Systems and methods 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 DOE Office of Science DE-SC0020958. The Government has certain rights in this invention.

[0002] The present disclosure relates to systems and methods for the separation and recovery of compounds from various media, and more particularly to an automated system and method for the separation and extraction of astatine from a dissolution solution containing bismuth and astatine dissolved in an acidic medium. [Background technology]

[0003] Astatine-211( 211 At) is one of the most promising alpha-emitting radionuclides for targeted alpha therapy. Targeted alpha therapy (TAT) agents have attracted great interest in the use of alpha-emitting radionuclides for the treatment of various diseases, e.g., cancer. One such isotope that has attracted great attention has a reasonably short half-life of about 7.2 hours and quantitative alpha emission from a simple decay scheme, with decay properties that are suitable for clinical practice. 211 At. 209 Bi(α,2n) 211 of At available through nuclear reactions 211 As a standard for producing At, natural bismuth ( 209 Bi) target bombardment is employed. There are only about 30 cyclotrons capable of producing usable quantities in the world, only seven of which are in the United States, only one of which currently serves 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, ovarian cancer, and in current studies to treat advanced hematopoietic malignancies.

[0004] The chemistry of astatine is one of the few areas in the periodic table that has remained relatively unexplored. This may be due to the fact that astatine's abundance on Earth is estimated at just 0.07 g, making it the least abundant of the naturally occurring elements, as it has no stable isotopes. Of the isotopes of astatine, the one with the longest half-life is: 211 Slightly longer-lived than At 210 It belongs to the At group and has a half-life of only about 8.1 hours.

[0005] Currently, there are two methods for the recovery of astatine: wet chemical processing and dry distillation. 211 These conventional techniques for recovering At have several drawbacks. First, the At that time, the At that time is recovered and purified. 211 The amount of At is about 1 to 10 ng, and the amount is macroscopic. 209 In analytical-scale separations, where Bi (1-10 g) constitutes the majority of the matrix, solvent extraction is not suitable as an efficient means for separation, since it is controlled to a single separation step per contact. Furthermore, analytical-scale separations must be performed in continuous-flow mode, which is the most efficient method for recovery and separation, but requires sophisticated equipment, thereby significantly increasing the cost of the process so as to hinder scalability. Secondly, these techniques imply conversion of the system from a nitrate to a chloride medium, which adds a slow, time-consuming step, either evaporation to remove the nitric acid, or chemical destruction of the nitrate ion by hydroxylammonium chloride. Furthermore, these conversions lead to loss 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 can lead to problems such as: 211 Prevents the separation of At and prevents recovery 211 It impairs the quality of the At. 211 The lability of the At isotope makes storage and export of the recovered compounds difficult. Summary of the Invention [Problem to be solved by the invention]

[0006] Therefore, there is a need for improved systems and methods for optimizing the separation and purification for the recovery of astatine. [Means for solving the problem]

[0007] According to one aspect of the present disclosure, a compound recovery system includes:

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

[0009] In another embodiment, the method for compound recovery comprises:

[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 lysis solution having the target material and one or more compounds therein; passing the lysis solution through a chromatography column to extract the one or more compounds from the lysis solution, wherein the one or more compounds are extracted into a resin bed disposed within the chromatography column; and washing the resin bed to remove unextracted solution from the column; each of the steps of exposing the target material, passing the lysis solution through the chromatography column, and washing the resin bed occurs in response to an automated or remotely located signal.

[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 conjunction with any other embodiment described herein to the extent that the embodiments are not mutually exclusive.

[0012] 1. A first column configured to extract astatine from a dissolution solution in which the astatine is dissolved, the first column having an extraction medium having an associated solvent; a pump in fluid communication with the column, the pump configured to deliver a lysis solution to the column; a control system in communication with the pump, the control system configured to regulate a flow of the dissolution solution through the pump via a signal, the signal being automated or remotely deployed; 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 configured to form a dissolution solution by mixing the 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 selectors configured to deliver a solvent or dissolution solution therethrough.

