Systems and methods for differentially activatable assemblies

Abstract

A method of designing an assembly includes defining an observable field, defining a model of the assembly based on a set of parameters, and performing an inverse optimization of the set of parameters such that the model of the assembly after activation produces the observable field. An assembly includes a first material and a second material. The assembly is configured to be differentially activatable via particle bombardment. An observable field of the assembly is complex. Advantageously the differentially activatable assembly can be stable prior to activation, self-contained, activated after construction, and provides unique three-dimensional or four-dimensional observable fields.

Description

SYSTEMS AND METHODS FOR DIFFERENTIALLY ACTIVATABLE ASSEMBLIESCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No. 63 / 578,436, filed August 24, 2023, which is hereby incorporated herein in its entirety by reference.FIELD

[0002] The present disclosure relates to radiation apparatuses, systems, and methods, for example, differentially activatable assembly apparatuses, systems, and methods.BACKGROUND

[0003] Radiation therapy utilizes ionizing radiation to control cell growth, typically as part of cancer treatment to destroy malignant cells. Ionizing radiation includes particle radiation (e.g., alpha, beta, proton, neutron, electron, etc.) or electromagnetic (EM) radiation (e.g., ultraviolet (UV), extreme UV (EUV), X-rays, gamma rays, etc.) that have sufficient energy to ionize atoms or molecules by detaching electrons from them. During treatment, ionizing radiation damages the DNA of cancerous tissue leading to cellular death.

[0004] Radiation therapy may be curative in a number of types of cancer if localized to one area. Current radiation therapy is used to direct radiation to a target region (e.g., a region containing a tumor) and destroy those cells within the target region. To reduce exposure of healthy tissue (e.g., tissue which radiation must pass through to treat the tumor), radiation beams can be aimed from different angles to intersect at the target region.

[0005] Radiobiology investigates the interaction of ionizing radiation with biological systems to help develop an improved delivery of radiation for radiation therapy. Similar to clinical techniques, current radiobiology aims to irradiate small target volumes with high levels of precision and accuracy. Biological systems, including but not limited to small animals, humans, tissues, cells, food, etc., can be used for irradiation applications and radiobiology investigations. For example, small animal models (e.g., mice) have beenapplied in radiobiology studies due to the genetic and physiologic similarities with humans. Further, complex emission profiles may be needed to maintain safety and high levels of precision and accuracy for different radiation applications (e.g., radiotherapy applications, irradiation applications, food sterilization, small animal irradiation, tissue irradiation, irradiation of animate and / or inanimate objects, for example, radiotherapy, atomic batteries, sterilization, etc.).

[0006] However, current radioactive emitters only provide uniform (non-complex) emission profiles for a limited number of materials and geometries, and are not suitable for high precision radiation applications requiring customized, unique emission profiles. Further, current radioactive emitters are unstable (e.g., radioactive) and activated prior to construction of the emitter, which limits the construction of radiation-shaping devices (e.g., collimators), is unsafe, and increases the risk of radiation exposure during handling and manipulation. In contrast, if assembling and / or manufacturing stable materials, precision and complexity of radiation-shaping devices (e.g., collimators) can both be increased. Additionally, current manufacturing of radioactive emitters is not optimized for the particular application and fails to consider the optimal materials, composition, geometry, and / or decay times to produce a desired unique three-dimensional or fourdimensional emission profile.SUMMARY

[0007] Accordingly, there is a need to develop a differentially activatable assembly that is stable prior to activation, self-contained, activated after construction, and optimized to provide complex (e.g., non-uniform) and unique three-dimensional or four-dimensional observable fields (e.g., emission profiles, etc.) for high precision radiation applications. Further, there is a need to utilize an inverse optimization model to determine the optimal design and construction of a differentially activatable assembly to produce a desired observable field (e.g., emission profile, etc.).

[0008] In some aspects, a method of designing a differentially activatable assembly can include defining an observable field. In some aspects, the method can further include defining a model of the differentially activatable assembly based on a set of parameters. In some aspects, the method can further include performing an inverse optimization of the set of parameters such that the model of the differentially activatable assembly afteractivation produces the observable field. Advantageously the method can perform an inverse optimization based on custom inputs or parameters (e.g., desired emission profile, energy deposition distribution, dose distribution, particle field, plurality of materials, half- lives, etc.) to model an optimal differentially activatable assembly capable of producing the desired observable field (e.g., emission profile, etc.) when activated.

[0009] In some aspects, the observable field can include an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof. In some aspects, the set of parameters describing the model can include one or more activatable materials, one or more non-activatable materials, a geometry of the materials, a distribution of the materials, activation cross-sections of the materials, decay characteristics of the materials, half-lives of the materials, radioactivity distributions of the materials, emitted particles of the materials, a particle field for activation of the materials, activation time, waiting period after activation, or a combination thereof.

[0010] In some aspects, the method can further include manufacturing the differentially activatable assembly based on the model after the inverse optimization. In some aspects, the method can further include activating the differentially activatable assembly after manufacturing to produce the observable field. Advantageously the optimized model of the differentially activatable assembly can be constructed and subsequently activated to produce the desired observable field (e.g., emission profile, etc.).

[0011] In some aspects, a system for designing a differentially activatable assembly can include a modeling system. In some aspects, the modeling system can be configured to define an observable field. In some aspects, the modeling system can be further configured to define a model of the differentially activatable assembly based on a set of parameters. In some aspects, the modeling system can be further configured to perform an inverse optimization of the set of parameters such that the model of the differentially activatable assembly after activation produces the observable field. Advantageously the system can perform an inverse optimization based on custom inputs or parameters (e.g., desired emission profile, energy deposition distribution, dose distribution, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable assembly capable of producing the desired observable field (e.g., emission profile, etc.) when activated.

[0012] In some aspects, the observable field can include an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof. In some aspects, the set of parameters describing the model can include one or more activatable materials, one or more non-activatable materials, a geometry of the materials, a distribution of the materials, activation cross-sections of the materials, decay characteristics of the materials, half-lives of the materials, radioactivity distributions of the materials, emitted particles of the materials, a particle field for activation of the materials, activation time, waiting period after activation, or a combination thereof.

[0013] In some aspects, the system can further include a manufacturing system configured to manufacture the differentially activatable assembly based on the model after the inverse optimization. In some aspects, the system can further include an activation system configured to activate the differentially activatable assembly after manufacturing to produce the observable field. Advantageously the optimized model of the differentially activatable assembly can be constructed and subsequently activated to produce the desired observable field (e.g., emission profile, etc.).

[0014] In some aspects, a method of designing a differentially activatable assembly can include defining an observable field (e.g., emission profile, etc.). In some aspects, the method can further include determining a particle field for activation of a volume of a material. In some aspects, the method can further include determining a plurality of materials each with different activation cross-sections and decay characteristics to form complex radioactivity distributions. In some aspects, the method can further include optimizing a distribution of the plurality of materials in a geometry based on the complex radioactivity distributions, the particle field, and the observable field (e.g., emission profile, etc.), thereby modeling the differentially activatable assembly to produce the observable field (e.g., emission profile, etc.) after bombardment via the particle field. Advantageously the method can perform an inverse optimization based on custom inputs or parameters (e.g., desired emission profile, energy deposition distribution, dose distribution, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable assembly capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field.

[0015] In some aspects, the observable field can include an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof.

[0016] In some aspects, the method can further include manufacturing the differentially activatable assembly based on the optimized distribution. In some aspects, the method can further include bombarding the manufactured differentially activatable assembly with the particle field, thereby activating the differentially activatable assembly to form a radioactive emitter and produce the observable field (e.g., emission profile, etc.). Advantageously the optimized model of the differentially activatable assembly can be constructed and subsequently activated to produce the desired observable field (e.g., emission profile, etc.).

[0017] In some aspects, the plurality of materials can include an activatable material and a non-activatable material. In some aspects, optimizing the distribution can include optimizing in three-dimensions. Advantageously the optimized three-dimensional distribution of activatable and non-activatable materials in the differentially activatable assembly can provide a unique three-dimensional observable field (e.g., emission profile, etc.) when activated.

[0018] In some aspects, optimizing the distribution can include optimizing in four- dimensions. In some aspects, optimizing in four-dimensions can include calculating waiting periods after activation based on different half-lives of the plurality of materials. Advantageously the optimized four-dimensional (3D over time) distribution of materials with different half-lives in the differentially activatable assembly can provide a unique four-dimensional (3D over time) observable field (e.g., emission profile, etc.) when activated.

[0019] In some aspects, optimizing the distribution can include using an optimization algorithm. In some aspects, the optimization algorithm can include simulated annealing, gradient descent, finite difference, interpolation, population models, regression, parameter adaptation, supervised machine learning, unsupervised machine learning, neural networks, classification models, clustering, vector quantization, stochastic gradient descent, implicit updates, leaky averaging, momentum methods, adaptive gradient (AdaGrad), backpropagation, root mean square propagation (RMSProp), adaptive moment estimation (Adam), or a combination thereof. Advantageously the optimizationalgorithm can perform an inverse optimization of the custom inputs or parameters (e.g., desired emission profile, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable assembly capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field.

[0020] In some aspects, a method of manufacturing a differentially activatable assembly can include optimizing a distribution of a plurality of materials in a geometry based on an observable field (e.g., emission profile, etc.), a particle field for activation, and relevant characteristics of the plurality of materials (such as density, atomic number, interaction cross sections, etc.). In some aspects, the method can further include manufacturing the differentially activatable assembly based on the optimized distribution. Advantageously the method can optimize a distribution of materials based on the custom inputs or parameters (e.g., desired emission profile, particle field, radioactivity distributions, etc.) in order to manufacture a differentially activatable assembly with the optimized distribution of materials that is capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field.

[0021] In some aspects, the method can further include activating the differentially activatable assembly after manufacturing the differentially activatable assembly thereby forming a radioactive emitter. Advantageously the method can provide a radiation-safe environment for finer manipulation of the materials during manufacturing of the differentially activatable assembly. Further advantageously the differentially activatable assembly can be activated after manufacturing, which increases safety and decreases the risk of radiation exposure during manufacturing.

[0022] In some aspects, manufacturing the differentially activatable assembly can include ion implanting one or more of the plurality of materials. In some aspects, ion implanting can have a spatial resolution in three-dimensions of at least 1 micron (e.g., 1 pm spatial resolution along X-axis, 1 pm spatial resolution along Y-axis, 1 pm spatial resolution along Z-axis). Advantageously a second material (e.g., activatable material) can be ion implanted within a first material (e.g., shielding material) with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0023] In some aspects, manufacturing the differentially activatable assembly can include depositing one or more of the plurality of materials. In some aspects, depositing caninclude epitaxy, physical vapor deposition (PVD), electron-beam PVD (EBPVD), sputter deposition, electrosputtering, chemical vapor deposition (CVD), plasma-enhanced CVD (PECVD), atomic layer deposition (ALD), powder bed deposition, or a combination thereof. Advantageously one or more of the plurality of materials can be deposited with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0024] In some aspects, manufacturing the differentially activatable assembly can include manufacturing with a computer controlled manufacturing system. In some aspects, the computer controlled manufacturing system can include a computer numerically controlled (CNC) machine, an additive manufacturing machine, a subtractive manufacturing machine, a drill, a lathe, a mill, a grinder, a router, a 3D printer, a lithographic machine, a photolithographic machine, an inkjet machine, a sintering machine, a fused deposition machine, or a combination thereof. Advantageously the computer controlled manufacturing system (e.g., lithographic machine) can form the distribution of materials of the differentially activatable assembly with high accuracy and precision (e.g., 1 mm spatial resolution, 100 pm spatial resolution, 10 pm spatial resolution, 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, sub-1 nm spatial resolution, etc.).

[0025] In some aspects, an assembly can include a first material and a second material. In some aspects, the assembly can include a deliberately designed three-dimensional (3D) distribution of the first and second materials. In some aspects, the deliberately designed 3D distribution can be determined by an inverse optimization. In some aspects, the second material can be within the first material. In some aspects, the first material can include a non-activatable material (e.g., a shielding material). In some aspects, the second material can include an activatable material (e.g., a radioactive source after activation). In some aspects, the assembly can be configured to be differentially activatable via particle bombardment. In some aspects, an observable field (e.g., emission profile, etc.) of the assembly can be complex. In some aspects, an observable field (e.g., emission profile, etc.) of the assembly can be a desired distribution. In some aspects, an observable field (e.g., emission profile, etc.) of the assembly can be deliberately designed.Advantageously the assembly can be activated differentially (e.g., differently based on anorientation of the assembly relative to a direction of the particle bombardment, differently based on differences in activation cross-sections with the particle bombardment, differently based on differences in decay rates, etc.) to provide a desired observable field (e.g., emission profile, etc.) that is complex. Further advantageously the assembly after activation can provide ionizing radiation, including but not limited to, X-rays, gamma rays, alpha particles, beta particles, protons, neutrons, electrons, or a combination thereof.

[0026] In some aspects, the observable field (e.g., emission profile, etc.) can be anisotropic. In some aspects, the assembly can have a unique geometry. In some aspects, the assembly can have a unique distribution of the first material (e.g., non-activatable material) and the second material (e.g., activatable material). In some aspects, the observable field (e.g., emission profile, etc.) can be a unique three-dimensional observable field (e.g., emission profile, etc.). In some aspects, the assembly can have a unique geometry and a unique distribution of the first material (e.g., non-activatable material) and the second material (e.g., activatable material). Advantageously the unique geometry and the unique distribution of the assembly can provide a unique three- dimensional observable field (e.g., emission profile, etc.) when activated.

