Target holder, system and method

Abstract

[0245] A target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator system comprises a holder body comprising: a target chamber that is at least partly delimited by a chamber base; an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet. The target holder further comprises a protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated. The aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture. The protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

Description

TARGET HOLDER, SYSTEM AND METHODCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of U.S. Provisional Application Serial No. 63 / 719,154, filed 12 November 2024, the entire contents of which is hereby incorporated herein by reference.FIELD OF THE DISCLOSURE

[0002] This disclosure relates to a target holder for holding a target material to be irradiated by a particle accelerator, a system, and methods of forming an isotope solution from an irradiated material.BACKGROUND

[0003] Radioisotopes are used in a number of fields, including medicine where radioisotopes (or “radiopharmaceuticals”) are used for diagnosis, treatment and research. Use of radioisotopes in medicine has provided major advances in diagnosing and treating cancer, brain diseases and cardiovascular diseases. However, there are significant challenges in producing and obtaining radioactive isotopes, which is limiting their use and availability. Often, radioisotopes are generated by directing a charged particle beam from a particle accelerator, such as a cyclotron, against a target material. For example, proton beams (including H- or D- charged particles) can be output from a cyclotron and directed to a target material to irradiate the target materials and produce radioactive isotopes. The complexity of particle accelerator systems and the associated cost and expertise required to operate these means that there are only a limited number of facilities producing radioisotopes. Where there are sites producing radioisotopes, there are competing demands for “beam time”. Typically, production of radiopharmaceuticals have a low-yield, meaning that the sites may forgo production of radiopharmaceuticals if there is demand for higher-yield radioisotopes or more profitable uses of the particle accelerator systems. Even where facilities are available, there are also significant logistical challenges in transporting radioisotopes from these facilities to the sites they are to be used. The halflife of radiopharmaceuticals is typically very short, in many cases with up to 90% of the radioisotope decaying during transport. Stringent safety requirements also limit distribution. These problems create an expensive and inconsistent supply, the latter of which is particularly problematic when scheduling treatments or investigations for patients.

[0004] To counter these problems, some medical facilities have started operating their own particle accelerator systems, such as cyclotrons, for creating radiopharmaceuticals. However, even small systems are complex and require significant investment and infrastructure. Generation of radioisotopes in situ also requires stringent safety measures, particularly relating to the recovery and handling of radioisotopes post-production and avoiding leakage of gases contaminated with radioisotopes (e.g. oxygen- 15 and nitrogen- 13) from the system.

[0005] Many of these local particle accelerator systems use liquid target materials, but these can suffer from the aforementioned low yields. Solid targets are known but are relatively infrequently used, at least in part due to difficulties associated with handling of solid targets after irradiation. For example,operators are required to process the solid targets after irradiation to recover the isotopes, leading to radiation exposure risks and particle accelerator downtime.

[0006] Accordingly, there is a need to improve the availability of radioisotopes, and particularly radiopharmaceuticals, by providing improved apparatus’ that can improve the efficiency of conventional particle accelerators and methods of using them.SUMMARY OF THE DISCLOSURE

[0007] In a first aspect, a target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator system is provided, the target holder comprising a holder body comprising: a target chamber that is at least partly delimited by a chamber base; an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet. The target holder further comprises a protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated. The aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture. The protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0008] In a second aspect, a system for holding a target material for irradiation by a charged particle beam of a particle accelerator is provided, the system comprising: a target holder comprising a holder body, the holder body comprising: a target chamber that is at least partly delimited by a chamber base; a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber; an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; and an inlet conduit in fluid communication with the target chamber for providing a solution to the target chamber, the inlet conduit extending from an entry port provided in and in fluid communication with the target chamber to an inlet port. The system also comprises a pump assembly fluidly connected to the target chamber via the outlet conduit and the inlet conduit, wherein the pump assembly is configured to: provide an etchant solution to the target chamber via the inlet conduit to etch at least a part of an irradiated material comprising radioisotopes to dissolve the radioisotopes in the etchant solution and thereby form an isotope solution; and remove the isotope solution from the target chamber via the exit port of the outlet conduit.

[0009] In a third aspect, there is provided a method of forming an isotope solution from an irradiated material comprising radioisotopes provided in a target holder. The target holder comprises a holder body comprising a target chamber that is at least partly delimited by a chamber base; a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber; an aperture in the holder body providing an inlet to the target chamber, wherein the apertureand support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port. The method comprises: providing an etchant solution to the target chamber to etch at least a part of an irradiated material comprising radioisotopes to dissolve the radioisotopes in the etchant solution and form an isotope solution; and removing the isotope solution from the target chamber via the exit port of the outlet conduit.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The present disclosure will now be described in more detail with reference to the accompanying drawings, which are not intended to be limiting:

[0011] Fig. 1 A provides a perspective view of a target holder according to an embodiment;

[0012] Fig. IB provides a cross-sectional view of the target holder of Fig. 1A through plane X;

[0013] Fig. 1C provides a cross-sectional view of another embodiment of a target holder of Fig. 1A through plane X;

[0014] Fig. 2 provides a perspective view of an embodiment of a separator member;

[0015] Fig. 3A provides a perspective view of a target holder, separator member and a connector assembly, the target holder and connector body being in an uncoupled configuration in Fig. 3A with the separator member received within the target holder;

[0016] Fig. 3B provides a cross-section through the target holder, separator member and connector assembly when the target holder, separator member and connector body are in a coupled configuration;

[0017] Fig. 3C provides a magnified view of a part of the connector assembly that allows for coupling with the target holder;

[0018] Fig. 3D provides a cross-section view of the target holder, separator member, target holder gasket and connector seal through a plane perpendicular to plane X;

[0019] Fig. 4 provides a schematic side view of an apparatus according to an embodiment;

[0020] Fig. 5 provides a schematic front perspective view of the apparatus of Fig. 4, with the target holder rack rotated out of alignment with the track;

[0021] Fig. 6 provides a schematic side view of a part of the apparatus of Fig. 4;

[0022] Fig. 7 provides a perspective view of an embodiment of a clamp member;

[0023] Fig. 8 provides a bottom view of the clamp member of Fig. 7;

[0024] Fig. 9 provides a front view of the clamp member of Fig. 7;

[0025] Fig. 10 provides a schematic perspective view of the internal structure of the clamp member, where the main body is transparent and drawn in outline;

[0026] Fig. 11 provides a schematic perspective underside view of a part of the apparatus of Fig. 4;

[0027] Fig. 12 provides a schematic depiction of a pump assembly according to an embodiment;

[0028] Fig. 13 provides a schematic depiction of a system comprising the apparatus; and

[0029] Fig. 14 provides a schematic depiction of an alignment / configuration of the clamp member, target holder and interface element.DETAILED DESCRIPTION

[0030] There is a need to reduce the complexity and risks associated with use of particle accelerator systems for creating radioisotopes so that radiopharmaceuticals can be more readily and efficiently produced. There is also a need to improve the yields of radioisotopes provided by these systems.

[0031] In a first aspect, a target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator system is provided, the target holder comprising a holder body comprising: a target chamber that is at least partly delimited by a chamber base; an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet. The target holder further comprises a protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated. The aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture. The protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0032] Such a target holder can advantageously provide a reusable holder or cartridge for holding a target material during irradiation and further for processing the irradiated material after irradiation. The structure of the target holder can improve yields by enabling use of solid targets, reduce downtime between irradiations, reduce the complexity of operation of the systems and reduce the risk associated with operation, for example by reducing the need for operator interaction with the system after irradiation. Together, these can improve efficiency, throughput and availability of these systems.

[0033] Recovery of radioisotopes after generation can be particularly difficult. Handling of radioisotopes requires stringent safety procedures and carries risks but this needs to be balanced with the need to quickly recover the radioisotopes, both to free up the particle accelerators for further use and to avoid unnecessary decay of the radioisotopes. The target holder allows the target material (such as a solid target) to be irradiated within the holder and for radioisotopes to subsequently be recovered from the holder in situ, reducing risk and operator intervention. Specifically, the protective layer and the provision of the outlet conduit means that an etchant solution can be used to etch radioactive isotopes from the support surface to form an isotope solution containing the radioactive isotopes without requiring interaction of a technician with the solid irradiated material, significantly reducing the complexity of the recovery process and significantly reducing the risk of exposure to radioactive material. The subsequent recovery of an isotope solution in this way also allows for more straightforward handling. It can, for example, be transferred via a conduit to a different location in a site where it can be processed further, without disrupting further irradiations in the location of thesystem. This also allows the holder to remain in the system, where it can be washed and reused (via the conduit), which can increase throughput.

[0034] The holder body and an additional protective layer can also provide improved performance. The protective layers disclosed herein have excellent corrosion resistance and are substantially inert to etchants that can be used to recover radioisotopes. The protective layers may also be inert to the particle beam under normal operating conditions and provide an excellent support surface for a target material. Accordingly, these provide an improved resistance to damage and a very low chance of contamination during recovery, enabling repeated reuse of the holder. However, one other significant consideration in producing radioisotopes is management of the heat caused by irradiation, which in turn can cause damage to the apparatus and form hot spots on a target material. By providing a protective layer, rather than forming the entire body from the material of the protective layer, this can allow for the benefits of the protective layer to be realised at the surface, while enabling the holder body to be formed of materials that have other beneficial properties, such as a higher heat conductivity or which allow for easier manufacture of the target chamber and the outlet conduit. In this way, the holder body or parts thereof (e.g. the chamber wall) can be manufactured from a material which provides efficient cooling without sacrificing the robustness of the holder at the surface. For example, copper is an excellent choice of material for heat conductivity but can react under certain corrosive conditions (such as using oxidising acids such as nitric acid to etch), but coating in one of the claimed protective layers or coatings can avoid these drawbacks while providing the high heat conductivity.

[0035] As set out above, the holder body comprises an outlet conduit in fluid communication with the target chamber so that a solution containing radioisotopes can be recovered from the target chamber. The outlet conduit may extend from an exit port provided in, and in fluid communication with, the target chamber to an etchant outlet. In some cases, the outlet conduit may also serve the purpose of providing fluids, such as etchant, to the target chamber and removing it therefrom.

[0036] In a second aspect, a system for holding a target material for irradiation by a charged particle beam of a particle accelerator is provided, the system comprising: a target holder comprising a holder body, the holder body comprising: a target chamber that is at least partly delimited by a chamber base; a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber; an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; and an inlet conduit in fluid communication with the target chamber for providing a solution to the target chamber, the inlet conduit extending from an entry port provided in and in fluid communication with the target chamber to an inlet port. The system also comprises a pump assembly fluidly connected to the target chamber via the outlet conduit and the inlet conduit, wherein the pump assembly is configured to: provide an etchant solution to the target chamber via the inlet conduit to etch at least a part of an irradiated material comprisingradioisotopes to dissolve the radioisotopes in the etchant solution and thereby form an isotope solution; and remove the isotope solution from the target chamber via the exit port of the outlet conduit.

[0037] As with the target holder of the first aspect, the system provides an improved way of producing and recovering radioisotopes. Through the use of the target holder and connected pump assembly, the system can advantageously reduce the downtime of isotope production systems, reduce the complexity of operation of the systems and reduce the risk associated with operation, for example by reducing the need for operator interaction with the system after irradiation. This is because this permits automated and machine-operated recovery of radioisotopes after their formation.Protective layer

[0038] The protective layer provides an etchant-resistance (i.e. acid or alkali-resistance) coating over the chamber base in the first aspect, and may also be present in the further aspects (such as the target holder of the second and third aspects). The protective layer may cover all of the internal surfaces of the target chamber. For example, the target chamber may comprise chamber sidewalls extending from the chamber base and further delimiting the target chamber, and the protective layer may also be provided over the chamber sidewalls.

[0039] The protective layer may extend at least partially into the outlet conduit to cover the internal surface(s) of the outlet conduit at the exit port, and in some cases may extend along the entirety of the outlet conduit. Where there are other ports and conduits fluidly connected to the target chamber, the protective layer may extend into each of the ports and conduits fluidly connected to the target chamber to cover the internal surfaces of the respective ports and conduits. Alternatively, this may be limited to those conduits through which etchant will pass.

[0040] The protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof. For example Ag, Au, Pt, Ta, W or Nb or combinations thereof, for example, Au, Ta or Pt. The metal or metal oxides may be present in an amount of at least 50 mol%, such as at least 75 mol%, at least 95 mol%, at least 99 mol%, or at least 99.9 mol%. The protective layer may be a metal layer (e.g. a metal alloy layer) or metal oxide layer comprising or consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof, for example Ag, Au, Pt, Ta, W or Nb or combinations thereof, for example, Au, Ta or Pt. Gold (Au) is advantageous because it has the characteristics discussed above, but also is compatible with materials that would typically be used to form the holder body, such as copper. Platinum (Pt) is highly corrosion-resistant and is resistant to irradiation, so provides a useful protective layer. Similarly, titanium (Ti) is strong and has good corrosion resistance.

[0041] By etchant-resistant, it is meant that the protective layer can withstand the presence of an alkali or acid etchant under the typical conditions used in recovery of isotopes. For example, the protective layer may have an acid-resistance defined by a loss of less than 1% of total weight when exposed to IM nitric acid for 30 minutes (e.g. at 25 °C). This may be an amount of an amount of less than 0.5% of total weight, such as less than 0.1% of total weight. Providing the protective layer on the support surface can provide the benefits of this corrosion resistance, while also enabling the holder body to be formed ofmaterials that have other properties. Accordingly, the protective layer may have a higher resistance to an etchant, such as nitric acid or hydrochloric acid, compared to the holder body. This can be determined based on ASTM G31-21 Standard Guide for Laboratory Immersion Corrosion Testing of Metals, which is incorporated herein by reference, or based on mass loss, for example when exposed to IM nitric acid for 30 minutes (at a temperature of 25 °C). The protective layer may be provided on the part of the holder by through any method known in the art, such as electroplating, electroless plating, or immersion plating.

[0042] The protective layer may have a thickness of from 500 nm to 1000 pm. For example, from 1 pm to 1000 pm, or 1 pm to 500 pm, or 1 pm to 50 pm. The thickness may be at least 1 pm, such as at least 5 pm, such as at least 7 pm. This may be up to 50 pm.Intermediate layer

[0043] The target holder may further comprise an intermediate layer provided at least between the protective layer and the part of the target holder on which the protective layer is provided. Accordingly, the intermediate layer is provided at least between the protective layer and the at least a portion of the chamber base within the target chamber that the protective layer is formed over. The intermediate layer accordingly provides an intervening layer which extends between the protective layer and the target holder. The intermediate layer provides an interface between the two, extending at least across substantially the same extent of the target holder so that substantially all or all of the protective layer is provided on intermediate layer on the target holder. The intermediate layer may have the same or a greater extent of coverage than the protective layer.

[0044] The intermediate layer provides a barrier layer between the target holder body and the protective layer which can protect the protective layer from damage or tarnishing from the target holder material from migration of ions from the target holder into the protective layer. Such migration can contaminate the outer surface, reducing the effectiveness of the damage resistance. For example, the intermediate layer can act as a barrier layer preventing migration of ions from the target holder into the protective layer. As an example, where a target holder comprises or is formed of copper, an intermediate layer (e.g., comprising or consisting of nickel) can prevent or reduce migration of copper ions into a protective layer (e.g., comprising or consisting of gold). An intermediate layer may also serve to increase the compatibility between the protective layer and the target body, allowing for a greater range of materials for each.

[0045] Accordingly, the intermediate layer may be a coating over (e.g. directly on or indirectly on) the chamber base in the first aspect, and may also be present in the further aspects (such as the target holder of the second and third aspects). The intermediate layer may cover all of the internal surfaces of the target chamber. For example, the target chamber may comprise chamber sidewalls extending from the chamber base and further delimiting the target chamber, and the intermediate layer may also be provided over the chamber sidewalls.

[0046] The intermediate layer may extend at least partially into the outlet conduit to cover the internal surface(s) of the outlet conduit at the exit port, and in some cases may extend along the entirety of theoutlet conduit. Where there are other ports and conduits fluidly connected to the target chamber, the intermediate layer may extend into each of the ports and conduits fluidly connected to the target chamber to cover the internal surfaces of the respective ports and conduits. Alternatively, this may be limited to those conduits through which etchant will pass.

[0047] The intermediate layer may comprise a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb, Pd, Co or combinations thereof. For example, Ag, Co, Ni, Rh and Pd. The metal or metal oxides may be present in an amount of at least 50 mol%, such as at least 75 mol%, at least 95 mol%, at least 99 mol%, or at least 99.9 mol%. The intermediate layer may be a metal layer (e.g. a metal alloy layer) or metal oxide layer comprising or consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb, Pd, Co or combinations thereof, for example Ag, Co, Ni, Rh and Pd. In one embodiment, the target holder chamber base (such as the target holder as a whole) may comprise or consist of copper, the intermediate layer may comprise or consist of nickel and the protective layer may comprise or consist of nickel.

