Lithium bonding to substrate

Abstract

Neutron generating targets, for example for use in boron neutron capture therapy ("BNCT"), and methods for manufacturing the neutron generating targets. This specification describes lithium-containing neutron generating targets useful for generating neutron beams for bombarding boron-containing compounds in boron neutron capture therapy of cancer. One method involves pressing a lithium foil against a substrate with sufficient force such that the lithium deforms during the pressing operation and adheres to the substrate, thereby forming a thin lithium layer on the surface of the substrate.

Description

[Technical field]

[0001] The present specification generally relates to methods for bonding a lithium layer to a substrate, and to using such methods to manufacture neutron producing targets. [Background technology]

[0002] Cancer is one of the leading causes of death in modern society. According to the Centers for Disease Control, the cancer mortality rate in 2020 was 144 per 100,000 people. Locally invasive malignancies such as brain cancer, head and neck cancer, and cutaneous and extracutaneous melanoma are of particular concern because effective means to treat or inhibit the growth of these cancers 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 that has 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]

[0003] The present specification describes a lithium-containing neutron generating target useful, inter alia, for generating a neutron beam for bombarding boron-containing compounds in boron neutron capture therapy ("BNCT") of cancer. The invention is based, at least in part, on the recognition that a well-bonded lithium layer of a desired thickness (e.g., 100 μm) can be created on the substrate surface by application of a mechanical force to a thin solid lithium film deposited on the surface of the target's substrate. In one embodiment, prior to depositing the lithium film (or, alternatively, foil) on the substrate, the substrate surface is coated with an intermediate layer (e.g., a pure Al layer) that promotes and facilitates adhesion of the lithium film to the substrate. Advantageously, the disclosed method requires much less time and energy compared to conventional techniques for producing lithium-containing targets, which include evaporating and condensing lithium metal on the substrate surface to generate the target. Using the disclosed method, a neutron generating target is generated having a clean lithium layer of a desired thickness bonded to the substrate surface that can be obtained quickly, inexpensively, and efficiently.

[0004] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this specification belongs. Methods and materials for use in this application are described herein, and 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, sequences, 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.

[0005] Other features and advantages of the present application will become apparent from the following detailed description and drawings, and from the claims. [Brief description of the drawings]

[0006] [Figure 1A] FIG. 1 is a high level schematic diagram of an exemplary neutron beam system. [Figure 1B]FIG. 2 is a more detailed schematic diagram of an exemplary neutron beam system. [Diagram 2] 1 is a cross-sectional view of an exemplary target assembly subsystem. [Figure 3A] 1A-1D are cross-sectional, front and rear perspective views of an exemplary neutron generating target; [Figure 3B] 1A-1D are cross-sectional, front and rear perspective views of an exemplary neutron generating target; [Figure 3C] 1A-1D are cross-sectional, front and rear perspective views of an exemplary neutron generating target; [Figure 4A] 1 is a flow chart of an exemplary process for manufacturing a neutron generating target by applying a mechanical force to a lithium foil positioned on top of a substrate. [Figure 4B] FIG. 2 is a cross-sectional view of an exemplary combination of lithium foil and a substrate for assembly into a neutron generating target. [Figure 4C] 1 is a flow chart of another exemplary process for producing a neutron generating target by preparing a substrate and lithium foil and then applying a mechanical force to the lithium foil positioned on the substrate. [Figure 5A] 1 is a flow chart of an exemplary process for manufacturing a neutron generating target by applying a mechanical force to a lithium foil positioned on top of an intermediate prelayer of a substrate. [Figure 5B] FIG. 1 is a cross-sectional view of an exemplary combination of lithium foil and substrate with an intermediate pre-layer for assembly into a neutron generating target. [Figure 5C] FIG. 1 is a cross-sectional view of an exemplary neutron generating target prepared by pressing a lithium foil onto a substrate having an intermediate prelayer. [Figure 5D] 1 is a flow chart of another exemplary process for manufacturing a neutron generating target by preparing a substrate, an intermediate layer, and a lithium foil, and then applying a mechanical force to the lithium foil positioned above the intermediate pre-layer on the substrate. [Figure 6A]1 is a flow chart of an exemplary process for manufacturing a neutron generating target by applying a mechanical force to a lithium foil positioned over a front layer of lithium on top of a substrate. [Figure 6B] FIG. 1 is a cross-sectional view of an exemplary combination of a lithium foil and a substrate with a lithium prelayer for assembly into a neutron generating target. [Figure 6C] FIG. 1 is a cross-sectional view of an exemplary neutron generating target prepared by pressing lithium foil onto a substrate having an intermediate pre-layer of lithium. [Figure 6D] 1 is a flow chart of another exemplary process for manufacturing a neutron generating target by preparing a substrate, a lithium prelayer, and a lithium foil, and then applying a mechanical force to the lithium foil positioned on top of the lithium prelayer on top of the substrate.

[0007] In the drawings, like reference numbers indicate like elements. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The lithium bonding techniques described herein can be used in a variety of applications where it is desirable to attach a lithium layer to a substrate, for example, by adhering the lithium layer to the substrate by mechanical forces. The lithium-bonded substrate 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 trapping charged particles in a vacuum), industrial manufacturing processes, beam systems for modifying material properties (e.g., surface treatment and modification), 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 lithium-bonded substrate is as a neutron generating target for boron neutron capture therapy ("BNCT").

[0009] In general, BNCT is a type of treatment for various types of cancer, including the most difficult types. 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" neutrons. In this technique, a boron-containing compound is administered to the patient (e.g., by injecting a parenteral composition into the patient's blood vessels) so that boron-10 selectively collects 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 particles of boron, various boron-containing nanoparticles, boronated cyclic or acyclic peptides with affinity for cancer cells (e.g., boronated arginyl glycylaspartic 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). For example, upon administration of the boron carrier compound, tumor concentrations of boron can reach about 20-50 μg 10 The boron concentration in the tumor can be in the range of 10 B / g. The tumor concentration of boron can be determined by any means generally known for this purpose, such as imaging, calibration, and / or biopsy. Once a sufficient amount of boron-10 has been collected in the tumor, the patient is subjected to radiation in the form of a neutron beam at or near the tumor site.

[0010] 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 7The neutron generating 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

[0011] 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)

[0012] This specification describes lithium-containing neutron generating targets useful for generating neutron beams for bombarding boron-containing compounds administered to a patient during BNCT. Figure 1A includes a schematic diagram of an example of a neutron beam system 10 that can be used to generate neutrons for BNCT using the lithium-containing neutron generating targets of the present disclosure.

[0013] As shown in FIG. 1A, the beam system 10 includes a source of hydrogen ions 12, a low energy beam line ("LEBL") 14, an accelerator 16 coupled to the LEBL 14, and a high energy beam line ("HEBL") 16 extending from the accelerator 16 to a target 100. The LEBL 14 is configured to transport a beam of negative hydrogen ions from the ion source 12 to an input of the accelerator 16, which is configured to generate a proton beam by accelerating the hydrogen ion beam transported by the LEBL 14. The HEBL 18 transports the proton beam from the output of the accelerator 16 to the target 100. Upon bombardment with protons of sufficient energy, the target 100 generates a neutron beam that is further directed to a tumor site (not shown) within a subject's body.