[0015] 4. A system according to clause 3 in which the orientation of one or more selectors is determined by a signal from a control system.

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

[0017] 6. The system of any one of clauses 3 to 5, wherein the one or more selectors include a single inlet and multiple outlets.

[0018] 7. The system of any one of clauses 3 to 6, wherein one or more selectors include a single outlet and multiple inlets.

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

[0020] 9. The system of clause 8, wherein the medium comprises one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

[0021] 10. The system of any one of clauses 1 to 9, wherein the extraction medium is a resin bed.

[0022] 11. The system of any one of clauses 1 to 10, wherein the solvent may comprise one or more of octanone, 3-octanone, or 1-octanol.

[0023] 12. The system of any one of clauses 1 to 11, wherein the extraction of astatine occurs without heating.

[0024] 13. The system of any one of clauses 1 to 12, further comprising a quality assurance device in fluid communication with the pump, the quality assurance device being configured to sample a portion of the lysis solution.

[0025] 14. The system of any one of clauses 1 to 13, further comprising a second column configured to receive a portion of the lysis solution therethrough.

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

[0027] 16. A system according to clause 14 or 15, in which a second column is arranged in parallel with the first column.

[0028] 17. A method for compound recovery, comprising: exposing the 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 lysis solution through a chromatography column to extract one or more compounds from the lysis solution, the one or more compounds being extracted into a resin bed disposed within the chromatography column; washing the resin bed to remove unextracted lysis solution from the column; Including, each of the steps of exposing the target material, passing a lysis solution through the chromatography column, and washing the resin bed occurs in response to an automated or remotely located signal; method.

[0029] 18. The method of clause 17, wherein the resin bed is washed with an acidic medium.

[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. The method of any one of clauses 17 to 19, further comprising the step of washing the chromatography column with an aqueous solution to remove the acidic medium from the chromatography column.

[0032] 21. The method of any one of clauses 17 to 20, wherein the lysis solution is formed over a period ranging from approximately 5 minutes to approximately 30 minutes.

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

[0034] 23. The method of any one 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 drying the column further comprises blowing air through the column until excess fluid is substantially removed.

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

[0037] 26. The method of any one of clauses 17 to 25, wherein the lysis solution is passed through the chromatography column by a pump in fluid communication with one or more selectors disposed between the pump and the column.

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

[0039] 28. The method of any one of clauses 17 to 27, further comprising the step of splitting the lysis solution into multiple streams, each stream entering a separate chromatography column.

[0040] 29. The process of any one of clauses 17 to 28, wherein the extraction of the compound or compounds occurs without heating.

[0041] 30. The method of any one of clauses 17 to 29, further comprising the step of sampling a portion of the lysis solution to determine its activity level prior to passing the portion of the lysis solution to the column.

[0042] Additional features of the present disclosure will become apparent to those skilled in the art upon consideration of the exemplary embodiments illustrating the currently recognized best modes of carrying out the present disclosure.

[0043] The present disclosure will become more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which: [Brief description of the drawings]