[0027] In some aspects, the assembly can have a unique decay time. In some aspects, the observable field (e.g., emission profile, etc.) can be a unique four-dimensional observable field (e.g., emission profile, etc.). In some aspects, the assembly can have a unique geometry, a unique distribution of the first material (e.g., non-activatable material) and the second material (e.g., activatable material), and a unique decay time. Advantageously the unique geometry, the unique distribution, and the unique decay time of the assembly can provide a unique four-dimensional (3D over time) observable field (e.g., emission profile, etc.) when activated.

[0028] In some aspects, the assembly can be self-contained. In some aspects, the assembly can be stable prior to activation. In some aspects, the assembly can be configured to be activated after construction of the assembly thereby forming a radioactive emitter (e.g., activated assembly). Advantageously the assembly prior to activation can provide a radiati on- safe environment for finer manipulation of the materials and can be activated after construction, which increases precision and complexity of radiation-shaping devices (e.g., collimators), increases safety, and decreases the risk of radiation exposure during handling and manipulation.

[0029] In some aspects, the second material (e.g., activatable material) can include a distribution of activatable atoms within the first material (e.g., non-activatable material). In some aspects, the distribution of activatable atoms can include a plurality of different distributions of activatable atoms. Advantageously the plurality of different distributions of activatable atoms (e.g., activatable radioactive sources) in the assembly can provide differentially activatable customized and complex observable fields (e.g., emission profiles, etc.).

[0030] In some aspects, the first material can include a distribution of non-activatable materials having varying attenuation and scattering properties within the first material. In some aspects, the distribution of non-activatable materials can include a plurality of pockets (e.g., voids) within the first material. In some aspects, the second material can include a distribution of activatable atoms within the first material, and the first material can include a distribution of non-activatable materials having varying attenuation and scattering properties (e.g., plurality of pockets) within the first material. In some aspects, the distribution of activatable atoms and the distribution of non-activatable materials can be uniquely distributed within the first material thereby forming a unique three- dimensional observable field (e.g., emission profile, etc.). Advantageously the unique distribution of the distribution of activatable atoms (e.g., activatable radioactive sources) and the distribution of non-activatable materials (e.g., plurality of pockets) in the assembly can provide a unique three-dimensional observable field (e.g., emission profile, etc.).

[0031] In some aspects, the first material (e.g., non-activatable material) and the second material (e.g., activatable material) can have a different activation cross-section. In some aspects, the first material (e.g., non-activatable material) and the second material (e.g., activatable material) can have a different half-life (e.g., time required for decaying quantity to fall to half its initial value). In some aspects, the first material and the second material can have a different activation cross-section and / or a different half-life. In some aspects, the second material can have a higher activation cross-section than the first material. In some aspects, the first material can have a lower activation cross-section and either a longer half-life or a shorter half-life relative to the second material. Advantageously the lower activation cross-section of the first material (e.g., non- activatable material) can serve as shielding and the higher activation cross-section of the second material (e.g., activatable material) can serve as an emitter to provide a uniquethree-dimensional observable field (e.g., emission profile, etc.). Further advantageously the longer half-life or shorter half-life of the first material (e.g., non-activatable material) relative to the second material (e.g., activatable material) can provide a unique fourdimensional (3D over time) observable field (e.g., emission profile, etc.).

[0032] In some aspects, the second material (e.g., activatable material) can include a neutron activated material. In some aspects, the neutron activated material can include cesium, cobalt, iron, iridium, or a combination thereof. In some aspects, the neutron activated material can include cesium-133 (133Cs). Advantageously the neutron activated material (e.g.,133Cs) can provide a stable (prior to activation) and self-contained differentially activatable assembly with a controlled activation and decay scheme (e.g., activation of133Cs to134Cs with a half-life of about 2 years).

[0033] In some aspects, the first material can include lead, a lead composite, tin, rubber, polyvinyl chloride, antimony, tungsten, bismuth, or a combination thereof. In some aspects, the first material can include lead (Pb). Advantageously the first material (e.g., Pb) can provide a majority of stable isotopes (e.g.,204Pb,206Pb,207Pb,208Pb) and only a limited number of radioactive isotopes (e.g.,205Pb,209Pb) with extremely long (e.g.,205Pb with a half-life of about 1.73 x 107years) or extremely short (e.g.,209Pb with a half-life of about 3.3 hours) half-lives for safe and stable shielding. In some aspects, first material can be composed of a purified form of lead (Pb), for example, first material can be 100% 206Pb such that activation of any Pb atoms creates another stable isotope (e.g.,207Pb or 2°8pb)

[0034] In some aspects, the first material can include an activatable material. In some aspects, the first material and the second material can produce different emitted particles. Advantageously different materials of the first material (e.g., first activatable material) and the second material (e.g., second activatable material) can form complex activity distributions. Further advantageously first and second activatable materials of first and second materials, respectively, can produce different emitted particles (e.g., high energy gamma rays and electrons) for different applications.

[0035] In some aspects, a longitudinal axis of the second material (e.g., activatable material) can be aligned along a longitudinal axis of the first material. Advantageously the alignment of the first material (e.g., shielding material) and the second material (e.g., activatable material) can produce a high fluence observable field (e.g., emission profile, etc.) in a direction along the longitudinal axis.

[0036] In some aspects, the assembly can further include a collimator coupled to the second material (e.g., activatable material). In some aspects, the collimator can be within the first material (e.g., shielding material). In some aspects, the collimator can include a void within the first material. In some aspects, a longitudinal axis of the void can be aligned along a longitudinal axis of the first material. In some aspects, the void can extend between a distal end of the second material and a distal end of the first material. Advantageously the collimator can produce asymmetries in the observable field (e.g., emission profile, etc.) and can collimate radiation emitted from the second material to produce a highly directional fluence. Further advantageously the collimator can be formed from (within) the first material itself with high precision (e.g., anisotropic milling or etching to form a defined void) to form a miniature, self-contained differentially activatable assembly.

[0037] In some aspects, the assembly can further include a pocket within the first material. In some aspects, the pocket can include a gas pocket or a vacuum pocket. In some aspects, the gas pocket can include air, nitrogen, helium, argon, carbon dioxide, or a combination thereof. In some aspects, the pocket can include a plurality of pockets within the first material. Advantageously the one or more pockets within the first material can create differential emission, scattering, and / or attenuation in the assembly to produce a unique (e.g., optimized) anisotropic observable field (e.g., emission profile, etc.) in three- dimensions around the assembly.

[0038] In some aspects, the assembly can have a volume of no greater than 100 cm3. In some aspects, the assembly can have a volume of no greater than 1 cm3. In some aspects, the assembly can have a volume of no greater than 100 mm3. In some aspects, the assembly can have a volume of no greater than 1 mm3. In some aspects, the assembly can have a volume of no greater than 100 pm3. In some aspects, the assembly can have a volume of no greater than 1 pm3. Advantageously the first material and the second material of the assembly can be formed with high precision (e.g., anisotropic milling, etching, ion implantation, deposition, melting, lithography, liquefaction, sintering, 3D printing, etc.) to form a miniature, self-contained differentially activatable assembly on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0039] In some aspects, the assembly can be cylindrical (e.g., a right cylinder, a rod). In some aspects, the assembly can be ellipsoidal (e.g., a sphere). In some aspects, the assembly can be a three-dimensional orthotope (e.g., a cube). Advantageously thedifferentially activatable assembly can have a unique geometry to provide a unique three- dimensional observable field (e.g., emission profile, etc.).

[0040] Implementations of any of the techniques described above can include a system, a method, a process, a device, and / or an apparatus. The details of one or more implementations are set forth in the accompanying drawings and the description below. Other features will be apparent from the description and drawings, and from the claims.

[0041] Further features and exemplary aspects of the aspects, as well as the structure and operation of various aspects, are described in detail below with reference to the accompanying drawings. It is noted that the aspects are not limited to the specific aspects described herein. Such aspects are presented herein for illustrative purposes only. Additional aspects will be apparent to persons skilled in the relevant art(s) based on the teachings contained herein.BRIEF DESCRIPTION OF THE DRAWINGS / FIGURES

[0042] The accompanying drawings, which are incorporated herein and form part of the specification, illustrate the aspects and, together with the description, further serve to explain the principles of the aspects and to enable a person skilled in the relevant art(s) to make and use the aspects.

[0043] FIG. 1 illustrates a modeling flow diagram for designing a differentially activatable assembly, according to an exemplary aspect.

[0044] FIG. 2 illustrates a modeling flow diagram for optimizing a distribution of materials in a differentially activatable assembly, according to an exemplary aspect.

[0045] FIG. 3 illustrates a manufacturing flow diagram for manufacturing a differentially activatable assembly, according to an exemplary aspect.

[0046] FIG. 4 is a schematic illustration of a system for designing and manufacturing a differentially activatable assembly, according to an exemplary aspect.

[0047] FIG. 5 is a schematic perspective illustration of a differentially activatable assembly, according to an exemplary aspect.

[0048] FIG. 6 is a plot of activations (creation of a certain isotope) per incident activation particle (e.g., neutron) for different material species produced from the differentially activatable assembly shown in FIG. 5, according to an exemplary aspect.

[0049] FIG. 7 is a plot of activity (decay of a certain isotope) per incident activation particle (e.g., neutron) over time for different material species produced from the differentially activatable assembly shown in FIG. 5, according to an exemplary aspect.

[0050] FIG. 8 is a plot of relative activity based on a ratio of total activity (e.g., sum of all isotopes) over time for an activatable material (e.g., Cs) to total activity of a shielding material (e.g., Pb) produced from the differentially activatable assembly shown in FIG. 5, according to an exemplary aspect.

[0051] FIG. 9 is a plot of a 2D fluence profile of the differentially activatable assembly shown in FIG. 5, according to an exemplary aspect.

[0052] FIG. 10 is a schematic perspective illustration of a differentially activatable assembly, according to an exemplary aspect.

[0053] FIG. 11 is a plot of activity (decay of a certain isotope) per incident activation particle (e.g., neutron) over time for different material species produced from the differentially activatable assembly shown in FIG. 10, according to an exemplary aspect.

[0054] FIGS. 12A-12C are plots of 2D fluence profiles of the differentially activatable assembly shown in FIG. 10, accordingly to exemplary aspects.

[0055] The features and exemplary aspects of the aspects will become more apparent from the detailed description set forth below when taken in conjunction with the drawings, in which like reference characters identify corresponding elements throughout. In the drawings, like reference numbers generally indicate identical, functionally similar, and / or structurally similar elements. Additionally, generally, the left-most digit(s) of a reference number identifies the drawing in which the reference number first appears. Unless otherwise indicated, the drawings provided throughout the disclosure should not be interpreted as to-scale drawings.DETAILED DESCRIPTION

[0056] This specification discloses one or more aspects that incorporate the features of this present invention. The disclosed aspect(s) merely exemplify the present invention. The scope of the invention is not limited to the disclosed aspect(s). The present invention is defined by the claims appended hereto.

[0057] The aspect(s) described, and references in the specification to “one aspect,” “an aspect,” “an example aspect,” “an exemplary aspect,” etc., indicate that the aspect(s)described can include a particular feature, structure, or characteristic, but every aspect may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same aspect. Further, when a particular feature, structure, or characteristic is described in connection with an aspect, it is understood that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other aspects whether or not explicitly described.

[0058] Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “on,” “upper” and the like, can be used herein for ease of description to describe one element or feature’s relationship to another element(s) or feature(s) as illustrated in the figures. The spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. The apparatus can be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein can likewise be interpreted accordingly.

[0059] The term “about” or “substantially” or “approximately” as used herein means the value of a given quantity that can vary based on a particular technology. Based on the particular technology, the term “about” or “substantially” or “approximately” can indicate a value of a given quantity that varies within, for example, 0.1-10% of the value (e.g., ±0.1%, ±1%, ±2%, ±5%, or ±10% of the value).

[0060] Numerical values, including endpoints of ranges, can be expressed herein as approximations preceded by the term “about,” “substantially,” “approximately,” or the like. In such cases, other aspects include the particular numerical values. Regardless of whether a numerical value is expressed as an approximation, two aspects are included in this disclosure: one expressed as an approximation, and another not expressed as an approximation. It will be further understood that an endpoint of each range is significant both in relation to another endpoint, and independently of another endpoint.

[0061] Aspects of the disclosure may be implemented in hardware, firmware, software, or any combination thereof. Aspects of the disclosure may also be implemented as instructions stored on a machine-readable medium (e.g., memory), which may be read and executed by one or more processors. A machine-readable medium may include any mechanism for storing or transmitting information in a form readable by a machine (e.g., a computing device). For example, a machine-readable medium may include read only memory (ROM); random access memory (RAM); magnetic disk storage media; opticalstorage media; flash memory devices; electrical, optical, acoustic, or other forms of propagated signals (e.g., carrier waves, infrared signals, digital signals, etc.); and others. Further, firmware, software, routines, and / or instructions may be described herein as performing certain actions. However, it should be appreciated that such descriptions are merely for convenience and that such actions in fact result from computing devices, processors, controllers, or other devices executing the firmware, software, routines, instructions, etc.