[0014] 1B is a more detailed schematic diagram 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 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 HEBL 18 that extends from the tandem accelerator 16 to a neutron target assembly 200 that houses a target (not shown). The pre-accelerator system 20 is configured to transport a hydrogen ion beam from the ion source 12 to an input (e.g., an input aperture) of the tandem accelerator 16, and therefore 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 generating a proton beam having an energy approximately equal to twice the voltage applied to an accelerating electrode positioned within the accelerator 16. The proton beam energy level is 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 accelerating the resulting protons downstream with the same applied voltage.

[0015] The HEBL 18 can transport the proton beam from the output of the accelerator 16 to a target 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. The illustrative HEBL 18 includes three branches 70, 80, and 90 that can extend to three different patient treatment rooms, and each branch can terminate in a target assembly 200 and downstream beam shaping devices (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 toward the corresponding target assembly, beam corrector 53, diagnostics such as current monitors 54 and 76, a fast beam position monitor 55 section, and a scanning magnet 74.

[0016] The design of the HEBL 18 depends on the configuration of the treatment facility (e.g., a single-level configuration of the treatment facility, a two-level configuration of the treatment facility, and the like). The proton beam can be delivered to a target assembly 200 (e.g., positioned near the treatment room) using bending magnets 56 and 58. A quadrupole magnet 72 can then be included to focus the proton beam to a certain size on the target. The proton beam then passes through one or more scanning magnets 74, which provide movement of the proton beam onto the target surface in a desired pattern (e.g., spiral, curvilinear, row and column staircase, combinations thereof, and others). The movement of the proton beam helps achieve a smooth and even time-averaged distribution of the proton beam on the lithium target, prevents overheating, and allows neutron generation to be as uniform as possible within the lithium layer (e.g., lithium layer 110 shown in FIG. 3A).

[0017] A current monitor 76 measures the beam current. The target assembly 200 can be physically isolated from the HEBL volume using a gate valve 77. The main function of the gate valve is to isolate the vacuum volume of the beamline from the target while loading the target and / or replacing a used target with a new target.

[0018] In this configuration, the beam is not bent 90 degrees by bending magnet 56, but rather goes straight to the right in FIG. 1B and then enters 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, bending magnet 58 can be replaced by a Y-shaped magnet to split the beamline in two directions for two different treatment rooms located on the same floor.

[0019] FIG. 2 is a cross-sectional view depicting an exemplary target assembly subsystem 201 suitable for use as the target assembly subsystem 200 of the neutron beam system 10 shown in FIGS. 1A and 1B. The neutron generating target 101 is enclosed between a cap 202 and a vacuum or near-vacuum interior region 210 of the HEBL 18. Arrow B indicates the direction of a charged particle (e.g., proton) beam that initially impacts a face on the upstream side 112 of the target 101. Cooling of the target 101 can be accomplished on the opposite downstream side 114 (where the neutron beam exits the target 101). The cap 202 can be bolted to the HEBL 18, thus providing both a vacuum-tight seal 206 between the target 101 and the vacuum region 210 of the HEBL 18, and a water-tight seal 205 between the target 101 and the cooling water inlets 204 and outlets 208.

[0020] Example of lithium layer FIG. 3A is a cross-sectional view depicting an exemplary lithium-containing neutron generating target of BCNT. FIGS. 3A and 3B are perspective views of the upstream 112 and downstream 114 sides of the target, respectively. The target includes a neutron generating layer of lithium 110. The lithium in this layer is Li 6 and Li 7 Naturally 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 about 99.9% by weight or about 100% by weight of the lithium material. 7 Contains Li 7 is concentrated, and Li 6 The lithium in layer 110 is also depleted. 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 these with isotopes.

[0021] The lithium layer 110 may be configured as a planar neutron generating layer coupled to a surface 121 of a substrate 120. 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, in turn, pass through the substrate 120 and exit the target downstream side 114. The thickness of the lithium layer 110 (e.g., the distance between the outer surface 302 of the layer 110 and the surface 121 of the substrate 120) 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 (about 92% lithium 7) for several proton energies. The right column lists a variable called "depth to threshold," which indicates the stopping range at which the average proton 7 Li(p,n) 7 It represents the distance that a proton travels inside a material before it slows down to the threshold energy for the Be reaction (about 1.88 MeV). If the protons slow down beyond this threshold energy, they cannot produce neutrons. For example, if the protons have an energy of 2.50 megaelectron volts (MeV), the high energy protons enter the lithium material and then travel about 90 microns through the lithium before slowing down to the threshold energy. In this example, if the lithium is less than 90 microns (μm) thick, the neutron yield will decrease and the lithium material will not be utilized most efficiently. It is substantially desirable to have a lithium layer thick enough for a neutron production target, but not so thick that a reduction in the energy of the protons below the threshold will dissipate excess heat in the lithium or generate undesirable gamma radiation. For example, for a 2.5 MeV proton beam, a lithium layer 200 mm thick may not be desirable to dissipate excess heat within the lithium layer. [Table 1]

[0022] The preferred thickness of the lithium layer 110 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. The preferred proton energy is about 2 MeV to about 3 MeV, or about 2.25 MeV to about 2.75 MeV. In the preferred coupling, 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.

[0023] Examples of target substrates The substrate 120 can be configured for heat removal to dissipate the high energy levels of the incident proton beam. As mentioned above, the thickness of the lithium layer 110 is determined so that the proton energy is reduced to the Li 7 (p,n)Be 7 The target is configured to allow protons to exit layer 110 relatively soon or immediately after dropping below a reaction threshold (e.g., lithium-7 threshold of 1.88 MeV). 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 an energy level around the threshold penetrate to substrate 120 and dissipate the remaining energy in substrate 120, or partly in substrate 120 and partly in one or more other components located downstream of the target.

[0024] The substrate 120 may be made of a material having a high thermal conductivity. A suitable value for the thermal conductivity of the substrate 120 is 300 W×m -1 ×K -1 Super, 400W×m -1 ×K -1 Over 500W×m -1 ×K -1 Over or about 400W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1The substrate material may be copper (Cu). Other suitable substrate materials include copper alloys, beryllium, chemical vapor deposition (CVD) diamond, or copper diamond powder composites. The target may include one or more materials that inhibit blistering, such as a tantalum layer between the lithium layer 110 and the substrate 120. Protons that leave the lithium layer and deposit on the substrate 120 can 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 cooling water flow rate. For example, the substrate 120 may contain a spiral channel 122, as depicted in FIG. 3B, or channels of any other dimensions and configurations desired. Suitable examples of coolants include water, ethanol, methanol, ethylene glycol, propylene glycol, or any mixture thereof. By cooling the substrate, the substrate temperature during proton bombardment can be controlled so as not to exceed the melting point of lithium (e.g., about 180° C. to about 182° C.). In some embodiments, the substrate temperature during operation is cooled so as not to exceed 100° C. In certain embodiments, the target is a round target that is a plate having a diameter of about 4 inches to about 8 inches, for example about 6 inches. The thickness of the target substrate can be about 6 mm to about 12 mm, such as about 8 mm to about 12 mm. In some embodiments, the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium layer in the target.

