includes one or more other elements, such as metals including, but not limited to, gallium (e.g., Cu-Ga-TiH2 alloy), indium (e.g., Cu-In-TiH2 alloy), or magnesium (e.g., Cu-Mg-TiH2 alloy).

[0040] In some embodiments, the brazing alloy for forming the brazing layer 312 comprises a mixture of copper particles, silver particles, and titanium or titanium hydride particles. At the eutectic melting temperature, these materials spontaneously alloy together to form an alloy with a lower melting point than either of the original materials. An example of a material for forming the brazing layer is the brazing alloy TICUSIL® available from Morgan Brazing Alloys. In some embodiments, the brazing alloy for forming the brazing layer 312 comprises a suspension of alloy particulates and granules of titanium (Ti), copper (Cu), and silver (Ag) in a hydrogel material as a continuous phase.

[0041] To form the braze layer 312, the substrate 120 can be prepared by cleaning or etching the surface 121 of the substrate 120 using any suitable cleaning agent or etching technique. For example, cleaning agents such as isopropanol, ethanol, methanol, acetone, or other solvents or detergents and water can be used for cleaning. Also, for example, etching can be performed by treating the surface 121 with an acid such as acetic acid, pyruvic acid, citric acid, oxalic acid, hydrochloric acid, nitric acid, phosphoric acid, or sulfuric acid, or by dry etching or plasma etching techniques. During dry etching, the surface 121 is cleaned by physical impact or chemical reaction between etching species (such as charged ions of argon, hydrogen, oxygen, or fluorine gas, or free radicals of these gases generated in a plasma) and impurities on the surface 121 of the substrate 120. Without being bound by any theory, it is believed that the plasma-activated atoms, radicals, and ions act like a sandblaster, breaking down organic and inorganic contaminants to form water (HO), carbon monoxide (CO), carbon dioxide (CO), and other volatile products that are easily removed from the surface. To form the braze layer 312, a braze alloy may be applied to the clean surface 121. In this example, a continuous phase of hydrogel is used for convenient and uniform application of the braze alloy to the surface 121. Following this, the braze alloy mixture applied to the surface 121 is contacted with the intermediate layer 302, and the intermediate target 100 (including the substrate 120, the intermediate layer 302 thereon, and the braze alloy hydrogel therebetween) is heated to a temperature of about 800°C to about 1,200°C. In some embodiments, the applied braze alloy mixture is heated to a temperature of about 900°C or about 1,000°C. During the heating step, the hydrogel phase decomposes and evaporates from the surface while the particles of titanium (Ti) or titanium hydride (TiH4), copper (Cu), and silver (Ag) alloy melt and bond with the material of the substrate 120 and the material of the intermediate layer 302.In one example, if the substrate material is copper and the interlayer 302 material is graphite, titanium hydride in the braze alloy decomposes and evolves hydrogen to reduce oxides on the surfaces to be joined, and the metal of the braze alloy (e.g., titanium, silver, and / or copper) melts and diffuses into the substrate 120, forming a metallurgical bond and simultaneously covalently bonding with the graphite of the interlayer 302 by forming titanium carbide (TiC). Thus, the braze layer 312 formed by this process provides a strong, mechanically robust connection between the substrate 120 and the interlayer 302. In another example, the braze layer 312 can be formed by soldering the substrate 120 and the interlayer 302 using a solder including an alloy of tin, lead, zinc, indium, and / or silver. In some embodiments, the thickness of the braze layer (the distance between the surface 121 of the substrate and the surface 318 of the braze layer, see numeral 313 in FIG. 4A) is from about 10 nm to about 500 μm, from about 100 nm to about 250 μm, from about 200 nm to about 200 μm, from about 500 nm to about 200 μm, from about 1 μm to about 150 μm, from about 1 μm to about 100 μm, or from about 10 μm to about 100 μm.

[0042] In some examples, the neutron-generating layer can extend beyond the edge of the intermediate layer to contact the surface of the substrate. Contacting a portion of the neutron-generating layer with the substrate surface can be advantageous; for example, if the intermediate layer is electrically insulating, electrical contact between the electrically conductive neutron-generating layer and the substrate can help dissipate charge that would otherwise accumulate on the neutron-generating layer and / or be dissipated by electrical arcing from the layer to the substrate.

[0043] An exemplary target configured in this manner is shown in Figure 6A, which shows a target 600 including an intermediate layer 602 that does not extend to the edge of the surface 121 of the substrate 120, but leaves a portion 621 of this surface exposed. A neutron-producing layer 610 extends beyond the edge of the intermediate layer 602 and contacts the exposed portion 621. The compositions of the intermediate layer 602 and the neutron-producing layer 610, respectively, can be the same as those described above.

[0044] The width W of exposed portion 621, which is the distance between the edge of intermediate layer 602 and the edge of substrate 120, can vary. In some examples, W is 1 cm or less (e.g., 5 mm or less, 1 mm or less).

[0045] 6A depicts the neutron-producing layer 610 extending evenly over the opposing edges of the intermediate layer 602, implementations are not so limited. More generally, the neutron-producing layer 610 can extend beyond the edges of the intermediate layer 602 and can contact the surface 121 of the substrate 120 continuously around the entire periphery of the intermediate layer 602 or simply at one or more discrete locations.

[0046] Additionally, in some examples, the neutron-producing layer can extend down the side of the substrate 120 to provide contact with the substrate material at an edge surface (e.g., alternatively, the top surface) of the substrate. An example of such a configuration is shown in FIG. 6B, where the target 601 includes an intermediate layer 604 that extends to the edge of the surface 121. The neutron-producing layer 612 extends down the edge of the substrate 120 beyond the edge of the intermediate layer 604 and contacts the edge surface 622 of the substrate 120.

[0047] If the neutron generating layer extends beyond the edge of the intermediate layer for charge dissipation purposes, the amount of surface contact between the neutron generating layer material and the surface of the substrate should be sufficient to provide an amount of electrical contact between the layer and the substrate to adequately dissipate charge during operation.

[0048] In examples where the intermediate layer 602 or 604 is comprised of two or more sublayers, the sublayers can extend different amounts above the top surface 121 of the substrate 120. For example, an upper sublayer can extend over only a portion of the sublayer below it, leaving a portion (e.g., an edge) of the lower sublayer exposed. The exposed portion of the lower sublayer can contact the neutron-generating layer. FIG. 6C shows an example of such a target 700, including an intermediate layer 702 between a neutron-generating layer 710 and a substrate 720. The intermediate layer 702 is comprised of a first sublayer 708 and a second sublayer 709 supported by the first sublayer. The first sublayer 708 extends above the surface 121 to the edge of the substrate 120. The second sublayer 709 extends over a central portion of the first sublayer but does not extend to the edge of the substrate 120, leaving a portion of the surface of the first sublayer exposed and in contact with the neutron generating layer 710.

[0049] In examples where the material forming the first sublayer is conductive but the material forming the second sublayer is not, contact between the neutron generating layer 710 and the first sublayer 708 at the edge of the target can facilitate charge dissipation from the neutron generating layer, as discussed above.

[0050] In one particular example, the first sub-layer is formed from graphite and the second sub-layer is formed from an electrically insulating nitride, such as TaN or other nitrides listed above.

[0051] In some examples, the first sublayer is formed from graphite and the second sublayer is formed from an electrically insulating form of carbon, such as diamond or diamond-like carbon (e.g., a form of carbon with a high degree of sp3 bonding).

[0052] 6D , in another example, a target 701 includes a multi-layer intermediate layer 704 between the substrate 120 and the neutron-generating layer 110. The intermediate layer is composed of a first sublayer 718 disposed on the surface 121 of the substrate and a second sublayer 719 disposed on top of the first sublayer. The first sublayer 718 does not extend to the edge of the substrate 120, leaving a portion of the surface 121 exposed at the edge of the target. The second sublayer 719 covers the top surface of the first sublayer and the exposed portion of the surface 121.

[0053] In examples where the first sublayer 718 is composed of an electrically insulating material and the second sublayer 719 is composed of a conductive material, connection of the second sublayer to a surface of the substrate exposed at the edge can facilitate charge dissipation from the neutron generating layer 110 by providing a conductive path to the substrate.

[0054] In one particular example, the first sub-layer is comprised of a nitride material (eg, TaN or other nitrides mentioned above) and the second sub-layer is comprised of graphite.

[0055] In some examples, the first sub-layer is comprised of an electrically insulating form of carbon, such as diamond or diamond-like carbon, and the second sub-layer is comprised of graphite.

[0056] Example of an embodiment of the neutron generating region 3A-3F, 4A, and 6A-6D provide cross-sectional views of various embodiments of a target 100 including a neutron-producing layer 110 or region 610. In some embodiments, the neutron-producing layer includes lithium. For example, the neutron-producing layer 110 includes about 75%, about 85%, about 90%, about 95%, or about 99% lithium by weight. In some embodiments, the neutron-producing layer 110 includes lithium compounds, including lithium oxide (LiO), lithium hydroxide (LiOH), lithium nitride (LiN), lithium carbonate (LiCO), and lithium fluoride (LiF). The lithium in this layer is Li 6 and Li 7Naturally occurring lithium can consist of two stable isotopes of Li. 7 The amount of isotope can range from about 90% to about 99% by weight, or from about 92% to about 98% by weight. In some embodiments, the lithium in layer 110 is such that the lithium material is about 99.9% by weight or about 100% by weight Li 7 Contains Li 7 is enriched, and Li 6 The lithium in layer 110 is also depleted by Li 3 , Li 4 , Li 8 , Li 11 , or Li 12 Other isotopes of lithium such as Li 6 and / or Li 7 It may contain any combination of isotopes.