[0062] The term “observable field” as used herein indicates an observable, dobs, that can be measured, for example, but not limited to, a physical quantity, a field, a distribution, an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, a derivative thereof, or any other observable quantity, field, or distribution. In some aspects, the observable field can be known. In some aspects, the observable field can be a desired observable field.

[0063] The term “model” as used herein indicates an observable field, Ftp), resulting from a current set of parameters, p, and a forward map, F, that maps p into Ftp). In some aspects, the observable field Ftp) can include a three-dimensional model of a differentially activatable assembly. In some aspects, the observable field Ftp) can include a four-dimensional model of a differentially activatable assembly. In some aspects, the set of parameters p can be unknown and adjustable.

[0064] In some aspects, the set of parameters p can be parameters of a differentially activatable assembly, for example, but not limited to, a geometry of the differentially activatable assembly, a volume of the differentially activatable assembly, materials of the differentially activatable assembly, spatial distribution of the materials, activation crosssections of the materials, half-lives of the materials, decay characteristics of the materials, emitted particles of the materials, radioactivity distributions of the materials, particle field for activation of the materials, activation time, waiting period after activation, or any other parameter of the differentially activatable assembly.

[0065] The term “inverse optimization” or “optimizing” as used herein indicates optimally solving an inverse problem, p = F^do , of a forward problem, obs = Ftp), to determine the set of parameters p that produce a known observable field dobs. In some aspects, the observable field dobs can be known and the set of parameters p can beunknown, and the set of parameters p can be solved (e.g., optimized) with the constraint that when the observable field F(p) is activated, the optimized model produces the known observable field dobs.

[0066] In some aspects, if the inverse F1does not exist, or if the solution is untenable due to various physical, technical, and / or computational constraints, then an objective function, G, can be defined to solve the inverse problem. For example, the objective function G can define a metric, G(dObs, Ftp)), that describes a difference between dobs and Fp), to be optimized (minimized or maximized). In some aspects, various optimization algorithms (e.g., gradient descent, simulated annealing, etc.) can be used to determine the set of parameters p that optimize G subject to physical and / or user-defined constraints (e.g., available materials, volume constraints, etc.).

[0067] The term “complex” as used herein indicates an observable field that depends on multiple factors and / or different parts. In some aspects, the complex observable field can be uniform (e.g., isotropic). In some aspects, the complex observable field can be non- uniform (e.g., anisotropic). In some aspects, the complex observable field can be based on a three-dimensional model. In some aspects, the complex observable field can be based on a four-dimensional model. In some aspects, the complex observable field can be dynamic and change over time (e.g., time-dependent). In some aspects, the complex observable field can include one or more fields or distributions. In some aspects, the complex observable field can include a combination or superposition of multiple fields or distributions. In some aspects, the complex observable field can include varied intensity in three-dimensions (e.g., intensity modulated radiotherapy (IMRT)). In some aspects, the complex observable field can include a mixed radiation field composed of a combination of ionizing radiation (e.g., electrons, gamma rays, etc.).

[0068] The term “desired” or “desired distribution” or “deliberately designed” as used herein indicates a unique, optimized, and / or predetermined value, distribution, or design for a particular application (e.g., radiotherapy application, irradiation application, etc.), for example, a desired observable field for a radiotherapy application (e.g., treatment planning) or a deliberately designed observable field for an irradiation application (e.g., food sterilization, tissue irradiation, animate object, inanimate object, radiotherapy, atomic batteries, sterilization).Exemplary Designing Method

[0069] As discussed above, radiation therapy utilizes ionizing radiation to control cell growth, typically as part of cancer treatment to destroy malignant cells. Ionizing radiation includes particle radiation (e.g., alpha, beta, proton, neutron, electron, etc.) or EM radiation (e.g., UV, EUV, X-rays, gamma rays, etc.) that have sufficient energy to ionize atoms or molecules by detaching electrons from them.

[0070] Current radiation therapy is used to direct radiation to a target region (e.g., a region containing a tumor) and destroy those cells within the target region. To reduce exposure of healthy tissue (e.g., tissue which radiation must pass through to treat the tumor), radiation beams can be aimed from different angles to intersect at the target region.

[0071] Current radiobiology aims to irradiate small target volumes with high levels of precision and accuracy. Biological systems, including but not limited to, small animals, humans, cells, food, etc., can be used for irradiation applications and radiobiology investigations. For example, small animal models (e.g., mice) have been applied in radiobiology studies due to the genetic and physiologic similarities with humans. Further, complex and unique emission profiles may be needed to maintain safety and high levels of precision and accuracy for different radiation applications (e.g., intraoperative radiotherapy, food sterilization, small animal irradiation, tissue irradiation, irradiation of animate and / or inanimate objects, for example, radiotherapy, atomic batteries, sterilization, etc.).

[0072] However, current radioactive emitters only provide uniform (non-complex) emission profiles for a limited number of materials and geometries, and are not suitable for high precision radiation applications requiring customized, unique emission profiles. Further, current radioactive emitters are unstable (e.g., radioactive) and activated prior to construction of the emitter, which limits the construction of radiation-shaping devices (e.g., collimators), is unsafe, and increases the risk of radiation exposure during handling, manipulation, and manufacturing. In contrast, if assembling and / or manufacturing stable materials, precision and complexity of radiation-shaping devices (e.g., collimators) can both be increased. Additionally, current manufacturing of radioactive emitters is not optimized for the particular application and fails to consider the optimal materials, composition, geometry, and / or decay times to produce a desired unique three-dimensional or four-dimensional emission profile.

[0073] Aspects of differentially activatable assembly apparatuses, systems, and methods as discussed below can provide a differentially activatable assembly that is stable prior to activation, self-contained, differentially activatable, activated after construction, and optimized to provide complex (non-uniform) and unique three-dimensional or fourdimensional emission profiles for high precision radiation applications. Further, aspects of differentially activatable assembly apparatuses, systems, and methods as discussed below can utilize an inverse optimization model to determine the optimal design and construction of a differentially activatable assembly to produce a desired observable field (e.g., emission profile, etc.).

[0074] FIG. 1 illustrates modeling flow diagram 100 for designing a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000), according to an exemplary aspect. It is to be appreciated that not all steps in FIG. 1 are needed to perform the disclosure provided herein. Further, some of the steps may be performed simultaneously, sequentially, and / or in a different order than shown in FIG. 1. Modeling flow diagram 100 shall be described with reference to FIGS. 1, 4-11, and 12A-12C. However, modeling flow diagram 100 is not limited to those example aspects. Although modeling flow diagram 100 is shown in FIG. 1 as a stand-alone method, aspects of this disclosure can be used with other apparatuses, systems, and / or methods, for example, modeling flow diagram 200, manufacturing flow diagram 300, system 400, differentially activatable assembly 500, and / or differentially activatable assembly 1000. In some aspects, modeling flow diagram 100 can be implemented by modeling system 410, processing system 430, manufacturing system 450, and / or activation system 470 of system 400 shown in FIG. 4.

[0075] In step 102, as shown in the example of FIGS. 1, 4-11, and 12A-12C, an observable field (e.g., emission profile, etc.) can be defined. In some aspects, the observable field (e.g., 2D fluence profile 900, 2D fluence profiles 1200A-1200C, etc.) can be a desired (e.g., unique, optimized) or deliberately designed observable field (e.g., emission profile, etc.), for example, for a particular application and / or treatment (e.g., radiotherapy applications, food sterilization, irradiation applications, small animal irradiation, tissue irradiation, irradiation of animate and / or inanimate objects, for example, radiotherapy, atomic batteries, sterilization, etc.). In some aspects, the observable field (e.g., emission profile, etc.) can be a unique anisotropic three- dimensional (3D) and / or four-dimensional (3D over time) observable field (e.g., emissionprofile, etc.). In some aspects, the observable field (e.g., emission profile, etc.) can be defined by observable field subsystem 412 of modeling system 410 of system 400 shown in FIG. 4, for example, a desired (e.g., unique, optimized) observable field (e.g., emission profile, etc.) for a particular application. In some aspects, the observable field can be defined by an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof.

[0076] In step 104, as shown in the example of FIGS. 1, 4-11, and 12A-12C, a model of a differentially activatable assembly based on a set of parameters can be defined. In some aspects, the set of parameters can include one or more activatable materials, one or more non-activatable materials, a geometry of the materials, a distribution of the materials, activation cross-sections of the materials, decay characteristics of the materials, half-lives of the materials, radioactivity distributions of the materials, emitted particles of the materials, a particle field for activation of the materials, activation time, waiting period after activation, or a combination thereof. In some aspects, the model can include a three- dimensional model of the differentially activatable assembly. In some aspects, the model can include a four-dimensional model of the differentially activatable assembly.

[0077] In step 106, as shown in the example of FIGS. 1, 4-11, and 12A-12C, an inverse optimization of the set of parameters can be performed such that the model of the differentially activatable assembly, after activation, produces the observable field. In some aspects, the inverse optimization can be based on the set of parameters (e.g., desired emission profile, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) capable of producing the observable field (e.g., emission profile, etc.) when activated, for example, by a particle field (e.g., thermal neutrons, etc.). In some aspects, the inverse optimization can be performed by optimization subsystem 422 of system 400 shown in FIG. 4, for example, an optimization algorithm.

[0078] In some aspects, step 106 can include using an optimization algorithm to optimize the set of parameters. For example, the optimization algorithm can include simulated annealing, gradient descent, finite difference, interpolation, population models, regression, parameter adaptation, supervised machine learning, unsupervised machinelearning, neural networks, classification models, clustering, vector quantization, stochastic gradient descent, implicit updates, leaky averaging, momentum methods, adaptive gradient (AdaGrad), backpropagation, root mean square propagation (RMSProp), adaptive moment estimation (Adam), or a combination thereof.

[0079] In step 108, optionally, as shown in the example of FIGS. 1, 4-11, and 12A-12C, a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) can be manufactured based on the optimized model after the inverse optimization determined in step 106. In some aspects, the optimized model can be manufactured by manufacturing system 450 of system 400 shown in FIG. 4, for example, differentially activatable assembly 1000 shown in FIG. 10 can be manufactured based on the optimized model.

[0080] In step 110, optionally, as shown in the example of FIGS. 1, 4-11, and 12A-12C, the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) can be activated after manufacturing in step 108 to produce the observable field. In some aspects, activation can include a particle field (e.g., thermal neutrons, etc.) for activation of a portion or all of the differentially activatable assembly. For example, the particle field can include bombardment by thermal neutrons for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). In some aspects, the particle field for activation of the differentially activatable assembly can be determined by particle field subsystem 414 and / or materials subsystem 416 of modeling system 410 of system 400 shown in FIG. 4, for example, bombardment by thermal neutrons for activation of133Cs.Exemplary Designing Method

[0081] FIG. 2 illustrates modeling flow diagram 200 for optimizing a distribution of materials in a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000), according to an exemplary aspect. It is to be appreciated that not all steps in FIG. 2 are needed to perform the disclosure provided herein. Further, some of the steps may be performed simultaneously, sequentially, and / or in a different order than shown in FIG. 2. Modeling flow diagram 200 shall be described with reference to FIGS. 2, 4-11, and 12A-12C. However, modeling flow diagram 200 is not limited to those example aspects. Although modeling flow diagram 200 is shown in FIG. 2 as a stand-alone method, aspects of this disclosure can be used with otherapparatuses, systems, and / or methods, for example, modeling flow diagram 100, manufacturing flow diagram 300, system 400, differentially activatable assembly 500, and / or differentially activatable assembly 1000. In some aspects, modeling flow diagram 200 can be implemented by modeling system 410 of system 400 shown in FIG. 4.

[0082] In step 202, as shown in the example of FIGS. 2, 4-11, and 12A-12C, an observable field (e.g., emission profile, etc.) can be defined. In some aspects, the observable field (e.g., 2D fluence profile 900, 2D fluence profiles 1200A-1200C, etc.) can be a desired (e.g., unique, optimized) observable field (e.g., emission profile, etc.), for example, for a particular application and / or treatment (e.g., radiotherapy applications, food sterilization, irradiation applications, small animal irradiation, tissue irradiation, irradiation of animate and / or inanimate objects, for example, radiotherapy, atomic batteries, sterilization, etc.). In some aspects, the observable field (e.g., emission profile, etc.) can be a unique anisotropic three-dimensional (3D) and / or four-dimensional (3D over time) observable field (e.g., emission profile, etc.). In some aspects, the observable field (e.g., emission profile, etc.) can be defined by observable field subsystem 412 of modeling system 410 of system 400 shown in FIG. 4, for example, a desired (e.g., unique, optimized) observable field (e.g., emission profile, etc.) for a particular application.

[0083] In step 204, as shown in the example of FIGS. 2, 4-11, and 12A-12C, a particle field (e.g., thermal neutrons, etc.) for activation of a volume of a material (e.g., second material 520, second material 1020, etc.) can be determined. For example, the particle field can include bombardment by thermal neutrons for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). In some aspects, the particle field can be determined by particle field subsystem 414 and / or materials subsystem 416 of modeling system 410 of system 400 shown in FIG. 4, for example, bombardment by thermal neutrons for activation of133Cs.