[0025] In some examples, a protective cover (e.g., a passivation region) can be positioned over the lithium layer 110 (e.g., in contact with the surface 302 of the lithium layer 110). Certain examples of passivation materials, as well as their thicknesses and other properties, are described in PCT Publication No. 2022 / 212821 A1, which is incorporated by reference in its entirety. Exemplary passivation materials include lithium fluoride, lithium sulfide, magnesium fluoride, carbon (C), diamond-like carbon, nanocrystalline diamond, polymers, and combinations thereof.

[0026] Example of a method for adhering a lithium layer to a substrate Lithium is a valuable neutron generating material, but there are significant challenges in depositing a clean layer of lithium of the necessary thickness on a target substrate. Lithium is a highly reactive and corrosive metal that is difficult to handle under normal ambient conditions (e.g., room temperature air found in typical laboratory spaces, and the like). Lithium reacts violently with moisture, nitrogen, and / or oxygen in the atmosphere, rapidly tarnishing and / or oxidizing. When exposed to air, lithium discolors and oxidizes, forming lithium nitride (Li 3 N), hydroxides (LiOH and LiOH-H 2 O), oxide (Li 2 O), or carbonate (Li 2 CO 3 , LiOH and CO 2 or any combination of the foregoing. These reaction products can flake off from the substrate in the form of dust and can prevent pure lithium from adhering to the target substrate (e.g., copper) material. As used herein, the term "pure" refers to a material (e.g., metals such as lithium, aluminum, copper, or gold) that is substantially uncontaminated. For example, pure lithium is about 99% or more by weight lithium, e.g., about 99.5% or more by weight lithium.

[0027] Conventionally, a vacuum deposition technique has been applied to avoid contamination of the lithium layer by its reaction products with air and / or moisture and to promote its attachment to the target substrate. However, this conventional method has significant drawbacks. For example, the evaporation of lithium onto the substrate takes a long time (e.g., up to 24 hours) and involves the use of a heated vacuum evaporator. In addition, it is very difficult to control where the evaporated gaseous lithium condenses in the vacuum chamber. Thus, solid lithium metal covers all surfaces of the chamber after condensation and cooling downtime, which requires additional time and cost to recover the lithium not deposited on the target substrate. Moreover, using the vapor deposition technique, it is difficult to precisely control the thickness of the lithium layer formed on the substrate surface, which is a critical parameter of the neutron generation process (as mentioned above).

[0028] FIG. 4A is a flow chart of an exemplary process 400 for manufacturing a neutron generating target. The process involves contacting a surface of a lithium foil with a surface of a substrate (406). In some examples, the contacting is continuous (e.g., an uninterrupted and uninterrupted contact is created between a first surface of the lithium foil and a surface of the substrate). In certain examples, a continuous contact is created between a surface of the lithium foil and a surface of the substrate such that 99% or more of the macroscopic area of ​​the surface of the lithium foil is in uninterrupted and / or uninterrupted contact with a corresponding amount of area of ​​the surface of the substrate. This can be accomplished by unrolling a lithium foil of a desired thickness (e.g., 100 μm) onto the surface of the substrate and pressing the lithium foil against the substrate to create contact (e.g., continuous contact) between the two surfaces.

[0029] In some examples, a free-standing foil, or a foil on a support (e.g., a plastic support), is created and applied to a substrate. Such foils can be created by "calendering" a volume of lithium, which typically involves grinding the lithium between two precision rollers to produce a foil of the desired thickness. This grinding process can be repeated multiple times until a foil having the desired thickness and width is achieved.

[0030] A mechanical force is applied (408) to the lithium foil to press it onto the substrate. The mechanical force may be applied, for example, using a hydraulic press or similar machine. In some cases, the mechanical force is between about 1 megapascal (MPa) and about 3 MPa. In such cases, suitable values ​​of the mechanical force include about 1 MPa, about 1.5 MPa, about 2 MPa, about 2.5 MPa, or about 3 MPa. In some examples, the mechanical force is equal to or greater than the compressive stress of lithium (e.g., about 2 MPa). In some cases, the foil may be applied by hand and the pressure is applied by hand. A pressure in the range of 5 kilopascals (kPa) to 500 kPa may be sufficient (e.g., a pressure of 5 kPa to 50 kPa, 5 kPa to 15 kPa). Steps 406 and 408 of process 400 may be performed using two separate pieces of equipment. For example, in step 406, the desired contact between the two surfaces may be made by hand (e.g., in a glove box) or using a manual or automated tool or instrument (e.g., a robotic arm), while in step 408, following the contacting, a second (separate) tool or instrument (e.g., a mechanical press) may be used to apply a mechanical force to bond the lithium to the substrate. In some embodiments, steps 406 and 408 of process 400 are performed using the same tool or machine. For example, a single instrument or device may be configured to both effect contact between the lithium foil and the substrate in step 406 and apply a mechanical force to the lithium foil to effect adhesion. An example of such an instrument is a mechanical press with a robotic arm.

[0031] FIG. 4C is a flow chart of another exemplary process 405 for manufacturing a neutron generating target. The process 405 includes roughening the surface of the substrate (401). The process 405 also includes etching the surface of the substrate (402). The etching (402) is performed after the surface is roughened. The etching can be performed using an acid, such as an organic acid or an inorganic acid. Examples of organic acids that can be used in the etching process include acetic acid, pyruvic acid, citric acid, oxalic acid, succinic acid, and tartaric acid. Examples of inorganic acids that can be used include hydrochloric acid, nitric acid, hydrofluoric acid, phosphoric acid, and sulfuric acid. Etching can also be performed by heating the surface of the substrate in an atmosphere of hydrogen or other chemically reactive gases and / or by dry etching, also known as plasma etching in the semiconductor industry. In the latter process, the surface is cleaned by a chemical reaction between the etching species (such as charged ions of argon, hydrogen, oxygen, or fluorine gas, or free radicals of these gases generated in the plasma) and impurities on the surface of the substrate. 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, leaving H2O that is easily removed from the surface. 2 O, CO, CO 2 , and other volatile products.

[0032] The process (405) also includes removing contaminants (404) from the first surface of the lithium foil (e.g., cleaning or roughening the first surface) to ensure that the exposed surface is sufficiently pure lithium. Because lithium metal is very reactive, cleaning is performed in an atmosphere of an inert gas, such as a noble gas (e.g., argon). For example, plasma cleaning of the lithium foil surface can be performed at atmospheric pressure or under vacuum in a glove box. Such decontamination in process 404 may be performed by high or low temperature plasma, as described above for the target substrate, but must not exceed the melting point of lithium.