[0057] In some embodiments, the neutron-generating layer 110 may be configured as a planar neutron-generating layer coupled to the surface 123 of the intermediate layer 302. A proton beam propagating in direction B (e.g., from the tandem accelerator 16 along the HEBL 18 as shown in FIG. 1A) interacts with the layer 110 to generate neutrons that then pass through the intermediate layer 302, the substrate 120, and exit the downstream side 114 of the target 100. The thickness of the neutron-generating layer 110 (e.g., the distance between the outer surface 123 of the intermediate layer 302 and the outer surface 316 of the neutron-generating layer 110; see numeral 314 in FIGS. 3A-4A ) may be selected depending on the energy of the protons propagating in direction B. Table 1 illustrates the range (sometimes referred to as the stopping range) of the average incident proton particle in naturally abundant lithium (approximately 92% lithium 7) for several proton energies. The right column lists the variable "threshold depth," which is the average proton 7 Li(p,n) 7This represents the distance a proton must travel within a material before slowing down to the threshold energy for the Be reaction (approximately 1.88 MeV). If a proton slows down beyond this threshold energy, it can no longer produce neutrons. For example, for a proton energy of 2.50 megaelectronvolts (MeV), the high-energy proton enters the lithium material and then travels approximately 90 micrometers through the lithium before slowing down to the threshold energy. In this example, if the lithium thickness is less than 90 micrometers (μm), the neutron yield decreases and the lithium material is not utilized most efficiently. It is substantially desirable to have a lithium layer thick enough for a neutron production target, but not so thick that the reduction in proton energy below the threshold dissipates excess heat in the lithium or produces undesirable gamma radiation (e.g., 200 μm for a 2.5 MeV proton energy). [Table 1]

[0058] In some embodiments, the thickness of the neutron-generating layer 110 (e.g., the distance from the surface 123 of the intermediate layer 302 and the outer surface of the neutron-generating layer 110, see numeral 314 in FIGS. 3A-4B ) is about 15 μm to about 180 μm, about 20 μm to about 150 μm, about 40 μm to about 120 μm, about 80 μm to about 120 μm, or about 90 μm to about 100 μm. In some embodiments, the proton energy is about 2 MeV to about 3 MeV, or about 2.25 MeV to about 2.75 MeV. In some embodiments, the proton energy is about 2.5 MeV, and the thickness of the lithium layer on the substrate surface is about 90 μm or about 100 μm.

[0059] In some embodiments, the neutron-producing layer 110 of FIGS. 3A-4A can be added to the intermediate target 100, which already includes the substrate 120 and intermediate layer 302. To add the neutron-producing layer 110 on the intermediate layer 302, the surface 123 of the intermediate layer 302 can be cleaned, for example, by etching the surface, as described above for etching and cleaning the surface 121 of the substrate 120. In one example, if the neutron-producing layer 110 includes lithium, the lithium can be deposited on the surface 123 of the intermediate layer 302 to a desired thickness using conventional evaporation techniques in a vacuum chamber. In another example, the lithium can be applied to the cleaned surface 123 by cold plasma spraying, which can be performed in a glove box or otherwise in an airless atmosphere, such as an inert gas atmosphere (e.g., nitrogen or argon). Strike plasma spraying can be performed at atmospheric pressure or under vacuum. In yet another example, a thin film of lithium foil can be applied to the clean surface 123 of the intermediate layer 302, followed by applying a mechanical force to the foil to press it into the intermediate layer 302. If the intermediate layer 302 comprises graphite, the lithium diffuses into the graphite layer, for example, to a depth of about 1 μm to about 20 μm, thereby forming a sufficient bond between the neutron-generating layer 110 and the intermediate layer 302. The mechanical force can be applied, for example, using a hydraulic press or similar machine; a skilled mechanical engineer would be able to select and implement an appropriate device. In some embodiments, the mechanical force is about 1 megapascal (MPa) to about 3 MPa. Suitable examples of processes for adding the neutron-generating layer 110 to the intermediate layer 302 are described, for example, in U.S. Patent Application No. 63 / 343,924, which is incorporated herein by reference in its entirety.

[0060] In some embodiments, the target 100 includes an adhesion layer 402 positioned between the intermediate layer 302 and the neutron-producing layer 110. Figure 4B is a cross-sectional view of an exemplary embodiment of the target 100 including the adhesion layer 402. The example target 100 of Figure 4B also includes an optional braze layer 312 and a substrate 120, as described herein.

[0061] Without being bound by any particular theory of conjecture, it is believed that the adhesion layer 402 may be a metal or an alloy of several metals that bonds the intermediate layer 302 to the neutron-generating layer 110. Suitable examples of materials for the adhesion layer include tantalum (Ta), titanium (Ti), zirconium (Zr), hafnium (Hf), vanadium (V), niobium (Nb), tantalum (Ta), holmium (Ho), nickel (Ni), palladium (Pd), platinum (Pt), zinc (Zn), silver (Ag), aluminum (Al), gold (Au), bismuth (Bi), silicon (Si), germanium (Ge), or mixtures or alloys thereof, carbides thereof, silicides thereof, or nitrides thereof. Exemplary silicides include tungsten silicide (WSi) (e.g., WSi2), platinum silicide (PtSi), and titanium silicide (TiSi) (e.g., TiSi2). Examples of metal mixtures that form the adhesion layer include magnesium-nickel alloys (e.g., MgNi), magnesium-iron alloys (e.g., MgFe), or similar alloys. Other examples of adhesion layer materials include lithium fluoride (LiF), silicon dioxide (SiO), iron oxide (FeO), and iron fluoride (FeF). In some cases, the adhesion layer includes titanium (Ti) and titanium carbide (TiC). Further examples of adhesion layer materials include diamond (e.g., chemical vapor deposition (CVD) diamond, nanodiamond, polycrystalline diamond) and diamond-like carbon. Additional examples of adhesion layer materials include metal nitrides with any ratio of nitrogen atoms to metal atoms. For example, an adhesion layer containing tantalum and nitrogen can include compounds of TaN, TaN, TaN, TaN, TaN, TaN, TaN, TaN, TaN, or any combination thereof.Further exemplary materials for the adhesion layer include titanium nitride (TiN), tantalum nitride (TaN), titanium tungsten nitride (TiWN), CrN, GaN, aluminum nitride (AlN), indium nitride (InN), boron nitride (BN) (e.g., hexagonal BN, cubic BN, amorphous BN), silicon nitride (SiN) (e.g., Si3N4), GeN (e.g., Ge3N4), zinc nitride (ZnN) (e.g., Zn3N2), lithium nitride (LiN), and the like. LiN) (e.g., Li3N), sodium nitride (NaN) (e.g., NaN3), potassium nitride (KN) (e.g., KN3), RbN (e.g., RbN3), cesium nitride (CsN) (e.g., CsN3), iron nitride (FeN) (e.g., Fe2N, Fe3N4, Fe4N, Fe7N3, Fe16N2), molybdenum nitride (MoN), tungsten nitride (WN), vanadium nitride (VN) (e.g., V2N), zirconium nitride (ZrN), ScN, YN, lanthanum nitride (LaN), cerium nitride (CeN), praseodymium nitride (PrN), neodymium nitride (NdN), samarium nitride (SmN), europium nitride (EuN), gadolinium nitride (GdN), terbium nitride (TbN), dysprosium nitride (DyN), holmium nitride (HoN), erbium nitride (ErN), thulium nitride (TmN), ytterbium nitride (YbN), lutetium nitride (LuN), nitride Examples of nitride compounds include beryllium (BeN) (e.g., BeN), magnesium nitride (MgN) (e.g., MgN), calcium nitride (CaN) (e.g., CaN), strontium nitride (SrN) (e.g., SrN), barium nitride (BaN) (e.g., BaN), indium gallium nitride (InGaN), lithium sodium nitride (LiNaN), and titanium molybdenum tantalum nitride (TiMoTaN).

[0062] Without being bound by theory, the metal oxide or metal fluoride material of the adhesion layer, when in contact with the lithium in the neutron-generating region, decomposes to release free metal that alloys with and diffuses into the lithium, creating good adhesion between the neutron-generating region and the intermediate layer 302. Exemplary materials included in the adhesion layer may include lithium oxide (LiO), lithium fluoride (LiF), lithium carbonate (LiCO), lithium hydroxide (LiOH), lithium sulfate (LiSO), lithium sulfide (LiS), lithium phosphide (LiP), lithium chloride (LiCl), and halogen salts of lithium (e.g., LiBr, LiI).

