System and method for automated separation and recovery of astatine

Abstract

Disclosed herein are systems and methods for automated separation and recovery of compounds from solutions. In some embodiments, the system can use a pump in fluid / pneumatic communication with a chromatography column to dissolve and recover astatine from a solution containing astatine, bismuth, and nitric acid. The system can communicate with a controller that can automate and / or remotely signal each component of the system to perform the recovery without manual user input.

Description

[Technical Field]

[0001] Government rights This invention was made with government support under the DOE Science Directorate DE-SC0020958. The government has certain rights in this invention.

[0002] This disclosure relates to systems and methods for the separation and recovery of compounds from various media, and more specifically, to automated systems and methods for the separation and extraction of astatine from dissolution solutions containing bismuth and astatine dissolved in an acidic medium. [Background technology]

[0003] Astatine-211 211 α) is one of the most promising alpha-emitting radionuclides for targeted alpha-emitting therapy. Targeted alpha-emitting (TAT) drugs are attracting considerable interest in the use of alpha-emitting radionuclides for the treatment of various diseases, such as cancer. One such isotope that is attracting significant attention has a moderately short half-life of about 7.2 hours and quantitative alpha emission from a simple decay scheme, possessing decay properties suitable for clinical use. 211 It is At. 209 Bi(α,2n) 211 The amount available via the AT nuclear reaction 211 As a standard for generating At, natural bismuth using an alpha particle beam ( 209 Bi) Impact on the target is employed. There are only about 30 cyclotrons in the world capable of producing usable quantities, and only 7 of them are in the United States, and currently only one of them is a supplier to the U.S. Department of Energy's isotope program. 211 The global supply of At remains limited. Despite its low availability, 211 At is being used in several clinical trials investigating the treatment of malignant brain tumors and ovarian cancer, and in current research to treat advanced hematopoietic malignancies.

[0004] The chemistry of astatine is one of the few relatively unexplored areas in the periodic table. This may be due to the fact that the abundance of astatine on Earth is estimated to be only 0.07 g, and it has no stable isotopes, making it the least abundant among the naturally occurring elements. Among the isotopes of astatine, the one with the longest half-life is 211 slightly longer-lived than 210 At, belonging to

[0005] Currently, there are two methods for the recovery of astatine: wet chemical treatment and dry distillation. These conventional methods for recovering 211 At from bismuth targets have several drawbacks. First, in an analytical-scale separation where the amount of 211 At to be recovered and purified is on the order of 1 - 10 ng and a macro amount of 209 Bi (1 - 10 g) occupies most of the matrix, solvent extraction is not suitable as an efficient means of separation because it is controlled to a single separation step per contact. Furthermore, analytical-scale separations need to be carried out in a continuous flow mode, which is the most efficient way for recovery and separation, but requires sophisticated equipment, thereby significantly increasing the cost of the process and hindering scalability. Second, these methods involve a system conversion from nitrate to chloride media, which adds a slow, time-consuming step, either evaporation to remove nitric acid or chemical destruction of nitrate ions by hydroxylammonium chloride. Additionally, these conversions lead to losses of volatile astatine and can introduce impurities into the system, for example, by stripping the compound from the container in which it is stored, which 211 hinders the separation of 211 At and degrades the quality of 211 At upon recovery. Finally,

Summary of the Invention

Problems to be Solved by the Invention

[0006] Therefore, there is a need for an improved system and method for optimizing the separation and purification for the recovery of astatine.

Means for Solving the Problems

[0007] According to one aspect of the present disclosure, a compound recovery system comprises the following.

[0008] A first column configured to extract astatine from a dissolution solution in which astatine is dissolved, the column having an extraction medium with an associated solvent, the first column; a pump in fluid communication with the column, the pump being configured to deliver the dissolution solution to the column; and a control system in communication with the pump, the control system being configured to regulate the flow of the dissolution solution through the pump via a signal, the signal being automated or located remotely.

[0009] In another aspect, a method for compound recovery includes the following.

[0010] Exposing a target material having one or more compounds therein to an acidic medium to dissolve the target material in the acidic medium to form a dissolution solution having the target material and the one or more compounds therein; passing the dissolution solution through a chromatography column to extract the one or more compounds from the dissolution solution, the one or more compounds being extracted into a resin bed disposed within the chromatography column; washing the resin bed to remove a non-extracted solution from the column; and each of the steps of exposing the target material, passing the dissolution solution through the chromatography column; and washing the resin bed occurs in response to an automated signal or a signal located remotely.

[0011] Additional embodiments, features, and advantages of the present disclosure will become apparent from the following detailed description and through the practice of the present disclosure. The processes and compounds of the present disclosure can be described as embodiments in any of the clauses listed below. It will be understood that any of the embodiments described herein can be used in connection with any other embodiment described herein, provided the embodiments are not mutually inconsistent.

[0012] 1. A first column configured to extract astatine from a dissolution solution in which astatine is dissolved, the column having an extraction medium with a relevant solvent, the first column; A pump in fluid communication with the column, the pump being configured to deliver the dissolution solution to the column, the pump; A control system in communication with the pump, the control system being configured to regulate the flow of the dissolution solution through the pump via a signal, the signal being automated or remotely located, the control system A compound recovery system comprising.

[0013] 2. The system of clause 1, further comprising a dissolution vessel in fluid communication with the pump and the column, the dissolution vessel being configured to form a dissolution solution by mixing an irradiated target material and a medium therein.

[0014] 3. The system of clause 2, further comprising one or more selectors in fluid communication with the pump, the one or more selectors being configured to deliver a solvent or a dissolution solution therethrough.

[0015] 4. The system of clause 3, wherein the orientation of the one or more selectors is determined by a signal from the control system.

[0016] 5. The system of clause 3 or 4, wherein the control system is configured to communicate with the pump and the one or more selectors substantially simultaneously.

[0017] 6. One or more selectors comprising a single inlet and multiple outlets, according to any one of the systems described in clauses 3 to 5.

[0018] 7. One or more selectors comprising a single exit and multiple inlets, according to any one of the systems described in clauses 3 to 6.

[0019] 8. The system of Clause 4, wherein one or more selectors are configured to fluidly communicate with one or more vials containing a solution, and a pump is configured to deliver the medium to a dissolution vessel through one or more selectors.

[0020] 9. A system of Clause 8 in which the medium contains one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

[0021] 10. Any one of the systems described in clauses 1 through 9, wherein the extraction medium is a resin bed.

[0022] 11. Any one of the systems from clauses 1 to 10, wherein the solvent may include one or more of octanone, 3-octanone, or 1-octanol.

[0023] 12. Any one of the systems described in clauses 1 through 11, wherein astatine extraction occurs without heating.

[0024] 13. Any one of the systems from clauses 1 to 12, further comprising a pump and a fluid-communicating quality assurance device configured to sample a portion of the dissolved solution.

[0025] 14. Any one of the systems from clauses 1 to 13, further comprising a second column configured to receive a portion of the dissolution solution through it.

[0026] 15. The system of clause 14, wherein the second column is arranged in series with the first column.

[0027] 16. The system of clause 14 or 15, wherein the second column is arranged in parallel with the first column.

[0028] 17. A method for recovering compounds, The process involves the steps of: exposing the target material containing one or more compounds to an acidic medium in order to dissolve the target material in the acidic medium in order to form a dissolution solution containing the target material and one or more compounds; A step of passing a dissolution solution through a chromatography column to extract one or more compounds from the dissolution solution, wherein one or more compounds are extracted onto a resin bed placed in the chromatography column. The steps include: cleaning the resin bed to remove unextracted soluble solution from the column; Includes, Each of the steps—exposing the target material, passing the dissolution solution through the chromatography column, and cleaning the resin floor—is triggered in response to an automated signal or a signal located remotely. method.

[0029] 18. The resin floor is cleaned with an acidic medium, according to the method of Clause 17.

[0030] 19. The method of Clause 17 or 18, wherein the acidic medium comprises one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

[0031] 20. Any one of the methods described in clauses 17 to 19, further comprising the step of washing the chromatographic column with an aqueous solution to remove an acidic medium from the chromatographic column.

[0032] 21. One of the methods described in clauses 17 to 20, wherein the dissolution solution is formed over a period of approximately 5 to 30 minutes.