[0033] Process 405 also includes steps 406 and 408, as described above with respect to FIG. 4A. Optionally, each step 401, 402, 404, 406, and 408 of process 405 is performed using separate equipment. For example, roughening the surface (401), etching the surface (402), and decontaminating the lithium foil (404) can be performed using three different plasma torches. Contacting the lithium with the substrate (406) can be performed manually or by a robotic arm, for example, in a glove box, and applying mechanical force (408) can be performed using a separate hydraulic press. Alternatively, any two or more of steps 401, 402, 404, 406, and 408 of manufacturing process 405 are performed using the same tool or machine. For example, a single piece of equipment can be configured and adapted to perform all of steps 401, 402, 404, 406, and 408.

[0034] 4B is a cross-sectional view depicting an exemplary intermediate article formed during the contacting lithium step (406) of the manufacturing process 400 or 405 (see FIGS. 4A and 4C). In this step, contact is made between the lithium foil 110 and the surface 121 of the substrate 120 (e.g., contact is made between a first surface 410 of the lithium foil 110 and the surface 121 of the substrate 120). A mechanical force is then applied to a second surface 412 of the lithium foil 110 (the second surface 412 being opposite the first surface 410 of the lithium foil 110) in a direction C perpendicular to the surfaces 410 and 121.

[0035] The first surface 410 of the lithium foil 110 is pre-treated with Li 2 O, LiOH, Li 2 CO 3 , and Li 3 O such as N 2 , N 2 , H 2 O or CO 2(If such a step is performed, the thin layer 414 may be at least partially removed from the surface 410 during the cleaning step (404).) Pure lithium metal adheres easily to the substrate material, but contaminants on the surface of the lithium foil may prevent bonding to the lithium substrate.

[0036] A mechanical force applied in a direction C to the second surface 412 at or around the compressive stress point induces lithium shear deformation, forcing the pure lithium metal in the foil 110 to crack and release contaminating compounds (e.g., Li 2 O, LiOH, or Li 2 CO 3 ) and thereby reach and bond with surface 121 of substrate 120 to form a neutron generating target consisting of a lithium layer on the surface of substrate 120.

[0037] In some implementations, explosive bonding can be used. For example, two pieces of metal can be placed together and an explosive can be detonated behind a press plate to apply a force from the press plate. The momentary application of force from the explosion presses the two pieces together, joining the two materials.

[0038] The mechanical force in direction C to the second surface 412 can be applied using a hydraulic press and / or a press die having a push rod. The press device (e.g., die) can be specially designed for lithium pressing. The surface of the die can be prepared (e.g., coated) prior to contact with lithium to allow good separation of the die from the lithium surface after pressing is completed.

[0039] The mechanical force applied to the surface 412 of the lithium modifies the thickness of the lithium foil 110 such that the thickness of the lithium foil 110 after pressing is less (e.g., about 99%, about 95%, about 90%, or about 80%) than the thickness of the lithium foil 110 before pressing.

[0040] FIG. 5A is a flow chart of another embodiment of a process 500 for manufacturing a neutron generating target. The process creates a first layer of material on the surface of a substrate that can form an alloy with (and / or otherwise chemically or physically adhere to) lithium metal (506). This first layer can be obtained by applying such material to the surface of the substrate. The material can be applied in a vacuum chamber using conventional vapor deposition techniques. Alternatively, the material can be applied by cold plasma spraying the material onto the surface of the substrate. Such spraying can be performed in a glove box or in an air-free atmosphere, such as an inert gas (e.g., argon) atmosphere. Plasma spraying can be performed at atmospheric pressure or under vacuum, depending on the material (e.g., Al or Pd), the desired thickness of the first layer, and other needs of the process.

[0041] Suitable examples of materials for the first layer include aluminum (Al), silver (Ag), gold (Au), zinc (Zn), bismuth (Bi), and palladium (Pd), or any combination thereof. Materials that can form an alloy with lithium metal can be pure aluminum (e.g., about 99% or more, about 99.5% or more by weight aluminum), pure gold (e.g., about 99% or more, about 99.5% or more by weight gold), pure palladium (e.g., about 99% or more, about 99.5% or more by weight palladium), or an alloy of aluminum and gold that can have about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 90% or more by weight aluminum, or about 50% or more, about 60% or more, about 70% or more, about 80% or more, or about 90% or more by weight gold.

[0042] Other suitable examples of first layer materials include chemically active adhesion materials (e.g., materials capable of reacting with and / or forming chemical bonds with the lithium surface). Examples of such materials include Si, SiO 2 , SiO, Si 3 N 4 , C 3 N 4, and other silicon and carbon based materials suitable for coating a surface, or any mixture or combination thereof.

[0043] For example, SiO 2 is deposited as a first layer 518 (FIG. 5B) on the surface of the substrate 120, the lithium foil 110 is believed to chemically adhere to the first layer 518 and form layer 526 (FIG. 5C) by the following chemical reaction with the lithium metal. Li+SiO 2 =2LiO+Si

[0044] When Si is deposited as a first layer 518 (FIG. 5B) on the surface of the substrate 120, the lithium foil 110 is believed to chemically adhere to the first layer and form a layer 526 (FIG. 5C) with the lithium metal by either of the following chemical reactions ((i) or (ii)): (i) Si+4Li=4Li 4 Si (approximately 200℃ or less) (ii) 2Li + 6Si = Li 2 S 6 (When some Li atoms have a temperature of about 600°C)

[0045] It is believed that the use of a chemically active adhesive material as the first layer 518 promotes physical adhesion of the lithium foil 110 to the substrate 120 .

[0046] Yet other suitable examples of materials for the first layer include materials that can form a buffer layer (or protective layer) as the first layer 518 on the surface of the substrate 120. Such materials are believed to function as both an adhesive and a stop layer for the lithium layer 110 to prevent interdiffusion (e.g., alloying) between Li and the substrate (e.g., Cu) material. Examples of such materials include TiNSi, TiN, TiWN, Cr, Ti, Ta, TaN, Mo, V, LiF, CrLiO 2 , CrLi 2 O 4 , CrLi 2 O 2as well as Li-based materials useful as electrode materials in Li-based batteries, or any mixture or combination thereof.

[0047] In some embodiments (e.g., when the first layer 518 functions as a stop / adhesion layer), a suitable combination (e.g., layering) of materials is used. For example, the first layer may be a Cr / Ti bilayer. Lithium metal is believed to be insoluble in chromium (e.g., there is substantially no or minimal diffusion of Li into Cr), while at the same time Cr has excellent adhesion to Cu (an example material of the substrate 120). Thus, a sublayer of Cr may be deposited on the surface of a Cu substrate, followed by another sublayer of Ti on top of the Cr to form the first layer 518. The first layer of such a combination is believed to promote adhesion between the lithium layer 110 and the substrate 120, while at the same time preventing lithium metal from diffusing into the substrate (e.g., a substrate made of Cu or its alloys). Alternatively, a thin sublayer of Ta, Mo, or V (instead of Ti) may be deposited on top of the Cr sublayer.