[0063] In some examples, the adhesion layer is deposited using plasma sputtering. Sputtering and other manufacturing processes can cause activation of nitrogen atoms that bond to the second and third materials. For example, the activated nitrogen atoms can bond to the graphite in the interlayer and to the lithium in the neutron-generating region. The resulting structure can then have an adhesion layer, which is a thin nitrogen (or nitrogen-based) layer positioned between the interlayer and the lithium and facilitating bonding between the interlayer and the lithium.

[0064] If the intermediate layer 302 includes graphite, a thin layer of titanium (Ti) metal can be deposited on the cleaned surface 123 of the intermediate layer 302 and then heated to a temperature of, for example, about 500°C to about 1,000°C. Without being bound by any particular theory, it is believed that the titanium (Ti) metal chemically reacts with carbon atoms of the graphite material at or near the surface 123 of the intermediate layer 302 to form titanium carbide (TiC), thereby covalently bonding the adhesion layer 402 to the intermediate layer 302. If the neutron-producing layer 110 includes lithium, a thin lithium foil can be applied over the titanium and titanium carbide layer 402, followed by applying a mechanical force to the lithium foil as described above. In this process, the titanium diffuses into and alloys with the lithium, for example, to a depth of about 10 nm to about 2 μm, thereby forming a sufficient bond between the neutron-producing layer 110 and the adhesion layer 402.

[0065] In some embodiments, the thickness of the adhesive layer (the distance between surface 123 of intermediate layer 302 and surface 408 of the adhesive layer, see, for example, numeral 406 in FIG. 4B ) is from about 10 nm to about 20 μm, from about 10 nm to about 10 μm, from about 50 nm to about 10 μm, from about 100 nm to about 1 μm, from about 100 nm to about 2 μm, from about 1 μm to about 2 μm, or from about 1 μm to about 10 μm.

[0066] In some embodiments, the target 100 includes a passivation region 410 positioned above the neutron-producing layer 110. Figure 4C is a cross-sectional view of an exemplary embodiment of the target 100 including the passivation region 410. Referring to Figure 4C, the example target 100 having the passivation region 410 also includes the neutron-producing layer 110 downstream of the passivation region 410, an intermediate layer 302 coupled to and supporting the neutron-producing layer 110, and a substrate 120 downstream of and supporting the intermediate layer 302. Examples of materials from which the passivation region 410 can be made include one or more of lithium fluoride (LiF), lithium sulfide (LiS), lithium carbonate (LiCO), or Li, magnesium fluoride (MgF), carbon (C), diamond-like carbon, (ultra)nanocrystalline diamond, or any other compound that is thermodynamically stable with a polymer such as parylene, polypropylene, or polyethylene. Other examples may include one or more of aluminum, silver, gold, titanium, stainless steel, aluminum silicide (AlSi), molybdenum, tungsten, tungsten carbide, tantalum, platinum, or other contamination barrier materials. Other materials known to inhibit the diffusion of lithium can be used to create the passivation region 410 located above the neutron-generating layer 110. Lithium-containing materials such as lithium nitride (LiN), lithium oxide (LiO), and lithium hydroxide (LiOH) do not exhibit substantially low lithium diffusion coefficients and are not used as materials for the passivation region 410. In some embodiments, the passivation region 410 has a lithium diffusion coefficient of 1×10 -13 Square centimeters per second (cm2 The region 410 has a diffusion coefficient of the material of the neutron-producing layer 110 (e.g., lithium) of no greater than 1 / s. The region 410 can also be configured to seal against the intrusion and diffusion of externally supplied substances (e.g., substances from the ambient environment, such as any one or combination of air, moisture, oxygen, nitrogen, carbon dioxide, hydrogen, or other gases) into or through the region 410 in an upstream-to-downstream direction. If such substances permeate into the target 100, they could potentially contaminate or react (e.g., oxidize) the neutron-producing material (e.g., lithium) in the layer 110. The ambient barrier properties of the passivation region 410 have a gas permeability ((cubic centimeters (cc) × millimeters (mm)) / (square meters (m) at 25 degrees Celsius)) of no greater than 100, preferably no greater than 3.1, for oxygen, nitrogen, and carbon dioxide. 2 ) × days × atmospheres (atm). In some exemplary embodiments, the thickness of the passivation region 410 (e.g., the distance between the surface 316 of the neutron generation region and the surface 414 of the passivation region 410, see, e.g., numeral 412 in FIG. 4C ) does not exceed 3 micrometers to minimize energy reduction of incoming protons in BNCT applications, although the region 410 is not so limited. In some embodiments, the thickness of the passivation region is from about 1 μm to about 10 μm, or from about 10 μm to about 100 μm. Certain embodiments of passivation materials, as well as their thicknesses and other properties, are described in U.S. Patent Application Publication No. 2023 / 0009459 A1, entitled “Materials and Configurations for Protection of Objective Materials,” which is incorporated herein by reference in its entirety for all purposes.

[0067] Example Target Substrate Embodiments 3A-4B and 6A-6D, the substrate 120 can be configured for heat removal to dissipate the high energy levels of the incident proton beam (which may be incident in direction B) and the resulting neutron beam that remains at the downstream side 114 of the target. As explained above, the thickness of the lithium layer 110 is determined so that the proton energy is sufficient to convert the Li 7 (p,n)Be 7 The protons are configured to be allowed to exit layer 110 relatively quickly or immediately after falling below a reaction threshold (e.g., 1.88 MeV for the lithium 7 isotope). This avoids further energy dissipation in layer 110, which is inefficient and would lead to heating of layer 110 without the production of neutrons. Protons at about the threshold energy level penetrate to intermediate layer 302 and dissipate their remaining energy in high thermal conductivity intermediate layer 302 and, therefore, in substrate 120. Substrate 120 can be made of a material with high thermal conductivity (e.g., a material that is a good conductor of heat), or a combination of such materials. In some embodiments, the thermal conductivity of substrate 120 is 300 W×m -1 ×K -1 or more than 400W x m -1 ×K -1 or more than 500W×m -1 ×K -1 or about 400W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1In some embodiments, the substrate material is copper (Cu). Other suitable examples of substrate materials include copper alloys, gold, silver, beryllium, beryllium oxide, alloys of any of the foregoing, chemical vapor deposition (CVD) diamond, or copper-diamond powder composites. Examples of high thermal conductivity alloys for the substrate 120 include Tumbaga (an alloy of gold and copper), Sterling (an alloy of copper and silver), and Electrum (an alloy of gold and silver). In some embodiments, the substrate 120 is made substantially of copper. For example, the substrate 120 contains about 90 weight percent (wt%), about 95 wt%, about 99 wt%, or about 100 wt% copper. In some embodiments, the substrate 120 is made from a material containing about 95 wt% to about 99 wt% copper. In some embodiments, the high thermal conductivity substrate 120 is made substantially of a copper-diamond powder composite. In some examples, the substrate includes graphite; for example, the substrate 120 can be made substantially of graphite.

[0068] Protons exiting the lithium layer and depositing in the intermediate layer 302 generate a significant heat load on the substrate. For example, at an energy level of 2.5 MeV, the exiting protons generate a heat load of about 20 kW to about 25 kW. Therefore, the substrate is actively cooled by a constant coolant flow rate. For example, the substrate 120 may include a spiral channel 122, as depicted in FIG. 3B, or channels of any other dimensions and configurations as desired. Suitable examples of coolants include water, ethanol, methanol, ethylene glycol, propylene glycol, or any mixture thereof. Cooling the substrate ensures that the substrate temperature during proton irradiation does not exceed the melting point of lithium (e.g., about 180°C to about 182°C). In some embodiments, the substrate temperature during operation does not exceed 100°C. In one embodiment, the target is a round (e.g., circular) target that is a plate having a width (e.g., a diameter) of about 4 inches to about 8 inches, or about 6 inches. The thickness of the target substrate 120 can be about 6 mm to about 12 mm, about 8 mm to about 12 mm, or about 8 mm. In some embodiments, the substrate is about 50 times (or five orders of magnitude), about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the neutron-generating layer 110 of the target 100. In general, the substrate 120 can be of any known shape and can be fabricated to fit into a target assembly (e.g., the target assembly 200 shown in FIG. 1B ). Suitable examples of shapes for the substrate 120 include a circle, a triangle, a rectangle, a square, a diamond, a trapezoid, a pentagon, a hexagon, or any combination of the foregoing. In one example, the shape of the substrate 120 is the same as the shape of the target 100 of the present disclosure. In this example, the substrate 120, the neutron-generating layer 110, the intermediate layer 302, and any of the optional layers described herein have substantially the same shape (e.g., a circle, a square, a rectangle, a pentagon, or a hexagon). In some embodiments, target 100 of the present disclosure (including layers 120, 302, and 110) has a circular shape. The widths (e.g., diameters) (measured perpendicular to the incident beam B) of each of the target components (120, 302, and 110, and optional layers) within target 100 can be the same or different.For example, the width of the target 100 and any of the components 120, 302, 110, etc., can be selected from 5 centimeters (cm) or more, 7 cm or more, 10 cm or more, 15 cm or more, 20 cm or more, about 5 cm to about 20 cm, about 5 cm to about 15 cm, and about 5 cm to about 10 cm. In another example, the target components, such as the substrate 120, the neutron-producing layer 110, the intermediate layer 302, and any of the optional layers, such as the braze layer and adhesive layer, can have different shapes. In this example, the substrate 120 can be a circle, the layer 302 can be a circle of substantially the same diameter as the substrate 120, and the neutron-producing layer can have a square or diamond shape.