[0084] In step 206, as shown in the example of FIGS. 2, 4-11, and 12A-12C, a plurality of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, etc.) with different activation cross-sections and decay characteristics can be determined to form radioactivity distributions (e.g., activity distribution 700, activity distribution 1100, etc.). In some aspects, the plurality of materials can be determined by materials subsystem 416, geometry (3D) subsystem 418, and / or half-lives (4D) subsystem 420 of modeling system 410 of system 400 shown in FIG. 4, for example, first material 1010 (e.g., Pb), plurality of second materials 1020a-1020e (e.g.,133Cs), and plurality of third materials 1030a-1030e (e.g., pockets of empty vacuum space). In some aspects, the plurality of materials can include an activatable material (e.g.,133Cs) and a non-activatable material (e.g., Pb). In some aspects, the plurality of materials can include a scattering and / or attenuating material (e.g., a gas pocket, a vacuum pocket, etc.).

[0085] In step 208, as shown in the example of FIGS. 2, 4-11, and 12A-12C, a distribution of the plurality of materials can be optimized in a geometry (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) based on the observable field (e.g., emission profile, etc.), the particle field, and the radioactivity distributions. In some aspects, optimizing the distribution can include optimizing in three-dimensions (3D). For example, the optimized three-dimensional distribution of activatable and non-activatable materials in the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000) can provide a unique three-dimensional (3D) observable field (e.g., emission profile, etc.) when activated. In some aspects, optimizing the distribution can include optimizing in four-dimensions (4D). In some aspects, optimizing in four-dimensions (3D over time) can include calculating waiting periods after activation based on different halflives of the plurality of materials. For example, the optimized four-dimensional (3D over time) distribution of materials with different half-lives in the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000) can provide a unique four-dimensional (3D over time) observable field (e.g., emission profile, etc.) when activated.

[0086] In some aspects, step 208 can perform an inverse optimization based on custom inputs or parameters (e.g., desired emission profile, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000) capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field. In some aspects, the inverse optimization can be performed by optimization subsystem 422 of system 400 shown in FIG. 4, for example, an optimization algorithm.

[0087] In some aspects, step 208 can include using an optimization algorithm to optimize the distribution. For example, the optimization algorithm can include simulated annealing, gradient descent, finite difference, interpolation, population models,regression, parameter adaptation, supervised machine learning, unsupervised machine learning, neural networks, classification models, clustering, vector quantization, stochastic gradient descent, implicit updates, leaky averaging, momentum methods, adaptive gradient (AdaGrad), backpropagation, root mean square propagation (RMSProp), adaptive moment estimation (Adam), or a combination thereof.

[0088] In step 210, optionally, as shown in the example of FIGS. 3-5 and 10, a differentially activatable differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) can be manufactured based on the optimized distribution determined in step 208. In some aspects, the optimized distribution can be manufactured by manufacturing system 450 of system 400 shown in FIG. 4, for example, differentially activatable assembly 1000 shown in FIG. 10 can be manufactured based on the optimized distribution.Exemplary Manufacturing Method

[0089] FIG. 3 illustrates manufacturing flow diagram 300 for manufacturing a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000), according to an exemplary aspect. It is to be appreciated that not all steps in FIG. 3 are needed to perform the disclosure provided herein. Further, some of the steps may be performed simultaneously, sequentially, and / or in a different order than shown in FIG. 10. Manufacturing flow diagram 300 shall be described with reference to FIGS. 3-11 and 12A-12C. However, manufacturing flow diagram 300 is not limited to those example aspects. Although manufacturing flow diagram 300 is shown in FIG. 3 as a stand-alone method, aspects of this disclosure can be used with other apparatuses, systems, and / or methods, for example, modeling flow diagram 100, modeling flow diagram 200, system 400, differentially activatable assembly 500, and / or differentially activatable assembly 1000. In some aspects, manufacturing flow diagram 300 can be implemented by modeling system 410, processing system 430, and / or manufacturing system 450 of system 400 shown in FIG. 4.

[0090] In step 302, as shown in the example of FIGS. 3-11 and 12A-12C, a distribution of a plurality of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) can be optimized in a geometry (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) based on an observable field (e.g., 2D fluence profile 900, 2Dfluence profiles 1200A-1200C, etc.), a particle field (e.g., thermal neutrons, etc.), and radioactivity distributions of the plurality of materials (e.g., activity distribution 700, activity distribution 1100, etc.). In some aspects, the distribution of materials can be optimized based on custom inputs or parameters (e.g., desired emission profile, particle field, radioactivity distributions, etc.) in order to manufacture a differentially activatable assembly with the optimized distribution of materials that is capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field. In some aspects, the optimized distribution of materials can be determined by modeling system 410 of system 400 shown in FIG. 4.

[0091] In step 304, as shown in the example of FIGS. 3-5 and 10, a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) can be manufactured based on the optimized distribution determined in step 302. In some aspects, the optimized distribution can be manufactured by manufacturing system 450 of system 400 shown in FIG. 4, for example, differentially activatable assembly 1000 shown in FIG. 10 can be manufactured based on the optimized distribution. In some aspects, step 304 can take place in a radiation-safe environment for finer manipulation of the materials during manufacturing of the differentially activatable assembly.

[0092] In some aspects, step 304 can include ion implanting one or more of the plurality of materials. For example, an activatable material (e.g., second material 520, second material 1020,133Cs, etc.) can be ion implanted into a non-activatable material (e.g., first material 510, first material 1010, Pb, etc.). In some aspects, ion implanting can have a spatial resolution in three-dimensions of at least 1 micron (e.g., 1 pm spatial resolution along X-axis, 1 pm spatial resolution along Y-axis, 1 pm spatial resolution along Z-axis). In some aspects, an activatable material (e.g., second material 520, second material 1020, 133Cs, etc.) can be ion implanted within a shielding material (e.g., first material 510, first material 1010, Pb, etc.) with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) on a small scale (e.g., millimeter, micrometer, nanometer, etc.). In some aspects, ion implanting can be performed by manufacturing system 450 of system 400 shown in FIG. 4.

[0093] In some aspects, step 304 can include depositing one or more of the plurality of materials. For example, depositing can include epitaxy, physical vapor deposition (PVD), electron-beam PVD (EBPVD), sputter deposition, electrosputtering, chemical vapor deposition (CVD), plasma-enhanced CVD (PECVD), atomic layer deposition (ALD), powder bed deposition, or a combination thereof. In some aspects, one or more of the plurality of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) can be deposited with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) on a small scale (e.g., millimeter, micrometer, nanometer, etc.). In some aspects, depositing can be performed by manufacturing system 450 of system 400 shown in FIG. 4.

[0094] In some aspects, step 304 can include manufacturing with a computer controlled manufacturing system. For example, the computer controlled manufacturing system can include a computer numerically controlled (CNC) machine, an additive manufacturing machine, a subtractive manufacturing machine, a drill, a lathe, a mill, a grinder, a router, a 3D printer, a lithographic machine, a photolithographic machine, an inkjet machine, a sintering machine, a fused deposition machine, or a combination thereof. In some aspects, the computer controlled manufacturing system (e.g., lithographic machine, 3D printer, etc.) can form the distribution of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) of the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) with high accuracy and precision (e.g., 1 mm spatial resolution, 100 pm spatial resolution, 10 pm spatial resolution, 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, sub-1 nm spatial resolution, etc.). In some aspects, the computer controlled manufacturing system can be part of manufacturing system 450 of system 400 shown in FIG. 4.

[0095] In step 306, optionally, as shown in the example of FIGS. 3-11 and 12A-12C, the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) can be activated with the particle field (e.g., thermal neutrons, etc.) to produce the observable field (e.g., 2D fluence profile 900, 2D fluence profiles 1200A-1200C, etc.). In some aspects, step 306 can be performed afterstep 304, which increases safety and decreases the risk of radiation exposure during manufacturing. In some aspects, activation can include bombardment of the manufactured differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) with the particle field (e.g., thermal neutrons, etc.). For example, the particle field can include bombardment of the entire manufactured differentially activatable assembly by thermal neutrons for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment).Exemplary Designing and Manufacturing System

[0096] FIG. 4 illustrates system 400 for designing, manufacturing, and activating a differentially activatable assembly, according to an exemplary aspect. System 400 can be configured to model an optimized distribution of materials in a geometry (e.g., inverse optimization), process the optimized model into manufacturing instructions, and manufacture a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) based on the optimized model. Although system 400 is shown in FIG. 4 as a stand-alone apparatus and / or system, aspects of this disclosure can be used with other apparatuses, systems, and / or methods, for example, modeling flow diagram 100, modeling flow diagram 200, manufacturing flow diagram 300, differentially activatable assembly 500, and / or differentially activatable assembly 1000.

[0097] As shown in FIG. 4, system 400 can include modeling system 410, processing system 430, manufacturing system 450, and activation system 470. Modeling system 410 can be configured to optimize a distribution of a plurality of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) in a geometry (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) based on an observable field (e.g., 2D fluence profile 900, 2D fluence profiles 1200A-1200C, etc.), a particle field (e.g., thermal neutrons, etc.), and radioactivity distributions of the plurality of materials (e.g., activity distribution 700, activity distribution 1100, etc.). As shown in FIG. 4, modeling system 410 can include observable field subsystem 412, particle field subsystem 414, materials subsystem 416, geometry (3D) subsystem 418, half-lives (4D) subsystem 420, and optimization subsystem 422. Further, modeling system 410 can be coupled (e.g.,electronically, etc.) to processing system 430 in order to send and receive data (e.g., 3D / 4D optimized model data) between modeling system 410 and processing system 430.

[0098] Observable field subsystem 412 can be configured to define a desired observable field (e.g., 3D or 4D). In some aspects, observable field subsystem 412 can receive a desired observable field (e.g., emission profile, etc.) from a user via processing system 430. In some aspects, observable field subsystem 412 can include an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof. In some aspects, observable field subsystem 412 can include a library or database of different observable fields (e.g., emission profiles, etc.) that can be selected (or modified) by a user or an optimization algorithm (e.g., optimization subsystem 422) to define a desired observable field.

[0099] Particle field subsystem 414 can be configured to determine a particle field (e.g., thermal neutrons, etc.) for activation of a volume of a material. In some aspects, particle field subsystem 414 can receive a determined particle field (e.g., thermal neutrons, etc.) from a user via processing system 430. In some aspects, particle field subsystem 414 can include a library or database of different particle fields that can be selected (or modified) by a user or an optimization algorithm (e.g., optimization subsystem 422) to determine a particle field for activation.

[0100] Materials subsystem 416 can be configured to determine a plurality of materials in a distribution. In some aspects, materials subsystem 416 can receive selected materials from a user via processing system 430. In some aspects, materials subsystem 416 can include a library or database of different materials (e.g., activatable materials, non- activatable materials, scattering materials, attenuating materials, activation cross-sections, decay characteristics, etc.) that can be selected (or modified) by a user or an optimization algorithm (e.g., optimization subsystem 422) to determine a plurality of materials for the distribution.

[0101] Geometry (3D) subsystem 418 can be configured to determine a geometry (e.g., 3D) of the distribution of materials. Geometry (3D) subsystem 418 can be further configured to determine an activity scheme of the distribution in three-dimensions (3D). In some aspects, geometry (3D) subsystem 418 can receive a selected geometry (3D) for the differentially activatable assembly from a user (e.g., a right cylinder, a sphere, a cube,etc.) via processing system 430. In some aspects, geometry (3D) subsystem 418 can include a library or database of different geometries (e.g., cylindrical, spherical, orthotope, etc.) that can be selected (or modified) by a user or an optimization algorithm (e.g., optimization subsystem 422) to determine a geometry of the differentially activatable assembly.

[0102] Half-Lives (4D) subsystem 420 can be configured to determine a decay scheme (waiting period) of the distribution in four-dimensions (3D over time). In some aspects, half-lives (4D) subsystem 420 can receive decay characteristics (e.g., half-life) of materials from a user via processing system 430. In some aspects, half-lives (4D) subsystem 420 can include a library or database of different decay characteristics (e.g., half-life) of materials that can be included or selected (or modified) by modeling system 410 (or by a user) to determine a decay scheme of the differentially activatable assembly.

[0103] Optimization subsystem 422 can be configured to optimize the distribution of materials in the geometry (3D) based on the observable field (e.g., observable field subsystem 412), the particle field (e.g., particle field subsystem 414), and radioactivity distributions of the materials (e.g., materials subsystem 416, geometry (3D) subsystem 418, half-lives (4D) subsystem 420). In some aspects, optimization subsystem 422 can perform an inverse optimization based on custom inputs or parameters (e.g., desired emission profile, particle field, plurality of materials, half-lives, etc.) to model an optimal differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field.

[0104] In some aspects, optimization subsystem 422 can include an optimization algorithm to perform the inverse optimization. For example, the optimization algorithm can include simulated annealing, gradient descent, finite difference, interpolation, population models, regression, parameter adaptation, supervised machine learning, unsupervised machine learning, neural networks, classification models, clustering, vector quantization, stochastic gradient descent, implicit updates, leaky averaging, momentum methods, adaptive gradient (AdaGrad), b ackpropagation, root mean square propagation (RMSProp), adaptive moment estimation (Adam), or a combination thereof. In some aspects, the optimized model of the differentially activatable assembly determined by optimization subsystem 422 can be transferred to processing system 430 for further processing (e.g., manufacturing control data, activation control data).