[0033] 22. The method of clause 20 or 21, further comprising the step of eluting one or more compounds from a resin in order to collect one or more compounds.

[0034] 23. Any one of the methods of clauses 20 to 22, further comprising the steps of drying the column to remove excess fluid from the column and sealing the column.

[0035] 24. The method of clause 23, wherein the step of drying the column further includes the step of blowing air through the column until the excess fluid is substantially removed.

[0036] 25. The method of clause 24, wherein after blowing air through the column, the column retains the compound.

[0037] 26. Any one of the methods of clauses 17 to 25, wherein the dissolution solution is passed through a chromatography column by a pump that is in fluid communication with one or more selectors positioned between the pump and the column.

[0038] 27. The method of clause 26, further comprising the step of adjusting the orientation of one or more selectors in response to a signal.

[0039] 28. A method of any one of the provisions of 17 to 27, further comprising the step of dividing a dissolved solution into multiple streams, each stream entering a separate chromatographic column.

[0040] 29. Any one of the methods described in clauses 17 to 28, wherein the extraction of one or more compounds occurs without heating.

[0041] 30. Any one of the methods in clauses 17 to 29, further comprising the step of sampling a portion of the dissolution solution to determine its activity level before passing a portion of the dissolution solution to the column.

[0042] Additional features of this disclosure will become apparent to those skilled in the art, considering exemplary embodiments that illustrate the best known way of implementing this disclosure.

[0043] This disclosure will be better understood from the following detailed description, which is associated with the attached drawings. [Brief explanation of the drawing]

[0044] [Figure 1] This is a perspective view of an exemplary embodiment of the compound separation and recovery system of this embodiment, which has a series of valves and a pump in fluid communication for dissolving an irradiated target material and flowing the solution to fill a column with the dissolved solution. [Figure 1B] This is an alternative perspective view of the system in Figure 1, showing the related system components and the components in an alternative orientation. [Figure 2A] This is a perspective view of one embodiment of a valve selector used in the system shown in Figure 1, which has an inlet and multiple outlets formed thereon. [Figure 2B] This is a perspective view of another embodiment of a valve used in the system shown in Figure 1, with a rotary valve formed on it. [Figure 2C] This is a perspective view of another embodiment of the valve used in the system of Figure 1, with another embodiment of the rotary valve formed thereon. [Figure 3] This is a schematic diagram of one exemplary embodiment of a control system capable of controlling one or more pumps in the system shown in Figure 1. [Figure 4] This is a schematic diagram of one exemplary embodiment of the automated compound recovery system of this embodiment. [Figure 5] This is a schematic diagram of one exemplary embodiment of a method for separating and recovering compounds from a target material. [Figure 6A] Figure 4 is a schematic diagram illustrating an exemplary embodiment of the flow sequence through the components of the automated compound recovery system. [Figure 6B] Figure 4 is a schematic diagram of the automated compound recovery system in target dissolution mode. [Figure 6C] Figure 4 is a schematic diagram of an automated compound recovery system for transferring dissolved solutions to a QA device. [Figure 6D] Figure 4 is a schematic diagram of the automated compound recovery system when the column is packed. [Figure 6E] Figure 4 is a schematic diagram of an automated compound recovery system for flushing the column with water. [Figure 7] This is a schematic diagram of one exemplary embodiment of a computer system in which the control system of the present disclosure is constructed. [Modes for carrying out the invention]

[0045] Astatine (At) can be produced by colliding alpha particles with bismuth-209. For example, in some embodiments, the target bismuth material is subjected to the following process within the target material. 211 Alpha particles are irradiated to produce At. Those skilled in the art will recognize that this collision typically occurs in a particle accelerator, such as a cyclotron. For example, in some embodiments, astatine-211 is irradiated for 9-10 hours onto a natural Bi metal target (isotopically pure, purchased from Goodfellow). 209 Bi, metallic purity ≥ 99.997%, undergoes a 28.8 MeV alpha particle collision (cross-sectional area of ​​approximately 0.9 burn). 209 Bi(α,2n) 211 It was produced by the At nuclear reaction in two separate runs. The method described above is purely illustrative, and it will be understood that one or more variables may vary in the process of producing astatine-211. Furthermore, to the extent that astatine is described herein, the astatine referred to is 209 Tom or 211 It will be understood that At and its cationic species may be. For example, At as described in the processes herein may be the cationic species AtO + It may be, but is still called At. Exemplary, the process may include generating At. The formed collision target may contain a mixture of At, unreacted Bi, and by-products.

[0046] The generated At must then be isolated from unreacted Bi. Described herein is a process for isolating At from compositions, such as those formed from collisions with Bi, using extraction chromatography. In exemplary embodiments, the process described herein involves dissolving the At-containing composition and then isolating At from the dissolved solution. The process described can be carried out without the need to convert the medium or solution used to initially dissolve the At / Bi composition, as will be discussed in more detail below.

[0047] This disclosure generally relates to systems and methods for automated and / or remotely controlled purification and collection of compounds. In some embodiments, the system may include a series of pumps and valves to control a column-based purification system, and the method may involve alpha-emitting therapeutic radioisotopes from a dissolved cyclotron target. 211 The system includes methods for the rapid separation and purification of At. In one embodiment, the system can dissolve the target material in a solution. In such embodiments, the system can bring the irradiated target material into contact with an aqueous solution to dissolve bismuth and astatine in the solution.

[0048] The aqueous solution may contain an acid, such as an organic acid or a mineral acid. The mineral acid may be nitric acid. The solution dissolves or substantially dissolves the composition to form a solution containing At and Bi. In some embodiments, the solution contains At, Bi, and an acid. In some embodiments, the solution contains At, Bi, and nitric acid. The target can be dissolved in a solution consisting of various media. Some additional non-limiting examples of aqueous solutions may include hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

[0049] In some embodiments, the solution has a specific concentration of acid, or is prepared to have a specific concentration of acid before the subsequent steps. Exemplarily, the acid may help dissolve the composition. For example, the presence of nitric acid may help dissolve the impacted Bi target.

[0050] Exemplary, the acid concentration may be about 1 M to about 10 M, about 1 M to about 8 M, about 2 M to about 8 M, or about 3 M to about 7 M. The acid concentration may be about 1 M, about 2 M, about 3 M, about 4 M, about 5 M, about 6 M, about 7 M, about 8 M, about 9 M, or about 10 M. The acid concentration may be adjusted according to the partition coefficient in the solvent used in subsequent steps. The ranges described herein are equally applicable when the acid is an organic acid or a mineral acid such as nitric acid.

[0051] The time it takes for the target to dissolve sufficiently in an acidic medium can vary depending on the medium used. For example, 209 Bi and 211 A target material containing At can be dissolved over a period of approximately 2 minutes to 1 hour, 5 minutes to 30 minutes, 8 minutes to 20 minutes, or 10 minutes to 15 minutes. In embodiments where the ionic medium contains nitric acid, the target material can be sufficiently dissolved in about 10 minutes to form a dissolved solution.

[0052] Figures 1A and 1B show exemplary embodiments of a compound separation and recovery system 100 for extracting one or more compounds from a dissolution solution. While the system of this embodiment is discussed in relation to the recovery of astatine from a dissolution solution formed by dissolving a target having bismuth and astatine in nitric acid, those skilled in the art will recognize that the systems and methods currently disclosed can be applied to the extraction and recovery of various compounds from solutions, drug samples from body fluids, proteins from viral serum, and other inorganic substances obtained during the dissolution of various irradiated cyclotron targets.

[0053] As shown in the figure, system 100 may include a pump 102 connected to a series of valves or selectors 104 for circulating fluid throughout system 100. Pump 102 can be used to set the flow rate of any fluid circulating within the system. For example, pump 102 can circulate an acidic medium and / or dissolving solution throughout the system at the same flow rate, different flow rates, flow rates that change over time, etc. Some non-limiting examples of the pumps of this embodiment may include, among other things, peristaltic pumps, syringe-free pumps, diaphragm pumps, piston pumps, gear pumps, vane pumps, positive displacement pumps, and / or centrifugal pumps.