[0069] In some embodiments, the substrate 120 of the target 100 of the present disclosure comprises the same material or mixture of materials as described herein for the intermediate layer 302. For example, the substrate 120 may contain graphite, such as oriented pyrolytic graphite (e.g., highly oriented pyrolytic graphite). FIG. 4D is a cross-sectional view of an exemplary embodiment of a target 100 including a substrate 120 prepared from a thermally conductive (e.g., high thermal conductivity) material described herein for the intermediate layer 302. Referring to FIG. 4D, the example target 100 also includes a neutron-generating layer 110 upstream of the substrate 120 and coupled to and supported by the substrate 120. FIG. 4E is a cross-sectional view of an exemplary embodiment of a target 100 including a substrate 120 prepared from highly oriented pyrolytic graphite. Referring to FIG. 4E, the target 100 also includes an adhesion layer 402 positioned between the substrate 120 and the neutron-generating layer 110. The adhesive layer may be any of the layers 402 discussed herein above with reference to Figure 4B.

[0070] How to use In certain examples, the present disclosure provides methods of using a lithium-containing target (e.g., target 100) of the present disclosure in BNCT to treat cancer. More specifically, the target may be included in a neutron beam system, such as system 10 shown schematically in FIGS. 1A and 1B. The target may be included in target assembly system 200, for example, to generate a neutron beam from a proton beam. In some embodiments, the present disclosure provides methods of treating cancer, for example, in a subject in need thereof. Prior to treatment, the subject may be diagnosed with cancer by a treating physician. The physician may use any diagnostic tool commonly known in the medical industry to diagnose cancer, such as a biopsy. Suitable examples of cancer include liver cancer (hepatocellular carcinoma, intrahepatic cholangiocarcinoma, hepatoblastoma, or hepatic adenoma), oral cancer, colon cancer, brain tumors (e.g., glioblastoma, meningioma, or medulloblastoma), head and neck cancer, lung cancer, breast cancer, gastric cancer, widespread squamous cell carcinoma, laryngeal cancer, melanoma, sarcoma, and extramammary Paget's disease. Cancer includes recurrent cancer, childhood cancer, and metastatic cancer.

[0071] An example of a method 500 for treating cancer in a patient is provided with reference to Figure 5. Referring to Figure 5, the method 500 for treating cancer includes administering to a subject a therapeutically effective amount of B 10 The method includes step 502 of administering a compound containing a selected B 10 The compounds contained therein have low systemic toxicity, rapid clearance from blood and normal tissues, high tumor uptake, and low normal tissue uptake. 10 B in tumor tissue after compound administration 10 and the amount of B in normal tissues 10 In some embodiments, the ratio of the amount of B to the amount of B is about 2:1 to about 5:1, or about 3:1 to about 4:1. 10 The therapeutic dose of the compound is about 1 to 100 mg B per kilogram (kg) of the subject's body weight. 10 For example, B 10 The therapeutic dose of the compound contained is approximately 5 mg B 10 / kg~about 100mgB 10 / kg, approximately 5 mgB 10 / kg~about 80mgB 10 / kg, or approximately 5 mgB 10 / kg~about 40mgB 10 / kg. B 10 The compound can be administered to a subject in a pharmaceutical composition or dosage form together with one or more pharmaceutically acceptable excipients. Suitable examples of such excipients include alumina, phosphate, colloidal silica, polyacrylate, polyethylene glycol-based polymers, and cellulose-based materials. 10 The compound can be administered to a subject by any suitable route of administration. For example, the compound can be administered orally, intradermally, or by intramuscular or intraperitoneal routes. 10 Examples of formulations and dosage forms for administering the compounds include tablets, capsules, and injectable solutions. 10 Suitable examples of compounds include boronated derivatives of natural and unnatural amino acids, polyamines, peptides, proteins, antibodies, nucleosides, sugars, porphyrins, and liposomes and nanoparticles. 10 The containing compound is a boronated derivative of an amino acid such as aspartic acid, tyrosine, cysteine, methionine, or serine. In some embodiments, B 10 The containing compound is boronophenylalanine, sodium borocaptate, or 1-amino-3-boronocyclopentanecarboxylic acid.

[0072] Referring to FIG. 5, the method 500 also includes: 10 The method also includes step 504 of waiting a sufficient amount of time for the contained compound to accumulate in the cancer tissue. The amount of waiting time can range from about 10 seconds (seconds) to about 2 hours (hours), from about 30 seconds to about 1 hour, or from about 1 minute to about 30 minutes (minutes). In one example, B 10 The compound contained about 20 to about 50 micrograms (μg) of B per gram (g) of tumor. 10 It can accumulate in cancer tissue at levels of B 10 Sufficient accumulation of B can be determined by any suitable technique, for example, by the treating physician. 10The level of B can be determined using a biopsy and elemental analysis of tumor tissue. 10 The level of can be determined using imaging (eg, fluorescence imaging, PET, X-ray, CT, or MRI).

[0073] Method 500 also includes step 506 of contacting an article of the present disclosure (e.g., neutron generating target 100 as described above) with a proton beam of appropriate energy (e.g., direction B) to generate a neutron beam. In some embodiments, the proton energy is about 2 MeV to about 3 MeV, about 2.25 MeV to about 2.75 MeV, or about 2.5 MeV. The method also includes step 508 of directing the neutron beam toward the cancerous tissue. Steps 506 and 508 can be performed as described above with reference to FIGS. 1A and 1B. In some embodiments, during operation of the target (e.g., in step 506), the target is maintained at its operating temperature of about 130°C to about 150°C, or about 140°C to about 150°C. For example, target 100 can be cooled by flow of a coolant through the target in channel 122 to remove heat. Suitable examples of coolant include water, alcohol, and antifreeze. In one example, the coolant is degassed, ultra-pure water.

[0074] Numbered paragraphs In some embodiments, the present invention can be described by reference to the following numbered paragraphs:

[0075] Paragraph 1. A neutron generating target comprising: a substrate comprising a first material; a neutron generating region supported by the substrate and including a second material different from the first material, the second material configured to generate neutrons when exposed to the charged particle beam; a neutron generating target comprising: an intermediate layer supported by a substrate and positioned between the substrate and a neutron generating region, the intermediate layer including a third material different from the first material and the second material, the third material configured to sequester hydrogen and facilitate heat transfer from the neutron generating region to the substrate.

[0076] Paragraph 2. The target of Paragraph 1, wherein the target has a width of between 5 centimeters (cm) and 20 cm.

[0077] Paragraph 3. The target of Paragraph 2, wherein the width is 10 cm.

[0078] Paragraph 4. The thermal conductivity of the first material is 300 watts per meter Kelvin (W × m -1 ×K -1 ~1000W×m -1 ×K -1 4. The target of any one of paragraphs 1 to 3, wherein

[0079] Paragraph 5. The target of any one of Paragraphs 1 to 4, wherein the first material is selected from copper, gold, diamond-like carbon, diamond, and copper-diamond composites.

[0080] Paragraph 6. The target of any one of Paragraphs 1 to 4, wherein the first material is copper.

[0081] Paragraph 7. The target of any one of Paragraphs 1 to 6, wherein the thickness of the substrate is between 5 millimeters (mm) and 12 mm.

[0082] Paragraph 8. The target of Paragraph 7, wherein the thickness of the substrate is selected from 5 mm, 8 mm, and 10 mm.

[0083] Paragraph 9. The target of any one of Paragraphs 1 to 8, wherein the substrate is at least 2 times, at least 5 times, at least 10 times, at least 20 times, at least 50 times, at least 60 times, at least 70 times, at least 80 times, at least 90 times, or at least 100 times thicker than the neutron-generating region.

[0084] Paragraph 10. The target of any one of Paragraphs 1 to 9, wherein the second material comprises lithium (Li).

[0085] Paragraph 11. The lithium in the neutron generating region is 92 weight percent (wt%) to 98 wt% Li 7 11. The target of paragraph 10, comprising an isotope.

[0086] Paragraph 12. The target of any one of Paragraphs 1 to 11, wherein the thickness of the neutron-generating region is between 15 micrometers (μm) and 180 μm.

[0087] Paragraph 13. The target of Paragraph 12, wherein the second layer has a thickness of 90 μm to 100 μm.

[0088] Paragraph 14. A target according to any one of Paragraphs 1 to 13, wherein the thermal conductivity of the third material is greater than or equal to the thermal conductivity of the first material.

[0089] Paragraph 15. The thermal conductivity of a third material is 400 W x m -1 ×K -1 ~2,500W×m -1 ×K -1 15. The target of paragraph 14,

[0090] Paragraph 16. The thermal conductivity of a third material is 1,000 W x m -1 ×K -1 , 1,500W x m -1 ×K -1 , 1,700W x m -1 ×K -1 , and 2,000W x m -1 ×K -116. The target of paragraph 15, selected from:

[0091] Paragraph 17. The target of any one of Paragraphs 1 to 16, wherein the thickness of the intermediate layer is between 10 μm and 1 mm.