[0105] Processing system 430 can be configured to process the optimized distribution of materials and convert the optimized model into a set of manufacturing instructions and / or steps. Processing system 430 can be further configured to process the optimized distribution of materials and convert the optimized model into a set of activation instructions and / or steps. As shown in FIG. 4, processing system 430 can be coupled to modeling system 410, manufacturing system 450, and activation system 470, and include I / O (input / output) subsystem 432, UI (user interface) subsystem 434, construction subsystem 436, and conversion subsystem 438. Further, processing system 430 can be coupled (e.g., electronically, etc.) to modeling system 410 in order to send and receive data (e.g., 3D / 4D input data) between processing system 430 and modeling system 410, processing system 430 can be coupled (e.g., electronically, etc.) to manufacturing system 450 in order to send and receive data (e.g., converted model data instructions) between processing system 430 and manufacturing system 450, and processing system 430 can be coupled (e.g., electronically, etc.) to activation system 470 in order to send and receive data (e.g., converted model data instructions) between processing system 430 and activation system 470.

[0106] I / O subsystem 432 can be configured to receive data relevant to optimize the model (e.g., desired emission profile, particle field information, etc.). In some aspects, a desired (unique) three-dimensional (3D) or four-dimensional (3D over time) observable field (e.g., emission profile, etc.) can be received by VO subsystem 432. In some aspects, a user may transfer a 3D or 4D data set to processing system 430, for example, via a storage medium, wirelessly, Internet, data packet, etc.

[0107] UI subsystem 434 can be configured to provide one or more user interfaces that allow a user to interact with processing system 430 and / or modeling system 410. In some aspects, UI subsystem 434 can provide a user interface for displaying a 3D or 4D model (e.g., desired emission profile, optimized differentially activatable assembly, etc.), for example, based on different treatment plan types or applications, and prompting the user to make a selection. In some aspects, UI subsystem 434 can receive user input via one or more input devices, for example, a keyboard, mouse, touch-screen, or any other suitable input device. In some aspects, UI subsystem 434 can display and manipulate a 3D or 4D optimized model of a differentially activatable assembly received from modeling system 410.

[0108] Construction subsystem 436 can be configured to construct 3D output data sets from the 3D optimized model of the differentially activatable assembly. In some aspects, the 3D output data set can include volumetric data (e.g., voxels, etc.) representing a geometry and material distribution of the optimized differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.).

[0109] Conversion subsystem 438 can be configured to convert the 3D output data sets into a set of manufacturing instructions and / or steps (e.g., control data) for manufacturing system 450. Conversion subsystem 438 can be further configured to convert the 3D / 4D output data sets into a set of activation instructions and / or steps (e.g., control data) for activation system 470. In some aspects, manufacturing system 450 can use control data from processing system 430 to manufacture optimized differentially activatable assembly in three-dimensions (3D). In some aspects, I / O subsystem 432 can transmit control data to manufacturing system 450, for example, via a wired or wireless connection, after conversion system 438 has converted the 3D output data sets to control data. In some aspects, activation system 470 can use control data from processing system 430 to activate a portion or all of manufactured differentially activatable assembly to produce the desired observable field (e.g., emission profile, etc.). In some aspects, I / O subsystem 432 can transmit control data to activation system 470, for example, via a wired or wireless connection, after conversion system 438 has converted the 3D / 4D output data sets to control data.

[0110] Manufacturing system 450 can be configured to manufacture a differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) with the optimized distribution of materials that is capable of producing the desired observable field (e.g., emission profile, etc.) when activated by the particle field. As shown in FIG. 4, manufacturing system 450 can be coupled (e.g., electronically, etc.) to processing system 430 in order to send and receive data (e.g., manufacturing instructions) between manufacturing system 450 and processing system 430.[OHl] In some aspects, manufacturing system 450 can include an ion implanter for ion implanting one or more of the plurality of materials. For example, an activatable material (e.g., second material 520, second material 1020,133Cs, etc.) can be ion implanted into a non-activatable or shielding material (e.g., first material 510, first material 1010, Pb, etc.).In some aspects, manufacturing system 450 can have a spatial resolution of ion implanting in three-dimensions of at least 1 micron (e.g., 1 pm spatial resolution along X- axis, 1 pm spatial resolution along Y-axis, 1 pm spatial resolution along Z-axis). In some aspects, an activatable material (e.g., second material 520, second material 1020,133Cs, etc.) can be ion implanted by manufacturing system 450 within a shielding material (e.g., first material 510, first material 1010, Pb, etc.) with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0112] In some aspects, manufacturing system 450 can include depositing one or more of the plurality of materials. For example, depositing can include epitaxy, physical vapor deposition (PVD), electron-beam PVD (EBPVD), sputter deposition, electrosputtering, chemical vapor deposition (CVD), plasma-enhanced CVD (PECVD), atomic layer deposition (ALD), powder bed deposition, or a combination thereof. In some aspects, one or more of the plurality of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) can be deposited by manufacturing system 450 with high accuracy and precision (e.g., 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, etc.) to form a miniature, self-contained differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0113] In some aspects, manufacturing system 450 can include a computer controlled manufacturing system. For example, the computer controlled manufacturing system can include a computer numerically controlled (CNC) machine, an additive manufacturing machine, a subtractive manufacturing machine, a drill, a lathe, a mill, a grinder, a router, a 3D printer, a lithographic machine, a photolithographic machine, an inkjet machine, a sintering machine, a fused deposition machine, or a combination thereof. In some aspects, the computer controlled manufacturing system (e.g., lithographic machine, 3D printer, etc.) of manufacturing system 450 can form the distribution of materials (e.g., first material 510, first material 1010, second material 520, second material 1020, third material 1030, Pb,133Cs, voids, etc.) of the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.)with high accuracy and precision (e.g., 1 mm spatial resolution, 100 pm spatial resolution, 10 pm spatial resolution, 1 pm spatial resolution, 100 nm spatial resolution, 10 nm spatial resolution, 1 nm spatial resolution, sub-1 nm spatial resolution, etc.).

[0114] Activation system 470 can be configured to activate (e.g., via a particle field) a manufactured differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) to produce the desired observable field (e.g., emission profile, etc.). As shown in FIG. 4, activation system 470 can be coupled (e.g., electronically, etc.) to processing system 430 in order to send and receive data (e.g., activation instructions) between activation system 470 and processing system 430.

[0115] In some aspects, activation system 470 can include a particle field to activate the differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) to produce the observable field (e.g., 2D fluence profile 900, 2D fluence profiles 1200A-1200C, etc.). For example, the particle field can include ionizing radiation (e.g., thermal neutrons, protons, electrons, alpha particles, beta particles, X-rays, gamma rays, etc.). In some aspects, activation system 470 can bombard the manufactured differentially activatable assembly (e.g., differentially activatable assembly 500, differentially activatable assembly 1000, etc.) with a particle field (e.g., thermal neutrons, etc.) to activate the manufactured differentially activatable assembly. For example, activation system 470 can bombard the entire manufactured differentially activatable assembly by thermal neutrons for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment).Exemplary Differentially Activatable Assemblies

[0116] As discussed above, current radioactive emitters only provide uniform (noncomplex) emission profiles for a limited number of materials and geometries, and are not suitable for high precision radiation applications requiring customized, unique emission profiles. Further, current radioactive emitters are unstable (e.g., radioactive) and activated prior to construction of the emitter, which limits the construction of radiation-shaping devices (e.g., collimators), is unsafe, and increases the risk of radiation exposure during handling, manipulation, and manufacturing. In contrast, if assembling and / or manufacturing stable materials, precision and complexity of radiation-shaping devices (e.g., collimators) can both be increased. Additionally, current manufacturing of radioactive emitters is not optimized for the particular application and fails to consider theoptimal materials, composition, geometry, and / or decay times to produce a desired unique three-dimensional or four-dimensional emission profile.

[0117] Aspects of differentially activatable assembly apparatuses, systems, and methods as discussed below can provide a differentially activatable assembly that is stable prior to activation, self-contained, differentially activatable, activated after construction, and optimized to provide complex (non-uniform) and unique three-dimensional or fourdimensional observable fields for high precision radiation applications. Further, aspects of differentially activatable assembly apparatuses, systems, and methods as discussed below can utilize an inverse optimization model to determine the optimal design and construction of a differentially activatable assembly to produce a desired observable field (e.g., emission profile, etc.).

[0118] FIGS. 5-9 illustrate differentially activatable assembly 500, according to exemplary aspects. Differentially activatable assembly 500 can be configured to be differentially activatable (e.g., differently based on an orientation of the differentially activatable assembly relative to a direction of the particle bombardment). Differentially activatable assembly 500 can be further configured to be stable prior to activation (e.g., radiation-safe until activation). Differentially activatable assembly 500 can be further configured to be self-contained (e.g., shielding and activatable materials in a single compact unit). Differentially activatable assembly 500 can be further configured to be activated after construction. Differentially activatable assembly 500 can be further configured to be optimized to provide complex (e.g., non-uniform, anisotropic) and unique three-dimensional (3D) and / or four-dimensional (3D over time) observable fields (e.g., emission profiles, etc.). In some aspects, differentially activatable assembly 500 can be a miniature differentially activatable assembly (e.g., volume of 10 mm3), for example, for biological systems irradiation applications (e.g., small animal, human, cell(s), tissue, food, etc.). In some aspects, differentially activatable assembly 500 can be used for radiation therapy and / or radiobiology, for example, to direct radiation with a complex observable field (e.g., emission profile, etc.) to a target region of a subject (e.g., small animal, mouse, human, etc.). In some aspects, differentially activatable assembly 500 can be used for atomic batteries. Although differentially activatable assembly 500 is shown in FIGS. 5-9 as a stand-alone apparatus and / or system, aspects of this disclosure can be used with other apparatuses, systems, and / or methods, for example, modeling flow diagram100, modeling flow diagram 200, manufacturing flow diagram 300, system 400, and / or differentially activatable assembly 1000.

[0119] As shown in FIG. 5, differentially activatable assembly 500 can include longitudinal axis 501, first material 510, second material 520, and collimator 530. Differentially activatable assembly 500 can be configured to be differentially activatable via particle bombardment (e.g., thermal neutrons). Differentially activatable assembly 500 can be further configured to produce a complex observable field (e.g., emission profile, etc.) upon activation. The geometrical arrangement of differentially activatable assembly 500, with second material 520 coupled to collimator 530 within first material 510 and along longitudinal axis 511 of first material 510, can produce (when activated) highly anisotropic emission along longitudinal axis 501 of differentially activatable assembly 500 and outward from distal end (aperture) 534 of collimator 530, for example, anisotropic emission 910 as shown in FIG. 9.

[0120] In some aspects, differentially activatable assembly 500 can be activated differentially to provide a desired observable field (e.g., emission profile, etc.) that is complex. For example, as shown in FIG. 9, differentially activatable assembly 500 can be activated differently based on an orientation of differentially activatable assembly 500 relative to a direction of the particle bombardment (e.g., thermal neutrons) to provide 2D fluence profile 900 with anisotropic emission 910. In some aspects, differentially activatable assembly 500 can provide (when activated) ionizing radiation, including but not limited to, X-rays, gamma rays, alpha particles, beta particles, protons, neutrons, electrons, or a combination thereof.

[0121] In some aspects, the observable field (e.g., emission profile, etc.) of differentially activatable assembly 500 can be anisotropic. For example, as shown in FIG. 9, differentially activatable assembly 500 can produce (when activated) anisotropic emission 910 along longitudinal axis 501 of differentially activatable assembly 500. In some aspects, differentially activatable assembly 500 can have a unique geometry. For example, as shown in FIG. 5, differentially activatable assembly 500 can have a cylindrical geometry (e.g., a right cylinder) with second material 120 (e.g., activatable material) and collimator 130 colinear along longitudinal axis 501 of differentially activatable assembly 500.

[0122] In some aspects, differentially activatable assembly 500 can be cylindrical (e.g., a right cylinder, a rod). For example, as shown in FIG. 5, differentially activatableassembly 500 can be a right cylinder. In some aspects, differentially activatable assembly 500 can be ellipsoidal (e.g., a sphere). In some aspects, differentially activatable assembly 500 can be a three-dimensional orthotope (e.g., a cube). For example, as shown in FIG.10, differentially activatable assembly 1000 can be a cube. In some aspects, differentially activatable assembly 500 can have a unique geometry to provide a unique three- dimensional (3D) observable field (e.g., emission profile, etc.).

[0123] In some aspects, differentially activatable assembly 500 can have a cylindrical geometry (e.g., a right cylinder) having a diameter in a range of about 1 mm to about 50 mm and a height in a range of about 5 mm to about 250 mm. For example, as shown in FIG. 9, differentially activatable assembly 500 can be a cylinder with a diameter of about 20 mm and a height of about 110 mm. In some aspects, differentially activatable assembly 500 can have a unique distribution of first material 510 and second material 520. For example, as shown in FIG. 5, second material 520 (e.g., activatable material) can be embedded within first material 510 (e.g., shielding material) and occupy a small portion of the volume of first material 510 (e.g., about 2%).