[0054] In some embodiments, the pump 102 can be regulated to change the flow rate of the liquid flowing through the system in response to an input. For example, in some embodiments, the pump 102 can be remotely controlled by signals from a control system 200 to guide the flow sequence of the entire system. Signals can be generated automatically via a program, remotely via user input, and / or manually by instructions to increase and / or decrease the flow rate. For example, the flow rate of the solution through the system can be about 365 mL / min, but in some embodiments it can range from about 0.0002 mL / min to 35 mL / min, while the flow rate of the dissolving solution can range from about 0.0002 mL / min to 35 mL / min. The control system 200 that controls the pump and the fluid flow will be discussed in more detail below.

[0055] Pump 102 can communicate fluidly with a series of valves 104. The valves 104 can be configured to change position between various orientations in order to allow fluid to flow in a given direction within the system 100. For example, the position of each valve 104 can be changed by a signal received from the pump and / or control system 200, which changes the direction of fluid flow through it.

[0056] Figure 1B shows additional components of the compound separation and recovery system 100. In addition to the valve 104 and dissolution box 112, system 100 may include an alternative peristaltic pump 114, a USB camera 116, a QA device for active sampling, a scrubber 130 containing a sodium hydroxide solution, and a charcoal vat 132 for removing astatine vapor. These components and their uses will be described in more detail below.

[0057] Figures 2A and 2C show the valve 104 in more detail. Each valve 104 may include an inlet 106 and one or more outlets 108 for distributing fluid throughout the system. As shown in Figure 2A, the selector 104 of this embodiment may include a single inlet 106 and ten outlets 108 extending therefrom, but it will be understood that in some embodiments the selector 104 may include nine or fewer outlets 108 or eleven or more outlets 108. Multiple outlets can support mixing or splitting batches of fluid flow into separate components of the system 100, for example, multiple chromatography columns, as will be discussed further below. In some embodiments the selector 104 may be a bidirectional selector valve supporting flow in a first direction from the source and flow in a second opposite direction returning to the source.

[0058] In some embodiments, the inlets and outlets can be reversed so that the selector can have multiple inlets and a single outlet. For example, the selector 104 may include a selector stator 110, for example, a plate 111 having a straight groove located behind a head having ports, the groove connecting the inlets 106 to one of the outlets 108 at a time via stepwise rotation of the plate 111. In embodiments in which the selector 104 includes a single outlet and multiple inlets, it will be understood that the plate 111 can similarly rotate to align the outlets 108 with the inlets 106.

[0059] Figure 2B shows an alternative embodiment of valve 104' of this embodiment, which has a rotary valve 110' above it. The rotary valve 110' may include a series of inlets 106' and outlets 108' arranged in a substantially circular arrangement around it. The rotary valve 110' can be rotated by the pump 102 and / or control system 200 to change the position of the valve in order to regulate the flow through the valve. The advantage of this type of valve is its ability to connect two adjacent ports at once and handle two streams simultaneously. For example, with a four-port valve, there are two possible positions, namely A and B, where position A connects port 1 to port 2 and port 3 to port 4, and position B connects port 1 to port 4 and port 2 to port 3. In comparison, selector 104 can only handle one stream at a time by connecting port 106 to one of the ports 108.

[0060] Figure 2C shows yet another embodiment of the valve 104' of this embodiment, which has another rotary valve 110" on top of it. Unlike the 6-port valve 104' of the embodiment in Figure 2B, this embodiment includes a 4-port valve 104" as shown. It will be understood that in some embodiments, valves with 2 ports, 3 ports, or 6 or more ports such as 8, 10, etc., may be used.

[0061] Those skilled in the art will recognize that the position of selector 104 or valve 104' can be controlled in conjunction with pump 102, but in some embodiments, the valve can be controlled independently. In some embodiments, changes in the position of selector 104 or valve 104' can occur in response to programming, remote user input, and / or manual rotation of the valve. Selector 104 or valve 104' can supply fluid or gas / air to other system components, such as a chromatography column (not shown), quality assurance devices, etc., as will be discussed further below. It will be understood that each selector 104 or valve 104' can be controlled independently of the other valves and / or the rest of the system 100.

[0062] In some embodiments, a selector 104 or valve 104' can flow a solution onto a target material to form a dissolution solution. As shown in the figure, the system 100 may include a dissolution box or container 112 configured to store material or solution for forming a dissolution solution. In one embodiment, the dissolution box 112 may be configured to receive a target therein. For example, once a target has been irradiated, the target can be placed inside the dissolution box 112. Furthermore, the dissolution box 112 may be in fluid communication with other system components to receive a solution that dissolves bismuth and astatine to form a dissolution solution. That is, the dissolution box 112 may be configured to receive fluid via a pump 102 to dissolve the material placed therein. The dissolution box 112 may be in fluid communication with a reservoir (up to 10 according to Figure 2A) containing mineral or organic acid and / or pure water to create a mixed solution of a desired concentration inside the dissolution box 112.

[0063] As described above, the compound recovery system 100 of this embodiment may include a control system 200, sometimes called a controller, an example of which is shown in Figure 3. The control system 200 can communicate with each of the components of the system 100 to control the behavior of each of the components of the system 100. In some embodiments, the control system 200 may be a personal computer or another computing source known to those skilled in the art, which can control the flow rate and direction of the fluid / air flow throughout the system 100. In some embodiments, control of the fluid / air flow rate and direction may occur by signaling the pump 102 and the selector 104 or valve 104', respectively, to flow the fluid / air according to inputs to the control system 200. As described above, the inputs in the control system 200 may be automated and / or remotely located, allowing the system 100 to operate without manual input.

[0064] The control system 200 may include a microcontroller 202 that can send control signals to a switch 204. These control signals can be used to regulate the volumetric flow rate of fluid / air by the pump 102. In some embodiments, the microcontroller 202 may be configured to output signals to other components of the system, such as the selector 104, columns, QA devices, etc. The switch 204 may be connected to a power supply 206, such as a direct current (DC) unit. While the control system 200 can be connected to the pump 102 as shown in the figure, it will be understood that in some embodiments, the control system 200 may be further connected to the selector 104, columns, QA devices, and other system components, as will be discussed in more detail below.

[0065] Figure 4 provides a more detailed schematic diagram of an exemplary embodiment of the automated compound recovery system 300 of this embodiment. As shown, the system 300 may include a pump 302, a plurality of valves / selectors 304, a dissolution box 312, and a column 320. The plurality of valves / selectors 304 may be arranged throughout the system 300 to facilitate the introduction of fluid / air into the system and the distribution of fluid / air throughout the system. For example, as shown, the plurality of valves / selectors 304 may include a solution selection valve 322 that is in fluid communication with one or more vials 324 containing a solution. For example, as shown, the solution selection valve 322 may be configured to receive fluid from the vials 324 for distribution throughout the system 300. In one embodiment, the solution in the vials 324 is an acidic medium, for example, nitric acid. The solution selection valve 322 may be connected to a bidirectional selection valve 326a that flows to the pump 302 in order to flow the solution into the dissolution box 312 containing the irradiated target material.

[0066] The controller 200 can communicate with the pump 302 and each of the multiple valves 304 to automate the fluid / air flow throughout the system and coordinate the flow sequence. The controller 200 can control multiple components in the system substantially simultaneously. For example, in some embodiments, the controller 200 can signal the pump 302 and the solution selection valve 322 to collect the solution from the bias 324 and flow the solution into the dissolution box 312. While the solution is flowing towards the dissolution box 312, the controller 200 can signal the bidirectional selection valves 326a and 326b to open to allow the fluid / air / gas to pass through the bidirectional selection valves 326a and 326b. Similarly, once the dissolution solution is prepared, the controller 200 can signal the bidirectional selection valve 326b to change direction so that the dissolution solution flows out of the dissolution box 312 and into the column 320 to begin astatine recovery.

[0067] Once the target material is sufficiently dissolved, the solution can be moved to column 320 through another valve 326b for the separation and extraction of astatine from the solution. Separation of astatine and bismuth after dissolution of the metal target in nitric acid is important in the system of this disclosure for the preparation of the final product. Column 320 can be configured to undergo an extraction chromatography process as the solution enters column 320. Liquid-phase-based chemistry is considered a more reliable method than dry distillation for astatine recovery. Those skilled in the art will recognize that passing a fluid through a tellurium column can lead to a lower astatine recovery yield and can strip compounds from the column walls, thereby contaminating the astatine product contained therein; therefore, the use of extraction chromatography in this embodiment is superior to conventionally used tellurium columns.