[0044] [Figure 1] FIG. 1 is a perspective view of an exemplary embodiment of a compound separation and recovery system according to the present embodiments having a pump in fluid communication with a series of valves that flow a solution to lyse irradiated target material and load the lysis solution into a column. [Figure 1B] 2 is an alternative perspective view of the system of FIG. 1 with components in alternative orientations showing relevant system components. [Figure 2A] FIG. 2 is a perspective view of one embodiment of a valve selector for use in the system of FIG. 1 having an inlet and multiple outlets formed thereon. [Figure 2B] FIG. 2 is a perspective view of another embodiment of a valve for use in the system of FIG. 1 having a rotary valve formed thereon. [Figure 2C] 2 is a perspective view of another embodiment of a valve for use in the system of FIG. 1 having another embodiment of a rotary valve formed thereon. [Diagram 3] FIG. 2 is a schematic diagram of one exemplary embodiment of a control system capable of controlling one or more pumps of the system of FIG. 1. [Figure 4] FIG. 2 is a schematic diagram of one exemplary embodiment of the automated compound recovery system of the present embodiments. [Diagram 5] FIG. 1 is a schematic diagram of one exemplary embodiment of a method for separating and recovering compounds from a target material. [Figure 6A] 5 is a schematic diagram of an exemplary embodiment of a flow sequence through components of the automated compound recovery system of FIG. 4. [Figure 6B] FIG. 5 is a schematic diagram of the automated compound recovery system of FIG. 4 in target dissolution mode. [Figure 6C] FIG. 5 is a schematic diagram of the automated compound recovery system of FIG. 4 for transfer of lysis solutions to a QA device. [Figure 6D] FIG. 5 is a schematic diagram of the automated compound recovery system of FIG. 4 when the column is packed. [Figure 6E] FIG. 5 is a schematic diagram of the automated compound recovery system of FIG. 4 for flushing the column with water. [Figure 7] FIG. 1 is a schematic diagram of one exemplary embodiment of a computer system upon which the control system of the present disclosure may be implemented. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] Astatine (At) can be produced by bombarding bismuth-209 with alpha particles. For example, in some embodiments, the target bismuth material has 211 The astatine-211 is then bombarded with alpha particles to produce At. One of skill in the art will recognize that this bombardment typically occurs in a particle accelerator, such as a cyclotron. For example, in some embodiments, astatine-211 is produced by irradiating a natural Bi metal target (isotopically pure Bi purchased from Goodfellow) for 9-10 hours. 209 Via 28.8 MeV alpha particle collisions (cross section of approximately 0.9 barns) of Bi, metal purity ≥ 99.997% 209 Bi(α,2n) 211 At nuclear reaction in two separate runs. It will be understood that the methods described above are purely exemplary and that one or more variables may be varied in the process of producing astatine-211. Additionally, to the extent astatine is described herein, the astatine referred to is 209 At or 211 It will be understood that At may be any cationic species thereof. For example, At described in the processes herein may be any cationic species AtO + However, it is still referred to as At. Illustratively, the process may include producing At. The formed bombarded target may include a mixture of At, unreacted Bi, and by-products.

[0046] The At produced must then be isolated from unreacted Bi. Described herein is a process for isolating At from a composition, such as a composition formed from bombardment with Bi, using extraction chromatography. In an exemplary embodiment, the process described herein dissolves a composition containing At and then isolates 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 discussed in more detail below.

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

[0048] The aqueous solution can include an acid, such as an organic acid or a mineral acid. The mineral acid can be nitric acid. The solution dissolves or substantially dissolves the composition to form a solution including At and Bi. In some embodiments, the solution includes At, Bi, and an acid. In some embodiments, the solution includes At, Bi, and nitric acid. The target can be dissolved in a solution of various media. Some additional non-limiting examples of the aqueous solution can 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 prior to a subsequent step to have a specific concentration of acid. Illustratively, the acid can help dissolve the composition. For example, the presence of nitric acid can help dissolve the bombarded Bi target.

[0050] Illustratively, the acid concentration can be about 1M to about 10M, about 1M to about 8M, about 2M to about 8M, or about 3M to about 7M. The acid concentration can be about 1M, about 2M, about 3M, about 4M, about 5M, about 6M, about 7M, about 8M, about 9M, or about 10M. The acid concentration can be adjusted depending on the partition coefficient in the solvent used in the subsequent step. 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 fully dissolve in an acidic medium can vary based on the medium used. For example, 209 Bi and 211 The target material having At therein may be dissolved over a period of time ranging from approximately about 2 minutes to about 1 hour, from approximately 5 minutes to about 30 minutes, from approximately 8 minutes to about 20 minutes, or from approximately 10 minutes to approximately 15 minutes. In embodiments in which the ionic medium includes nitric acid, the target material may be sufficiently dissolved in approximately 10 minutes to form a dissolved solution.