[0124] In some aspects, differentially activatable assembly 500 can have a volume of no greater than 100 cm3. In some aspects, differentially activatable assembly 500 can have a volume of no greater than 1 cm3. In some aspects, differentially activatable assembly 500 can have a volume of no greater than 100 mm3. In some aspects, differentially activatable assembly 500 can have a volume of no greater than 1 mm3. In some aspects, differentially activatable assembly 500 can have a volume of no greater than 100 pm3. In some aspects, differentially activatable assembly 500 can have a volume of no greater than 1 pm3. In some aspects, first material 510 and second material 520 of differentially activatable assembly 500 can be formed with high precision (e.g., anisotropic milling, etching, ion implantation, deposition, melting, lithography, liquefaction, sintering, 3D printing, etc.) to form a miniature, self-contained differentially activatable assembly 500 on a small scale (e.g., millimeter, micrometer, nanometer, etc.).

[0125] In some aspects, the observable field (e.g., emission profile, etc.) of differentially activatable assembly 500 can be a unique three-dimensional (3D) observable field (e.g., emission profile, etc.). For example, as shown in FIG. 9, differentially activatable assembly 500 can produce 2D fluence profile 900 with anisotropic emission 910. In some aspects, differentially activatable assembly 500 can have a unique geometry and a unique distribution of first material 510 (e.g., shielding material) and second material 520 (e.g.,activatable material) to provide a unique three-dimensional (3D) observable field (e.g., emission profile, etc.) when activated.

[0126] In some aspects, differentially activatable assembly 500 can have a unique decay time. For example, as shown in FIG. 8, differentially activatable assembly 500 can have relative activity distribution 800 over time with relative activity 810 transferring from first material 510 (e.g., Pb) to second material 520 (e.g., Cs), for example, after about 150 hours post-bombardment by neutrons for about 48 hours. In some aspects, the observable field (e.g., emission profile, etc.) of differentially activatable assembly 500 can be a unique four-dimensional (3D over time) observable field (e.g., emission profile, etc.). For example, as shown in FIGS. 8 and 9, differentially activatable assembly 500 can have a unique geometry, a unique distribution of first material 510 and second material 520, and a unique decay time (e.g., relative activity 810 shown in FIG. 8) to provide a unique fourdimensional (3D over time) observable field (e.g., emission profile, etc.) when activated.

[0127] First material 510 can be configured to provide shielding of second material 520 (e.g., activatable material). First material 510 can be further configured to surround second material 520. First material 510 can be further configured to provide collimation (e.g., via collimator 530) of emission from second material 520. As shown in FIG. 5, first material 510 can include longitudinal axis 511, proximal end (bottom surface) 512, and distal end (top surface) 514. In some aspects, longitudinal axis 511 of first material 510 can be aligned (e.g., colinear) along longitudinal axis 501 of differentially activatable assembly 500. In some aspects, first material 510 can be a shielding material, for example, lead (Pb). In some aspects, first material 510 can be a non-activatable material, for example, a purified form of lead (Pb) (e.g., 100%206Pb such that activation of any Pb atoms creates another stable isotope,207Pb or208Pb) or a purified form of gadolinium (Gd) (e.g.,157Gd).

[0128] In some aspects, first material 510 can have a cylindrical geometry. For example, as shown in FIG. 5, first material 510 can be a right cylinder with proximal end (bottom surface) 512 and distal end (top surface) 514. In some aspects, first material 510 can encapsulate a portion of second material 520. For example, as shown in FIG. 5, first material 510 can encapsulate second material 520 except at distal end 524 of second material 520 (e.g., coupled to void 531 of collimator 530). In some aspects, first material 510 can encapsulate all of second material 520.

[0129] In some aspects, first material 510 can include lead, a lead composite, tin, rubber, polyvinyl chloride, antimony, tungsten, bismuth, or a combination thereof. For example, first material 510 can include lead (Pb). In some aspects, first material 510 can include a material or plurality of materials that provide a majority of stable isotopes and either no radioactive isotopes or a limited number of radioactive isotopes. For example, first material 510 can be lead (Pb) with a majority of stable isotopes (e.g.,204Pb,206Pb,207Pb, 208Pb) and only a limited number of radioactive isotopes (e.g.,205Pb,209Pb) with extremely long (e.g.,205Pb with a half-life of about 1.73 x 107years) or extremely short (e.g.,209Pb with a half-life of about 3.3 hours) half-lives for safe and stable shielding. In some aspects, first material 510 can be composed of a purified form of lead (Pb), for example, 100%206Pb such that activation of any Pb atoms creates another stable isotope (e.g.,207Pb or208Pb).

[0130] In some aspects, first material 510 can include an activatable material. For example, first material 510 can be lead (Pb) with radioactive isotope209Pb having an extremely short half-life (e.g., about 3.3 hours) that undergoes beta decay and emits an electron. In some aspects, first material 510 and second material 520 can produce different emitted particles (e.g., for different applications and / or shielding). For example, first material 510 can be lead (Pb) with radioactive isotope209Pb having an extremely short half-life (e.g., about 3.3 hours) that undergoes beta decay and emits an electron, and second material 520 can be cesium (133Cs) with radioactive isotope134Cs having a moderate half-life (e.g., about 2.1 years) that undergoes beta decay and emits high energy gamma rays (e.g., 605 keV and 796 keV). In some aspects, different materials of first material 510 and second material 520 can form complex activity distributions. For example, as shown in FIG. 8, relative activity 810 can have a sigmoid shape as activity transfers over time from first material 510 (e.g., Pb) to second material 520 (e.g., Cs).

[0131] In some aspects, first material 510 can include a plurality of third materials within first material 510. For example, as shown in FIG. 10, first material 1010 of differentially activatable assembly 1000 can include a plurality of third materials 1030a-1030e (e.g., spherical gas pockets or vacuum pockets). In some aspects, second material 520 can include a plurality of second materials within first material 510. For example, as shown in FIG. 10, second material 1020 (e.g., activatable material) of differentially activatable assembly 1000 can include a plurality of second materials 1020a-1020e (e.g., cylindrical 133Cs). In some aspects, first material 510 can include a plurality of third materials withinfirst material 510 and second material 520 can include a plurality of second materials within first material 510. For example, the plurality of second materials (e.g., plurality of second materials 1020a-1020e shown in FIG. 10) and the plurality of third materials (e.g., plurality of third materials 1030a-1030e shown in FIG. 10) can be uniquely (optimally) distributed within first material 510 thereby forming a unique three-dimensional (3D) observable field (e.g., emission profile, etc.).

[0132] In some aspects, differentially activatable assembly 500 can further include a third material within first material 510. For example, as shown in FIG. 10, differentially activatable assembly 1000 can include third material 1030 (e.g., a pocket) within first material 1010. In some aspects, the pocket (e.g., third material 1030 shown in FIG. 10) can include a gas pocket or a vacuum pocket. For example, the gas pocket can include air, nitrogen, helium, argon, carbon dioxide, or a combination thereof. In some aspects, one or more pockets (e.g., third material 1030 shown in FIG. 10) within first material 510 can create differential emission, scattering, and / or attenuation in differentially activatable assembly 500 to produce a unique (e.g., optimized) observable field (e.g., emission profile, etc.) in three-dimensions (3D) around differentially activatable assembly 500.

[0133] Second material 520 can be configured to provide emission (e.g., gamma rays) when activated (e.g., via particle bombardment). Second material 520 can be further configured to be within first material 510. Second material 520 can be further configured to be differentially activatable via particle bombardment. As shown in FIG. 5, second material 520 can include longitudinal axis 521, proximal end 522, and distal end 524. In some aspects, longitudinal axis 521 of second material 520 can be aligned (e.g., colinear) along longitudinal axis 511 of first material 510. For example, as shown in FIGS. 5 and 9, alignment of first material 510 and second material 520 along longitudinal axis 511 (e.g., longitudinal axis 521 is colinear with longitudinal axis 511) can produce a high fluence emission profile (e.g., 2D fluence profile 900) in a direction along longitudinal axis 511 (e.g., anisotropic emission 910). In some aspects, second material 520 can be an activatable material, for example, cesium (Cs). In some aspects, second material 520 can be a stable activatable material prior to activation (e.g.,133Cs) and a radioactive emitter after activation (e.g.,134Cs).

[0134] In some aspects, second material 520 can include a neutron activated material. For example, the neutron activated material can include cesium, cobalt, iron, iridium, or a combination thereof. In some aspects, the neutron activated material can include cesium-133 (133Cs). For example, second material 520 can include cesium-133 (133Cs) that can be activated by thermal neutrons into radioactive isotope cesium-134 (134Cs). In some aspects, second material 520 can include a stable (prior to activation) and self-contained differentially activatable assembly having a controlled activation and decay scheme. For example, as shown in FIGS. 5 and 7, second material 520 can include a neutron activated material (e.g.,133Cs) that provides a stable (prior to activation) and self-contained differentially activatable assembly with a controlled activation and decay scheme (e.g., activation of133Cs to134Cs with a half-life of about 2 years).

[0135] In some aspects, second material 520 can include a plurality of second materials within first material 510. For example, as shown in FIG. 10, second material 1020 (e.g., activatable material) of differentially activatable assembly 1000 can include a plurality of second materials 1020a-1020e (e.g., cylindrical133Cs). In some aspects, the plurality of second materials can include different activatable materials to provide differentially activatable customized and complex observable fields. For example, as shown in FIG. 10, plurality of second materials 1020a-1020e of differentially activatable assembly 1000 can include different activatable materials (e.g.,133Cs,59Co,54Fe,191Ir,127I, etc.), for example, second materials 1020a- 1020c can include133Cs and second materials 1020d-1020e can include59Co.

[0136] In some aspects, first material 510 and second material 520 can have different activation cross-sections. For example, first material 510 (e.g., Pb) can have an activation cross-section of about 0.001 bam (1 barn equal to 100 fm2) and second material 520 (e.g., 133Cs) can have an activation cross-section of about 26 barn. In some aspects, first material 510 and second material 520 can have a different specific activity (e.g., amount of radioactivity per unit mass of a compound). For example, first material 510 (e.g., Pb) can have a specific activity of about 8.8 Ci / g (1 Ci equal to 37 x 106Bq) and second material 520 (e.g.,133Cs) can have a specific activity of about 7.4 MCi / g. In some aspects, first material 510 and second material 520 can have a different half-life (e.g., time required for decaying quantity to fall to half its initial value). For example, first material 510 (e.g., Pb) can have radioactive isotopes (e.g.,205Pb,209Pb) with extremely long (e.g., 205Pb with a half-life of about 1.73 x 107years) or extremely short (e.g.,209Pb with a halflife of about 3.3 hours) half-lives for safe and stable shielding, and second material 520 (e.g.,133Cs) with radioactive isotope (e.g.,134Cs) having a moderate half-life (e.g., about 2.1 years).

[0137] In some aspects, first material 510 and second material 520 can have a different activation cross-sectionand / or a different half-life. In some aspects, second material 520 can have a higher activation cross-section than first material 510. For example, first material 510 (e.g., Pb) can have an activation cross-section of about 0.001 barn and second material 520 (e.g.,133Cs) can have an activation cross-section of about 26 barn. In some aspects, first material 510 can have a lower activation cross-section and either a longer half-life or a shorter half-life relative to second material 520. For example, the lower activation cross-section of first material 510 (e.g., Pb) can serve as shielding and the higher activation cross-section of second material 520 (e.g.,133Cs) can serve as an emitter to provide a unique three-dimensional (3D) observable field (e.g., emission profile, etc.). For example, the longer half-life or shorter half-life of first material 510 (e.g., Pb) relative to second material 520 (e.g.,133Cs) can provide a unique fourdimensional (3D over time) observable field (e.g., emission profile, etc.).

[0138] Collimator 530 can be configured to collimate emission from second material 520 (e.g., activatable material). Collimator 530 can be further configured to be within (e.g., part of) first material 510. Collimator 530 can be further configured to be a void (e.g., empty space) within first material 510. As shown in FIG. 5, collimator 530 can include void 531, proximal end 532, longitudinal axis 533, and distal end (opening) 534. In some aspects, longitudinal axis 533 of void 531 can be aligned (e.g., colinear) along longitudinal axis 511 of first material 510 and longitudinal axis 521 of second material 520.

[0139] In some aspects, collimator 530 can be coupled to second material 520. For example, as shown in FIG. 5, proximal end 532 of collimator 530 can be coupled to distal end 524 of second material 520. In some aspects, collimator 530 can be within first material 510. For example, as shown in FIG. 5, void 531 (e.g., empty space) can be formed within first material 510 (e.g., shielding material). In some aspects, for example, as shown in FIG. 5, longitudinal axis 533 of void 531 can be aligned (e.g., colinear) along longitudinal axis 511 of first material 510. In some aspects, for example, as shown in FIG. 5, void 531 can extend between distal end 524 of second material 520 and distal end (top surface) 514 of first material 510. In some aspects, collimator 530 can produce asymmetries in the observable field (e.g., emission profile, etc.) and can collimate radiation emitted from second material 520 (e.g., activatable material) to produce a highly directional fluence. For example, as shown in FIG. 9, 2D fluence profile 900 ofdifferentially activatable assembly 500 can include anisotropic emission 910 formed along longitudinal axis 533 of collimator 530. In some aspects, collimator 530 can be formed from (or within) first material 510 itself with high precision (e.g., anisotropic milling or etching to form a defined void) to form a miniature, self-contained differentially activatable assembly 500.