[0068] In some embodiments, At is isolated by using a resin in ion exchange chromatography. The resin may be in the form of resin beads. The resin beads may be dispersed over the entire length of column 320. Alternatively, the resin may be used in a bulk process. Exemplary resins include polymer beads and glass beads. In some embodiments, the beads include zeolite, molecular sieves, polymer resin, or glass beads. In some embodiments, the beads are porous. The beads may be inert. In some embodiments, the beads include a styrene-divinylbenzene copolymer. In some embodiments, the benzene in the copolymer does not contain functional groups.

[0069] In some embodiments, the porous resin is a polyacrylate resin or porous glass beads. 0.7 mLg in 20% ethanol purchased from Sigma-Aldrich. -1Amberchrom® CG300M porous beads, having a pore volume and a particle size of 50-100 μm slurry, can be used in extraction chromatography. Amberchrom® CG300M is a styrene-divinylbenzene copolymer that does not have functional groups in the benzene ring. In some embodiments, before use, the beads can be dried at 80°C for a minimum of 20 hours to remove any solvent from the pores.

[0070] The resin bed may contain biocompatible ligands incorporated therein. In one embodiment, the ligand is an organic solvent incorporated into the resin bed, but it will be understood that alcohols, aldehydes, ketones, water-immiscible ketones, organic acids, esters, ethers, amides, carbonates, carboxylates, carbamates, and / or organophosphorus compounds, such as trialkylphosphine oxides and trialkyl phosphates, and other compounds may be incorporated into the beads. For example, by immersing the beads in an organic solvent, one or more of octanone, 3-octanone, etc., can be impregnated into the dry resin. The organic solvent can be used for adsorption to the beads to extract astatine from the dissolution, and the remainder of the dissolution is passed through the column. For example, for a dissolution containing bismuth and astatine, 211 At is extracted into the organic solvent impregnated into the resin bed, but bismuth, the main component of the dissolution solution, is not extracted. Therefore, the organic solvent is absorbed into the resin bed. 211 The solution can be separated so that the bismuth remains in the solution, containing the At extract. Some additional non-limiting examples of organic solvents may include alcohols, aldehydes, ketones, immiscible ketones as the organic phase, such as methyl isobutyl ketone, decane, esters, amides, carbonates, carboxylates, water-immiscible alcohols, organic acids, organophosphorus compounds, and / or carbamates, such as alcohols, aldehydes, ketones, n-octanone in the case of n=1, 2, 3.

[0071] In some embodiments, the organic solvent is polar. In some embodiments, the organic solvent is optionally substituted with C1-C 18 It contains alkyl, where C1~C 18 Each hydrogen atom of an alkyl group is optionally substituted by a functional group. C1~C 18 Optional substitutions in alkyl groups are commonly known in the art and include halogens, hydroxyls, amines, thiols, oxo, ketones, carboxylates, aldehydes, amides, carbonates, carbamates, and combinations thereof. In some embodiments, the organic solvent comprises aldehydes, ketones, esters, amides, carbonates, carboxylates, or carbamates. In some embodiments, the organic solvent comprises C1-C12 C 18 , C1~C 12 , or containing C1-C6 alkyl. In some embodiments, the organic solvent is of the formula C1-C6 alkyl-C(O)-C1-C6 alkyl. In some embodiments, the organic solvent is of the formula C1-C6 alkyl-C(O)-C1-C6 alkyl, where each hydrogen atom in the C1-C6 alkyl is optionally substituted. In some embodiments, the organic solvent is C1-C 18 These are alkanols. Exemplary examples of organic solvents may include mixtures of organic solvents described herein.

[0072] In some embodiments, the solvent for the impregnation resin is a solvent that provides a D-value partition coefficient of at least 10 for At in aqueous solutions, such as an aqueous solution containing nitric acid. In exemplary embodiments, At has a D-value partition coefficient of at least about 20, at least about 40, at least about 60, or at least about 80 in organic solvents. Exemplarily, the partition coefficient may be measured in aqueous solutions containing an acid such as nitric acid. In some embodiments, At has a partition coefficient of at least about 20 or at least about 40 between octanone and an aqueous solution containing about 2-6 M nitric acid.

[0073] The term "alkyl" refers to a monovalent carbon-hydrogen group, either linear or branched. In some embodiments, the number of atoms in "alkyl" is C1-C 18 Alkyl, C1-C 12 It may be advantageous to limit alkyl groups to a specific range of atoms, such as C1-C6 alkyl groups. Examples of alkyl groups include methyl (Me), ethyl (Et), n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl (tBu), pentyl, isopentyl, tert-pentyl, hexyl, isohexyl, and groups that, in light of those skilled in the art and the teachings provided herein, are equivalent to any one of the aforementioned examples. It will be understood that alkyl groups can be unsubstituted or substituted as described herein. Alkyl groups can be substituted with any of the substituents in the various embodiments described herein, and include one or more such substituents. The term "alk-" forms a prefix, and the remainder may be a functional group. For example, "alkanol" is an alkyl group substituted with an alcohol.

[0074] The term “substituted” means that the specified group or part has one or more substituents. The term “unsubstituted” means that the specified group does not have substituents. When the term “substituted” is used to describe a structural system, substitution means that it occurs at any valence-allowed position on the system. In some embodiments, “substituted” means that the specified group or part has one, two, or three substituents. For example, two hydrogen atoms on the carbon of an alkyl group may be substituted by an oxo (=O) group to form a carbonyl (C=0). In other embodiments, “substituted” means that the specified group or part has one or two substituents. Still in other embodiments, “substituted” means that the specified group or part has one substituent. Those skilled in the art will recognize that the terms “halogen” or “halo” refer to chlorine, fluorine, bromine, or iodine.

[0075] Conventional methods for astatine capture involve heating the target until the soluble solution turns into a gas, and then dry distillation in which the gas is recovered. The system and method of this embodiment do not require heating. Rather, the use of a solid resin bed impregnated with an organic solvent for extracting astatine from the soluble solution improves the efficiency of astatine extraction in this embodiment and enables the automation of the system of this disclosure. For example, by performing the dissolution of the irradiated target in the same acidic medium used for recovery, such as nitric acid, the extraction and recovery of astatine can be accelerated without requiring additional chemical operations or evaporation of the soluble solution. Conventional chromatography techniques utilize a liquid-liquid extraction process in which two immiscible liquids interact to extract a compound, such as astatine, from a soluble solution. The use of liquids when performing extraction requires the conversion of solvents to extract the desired compound, resulting in multiple liquid-liquid extraction steps within the column. For example, if a nitric acid medium is used to form the soluble solution in conventional chromatography, the nitric acid medium needs to be converted to a hydrochloric acid medium, such as hydrochloric acid, along with the development of a phase interface sensor, before astatine can be extracted. After conversion, the dissolved solution reacts with a hydrochloric acid medium to extract astatine in conventional methods. In some embodiments, the liquid-liquid extraction process may require further chemical decomposition of the nitrate with hydroxyammonium chloride, as described above, and / or heating to complete the extraction process. In comparison, the solid-liquid extraction of this embodiment performs direct extraction of the compound from the nitric acid medium without conversion, resulting in higher conversion efficiency and shorter extraction time. Furthermore, the solid-liquid extraction process using a resin bed of this embodiment occurs without heating. Still further, in some embodiments, the solid-liquid extraction process can be performed in a continuous flow rather than a batch flow, which further improves efficiency and shortens the recovery period of astatine from the dissolved solution. For example, under a continuous flow, the solution passing through column 320 can come into contact with multiple stages of beads along its way, thereby repeatedly exposing the solution to organic solvents impregnated therein, increasing the recovery of the compound of interest.In other words, the solution flows continuously from one stage of the beads to the next, and astatine extraction occurs at each stage.

[0076] In some embodiments, the system may include a quality assurance (QA) device or product vial 326 for measuring the activity of the dissolution solution. For example, a portion of the dissolution solution may flow into the QA device 326 to measure various parameters of the dissolution solution, such as concentration, liquid fraction, activity, radioactive impurities, and dose rate. As shown in the figure, the QA device 326 may be a tube that is in fluid communication with the dissolution box 312. Once sampled, the dissolution solution can then be packed into a column 320 for the recovery of astatine.