[0052] 1A-1B illustrate an exemplary embodiment of a compound separation and recovery system 100 for extracting one or more compounds from a lysis solution. Although the system of this embodiment is discussed with respect to the recovery of astatine from a lysis solution formed by dissolving a target having bismuth and astatine in nitric acid, those skilled in the art will recognize that the presently disclosed system and method can be applied to the extraction and recovery of a variety of compounds from solution, drug samples from bodily fluids, proteins from virus sera, and other inorganic materials obtained upon dissolution of various irradiated cyclotron targets.

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

[0054] In some embodiments, the pump 102 can be adjusted to change the flow rate of the liquids flowing through the system in response to inputs. For example, in some embodiments, the pump 102 can be remotely controlled by signals from the control system 200 to direct the flow sequence throughout the system. The 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 can range from about 0.0002 mL / min to 35 mL / min, while the flow rate of the dissolution solution can range from about 0.0002 mL / min to 35 mL / min. The control system 200 that controls the pumps and fluid flows is discussed in more detail below.

[0055] The pump 102 may be in fluid communication with a series of valves 104. The valves 104 may be configured to change position between various orientations to cause fluid to flow in a given direction within the system 100. For example, the position of each valve 104 may be changed by a signal received from the pump and / or the control system 200, which changes the direction of fluid flow therethrough.

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

[0057] 2A-2C show the valves 104 in more detail. Each valve 104 can include an inlet 106 and one or more outlets 108 for distributing fluids throughout the system. As shown in FIG. 2A, the selector 104 in this embodiment can include a single inlet 106 and ten outlets 108 extending therefrom, although it will be understood that in some embodiments, the selector 104 can include nine or fewer outlets 108 or more than ten outlets 108. The multiple outlets can support mixing or splitting batches of fluid flow to separate components of the system 100, such as multiple chromatography columns, as discussed further below. In some embodiments, the selector 104 can be a bidirectional selection valve that supports flow in a first direction from a source and flow in a second, opposite direction back 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 can include a selector stator 110, e.g., a plate 111 with linear grooves located behind a head having ports, the grooves connecting the inlets 106 to one of the outlets 108 at a time via incremental rotation of the plate 111. It will be appreciated that in embodiments in which the selector 104 includes a single outlet and multiple inlets, the plate 111 can be similarly rotated to align the outlets 108 with the inlets 106.

[0059] FIG. 2B shows an alternative embodiment of the valve 104' of this embodiment having a rotary valve 110' thereon. The rotary valve 110' can include a series of inlets 106' and outlets 108' arranged in a substantially circular arrangement around its circumference. The rotary valve 110' can be rotated by the pump 102 and / or the control system 200 to vary the position of the valve to regulate the flow through the valve. The advantage of this type of valve is the ability to connect two adjacent ports at once and handle two streams simultaneously. For example, considering a four-port valve, there are two possible positions, namely A and B, 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, the selector 104 can only handle one stream at a time by connecting port 106 to one of the ports 108.

[0060] FIG. 2C shows yet another embodiment of the valve 104' of this embodiment having another rotary valve 110" thereon. Unlike the six-port valve 104' of the embodiment of FIG. 2B, this embodiment includes a four-port valve 104" as shown. It will be appreciated that in some embodiments, valves having two ports, three ports, or more than six ports, e.g., eight, ten, etc., can be used.

[0061] Those skilled in the art will recognize that while the position of the selector 104 or valve 104' can be controlled in conjunction with the pump 102, in some embodiments the valves can be controlled independently. In some embodiments, the change in position of the selector 104 or valve 104' can occur in response to a program, a remote user input, and / or a manual rotation of the valve. The selector 104 or valve 104' can direct fluid or gas / air to other system components, e.g., a chromatography column (not shown), quality assurance devices, etc., as discussed further below. It will be appreciated that each selector 104 or valve 104' can be controlled independently of the other valves and / or the remaining components of the system 100.