[0048] The intermediate layer may have a thickness of from 500 nm to 1000 pm. For example, from 1 pm to 1000 pm, or 1 pm to 500 pm, or 1 pm to 50 pm. The thickness may be at least 1 pm, such as at least 5 pm, such as at least 7 pm. This may be up to 50 pm.

[0049] The intermediate layer may be provided on the part of the holder by through any method known in the art, such as electroplating, electroless plating, or immersion plating.Holder Body

[0050] The chamber base may comprise or consist of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof. The holder body (or housing) may be made out of any suitable material known in the art, such as a metal. For example, the holder body may be formed of or comprise Cu, Al, Ti, W, Ta, Ag, Au, Nb (e.g. including a metal alloy) or a combinations thereof . Where a protective layer is present, this can include, e.g. oxides of these metals. This may be that the holder body comprises at least 50 mol% of these metals, such as at least 75 mol%, at least 95 mol%, at least 99 mol%, or at least 99.9 mol%. Copper has been found to be an effective choice of metal, since it has a high heat conductivity and hence can dissipate the heat caused by the irradiation effectively. It is also formable by methods which allow for formation of more complex fluid pathways, for example, compared to those required for other materials more resistant to exposure to etchants and / or irradiation. Manufacturing techniques may include machining (e.g., computer numerical control (CNC) machining), 3D printing (e.g. using selective laser sintering (SLS), Direct Metal Laser Sintering (DMLS) and Fused Deposition Modelling (FDM)).

[0051] The target chamber is at least partly delimited by the chamber base and may further be delimited by sidewalls extending from the chamber base. The top of the sidewalls may define the aperture or the aperture may be formed in one of the walls (such as the side walls, or a cover extending between the top of the sidewalls). The support surface is defined by the protective layer but may only comprise a part of the protective layer, such as the part provided on the chamber base. The support surface is arranged such that a target material provided on the support surface can be irradiated by the charged particlebeam through the aperture (for example, this may be opposite the aperture). The target chamber may have a height as measured from the support surface to the top of the sidewalls (e.g. at the sealing surface) of less than or equal to 10 mm, such as less than or equal to than 5 mm, or less than or equal to 2mm. A shorter chamber height may provide for improved foil compression onto the target material provided on the support surface, thus increasing the heat contact and conduction.

[0052] The outlet port of the outlet conduit can be provided on an outer surface of the target holder. A valve may be provided for opening and closing the outlet conduit. The holder body may further comprise an inlet conduit in fluid communication with the target chamber for providing an etchant solution to the target chamber. The inlet conduit can comprise and extend from an inlet port to an entry port provided in the target chamber. The inlet port can be provided on an outer surface of the target holder. A valve may be provided for opening and closing the inlet conduit. The protective layer may extend at least partially into the inlet conduit to cover internal surfaces of the inlet conduit at the entry port, thereby also protecting this part of the inlet port to exposure from the particle beam and the etchant. In some cases, the protective layer may extend along the entirety of the outlet conduit. The entry port and exit port can be arranged to provide and remove, respectively, etchant fluid (e.g. an acid or base) a wash fluid (e.g. an acid, base, buffer, water, gas) to a support surface in the target chamber.

[0053] The holder body may comprise less than or equal to four conduits (including the outlet and inlet conduits) connected to the target chamber, excluding the aperture. This may be less than or equal to two conduits (e.g. a single inlet and a single outlet). Limiting the number of conduits can limit potentially issues associated with air pockets forming. Fewer conduits can also lead to a lower risk of the surface underneath the protective layer being exposed (for example, due to it being missed or uneven plating), which in turn improves the quality and consistency of the etching process. All of these lead to a reduced chance of damage and contamination.

[0054] The inlet port and the outlet port may be provided on the same surface of the target holder. Where a target coolant conduit is present, the port of the target coolant conduit and the inlet port and outlet port can all be provided on the same surface of the target holder, such as an end face. This simplifies interconnection to the target holder, since all interfaces are accessible from the same direction. The end face may be located at the forward end of the target holder, relative to movement from an unloaded to a loaded position. This can enable automatic connection of the interfaces to respective fluid connectors as the target holder moves from an unloaded to a loaded position.

[0055] The target material may be a solid (e.g. a metal or metal salt) or a liquid (e.g. a solution containing the target material, such as a metal dissolved in acid). The target material may be copper, silver, cobalt, iron, cadmium, zinc, indium, gallium, lutetium, tellurium, or a metallic salt thereof. The radioisotopes produced from irradiating the target material may be, for example,15O,nC gas, liquid18F,68Ga,67Ga,89Zr,64Cu,13N,123 / 124I,177Y,99mTc,inIn,44Sc,13C or combinations thereof. In some embodiments, the radioisotopes formed comprise or consist of at least one of68Ga,64Cu,89Zr and124I.

[0056] The support surface may be a planar support surface and can be arranged at an angle as relative to a central axis defined by the continuous beam path at the aperture, wherein as is from 10 to 25 degreesor from 155 to 170 degrees. 03 may be from 10 to 25 degrees or from 155 to 170 degrees. This may be from 15 to 20 degrees (such as 18 degrees) or from 160 to 165 degrees (such as 162 degrees). The angle increases the area of the target that is irradiated by the beam. In this way, the beam energy is distributed over a larger area, for example compared to a 90-degree beam strike (in some cases, the area is three times as large). Within the beam, hot spots are reduced.Target Holder Heat Management

[0057] The holder body may further comprise a target coolant conduit extending at least partially through the holder body adjacent the target chamber for conveying a coolant fluid for cooling a target material provided on the support surface. Provision of coolant adjacent the support surface (e.g. at least partly long or beneath the chamber base) provides cooling for keeping a target material and the target holder cool during irradiation. The target holder coolant conduit may be fluidly isolated from the target chamber. Accordingly a further coolant fluid, such as water, can be used to cool the clamp member but with a greater choice of coolants, since this is not limited to coolants which are inert to the beam. The thickness between the target coolant conduit and the protective layer defining the support surface (i.e. the thickness of the chamber base at least one point between the target coolant conduit and the target chamber) may be less than or equal to 3 mm, such as less than or equal to 2 mm to enhance heat transfer.

[0058] The materials used in the holder body may be selected such that the chamber base has a heat conductivity which is greater than the heat conductivity of the protective layer, for example as measured by ASTM E1225-20 Standard Test Method for Thermal Conductivity of Solids Using the Guarded-Comparative -Longitudinal Heat Flow Technique, which is incorporated herein by reference. This may be at a heat conductivity measured at a temperature between 152 to 350 °C. Accordingly, the chamber base may comprise or consist of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof. This can include, e.g. oxides of these metals. This may be that the holder body comprises at least 50 mol% of these metals, such as at least 75 mol%, at least 95mol%, at least 99 mol%, or at least 99.9 mol%. Copper has been found to be an effective choice of metal, since it has a high heat conductivity and hence can dissipate the heat caused by the irradiation effectively.

[0059] The target coolant conduit may comprise a port through which coolant fluid can be received. This can provide an inlet. For example, the target coolant conduit may extend from the inlet (e.g. defined by the port) to the outlet. The target holder may further comprise a separator member provided in the target coolant conduit and configured to separate the port into an inlet and an outlet and, further, to separate the target coolant conduit to define a flow path extending through the target coolant conduit from the inlet to the outlet. The separator member may further comprise at least one wall extending along the target coolant conduit configured to divide at least a part of the target coolant conduit into two parallel flow paths. The separator member can accordingly separate a single conduit into a flow path by dividing the conduit into at least two fluidly connected channels. The target coolant conduit may be a single conduit extending along a single axis from the port provided at one face of the target holder. The separator member, which is separate to the holder body, provides a way of providing fluid pathways through the target holder without requiring complex fluid pathways to be directly formed inthe holder body. This can provide flexibility in the manufacture of the holder body, which has constraints due to the limited materials that can be used (e.g. to be irradiation-resistant and have good heat conductivity). Instead, only a single port and conduit for cooling need be formed in the holder body. This means that that target holder can be formed by e.g. CNC processes, but the separator member can be formed by a method more suited to forming smaller fluid pathways (such as 3D printing). Alternatively, the separator member may be an integral part of the holder body, such that the holder body comprises the separator member. In this case, the separator member is an integral wall within the target holder defining in part an inlet and outlet and the flow paths extending into and out of the target holder.

[0060] In some embodiments, the separator member comprises a separator plate configured to separate the port into the inlet and outlet, for example, by extending across the port to separate the port into two separate apertures or openings. The separator plate may further extend from the port through the target coolant conduit to separate the conduit into a first (e.g. upper) flow path and a second (e.g. lower) flow path, which paths are fluidly connected. The first flow path is defined by the target coolant conduit and a first surface of the plate. The second flow path is defined by the target coolant conduit and the opposite, second surface of the plate. The fluid connection can be at an opposite end of the target coolant conduit to the port, for example defined by an aperture or recess in the plate.Sealing Gaskets

[0061] The holder body may further comprise a sealing surface for forming a seal with a surface of a particle accelerator system, wherein the aperture extends through or is provided in the sealing surface. The sealing surface may comprise a target holder gasket channel formed in the sealing surface extending around the aperture. The sealing surface can be a part of the same element as the target chamber (such that they are integrally formed) or these may be formed as separate components. For example, the holder body may define the sealing surface. Alternatively, there may be a further component, such as a connector, defining the sealing surface and aperture.

[0062] The target holder may further comprise a sealing gasket (a “target holder sealing gasket”) provided in the gasket channel and arranged around the aperture. The sealing gasket may comprise a first engagement feature and the gasket channel comprises a second engagement feature, wherein the first engagement feature and second engagement feature are complimentary and are configured to retain the sealing gasket in the gasket channel. The gasket channel may have a depth of up to 60%, such as up to 80% of the thickness of the gasket such that the gasket protrudes from the channel.

[0063] The sealing gaskets disclosed herein used, including the target holder sealing gasket and connector gasket (below), may each (or all) be polymeric gaskets, such as elastomeric gaskets. For example, each may comprise or consist of a polymer, such as a fluoroelastomer (for example, a perfluoroelastomer), an ethylene -propylene elastomer (such as ethylene-propylene diene (EPDM)) or polytetrafluoroethylene (PTFE). In some embodiments, the front sealing gasket, the rear sealing gasket, the target holder sealing gasket, interface gasket and / or and the connector gasket may comprise or consist of a copolymer comprising vinylidene fluoride (VF2) or tetrafluorethylene and at least one othercopolymerizable fluorine -containing monomer, for example selected from at least one of hexafluoropropylene (HFP), tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), vinyl fluoride (VF), and a fluorovinyl ether (for example, a perfluoro(alkyl vinyl ether) (PAVE), such as perfluoro(methyl vinyl ether), perfluoro(ethyl vinyl ether) and perfluoro(propyl vinyl ether)). For example, a copolymer selected from vinylidene fluoride (VF2) and hexafluoropropylene (HFP); vinylidene fluoride (VF2), hexafluoropropylene (HFP) and tetrafluoroethylene (TFE); tetrafluoroethylene (TFE), vinyl fluoride (VF2), hexafluoropropylene (HFP), and a cure site monomer; tetrafluoroethylene (TFE) and perfluoromethylvinyl ether (PMVE); Exemplary sealing gaskets include Viton gaskets, Kalrez gaskets and Chemraz gaskets, for example a Viton sealing gasket with a shore A hardness of from 75-90. These materials are advantageously inert to acid and resistant to damage during irradiation and, accordingly, provide a robust seal which retains the closed environment within the conduits and target chamber.System

[0064] In the second aspect, there is a system comprising a target holder, such as that according to any of the disclosures set out herein, such as that according to the first aspect or any of the disclosures relating thereto. The system further includes a pump assembly fluidly connected to the target chamber via the outlet conduit and the inlet conduit. This can be used for providing etchant fluid (e.g. an acid or base), a wash fluid (e.g. an acid, base, buffer, water, gas) or a drying fluid (e.g. nitrogen, helium, or air). The pump assembly may comprise at least one pump fluidly connected to the inlet conduit and configured to pump fluid (e.g. liquid) into the inlet conduit. The pump (or a further pump) may be fluidly connected to the outlet conduit and configured to draw fluid (e.g. liquid) out of the outlet conduit.

[0065] The pump assembly may be further configured to reduce the pressure within the target chamber (e.g. provide a vacuum) and may further reduce the pressure within any associated conduits. The pump assembly may be configured to draw fluid from the target chamber to reduce the pressure. Reducing the pressure can reduce the chance of bubble formation in the target chamber or conduits, which in turn can improve the recovery of the radioactive isotopes.

[0066] The pump assembly may be further configured to provide a solution to the target chamber at flow rate of from 1 mL / min to 50 mL / min. This flow rate has been found to provide reliable and consistent etching of irradiated material, for example when using the etchant solutions disclosed herein. This may be 10 mL / min to 50 mL / min, such as 10 mL / min to 35 mL / min or 35 mL / min to 50 mL / min. This may be from 40 mL / min to 45 mL / min. This can be a wash solution, which may then be followed by an etchant solution, or it may be the etchant solution. It has by found that the provision of solution at this relatively fast flow rate (e.g. 10 mL / min or higher, such as 35 mL / min or higher) can reduce bubble formation (or remove bubbles) within the chamber and the fluid conduits. Where the pressure is reduced in the target chamber, the provision of fluid at this flow rate may be carried out after the reduction of pressure.

[0067] If bubbles are detected, either by an operator or by a sensor of the system, the pump assembly may be further configured to remove the liquid from the target chamber and respective conduits. Thiscan be pumping a gas (e.g. air, nitrogen or helium) into the target chamber and respective conduits using the pump assembly. The pump assembly may then provide a solution to the target chamber.

[0068] The pump assembly may further comprise a heater arranged to heat fluid (e.g. an etchant solution) provided to the target chamber. This can improve the recovery of isotopes and can ensure a relatively consistent and predictable recovery. After irradiation, the target holder will be at a raised temperature. Accordingly, fluid provided during the etching process and entering the hot chamber will be heated and the etching process take place at a first, peak temperature of the etching fluid. This may improve the efficiency of the etching process and, hence, recovery. However, as the heat dissipates, the temperature within the chamber will drop, which can impact the etching process. How this drops can be unpredictable and depend on a number of factors, including the environment and processing conditions. By heating fluid to a raised temperature (which can be between room temperature and the peak temperature, for example at least 30 °C, such as from 30 to 50 °C), this can keep the temperature that the etching occurs at a more consistent level, making the process more predictable and, further, improve the efficiency by operating at a higher temperature.

[0069] Accordingly, the heater may be configured or arranged to heat etchant solution to be provided to or as the etchant fluid is provided to the target chamber. For example, the pump assembly may comprise a supply conduit fluidly connecting a liquid or fluid supply module (which may comprise etchant solution) to the inlet conduit of the holder body and the heater may be arranged to heat the supply conduit so as to warm the etchant solution in the supply conduit. This can, in some configurations, allow for heating of plural fluids where there are multiple fluid supply modules connected to the supply conduit.

[0070] The heater may be configured to heat fluid to a set temperature at the heater (or within the supply conduit). For example, a controller may be configured to control the heater so as to follow a single heating profile. Alternatively, the heater may follow a gradient or ramp program. That is, the heater may be configured to vary the heating provided to the fluid. For example, to maintain a particular fluid temperature within the target chamber. This can compensate for the dissipation of heat from the target holder. A controller may be configured to control the heater so as to follow a ramp or gradient heating profile.Connector Assembly

[0071] The system may further comprise a connector assembly configured to connect to the target holder. The connector assembly may comprise a connector body comprising a connector discharge conduit for removing an isotope solution from the target holder, the connector discharge conduit comprising and extending from a discharge inlet to a discharge outlet. The connector body may further comprise a connector supply conduit for supplying a fluid to the target chamber, the connector supply conduit extending from a supply port for connection to a fluid source to a supply outlet. The supply outlet is configured to operably connect with the inlet port of the target holder to provide fluid communication from the supply port to the target chamber. The discharge inlet is configured to operably connect with the outlet port of the target holder to provide fluid communication from the target chamberto the discharge outlet. The provision of a connector assembly provides a hub for all of the fluid interconnections which is separate to the target holder, so that the target holder only needs to be connected to a single component (the connector assembly) when moving or switching the target holder, rather than a series of conduits or tubing. This can reduce complexity of operation and reduce downtime. The pump assembly may be fluidly connected to the target chamber via connector assembly.

[0072] The holder body may comprise a holder mating surface on which the inlet port and outlet port are provided and the connector assembly may comprise a connector mating surface on which the supply outlet and discharge inlet are provided, wherein, when the target holder and connector assembly are operably connected, the holder mating surface and connector mating surface connect and are in opposing relationship causing the outlet port to fluidly connect to the discharge inlet and the inlet port to fluidly connect to the supply outlet.

[0073] One of the outlet port and the discharge inlet may comprise a first projecting nozzle and the other may comprise a corresponding first connector recess. One of the inlet port and the supply outlet may comprise a second projecting nozzle and the other may comprise a corresponding second connector recess. In each case, the projecting nozzle and corresponding connector recess are connectable to form the fluid connection and can provide a seal across their corresponding tapering surfaces defined by these shapes. The nozzles may have a conical or frustoconical shape. This arrangement permits the easy and reliable interconnection of these parts. In particular, since the shape enables one to move slide relative to the other into a position where the nozzle and recess engage .