[0077] In some embodiments, the frequency of flowing the dissolution solution through the QA device 326 can be gradually reduced over time. For example, sampling can be performed more frequently towards the start of the extraction process to ensure that the activity of the dissolution solution is within an acceptable range. As the process progresses, the fluid flow through the QA device 326 can be reduced in frequency and eventually stopped, as long as the activity level is maintained within a desired range. The activity level can be monitored by the control system 200, which is configured to restart sampling and / or increase the sampling frequency if the activity level of the dissolution solution deviates from an acceptable range.

[0078] The QA device 326 can have a volume in the range of approximately 20 milliliters to approximately 80 milliliters, approximately 30 milliliters to approximately 70 milliliters, approximately 40 milliliters to approximately 60 milliliters, or a value of approximately 50 milliliters. Those skilled in the art will recognize that the volume of the QA device can be selected so that a sufficient sample is tested to ensure that the dissolution solution contains the desired relative concentrations of bismuth and astatine products.

[0079] The system 300 can be remotely controlled. For example, the controller 200 can be programmed to automate the collection of astatine without manual input from the user. In such embodiments, the worker can monitor the chemical processes occurring during irradiation, separation, and / or recovery without manually interacting with the components, thereby reducing the worker's exposure to radiation and / or hazardous chemicals. Furthermore, once the target is placed in the dissolution box 312, the control system 200 can be remotely adjusted by the user. It will be understood that although the system is automated, one or more features or inputs can be performed manually.

[0080] Once astatine recovery is complete, in some embodiments, the column 320 can be connected to one or more fraction collection valves 328 via fluid / air. As shown in the figure, the astatine can flow from the column 320 through the fraction collection valves 328 into one or more dispensing vials 329. Each fraction collection valve 328 can be connected to a dispensing vial 329 to collect a given amount of astatine into the dispensing vial 329. The amount of astatine flowing through the valves 328 can be automated by a control system 200, with each valve 328 receiving an equal amount of astatine, although in some embodiments, each vial 329 may receive independent different amounts. In some embodiments, waste products can be flowed out of the column 320 through the fraction collection valves 328 so that they are disposed of in accordance with health and safety laws.

[0081] Furthermore, those skilled in the art will recognize that the system can be modified. For example, although a single column is shown in Figure 4, in some embodiments, a batch of dissolution solution flowing from the dissolution box 312 can be divided into multiple columns. The multiple columns can be of equal size and / or equal geometric shape, but in some embodiments, the columns can be of different sizes and / or different geometric shapes. Furthermore, the columns within the multiple columns can contain the same resin / bed, but in some embodiments, the columns within the multiple columns can contain different resin / beds. In some embodiments, the multiple columns can be arranged in series so that a single flow of solution passes through two or more columns. In alternative embodiments, the multiple columns can be arranged in parallel so that a batch of dissolution solution is divided before it flows through the columns.

[0082] In some embodiments, the column 320 can retain astatine without collecting it in a dispensing vial 329. For example, in some embodiments, after the astatine is recovered, no astatine flows into the dispensing vial distal to the column 320. Rather, in such embodiments, the fraction collection valve 328 can drain waste, such as a soluble solution containing bismuth and nitric acid, from the recovery process passing through it. The recovered astatine can instead remain in the column 320 along with the organic solvent, and air can be blown through the column to remove any excess liquid through the fraction collection valve 328. Once the column is sufficiently dry, the column impregnated with a concentrated astatine solution in a resin bed can be packaged and transported for use in other systems.

[0083] Figure 5 shows an exemplary method 500 for recovering a target compound using the system of the present disclosure. As discussed above, the method involves irradiating alpha particles with 209While the recovery of astatine from Bi target materials is discussed, the steps of Method 500 of this disclosure can be used to separate and recover various compounds of interest from solutions. Furthermore, it will be recognized that the control system 200 can automate and / or remotely control each of the steps of Method 500 by signals transmitted to one or more components of the system, as described in detail above.

[0084] As shown in the figure, an irradiated target material containing bismuth and astatine can be exposed to a nitric acid solution to form a dissolution solution in which bismuth and astatine dissolve in nitric acid (S502). In some embodiments, exposure of the target material can occur in a dissolution box, where the target material is placed and the nitric acid solution is introduced into it. In some embodiments, the control system 200 can instruct one or more of the pumps 302 and / or valves 304 to flow the nitric acid solution into the dissolution box 312. In some embodiments, the control system 200 can remotely signal a solution selection valve 322 to flow the nitric acid solution through it, and can signal pumps 302 to flow the nitric acid solution into the dissolution box 312. The solution can flow onto the target material substantially continuously and / or in batches to facilitate the dissolution of the target material.

[0085] Once the target material is sufficiently dissolved in nitric acid to form a solubility solution, the solubility solution can be passed to the column (S504). As shown in Figure 4, the solubility solution can flow to the column 320 through a bidirectional selective valve 326b, but in some embodiments, the solubility solution can flow directly from the dissolution box 312 to the column 320. In the column 320, the solubility solution can come into contact with a resin bed impregnated with an organic solvent to extract astatine from the solubility solution.

[0086] Optionally, in some embodiments, a portion of the dissolution can flow toward the QA device 326 to measure the activity of the dissolution (S505). In such embodiments, the QA device 326 can sample the dissolution to measure the activity level of dissolved astatine in the dissolution. Once sampled, the dissolution can be backflowed into the column 320 through bidirectional selective valves 326a, 326b for the recovery of astatine from the dissolution.

[0087] After contact with a solution containing a mixture containing At, the resin can be washed (S506). The washing step may include washing the resin with an aqueous solution. In some embodiments, the aqueous solution contains an acid. In some embodiments, the aqueous washing solution contains an acid at a lower concentration than the acid concentration used to dissolve the At / Bi composition. For example, if the acid concentration in the aqueous solution that dissolves the At / Bi composition is about 6 M, the acid concentration in the washing solution may be less than about 6 M, e.g., about 2 M. In some embodiments, the acid concentration is less than about 10 M, less than about 8 M, less than about 6 M, or less than about 4 M. In some embodiments, the acid concentration is up to about 8 M, up to about 6 M, or up to about 4 M. In exemplary embodiments, the acid used in the washing step is the same acid as the acid in the previous step, e.g., nitric acid.

[0088] Alternatively, the acid could be a different acid. For example, the acid could be HClO4, HCl, HBr, or H2SO4. Exemplarily, changing the acid used in the washing step could change the counterion of the isolated At recovered by the elution step.

[0089] In some embodiments, the step of washing the resin is measured as a ratio of floor volumes. For example, the resin may be washed with a solution having a volume of at least about 2 floor volumes, at least about 3 floor volumes, at least about 4 floor volumes, at least about 5 floor volumes, or at least about 6 floor volumes. In exemplary embodiments, the resin may be washed sequentially with an aqueous solution containing an acid and an aqueous solution without an acid. The washing step may be modified by means known in the art to include additional or fewer washing steps of aqueous solutions.

[0090] In embodiments where the aqueous washing solution contains an acid, a separate washing step can be used to remove the acid from the column (S508). For example, an aqueous solution of water can be used to wash the column to remove the acid from it. Once the acid has been washed away, the column is used for extraction. 211 This may include resin flooring to which At has adhered.

[0091] In some embodiments, astatine can be eluted or detached from the resin (S510). Exemplarily, the elution step involves dissociating At from the resin to allow At to be collected. The elution step may be performed by contacting the resin with an organic solvent. In some embodiments, the organic solvent is the same solvent used to impregnate the resin. In some embodiments, the organic solvent in the elution step is miscible with the solvent used to impregnate the resin. In some embodiments, the organic solvent is optionally substituted with C1-C 18 It contains alkyl, where C1~C 18 Each hydrogen atom of the alkyl group is optionally substituted with a functional group. C1~C 18Optional substitutions in alkyl groups are commonly known in the art and include halogens, hydroxyls, amines, thiols, oxo, ketones, carboxylates, aldehydes, amides, carbonates, carbamates, and combinations thereof. In some embodiments, the organic solvent comprises aldehydes, ketones, esters, amides, carbonates, carboxylates, or carbamates. In some embodiments, the organic solvent comprises C1-C12 C 18 , C1~C 12 , or containing C1-C6 alkyl. In some embodiments, the organic solvent is of the formula C1-C6 alkyl-C(O)-C1-C6 alkyl. In some embodiments, the organic solvent is of the formula C1-C6 alkyl-C(O)-C1-C6 alkyl, where each hydrogen atom in the C1-C6 alkyl is optionally substituted. In some embodiments, the organic solvent is octanone. In some embodiments, the organic solvent is 3-octanone. In some embodiments, the organic solvent is C1-C 18 It is an alkanol. In some embodiments, the solvent includes ethanol.