[0048] In some embodiments, the first layer material is Pd and the amount of Pd in ​​the resulting lithium layer of the target is about 0.5% to about 1% by weight. In further embodiments, the first layer material is Al and the amount of Al in the resulting lithium layer is less than about 10% by weight. In still other embodiments, the first layer material is Au and the amount of Au in the resulting lithium layer is less than about 0.1% by weight.

[0049] The thickness of the first layer 518 may be selected depending on the particular needs of the process. For example, the thickness of the first layer may be about 1 nm to about 5 nm, about 2 nm to about 3 nm, about 10 nm to about 20 nm, about 10 nm to about 50 nm, about 10 nm to about 100 nm, about 0.01 μm to about 0.3 μm, about 0.01 μm to about 0.2 μm, about 0.05 μm to about 0.2 μm, about 0.05 μm to about 0.2 μm, about 0.01 μm to about 0.1 μm, or about 0.5 μm to about 1 μm. In some embodiments, the thickness of the first layer is about 0.01 μm, about 0.05 μm, about 0.1 μm, or about 0.2 μm. The thickness of the first layer may be selected based on the maximum amount of first layer material that does not interfere with the neutron generating function of the lithium layer. For example, the amount of the first layer material in the lithium layer after the neutron generating target is formed in step 512 is about 0.1% to about 10% by weight, about 0.1% to about 5% by weight, about 0.5% to about 2% by weight, or about 0.5% to about 1% by weight. In some embodiments, the amount of the first layer material in the lithium layer of the neutron generating target is about 0.5%, about 1%, about 2%, about 5%, or about 10% by weight.

[0050] The first layer material is preferably selected so that the neutron yield of the target is about 90%, about 80%, or about 75% or more of the neutron yield generated by a lithium target fabricated without any first layer material. It is believed that some of the metals (such as Al, Au, or Pd) that make up the first layer absorb neutrons generated by the lithium target when the target is bombarded with protons. Thus, the amount of first layer material can be carefully selected to allow efficient adhesion of the lithium foil to the surface of the substrate while allowing sufficient neutron yield to reach the tumor site in the patient.

[0051] 5A, once the first layer is applied to the surface of the substrate (508), the process 500 contacts the surface of the lithium foil and the first layer (e.g., the surface of the first layer) on the substrate (510). The contacting can be continuous (e.g., creating unbroken and uninterrupted contact between the first surface of the lithium foil and the surface of the first layer, as described above). The contacting step may be performed in a manner similar to step 406 in process 400, as described herein.

[0052] 5A, as a final step in process 500, a mechanical force may be applied (512) to the lithium foil to press it into the first layer on the substrate. This pressing may be done in a manner similar to step 408 in process 400 or 405.

[0053] 5B is a cross-sectional view of an exemplary intermediate device formed while combining lithium foil and a substrate created in manufacturing a neutron generating target. Contact (e.g., continuous contact) is formed between a first surface 516 of the lithium foil 110 and a surface 520 of the first layer 518. During application of a mechanical force (512, FIG. 5A), it is believed that the material of the first layer 518 diffuses (or dissolves) into the lithium foil 110 to form an alloy such that the lithium foil 110 adheres to the substrate 120 to obtain a neutron generating target containing a lithium layer on the surface of the substrate. In some embodiments, the diffusion coefficient of the first layer material (e.g., Al, Au, or Pd) for lithium is about 1×10 -10~ Approximately 1×10 -9 cm 2 / s.

[0054] A cross-sectional view of an example of the resulting target is shown diagrammatically in Figure 5C. Referring to Figure 5C, lithium layer 110 is bonded to substrate 120 by an alloy 526 of the first layer material and lithium. As noted above, the percentage of the first layer material (such as Al) in the combined amount of lithium and first layer material in layers 110 and 526 typically ranges from about 0.1% to about 10% by weight. This amount is selected based on the type of first layer material such that the neutron yield is not reduced by more than about 25% compared to the neutron yield obtained from a target fabricated without alloy 526.

[0055] FIG. 5D is a flow chart of another exemplary process 501 for manufacturing a neutron generating target. The process includes roughening the surface of a substrate (502), etching the surface of the substrate (504), and removing contaminants from a first surface of a lithium foil (e.g., cleaning or roughening the first surface) to expose lithium (506). Steps 502, 504, and 506 of process 501 may be performed in a manner similar to corresponding steps 401, 402, and 404, respectively, of process 405 shown in FIG. 4C. Referring to FIG. 5D, process 501 also includes steps 508, 510, and 512, which may be performed in a manner similar to steps 508, 510, and 512 described for process 500 described with reference to FIG. 5A. Optionally, process 501 also includes heating the neutron generating target produced during step 512 (514). The heating can be to a temperature below the melting point of lithium (e.g., a temperature below 180°C). Heating can have various beneficial effects on lithium adhesion to the first layer. For example, heating can increase diffusion between the first layer and the lithium foil. Alternatively, or in addition, heating can induce and / or increase alloying between the material of the first layer and the lithium foil. The target can be heated to about 80°C or more, about 100°C or more, about 110°C or more, about 120°C or more, about 130°C or more, about 140°C or more, about 150°C or more, such as about 160°C. The target can be heated for a time sufficient to induce and / or increase the diffusion process and / or to induce and / or increase alloying. For example, the target can be heated for about 1 second or more, about 10 seconds or more, about 30 seconds or more, about 1 minute or more, about 5 minutes or more, about 10 minutes or more, or about 30 minutes or more, such as up to 1 hour. The target may be heated during application of the mechanical force (512).

[0056] FIG. 6A is a flow chart of an exemplary process 600 for manufacturing a neutron generating target. The process produces a first layer of lithium on a surface of a substrate (608). This first layer of lithium may be obtained by applying lithium to the surface of the substrate. The application of lithium to the substrate surface may be performed in a manner similar to that described for the application of the first layer in step 508 of the process 500 of FIG. 5A. The thickness of the first lithium layer in step 608 may be selected depending on the specific needs of the process. For example, the thickness of the first layer of lithium may be about 0.01 μm to about 0.3 μm, about 0.01 μm to about 0.2 μm, about 0.05 μm to about 0.2 μm, about 0.05 μm to about 0.2 μm, or about 0.01 μm to about 0.1 μm. In some embodiments, the thickness of the first layer of lithium in step 608 is about 0.01 μm, about 0.05 μm, about 0.1 μm, or about 0.2 μm. The thickness of the first layer of lithium prepared in step 608 may be selected to allow efficient adhesion of the lithium foil to the surface of the substrate.

[0057] Once the first layer is applied to the surface of the substrate, the process creates contact (e.g., continuous contact) between one surface of the lithium foil and the first layer of lithium on the substrate (e.g., a surface of the first layer of lithium) (610). This pressing can be performed in a manner similar to that described for step 406 of process 400 or step 510 of step 500.

[0058] A mechanical force may then be applied (612) to the lithium foil to press it into the first layer on the substrate. This step may be performed in a manner similar to step 408 in process 400 or step 512 in process 500.