[0074] Where a target coolant conduit is present, the connector body may further comprise a coolant supply conduit comprising and extending from a coolant inlet for connection to a coolant fluid source to a supply port configured to operably connect with the port of the target holder to provide fluid communication from the coolant inlet to the target coolant conduit. The port of the target coolant conduit may be provided on the holder mating surface and the supply port may be provided on the connector mating surface such that connection of the holder mating surface and connector mating surface causes the port to fluidly connect to the supply port. The connector body may also further comprise a coolant discharge conduit comprising and extending from a discharge port configured to operably connect to the port of the target holder to a coolant outlet so it can be removed from the target holder, and the system. These may be provided on the connector mating surface and holder mating surface, respectively. The connector assembly may further comprise a projecting nozzle or recess incorporating the supply port and the discharge port, and the target holder may comprise the other of a corresponding projecting nozzle or recess corresponds forming the perimeter of the port connectable to form the fluid connection. This may be present with the other inlets and outlets having corresponding shapes.

[0075] A gasket (“connector gasket”) may be provided between the holder mating surface and the connector mating surface to provide a seal around each of the holder mating surface and the connector mating surface, incorporating the fluid connections provided thereon. The gasket may comprise an engagement feature configured to retain the gasket relative to the target body and / or the connector body. For example, engagement features may be provided around the holder mating surface or the connectormating surface and corresponding engagement features may be provided on the gasket to retain the gasket thereon. This can reduce the likelihood of leakage and reduce operation interaction, and can enable machine-controlled switching of target holders.

[0076] The connector assembly or connector body may comprise or be formed from (e.g. consists of) an etchant-resistant polymer. For example, PEEK, polyethylene, polyurethane, polyethylene terephthalate, polyvinyl chloride, etc. Manufacturing techniques may include machining (e.g., CNC machining), 3D printing (e.g. using DMLS and FDM). This may be that the connector assembly comprises at least 50 mol% of these polymers, such as at least 75 mol%, at least 95mol%, at least 99 mol%, or at least 99.9 mol%. Alternatively, it may be formed from or comprise Cu, Al, Ti, W, Ta, Ag, Au, Nb, a combination thereof or a combination with other metals (e.g. a metal alloy). This can include, e.g. oxides of these metals. This may be that the holder body comprises at least 50 mol% of these metals, such as at least 75 mol%, at least 95mol%, at least 99 mol%, or at least 99.9 mol%. A connector protective layer may further provided on internal surfaces of the connector discharge conduit, the connector protective layer comprising a metal or metal oxide comprising or consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof, for example Ag, Au, Pt, Ta, W or Nb or combinations thereof, for example, Au, Ta or Pt. The metal or metal oxides may be present in an amount in the protective layer of at least 50 mol%, such as at least 75 mol%, at least 95mol%, at least 99 mol%, or at least 99.9 mol%. This can include alloys of these metals with other components. This provides many of the same benefits as forming the target holder from these materials, since etchant and isotopes will pass through the connector body, where present.Coolant device

[0077] The system or apparatus may further comprise a coolant device configured to provide a coolant fluid to the target holder coolant conduit. The cooling device may comprise a coolant fluid, such as a coolant liquid or coolant gas. This can be water or an aqueous-based coolant. The coolant gas may be provided at a pressure of from 10 to 200 PSI, such as 50 PSI.Apparatus and Frame

[0078] The target holder and, where present, connector body can be used with or form part of an apparatus for guiding a charged particle beam from a particle accelerator to a target material to be irradiated. In some embodiments, the apparatus (or a system comprising the apparatus) may be for irradiating a target material and may comprise a particle accelerator (such as a cyclotron) and the target holder. Accordingly, systems for irradiating a target material to produce radioisotopes may comprise an apparatus as disclosed herein together with a particle accelerator. The system may further comprise a control unit or processor configured to control operation of the apparatus and may further control operation of the particle accelerator. The control unit may be configured to perform any of the methods disclosed herein. The system in the second aspect further comprises a pump assembly and may further comprise a coolant device for supplying coolant fluids to the coolant conduits and / or wash fluids to the target holder. Other systems may comprise a pump assembly for supplying etchant.

[0079] The system or apparatus may further comprise a frame (or housing) configured to receive the target holder and the target holder may be moveable relative to the frame from an unloaded position to a loaded position in which the target holder and connector assembly are operably connected. Accordingly, in this position, the conduits are all aligned. Further, this may also align the target chamber with the continuous beam path so that a target material provided therein can be irradiated by the proton beam. There may be, for example, a port or dock configured to receive and retain the target holder in the loaded position. Accordingly, the frame may comprise a first position (or end) defining an unloaded position and a second position (or end) defining the loaded position. The frame may further comprise a track extending between the first and second positions (corresponding to first and second ends of the track) and the target holder may be configured to engage and be moveable along the track. Other components of the apparatus, such as the interface element and / or these may be provided on the frame.

[0080] The system or apparatus may further comprise a target holder actuator configured to move the target holder from the unloaded position to the loaded position. The target holder actuator may comprise a first moveable member configured to engage (directly or indirectly) the target holder such that movement of the first moveable member causes movement of the target holder; and a first driver configured to move the first moveable member. Where there is a track, the first moveable member may be configured to move the target holder along the track from the first end to the second end. The target holder actuator may be a linear actuator configured to move the target holder along a single axis (e.g. defined by the track). This can be a screwjack actuator, for example. These simplify the mechanism by enabling only a single motion.

[0081] The system or apparatus may further comprise a target holder actuator sensor configured to detect a position of the target holder (e.g. the loaded and / or unloaded position). The target holder actuator sensor may be positioned outside of a post-target region located behind the support surface in a beam direction defined by the direction of the continuous beam path at the support surface. Arrangement of the sensor in this way is advantageous as it reduces degradation and interference with the sensor. Where a sensor is located within the behind the target or along the beam path, there may be interference from the beam striking (or e.g. neutrons emitted behind the target) which causes degradation of components. Locating the sensor outside of this region improves longevity of the sensor.

[0082] The system or apparatus may further comprise a target holder rack or magazine provided on the frame (e.g. at or adjacent the first end) and comprising at least one slot configured to receive a target holder. There may be a plurality of slots, each configured to receive a target holder. The target holder actuator is configured to move the target holder from the target holder rack to the loaded position. The actuator, or a further actuator, may be configured to move the target holder from a slot to the first end of the frame. The target holder rack can act as a store for the target holder before and / or after irradiation, including for multiple target holders reducing operator interaction with the system.

[0083] The target holder rack may be moveable relative to the frame (e.g. a track, where present) and, in some cases, the target holder actuator. This may be to allow removal or insertion of a target holder from the rack. For example, the target holder rack may rotate out of alignment with the track.Alternatively or additionally, where the target holder rack comprises a plurality of slots, the target holder rack may be moveable with respect to the track to align one of the slots, and hence one of the target holders, with the frame (e.g. track) and with the target holder actuator such that a respective target holder received within the slot can be moved to the loaded position.Interface with apparatus and system

[0084] As set out herein, the target holder forms a part of a wider system for generating radioisotopes. It may interface with a particle accelerator, such as a cyclotron, and there may be an apparatus for guiding a charged particle beam provided between the particle accelerator and the target holder. The apparatus can hold the target material in position so that the particle beam can accurately irradiate the target material. Specifically, the target holder can operably connect to the apparatus to form a continuous beam path with the particle accelerator and apparatus.

[0085] The apparatus for guiding a charged particle beam from a particle accelerator to a target material to be irradiated may comprise an interface element for interface element for connection with a particle accelerator, the interface element comprising an interface conduit through which a charged particle beam can pass, the interface conduit extending from an interface inlet for connection with a beam exit aperture of a particle accelerator to an interface outlet. The apparatus may also comprise a clamp member configured to operably connect to the interface element in an engaged position of the clamp member, the clamp member comprising a first surface; a second surface provided on an opposite side of the clamp member to the first surface; and an intermediate conduit through which a charged particle beam can pass extending from an intermediate conduit inlet provided in the first surface to an intermediate conduit outlet provided in the second surface. The clamp member is moveable into an engaged position to operably connect to the interface element and wherein, in the engaged position, the intermediate conduit inlet is operably connected to the interface outlet so that the intermediate conduit and the interface conduit provide a continuous beam path through which a charged particle beam can be guided towards a target material. Further, in the engaged position of the clamp member, the second surface of the clamp member may be operably connected to the sealing surface of the target holder (when the target holder is in the loaded position) such that the interface conduit, the intermediate conduit and the aperture are operably connected to provide a continuous beam path through which a charged particle beam can pass.

[0086] The apparatus advantageously can reduce the downtime of a system between operations as well as reducing the amount of operator interaction with the system after irradiation. This also can reduce the risks of leakage of radioisotopes and, more generally, exposure of the operator to radioisotopes. The movement of the clamp member and target holder can allow for the automatic and reliable exchange of target holders and other components (such as foils) thereby providing an improved process.

[0087] The clamp member may comprise a main body through which the intermediate conduit extends and comprising sidewalls, where an external surface of one sidewall defines or comprises the first surface and an external surface of another sidewall defines or comprises the second surface.

[0088] A first foil portion can be provided to the first surface to cover the intermediate conduit inlet and a second foil portion can be provided to the second surface to cover the intermediate conduit outlet. In this way, when the clamp member is in the engaged position and the target holder is in the loaded position, the first foil portion can be held (i.e. clamped or sealed) between the first surface and the interface element to seal both the interface outlet and the intermediate conduit inlet and the second foil portion can be held between the second surface and the target holder to seal the intermediate conduit outlet and the aperture. The sealing of the second foil portion over the aperture seals the target chamber so that an isolated environment can be provided within the chamber. For example, a vacuum can be formed within the chamber and irradiated target material (i.e. radioisotopes) can be retained within the chamber. There may be other openings or apertures within the chamber, but during use these may be sealed (e.g. by other seals).

[0089] The apparatus further comprises a foil dispenser configured to provide a first foil portion to the first surface as set out above and / or a second foil portion to the second portion as set out above. This can provide a more robust and easier-to-service interface between a particle accelerator and the apparatus / system (including the target holder). The interface element can be configured to form an airtight seal with the particle accelerator using standard interconnections. The apparatus can maintain this air-tight environment by sealing the interface conduit of the interface element using a foil dispenser to provide foil to the outlet of the interface conduit and sealing this with a clamping member which can clamp the foil against the interface element in an engaged position. Similarly, foil provided over the target holder can provide optimal beam properties and provide a sealed environment for processing. The use of the foil dispenser can reduce the interaction between an operator and the system. A foil in a particle accelerator system will need replacing at regular intervals as it can be deformed during clamping (e.g. leading to wrinkles and a reduced quality seal) and will degrade overtime due to exposure to the beam. Use of the foil dispenser and an engageable clamp member to replace the foil in this location can reduce the overall complexity of operation, reduce downtime and reduce the risk of exposure of an operator to radioisotopes, since an operator does not need to manually change replace the foil. Moreover, the position of the foil portions and sealing also enables cooling of the foil through the clamp member. That is, the two foil portions can seal off on either end of the intermediate conduit provide a sealed environment within the clamp member, which in turn can be used for cooling the foil portions. Without cooling, the power dissipated in the foil portions would increase exponentially without such cooling, potentially leading to foil meltdown. Further, as will be appreciated, a foil can be used for beam modification, such as for changing charge state, degrading or adjusting the energy, and beam shaping.

[0090] Where present, the foil dispenser may comprise a first foil receiver (or “holder”) for receiving at least a portion of a foil sheet and a second foil receiver (or “holder”) for receiving at least a portion of a foil sheet, the first foil receiver and the second foil receiver being arranged relative to each other to define a foil dispensing path therebetween with the foil dispensing path traversing the first surface and second surfaces of the clamp member such that a foil sheet received on and extending between the first foil receiver and the second foil receiver covers the intermediate conduit inlet and the intermediateconduit outlet. The foil dispenser can accordingly provide a sheet of foil which can extend over both of the intermediate conduit inlet and intermediate conduit outlet. Dispensing the foil sheet can accordingly comprise moving the foil sheet between the first and second foil receivers. This arrangement can provide straightforward and operator-free replacement as the foil sheet can be moved along the dispensing pathway to provide a new portion of the foil sheet to the first surface. An unused portion of the foil sheet may reside on the first foil receiver and the second foil receiver may receive the used portion of the foil sheet, and replacement can comprise moving the foil sheet from the first foil receiver to the second foil receiver. The first and second foil receivers may, for example, be each be a spool. The foil dispenser may further comprise a foil sheet driver configured to move at least one of the first foil receiver or the second foil receiver to move a foil sheet along the foil dispensing path. The foil dispenser may further comprise a foil sheet driver configured to move at least one of the first foil receiver or the second foil receiver to move a foil sheet along the foil dispensing path. The foil dispenser may further comprise foil sheet provided on the first foil receiver and the second foil receiver extending therebetween along the foil dispensing path, the foil sheet defining the first foil portion and the second foil portion. The foil sheet can define plural first and second foil portions. One of the first or second foil receiver may comprise a foil sheet spool comprising a foil sheet. The apparatus may comprise a control unit configured to control operation of the foil dispenser. For example, this may actuate the foil sheet driver, where present.

[0091] The foil or foil sheet may be a metal foil, such as Al foil, Ta foil, Ti foil, Havar (cobalt alloy) foil, or any other suitable metal foil. For example, the foil sheet (e.g. at the first and second portions) can have a thickness of from 10 to 100 pm, such as from 20 to 50 pm. These foils are particularly suited for providing a specific beam energy range of 12-13 MeV (which can provide optimal yield, depending on the radioisotope being produced) and the thickness aligns optimally with the maximum excitation function of the beam energy, particularly when provided on the angled first and second surfaces. The width of the foil can be selected to seal the conduits and may be at least 10mm, for example from 10mm to 100mm. The length of the foil may be at least 20 cm, such as at least 30 cm or at least 100cm, such as 20 to 200 cm. An exemplary foil suited for production of radioisotopes using the disclosed apparatuses is a 30 pm thick Ta foil.

[0092] The support surface may be provided at a distance of less than or equal to 400mm from the second foil portion, such as less than or equal to 300 mm, less than or equal to 200 mm. This may be at least 50 mm. These may be arranged substantially parallel to one another.

[0093] The clamp member may further comprise a foil coolant conduit in fluid communication with the intermediate conduit for conveying a coolant fluid to the intermediate conduit. Cooling the foil portions effectively is critical, since foil failure can be caused by overheating. This in turn can lead escape of radioisotopes, from both the target material and the gases in the beam pathway. Provision of this directly into the continuous beam pathway and directed across exposed surfaces of the foil portions is desirable since it this is one of the hottest regions in the apparatus.

[0094] The clamp member is moveable between an engaged position and a disengaged position. The loaded position is one in which the target holder can be connected to the clamp member when the clamp member is in an engaged position. Accordingly, the loaded position may be one where the target holder can be engaged with the clamp member but is not necessarily engaged because the clamp member is not in an engaged position. Movement of the clamp member into the engaged position of the clamp member would accordingly lead to the connection of these parts. Alternatively or additionally, it may be that movement into the loaded position is only achievable when the clamp member is in the engaged position. It will be appreciated that various configurations are possible in this respect. The unloaded position is accordingly a position in which the target holder is not in this position, such that it is not engageable by the clamp member in the engagement position of the clamp member.

[0095] The apparatus may further comprise a clamp member actuator configured to move the clamp member into the engaged position (e.g. between the engaged position and the disengaged position). The clamp member actuator may comprise a second moveable member configured to engage (directly or indirectly) the clamp member such that movement of the second moveable member causes movement of the clamp member; and a second driver configured to move the second moveable member.

[0096] The second surface of the clamp member may comprise a second gasket channel extending around the intermediate conduit outlet for receiving a rear sealing gasket. The second gasket channel may be formed in a main body of the clamp member. The clamp member may further comprise a rear sealing gasket provided in the second gasket channel and arranged around the intermediate conduit outlet; and / or the target holder may further comprise a rear sealing gasket provided in the target holder gasket channel arranged around the aperture, where present. In the engaged position of the clamp member, the rear sealing gasket may provide a seal between the second surface and the sealing surface around the intermediate conduit outlet and the aperture (with the foil portion therebetween). One gasket may be sufficient to form a seal between the second surface and target holder, but in some embodiments both the second gasket channel and the target holder gasket channel may be present.

[0097] Any gasket channel present in the apparatus may have a depth of up to 60%, such as up to 80% of the thickness of the gasket. Any gasket channel present in the apparatus may further comprise a cutout provided on a periphery of the corresponding channel for release of a gasket. Removal and insertion of gaskets into channels can be time consuming and require tools, but the provision of a cutout can provide a user with an area to grasp the gasket for easier removal. Any gasket channel present in the apparatus may have a retention feature for retaining the corresponding gasket (not shown) within the channel. For example, at least one (or each) channel may comprise at least one engagement section which, when viewed in a cross section, comprises a narrowed neck portion. The engagement section is a section whose shape retains the gasket therein in normal use. The gasket may comprise a corresponding shape to interlock with the engagement section. For example, this may be a tongue and groove coupling. An example of an engagement section would be a dove-tail shape.