[0092] Paragraph 18. The target of any one of Paragraphs 1 to 17, wherein the third material comprises carbon, germanium, silicon, a silicon oxide compound, a silicon nitride compound, a carbon nitride compound, or any combination thereof.

[0093] Paragraph 19. The target of any one of Paragraphs 1 to 18, wherein the third material comprises graphite.

[0094] Paragraph 20. The target of Paragraph 19, wherein the graphite is selected from oriented solid graphite, non-oriented solid graphite, fibrous graphite, carbon fiber reinforced graphite, porous graphite, carbon nanotube-based graphite, and graphene.

[0095] Paragraph 21. The target of Paragraph 20, wherein the third material comprises 99% or 99.5% by weight of oriented pyrolytic graphite.

[0096] Paragraph 22. The target of Paragraph 20, wherein the third material comprises 99% or 99.5% by weight of porous graphite.

[0097] Paragraph 23. The target of any one of Paragraphs 1 to 17, wherein the third material comprises platinum, tantalum, titanium, aluminum, tin, zirconium, hafnium, vanadium, niobium, holmium, nickel, palladium, zinc, magnesium-nickel alloy, magnesium-iron alloy, or a salt, oxide, silicide, nitride, or carbide thereof, or a combination thereof.

[0098] Paragraph 24. A target according to Paragraph 23, wherein the third material comprises 99% or 99.5% by weight platinum.

[0099] Paragraph 25. The target of any one of Paragraphs 1 to 24, wherein the target includes a brazing layer positioned between the substrate and the intermediate layer and configured to facilitate bonding of the substrate to the intermediate layer via metallic bonding, covalent bonding, electrostatic interaction, inter-material diffusion, or any combination thereof.

[0100] Paragraph 26. The target of Paragraph 25, wherein the braze layer comprises an alloy including titanium, copper, and silver.

[0101] Paragraph 27. The target of Paragraph 25, wherein the brazing layer has a thickness of 1 μm to 10 μm.

[0102] Paragraph 28. A target according to any one of Paragraphs 1 to 27, wherein the target includes an adhesion layer positioned between the intermediate layer and the neutron-generating region and configured to facilitate bonding of the intermediate layer to the neutron-generating region via metallic bonding, covalent bonding, electrostatic interaction, inter-material diffusion, or any combination thereof.

[0103] Paragraph 29. A target according to Paragraph 28, wherein the adhesion layer comprises titanium, zirconium, hafnium, vanadium, niobium, tantalum, holmium, nickel, palladium, platinum, zinc, silver, aluminum, gold, bismuth, or mixtures or alloys thereof, or carbides thereof.

[0104] Paragraph 30. A target according to Paragraph 28, wherein the adhesion layer comprises 90% or 95% by weight titanium.

[0105] Paragraph 31. The target of Paragraph 28, wherein the adhesion layer has a thickness of 100 nanometers (nm) to 2 μm.

[0106] Paragraph 32. A target according to any one of Paragraphs 1 to 31, wherein the target comprises a passivation region, the passivation region being supported by the substrate, positioned above the neutron generation region, and configured to seal against diffusion of a third material into the passivation region and against diffusion of ambient substances into the passivation region.

[0107] Paragraph 33. A target according to Paragraph 32, wherein the passivation region comprises lithium fluoride, lithium sulfide, lithium carbonate, magnesium fluoride, carbon, diamond-like carbon, (ultra)nanocrystalline diamond, or a polymer.

[0108] Paragraph 34. The target of Paragraph 32, wherein the thickness of the passivation region is between 1 μm and 10 μm.

[0109] Paragraph 35. Passivation area is 1 × 10 per second -13 Square centimeters (cm 2 33. The target of paragraph 32, having a diffusion coefficient for the second material of less than or equal to 1 / s.

[0110] Paragraph 36. The passivation area is 100 (cm 3 ×mm) / (m 2 34. The target of paragraph 33, having a gas permeability of not more than 1000 kJ / h (x days x atm).

[0111] Paragraph 37. A neutron generating target comprising: a substrate comprising non-porous graphite; a neutron generating region supported by a substrate and including a material configured to generate neutrons when exposed to a charged particle beam.

[0112] Paragraph 38. The target of Paragraph 37, wherein the non-porous graphite is selected from oriented solid graphite, non-oriented solid graphite, fibrous graphite, carbon fiber reinforced graphite, carbon nanotube-based graphite, and graphene.

[0113] Paragraph 39. The target of Paragraph 37, wherein the substrate comprises 99 weight percent (wt%) or 99.5 wt% oriented pyrolytic graphite.

[0114] Paragraph 40. The target of any one of Paragraphs 37 to 39, wherein the target has a width of between 5 centimeters (cm) and 20 cm.

[0115] Paragraph 41. A target according to Paragraph 40, having a width of 10 cm.

[0116] Paragraph 42. The target of any one of Paragraphs 37 to 41, wherein the thickness of the substrate is between 5 millimeters (mm) and 12 mm.

[0117] Paragraph 43. The target of Paragraph 42, wherein the thickness of the substrate is selected from 5 mm, 8 mm, and 10 mm.

[0118] Paragraph 44. The target of any one of Paragraphs 37 to 43, wherein the substrate is at least 2 times, at least 5 times, at least 10 times, at least 20 times, at least 50 times, at least 60 times, at least 70 times, at least 80 times, at least 90 times, or at least 100 times thicker than the neutron-generating region.

[0119] Paragraph 45. The thermal conductivity of non-porous graphite is 400 W per meter Kelvin (W × m -1 ×K -1 )~2,500W×m -1 ×K -1 45. The target of any one of paragraphs 37 to 44, wherein

[0120] Paragraph 46. The thermal conductivity of non-porous graphite is 1,000 W x m -1 ×K -1 , 1,500W x m -1 ×K -1 , 1,700W x m -1 ×K -1 , and 2,000W x m -1 ×K -1 46. ​​A target according to paragraph 45, selected from:

[0121] Paragraph 47. A target according to any one of Paragraphs 37 to 46, wherein the material of the neutron-generating region comprises lithium (Li).

[0122] Paragraph 48. The lithium in the neutron generating region is 92% to 98% by weight Li 7 48. A target according to paragraph 47, comprising an isotope.

[0123] Paragraph 49. The target of any one of Paragraphs 37 to 48, wherein the thickness of the neutron-generating region is between 15 micrometers (μm) and 180 μm.

[0124] Paragraph 50. A target according to Paragraph 49, wherein the thickness of the neutron generating region is between 90 μm and 100 μm.

[0125] Paragraph 51. A target according to any one of Paragraphs 37 to 50, wherein the target includes an adhesion layer positioned between the substrate and the neutron-generating region and configured to facilitate bonding of the substrate to the neutron-generating region via metallic bonding, covalent bonding, electrostatic interaction, inter-material diffusion, or any combination thereof.

[0126] Paragraph 52. A target according to Paragraph 51, wherein the adhesion layer comprises titanium, zirconium, hafnium, vanadium, niobium, tantalum, holmium, nickel, palladium, platinum, zinc, silver, aluminum, gold, bismuth, or mixtures or alloys thereof, or carbides thereof.

[0127] Paragraph 53. A target according to Paragraph 51, wherein the adhesion layer comprises 90% or 95% by weight titanium.

[0128] Paragraph 54. The target of Paragraph 51, wherein the adhesion layer has a thickness of 100 nanometers (nm) to 2 μm.

[0129] Paragraph 55. A target according to any one of Paragraphs 37 to 54, wherein the target comprises a passivation region, the passivation region being supported by the substrate, positioned above the neutron generation region, and configured to seal against diffusion of a third material into the passivation region and against diffusion of ambient substances into the passivation region.

[0130] Paragraph 56. A target according to Paragraph 55, wherein the passivation region comprises lithium fluoride, lithium sulfide, lithium carbonate, magnesium fluoride, carbon, diamond-like carbon, (ultra)nanocrystalline diamond, or a polymer.

[0131] Paragraph 57. The target of Paragraph 55, wherein the thickness of the passivation region is between 1 μm and 10 μm.

[0132] Paragraph 58. Passivation area is 1 × 10 per second -13 Square centimeters (cm 2 56. The target of paragraph 55, having a diffusion coefficient for the second material of less than or equal to 1 / s.

[0133] Paragraph 59. The passivation area is 100 (cm 3 ×mm) / (m 2 56. The target of paragraph 55, having a gas permeability of not more than 1000 kJ / h (x days x atm).

[0134] Paragraph 60. A neutron beam system comprising: a charged particle accelerator; a beamline extending from a charged particle accelerator to a neutron generating target configured in accordance with any one of paragraphs 1 to 59.