[0059] 6D is a flow chart of another exemplary process 601 for manufacturing a neutron generating target. Process 601 includes roughening a surface of a substrate (602), etching the surface of the substrate (604), and removing contaminants from a first surface of a lithium foil (e.g., by cleaning or roughening the first surface) to expose lithium (606). These steps may be performed in a manner similar to corresponding steps 401, 402, and 404, respectively, of process 400, or steps 502, 504, and 506, respectively, of process 500.

[0060] Process 601 also includes steps 608, 610, and 612, which can be performed in a manner similar to steps 508, 510, and 512, respectively, described for processes 500 and 501 (with reference to FIGS. 5A and 5D). In some embodiments, process 601 also includes a step that includes heating the neutron generating target (614) during the step of applying a mechanical force (612) to promote diffusion between the lithium of the first layer and the lithium foil. This step can be performed in a manner and with parameters similar to those of step 514 of process 500 described above.

[0061] 6B is a cross-sectional view of an exemplary intermediate device (combination of lithium foil and substrate for producing a neutron generating target) formed during step 610 of process 600 of FIG. 6A. In this step, contact is formed between a first surface 620 of the lithium foil 110 and a surface 618 of the first layer 616. During application of a mechanical force (612) to a second surface 622 of the lithium foil 110, the lithium of the first layer 616 is believed to diffuse (or dissolve) into the lithium foil 110 to form a lithium layer, such that the lithium foil 110 adheres to the surface 121 of the substrate 120 to obtain a neutron generating target containing a lithium layer on the surface of the substrate.

[0062] A cross-sectional view of the resulting exemplary target is shown diagrammatically in FIG. 6C. The lithium layer 624, consisting of lithium forming the first layer 618 and the lithium foil 110, adheres to the surface 121 of the substrate 120 for initial adhesion and bonding of the first layer of lithium during deposition of this first layer of lithium on the substrate. The process 601 may also include a step including heating (614) the neutron generating target while applying a mechanical force (612) to enhance adhesion (e.g., by enhancing diffusion) between the lithium of the first layer and the lithium foil to obtain a continuous layer of lithium on the surface of the substrate. As described above, the heating may be to a temperature below the melting point of lithium. This step may be performed using methods and parameters similar to those of step 514 of the process 500 described above.

[0063] In some examples, the substrate and / or lithium foil (e.g., with or without the first layer) can be vibrated (e.g., ultrasonically vibrated) while the foil is pressed against the substrate. Vibrating the substrate and / or lithium foil can enhance adhesion between the substrate and the foil, e.g., by creating friction between the surfaces. The vibrating can be performed while heating the target. In some examples, the vibration has a frequency in the range of 1 kHz to 100 kHz (e.g., in the range of 5 kHz to 25 kHz).

[0064] While the above method involves roughening and etching the surface of the substrate to which the lithium layer (and optionally the first layer of another material) is adhered, alternative or additional treatments of the substrate surface can be performed. For example, in some cases, the substrate surface can be cleaned by heating the surface. For example, sufficient heating of a copper surface can clean the copper surface by reducing the surface oxide. Heating a copper substrate to about 300° C. or higher while maintaining the substrate in an inert atmosphere (e.g., argon) can reduce the copper oxide to copper at the substrate surface. Generally, any atmosphere without an element to remove (e.g., oxygen in the form of copper oxide) can function as a reducing atmosphere. In addition to argon, other possible gases suitable for reducing surface oxides are neon, helium, krypton, xenon, and N. 2 In some cases, CO2 may be the preferred gas, with oxygen being more strongly bound to the oxygen in, for example, copper oxide. A forming gas, such as a mixture of an inert gas and hydrogen, may be used. At low pressures, only hydrogen may be used.

[0065] In general, the thermal cleaning can be performed before, after, or instead of the roughening and / or etching steps. In addition to the embodiments in the appended claims and described above, each of the embodiments in the following numbered paragraphs are also innovative.

[0066] Paragraph 1. A method for manufacturing a neutron generating target, the method comprising: (i) contacting a first surface of a lithium foil with a surface of a substrate; and (ii) applying a mechanical force to a second surface of the lithium foil opposite the first surface of the lithium foil, thereby adhering the first surface of the lithium foil to the surface of the substrate to obtain a neutron generating target comprising a lithium layer on the surface of the substrate.

[0067] Paragraph 2. The method of Paragraph 1, wherein the contacting is continuous.

[0068] Paragraph 3. The method of Paragraph 1 or 2, comprising roughening a surface of the substrate prior to contacting the first surface of the lithium foil with the surface of the substrate.

[0069] Paragraph 4. The method of any one of Paragraphs 1-3, comprising etching a surface of the substrate.

[0070] Paragraph 5. The method of Paragraph 4, wherein etching the surface of the substrate is performed using an acid.

[0071] Paragraph 6. The method of Paragraph 4, wherein etching the surface of the substrate is effected by heating the substrate in the presence of hydrogen.

[0072] Paragraph 7. The method of any one of Paragraphs 1-6, comprising removing contaminants from the first surface of the lithium foil to expose the lithium.

[0073] Paragraph 8. The lithium foil comprises about 92 weight percent (wt%) to about 98 wt% Li 7 8. The method of any one of paragraphs 1 to 7, including an isotope.

[0074] Paragraph 9. The method of any one of Paragraphs 1 to 8, wherein the lithium foil has a thickness of about 15 micrometers (μm) to about 180 μm.

[0075] Paragraph 10. The method of paragraph 9, wherein the lithium foil has a thickness of about 90 μm to about 100 μm.

[0076] Paragraph 11. The thermal conductivity of the substrate is about 300 W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1 The method of any one of paragraphs 1 to 10.

[0077] Paragraph 12. The method of any one of Paragraphs 1 to 11, wherein the substrate consists essentially of copper.

[0078] Paragraph 13. The method of any one of Paragraphs 1 to 11, wherein the substrate comprises diamond.

[0079] Paragraph 14. The method of any one of Paragraphs 1 to 11, wherein the substrate comprises a copper diamond powder composite.

[0080] Paragraph 15. The method of any one of Paragraphs 1 to 14, wherein the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium foil.

[0081] Paragraph 16. The method of any one of Paragraphs 1 to 15, wherein the mechanical force is from about 1 megapascal (MPa) to about 3 MPa.

[0082] Paragraph 17. The method of Paragraph 16, wherein the mechanical force is about 2 MPa.

[0083] Paragraph 18. A method of manufacturing a neutron generating target, the method comprising: (i) applying a material to a surface of a substrate to obtain a first layer on the surface of the substrate, the material being capable of forming an alloy with or otherwise chemically or physically adhering to lithium metal; (ii) contacting the first layer with a first surface of a lithium foil; and (iii) applying a mechanical force to a second surface of the lithium foil opposite the first surface of the lithium foil, thereby adhering the first layer to the lithium foil and the substrate to obtain a neutron generating target comprising a lithium layer on the surface of the substrate.

[0084] Paragraph 19. The method of Paragraph 18, wherein the contacting is continuous.