[0098] The target holder actuator may be configured to retain the target holder in the loaded position against the clamp member, for example by remaining in a fixed position bearing against the targetholder (e .g . the moveable member may be fixed) . This can help to ensure that the seal between the target holder and the clamp member is held. The system or apparatus may further comprise a biasing element provided between the first moveable member and the target holder and is configured such that, in the loaded position of the target holder, the biasing element further provides a force acting on the target holder to retain the target holder in the loaded position. In other words, the first moveable member locks the target holder in position and the biasing element further resists movement of the target holder out of the loaded position. This can reduce the risk of a leak between the target holder (i.e. the connector) and other components, such as the connector body, which cause leak of radioactive material or leak of cooling fluids (e.g. from either interface) or etchant (containing radioactive isotopes, during etching of the irradiated target material). Even where an inert gas is used as a cooling fluid, impurities such as nitrogen or oxygen can be present, which can form oxygen- 15 and nitrogen- 13 during irradiation. Even if an adequate detection system is in place, this can still necessitate an immediate production shutdown. The biasing element biases the target holder so that there is additional and positive force acting to retain the target member in position. This can also overcome intolerances in parts, such as deformation of the sealing gaskets, and ensures there is some redundancy in the event of a reduction in force provided by the first driver and / or first moveable member or a failure in these systems. Further, this enables additional pressure to be applied by the actuator in a controlled manner after the target holder is in the loaded position. The biasing element can be provided as a part of the first moveable member. The biasing element may be a spring. By “provided between” it is meant that the biasing element is functionally provided between the first moveable member and the target holder in the drive train from the first moveable member to the target holder. Accordingly, the biasing element may only indirectly contact these, provided that this provides the required functional force. For example, the biasing element may bear against the first moveable member at one end and bear against the target holder or a part (such as a second moveable member) acting on the target holder at the other end. There may be further elements between the first moveable member and the target holder and the biasing element may directly contact these further elements. The system or apparatus may further comprise a sensor configured to detect relative movement of the first moveable member and either the target holder or a part acting on the target holder at the other end of the biasing element. In this way, the compression of the biasing element can be determined.Method

[0099] The method of the third aspect comprises providing an etchant solution to the target chamber to etch at least a part of an irradiated material comprising radioisotopes to form an isotope solution comprising radioisotopes; and removing the isotope solution from the target chamber via the exit port of the outlet conduit. The method may further comprise providing the target holder, for example a target holder according to any of the disclosures set out herein.

[0100] The method accordingly etches an irradiated solid material comprising radioisotopes to recover the radioisotopes in a solution form, providing an improved means of recovery. The step of providing the etchant solution may be a single step (e.g. a discrete amount of an etchant or a continuous supplyfor a period of time) or this may comprise providing the etchant solution in a plurality of steps or cycles. This may comprise providing the etchant solution in a plurality of aliquots, with each removed from the target chamber during or prior to the addition of the next aliquot. These may then be recombined.

[0101] The method may further comprise providing etchant solution via the inlet conduit. For example, using a pump assembly. This allows etchant (in the form of an aqueous solution) to be delivered to the target chamber and recover newly formed radioisotope to be recovered from the target chamber. This is preferably carried out in the loaded position of the target holder.

[0102] The etchant solution may be an acid solution or a basic solution. The etchant solution may comprise or consist of hydrochloric acid, nitric acid or sodium hydroxide. This may be 0.1 to 2M hydrochloric or nitric acid, for example 0.2 to IM or 0.2 to 0.5M. These lower molarities provide a more controlled etch with less pitting and, accordingly, allow for any target material remaining on the support surface to be more reliably irradiated again with less chance of failure (e.g. activation of the target holder itself). Plural etch cycles may be used to recover the material. The volume of etchant can be selected to provide at least a stoichiometric equivalent to the moles of irradiated metal (or total target metal, in some cases) within the cartridge. One combination of materials which has been found to provide a reliable radioisotope production arrangement is the use of a solid zinc target material to produce68Ga, followed by recovery using a 0.2 to 0.5M nitric acid etch (which may include a plurality of etch cycles) and etching from 1 to 10 pm thickness from the irradiated target material.

[0103] The irradiated material may comprise radioisotopes formed from an isotope precursor (i.e. the target material) through irradiation and a further portion comprising the isotope precursor (i.e. unirradiated target material). For example, there may be a top layer or a region of a top layer comprising radioisotopes and a layer beneath the top layer comprising or consisting of (for example, comprising at least 95mol%, such as at least 99 mol%) isotope precursor. The method may further comprise allowing the etchant solution to reside in the target chamber for an etching time period before removing the etchant solution and the isotope solution from the target chamber, the etching time period being selected to etch the irradiated material and dissolve the radioisotopes in the etchant solution without etching the further portion comprising isotope precursor. It will be appreciated that at least some portion of the precursor may be etched in practice, but by leaving a portion of the precursor behind in the target chamber, the irradiation process can be repeated. Moreover, by etching in the target chamber after irradiation and with the target holder in situ (i.e. in the loaded position with the clamp member engaged in the engaged position), the subsequent irradiation can be carried out more quickly. The etching time period may be selected to etch an amount of the irradiated material of from 1pm to 20pm. This may be 2 to 5 pm thickness from the irradiated target material. Where the irradiated target was a thin target layer, this may comprise etching the entire irradiated material down (e.g. down to the protective layer, where present). The etching time period may be a total etching time period comprised of a plurality of separate etching times in a cycle. For example, the etching time period (n x t) may be comprised of n cycles of t length of time. In some cases, the etching time may be determined by the desired number ofcycles and the desired quantity of etchant solution (this may be based on the flow rate, for example, where a continuous supply of etchant is used).

[0104] The method may further comprise reducing the pressure in the target chamber prior to providing an etchant solution (this may include reducing the pressure in any associated conduits). This can reduce the likelihood of bubble and dead space formation in the target chamber or conduits, which in turn can improve the recovery of the radioactive isotopes. This may be to provide a vacuum in the interface conduit. By vacuum, it is meant reducing the pressure relative to the ambient atmosphere. This may be reducing the pressure to less than or equal to IxlO-2mBar, such as less than or equal to IxlO-3mBar, such as from IxlO-2to mBar to 1 xlO-7mBar.

[0105] A solution (e.g. etchant or wash) may be provided to the target chamber at flow rate of from 1 mL / min to 50 mL / min. This flow rate has been found to provide reliable and consistent etching of irradiated material, for example when using the etchant solutions disclosed herein. This may be 10 mL / min to 50 mL / min, such as 10 mL / min to 35 mL / min or 35 mL / min to 50 mL / min. This may be from 40 mL / min to 45 mL / min. For example, the etchant solution may be provided to the target chamber at flow rate of from 10 mL / min to 50 mL / min. Alternatively or additionally, a wash solution may be provided to the target chamber at flow rate of from 1 mL / min to 50 mL / min. This may be 10 mL / min to 50 mL / min, such as 10 mL / min to 35 mL / min or 35 mL / min to 50 mL / min. This may be prior to the providing the etchant solution. It has by found that the provision of solution at this relatively fast flow rate (e.g. 10 mL / min or higher, such as 35 mL / min or higher) can reduce bubble formation (or remove bubbles) within the chamber and the fluid conduits. Where the pressure is reduced in the target chamber, the provision of fluid at this flow rate may be carried out after the reduction of pressure.

[0106] To control the thickness of the target material etched, the concentration of the etchant solution used can be varied during an etching cycle. This controls how much material is removed ensuring that the remaining target material (i.e. the precursor material) remains within the desired thickness parameters for optimal isotope production. This can be achieved by analysis of an isotope solution or a portion thereof (e.g. by determining levels of impurities, which could be as a result of etching of the target holder or protective layer, where present) or by analysis of the target material / support surface. Accordingly, the method may comprise adjusting the etchant solution based on the analysis. This may be after the step of removing the etchant solution from the target chamber and the adjustment may be applied to a subsequent etching step. This allows for control based on the specific target material and target holder properties. Alternatively, the method may comprise providing the etchant in a plurality of aliquots and this may be carried out by analysing one aliquot and adjusting at least one subsequent aliquot. The pump assembly of the system may be configured to adjust the etchant. A control unit of the system may carry out the determination of the adjustment.

[0107] The method may further comprise, after recovery of an isotope solution, determining an amount of impurities in the isotope solution or in a wash solution. Based on the amount of impurities, the system or an operator can decide whether the target holder can be used for another irradiation and / orguide etchant cycles. A higher level of impurities, i.e. impurities derived from at least one material from which the target holder is made, can be indicative of damage to the target holder.

[0108] The method of the third aspect may be a method of controlling an apparatus so as irradiate a target material to generate radioisotopes. Accordingly, a target material for radiation may be provided on the support surface of the target holder and the method may further comprises irradiating the target material using a charged particle beam to provide an irradiated material comprising radioisotopes.

[0109] Where the holder body further comprises a target coolant conduit, the method further may further comprise cooling the support surface by providing a coolant fluid to the target coolant conduit.

[0110] The method may comprise dispensing a first foil portion to the first surface to cover the intermediate conduit inlet and a second foil portion to the second surface to cover the intermediate conduit outlet using the foil dispenser and subsequently moving the clamp member into the engaged position. The method may further comprise providing a coolant fluid to the intermediate conduit to reduce the temperature of the first foil portion and the second foil portion. The coolant fluid may be selected from helium, neon, argon or combinations thereof.

[0111] The method may further comprise cooling the clamp member by providing a coolant fluid to the clamp member coolant conduit.

[0112] The method may further comprise, prior to moving the clamp member into an engaged position, moving the target holder relative to the frame from the unloaded position to the loaded position so that the sealing surface and aperture are operably connectable to the clamp member. The method may further comprise applying a biasing force to the target holder when the target holder is in the loaded position to retain the target holder in the loaded position. This can be a spring force.Implementation of System and Method

[0113] In one aspect, there is provided a computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the methods disclosed herein.

[0114] In one aspect, there is provided one or more non -transitory computer readable media having a computer program stored thereon, the computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the methods disclosed herein.

[0115] Control units (or controllers) (such as computing devices or processors) set out herein may be implemented in any suitable manner, with software and / or hardware, to perform the various functions required. One or all of the control units and computing devices may, for example, employ one or more microprocessors programmed using software (for example, microcode) to perform the required functions. Examples of processor components that may be employed in various aspects include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field-programmable gate arrays (FPGAs). In various implementations, control units and computing devices (such as processors) may be associated with one or more non -transitory storage media such as volatile and non-volatile computer memory such as RAM, PROM, EPROM, and EEPROM. The non-transitorystorage media may be encoded with one or more programs that, when executed on one or more processors and / or controllers, perform the required functions. Various storage media may be fixed within a processor or controller or may be transportable, such that the one or more programs stored thereon can be loaded into the control units and computing devices (such as processors). The apparatus, and where present system, may comprise each of these components, where present, in a single device or at a single location, or these may each individually or as a whole be distributed across a network, such as the internet. The system can also contain antenna, such as RFID structures, such that the outputs can be wirelessly transmitted and / or inputs can be wirelessly transmitted. The apparatus and system can also be configured such that the data generated is encrypted. In some non-limiting examples, the system includes a user interface, such as a display. Alternatively or additionally, the system may include a communications interface device, such as a wireless transmitter, configured to receive and transmit data to an external device, such as a personal computer, tablet, smartphone, remote server, etc.Definitions

[0116] By “continuous beam path”, it is meant a pathway or conduit along which a particle beam (such as a proton beam) can pass. This may extend along a single axis or it may curve, provided that the beam can traverse the pathway. By continuous, it is meant continuous from the interface element to the target material, where the beam terminates. There may be objects along the pathway which can interact with the beam, such as the foil portions. The environments along the pathway may vary, for example with a vacuum provided in one section of the beam pathway and a gaseous atmosphere in another section.

[0117] By opposite sides, it is meant that the first and second surfaces facing in opposite directions away from one another and are not coplanar. For example, the first and second surfaces may be arranged such that at least one plane perpendicular to and extending through each surface intersects. That is, in one example of opposite sides, at least one plane perpendicular to and extending through the first surface and at least one plane to and extending through the second surface intersect each other.

[0118] In referring to “conduits” herein, the conduits have been described as extending from an inlet to an outlet and, accordingly, the conduits comprise an inlet and an outlet. In some cases, there may be plural inlet(s) and / or outlet(s) and / or the conduits may extend beyond the inlets and outlets.

[0119] By “operably connect”, it is meant that the two parts connect in a functional manner, for example, to enable an operation to be performed (e.g. to allow for a seal to be formed therebetween and for a particle beam to pass therethrough). This may not require direct physical connection between the parts. For example, two operably connecting components may be in close proximity or may bear against each other through another entity, such as receiving a foil sheet therebetween.Specific implementations

[0120] An exemplary particle accelerator may be a cyclotron. A cyclotron is a type of particle accelerator in which a beam of charged particles (e.g., H- charged particles or D- charged particles) are accelerated outwardly along a spiral orbit. The cyclotron directs the beam into a target material to generate the radioisotopes. An exemplary cyclotron is disclosed in US Patent No. 10,123,406, theentirety, including structural components and operational controls, is hereby incorporated by reference. A particle beam is directed by the cyclotron along a beam transport path, out of a beam exit aperture of the cyclotron and into an apparatus so that the particle beam is incident upon the designated target material within the apparatus. The cyclotron may include a magnetic field assembly, which generates a magnetic field for directing the charged particles along the beam transport path, and an electrical field assembly, which accelerates the particle beam. An ion source may provide the charged particles and may include a gas source (such as a source of hydrogen gas or deuterium gas) from which the charged particles are generated. A control system is provided for controlling the operation of the particle accelerator.

[0121] An example apparatus for use with such a system is disclosed in W02020 / 046924 Al, which is incorporated herein by reference.

[0122] Figs. 1 A and IB depicts a target holder 180 which can receive a target material to be irradiated and which can be used together with a particle accelerator, such as cyclotron, to produce radioisotopes. Fig. 1C depicts the target holder 180 with a different coating configuration. Fig. 2 depicts a separator member 190 which can be received within the target holder 180. The target holder 180 and separator member 190 are depicted with a connector assembly 195 in Figs 5A-C, with Fig. 3B providing a cross-sectional view through the target holder 180, separator member 190 and connector assembly 195.

[0123] The target holder 180 is a rectangular-shaped cartridge defined by a holder body 181 (or housing). The holder body 181 defines a sealing surface 181a on its upper face and comprises a target chamber 182 defined by a recess in the sealing surface 181a. In particular, the target chamber 182 comprises a chamber base 182a, a plurality of sidewalls 182b extending between the chamber base 182a and the sealing surface 181a and an aperture 182c which provides communication between the target chamber 182 and the exterior through the sealing surface 181a. As is visible in the cross-sectional drawing of Fig. IB, an etch-resistance protective layer 188 is provided on the exterior surface of the chamber base 182a and extends onto the sidewalls 182b so that the entire interior surface of the target chamber 182 is coated by the protective layer 188. Accordingly, the protective layer 188 provides a support surface across the chamber base 182a for supporting a target material to be irradiated and is provided opposite the aperture 182c so that it terminates the beam path and a material provided there on can be irradiated. Although not depicted, the protective layer 188 may further cover all surfaces of the holder body 181, including the internal surfaces of the various fluid pathways, such as outlet conduit 184 and inlet conduit 183 (discussed below).

[0124] As set out in more detail below, the target holder 180 is configured to operably connect to an apparatus 100 which can guide a particle beam received from a particle accelerator to the target chamber 182. When connected to apparatus 100, the aperture 182c forms a part of a continuous beam path leading to the support surface so that the support surface terminates the beam path and a material provided there on can be irradiated. The target holder 180 further comprises a target holder gasket channel 181b provided in the sealing surface 181a and extending around the aperture 182c so that it can seal the aperture 182c when connected to the apparatus 100 to thereby prevent leakage of material and fluidsfrom the target chamber 182. A corresponding target holder gasket 181c provided in the target holder gasket channel 181b is shown in Fig. 3D. The target holder gasket channel 181b and the target holder gasket 181c have complimentary engagement features using a tongue and groove-type fitting, whereby the walls of the target holder gasket channel 181b in cross-section tapers from a wider base towards a top opening so as to form a narrowed neck portion and the target holder gasket 181c has a wider base which engages the wider base of the target holder gasket channel 181b (the base is wider than the narrow neck portion).

[0125] The target material may be a solid (e.g., a metal or metal salt) or a liquid (e.g. a solution containing the target material, such as a metal dissolved in acid) and is provided to the support surface of the target chamber 182 (i.e. the chamber base 182a). The target holder 180 will be described herein with reference to a solid target formed on the support surface so as to provide a layer over a portion of the chamber base 182a and protective layer.