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

[0063] As mentioned above, the compound recovery system 100 of the present embodiment can include a control system 200, sometimes referred to as a controller, an example of which is shown in FIG. 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 can be a personal computer or another computing source known to those skilled in the art that can control the flow rate and direction of the fluid / air flow throughout the system 100. In some embodiments, control of the flow rate and direction of the fluid / air can occur by signaling the pump 102 and the selector 104 or the valve 104', respectively, to flow the fluid / air according to the inputs to the control system 200. As mentioned above, the inputs in the control system 200 can be automated and / or located remotely, allowing the system 100 to operate without manual inputs.

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

[0065] FIG. 4 illustrates in further detail a schematic diagram of an exemplary embodiment of the automated compound recovery system 300 of the present embodiment. As shown, the system 300 can include a pump 302, a plurality of valves / selectors 304, a dissolution box 312, and a column 320. The plurality of valves / selectors 304 can be disposed throughout the system 300 to facilitate the introduction of fluid / air into the system and the distribution of the fluid / air throughout the system. For example, as shown, the plurality of valves / selectors 304 can include a solution selection valve 322 in fluid communication with one or more vials 324 having a solution therein. For example, as shown, the solution selection valve 322 can be configured to receive fluid from the vial 324 for distribution throughout the system 300. In one aspect, the solution in the vial 324 is an acidic medium, e.g., nitric acid. The solution selection valve 322 can be connected to a two-way selection valve 326a flowing to the pump 302 to flow the solution to the dissolution box 312 containing the irradiated target material therein.

[0066] The controller 200 can communicate with each of the pump 302 and 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 vias 324 and flow the solution to the dissolution box 312. While flowing the solution toward the dissolution box 312, the controller 200 can signal the two-way selection valves 326a, 326b to open to allow the fluid / air / gas to pass through the two-way selection valves 326a, 326b. Similarly, once the dissolution solution is prepared, the controller 200 can signal the two-way 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 the recovery of astatine.

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

[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 throughout the length of the 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 zeolites, molecular sieves, polymer resins, or glass beads. In some embodiments, the beads are porous. The beads may be inert. In some embodiments, the beads include styrene-divinylbenzene copolymers. In some embodiments, the benzene of the copolymer does not include functional groups.

[0069] In some embodiments, the porous resin is a polyacrylate resin or porous glass beads. 0.7 mL of 20% ethanol purchased from Sigma-Aldrich -1Amberchrom® CG300M porous beads having a pore volume of 100 μm and a particle size of 50-100 μm slurry can be used in extraction chromatography. Amberchrom® CG300M is a styrene-divinylbenzene copolymer with no functional groups on the benzene ring. In some embodiments, prior to 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 can include a biologically friendly ligand incorporated therein. In one embodiment, the ligand is an organic solvent incorporated into the resin bed, but it will be understood that other compounds such as alcohols, aldehydes, ketones, water-immiscible ketones, organic acids, esters, ethers, amides, carbonates, carboxylates, carbamates, and / or organophosphorus compounds, e.g., trialkylphosphine oxides and trialkyl phosphates, can be incorporated into the beads. For example, the dried resin can be impregnated with one or more of octanone, 3-octanone, etc., by immersing the beads in an organic solvent. The organic solvent can be used for adsorption onto the beads to extract astatine from the lysis solution, while the remainder of the lysis solution passes through the column. For example, for a lysis solution containing bismuth and astatine, 211 At is extracted into the organic solvent impregnated in the resin bed, but bismuth, the main component of the dissolution solution, is not extracted. 211 The dissolution solution can be separated to include the At extract and the bismuth remains in solution. Some additional non-limiting examples of organic solvents can include alcohols, aldehydes, ketones, immiscible ketones as the organic phase, such as n-octanone where n=1, 2, 3, methyl isobutyl ketone, decanone, esters, amides, carbonates, carboxylates, water immiscible alcohols, organic acids, organophosphorus compounds, and / or carbamates.