[0085] Paragraph 20. The method of Paragraph 18, further comprising heating the neutron generating target while applying a mechanical force to promote diffusion and / or induce alloying between the material of the first layer and the lithium foil, and / or vibrating the neutron generating target while applying a mechanical force to create friction between the first layer and the first surface of the lithium foil.

[0086] Paragraph 21. The method of Paragraph 18, wherein the heating is carried out at a temperature of about 180 degrees Celsius (°C) or less.

[0087] Paragraph 22. The method of Paragraph 19, wherein the heating is carried out at a temperature of about 100°C to about 120°C.

[0088] Paragraph 23. The method of any one of Paragraphs 18 to 22, comprising roughening the surface of the substrate prior to applying the material to the surface of the substrate.

[0089] Paragraph 24. The method of Paragraph 23, wherein roughening the surface of the substrate comprises etching the surface of the substrate.

[0090] Paragraph 25. The method of Paragraph 24, wherein etching the surface of the substrate is performed using an acid.

[0091] Paragraph 26. The method of Paragraph 24, wherein etching the surface of the substrate is effected by heating the substrate in the presence of hydrogen.

[0092] Paragraph 27. The method of any one of Paragraphs 18-26, comprising removing contaminants from the first surface of the lithium foil to expose the lithium.

[0093] Paragraph 28. The lithium foil comprises about 92 weight percent (wt%) to about 98 wt% Li 7 28. The method of any one of paragraphs 18 to 27, including an isotope.

[0094] Paragraph 29. The method of any one of Paragraphs 18 to 27, wherein the lithium foil has a thickness of about 15 micrometers (μm) to about 180 μm.

[0095] Paragraph 30. The method of Paragraph 29, wherein the lithium foil has a thickness of about 90 μm to about 100 μm.

[0096] Paragraph 31. The thermal conductivity of the substrate is about 300 W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1 Any one of the methods of paragraphs 18 to 30.

[0097] Paragraph 32. The method of any one of Paragraphs 18 to 31, wherein the substrate consists essentially of copper.

[0098] Paragraph 33. The method of any one of Paragraphs 18 to 31, wherein the substrate comprises diamond.

[0099] Paragraph 34. The method of any one of Paragraphs 18 to 31, wherein the substrate comprises a copper diamond powder composite.

[0100] Paragraph 35. The method of any one of Paragraphs 18 to 34, wherein the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium foil.

[0101] Paragraph 36. The method of any one of Paragraphs 18 to 35, wherein the mechanical force is from about 1 megapascal (MPa) to about 3 MPa.

[0102] Paragraph 37. The method of Paragraph 36, wherein the mechanical force is about 2 MPa.

[0103] Paragraph 38. The material is essentially Al, Ag, Au, Zn, Bi, Pd, Si, SiO 2 , SiO, Si 3 N 4 , C 3 N 4, TiNSi, TiN, Cr, Ti, Ta, Mo, V, LiF, CrLiO 2 , CrLi 2 O 4 , or CrLi 2 O 2 or any combination thereof.

[0104] Paragraph 39. The method of Paragraph 38, wherein the material consists essentially of aluminum.

[0105] Paragraph 40. The method of any one of Paragraphs 18 to 39, wherein applying the material comprises performing vapor deposition or plasma deposition of the material on the surface of the substrate.

[0106] Paragraph 41. The method of Paragraph 40, wherein the vapor deposition or plasma deposition is carried out at atmospheric pressure.

[0107] Paragraph 42. The method of Paragraph 40, wherein the vapor deposition or plasma deposition is carried out under vacuum.

[0108] Paragraph 43. The method of any one of Paragraphs 18 to 42, wherein the first layer has a thickness of about 0.002 μm to about 1 μm.

[0109] Paragraph 44. The method of Paragraph 43, wherein the first layer has a thickness of about 0.1 μm.

[0110] Paragraph 45. The method of any one of Paragraphs 18 to 44, wherein the material is capable of forming an alloy in the lithium layer and the amount of the material in the lithium layer of the neutron generating target is from about 0.5% to about 10% by weight.

[0111] Paragraph 46. The method of any one of paragraphs 18 to 45, wherein the neutron generating target is capable of producing a neutron yield that is at least 90% of the neutron yield produced by a target prepared without a material capable of forming an alloy with lithium metal.

[0112] Paragraph 47. A combination of lithium foil and a substrate for producing a neutron generating target, the combination comprising: a substrate; a first layer of a material capable of forming an alloy with, or otherwise chemically or physically adhering to, lithium metal positioned on the substrate; and lithium foil, the first surface of the lithium foil being in contact with the first layer.

[0113] Paragraph 48. The combination of Paragraph 47, wherein the contact between the lithium foil and the first layer is continuous.

[0114] Paragraph 49. The lithium foil comprises about 92 weight percent (wt%) to about 98 wt% Li 7 Combinations of paragraph 48, including isotopes.

[0115] Paragraph 50. The combination of any one of Paragraphs 47 to 49, wherein the lithium foil has a thickness of about 15 μm to about 180 μm.

[0116] Paragraph 51. The combination of Paragraph 50, wherein the lithium foil has a thickness of about 90 μm to about 100 μm.

[0117] Paragraph 52. The thermal conductivity of the substrate is about 300 W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1 Any one of paragraphs 47 to 51 in any combination.

[0118] Paragraph 53. The combination of any one of Paragraphs 47 to 52, wherein the substrate consists essentially of copper.

[0119] Paragraph 54. The combination of any one of Paragraphs 47 to 52, wherein the substrate comprises diamond.

[0120] Paragraph 55. The combination of any one of Paragraphs 47 to 52, wherein the substrate comprises a copper diamond powder composite.

[0121] Paragraph 56. The combination of any one of Paragraphs 47 to 55, wherein the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium foil.

[0122] Paragraph 57. The material is essentially Al, Ag, Au, Zn, Bi, Pd, Si, SiO 2 , SiO, Si 3 N 4 , C 3 N 4 , TiNSi, TiN, TiWN, Cr, Ti, Ta, TaN, Mo, V, LiF, CrLiO 2 , CrLi 2 O 4 , or CrLi 2 O 2 or any combination of any one of paragraphs 47 to 56.

[0123] Paragraph 58. A combination as claimed in paragraph 57, in which the material consists essentially of aluminium.

[0124] Paragraph 59. The combination of any one of Paragraphs 47 to 58, wherein the first layer has a thickness of from about 0.002 μm to about 1 μm.

[0125] Paragraph 60. The combination of Paragraph 59, wherein the thickness of the first layer is about 0.1 μm.

[0126] Paragraph 61. The combination of any one of Paragraphs 47 to 60, wherein the amount of material capable of forming an alloy with lithium metal in the combined amount of the first layer and the lithium foil is from about 0.1% to about 10% by weight.

[0127] Paragraph 62. The combination of Paragraph 61, wherein the amount is from about 0.5% to about 1% by weight.