[0126] The target holder 180 further comprises an inlet conduit 183 extending through the holder body 181 from an inlet port 183a provided on the forward end face of the target holder 180 to an entry port 183b provided in the target chamber 182 so that fluids, such as etchants and wash solutions, can be provided to the target chamber 182. The target holder 180 also comprises an outlet conduit 184 which comprises and extends from an exit port 184a provided in the target chamber 182 (on the opposite sidewall 182b to the entry port 183b) to an outlet port 184b provided on the forward end surface of the target holder 180. The outlet conduit enables fluids to be recovered from the target chamber 182. In the depicted target holder 180, the entry port 183b and exit port 184a are provided on opposite sides and ends of the target chamber 182 so that fluid must go across the support surface . Further, the target holder comprises only two conduits connected to the target chamber 182 which reduces the likelihood of bubble formation as fluid is provided to the target chamber 182.

[0127] The target holder 180 further comprises a target coolant conduit 185 extending through the holder body 181 directly beneath the target chamber 182 which is used for conveying a coolant fluid to cool the holder body 181, and specifically for cooling a target material provided on the support surface . The target coolant conduit 185 has a single opening or aperture defining a port 185a in the forward end surface and extends through the body in elongate oval cylinder shape (i.e. a prism with an oval or stadium cross-section) which extends through the length of the holder body 181.

[0128] Provided within the target coolant conduit 185 is the separator member 190. The separator member 190 comprises a horizontal elongate plate 191 which is sized to extend across the width and along the length of the target coolant conduit 185 to separate the target coolant conduit 185 into two separate compartments or conduits: an upper conduit and a lower conduit which are fluidly connected at one end by an aperture 194 through the horizontal plate 191. Aside from the aperture 194, the upper and lower conduits are fluidly isolated. Further, the horizontal plate 191 is configured to separate the port 185a into two separate apertures: an upper (e.g. inlet) aperture and a lower (e.g. outlet) aperture. Fluid provided to upper inlet will travel along the upper conduit, directly beneath the target chamber 182, will reach the end of the target coolant conduit 185, pass through aperture 194 and enter the lowerconduit where it will travel to the lower outlet where it can be discharged from the apparatus 100. The separator member 190 further comprises plural parallel walls 192a, 192b projecting perpendicularly from the horizontal plate 192 on both of its upper and lower surfaces and extending along its length in the direction of the elongate extension of the target coolant conduit. This further divides each of the upper conduit and the lower conduit into parallel flow paths, which can reduce turbulence in the flow.

[0129] The target holder 180 is operably connectable to a connector assembly 195 to provide fluids to the inlet conduit and target coolant conduit 185, as well as remove fluid from the outlet conduit and the target coolant conduit 185. The connector assembly 195 itself will connect to the fluid sources and waste and provides a hub to which the target holder 180 can easily connect without requiring an operator to manually connect each fluid source and waste when one target holder 180 is exchanged for another. The connector assembly 195 comprises a connector body 195a comprising a connector discharge conduit through which fluids, such as for an isotope solution, can be removed from the target holder 180, which connector discharge conduit comprises and extends from a discharge inlet 196a to a discharge outlet 196b. The discharge inlet 196a fluidly connects to the outlet port 184b of the target holder 180. The connector body 195a also comprises a connector supply conduit extending from a supply outlet 198a for connection to a fluid source to a supply outlet 198b which fluidly connects to the inlet port 183a of the target holder 180. The connector body 195a also comprises a coolant supply conduit extending from a coolant inlet 197a to a coolant supply port 197b which fluidly connects to the upper part of the port 185a of the target holder 180 to provide coolant to the inlet defined by the separator member 190 and the port 185a, and a coolant discharge conduit which extends from a discharge port 197c fluidly connected to the port 185a to a coolant outlet 197d to receive fluid from the outlet defined by the separator member 190 and the port 185a and transfer it out of the apparatus. For connecting to the port 185a, the supply port 197 has a slot shape corresponding to the shape of the top portion of port 185a. Similarly, the discharge port 197c has a slot shape corresponding to the shape of the bottom portion of port 185a beneath the coolant supply port 197b (see Fig. 3c).

[0130] Each of the discharge inlet 196a, supply outlet 198a, coolant supply port 197b and discharge port 197c are provided on the same face of the connector assembly 195, which face is opposite the forward end face of the target holder 180. Accordingly, connection of these can be achieved by a straightforward linear movement of the target holder 180 into engagement with the connector assembly 195. This is also in part enabled by the shape of the interconnections. Specifically, the discharge inlet 196a comprises a first projecting nozzle and the outlet port 184b of the target holder 180 comprises a corresponding first connector recess. The first projecting nozzle and first connector recess connect to form the fluid connection and provide a seal across their corresponding tapering surfaces defined by these shapes. Similarly, the supply outlet 198a comprises a second projecting nozzle and the inlet port 183a of target holder 180 comprises a corresponding second connector recess. These connect to form the fluid connection and provide a seal across their corresponding tapering surfaces defined by these shapes. Further, the connector assembly 195 further comprises a projecting nozzle which incorporatesboth of the coolant supply port 197b and discharge port 197c which projection engages with a recess 185b forming a part of the perimeter of port 185a.

[0131] As depicted in Fig. 3D, a connector gasket 187 is provided between the opposing surfaces defined by the end of the target holder 180 and the connector body 195a. The connector gasket 187 is retained in place by a projecting rim 187a provided around the end of the target holder 180, which projecting rim 187a includes engagement features 187b which engage with corresponding engagement features 187c on the connector gasket 187. These all provide a leak-resistance etchant-resistant and radiation-resistant connection, the structure of which can enable automated switching of target holders 180. The connector gasket 187 further comprises a first aperture 187d providing a through passage for the supply outlet 198b to fluidly connect to the inlet port 183a, a second aperture (not shown) providing a through passage for discharge inlet 196a to fluidly connect to the outlet port 184b and a third aperture 187e through which connecting port 185a fluidly connects to the connector body 195a.

[0132] Fig. 1C depicts an alternative configuration ofthe coating on a target holder. The target holder 180’ depicted in Fig. ICis identical to that ofthe targetholder 180 ofFigs. lAand IB with the exception of the coating configuration. The target holder 180’ accordingly comprises a holder body 181’ defining a sealing surface 181a’ on its upper face and comprises a target chamber defined by a recess in the sealing surface 181a’. The target chamber 182’ comprises a chamber base 182a’, a plurality of sidewalls 182b’ extending between the chamber base 182a’ and the sealing surface 181a’ and an aperture which provides communication between the target chamber 182’ and the exterior through the sealing surface 18 la’ . As is visible in the cross-sectional drawing of Fig. 1 C, the target holder 180’ is provided with a different coating configuration in which there are plural layers. Specifically, an etch-resistance protective layer 188’ is provided on the chamber base 182a’ and extends onto the sidewalls 182b’ so that the entire interior surface of the target chamber 182’ is coated by the protective layer 188’. However, in this target holder 180’, there is an intermediate layer 189’ provided between the protective layer 188’ and the interior surfaces of the target chamber 182’. The intermediate layer 189’ is accordingly disposed or provided directly on the surfaces of the target holder 180’ with the protective layer 188’ disposed or provided on the surface of the intermediate layer 189’. Accordingly, the protective layer 188 provides a support surface across the chamber base 182a’ for supporting a target material to be irradiated and is provided opposite the aperture 182c’ so that it terminates the beam path and a material provided there on can be irradiated. The intermediate layer 189’ provides an intervening layer between the protective layer 188’ and the target holder 180’, which can improve the adherence of the layers and the stability of the protective layer 188’. Although not depicted, the intermediate layer 189’ and the protective layer 188 may further cover all surfaces of the holder body 181 ’, including the internal surfaces of the various fluid pathways, such as any outlet conduits and inlet conduits.

[0133] Figs. 4 and 5 depict an apparatus 100 for guiding a charged particle beam received from a particle accelerator to a target material to be irradiated, which apparatus 100 comprises the target holder 180 (and, in another embodiment, may comprise the target holder 180’ of Fig. 1 C) . The apparatus 100 comprises an interface element 120 for connection with a particle accelerator, such as a cyclotron. Theinterface element 120 is provided at the forward end of the apparatus 100 and comprises an interface conduit 125 through which the charged particle beam can pass. Specifically, the interface conduit 125 comprises and extends from an interface inlet 125a which is configured to connect with a beam exit aperture (not shown) of a particle accelerator to an interface outlet 125b (Fig. 6) where the beam can exit. The interface conduit 125 extends along a single central axis A.

[0134] The apparatus 100 also comprises a clamp member 140 (shown in isolation in Figs 7-10) located behind the interface element 120 (i.e. downstream in the beam pathway) which operably connects to the interface conduit 125. Referring to Fig. 6, which provides a magnified side view of a part of the front of the apparatus 100, the clamp member 140 is formed of a main body 142 (Fig. 7) which has a substantially triangular prism-shape (i.e. V-shaped from a side view) and which is pivotally mounted at its upper forward edge to the interface element 120 via a hinge 128 (Figs. 4 and 6). Hinge 128 allows the clamp member 140 to pivotally move between a disengaged position where it is spaced apart from the interface outlet 125b of the interface element 120 and an engaged position in which it engages the interface element 120 to provide a continuous beam pathway with the interface conduit 125 via the interface outlet 125b. The main body 142 has a first sidewall 144 at its forward end facing the interface element 120 and the outer surface of which defines a first surface and further a second sidewall 146 at its rear end provided on an opposite side of the main body 142 to the first sidewall 144 and the outer surface of which defines a second surface. Accordingly, the first sidewall 144 defines one of the angled surfaces of the V-shape and the second sidewall 146 defines the second of the angled surface of the V-Shape. The angles at which the first sidewall 144 and second sidewall 146 are arranged have been selected to as to optimise the irradiation of the target and the properties of the beam after traversing through the apparatus 100. In particular, and referring now to Fig. 14, when in the engaged position of the clamp member 140, the first surface defined by the first sidewall 144 is arranged at an angle ai relative to the central axis A defined by the charged particle beam (and hence the continuous beam path) at the first surface, ai can be from 35 to 50 degrees, but is specifically 42 degrees in the depicted clamp member 140. Furthermore, in the engaged position of the clamp member 140, the second surface defined by the second sidewall 146 is arranged at an angle a2 relative to a central axis defined by the continuous beam path at the second surface. a2 can be from 10 to 25 degrees, but is specifically 18 degrees in the depicted clamp member. Accordingly, the first surface as defined by the first sidewall 144 and second surface as defined by the second sidewall 146 are at an angle cu relative to one another of 120 degrees. These can be seen most clearly in the schematic depiction of the clamp member 140, the interface element 120 and the target holder 180 in Fig. 14. These angles are particularly advantageous with respect to beam profile and efficient irradiation of the target material and each of the first surface and second surface is intended to receive a foil portion to cover and seal the intermediate conduit inlet 145a and to the intermediate conduit outlet 145b, respectively.

[0135] Figs. 7 to 9 depict the clamp member 140 in isolation. As can be seen, the clamp member 140 further comprises an intermediate conduit 145 extending through the main body 142, the intermediate conduit 145 comprising and extending from an intermediate conduit inlet 145a provided in the firstsidewall 144 to an intermediate conduit outlet 145b provided in the second sidewall 146. The intermediate conduit 145 provides a passage through which a charged particle beam can pass and extends along axis A. The intermediate conduit 145 has a circular cross-section, but the angled first sidewall 144 and second sidewall 146 mean that intermediate conduit inlet 145a and the intermediate conduit outlet 145b have an oval and stadium (obround) shaped openings.

[0136] The clamp member 140 further comprises a first gasket channel 147a in the first sidewall 144 extending continuously around the intermediate conduit inlet 145a. A front sealing gasket is provided in the first gasket channel 147a and projects from the first surface (omitted from Figs. 8 and 9). In the engaged position of the clamp member 140, the front sealing gasket provides a seal between the first surface and the interface element 120 around the intermediate conduit inlet 145a and interface outlet 125b. A cutout 149a is provided on a periphery of the first gasket channel 147a for assisting release of the front sealing gasket. The interface element 120 also comprises an interface gasket channel provided in the interface element extending around the interface outlet 125b for receiving a second, front sealing gasket. The interface gasket channel and the first gasket channel 147a are sized so that they are concentric with the inner of the two having a smaller outer circumference than the other, so that each can press a foil portion against the outer surface of the other.

[0137] The target holder 180 can engage the clamp member 140. Specifically, the sealing surface 181a of the target holder 180 is arranged to bear against the second surface of the clamp member 140. In this position, the aperture 182c aligns with the intermediate conduit outlet 145b to form part of the beam path together with the intermediate conduit 145 and the interface conduit 125. The clamp member 140 further comprises a second gasket channel 147b in the second sidewall 146 extending around the intermediate conduit outlet 145b. A rear sealing gasket is provided in the second gasket channel 147b and projects from the second surface (omitted from Figs. 8 and 9). A cutout 149b (Fig. 8) is provided on a periphery of the second gasket channel 147b for assisting release of the rear sealing gasket. The target holder gasket channel 181b and the second gasket channel 147b are sized so that they are concentric with the inner of the two having a smaller outer circumference than the other, so that each can press a foil portion against the outer surface of the other.

[0138] As depicted in Fig. 10, the clamp member 140 is further provided with integrated coolant conduits for keeping the clamp member 140 and related components, e.g. foil, cool during irradiation (here the main body 142 is provided as a transparent component so that the integrated coolant conduits are visible). In particular, the clamp member 140 further comprises a foil coolant conduit 152 extending through the main body 142 and in fluid communication with the intermediate conduit 145 for conveying a coolant fluid to the intermediate conduit 145 so that the foil portions covering the intermediate conduit inlet 145a and intermediate conduit outlet 145b are cooled. The foil coolant conduit 152 comprises and extends from a coolant inlet 152a to a plurality of coolant outlets 152b which open into the intermediate conduit 145. The coolant inlet 152a is provided on an outer side face of the main body 142 where it can be connected to a coolant fluid source. The foil coolant conduit 152 extends initially as a single pathway before branching off into two legs extending in opposite directions, one leg extending towards theintermediate conduit inlet 145a and the other to the intermediate conduit outlet 145b. Coolant outlets 152b are provided on each of the legs. The plurality of coolant outlets 152b are provided in two sets. A first group of the coolant outlets 152b is arranged opposite the intermediate conduit inlet 145a and a second group is arranged opposite the intermediate conduit outlet 145b. The coolant outlets 152b opposite the intermediate conduit inlet 145a are angled to direct coolant fluid to the intermediate conduit inlet 145a (i.e. in a direction so that fluid is directed towards a foil portion provided over the intermediate conduit inlet 145a). This angle can be from 45 degrees to 90 degrees relative to the face of the intermediate conduit inlet 145a (i.e. the first surface defined by the first sidewall 144), for example. The second group of the coolant outlets 152b opposite the intermediate conduit outlet 145b are angled to direct coolant fluid to the intermediate conduit outlet 145b. This angle can be from 45 degrees to 90 degrees relative to the face of the intermediate conduit outlet 145b (i.e. the second surface defined by the second sidewall 146), for example, but is depicted as being at an angle of about 90 degrees. The foil coolant conduit 152 substantially follows the V-shape of the main body 142; that is, each portion of the foil coolant conduit 152 is approximately parallel to the surface it is adjacent to (i.e. one of the respective first surface and second surfaces).

[0139] The clamp member 140 further comprises a coolant discharge conduit 153 extending from an inlet 153a in the intermediate conduit 145 to an outlet 153b on the main body 142 for discharging coolant fluid from the intermediate conduit 145. The inlet 153a is located between the first group of coolant outlets 152b and the second group of coolant outlets 152b. This can avoid or reduce the likelihood of a flow of hotter fluid returning from one foil portion then passing over the other foil portion. Both can preferentially be fed with fresh coolant through the plurality of coolant outlets 152b. The coolant discharge conduit 153 extends to an outlet 153b provided on an outer face of the main body 142 where it can be connected to a waste pipe (not shown).

[0140] The clamp member 140 further comprises a clamp member coolant conduit 157 for conveying an additional coolant fluid for cooling the clamp member 140. The clamp member coolant conduit 157 is a separate coolant system within the main body 142 and is fluidly isolated from the intermediate conduit 145 (and hence also from the foil coolant conduit 152 and the coolant discharge conduit 153). The clamp member coolant conduit 157 comprises and extends from an inlet 157a which terminates at a connector on a side face of the main body 142, through and around the periphery of the main body 142 to an outlet 157b which terminates at a connector on a side face of the main body 142 at a position adjacent the inlet 157a.

[0141] As is most visible in Figs. 4 and 5, the apparatus 100 further comprises a first side plate 170a and a second side plate 170b (omitted from Fig. 6) provided on either side of the clamp member 140 when the apparatus 100 is assembled. These are provided for ease of manufacture and loading, but their functionality could be achieved in other ways (such as integral formation in the main body 142). Both the first and second side plates 170a, 170b comprise connectors (not visible) on their inwardly facing surfaces for connecting to corresponding connectors 172a-f on the outer surface of the main body 142. These can allow for quick attachment and release of the first and second side plates 170a, 170b. Thefirst side plate 170a attaches to the nearside of the clamp member 140 as it is shown in Figs. 4 and 5. The second side plate 170b attaches to the (opposite) far side of the clamp member 140. Each of the first and second side plates 170a, 170b are also provided with at least one cutout 171a, corresponding to the connectors of the main body 142 to allow connection of the foil coolant conduit 152, the coolant discharge conduit 153 and the clamp member coolant conduit 157 to coolant fluid sources and waste, and a further cutout 172g corresponding to the hinge 128. The first and second side plates 170a, 170b each further include an actuator slot 173a, 173b provided at their base and which extend along their length (see Fig. 11), as set out in more detail below.