[0135] Paragraph 61. A method of treating cancer in a subject in need thereof, comprising: (i) To the target, B 10 administering a therapeutically effective amount of a compound comprising: (ii)B 10 and waiting a sufficient amount of time for the compound to accumulate in cancer tissue within the subject. (iii) contacting a neutron generating target of any one of paragraphs 1 to 59 with a proton beam to produce a neutron beam; (iv) directing the neutron beam at the cancerous tissue.

[0136] Paragraph 62. The method of Paragraph 61, wherein the cancer is selected from liver cancer, oral cancer, colon cancer, brain cancer, head and neck cancer, lung cancer, breast cancer, gastric cancer, widespread squamous cell carcinoma, laryngeal cancer, melanoma, sarcoma, and extramammary Paget's disease.

[0137] Paragraph 63. Therapeutic doses are between 1 milligram (mg) and 100 mg per kilogram (kg) of subject's body weight. 10 62. The method of paragraph 61, wherein

[0138] Paragraph 64.B 10 Compounds containing B were administered at 20-50 micrograms (μg) per gram (g) of tumor. 10 64. The method of paragraph 63, wherein the compound accumulates in the cancer tissue at a level of

[0139] Paragraph 65. The method of any one of Paragraphs 61 to 64, wherein the sufficient amount of time is between 30 seconds and 1 hour.

[0140] Paragraph 66. A method according to any one of Paragraphs 61 to 65, wherein the energy of the proton beam is between 2 megaelectronvolts (MeV) and 3 MeV.

[0141] Paragraph 67. A method according to any one of Paragraphs 61 to 66, comprising cooling the target during the contacting of step (iii) to maintain its operating temperature between 130 and 150 degrees Celsius (°C).

[0142] Paragraph 68. The method of Paragraph 67, wherein cooling comprises contacting the target with a cooling liquid, thereby removing heat from the substrate.

[0143] Paragraph 69. The method of Paragraph 68, wherein the coolant is selected from water, alcohol, antifreeze, or combinations thereof.

[0144] Paragraph 70. The target of Paragraph 23, wherein the third material is essentially TaN, TiN, WN, NbN, MoN, CrN, VN, ZrN, HfN, or a combination thereof.

[0145] Paragraph 71. A target according to Paragraph 23, wherein the third material is an electrically insulating material.

[0146] Paragraph 72. A target according to any one of Paragraphs 1 to 23, 70 or 71, wherein the second material extends from the neutron-generating region beyond an edge of the intermediate layer so as to contact a surface of the substrate.

[0147] Paragraph 73. A target according to Paragraph 72, wherein the second material contacts a surface of the substrate on the same surface that supports the intermediate layer.

[0148] Paragraph 74. A target according to Paragraph 72, wherein the second material contacts a surface of the substrate on a side of the substrate different from the surface supporting the intermediate layer.

[0149] Paragraph 75. The target of any one of Paragraphs 1-23, 70, and 71, wherein the intermediate layer includes at least a first sublayer that does not extend to an edge of the substrate.

[0150] Paragraph 76. A target according to Paragraph 75, wherein the intermediate layer includes at least a second sub-layer that extends to an edge of the substrate.

[0151] Paragraph 77. A target according to Paragraph 76, wherein the second sublayer is between the substrate and the first sublayer, and a portion of the surface of the second sublayer is exposed at an edge of the first sublayer.

[0152] Paragraph 78. A target according to Paragraph 77, wherein the second material contacts the exposed portion of the surface of the second sub-layer.

[0153] Paragraph 79. A target according to Paragraph 78, wherein the second material is lithium, the first sub-layer is constituted by a nitride, and the second sub-layer is constituted by graphite.

[0154] Paragraph 80. A target according to Paragraph 76, wherein the first sublayer is between the substrate and the second sublayer, and the second sublayer contacts a portion of the surface of the substrate exposed at an edge of the first sublayer.

[0155] Paragraph 81. A neutron generating target comprising: a substrate comprising a first material; a neutron generating region supported by the substrate and including a second material different from the first material, the second material configured to generate neutrons when exposed to the charged particle beam and being an electrically conductive material; an intermediate layer supported by the substrate and positioned between the substrate and the neutron-generating region, the intermediate layer including a third material different from the first material and the second material, the third material being an electrically insulating material; A neutron generating target, wherein the second material extends from the neutron generating region beyond the edge of the third material.

[0156] Paragraph 82. A target according to Paragraph 81, wherein the first material is a metal.

[0157] Paragraph 83. A target according to Paragraph 81 or 82, wherein the second material is lithium.

[0158] Paragraph 84. The target of any one of Paragraphs 81 to 83, wherein the third material is TaN, TiN, WN, NbN, MoN, CrN, VN, ZrN, HfN, or a combination thereof.

[0159] Paragraph 85. A target according to any one of Paragraphs 81 to 84, wherein the second material extends from the neutron-generating region beyond an edge of the intermediate layer so as to contact the surface of the substrate.

[0160] Paragraph 86. A target according to Paragraph 85, wherein the second material contacts a surface of the substrate on the same surface that supports the intermediate layer.

[0161] Paragraph 87. A target according to Paragraph 85, wherein the second material contacts a surface of the substrate on a side of the substrate different from the surface supporting the intermediate layer.

[0162] Paragraph 88. A target according to any one of Paragraphs 81 to 84, wherein the intermediate layer includes at least a first sub-layer that does not extend to an edge of the substrate.

[0163] Paragraph 89. A target according to Paragraph 88, wherein the first sub-layer is composed of a third material.

[0164] Paragraph 90. A target according to Paragraph 88 or 89, wherein the intermediate layer includes at least a second sub-layer that extends to an edge of the substrate.

[0165] Paragraph 91. A target according to Paragraph 90, wherein the second sublayer is between the substrate and the first sublayer, and a portion of the surface of the second sublayer is exposed at an edge of the first sublayer.

[0166] Paragraph 92. A target according to Paragraph 91, wherein the second material contacts the exposed portion of the surface of the second sub-layer.

[0167] Paragraph 93. A target according to Paragraph 92, wherein the second material is lithium, the first sub-layer is constituted by a nitride, and the second sub-layer is constituted by graphite.

[0168] Paragraph 94. A target according to Paragraph 89, wherein the first sublayer is between the substrate and the second sublayer, and the second sublayer contacts a portion of the surface of the substrate exposed at an edge of the first sublayer.

[0169] Paragraph 95. A neutron generating target comprising: a substrate comprising a volume of copper or graphite, the volume comprising a flat surface and one or more channels; a neutron generating layer supported by the flat surface of the substrate and constituted by lithium; and one or more intermediate layers supported by the flat surface of the substrate between the substrate and the neutron generating layer, the one or more intermediate layers comprising a layer of a nitride material.

[0170] Paragraph 96. A neutron generating target according to Paragraph 95, wherein the nitride material is TiN or TaN.

[0171] Paragraph 97. A neutron generating target according to Paragraph 95 or 96, wherein the layer of nitride material is the only intermediate layer between the substrate and the neutron generating layer.

[0172] Paragraph 98. A neutron generating target according to Paragraph 97, wherein the substrate comprises graphite.

[0173] Paragraph 99. A neutron generating target according to Paragraph 95 or 96, wherein the substrate comprises copper.

[0174] Paragraph 100. A neutron generating target according to Paragraph 99, wherein the one or more intermediate layers comprises a graphite layer between the layer of nitride material and the substrate.

[0175] Paragraph 101. The neutron generating target of Paragraph 100, wherein the one or more intermediate layers comprises a braze layer between the substrate and the graphite layer.

[0176] Paragraph 102. A neutron generating target according to any one of Paragraphs 95 to 101, including a lithium protective layer disposed on an opposite side of the neutron generating layer from the substrate.

[0177] Paragraph 103. A neutron generating target according to Paragraph 102, wherein the lithium protective layer comprises LiF.

[0178] Paragraph 104. The neutron generating target of Paragraph 101, wherein the braze layer comprises a copper titanium alloy.

[0179] Paragraph 105. A neutron generating target according to Paragraph 104, wherein the copper titanium alloy comprises a metallic element comprising gallium, indium, or magnesium.

[0180] Paragraph 106. The target of Paragraph 52, wherein the adhesion layer comprises a metal nitride, a metal silicide, a metal carbide, or a metal alloy.

[0181] Paragraph 107. A target according to Paragraph 52, wherein the adhesion layer comprises titanium nitride, tantalum nitride, or titanium tungsten nitride.

[0182] Paragraph 108. A neutron generating target according to Paragraph 101, wherein the sub-intermediate layer is a braze layer.

[0183] Paragraph 109. A neutron generating target according to Paragraph 95, wherein the nitrogen-containing layer consists essentially of nitrogen.

[0184] Paragraph 110. A neutron generating target according to Paragraph 96, wherein the nitride material is tantalum nitride or titanium nitride.