[0128] Paragraph 63. A method of manufacturing a neutron generating target for boron neutron capture therapy, the method comprising: (i) applying lithium to a surface of a substrate to obtain a first layer of lithium on the surface of the substrate; (ii) contacting the first layer of lithium on the surface of the substrate and a first surface of a lithium foil with each other; and (iii) applying a mechanical force to a second surface of the lithium foil opposite the first surface of the lithium foil sufficient to cause diffusion of lithium from the first layer into the lithium foil, adhering the lithium foil to the substrate to obtain a neutron generating target comprising a lithium layer on the surface of the substrate.

[0129] Paragraph 64. The method of Paragraph 63, wherein the contact between the first layer of lithium and the first surface of the lithium foil is continuous.

[0130] Paragraph 65. The method of Paragraph 63, further comprising heating the neutron generating target during application of the mechanical force to induce or promote diffusion between the material of the first layer and the lithium foil, and / or vibrating the neutron generating target during application of the mechanical force to create friction between the first layer of lithium and the first surface of the lithium foil.

[0131] Paragraph 66. The method of Paragraph 65, wherein the heating comprises a temperature of about 180 degrees Celsius (°C) or less.

[0132] Paragraph 67. The method of Paragraph 66, wherein the heating comprises a temperature of about 100°C to about 120°C.

[0133] Paragraph 68. The method of any one of Paragraphs 63 to 67, comprising roughening the surface of the substrate prior to applying lithium to the surface of the substrate.

[0134] Paragraph 69. The method of Paragraph 68, comprising etching a surface of the substrate.

[0135] Paragraph 70. The method of Paragraph 69, wherein etching the substrate surface is performed using an acid.

[0136] Paragraph 71. The method of Paragraph 69, wherein etching the surface of the substrate is effected by heating the substrate in the presence of hydrogen.

[0137] Paragraph 72. The method of any one of Paragraphs 63 to 71, comprising removing contaminants from the first surface of the lithium foil to expose the lithium.

[0138] Paragraph 73. The lithium foil comprises about 92 weight percent (wt%) to about 98 wt% Li 7 73. The method of any one of paragraphs 63 to 72, including an isotope.

[0139] Paragraph 74. The method of any one of Paragraphs 63 to 73, wherein the lithium foil has a thickness of about 15 micrometers (μm) to about 180 μm.

[0140] Paragraph 75. The thermal conductivity of the substrate is about 300 W x m -1 ×K -1 ~Approx. 1000W×m -1 ×K -1 Any one of paragraphs 63 to 74.

[0141] Paragraph 76. The method of any one of Paragraphs 63 to 75, wherein the substrate comprises copper.

[0142] Paragraph 77. The method of any one of Paragraphs 63 to 75, wherein the substrate comprises diamond.

[0143] Paragraph 78. The method of any one of Paragraphs 63 to 75, wherein the substrate comprises a copper diamond powder composite.

[0144] Paragraph 79. The method of any one of Paragraphs 63 to 78, wherein the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium foil.

[0145] Paragraph 80. The method of any one of Paragraphs 63 to 79, wherein the mechanical force is from about 1 megapascal (MPa) to about 3 MPa.

[0146] Paragraph 81. The method of Paragraph 80, wherein the mechanical force is about 2 MPa.

[0147] Paragraph 82. The method of any one of Paragraphs 63 to 81, wherein applying lithium to the surface of the substrate to obtain a first layer of lithium on the surface of the substrate comprises vapor deposition or plasma deposition of lithium on the surface of the substrate.

[0148] Paragraph 83. The method of Paragraph 82, wherein the vapour deposition or plasma deposition is carried out at atmospheric pressure.

[0149] Paragraph 84. The method of Paragraph 82, wherein the vapor deposition or plasma deposition is carried out under vacuum.

[0150] Paragraph 85. The method of any one of Paragraphs 63 to 84, wherein the first layer has a thickness of about 0.01 μm to about 0.3 μm.

[0151] Paragraph 86. The method of Paragraph 85, wherein the first layer has a thickness of about 0.1 μm.

[0152] Paragraph 87. The method of Paragraph 1 or 2, wherein the first surface of the lithium foil is in contact with the surface of the substrate such that 99% or more of the macroscopic area of ​​the first surface of the lithium foil is in contact with a corresponding amount of area of ​​the surface of the substrate.

[0153] Paragraph 88. The method of Paragraphs 18 or 19, wherein the first surface of the lithium foil is in contact with the first layer such that 99% or more of the macroscopic area of ​​the first surface of the lithium foil is in contact with a corresponding amount of area of ​​the surface of the substrate.

[0154] Paragraph 89. A combination of Paragraphs 47 or 48, wherein 99% or more of the macroscopic area of ​​the first surface of the lithium foil is in contact with a corresponding amount of area of ​​the surface of the substrate.

[0155] Paragraph 90. The method of Paragraph 63 or 64, wherein the first surface of the lithium foil is in contact with the first layer of lithium such that 99% or more of the macroscopic area of ​​the first surface of the lithium foil is in contact with the first layer of lithium.

[0156] Other embodiments Although 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 present application, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

[0157] 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. If a particular feature, element, component, function, or step is described with respect to only one embodiment, it should be understood that that feature, element, component, function, or step can be used with all other embodiments described herein, unless otherwise specified.

Claims

1. A method for manufacturing a neutron generation target, (i) bringing the first surface of the lithium foil into contact with the surface of the substrate, (ii) A method comprising applying a mechanical force to a second surface of the lithium foil opposite to the first surface of the lithium foil, thereby bonding the first surface of the lithium foil to the surface of the substrate, thereby obtaining the neutron generating target comprising a lithium layer on the surface of the substrate.

2. The method according to claim 1, wherein the contact is continuous.

3. The method according to claim 1, comprising one or more of the following steps before bringing the first surface of the lithium foil into contact with the surface of the substrate: roughening the surface of the substrate or etching the surface of the substrate.

4. The method according to claim 3, wherein etching of the surface of the substrate is performed using an acid.

5. The method according to claim 3, wherein etching of the surface of the substrate is performed by heating the substrate in the presence of hydrogen.

6. The method according to claim 1, comprising removing contaminants from the first surface of the lithium foil to expose lithium.

7. The lithium foil contains approximately 92% by weight (weight) to approximately 98% by weight Li ７ The method according to claim 1, comprising an isotope.

8. The method according to claim 1, wherein the thickness of the lithium foil is approximately 15 micrometers (μm) to approximately 180 μm.

9. The method according to claim 8, wherein the thickness of the lithium foil is approximately 90 μm to approximately 100 μm.

10. The thermal conductivity of the aforementioned substrate is approximately 300 W × m －１ ×K －１ ~Approx. 1000W×m －１ ×K －１ The method according to claim 1.

11. The method according to claim 1, wherein the substrate is essentially made of copper.

12. The method according to claim 1, wherein the substrate comprises diamond or a copper-diamond composite.

13. The method according to claim 1, wherein the substrate is about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times thicker than the lithium foil.

14. The method according to claim 1, wherein the mechanical force is approximately 1 megapascal (MPa) to approximately 3 MPa.

15. The method according to claim 14, wherein the mechanical force is approximately 2 MPa.

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