[0142] The apparatus 100 and system 1 can be used with plural target holders 180, each comprising a target material. To store (either prior to or after irradiation) the target holders 180, the apparatus 100 further comprises a target holder rack 135 (or “magazine”). The apparatus 100 also comprises a frame 130 on which the target holder rack 135 and the interface element 120 are both provided and to which the clamp member 140 is connected. The frame 130 comprises a track which extends between the target holder rack 135 and the clamp member 140 so that a target holder 180 can be moved along the track from the target holder rack 135 from an unloaded position into a loaded position where the target holder 180 can engage with the clamp member 140. The target holder rack 135 comprises plural slots 186 or shelves, each slot 186 configured to receive a respective target holder 180. The target holder rack 135 is rotatable in and out of alignment with the frame 130 between a first, closed position of the target holder rack 135 in which it is connected to the track of the frame 130 (Fig. 4) and a second, open position (Fig. 5) where the target holder rack 135 is disengaged from the track of the frame 130. In the closed position, one of the slots 186 is aligned with the track so that the target holder 180 can be moved onto the track. The slots 186 can also be repositioned by movement of the target holder rack 135 up and down relative to the frame 130 to move a desired target holder 180 into position for loading.

[0143] As explained above, each target holder 180 can be moved relative to the frame 130 along the track from a first end (an unloaded position) to the second end (a loaded position) in which the corresponding sealing surface 18 la and aperture 182c can be operably connectable to the clamp member 140, when the clamp member 140 is moved into the engaged position. Accordingly, in this loaded position and the clamp member 140 is moved into the engaged position, the target chamber 182 is aligned with the continuous beam path along axis A so that a target material provided therein can be irradiated by the beam. Movement of each target holder 180 along the track between the unloaded position and the loaded position is controlled by a target holder actuator 115 (see Figs. 4 and 11). The target holder actuator 115 is a screwjack comprising an actuator part 116a (or “driver”) provided at the rear end of the apparatus 100 and connected to an elongate threaded member 116b at a first end of the elongate threaded member 116b. Rotation of the actuator part 116a causes rotation of the elongate threaded member 116b. The elongate threaded member 116b extends along the length of the apparatus 100 and is secured at its opposite, second end to the front of the apparatus 100 adjacent to the clamp member 140. Provided on the elongate threaded member 116b and engaged with the screw thread is a connector 117 such that rotation of the elongate threaded member 116b causes linear movement of theconnector 117 along the length of the elongate threaded member 116b. The connector 117 is configured to engage a target holder 180 such that movement of this part of the target holder actuator 115 causes movement of a target holder 180 from the target holder rack 135 to the track, and between the unloaded position and the loaded position. Referring to Fig. 11, the elongate threaded member 116b is parallel to the continuous beam path and the track on which the target holder 180 moves. The connector 117 extends out from the elongate threaded member 116b to the axis along which the track extends to engage the target holder 180. When the connector 117 is located at the second end of the elongate threaded member 116b, it is positioned behind the target holder rack 135 (i.e. with the target holder rack 135 between the connector 117 and the clamp member 140). The connector 117 can then be moved forwardly through a slot 136 of the target holder rack 135 to engage a target holder 180 located in the slot 136 and moves this forward onto the track of the frame 130. Further movement forward of the connector 117 moves the target holder 180 along the track and into the loaded position. The connector 117 is formed of three parts: a first moveable member 117a which is the component provided directly in contact with the elongate threaded member 116b; a second moveable member 117c which is the component provided in contact with the target holder 180 and is located forwardly compared to the first moveable member 117a; and a spring element provided between and connecting the first moveable member 117a and the second moveable member 117c. During movement of the connector 117, the spring element can serve to transmit the force from the elongate threaded member 116b to the second moveable member 117c. In the loaded position of the target holder 180, the first moveable member 117a is held in a fixed position, since the elongate threaded member 116b is not moving. This helps to secure the target holder 180 in that position. However, the spring element further provides a force acting on the second moveable member 117c causing it to bear against the back end of the target holder 180 and retaining the target holder 180 in the loaded position.

[0144] The apparatus 100 further comprises a first actuator sensor 118 configured to detect when the target holder 180 is in the loaded position and a second actuator sensor 119 configured to detect when the target holder 180 is in the unloaded position (including returned to the corresponding slot 136). To avoid damage to the first and second actuator sensors 118, 119, these are positioned outside of the beam path and out of the region behind the target (i.e. a post-target region located behind the support surface in the direction along which the beam travels if projected through the support surface). The first actuator sensor 118 is located at the front of the apparatus 100 adjacent the clamp member 140. To avoid having to place the second actuator sensor 119 in the post-target region where a sensor detecting an unloaded position would tend be located, the switch 119a of the second actuator sensor 119 is located outside of this post-target region adjacent (but laterally spaced apart from the clamp member 140) and a linkage 119b extends essentially parallel to the beam path and the elongate threaded member 116b rearwardly to the target holder rack 135. Here the second actuator sensor 119 is provided with a projection 119c which projects from the rearward end of the linkage 119b, the projection 119c being arranged so that it is actuated by the connector 117 when it reaches the rearward position equivalent to the target holder 180 being located in a slot 136.

[0145] Movement of the clamp member 140 between the engaged and disengaged positions is achieved using a clamp member actuator 110 which indirectly acts on the clamp member 140. The clamp member actuator 110 (as best seen in Fig. 11) is a screw jack comprising an actuator part Il la (or “driver”) provided centrally beneath the track of the apparatus 100 and connected to an elongate threaded member 11 lb at a first end of the elongate threaded member 11 lb. Rotation of the actuator part Illa causes rotation of the elongate threaded member 11 lb. The elongate threaded member 111b extends forwardly towards the front of the apparatus 100 and is secured at its opposite, second end to the front of the apparatus 100 beneath the clamp member 140 and interface element 120. Provided on the elongate threaded member 111b and engaged with the screw thread is a connector 112 such that rotation of the elongate threaded member 111b causes linear movement of the connector 112 along the length of the elongate threaded member 111b. The connector 112 indirectly engages the clamp member 140 such that movement of the connector 112 causes movement of the clamp member 140 between the engaged and disengaged positions. In particular, the connector comprises a first set of two track followers 112d provided on one side of the connector 112 which project laterally outwardly and which are configured to engage the actuator slot 173a of the first side plate 170a and a second set of two track followers 112e provided on the other side of the connector 112 which project laterally outwardly and which are configured to engage the actuator slot 173b of the second side plate 170b. Movement of the first and second sets of track followers 112d, 112e is caused by movement of the actuator part Illa and the corresponding rotation of the threaded member 111b. The actuator slots 173b are shaped with an elongate and curved profile and are positioned so that movement of the first and second sets of track followers 112d, 112e from front to back along the actuator slots 173b draws the first and second side plates 170a, 170b downwardly, which causes rotation or pivoting of the clamp member 140 downwardly around the hinge 128 from the disengaged position in which it is separated from the rest of the apparatus 100 (specifically, spaced apart from the interface element and, where in the loaded position, a target holder 180) to the engaged position in which the clamp member 140 clamps down on the interface element 120 and sealing surface 181a of the target holder 180. Further movement along the actuator slots 173a, 173b applies pressure to these surfaces to retain and hold a seal between these parts. Conversely, movement of the first and second sets of track followers 112d, 112e back towards the rear of the apparatus 100 along the actuator slots 173b causes the first and second side plates 170a, 170b to be pushed upwardly relative to the frame 130, causing the clamp member 140 to pivot upwardly around hinge 128 into the disengaged position. The connector 112 is formed of three parts: a first moveable member 112a which is the component provided directly in contact with the elongate threaded member 11 lb; a second moveable member 112c which is the component provided in contact with the first and second side plates 170a, 170b and a spring element provided between and connecting the first moveable member 112a and the second moveable member 112c. During movement of the connector 112, the spring element 112b can serve to transmit the force from the elongate threaded member 11 lb to the second moveable member 112c. In the engaged position, the first moveable member 112a is held in a fixed position, since the elongate threaded member 11 lb is not moving. This helps to secure the targetholder 180 in that position. However, the spring element 112b further provides a force acting on the second moveable member 112c, biasing the first and second sets of track followers 112d, 112e towards the engaged position thereby applying further downward pressure to the first and second side plates 170a, 170b. It also allows for additional application of pressure once the target holder 180 is in the loaded position in a controlled manner. The apparatus 100 further comprises a sensor configured to detect relative movement of the first moveable member 112a and the second moveable member 112c, the sensor comprising a projecting member 112f which extends forward from the first moveable member 112a towards the second moveable member 112c and contacts a switch (not shown) on the first moveable member 112a. Compression of the spring element 112b can accordingly be determined.

[0146] To detect the position of the clamp member actuator 110, the apparatus 100 further comprises a third actuator sensor 113. The third actuator sensor 113 is located at the forward end of apparatus 100 outside of the post-target region. A fourth actuator sensor 114 configured to detect when the clamp member 140 is in the disengaged position is also provided. This is also positioned outside of the posttarget region by locating a switch 114a of the fourth actuator sensor 114 outside of this post-target region adjacent (but laterally spaced apart from the clamp member 140) and providing a linkage 114b which extends essentially parallel to the beam path and the elongate threaded member 111b rearwardly. A projection 114c projects from the rearward end of the linkage 114b and is arranged so that it is actuated by the connector 112 when the clamp member 140 is disengaged.

[0147] In the apparatus 100, a single foil sheet 165 is used to provide a first foil portion and a second foil portion to the beam pathway. The foil dispenser 160 comprises a first spool 161 for receiving a first end of the foil sheet 165 and a second spool 162 for receiving the opposite, second end of the foil sheet 165 such that the foil sheet 165 extends between them. The first spool 161 is arranged in a recess 141a provided on the top surface of the clamp member 140 and is attached at one end to the first side plate 170a and at the other to the second side plate 170b (but is rotatable relative to these). Similarly, the second spool 162 is arranged in a recess 141b provided on the top surface of the clamp member 140 and is attached at one end to the first side plate 170a and at the other to the second side plate 170b (but is rotatable relative to these). Removal of the first side plate 170a enables the replacement of the first spool 161 and second spool 162. The first spool 161 is driven by a motor 161a which rotates the first spool 161 drawing an unused portion of the foil sheet 165 from the second spool 162. The arrangement of the first spool 161 and second spool 162 defines a foil dispensing path which extends from the second spool 162 across the first surface of the clamp member 140 to provide the first foil portion for sealing the intermediate conduit inlet 145a and across the second surface of the clamp member 140 to provide the second foil portion for sealing the intermediate conduit outlet 145b and onto the first spool 161. As can be seen in Figs. 7 to 9, ridges 165a, 165b are provided on either side of the clamp member 140 and serve as guides for the foil sheet extending on the foil dispensing pathway around the clamp member 140. Accordingly, when a target holder 180 is in the loaded position and the clamp member 140 is in the engaged position, the foil sheet 165 will be clamped or sealed between the first surface and the interface element 120 to seal the interface outlet 125b and the intermediate conduit inlet 145a andfurther will be clamped or sealed between the second surface and the sealing surface 181a of the target holder 180 to seal the intermediate conduit outlet 145b and the aperture 182c.

[0148] A foil dispenser sensor 164 for monitoring the dispensing of the foil sheet 165 is provided. The foil dispenser sensor 164 comprises a switch 164b held in a mount 164c attached to the second side plate 170b and projecting inwardly towards the first side plate 170a so that the switch 164b is located adjacent the second spool 162. The switch 164b can be actuated by a switch member 164a which projects from the switch 164b and is biased towards the second spool 162 to engage with a series of notches 162a provided around the circumference of the second spool 162. Rotation of the second spool 162 causes the switch member 164a to move in and out of the notches 162a and thereby actuate the switch member 164a. The use of the switch member 164a and notches 162a provides a reliable mechanical counting mechanism which is less likely to be subject to interference caused by heat or interference from the particle beam (or the products thereof), e.g. compared to electronic counters.

[0149] Fig. 13 depicts a system 1 comprising the apparatus 100 and a particle accelerator 10’ (such as a cyclotron) the system being for irradiating a target material to produce radioisotopes. In addition to or as part of the apparatus 100, the system 1 further comprises a control unit 105 (or processor) which is configured to control operation of the apparatus 100 and may further control operation of the particle accelerator 10’. The system 1 further comprises a coolant device 106, a pump assembly 200 and a processing module 255 fluidly connected to the pump assembly 200 (via outlet pipe 213’) for storing and processing solutions recovered from the target holder 180. The control unit 105 associated with or a part of the apparatus 100 can be configured to control operation of the apparatus 100, including any of the method steps set out herein. For example, the control unit 105 can control movement of the clamp member 140 between the engaged and disengaged positions and movement of the target holder 180 (e.g. between the unloaded and loaded positions) and the target holder rack 135.

[0150] Fig. 12 schematically depicts the pump assembly 200. The pump assembly 200 is fluidly connected to the target chamber 182 of the target holder 180 via the connector supply conduit, which is connected to the inlet conduit of the target holder 180 in a loaded position of the target holder 180. The pump assembly 200 can be used to provide etchant fluid (e.g. an acid or base), a wash fluid (e.g. an acid, base, buffer, water, gas) or a drying fluid (e.g. nitrogen, helium, or air). In addition or separately there may be a waste or storage outlet for receiving fluids after passing through the apparatus 100, from the respective outlets. In particular, the pump assembly 200 comprises a pumping module 210, a liquid supply module 220 for storing the liquids / solutions and a gas supply module 230 for storing gases, such as gases for drying, for use in the apparatus 100. Provision of separate modules advantageously permits replacement of individual modules without requiring the entire pump assembly 200 to be replaced. This is useful for the consumable parts, e.g. the liquid supply module 220 and gas supply module 230, but also for the pumping module 210 since more straightforward maintenance can reduce downtime of the whole system. Each of these modules 210, 220, 230 may be provided as a single unit within a housing or mounted on a frame. The pumping module 210 comprises a first pump 215, which in this system 1 takes the form of a syringe having a first pump actuator 215a which is moveable to draw and pumpliquid. The first pump 215 is connected to a first valve 217, which in turn is fluidly connected to the connector supply conduit of the connector assembly 195 via a first pipe 218 and further is fluidly connected to the liquid supply module 220, the gas supply module 230 and a waste vessel 250. The first valve 217 is arranged so that it controls flow of fluid from the liquid supply module 220 and the gas supply module 230 into the first pump 215 and then on into the apparatus 100 or the waste vessel 250. First pump 215 can draw fluid from one of the liquid supply module 220 and the gas supply module 230 based on the position of the first valve 217. To then expel the fluid, the first pump actuator 215a can be reversed and the valve switched to direct fluid to the apparatus 100 or waste vessel 250.

[0151] The liquid supply module 220 comprises two etchant solution reservoirs 221a, 221b containing different concentrations of etchant solutions and a wash fluid reservoir 225 containing a wash solution. A liquid module valve 222 is fluidly connected to each of the reservoirs 221a, 221b, 225 in this liquid supply module 220 and controls which of these is fluidly connected to the pumping module 210.

[0152] The pumping module 210 further comprises a second pump 211 in the form of a syringe having a second pump actuator 211a which is moveable to draw and pump fluid. The second pump 211 is connected to a second valve 212. The second valve 212 in turn connects to the connector discharge conduit of the connector assembly 195 via a second pipe 213 and further to the waste vessel 250. This allows second pump 211 to draw fluid from the apparatus 100 and either provide the solution to the processing module 255 via an outlet pipe 213’, where it can be processed and / or stored, or discharge it to the waste vessel 250.

[0153] The processing module 255 is used to process and / or store solutions recovered from the target chamber 182, for example of the isotope solution generated during etching (i.e. the etchant and recovered isotopes). The processing module 255 may accordingly comprise a series of storage vessels for storing recovered isotope solution, as well as various solutions and equipment (such as filters) for processing the isotope solution. This can include filters for filtering out unwanted components etched from the surfaces of the target holder 180 during recovery. Processing may include concentrating the isotope solution recovered from the target holder 180, which may be in an initial dilute form as a result of the etching process.

[0154] The control unit 105 associated with or a part of the apparatus 100 can be configured to control operation of the apparatus 100, including any of the method steps set out herein. The control unit 105, which may be a processor or a plurality of processors, can be configured to control operation of the pump assembly, including the valves and pumps. The control unit 105 may be further configured to control operation of the coolant device 106 and the foil dispenser. The coolant device 106 is configured to provide a coolant fluid to the various coolant conduits, and therefore comprises at least one source of coolant fluid. This includes being configured to provide coolant fluid (such as helium) to the foil coolant conduit 152 of the clamp member 140, provide coolant fluid (such as an aqueous coolant) to the clamp member coolant conduit 157 and provide coolant fluid (such as an aqueous coolant) to the target coolant conduit 185. The coolant device 106 may include connectors and conduits or tubing for connecting to the inlets of the abovementioned conduits.