[0185] Other embodiments While the present application has been described in conjunction with its detailed description, it should be understood that the foregoing description is intended to be illustrative, and not limiting, of the scope of the application, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

[0186] It should be noted that all features, elements, components, functions, and steps described with respect to any embodiment provided herein are intended to be freely combinable and interchangeable with those from any other embodiment. When a particular feature, element, component, function, or step is described with respect to only one embodiment, it should be understood that the feature, element, component, function, or step can be used with all other embodiments described herein, unless expressly stated otherwise. Accordingly, this paragraph serves as a prior basis and written support for the introduction of claims that combine features, elements, components, functions, and steps from different embodiments, or substitute features, elements, components, functions, and steps from one embodiment for features, elements, components, functions, and steps from another embodiment, even if the following description does not explicitly state that such combinations or substitutions are possible in a particular instance. It is clearly recognized that an explicit enumeration of all possible combinations and permutations would be unduly burdensome, especially given that the permissibility of each and every such combination and permutation would be readily recognized by those skilled in the art.

Claims

1. 1. A neutron generating target comprising: a substrate comprising a first material; a neutron generating region supported by the substrate and including a second material different from the first material, the second material configured to generate neutrons when exposed to a charged particle beam; an intermediate layer supported by the substrate and positioned between the substrate and the neutron-generating region, the intermediate layer including a third material different from the first material and the second material, the third material configured to sequester hydrogen and to facilitate heat transfer from the neutron-generating region to the substrate.

2. The target of claim 1 , wherein the target has a width between 5 centimeters (cm) and 20 cm.

3. 3. The target of claim 2, wherein the width is 10 cm.

4. The thermal conductivity of the first material is 300 watts per meter Kelvin (W×m －１ ×K －１ ) ~ 1000W x m －１ ×K －１ The target according to any one of claims 1 to 3,

5. The target of any one of claims 1 to 4, wherein the first material is selected from copper, gold, diamond-like carbon, diamond, and copper-diamond composites.

6. The target according to any one of claims 1 to 4, wherein the first material is copper.

7. The target according to any one of claims 1 to 6, wherein the substrate has a thickness of 5 millimeters (mm) to 12 mm.

8. 8. The target of claim 7, wherein the thickness of the substrate is selected from 5 mm, 8 mm, and 10 mm.

9. 9. The target of claim 1, wherein the substrate is at least 2 times, at least 5 times, at least 10 times, at least 20 times, at least 50 times, at least 60 times, at least 70 times, at least 80 times, at least 90 times, or at least 100 times thicker than the neutron generation region.

10. The target according to any one of claims 1 to 9, wherein the second material comprises lithium (Li).

11. The lithium in the neutron generating region is 92 weight percent (wt%) to 98 wt% Li ７ The target of claim 10 comprising an isotope.

12. The target of any one of claims 1 to 11, wherein the thickness of the neutron-generating region is between 15 micrometers (µm) and 180 µm.

13. The target of claim 12, wherein the thickness of the second layer is between 90 μm and 100 μm.

14. The target according to any one of claims 1 to 13, wherein the thermal conductivity of the third material is equal to or greater than the thermal conductivity of the first material.

15. The thermal conductivity of the third material is 400 W x m －１ ×K －１ ~2,500W x m －１ ×K －１ 15. The target of claim 14, wherein:

16. The thermal conductivity of the third material is 1,000 W x m －１ ×K －１ , 1,500W x m －１ ×K －１ , 1,700W x m －１ ×K －１ , and 2,000W x m －１ ×K －１ The target of claim 15, wherein the target is selected from:

17. The target according to any one of claims 1 to 16, wherein the intermediate layer has a thickness of 10 µm to 1 mm.

18. The target of any one of claims 1 to 17, wherein the third material comprises carbon, germanium, silicon, a silicon oxide compound, a silicon nitride compound, a carbon nitride compound, or any combination thereof.

19. The target of any one of claims 1 to 18, wherein the third material comprises graphite.

20. 20. The target of claim 19, wherein the graphite is selected from oriented solid graphite, non-oriented solid graphite, fibrous graphite, carbon fiber reinforced graphite, porous graphite, carbon nanotube based graphite, and graphene.

21. 21. The target of claim 20, wherein the third material comprises 99% or 99.5% by weight of oriented pyrolytic graphite.

22. 21. The target of claim 20, wherein the third material comprises 99% or 99.5% by weight porous graphite.

23. 18. The target of any one of claims 1 to 17, wherein the third material comprises platinum, tantalum, titanium, aluminum, tin, zirconium, hafnium, vanadium, niobium, holmium, nickel, palladium, zinc, a magnesium-nickel alloy, a magnesium-iron alloy, or a salt, oxide, silicide, nitride, or carbide thereof, or a combination thereof.

24. 24. The target of claim 23, wherein the third material comprises 99% or 99.5% platinum by weight.

25. 25. The target of any one of claims 1 to 24, wherein the target comprises a sub-intermediate layer positioned between the substrate and the intermediate layer and configured to facilitate bonding of the substrate to the intermediate layer via metallic bonding, covalent bonding, electrostatic interaction, inter-material diffusion, or any combination thereof.

26. 26. The target of claim 25, wherein the sub-intermediate layer comprises an alloy including titanium, copper, and silver.

27. 26. The target of claim 25, wherein the sub-intermediate layer has a thickness of 1 μm to 10 μm.

28. 28. The target of any one of claims 1 to 27, wherein the target comprises an adhesion layer positioned between the intermediate layer and the neutron-generating region and configured to facilitate bonding of the intermediate layer to the neutron-generating region via metallic bonding, covalent bonding, electrostatic interaction, inter-material diffusion, or any combination thereof.

29. 30. The target of claim 28, wherein the adhesion layer comprises titanium, zirconium, hafnium, vanadium, niobium, tantalum, holmium, nickel, palladium, platinum, zinc, silver, aluminum, gold, bismuth, or mixtures or alloys thereof, or carbides thereof.

30. 30. The target of claim 28, wherein the adhesion layer comprises 90% or 95% titanium by weight.

31. 30. The target of claim 28, wherein the adhesion layer has a thickness of from 100 nanometers (nm) to 2 μm.

32. 32. The target of any one of claims 1 to 31, wherein the target comprises a passivation region supported by the substrate, positioned above the neutron-generating region, and configured to seal against diffusion of the third material into the passivation region and against diffusion of ambient substances into the passivation region.

33. 33. The target of claim 32, wherein the passivation region comprises lithium fluoride, lithium sulfide, lithium carbonate, magnesium fluoride, carbon, diamond-like carbon, (ultra)nanocrystalline diamond, or a polymer.

34. 33. The target of claim 32, wherein the passivation region has a thickness of 1 μm to 10 μm.

35. The passivation region is irradiated at a rate of 1×10 per second. －１３ Square centimeter (cm ２ 33. The target of claim 32, having a diffusion coefficient for the second material of less than or equal to 1 / s.

36. The passivation region is 100 (cm ３ × mm) / (m ２ 34. The target of claim 33, having a gas permeability of less than or equal to 1000 kJ / s.

37. 1. A neutron generating target comprising: a substrate comprising non-porous graphite; a neutron generating region supported by a substrate and including a material configured to generate neutrons when exposed to a charged particle beam.

38. 38. The target of claim 37, wherein the non-porous graphite is selected from oriented solid graphite, non-oriented solid graphite, fibrous graphite, carbon fiber reinforced graphite, carbon nanotube based graphite, and graphene.

39. 38. The target of claim 37, wherein the substrate comprises 99 weight percent (wt%) or 99.5 wt% oriented pyrolytic graphite.

40. The target of any one of claims 37 to 39, wherein the target has a width of between 5 centimeters (cm) and 20 cm.

41. 41. The target of claim 40, wherein the width is 10 cm.

42. The target of any one of claims 37 to 41, wherein the substrate has a thickness of 5 millimeters (mm) to 12 mm.

43. 43. The target of claim 42, wherein the thickness of the substrate is selected from 5 mm, 8 mm, and 10 mm.

44. 44. The target of any one of claims 37 to 43, wherein the substrate is at least 2 times, at least 5 times, at least 10 times, at least 20 times, at least 50 times, at least 60 times, at least 70 times, at least 80 times, at least 90 times, or at least 100 times thicker than the neutron generation region.

45. The thermal conductivity of the non-porous graphite is 400 W per meter Kelvin (W×m －１ ×K －１ ) ~ 2,500W x m －１ ×K －１ The target according to any one of claims 37 to 44, wherein

46. The thermal conductivity of the non-porous graphite is 1,000 W x m －１ ×K －１ , 1,500W x m －１ ×K －１ , 1,700W x m －１ ×K －１ , and 2,000W x m －１ ×K －１ 46. ​​The target of claim 45, selected from:

47. The target of any one of claims 37 to 46, wherein the material of the neutron-generating region comprises lithium (Li).

48. The lithium in the neutron generating region is 92% by weight to 98% by weight Li ７ 48. The target of claim 47, comprising an isotope.

49. The target of any one of claims 37 to 48, wherein the neutron-generating region has a thickness of from 15 micrometers (μm) to 180 μm.

50. 50. The target of claim 49, wherein the thickness of the neutron-producing region is between 90 μm and 100 μm.

51. 51. The target of any one of claims 37 to 50, wherein the target comprises an adhesion layer positioned between the substrate and the neutron-generating region and configured to facilitate bonding of the substrate to the neutron-generating region via metallic bonding, covalent bonding, electrostatic interactions, inter-material diffusion, or any combination thereof.