[0092] Exemplary, the processes described herein recover at least about 80%, at least about 85%, at least about 90%, or at least about 95% of At from a composition containing At. In some embodiments, the processes recover about 80% to about 99%, about 85% to about 99%, or about 90% to about 99% of At from a composition containing At.

[0093] Exemplary, the eluted At has a higher purity of At than the composition containing At prior to the chromatography step. In some embodiments, the eluted At has a purity of at least about 90%, at least about 95%, or at least about 99%.

[0094] The processes described herein may be carried out in less than about 1 hour, less than about 30 minutes, less than about 15 minutes, or less than about 10 minutes. Exemplarily, the process is carried out in a shorter time compared to a comparative process that requires the step of dissolving the At / Bi composition in a nitric acid solution, evaporating the nitric acid solution, and reconstituting the residue in hydrochloric acid before chromatography, or compared to a comparative process that requires the destruction of nitrates before chromatography. The processes described herein isolate At in a specific proportion of its half-life. In some embodiments, the process is 211 The process is executed at approximately 20%, 15%, 10%, or 5% of the half-life of At, such as At.

[0095] The purified collected by this system 211 It will be understood that at isotopes can have a variety of applications. Astatine (At) may be useful as a radiolabel for therapeutic drugs. For example, the astatine of this embodiment can be included in a product suitable for therapeutic medical applications such as the treatment of cancer in human patients. In some embodiments, the process may further include labeling the therapeutic drug with eluted At. This may be done directly with a column fraction of eluted At, or it may involve concentrating a fraction containing At and suspending or dissolving At in a solution used for the labeling step.

[0096] Alternatively, in some embodiments, astatine can be stored and transported within the column rather than eluted from the column. In embodiments in which the column is transported, it will be understood that the astatine remains in the column and, as discussed with respect to Figure 4, the fraction collection valve 328 can be removed from the system 300 and / or used to filter waste from the column 320. To prepare the column for transport, the column 320 can be dried to remove any excess fluid from the column (S512). In some embodiments, air can be blown through the column to remove excess fluid. Once the column is sufficiently dry, the column, having the astatine stored therein on the resin bed, can be packaged and transported. Those skilled in the art will recognize that transporting a dry column containing astatine involves considerably fewer constraints than those imposed on transporting a solution containing the compound, e.g., a dissolution solution.

[0097] Astatine in a dry column can have various applications. For example, in some embodiments, the dry column can be delivered to a facility for column elution in order to recover the astatine stored in the column. In some embodiments, the dry column can be used to label biomolecules. In some embodiments, astatine can be used in the treatment of cancer by targeting cancer cells. For example, the radioactive decay of astatine can be utilized by adding astatine to biologically relevant molecules such as the anti-tenacin monoclonal antibody 81C6(ch81C6),F(ab')2, a fragment of the mouse IgG1 monoclonal antibody MX35, and / or an anti-CD45 monoclonal antibody in the column. The astatine and molecules can then be detached from the column and injected into the patient's body as a cancer treatment drug.

[0098] It will be understood that the system of this embodiment can be made compact to facilitate the transport of system components between various locations. For example, the system described above, along with all corresponding piping, can be housed in a cube of approximately 1' × 1' × 1'. In some embodiments, the system, including the dissolution box and column, can be made compact enough to be housed and operated within a fume hood, glove box, or biosafety cabinet. Furthermore, as discussed above, the dissolution and recovery of astatine by the method of this disclosure can be performed without heating any part of the system. The method of this disclosure does not utilize additional chemical operations such as conversion of the ionic medium before separation or evaporation of the dissolution solution to separate, extract, and recover astatine from the target material.

[0099] Figures 6A to 6E illustrate in more detail the flow sequence through the automated compound recovery system 300 for the steps of method 500. For example, as shown in Figure 6A, the solution selection valve 322 can be in fluid communication with multiple vials 324. The vials can contain several fluids, such as acid, water, and / or solvent, stored therein, as shown in the figure. As discussed above, the solution selection valve 322 can include multiple inlets 306, each inlet connected to one of the vials 324, and a single outlet 308 is configured to allow the contents of the vials 324 to flow throughout the system 300. The fluid flowing out through the outlet 308 can flow to a bidirectional selection valve 326a and a pump 302. From the pump 302, the fluid can flow to a second bidirectional selection valve 326b and a dissolution box 312 to dissolve the target material in the dissolution solution. From the dissolution box 312, the dissolution solution can, in some embodiments, flow through a third bidirectional select valve 326c to a product vial or QA device 326 for sampling. The dissolution box 312 can also be fluidly connected to a fourth bidirectional select valve 326d to pass gaseous material, such as vapor, to the scrubber vat 330 and charcoal vat 332 in order to remove astatine vapor. In some embodiments, it will be understood that the fourth bidirectional select valve is configured to allow gas to flow through it instead of liquid. The dissolution box 312 can also be fluidly connected to the column 320 and fraction collection valve 328, as will be discussed in more detail below.

[0100] Figure 6B shows the flow sequence for forming the dissolution solution (S502) in system 300. As shown, the acid from vial 324, for example nitric acid, can enter one of the multiple inlets 306 of solution selection valve 322 (A) and exit through outlet 308 to flow to bidirectional selection valve 326a (B). From bidirectional selection valve 326a, the acid flows to pump 302 (C), then through bidirectional selection valve 326b (D), and is pumped to dissolution box 312 to form the dissolution solution (E). Once sufficiently dissolved, the vapor generated by the formation of the dissolution solution can flow out of dissolution box 312 to a fourth bidirectional selection valve 326d (F) and into scrubber bat 330 and charcoal bat 332. Bats 330 and 332 can perform a safe washing of astatine to ensure that the vapor does not escape from the solution. For example, gas, such as vapor, flowing out from the fourth bidirectional select valve 326d can enter a scrubber vat 330 containing a sodium hydroxide solution. The sodium hydroxide in the scrubber vat 330 can interact with the gas produced by the dissolving solution to neutralize the astatine vapor generated from the gas produced by the dissolving solution. The unreacted astatine vapor can then be passed to a charcoal vat 332, which acts as a filter for any gas from the dissolving solution to prevent leakage of unreacted astatine vapor from the gas into the laboratory and / or the surrounding environment.

[0101] Figure 6C shows the flow for the transfer of the dissolution solution from the dissolution box 312 to the QA device 326 (S505). As shown in the figure, the dissolution solution passes through the third bidirectional select valve 326c so that it exits the dissolution box 312 in flow (G) and is then passed to the QA device 326 for sampling activity (H). Once sampled, the QA device 326 can be fluidly communicated with the third bidirectional select valve 326c and bidirectional select valve 326a via flow (I) to remove air from the QA device 326 to the pump 302. During operation, the pump 302 can draw vapor from the QA device 326 by negative pressure, and the pump draws air, not liquid, from the QA device via flow (I). Drawing vapor from the QA device 326 can act as a safety measure to ensure there are no leaks in the system. Pump 302 can create a corresponding pressure within the dissolution box 312 via a flow (J) that passes through the bidirectional selective valve 326b and enters the dissolution box 312, in order to remove air and potentially harmful astatine gas from the dissolution box 312. As described above, the use of the QA device 326 may be optional, but in some embodiments, sampling via the QA device 326 may become less frequent over time.