[0155] Although not depicted, the pump assembly 200 may optionally further comprise a heater arranged to heat fluid (e.g. an etchant solution) provided to the target chamber 182. This can improve the recovery of isotopes and can ensure a relatively consistent and predictable recovery, as set out above. The heater may be provided at any point in the flow path, including along the fluid pathway(s) or at the respective fluid sources of the liquid supply module 220 (e.g. etchant solution reservoirs 221a, 221b); however, in one embodiment the heater (which may be a single heating module or plural heating modules) may be configured to heat fluid moving through first pipe 218 to the connector supply conduit of the connector assembly 195. The heater may be controlled by the control unit 105 which may be configured to control the heater. For example, the control unit 105 may be configured to control the heater so as to follow a single heating profile. Alternatively, the control unit may be configured to control the heater so as to follow a ramp or gradient heating profile.

[0156] In use, the apparatus 100 is connected to a particle accelerator 10’ by connecting the interface element 120, and specifically, by connecting the interface inlet 125a to a beam outlet aperture of the particle accelerator 10’. At least one target holder 180 comprising target material provided on the support surface can be loaded into a slot 136 of the target holder rack 135. When required, the target holder rack 135 can be moved so that a slot 136 containing a target holder 180 can be aligned with the track of the frame 130. The target holder actuator 115, which is positioned in this initial configuration with the connector 117 located at the rear of the apparatus 100 (relative to the particle accelerator 10’), is actuated to engage the target holder 180 from behind and move it from the slot 136 onto the track of the frame 130. The target holder actuator 115 further moves the connector 117 along the elongate threaded member 116b, and hence the target holder 180, until the target holder 180 engages the connector assembly 195, where it is in the loaded position. In this position, the discharge inlet 196a fluidly connects to the outlet port 184b of the target holder 180; the supply outlet 198a fluidly connects to the inlet port 183a of the target holder 180; the coolant supply port 197b fluidly connects to the upper part of the port 185a; and the discharge port 197c fluidly connects to the lower part of the port 185a.

[0157] Before, during or after moving the target holder 180 from the unloaded position to the loaded position and with the clamp member 140 in the disengaged position, a foil sheet 165 may be provided to the clamp member 140. In the first use, this may be providing a new first spool 161 and second spool 162 ontothe second side plate 170b and the recesses 141a, 141b ofthe clamp member 140 and providing the foil sheet 165 around the dispensing path of the clamp member 140. The first side plate 170a can be attached to the side of the clamp member 140 and the remainder of the apparatus 100 in this position. Alternatively or additionally (and with the first side plate 170a in position), this may comprise actuating the foil dispenser to cause the first spool 161 to rotate and draw a new portion of the foil sheet 165 from the second spool 162 around the dispensing path. The first side plate 170a can be attached to the side of the clamp member 140 and the remainder of the apparatus 100 in this position.

[0158] Once the foil sheet 165 has been provided to the first and second surfaces, the clamp member 140 can be moved into the engaged position by actuating the clamp member actuator 110. Movement of the connector 112 forwardly causes the first and second sets of track followers 112d, 112e to movealong their respective actuator slots 173a, 173b. The shape of the actuator slots 173a, 173b, specifically the upward trajectory, causes the first and second side plates 170a, 170b to be pulled downwardly, which pulls the clamp member down 140. The clamp member 140 is then engaged with and clamped down against the target holder 180 and the interface element 120. This also seals the first foil portion between the first surface and the interface element 120 over the interface outlet 125b and the intermediate conduit inlet 145a and seals the second foil portion over the intermediate conduit outlet 145b and the sealing surface 181a. Other seals, where present, may also be engaged at this point to create a sealed target chamber 182, sealed intermediate conduit 145 and sealed interface conduit 125.

[0159] The particle accelerator 10’ is then operated to irradiate the target material using a particle beam provided along the continuous beam path to form an irradiated material comprising radioisotopes.

[0160] After irradiation, the radioisotopes are recovered. Where using a solid target, this is achieved by recovering the radioisotopes in solution. This comprises providing an etchant solution to the target chamber 182 via the inlet port 183a and the entry port 183b in the target chamber 182 using the pump assembly 200. To reduce the chance of bubble formation in the target chamber 182 or conduits, the pressure in the target chamber 182 may be reduced prior to etching. The pump assembly 200 can be actuated to provide the vacuum by drawing all of the fluid out of the target chamber 182.

[0161] At least a part of the irradiated material on the support surface can be etched to dissolve the radioisotopes in the etchant solution to from an isotope solution. The isotope solution is then removed from the target chamber 182 via the exit port 184a in the target chamber 182 and through the outlet port 184b. This is then transferred to the processing module 255, where it can be processed and / or stored. The provision of the isotope solution after irradiation of a solid target material is particularly flexible, since it allows for higher efficiencies (as compared to liquid targets) but the subsequent recovery in this way allows for more straightforward handling. For example, the isotope solution can be transferred via a conduit to a different location in a site where it can be processed further, without disrupting further irradiations in the location of the system 1. Depending on the thickness of the initial target material on the support surface and / or the irradiation parameters, only a portion of the target material may be irradiated. That is, the irradiated material may comprise radioisotopes on its surface but may have a lower portion beneath this comprising isotope precursor. Recovery may include allowing the etchant solution to reside in the target chamber 182 for an etching time period before removing the etchant solution and the isotope solution from the target chamber 182, the etching time period being selected to etch the irradiated material and dissolve the radioisotopes in the etchant solution without etching the further portion comprising isotope precursor. This can be achieved using by regularly monitoring the thickness of the target material and / or performing material integrity checks. Further, calibration and alignment of the beam may further help to avoid unintended removal.

[0162] The target holder 180 may then be rinsed through the use of a rinse or wash fluid provided to the target chamber 182 by the pump assembly 200. This will remove any residual isotopes or acid from the apparatus 100. A further fluid (gas, such as an inert gas such as nitrogen, helium or air) may be provided by the pump assembly 200 to dry the target chamber 182.

[0163] Where a target holder 180 is depleted or an alternative target holder 180 is to be removed, it can be removed by the reverse of the insertion process. That is, the coolant fluids within the target holder 180 and the clamp member 140 are removed. Drying of the clamp member coolant conduit 157 can be achieved using the pump assembly 200 and is advantageous in systems 1 which include moisture sensors for detecting leaks, as this reduce the risk of accidental alerts. After removing fluids, the clamp member 140 is moved to the disengaged position and the target holder 180 can be moved to the unloaded position using the target holder actuator 115 and returned to the target holder rack 135. The foil sheet 165 may then be replaced, either by actuation of the foil dispenser or replacement of the first spool 161 and second spool 162.

[0164] As demonstration of the benefits of the configurations set out above, exemplary configurations of the apparatus 100 can include the following parameters set out in Table 1.Table 1

[0165] Each of the above examples have been found to provide effective management of beam properties and to provide an efficient arrangement for generation of radioisotopes using a solid target. For example, using a typical cyclotron beam can have a beam energy of 14.5 to 16.5 MeV, but the exemplary configurations can reduce this to an ideal beam energy range of 12 to 13 MeV, such as 12.7 to 13 MeV. This can also result in -500 W beam power dissipated on foil sheet, with 800W - IkW on the target material. Moreover, the spot size caused by these angles enlarges the strike area on the support surface and spreads the power dissipation across this area, as compared to a 90-degree angle beam strike. Within a beam, there are intense hot spots that can significantly increase the likelihood of the typical target evaporating, melting, or failing. The angles and foil portions set out herein can control and avoid these hot spots. This broader, thinner irradiation area also has synergy with isotope recovery from a solid target. Specifically, this results in a broader, thinner area with isotopes for recovery, allowing for more gentle etching techniques to be used, which in turn reduces the risk of damage to the target chamber 182.

[0166] One exemplary target holder 180 comprises a holder body 181 consisting of copper. The holder body 181 in this example is provided with a thickness of the chamber base as 1.2mm - i.e. the thickness of the chamber base at at least one point between the target coolant conduit and the target chamber. This provides excellent heat conduction and dissipation. The target chamber 181a has a depth of 2mm and a length of 32mm. The entire holder body 181, including the chamber base 182a, the sidewalls 182b and the entry port 183b and exit port 184a are coated with a protective layer 188 consisting of gold. The gold protective layer was formed with a thickness of approximately 7 pm. This was achieved by immersing the holder body 181 in an electroplating solution with 3 automated syringeswhich monitored the electroplating solution level, pH, temperature and forcing the fluid to travel through the various internal channels and surface of the holder body 181 while plating to assure internal plating. The compatibility and properties of gold and copper provided an excellent and robust holder body. The connector assembly 195 used with was formed from (consisted of) PEEK.

[0167] In one specific example, a solid zinc target material was provided onto the support surface defined by the chamber base 182a and the protective layer. A GE PETtrace cyclotron was used to irradiate the zinc target using a proton beam (with the configuration set out for Example 2, above) providing a beam power of approximately 800W and forming68Ga radioisotopes. During irradiation, the target holder 180 to reached approximately 250 °C using water as a coolant. As a target holder of the same dimensions and formed from other materials is expected to reach approximately 400 °C at the same beam power. The lower temperature of the exemplary target body not only leads to a faster irradiation cycle (less cooling time afterwards), but also significantly reduces the risk of damage. For example, zinc melts at 419 °C and so the target holder 180 being at 400 °C may prevent further reuse.

[0168] The radioisotopes formed were recovered by providing 0.25M nitric acid in 20 cycles of etching to the target chamber 182. The total amount recovered was 50 mg.

[0169] Another exemplary target holder 180’ comprises a holder body 181’ consisting of copper. The holder body 181 ’ in this example is provided with a thickness of the chamber base as 1 ,2mm - i.e. the thickness of the chamber base at at least one point between the target coolant conduit and the target chamber. This provides excellent heat conduction and dissipation. The target chamber 181a has a depth of 2mm and a length of 32mm. The entire holder body 181’, including the chamber base 182a’, the sidewalls 182b’ and the entry port and exit port are coated with an intermediate layer 189’ consisting of nickel and a protective layer 188’ provided over the intermediate layer 189’ and consisting of gold. The gold protective layer was formed with a thickness of approximately 7 pm. Forming the intermediate layer 189’ and the protective layer 188’ was achieved by immersing the holder body 181’ in an electroplating solution with 3 automated syringes which monitored the electroplating solution level, pH, temperature and forcing the fluid to travel through the various internal channels and surface of the holder body 181 while plating to assure internal plating. The compatibility and properties of gold, nickel and copper provided an excellent and robust holder body.

[0170] The detailed description and specific examples, while indicating exemplary aspects of the apparatus 100, systems 1 and methods, are intended for purposes of illustration only and are not intended to limit the scope. These and other features, aspects, and advantages of the apparatus 100, systems and methods of the present disclosure can be better understood from the description, appended claims or aspects, and accompanying drawings. It should be understood that the Figures are merely schematic and are not drawn to scale. In the aspects or claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent aspects or claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

[0171] Clauses seting out specific examples of the disclosure are provided below:

[0172] Clause 1. A target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator, the target holder comprising: a holder body comprising: a target chamber that is at least partly delimited by a chamber base; an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; and a protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated; wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture; and wherein the protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0173] Clause 2. The target holder of clause 1, wherein the target chamber is further delimited by chamber sidewalls extending from the chamber base, and wherein the protective layer is provided over the chamber sidewalls and the chamber base within the target chamber so as to cover internal surfaces of the target chamber.

[0174] Clause 3. The target holder of any preceding clause, wherein the protective layer extends at least partially into the outlet conduit so as to cover internal surfaces of the outlet conduit at the exit port.

[0175] Clause 4. The target holder of any preceding clause, wherein the holder body further comprises an inlet conduit in fluid communication with the target chamber for providing an etchant solution to the target chamber.

[0176] Clause 5. The target holder of clause 4, wherein the inlet conduit extends from an inlet port to an entry port provided in and in fluid communication with the target chamber; and wherein the protective layer extends at least partially into the inlet conduit so as to cover internal surfaces of the inlet conduit at the entry port.

[0177] Clause 6. The target holder of any preceding clause, wherein the protective layer is a metal layer or metal oxide layer comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0178] Clause 7. The target holder of clause 6, wherein the protective layer is a metal layer or metal oxide layer consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0179] Clause 8. The target holder of any preceding clause, wherein the protective layer has a thickness of from 5 nm to 1000 micrometres.

[0180] Clause 9. The target holder of any preceding clause, wherein the protective layer has acidresistance defined by a loss of less than 10% of total weight when exposed to IM nitric acid for 30 minutes.

[0181] Clause 10. The target holder of any preceding clause, wherein the chamber base has a heat conductivity which is greater than the heat conductivity of the protective layer.

[0182] Clause 11. The target holder of clause 10, wherein the chamber base comprises a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0183] Clause 12. The target holder of one of clause lO or clause 11, wherein the chamber base consists of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0184] Clause 13. The target holder of any of clauses 11 to 13, wherein the holder body comprises or consists of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0185] Clause 14. The target holder of any preceding clause, wherein the holder body further comprises a target coolant conduit extending at least partially through the holder body adjacent the target chamber for conveying a coolant fluid for cooling a target material for irradiation provided on the support surface .

[0186] Clause 15. The target holder of clause 14, wherein the target coolant conduit at least partly extends along or beneath the chamber base so as to convey coolant fluid for cooling a target material for irradiation provided on the support surface.

[0187] Clause 16. The target holder of clause 15, wherein the holder body further comprises a port in fluid communication with the target coolant conduit and through which coolant fluid can be provided to the target coolant conduit; and wherein the target holder further comprises a separator member provided in the target coolant conduit and configured to separate the port into an inlet and an outlet and, further, to separate the target coolant conduit so as to define a flow path extending through the target coolant conduit from the inlet to the outlet.

[0188] Clause 17. The target holder of clause 16, wherein the separator member further comprises at least one wall extending along the target coolant conduit configured to divide at least a part of the target coolant conduit into two parallel flow paths.

[0189] Clause 18. The target holder of any preceding clause, wherein the holder body further comprises: a sealing surface for forming a seal with a surface of a particle accelerator, wherein the aperture extends through the sealing surface; and wherein sealing surface comprises a gasket channel formed in the sealing surface extending around the aperture.

[0190] Clause 19. The target holder of clause 18, wherein the target holder further comprises a sealing gasket provided in the gasket channel and arranged around the aperture, optionally wherein the sealing gasket comprises or consist of a polymer selected from a fluoroelastomer, an ethylene -propylene elastomer or polytetrafluoroethylene (PTFE).

[0191] Clause 20: The target holder of clause 19, wherein the sealing gasket comprises a first engagement feature and the gasket channel comprises a second engagement feature, wherein the first engagement feature and second engagement feature are complimentary and are configured to retain the sealing gasket in the gasket channel.

[0192] Clause 21. The target holder of any preceding clause, wherein the target chamber has a height of less than or equal to 10 mm, optionally less than or equal to than 5 mm.

[0193] Clause 22. The target holder of any preceding clause, further comprising an intermediate layer provided between the protective layer and the at least a portion of the chamber base on which the protective layer is formed.

[0194] Clause 23, The target holder of clause 22, wherein the intermediate layer comprises a metal or metal oxide comprising Ag, Co, Ni, Rh and Pd or combinations thereof, optionally wherein the intermediate layer comprises or consists of a metal or metal oxide comprising Ag, Co, Ni, Rh and Pd or combinations thereof. The intermediate layer may comprise or consist of Nickel.

[0195] Clause 24. A system for holding atarget material for irradiation by a charged particle beam of a particle accelerator, the system comprising: a target holder comprising a holder body, the holder body comprising: a target chamber that is at least partly delimited by a chamber base; a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber; an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; and an inlet conduit in fluid communication with the target chamber for providing a solution to the target chamber, the inlet conduit extending from an entry port provided in and in fluid communication with the target chamber to an inlet port, and a pump assembly fluidly connected to the target chamber via the outlet conduit and the inlet conduit, wherein the pump assembly is configured to: provide an etchant solution to the target chamber via the inlet conduit to etch at least a part of an irradiated material comprising radioisotopes so as to dissolve the radioisotopes in the etchant solution and thereby form an isotope solution; and remove the isotope solution from the target chamber via the exit port of the outlet conduit.

[0196] Clause 25. The system of clause 24, wherein the pump assembly is configured to provide a solution to the target chamber at flow rate of from 10 mL / min to 50 mL / min.

[0197] Clause 26. The system of any one of clauses 24 or 25, wherein the pump assembly is further configured to reduce the pressure within the target chamber, optionally wherein the pump assembly is further configured to draw gas from the target chamber to reduce the pressure within the target chamber.

[0198] Clause 27. The system of any of clauses 24 to 26, wherein the target holder is according to any one of clauses 1 to 23.