[0140] FIG. 6 illustrates activations distribution 600 (creation of a certain isotope) per incident activation particle (e.g., neutron) for different material species 604 (e.g.,134Cs, 202Pb,205Pb,209Pb,210Pb) produced from differentially activatable assembly 500 shown in FIG. 5, according to an exemplary aspect. Activations distribution 600 shows a plot of activations 610, 620, 630, 640, 650 (creation of a certain isotope) for134Cs,202Pb,205Pb, 209Pb,210Pb, respectively, based on activations (creation of a certain isotope) per incident neutron 602. Activations is the number of nuclei of a certain isotope that are created during bombardment (e.g., 10 activations of202Pb means 10202Pb nuclei were created from the capture of neutrons by 201Pb). Activations distribution 600 is based on activation of second material 520 (e.g.,133Cs to134Cs) via particle bombardment (e.g., thermal neutrons) of the entire differentially activatable assembly 500 shown in FIG. 5. As shown in FIG. 6,134Cs has activations 610 of about 6.5 x 10'6activations per neutron, 202Pb has activations 620 of about 0 activations per neutron (negligible),205Pb has activations 630 of about 2.3 x 10'5activations per neutron,209Pb has activations 640 of about 1 x 10'7activations per neutron, and210Pb has activations 630 of about 0 activations per neutron (negligible).

[0141] FIG. 7 illustrates activity distribution 700 (decay of a certain isotope) per incident activation particle (e.g., neutron) over time 704 for different material species (e.g.,134Cs, 202Pb,205Pb,209Pb,210Pb) produced from differentially activatable assembly 500 shown in FIG. 5, according to an exemplary aspect. Activity distribution 700 shows a plot of activity schemes 710, 720, 730, 740, 750 (decay of a certain isotope) for134Cs,202Pb, 2°5pb,209pb,210pb, respectively, based on activity (decay of a certain isotope) per incident neutron 702. Activity is the number of atoms of a certain isotope times that isotope’s decay constant. Activity distribution 700 is based on activity (decay of a certain isotope) of second material 520 (e.g., decay of radioactive134Cs to stable133Cs) after particle bombardment (e.g., thermal neutrons) of the entire differentially activatable assembly 500 shown in FIG. 5 for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). As shown in FIG. 7,134Cs has an activity scheme 710 thatincreases approximately linearly from zero to about 1.2 x 10'8decays per incident neutron after about 48 hours,202Pb has an activity scheme 720 of about 0 decays per incident neutron (negligible),205Pb has an activity scheme 730 of about 0 decays per incident neutron (negligible),209Pb has an activity scheme 740 that increases exponentially from zero to about 1.22 x 10'7decays per incident neutron after about 48 hours and then exponentially decays to about zero after about 80 hours, and210Pb has an activity scheme 750 of about 1 x 10'10decays per incident neutron (negligible).

[0142] FIG. 8 illustrates relative activity distribution 800 based on a ratio of total activity 802 (e.g., sum of all isotopes) over time 804 for second material 520 (e.g.,134Cs) to total activity of first material 510 (e.g.,202Pb,205Pb,209Pb,210Pb) produced from differentially activatable assembly 500 shown in FIG. 5, according to an exemplary aspect. Relative activity distribution 800 shows a plot of relative activity 810 for a total of134Cs activity to a total of Pb activity (e.g., sum of202Pb,205Pb,209Pb, and210Pb). Relative activity distribution 800 is based on activity of second material 520 (e.g., decay of radioactive 134Cs to stable133Cs) after particle bombardment (e.g., thermal neutrons) of the entire differentially activatable assembly 500 shown in FIG. 5 for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). As shown in FIG. 8, relative activity 810 reaches of maximum of about 2.4 x 106after about 150 hours, indicating that after about 150 hours a majority of activity in differentially activatable assembly 500 is from second material 520 (e.g.,134Cs) and very little activity resides in first material 510 (e.g., Pb).

[0143] FIG. 9 illustrates 2D fluence profile 900 of differentially activatable assembly 500 shown in FIG. 5, according to an exemplary aspect. As discussed above, the geometrical arrangement of differentially activatable assembly 500, with second material 520 coupled to collimator 530 within first material 510 and along longitudinal axis 511 of first material 510, can produce (when activated) highly anisotropic emission along longitudinal axis 501 of differentially activatable assembly 500 and outward from distal end (aperture) 534 of collimator 530. 2D fluence profile 900 is based on activation of plurality of second materials 1020a-1020e (e.g., stable133Cs to radioactive134Cs) via particle bombardment (e.g., thermal neutrons) of the entire differentially activatable assembly 1000 shown in FIG. 10 for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). As shown in FIG. 9, 2D fluence profile 900can include anisotropic emission 910 formed from collimator 530 of differentially activatable assembly 500.Exemplary Alternative Differentially Activatable Assemblies

[0144] FIGS. 10, 11, and 12A-12C illustrate differentially activatable assembly 1000, according to exemplary aspects. The aspects of differentially activatable assembly 500 shown in FIG. 5, for example, and the aspects of differentially activatable assembly 1000 shown in FIG. 10 may be similar. Similar reference numbers are used to indicate features of the aspects of differentially activatable assembly 500 shown in FIG. 5 and the similar features of the aspects of differentially activatable assembly 1000 shown in FIG. 10. One difference between the aspects of differentially activatable assembly 500 shown in FIG. 5 and the aspects of differentially activatable assembly 1000 shown in FIG. 10 is that differentially activatable assembly 1000 includes a unique (e.g., optimized) assortment of second material 1020 (e.g., plurality of second materials 1020a-1020e) and / or third material 1030 (e.g., plurality of third materials 1030a-1030e) within first material 1010, rather than second material 520 and collimator 530 within first material 510 of differentially activatable assembly 500 shown in FIG. 5. Although differentially activatable assembly 1000 is shown in FIGS. 10, 11, and 12A-12C as a stand-alone apparatus and / or system, aspects of this disclosure can be used with other apparatuses, systems, and / or methods, for example, modeling flow diagram 100, modeling flow diagram 200, manufacturing flow diagram 300, system 400, and / or differentially activatable assembly 500.

[0145] Differentially activatable assembly 1000 can be configured to have a unique (e.g., optimized) distribution of one or more second materials 1020 (e.g., plurality of second materials 1020a-1020e) and / or one or more third materials 1030 (e.g., plurality of third materials 1030a-1030e) within first material 1010 to create differential emission, scattering, and attenuation to provide a unique observable field (e.g., emission profile, etc.) in three-dimensions (3D) around the surface of differentially activatable assembly 1000 when activated. Differentially activatable assembly 1000 can be configured to be differentially activatable (e.g., differently based on an orientation of the differentially activatable assembly relative to a direction of the particle bombardment). Differentially activatable assembly 1000 can be further configured to be stable prior to activation (e.g., radiation-safe until activation). Differentially activatable assembly 1000 can be furtherconfigured to be self-contained (e.g., shielding and activatable materials in a single compact unit). Differentially activatable assembly 1000 can be further configured to be activated after construction. Differentially activatable assembly 1000 can be further configured to be optimized to provide complex and unique three-dimensional (3D) and / or four-dimensional (3D over time) observable fields. In some aspects, differentially activatable assembly 1000 can be a miniature differentially activatable assembly (e.g., volume of 1 mm3), for example, for biological systems irradiation applications (e.g., small animal, human, cell(s), tissue, food, etc.). In some aspects, differentially activatable assembly 1000 can be used for radiation therapy and / or radiobiology, for example, to direct radiation with a complex observable field (e.g., emission profile, etc.) to a target region of a subject (e.g., small animal, mouse, human, etc.). In some aspects, differentially activatable assembly 1000 can be used for atomic batteries.

[0146] As shown in FIG. 10, differentially activatable assembly 1000 can include first material 1010, second material 1020, and third material 1030. Differentially activatable assembly 1000 can be configured to be differentially activatable via particle bombardment (e.g., thermal neutrons). Differentially activatable assembly 1000 can be further configured to produce a complex observable field (e.g., emission profile, etc.) upon activation. The unique (e.g., optimized) geometrical arrangement of differentially activatable assembly 1000, with one or more second materials 1020 (e.g., plurality of second materials 1020a-1020e) and / or one or more third materials 1030 (e.g., plurality of third materials 1030a-1030e) within first material 1010, can produce (when activated) complex (e.g., highly anisotropic) emission in three-dimensions (3D).

[0147] In some aspects, differentially activatable assembly 1000 can be activated differentially to provide a desired observable field (e.g., emission profile, etc.) that is complex. For example, as shown in FIGS. 12A-12C, differentially activatable assembly 1000 can be activated differently (e.g., X-Z plane, X-Y plane, Y-Z plane) based on an orientation of differentially activatable assembly 1000 relative to a direction of the particle bombardment (e.g., thermal neutrons) to provide unique and different 2D fluence profiles 1200A, 1200B, 1200C. In some aspects, differentially activatable assembly 1000 can provide (when activated) ionizing radiation, including but not limited to, X-rays, gamma rays, alpha particles, beta particles, protons, neutrons, electrons, or a combination thereof.

[0148] First material 1010 (e.g., shielding material) can be configured to provide shielding of second material 1020 and / or third material 1030. First material 1010 can be further configured to surround (encapsulate) second material 1020 and / or third material 1030. In some aspects, first material 1010 can include lead, a lead composite, tin, rubber, polyvinyl chloride, antimony, tungsten, bismuth, or a combination thereof. For example, first material 1010 can include lead (Pb). In some aspects, first material 1010 can be a shielding material, for example, lead (Pb). In some aspects, first material 1010 can be a non-activatable material, for example, a purified form of lead (Pb) (e.g., 100%206Pb such that activation of any Pb atoms creates another stable isotope,207Pb or208Pb) or a purified form of gadolinium (Gd) (e.g.,157Gd).

[0149] Second material 1020 (e.g., activatable material) can be configured to provide emission (e.g., gamma rays) when activated (e.g., via particle bombardment). Second material 1020 can be further configured to be within first material 1010. Second material 1020 can be further configured to be differentially activatable via particle bombardment. As shown in FIG. 10, second material 1020 can include a plurality of second materials 1020a-1020e (e.g., cylindrical133Cs) uniquely (e.g., optimally) distributed within first material 1010. In some aspects, for example, as shown in FIG. 10, plurality of second materials 1020a-1020e (e.g., activatable material) can be uniquely distributed within first material 1010 thereby forming a unique three-dimensional (3D) and / or four-dimensional (3D over time) observable field (e.g., emission profile, etc.). In some aspects, second material 1020 can be an activatable material, for example, cesium (Cs). In some aspects, second material 1020 can be a stable activatable material prior to activation (e.g.,133Cs) and a radioactive emitter after activation (e.g.,134Cs).

[0150] Third material 1030 (e.g., a pocket) can be configured to create differential emission, scattering, and / or attenuation of emission from second material 1020. Third material 1030 can be further configured to be within first material 1010. As shown in FIG. 10, third material 1030 can include a plurality of third materials 1030a-1030e (e.g., a gas pocket or a vacuum pocket) uniquely (e.g., optimized) distributed within first material 1010. In some aspects, for example, as shown in FIG. 10, plurality of third materials 1030a-1030e can be uniquely distributed within first material 1010 thereby forming a unique three-dimensional (3D) and / or four-dimensional (3D over time) observable field (e.g., emission profile, etc.). In some aspects, third material 1030 can include a gas pocket or a vacuum pocket. For example, third material 1030 can be a vacuum pocket. In someaspects, third material 1030 can be a gas pocket, for example, that can include air, nitrogen, helium, argon, carbon dioxide, or a combination thereof. In some aspects, one or more third materials 1030 (e.g., plurality of third materials 1030a-1030e) can be formed in first material 1010 via gas injection, ablation, heating, pressurizing, melting, rapid phase changes, etching, chemical treatment, deposition, sputtering, 3D printing, or a combination thereof.

[0151] In some aspects, third material 1030 can be a shielding material, for example, lead (Pb). In some aspects, third material 1030 can be a non-activatable material, for example, a gas pocket, a vacuum pocket, a purified form of lead (Pb) (e.g., 100%206Pb) or a purified form of gadolinium (Gd) (e.g.,157Gd). In some aspects, third material 1030 can be an activatable material, for example, cesium (Cs). In some aspects, third material 1030 can be a stable activatable material prior to activation (e.g.,133Cs) and a radioactive emitter after activation (e.g.,134Cs). In some aspects, third material 1030 can include a non-activatable material and an activatable material. For example, third material 1030 can include plurality of third materials 1030a-1030e, with third materials 1030a-1030b being a non-activatable material (e.g., a vacuum pocket) and third materials 1030c-1030e being an activatable material (e.g.,133Cs,59Co,54Fe,191Ir,127I, or a combination thereof).

[0152] In some aspects, differentially activatable assembly 1000 can include plurality of second material 1020a-1020e and plurality of third materials 1030a-1030e within first material 1010. For example, as shown in FIG. 10, plurality of second materials 1020a- 1020e and plurality of third materials 1030a-1030e can be uniquely distributed within first material 1010 thereby forming a unique three-dimensional (3D) observable field (e.g., emission profile, etc.).