52. 52. The target of claim 51 , wherein the adhesion layer comprises titanium, zirconium, hafnium, vanadium, niobium, tantalum, holmium, nickel, palladium, platinum, zinc, silver, aluminum, gold, bismuth, or mixtures or alloys thereof, or carbides thereof.

53. 52. The target of claim 51, wherein the adhesion layer comprises 90% or 95% titanium by weight.

54. 52. The target of claim 51, wherein the adhesion layer has a thickness of from 100 nanometers (nm) to 2 μm.

55. 55. The target of any one of claims 37 to 54, wherein the target comprises a passivation region supported by the substrate, positioned over the neutron-generating region, and configured to seal against diffusion of the third material into the passivation region and against diffusion of ambient substances into the passivation region.

56. 56. The target of claim 55, wherein the passivation region comprises lithium fluoride, lithium sulfide, lithium carbonate, magnesium fluoride, carbon, diamond-like carbon, (ultra)nanocrystalline diamond, or a polymer.

57. 56. The target of claim 55, wherein the passivation region has a thickness of 1 μm to 10 μm.

58. The passivation region is irradiated at a rate of 1×10 per second. －１３ Square centimeter (cm ２ 56. The target of claim 55, having a diffusion coefficient for the second material of less than or equal to 1 / s.

59. The passivation region is 100 (cm ３ × mm) / (m ２ 56. The target of claim 55, having a gas permeability of less than or equal to 1000 kJ / s.

60. 1. A neutron beam system comprising: a charged particle accelerator; a beamline extending from the charged particle accelerator to a neutron generating target configured in accordance with any one of claims 1 to 59.

61. 1. A method of treating cancer in a subject in need thereof, comprising: (i) the target, B １０ administering a therapeutically effective amount of a compound comprising: (ii) B １０ waiting a sufficient amount of time for the compound to accumulate in cancerous tissue within the subject; (iii) contacting the neutron generating target of any one of claims 1 to 59 with a proton beam to generate a neutron beam; (iv) directing the neutron beam at the cancerous tissue.

62. 62. The method of claim 61, wherein the cancer is selected from liver cancer, oral cancer, colon cancer, brain cancer, head and neck cancer, lung cancer, breast cancer, gastric cancer, widespread squamous cell carcinoma, laryngeal cancer, melanoma, sarcoma, and extramammary Paget's disease.

63. The therapeutic amount is 1 milligram (mg) to 100 mg of B per kilogram (kg) of the subject's body weight. １０ 62. The method of claim 61, wherein:

64. B １０ The compound comprising: １０ 64. The method of claim 63, wherein the compound accumulates in the cancer tissue at a level of

65. 65. The method of any one of claims 61 to 64, wherein the sufficient amount of time is from 30 seconds to 1 hour.

66. 66. The method of any one of claims 61 to 65, wherein the energy of the proton beam is between 2 megaelectronvolts (MeV) and 3 MeV.

67. 67. The method of any one of claims 61 to 66, comprising cooling the target during the contacting of step (iii) to maintain its operating temperature between 130 degrees Celsius (°C) and 150°C.

68. 68. The method of claim 67, wherein the cooling comprises contacting the target with a cooling fluid, thereby removing heat from the substrate.

69. 69. The method of claim 68, wherein the coolant is selected from water, alcohol, antifreeze, or combinations thereof.

70. 24. The target of claim 23, wherein the third material consists essentially of TaN, TiN, WN, NbN, MoN, CrN, VN, ZrN, HfN, or combinations thereof.

71. 24. The target of claim 23, wherein the third material is an electrically insulating material.

72. 72. The target of any one of claims 1 to 23, 70 or 71, wherein the second material extends from the neutron-producing region beyond an edge of the intermediate layer so as to contact a surface of the substrate.

73. 73. The target of claim 72, wherein the second material contacts the surface of the substrate on the same surface that supports the intermediate layer.

74. 73. The target of claim 72, wherein the second material contacts the surface of the substrate on a side of the substrate different from the surface supporting the intermediate layer.

75. 72. The target of any one of claims 1-23, 70 and 71, wherein the intermediate layer includes at least a first sub-layer that does not extend to an edge of the substrate.

76. 76. The target of claim 75, wherein the intermediate layer includes at least a second sub-layer that extends to an edge of the substrate.

77. 77. The target of claim 76, wherein the second sublayer is between the substrate and the first sublayer, and a portion of a surface of the second sublayer is exposed at an edge of the first sublayer.

78. 78. The target of claim 77, wherein the second material contacts the exposed portion of the surface of the second sublayer.

79. 79. The target of claim 78, wherein the second material is lithium, the first sub-layer is comprised of a nitride, and the second sub-layer is comprised of graphite.

80. 77. The target of claim 76, wherein the first sublayer is between the substrate and the second sublayer, and the second sublayer contacts a portion of the surface of the substrate exposed at an edge of the first sublayer.

81. 1. A neutron generating target comprising: a substrate comprising a first material; a neutron generation region supported by the substrate and including a second material different from the first material, the second material configured to generate neutrons when exposed to a charged particle beam and being an electrically conductive material; and an intermediate layer supported by the substrate and positioned between the substrate and the neutron-generating region, the intermediate layer including a third material different from the first material and the second material, the third material being an electrically insulating material; A neutron generating target wherein the second material extends from the neutron generating region beyond an edge of the third material.

82. 82. The target of claim 81, wherein the first material is a metal.

83. 83. The target of claim 81 or 82, wherein the second material is lithium.

84. 84. The target of any one of claims 81 to 83, wherein the third material consists essentially of TaN, TiN, WN, NbN, MoN, CrN, VN, ZrN, HfN, or combinations thereof.

85. 85. The target of any one of claims 81 to 84, wherein the second material extends from the neutron-producing region beyond an edge of the intermediate layer so as to contact a surface of the substrate.

86. 86. The target of claim 85, wherein the second material contacts the surface of the substrate on the same surface that supports the intermediate layer.

87. 86. The target of claim 85, wherein the second material contacts the surface of the substrate on a side of the substrate different from the surface supporting the intermediate layer.

88. 85. The target of any one of claims 81 to 84, wherein the intermediate layer comprises at least a first sub-layer that does not extend to an edge of the substrate.

89. 89. The target of claim 88, wherein the first sublayer is composed of the third material.

90. 90. The target of claim 88 or 89, wherein the intermediate layer includes at least a second sub-layer that extends to an edge of the substrate.

91. 91. The target of claim 90, wherein the second sublayer is between the substrate and the first sublayer, and a portion of a surface of the second sublayer is exposed at an edge of the first sublayer.

92. 92. The target of claim 91, wherein the second material contacts the exposed portion of the surface of the second sublayer.

93. 93. The target of claim 92, wherein the second material is lithium, the first sub-layer is comprised of a nitride, and the second sub-layer is comprised of graphite.

94. 90. The target of claim 89, wherein the first sublayer is between the substrate and the second sublayer, and the second sublayer contacts a portion of the surface of the substrate exposed at an edge of the first sublayer.

95. 1. A neutron generating target comprising: a substrate comprising a volume of copper or graphite, said volume comprising a flat surface and one or more channels; a neutron generating layer supported by the planar surface of the substrate and consisting essentially of lithium; one or more intermediate layers supported by the planar surface of the substrate between the substrate and the neutron generating layer, the one or more intermediate layers including a layer containing nitrogen.

96. 96. The neutron generating target of claim 95, wherein the layer comprising nitrogen comprises a nitride material.

97. 97. The neutron generating target of claim 95 or 96, wherein the layer of nitride material is the only intermediate layer between the substrate and the neutron generating layer.

98. 98. The neutron generating target of claim 97, wherein the substrate consists essentially of graphite.

99. 97. The neutron generating target of claim 95 or 96, wherein the substrate consists essentially of copper.

100. 100. The neutron generating target of claim 99, wherein the one or more intermediate layers comprises a graphite layer between the layer of nitride material and the substrate.

101. 101. The neutron generating target of claim 100, wherein the one or more intermediate layers comprises a sub-intermediate layer between the substrate and the graphite layer.

102. 102. The neutron generating target of any one of claims 95 to 101, further comprising a lithium protective layer disposed on an opposite side of the neutron generating layer from the substrate.

103. 103. The neutron generating target of claim 102, wherein the lithium protective layer consists essentially of LiF.

104. 102. The neutron generating target of claim 101, wherein the sub-intermediate layer comprises a copper titanium alloy.

105. 105. The neutron generating target of claim 104, wherein the copper titanium alloy comprises a metallic element comprising gallium, indium, or magnesium.

106. 53. The target of claim 52, wherein the adhesion layer comprises a metal nitride, a metal silicide, a metal carbide, or a metal alloy.

107. 53. The target of claim 52, wherein the adhesion layer comprises titanium nitride, tantalum nitride, or titanium tungsten nitride.

108. 102. The neutron generating target of claim 101, wherein the sub-intermediate layer is a braze layer.

109. 96. The neutron generating target of claim 95, wherein the nitrogen-containing layer consists essentially of nitrogen.

110. 97. The neutron generating target of claim 96, wherein the nitride material is tantalum nitride or titanium nitride.

Images