[0102] Figure 6D shows the packing of column 320 (S504) in more detail. As shown, the dissolution can exit the dissolution box (K), pass through the third bidirectional select valve 326c, and enter the product vial 326 for sampling. Once the activity has been measured, the dissolution can pass through the third bidirectional select valve 326c and bidirectional select valve 326a so that it exits the QA device 326 via flow (L) and flows to the pump 302. From the pump 302, the dissolution can be pumped (M) to the fraction collection valve 328 via bidirectional select valve 326b. As shown, the fraction collection valve 328 may include a single inlet 336 and multiple outlets 338, each connected to the corresponding column 320. The dissolution can flow (M) into the inlet 336 toward the outlet 338 corresponding to the column 320 for collection (N). In some embodiments, the column 320 and the fraction collection valve 328 can be juxtaposed. That is, in some embodiments, the flow of the dissolved solution (M) from the pump 302 can enter the column 320 before passing through the fraction collection valve 328. In such embodiments, the flow of fluid (N) exiting the column 320 can pass through the outlet 338 of the fraction collection valve 328 so as to be collected in the dispensing vial 329, as discussed in Figure 4.

[0103] Figure 6E shows in more detail the washing of column 320 to remove unextracted species from the column (S508). As shown in the figure, water can flow out (O) through the solution selection valve 322, through one of the inlets 306, and out through the outlet 308. Once the water has left the solution selection valve 322, it can pass through the bidirectional selection valve 326a and enter the pump 302 (P). From the pump 302, the water can be pumped (Q) through the bidirectional selection valve 326b to the fraction collection valve 328. From the fraction collection valve, the water can flow into column 320 to flush the column from unextracted species. Those skilled in the art will recognize that the sequence for washing the column can be analogous to the sequence for drying the column (S512). For example, one of the inlets 306 of the solution selection valve 322 can be connected to the atmosphere to force air through the lines of the system 300 in order to dry column 320.

[0104] As described above, in some embodiments, systems 100, 300 can be coupled and / or otherwise associated with a controller 200 configured to automate and / or remotely control the steps of method 500. For example, the controller 200 can control the fluid flow and / or pressure of the pump 302 and the orientation of the valve 304 throughout the extraction process, and such a configuration is understood in light of the present disclosure. Figure 7 is a block diagram of one exemplary embodiment of a computer system 1500 that can build, run, train, etc., the controller or control system 200 of the present disclosure. For example, any module or system is an example of system 1500 described herein. System 1500 may include a processor 1510, memory 1520, storage device 1530, and input / output device 1540. Each of the components 1510, 1520, 1530, and 1540 can be interconnected using, for example, a system bus 1550. The processor 1510 can process instructions to be executed within the system 1500. The processor 1510 may be a single-threaded processor, a multi-threaded processor, or a similar device. The processor 1510 may process instructions stored in memory 1520 or on storage device 1530. The processor 1510 may perform operations such as starting and stopping fluid flow, controlling fluid paths or pressure, and system configuration, which may be automatic, responsive to various parameters, and / or manually controlled by a user, including responding to signals, parameters, etc., and / or based on observations / preferences, etc., among other features described in connection with this disclosure, as a non-limiting example. The controller 1500 may optimize its operation in response to various conditions of the solution entering the system, various power prices, and other factors that may relate to the energy efficiency, reliability, maintenance, or leveled cost of the solution used to dissolve the irradiated target.In some cases, the controller 1500 can optimize its operation in response to the desired dissolution concentration, type of acidic medium, and / or operating pressure. The controller 1500 can further incorporate machine learning techniques, artificial intelligence, and / or digital twins, which can help improve performance.

[0105] Memory 1520 can store information within system 1500. In some implementations, memory 1520 can be a computer-readable medium. Memory 1520 can be, for example, a volatile memory unit or a non-volatile memory unit. In some implementations, memory 1520 can store information related to fluid paths and system components, such as when and / or under what conditions the permeation generation configuration and flushing configuration should be implemented, as well as different conditions for various loops permitted by the system, among other information, such as flash time, permeation salinity, and / or operating pressure, which can enable machine learning optimization of the system.

[0106] The storage device 1530 can provide high-capacity storage for the system 1500. In some implementations, the storage device 1530 can be a non-temporary computer-readable medium. The storage device 1530 can include, for example, a hard disk drive, an optical disk drive, a solid-state drive, a flash drive, a magnetic tape, and / or any other high-capacity storage device. Alternatively, the storage device 1530 may be a cloud storage device, for example, a logical storage device that includes multiple physical storage devices distributed over a network and accessed using the network. In some implementations, information stored on memory 1520 can also be stored on the storage device 1530, or can be stored on the storage device 1530 instead.

[0107] The input / output device 1540 can provide input / output operation for system 1500. In some implementations, the input / output device 1540 may include one or more of the following: network interface devices (e.g., Ethernet card or InfiniBand interconnect), serial communication devices (e.g., RS-232 10-port, or 9-pin or 25-pin RS-232), and / or wireless interface devices (e.g., short-range wireless communication devices, 802.7 cards, 3G wireless modems, 4G wireless modems, 5G wireless modems). In some implementations, the input / output device 1540 may include a driver device configured to receive input data and send output data to other input / output devices, such as a keyboard, printer, and / or display device. In some implementations, mobile computing devices, mobile communication devices, and other devices may be used.

[0108] In some implementations, system 1500 can be a microcontroller. A microcontroller is a device that contains multiple elements of a computer system within a single electronic package. For example, a single electronic package may include a processor 1510, memory 1520, storage device 1530, and / or input / output device 1540.

[0109] While exemplary processing systems have been described above, the implementations of the subject matter and functional operation described above can be implemented in other types of digital electronic circuits, or in computer software, firmware, or hardware, or in one or more combinations thereof, including the structures disclosed herein and their structural equivalents. The implementations of the subject matter described herein can be implemented as one or more computer program products, i.e., tangible program carriers, for example, one or more modules of computer program instructions encoded on a computer-readable medium, for execution by or control of the operation of a fluid filtration system. The computer-readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of a material that provides a machine-readable propagating signal, or one or more combinations thereof.

[0110] Various embodiments of this disclosure can be implemented, at least in part, in any conventional computer programming language. For example, some embodiments can be implemented in procedural programming languages ​​(e.g., "C" or ForTran95), object-oriented programming languages ​​(e.g., "C++"), and / or other programming languages ​​(e.g., Java, Javascript, LabVIEW, PHP, Python, and / or SQL). Other embodiments can be implemented as pre-configured standalone hardware elements and / or pre-programmed hardware elements (e.g., application-specific integrated circuits, FPGAs, and digital signal processors), or other related components.

[0111] The term “computer system” may, in non-limiting examples, encompass all devices, machines, and apparatus for processing data, including programmable processors, computers, or multiple processors or computers. In addition to hardware, a processing system may include code that creates the execution environment for the computer program in question, such as processor firmware, protocol stacks, database management systems, operating systems, or one or more combinations thereof.

[0112] Computer programs (also known as programs, software, software applications, scripts, executable logic, or code) can be written in any form of programming language, including compiled or interpreted languages, or declarative or procedural languages, and can be deployed in any form, including as standalone programs or as modules, components, subroutines, or other units suitable for use in a computing environment. Computer programs do not necessarily correspond to files in a file system. A program can be stored in part of a file that holds other programs or data (e.g., one or more scripts stored within a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., a file storing one or more modules, subprograms, or parts of code). A computer program can run on one computer, or be located in one place, or be deployed to run on multiple computers distributed across multiple locations and interconnected by a communication network.

[0113] Such implementations may include a set of computer instructions fixed on any tangible, non-temporary medium, such as a computer-readable medium. The set of computer instructions can embody all or some of the functions already described herein with respect to the system. Computer-readable mediums suitable for storing computer program instructions and data include, for example, all forms of non-volatile or volatile memory, media, and memory devices, including semiconductor memory devices such as EPROMs, EEPROMs, and flash memory devices; magnetic disks such as internal hard disks or removable disks; or magnetic tapes, magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and memory may be complemented by or incorporated into dedicated logic circuits. The components of the system can be interconnected by digital data communication of any form or medium, such as a communication network. Examples of communication networks include local area networks ("LANs") and wide area networks ("WANs"), such as the Internet.

[0114] Those skilled in the art should understand that such computer instructions can be written in several programming languages ​​for use in many computer architectures or operating systems. Furthermore, such instructions can be stored in any memory device, such as semiconductor, magnetic, optical, or other memory devices, and can be transmitted using any communication technology, such as optical, infrared, microwave, or other transmission techniques.