[0153] FIG. 11 illustrates activity distribution 1100 (decay of a certain isotope) per incident activation particle (e.g., neutron) over time 1104 for different material species (e.g.,134Cs,205Pb,209Pb) produced from differentially activatable assembly 1000 shown in FIG. 10, according to an exemplary aspect. Activity distribution 1100 shows a plot of activity schemes 1110, 1120, 1130, 1140, 1150, 1160, 1170 (decay of a certain isotope) for the five plurality of second materials 1020a-1020e (e.g.,134Cs) and first material 1010 (e.g.,205Pb,209Pb) shown in FIG. 10, respectively, based on activity (decay of a certain isotope) per incident neutron 1102. Activity distribution 1100 is based on activity (decay of a certain isotope) of plurality of second materials 1020a-1020e (e.g., decay of radioactive134Cs to stable133Cs) after particle bombardment (e.g., thermal neutrons) ofthe entire differentially activatable assembly 1000 shown in FIG. 10 for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment).

[0154] As shown in FIG. 11,134Cs of second materials 1020a has an activity scheme 1110 that increases approximately linearly from zero to about 4.5 x 10'8decays per incident neutron after about 48 hours,134Cs of second materials 1020b has an activity scheme 1120 that increases approximately linearly from zero to about 4.6 x 10'8decays per incident neutron after about 48 hours,134Cs of second materials 1020c has an activity scheme 1130 that increases approximately linearly from zero to about 4.8 x 10'8decays per incident neutron after about 48 hours,134Cs of second materials 1020d has an activity scheme 1140 that increases approximately linearly from zero to about 4.2 x 10'8decays per incident neutron after about 48 hours,134Cs of second materials 1020e has an activity scheme 1150 that increases approximately linearly from zero to about 3.9 x 10'8decays per incident neutron after about 48 hours,205Pb has an activity scheme 1160 of about 1 x 10'10decays per incident neutron (negligible), and209Pb has an activity scheme 1170 that increases exponentially from zero to about 1.25 x 10'8decays per incident neutron after about 48 hours and then exponentially decays to about zero after about 80 hours.

[0155] FIGS. 12A-12C illustrate 2D fluence profiles 1200A, 1200B, 1200C of differentially activatable assembly 1000 shown in FIG. 10, according to exemplary aspects. As discussed above, the geometrical and compositional arrangement of differentially activatable assembly 1000, with a unique (e.g., optimized) distribution of one or more second materials 1020 (e.g., plurality of second materials 1020a-1020e) and one or more third materials 1030 (e.g., plurality of third materials 1020a-1020e), can produce (when activated) a unique and complex three-dimensional (3D) and / or fourdimensional (3D over time) observable field (e.g., emission profile, etc.). 2D fluence profiles 1200A, 1200B, 1200C are based on activation of plurality of second materials 1020a-1020e (e.g., stable133Cs to radioactive134Cs) via particle bombardment (e.g., thermal neutrons) of the entire differentially activatable assembly 1000 shown in FIG. 10 for about 48 hours followed by about 300 hours of down time (e.g., no particle bombardment). As shown in FIG. 12A, 2D fluence profile 1200A illustrates unique three- dimensional (3D) observable field (e.g., fluence profile, etc.) of differentially activatable assembly 1000 in the X-Z plane. As shown in FIG. 12B, 2D fluence profile 1200B illustrates unique three-dimensional (3D) observable field (e.g., fluence profile, etc.) ofdifferentially activatable assembly 1000 in the X-Y plane. As shown in FIG. 12C, 2D fluence profile 1200C illustrates unique three-dimensional (3D) observable field (e.g., fluence profile, etc.) of differentially activatable assembly 1000 in the Y-Z plane.

[0156] It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by those skilled in relevant art(s) in light of the teachings herein.

[0157] The following examples are illustrative, but not limiting, of the aspects of this disclosure. Other suitable modifications and adaptations of the variety of conditions and parameters normally encountered in the field, and which would be apparent to those skilled in the relevant art(s), are within the spirit and scope of the disclosure.

[0158] While specific aspects have been described above, it will be appreciated that the aspects can be practiced otherwise than as described. The description is not intended to limit the scope of the claims.

[0159] The aspects have been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.

[0160] The foregoing description of the specific aspects will so fully reveal the general nature of the aspects that others can, by applying knowledge within the skill of the art, readily modify and / or adapt for various applications such specific aspects, without undue experimentation, without departing from the general concept of the aspects. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed aspects, based on the teaching and guidance presented herein.

[0161] The breadth and scope of the aspects should not be limited by any of the abovedescribed exemplary aspects, but should be defined only in accordance with the following claims and their equivalents.

Claims

WHAT IS CLAIMED IS:

1. A method of designing a differentially activatable assembly, the method comprising: defining an observable field; defining a model of the differentially activatable assembly based on a set of parameters; and performing an inverse optimization of the set of parameters such that the model of the differentially activatable assembly after activation produces the observable field.

2. The method of claim 1, wherein the observable field comprises an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof.

3. The method of claim 1, wherein the set of parameters describing the model comprises one or more activatable materials, one or more non-activatable materials, a geometry of the materials, a distribution of the materials, activation cross-sections of the materials, decay characteristics of the materials, half-lives of the materials, radioactivity distributions of the materials, emitted particles of the materials, a particle field for activation of the materials, activation time, waiting period after activation, or a combination thereof.

4. The method of claim 1, further comprising manufacturing the differentially activatable assembly based on the model after the inverse optimization.

5. The method of claim 4, further comprising activating the differentially activatable assembly after manufacturing to produce the observable field.

6. A system for designing a differentially activatable assembly, the system comprising: a modeling system configured to: define an observable field; define a model of the differentially activatable assembly based on a set of parameters; andperform an inverse optimization of the set of parameters such that the model of the differentially activatable assembly after activation produces the observable field.

7. The system of claim 6, wherein the observable field comprises an emission profile, a fluence profile, an energy deposition distribution, a dose distribution, a radiobiological effect distribution, a current generation, a charge generation, a particle flux, an ionization distribution, a heat distribution, a combination thereof, or a derivative thereof.

8. The system of claim 6, wherein the set of parameters describing the model comprises one or more activatable materials, one or more non-activatable materials, a geometry of the materials, a distribution of the materials, activation cross-sections of the materials, decay characteristics of the materials, half-lives of the materials, radioactivity distributions of the materials, emitted particles of the materials, a particle field for activation of the materials, activation time, waiting period after activation, or a combination thereof.

9. The system of claim 6, further comprising a manufacturing system configured to manufacture the differentially activatable assembly based on the model after the inverse optimization.

10. The system of claim 9, further comprising an activation system configured to activate the differentially activatable assembly after manufacturing to produce the observable field.

11. A method of designing a differentially activatable assembly, the method comprising: defining an observable field; determining a particle field for activation of a volume of a material; determining a plurality of materials each with different activation cross-sections and decay characteristics to form complex radioactivity distributions; and optimizing a distribution of the plurality of materials in a geometry based on the complex radioactivity distributions, the particle field, and the observable field, thereby modeling the differentially activatable assembly to produce the observable field after bombardment via the particle field.

12. The method of claim 11, further comprising manufacturing the differentially activatable assembly based on the optimized distribution.

13. The method of claim 12, further comprising bombarding the manufactured differentially activatable assembly with the particle field, thereby activating the differentially activatable assembly to form a radioactive emitter and produce the observable field.

14. The method of claim 11, wherein the plurality of materials comprises an activatable material and a non-activatable material.

15. The method of claim 11, wherein optimizing the distribution comprises optimizing in three-dimensions.

16. The method of claim 11, wherein optimizing the distribution comprises optimizing in four-dimensions.

17. The method of claim 16, wherein optimizing in four-dimensions comprises calculating waiting periods after activation based on different half-lives of the plurality of materials.

18. The method of claim 11, wherein optimizing the distribution comprises using an optimization algorithm.

19. The method of claim 18, wherein the optimization algorithm comprises simulated, annealing, gradient descent, finite difference, interpolation, population models, regression, parameter adaptation, supervised machine learning, unsupervised machine learning, neural networks, classification models, clustering, vector quantization, stochastic gradient descent, implicit updates, leaky averaging, momentum methods, adaptive gradient (AdaGrad), backpropagation, root mean square propagation (RMSProp), adaptive moment estimation (Adam), or a combination thereof.

20. A method of manufacturing a differentially activatable assembly, the method comprising:optimizing a distribution of a plurality of materials in a geometry based on an observable field, a particle field for activation, and radioactivity distributions of the plurality of materials; and manufacturing the differentially activatable assembly based on the optimized distribution.

21. The method of claim 20, further comprising activating the differentially activatable assembly after manufacturing the differentially activatable assembly thereby forming a radioactive emitter.

22. The method of claim 20, wherein manufacturing the differentially activatable assembly comprises ion implanting one or more of the plurality of materials.

23. The method of claim 22, wherein ion implanting comprises a spatial resolution in three- dimensions of at least 1 micron.

24. The method of claim 20, wherein manufacturing the differentially activatable assembly comprises depositing one or more of the plurality of materials.

25. The method of claim 24, wherein depositing comprises epitaxy, physical vapor deposition (PVD), electron-beam PVD (EBPVD), sputter deposition, electrosputtering, chemical vapor deposition (CVD), plasma-enhanced CVD (PECVD), atomic layer deposition (ALD), powder bed deposition, or a combination thereof.

26. The method of claim 20, wherein manufacturing the differentially activatable assembly comprises manufacturing with a computer controlled manufacturing system.

27. The method of claim 26, wherein the computer controlled manufacturing system comprises a computer numerically controlled (CNC) machine, an additive manufacturing machine, a subtractive manufacturing machine, a drill, a lathe, a mill, a grinder, a router, a 3D printer, a lithographic machine, a photolithographic machine, an inkjet machine, a sintering machine, a fused deposition machine, or a combination thereof.

28. An assembly comprising: a first material; and a second material, wherein the assembly is configured to be differentially activatable via particle bombardment, and wherein an observable field of the assembly after activation is complex.

29. The assembly of claim 28, wherein the observable field is anisotropic.

30. The assembly of claim 28, wherein the assembly comprises: a unique geometry; and a unique distribution of the first material and the second material, wherein the observable field is a unique three-dimensional observable field.

31. The assembly of claim 28, wherein the assembly comprises: a unique geometry; a unique distribution of the first material and the second material; and a unique decay time, wherein the observable field is a unique four-dimensional observable field.

32. The assembly of claim 28, wherein the assembly is self-contained.

33. The assembly of claim 28, wherein the assembly is stable prior to activation.

34. The assembly of claim 28, wherein the assembly is configured to be activated after construction of the assembly thereby forming a radioactive emitter.

35. The assembly of claim 28, wherein the second material comprises a distribution of activatable atoms within the first material.

36. The assembly of claim 35, wherein the distribution of activatable atoms comprises a plurality of different distributions of activatable atoms.

37. The assembly of claim 28, wherein: the second material comprises a distribution of activatable atoms within the first material, the first material comprises a distribution of non-activatable materials having varying attenuation and scattering properties within the first material, and the distribution of activatable atoms and the distribution of non-activatable materials are uniquely distributed within the first material thereby forming a unique three- dimensional observable field.

38. The assembly of claim 28, wherein the first material and the second material have a different activation cross-section and / or a different half-life.

39. The assembly of claim 38, wherein the second material has a higher activation crosssection than the first material.

40. The assembly of claim 38, wherein the first material comprises a lower activation crosssection and either a longer half-life or a shorter half-life relative to the second material.

41. The assembly of claim 28, wherein the second material comprises a neutron activated material.

42. The assembly of claim 41, wherein the neutron activated material comprises cesium, cobalt, iron, iridium, or a combination thereof.

43. The assembly of claim 42, wherein the neutron activated material comprises cesium-133.

44. The assembly of claim 28, wherein the first material comprises lead, a lead composite, tin, rubber, polyvinyl chloride, antimony, tungsten, bismuth, or a combination thereof.

45. The assembly of claim 44, wherein the first material comprises lead.

46. The assembly of claim 28, wherein the first material comprises an activatable material.

47. The assembly of claim 46, wherein the first material and the second material produce different emitted particles.

48. The assembly of claim 28, wherein a longitudinal axis of the second material is aligned along a longitudinal axis of the first material.

49. The assembly of claim 28, further comprising a collimator coupled to the second material.

50. The assembly of claim 49, wherein the collimator is within the first material.

51. The assembly of claim 50, wherein the collimator comprises a void within the first material.

52. The assembly of claim 51, wherein a longitudinal axis of the void is aligned along a longitudinal axis of the first material.

53. The assembly of claim 51, wherein the void extends between a distal end of the second material and a distal end of the first material.

54. The assembly of claim 28, further comprising a pocket within the first material.

55. The assembly of claim 54, wherein the pocket comprises a gas pocket or a vacuum pocket.

56. The assembly of claim 55, wherein the gas pocket comprises air, nitrogen, helium, argon, carbon dioxide, or a combination thereof.

57. The assembly of claim 54, wherein the pocket comprises a plurality of pockets within the first material.

58. The assembly of claim 28, wherein the assembly has a volume of no greater than 100 mm3.

59. The assembly of claim 28, wherein the assembly has a volume of no greater than 1 mm3.

60. The assembly of claim 28, wherein the assembly is cylindrical.

61. The assembly of claim 28, wherein the assembly is ellipsoidal.

62. The assembly of claim 28, wherein the assembly is a three-dimensional orthotope.

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