[0199] Clause 28. The system of any of clauses 24 to 27, further comprising a connector assembly configured to connect to the target holder, the connector assembly comprising: a connector body comprising: a connector discharge conduit for removing an isotope solution from the target holder, the connector discharge conduit extending from a discharge inlet to a discharge outlet, a connector supply conduit for supplying a fluid to the target chamber, the connector supply conduit extending from a supply inlet for connection to a fluid source to a supply outlet; and wherein the supply outlet is configured to operably connect with the inlet port of the target holder so as to provide fluid communication from the supply inlet to the target chamber; and wherein the discharge inlet is configured to operably connect with the outlet port of the target holder so as to provide fluid communication from the target chamber to the discharge outlet.

[0200] Clause 29. The system of clause 28, wherein the pump assembly is fluidly connected to the target chamber via the inlet conduit and the connector supply conduit.

[0201] Clause 30. The system of clause 28 or clause 29, wherein the holder body comprises a holder mating surface and the connector assembly comprises a connector mating surface wherein, when the target holder and connector assembly are operably connected, the holder mating surface and connector mating surface connect and are in opposing relationship; and wherein the inlet port and outlet port of the target holder are provided on the holder mating surface and the supply outlet and discharge inlet are provided on the connector mating surface and are arranged such that connection of the holder mating surface and connector mating surface causes the outlet port to fluidly connect to the discharge inlet and the inlet port to fluidly connect to the supply outlet.

[0202] Clause 31. The system of clause 29, wherein one of the outlet port and the discharge inlet comprises a first projecting nozzle and the other of the outlet port and the discharge inlet comprises a corresponding first connector recess, wherein the first projecting nozzle and first connector recess connect to form the fluid connection; and wherein one of the inlet port and the supply outlet comprises a second projecting nozzle and the other of the inlet port and the supply outlet comprises a corresponding second connector recess, which projecting nozzle and connector recess connect to form the fluid connection.

[0203] Clause 32. The system of one of clause 29 or clause 30, wherein the holder body further comprises: a target coolant conduit extending at least partially through the holder body adjacent the target chamber for conveying a coolant fluid for cooling a target material for irradiation provided on the support surface; and a port in fluid communication with the target coolant conduit and through which coolant fluid can be provided to the target coolant conduit; and wherein the connector body further comprises: a coolant supply conduit extending from a coolant inlet for connection to a coolant fluid source to a connector supply port, the connector supply port being configured to operably connect with the port of the target holder so as to provide fluid communication from the coolant inlet to the target coolant conduit.

[0204] Clause 33. The system of clause 32, wherein the port of the target coolant conduit is provided on the holder mating surface and the connector supply port is provided on the connector mating surface such that connection of the holder mating surface and connector mating surface causes the port to fluidly connect to the coolant inlet.

[0205] Clause 34. The system of any of clauses 28 to 33, further comprising a connector gasket provided between the holder mating surface and the connector mating surface, the connector gasket providing a seal around each of the holder mating surface and the connector mating surface, optionally wherein the connector gasket comprises or consist of a polymer selected from a fluoroelastomer, an ethylene -propylene elastomer or polytetrafluoroethylene (PTFE).

[0206] Clause 35. The system of clause 34, wherein the gasket comprises an engagement feature configured to retain the gasket relative to the holder mating surface and / or the connector mating surface .

[0207] Clause 36. The system of any of clauses 28 to 35, wherein the connector assembly comprises or consists of an etchant-resistant polymer.

[0208] Clause 37. The system of any of clauses 28 to 36, wherein a connector protective layer is provided on internal surfaces of the connector discharge conduit, the connector protective layer comprising a metal or metal oxide comprising or consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

[0209] Clause 38. The system of any of clauses 28 to 37, further comprising a frame configured to receive the target holder; and wherein the target holder is moveable relative to the frame from an unloaded position to a loaded position in which the target holder and connector assembly are operably connected.

[0210] Clause 39. The system of clause 38, further comprising a target holder actuator configured to move the target holder from the unloaded position to the loaded position, the target holder actuator comprising: a first moveable member configured to move the target holder; and a first driver configured to move the first moveable member.

[0211] Clause 40. The system of clause 39, wherein the target holder actuator further comprises a biasing element provided between the first moveable member and the target holder; and wherein the target holder actuator is configured such that, in the loaded position of the target holder, the first moveable member is stationary with respect to the frame so as to hold the target holder in the loaded position and the biasing element further provides a force acting on the target holder so as to retain the target holder in the loaded position.

[0212] Clause 41. The system of any of clauses 38 to 40, further comprising a target holder rack provided on the frame and comprising at least one slot configured to receive the target holder in the unloaded position, wherein the target holder actuator is configured to move the target holder from the target holder rack in the unloaded position to the loaded position.

[0213] Clause 42. A method of forming an isotope solution from an irradiated material comprising radioisotopes provided in a target holder, the target holder comprising: a holder body comprising: a target chamber that is at least partly delimited by a chamber base; a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber; an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port, wherein the method comprises: providing an etchant solution to the target chamber to etch at least a part of an irradiated material comprising radioisotopes so as to dissolve the radioisotopes in the etchant solution and form an isotope solution; and removing the isotope solution from the target chamber via the exit port of the outlet conduit.

[0214] Clause 43. The method of clause 42, wherein the irradiated material comprises the radioisotopes formed from an isotope precursor through irradiation and a further portion comprising isotopeprecursor; and wherein the method further comprises allowing the etchant solution to reside in the target chamber for an etching time period before removing the etchant solution and the isotope solution from the target chamber, the etching time period being selected to etch the irradiated material and dissolve the radioisotopes in the etchant solution without etching the further portion comprising isotope precursor.

[0215] Clause 44. The method of one of clause 42 or clause 43, wherein the etching time period is selected to etch an amount of the irradiated material of from 1pm to 20pm.

[0216] Clause 45. The method of any of clauses 42 to 44, further comprising reducing the pressure in the target chamber prior to providing an etchant solution.

[0217] Clause 46. The method of any of clauses 42 to 45, wherein a solution is provided to the target chamber at flow rate of from 10 mL / min to 50 mL / min.

[0218] Clause 47. The method of any of clauses 42 to 46, wherein the etchant solution comprises nitric acid.

[0219] Clause 48. The method of any of clauses 42 to 47, wherein a target material for radiation is provided on the support surface of the target holder; and wherein the method further comprises: irradiating the target material using a charged particle beam to provide an irradiated material comprising radioisotopes.

[0220] Clause 49. The method of clause 48, wherein the holder body further comprises a target coolant conduit extending at least partially through the holder body adjacent the target chamber for conveying a coolant fluid for cooling a target material for irradiation provided on the support surface; and wherein the method further comprises cooling the support surface by providing a coolant fluid to the target coolant conduit.

[0221] Clause 50. The method of any of clauses 42 to 49, wherein the target holder is a target holder as defined in any one of clauses 1 to 23.

[0222] Clause 51. A computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the method of any of clauses 42 to 50.

[0223] Clause 52. One or more non-transitory computer readable media having a computer program stored thereon, the computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the method of any of clauses 42 to 50.

[0224] Clause 53: A target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator, the target holder comprising: a holder body comprising: a target chamber that is at least partly delimited by a chamber base; an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port, the chamber base defining a support surface for supporting a target material to be irradiated; wherein the aperture and support surface are arranged such that a target materialprovided on the support surface can be irradiated by a charged particle beam passing through the aperture.

[0225] Clause 54: The target holder of clause 53, wherein and a protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated; wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture.

[0226] Clause 55. The target holder of clause 54, wherein the protective layer has a thickness of from 5 nm to 1000 micrometres.

[0227] Clause 56. The target holder of clause 54 or clause 55, wherein the target chamber is further delimited by chamber sidewalls extending from the chamber base, and wherein the protective layer is provided over the chamber sidewalls and the chamber base within the target chamber so as to cover internal surfaces of the target chamber.

[0228] Clause 57. The target holder of any of clauses 54 to 56, wherein the protective layer extends at least partially into the outlet conduit so as to cover internal surfaces of the outlet conduit at the exit port.

[0229] Clause 58. The target holder of any of clauses 54 to 57, wherein the chamber base has a heat conductivity which is greater than the heat conductivity of the protective layer.

[0230] Clause 59. The target holder of any of clauses 54 to 58, wherein the chamber base comprises a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0231] Clause 60. The target holder of one of clause 59, wherein the chamber base consists of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0232] Clause 61. The target holder of any of clauses 58 to 60, wherein the holder body comprises or consists of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

[0233] Clause 62. The target holder of any of clauses 53 to 61, wherein the holder body further comprises a target coolant conduit extending at least partially through the holder body adjacent the target chamber for conveying a coolant fluid for cooling a target material for irradiation provided on the support surface.

[0234] Clause 63. The target holder of clause 62, wherein the target coolant conduit at least partly extends along or beneath the chamber base so as to convey coolant fluid for cooling a target material for irradiation provided on the support surface.

[0235] Clause 64. The target holder of clause 63, wherein the holder body further comprises a port in fluid communication with the target coolant conduit and through which coolant fluid can be provided to the target coolant conduit; and wherein the target holder further comprises a separator member provided in the target coolant conduit and configured to separate the port into an inlet and an outlet and, further, to separate the target coolant conduit so as to define a flow path extending through the target coolant conduit from the inlet to the outlet.

[0236] Clause 65. The target holder of clause 64, wherein the separator member further comprises at least one wall extending along the target coolant conduit configured to divide at least a part of the target coolant conduit into two parallel flow paths.

[0237] Clause 66. The target holder of any of clauses 53 to 65, wherein the holder body further comprises: a sealing surface for forming a seal with a surface of a particle accelerator, wherein the aperture extends through the sealing surface; and wherein sealing surface comprises a gasket channel formed in the sealing surface extending around the aperture.

[0238] Clause 67. The target holder of clause 66, wherein the target holder further comprises a sealing gasket provided in the gasket channel and arranged around the aperture, optionally wherein the sealing gasket comprises or consist of a polymer selected from a fluoroelastomer, an ethylene -propylene elastomer or polytetrafluoroethylene (PTFE).

[0239] Clause 68: The target holder of clause 67, wherein the sealing gasket comprises a first engagement feature and the gasket channel comprises a second engagement feature, wherein the first engagement feature and second engagement feature are complimentary and are configured to retain the sealing gasket in the gasket channel.

[0240] Clause 69. The target holder of any of clauses 53 to 68, wherein the target chamber has a height of less than or equal to 10 mm, optionally less than or equal to than 5 mm.

[0241] Clause 70. The target holder of any of clauses 53 to 69, wherein the holder body further comprises an inlet conduit in fluid communication with the target chamber for providing an etchant solution to the target chamber.

[0242] Clause 71. The target holder of clause 70, wherein the inlet conduit extends from an inlet port to an entry port provided in and in fluid communication with the target chamber.

[0243] Clause 72. The target holder of any of clauses 53 to 73, further comprising an intermediate layer provided between the protective layer and the at least a portion of the chamber base on which the protective layer is formed.

[0244] Clause 73. The target holder of clause 74, wherein the intermediate layer comprises a metal or metal oxide comprising Ag, Co, Ni, Rh and Pd or combinations thereof, optionally wherein the intermediate layer comprises or consists of a metal or metal oxide comprising Ag, Co, Ni, Rh and Pd or combinations thereof. The intermediate layer may comprise or consist of Nickel.

Claims

CLAIMS1. A target holder for holding a target material for irradiation by a charged particle beam of a particle accelerator system, the target holder comprising:a holder body comprising:a target chamber that is at least partly delimited by a chamber base;an aperture in the holder body providing an inlet to the target chamber; and an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; anda protective layer provided on at least a portion of the chamber base within the target chamber, the protective layer defining a support surface for supporting a target material to be irradiated;wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam passing through the aperture; andwherein the protective layer comprises a metal or metal oxide comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

2. The target holder of claim 1, wherein the target chamber is further delimited by chamber sidewalls extending from the chamber base, and wherein the protective layer is further provided over the chamber sidewalls.

3. The target holder of any preceding claim, wherein the protective layer extends at least partially into the outlet conduit to cover the internal surface of the outlet conduit at the exit port.

4. The target holder of any preceding claim, wherein the holder body further comprises an inlet conduit in fluid communication with the target chamber for providing a solution to the target chamber, the inlet conduit extending from an inlet port to an entry port provided in and in fluid communication with the target chamber; and wherein the protective layer extends at least partially into the inlet conduit to cover the internal surface of the inlet conduit at the entry port.

5. The target holder of any preceding claim, wherein the protective layer is a metal layer or metal oxide layer comprising Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof, optionally wherein the protective layer is a metal layer or metal oxide layer consisting of Ag, Au, Ru, Rh, Os, Ir, Pt, Zr, Ti, Nb, Ta, Ni, W, Nb or combinations thereof.

6. The target holder of any preceding claim, wherein chamber base has a heat conductivity which is greater than the heat conductivity of the protective layer.

7. The target holder of claim 6. wherein the chamber base comprises a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof, optionally wherein the chamber base consists of a metal or metal oxide comprising Cu, Al, Ti, W, Ta, Ag, Au, Nb or combinations thereof.

8. The target holder of any preceding claim, wherein the holder body further comprises a target coolant conduit extending at least partially through the holder body along or beneath the chamber base for conveying a coolant fluid for cooling a target material provided on the support surface; and wherein the target coolant conduit comprises a port through which coolant fluid can be received; and wherein the target holder further comprises a separator member provided in the target coolant conduit and configured to separate the port into an inlet and an outlet and, further, to separate the target coolant conduit into a flow path extending through the target coolant conduit from the inlet to the outlet.

9. The target holder of any preceding claim, wherein the holder body further comprises: a sealing surface for forming a seal with a surface of a particle accelerator, wherein the aperture extends through the sealing surface; and wherein sealing surface comprises a gasket channel formed in the sealing surface extending around the aperture; and wherein the target holder further comprises a sealing gasket provided in the gasket channel and arranged around the aperture, optionally wherein the sealing gasket comprises or consist of a polymer selected from a fluoroelastomer, an ethylene -propylene elastomer or polytetrafluoroethylene (PTFE).

10. The target holder of any preceding claim, further comprising an intermediate layer provided between the protective layer and the at least a portion of the chamber base on which the protective layer is formed.

11. A system for holding a target material for irradiation by a charged particle beam of a particle accelerator, the system comprising:a target holder comprising a holder body, the holder body comprising:a target chamber that is at least partly delimited by a chamber base;a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber;an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture;an outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port; andan inlet conduit in fluid communication with the target chamber for providing a solution to the target chamber, the inlet conduit extending from an entry port provided in and in fluid communication with the target chamber to an inlet port, and a pump assembly fluidly connected to the target chamber via the outlet conduit and the inlet conduit,wherein the pump assembly is configured to:provide an etchant solution to the target chamber via the inlet conduit to etch at least a part of an irradiated material comprising radioisotopes to dissolve the radioisotopes in the etchant solution and thereby form an isotope solution; andremove the isotope solution from the target chamber via the exit port of the outlet conduit.

12. The system of claim 11, wherein the pump assembly is configured to provide a solution to the target chamber at flow rate of from 10 mL / min to 50 mL / min.

13. The system of one of claim 11 or claim 12, wherein the pump assembly is further configured to reduce the pressure within the target chamber.

14. A method of forming an isotope solution from an irradiated material comprising radioisotopes provided in a target holder, the target holder comprising:a holder body comprising:a target chamber that is at least partly delimited by a chamber base;a support surface for supporting a target material for irradiation, wherein the support surface is provided in the target chamber;an aperture in the holder body providing an inlet to the target chamber, wherein the aperture and support surface are arranged such that a target material provided on the support surface can be irradiated by a charged particle beam through the aperture; andan outlet conduit for removing an etchant solution from the target chamber, the outlet conduit extending from an exit port provided in and in fluid communication with the target chamber to an outlet port,wherein the method comprises:providing an etchant solution to the target chamber to etch at least a part of an irradiated material comprising radioisotopes to dissolve the radioisotopes in the etchant solution and form an isotope solution; andremoving the isotope solution from the target chamber via the exit port of the outlet conduit.

15. The method of claim 14, wherein the irradiated material comprises the radioisotopes formed from an isotope precursor through irradiation and a further portion comprising isotope precursor; andwherein the method further comprises allowing the etchant solution to reside in the target chamber for an etching time period before removing the etchant solution and the isotope solution from the target chamber, the etching time period being selected to etch the irradiated material and dissolve the radioisotopes in the etchant solution without etching the further portion comprising isotope precursor.

16. The method of claim 14 or claim 15, wherein the etching time period is selected to etch an amount of the irradiated material of from 1pm to 20pm.

17. The method of any of claims 14 to 16, further comprising reducing the pressure in the target chamber prior to providing an etchant solution.

18. The method of any of claims 14 to 17, wherein a solution is provided to the target chamber at flow rate of from 10 mL / min to 50 mL / min.

19. A computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the method of any of claims 14 to 18.

20. One or more non-transitory computer readable media having a computer program stored thereon, the computer program comprising computer program code which is configured, when said computer program is run on one or more physical computing devices, to cause said one or more physical computing devices to implement the method of any of claims 14 to 18.

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