[0115] Among other methods, such computer program products may be distributed as removable media (e.g., shrink-wrapped software) with accompanying printed or electronic documentation, pre-loaded onto a computer system (e.g., on system ROM or a fixed disk), or distributed from a server or electronic bulletin board via a network (e.g., the Internet or the World Wide Web). In fact, some embodiments may be implemented in a Software as a Service ("SAAS") or cloud computing model. Of course, some embodiments of this disclosure may be implemented as a combination of both software (e.g., computer program products) and hardware. Still other embodiments of this disclosure may be implemented entirely as hardware or entirely as software. [Explanation of Symbols]

[0116] 100 Compound separation and recovery systems, systems, compound recovery systems 102 pump 104 Valve or selector, valve, selector 104' valve, 6-port valve 104" 4-port valve 106 Entrance, Port 106' entrance Exit 108, Port 108' Exit 110 Selector Stator 110' Rotary Valve 110" Rotary Valve 111 Plate 112 Dissolving box, dissolving box or container 114 Peristaltic pump 116 USB Cameras 130 Scrubber 132 Charcoal Bat 200 Control systems, controllers, controllers or control systems 202 Microcontrollers 204 Switch 206 Power supply 300 Automated Compound Recovery System, System 302 Pump 304 Valve / Selector 306 Entrance 308 Exit 312 Dissolution Box 320 columns 322 Solution Selection Valve 324 vials 326 Quality Assurance (QA) devices or product vials, QA devices 326a Bidirectional Select Valve 326b Bidirectional selection valve, second bidirectional selection valve 326c Third bidirectional select valve 326d Fourth bidirectional select valve 328 Fraction Collection Valve, Valve 329 Dispensing vials, vials 330 Scrubba Bat, Bat 332 Charcoal bat, bat 336 Entrance 338 Exit 1500 Computer systems, systems 1510 Processor 1520 memory 1530 Storage Devices 1540 Input / Output Devices 1550 System Bus

Claims

1. A first column configured to extract astatine from a solution in which astatine is dissolved, wherein the first column has an extraction medium having an associated solvent, A pump that is in fluid communication with the first column, and is configured to deliver the dissolution solution to the first column, A control system that communicates with the pump, wherein the control system is configured to regulate the flow of the dissolved solution through the pump via signals, and the signals are automated or remotely controlled. Equipped with, A compound recovery system that extracts astatine without heating.

2. A first column configured to extract astatine from a solution in which astatine is dissolved, wherein the first column has an extraction medium having an associated solvent, A pump that is in fluid communication with the first column, and is configured to deliver the dissolution solution to the first column, A control system that communicates with the pump, wherein the control system is configured to regulate the flow of the dissolved solution through the pump via signals, and the signals are automated or remotely controlled. Equipped with, A compound recovery system further comprising a second column configured to receive a portion of the aforementioned dissolution solution through it.

3. The system according to claim 1 or 2, further comprising a dissolution vessel having fluid communication with the pump and the first column, the dissolution vessel being configured to form the dissolution solution by mixing the irradiated target material and a medium therein.

4. The system according to claim 3, further comprising one or more selectors having fluid communication with the pump, configured to deliver the solvent or the dissolving solution through them.

5. The system according to claim 4, wherein the orientation of one or more selectors is determined by the signal from the control system.

6. The system according to claim 4, wherein the control system is configured to communicate substantially simultaneously with the pump and the one or more selectors.

7. The system according to claim 4, wherein the one or more selectors include a single inlet and a plurality of outlets.

8. The system according to claim 4, wherein the one or more selectors include a single outlet and a plurality of inlets.

9. The system according to claim 5, wherein one or more selectors are in fluid communication with one or more vials containing a solution, and the pump is configured to deliver the medium to the dissolution container through the one or more selectors.

10. The system according to claim 9, wherein the medium comprises one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

11. The system according to claim 1 or 2, wherein the extraction medium is a resin bed.

12. The system according to claim 1 or 2, wherein the solvent may include one or more of octanone, 3-octanone, or 1-octanol.

13. The system according to claim 1 or 2, further comprising a quality assurance device in fluid communication with the pump, configured to sample a portion of the dissolved solution.

14. The system according to claim 2, wherein the second column is arranged in series with the first column.

15. The system according to claim 2, wherein the second column is arranged in parallel with the first column.

16. A method for recovering compounds, In order to form a dissolution solution having a target material and one or more compounds therein, the step of exposing the target material having one or more compounds therein to the acidic medium in order to dissolve the target material in the acidic medium, A step of passing the dissolution solution through a chromatography column in order to extract one or more of the compounds from the dissolution solution, wherein the one or more compounds are extracted onto a resin bed placed in the chromatography column. The steps include: washing the resin bed to remove the unextracted soluble solution from the chromatography column; To remove the acidic medium from the chromatography column, the chromatograph column is washed with an aqueous solution. The steps include drying the chromatography column to remove excess fluid from it, and sealing the chromatography column. Includes, Each of the steps of exposing the target material, passing the dissolution solution through the chromatography column, and cleaning the resin floor is generated in response to an automated signal or a signal located remotely. method.

17. A method for recovering compounds, In order to form a dissolution solution having a target material and one or more compounds therein, the step of exposing the target material having one or more compounds therein to the acidic medium in order to dissolve the target material in the acidic medium, A step of passing the dissolution solution through a chromatography column in order to extract one or more of the compounds from the dissolution solution, wherein the one or more compounds are extracted onto a resin bed placed in the chromatography column. The steps include: washing the resin bed to remove the unextracted soluble solution from the chromatography column; The steps include dividing the aforementioned dissolved solution into multiple streams, each stream entering a separate chromatography column, Includes, Each of the steps of exposing the target material, passing the dissolution solution through the chromatography column, and cleaning the resin floor is generated in response to an automated signal or a signal located remotely. method.

18. A method for recovering compounds, In order to form a dissolution solution having a target material and one or more compounds therein, the step of exposing the target material having one or more compounds therein to the acidic medium in order to dissolve the target material in the acidic medium, A step of passing the dissolution solution through a chromatography column in order to extract one or more of the compounds from the dissolution solution, wherein the one or more compounds are extracted onto a resin bed placed in the chromatography column. The steps include: washing the resin bed to remove the unextracted soluble solution from the chromatography column; Includes, Extraction of the one or more compounds occurs without heating. Each of the steps of exposing the target material, passing the dissolution solution through the chromatography column, and cleaning the resin floor is generated in response to an automated signal or a signal located remotely. method.

19. A method for recovering compounds, In order to form a dissolution solution having a target material and one or more compounds therein, the step of exposing the target material having one or more compounds therein to the acidic medium in order to dissolve the target material in the acidic medium, A step of passing the dissolution solution through a chromatography column in order to extract one or more of the compounds from the dissolution solution, wherein the one or more compounds are extracted onto a resin bed placed in the chromatography column. The steps include: washing the resin bed to remove the unextracted soluble solution from the chromatography column; Before transferring a portion of the dissolution solution to the chromatography column, a step of sampling a portion of the dissolution solution in order to determine its activity level, Includes, Each of the steps of exposing the target material, passing the dissolution solution through the chromatography column, and cleaning the resin floor is generated in response to an automated signal or a signal located remotely. method.

20. The method according to any one of claims 16 to 19, wherein the resin floor is cleaned with the acidic medium.

21. The method according to any one of claims 16 to 19, wherein the acidic medium comprises one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

22. The method according to any one of claims 16 to 19, wherein the dissolving solution is formed over a period of approximately 5 minutes to approximately 30 minutes.

23. The method according to claim 16, further comprising the step of eluting the one or more compounds from the resin bed in order to collect the one or more compounds.

24. The method according to claim 16, wherein the step of drying the chromatography column further includes the step of blowing air through the chromatography column until the excess fluid is substantially removed.

25. The method according to claim 24, wherein after blowing air through the chromatographic column, the chromatographic column retains the compound.

26. The method according to any one of claims 16 to 19, wherein the dissolution solution is passed through the chromatographic column by the pump, which is in fluid communication with one or more selectors positioned between the pump and the chromatographic column.

27. The method according to claim 26, further comprising the step of adjusting the orientation of one or more selectors in response to a signal.

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