[0071] In some embodiments, the organic solvent is polar. In some embodiments, the organic solvent is optionally substituted C 1 ~C 18 alkyl, where C 1 ~C 18 Each hydrogen atom of the alkyl is optionally replaced by a functional group. 1 ~C 18 Optional substitutions on the alkyl are generally known in the art and include halogen, hydroxyl, amine, thiol, oxo, ketone, carboxylate, aldehyde, amide, carbonate, carbamate, combinations thereof, and the like. In some embodiments, the organic solvent comprises an aldehyde, ketone, ester, amide, carbonate, carboxylate, or carbamate. In some embodiments, the organic solvent comprises an aldehyde, ketone, ester, amide, carbonate, carboxylate, or carbamate. 1 ~C 18 , C 1 ~C 12 , or C 1 ~C 6 In some embodiments, the organic solvent comprises a carboxylic acid selected from the group consisting of a carboxylic acid and a carboxylic acid of formula C. 1 ~C 6 Alkyl-C(O)-C 1 ~C 6 In some embodiments, the organic solvent is of formula C 1 ~C 6 Alkyl-C(O)-C 1 ~C 6 alkyl, where C 1 ~C 6 Each hydrogen atom in the alkyl is optionally substituted. In some embodiments, the organic solvent is 1 ~C 18 Illustratively, the organic solvent may comprise a mixture of the organic solvents described herein.

[0072] In some embodiments, the solvent of the impregnated resin is a solvent that provides a D-value partition coefficient for At of at least 10 with respect to an aqueous solution, such as an aqueous solution containing nitric acid. In exemplary embodiments, At has a D-value partition coefficient in an organic solvent of at least about 20, at least about 40, at least about 60, or at least about 80. Illustratively, the partition coefficient can be measured with respect to an aqueous solution 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 straight or branched chain monovalent hydrocarbon group. In some embodiments, the number of atoms in an "alkyl" is 1 ~C 18 Alkyl, C 1 ~C 12 Alkyl, or C 1 ~C 6 It may be advantageous to restrict the group to a particular range of atoms, such as alkyl. 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 would be considered equivalent to any one of the preceding examples in light of the skill of the art and the teachings provided herein. It will be understood that the alkyl group can be unsubstituted or substituted as described herein. The alkyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents. The term "alk-" forms a prefix, and the remainder may be a functional group. For example, an "alkanol" is an alkyl group substituted with an alcohol.

[0074] The term "substituted" means that the specified group or moiety has one or more substituents. The term "unsubstituted" means that the specified group has no substituents. When the term "substituted" is used to describe a structural system, it means that the substitution occurs at any valence-allowed position on the system. In some embodiments, "substituted" means that the specified group or moiety has one, two, or three substituents. For example, two hydrogen atoms on a carbon of an alkyl group can be replaced by an oxo (=O) group to form a carbonyl (C=0). In other embodiments, "substituted" means that the specified group or moiety has one or two substituents. In still other embodiments, "substituted" means that the specified group or moiety has one substituent. Those of skill in the art will recognize that the term "halogen" or "halo" refers to chlorine, fluorine, bromine, or iodine.

[0075] Conventional methods of astatine capture include dry distillation, where the target is heated until the dissolution solution turns into a gas, and then the gas is collected. The system and method of the present embodiment do not require heating. Rather, the use of a solid resin bed impregnated with an organic solvent to extract astatine from the dissolution solution improves the efficiency of the extraction of astatine in the present embodiment and allows the system of the present disclosure to be automated. For example, by performing dissolution of the irradiated target in the same acidic medium, e.g., nitric acid medium, as the medium used for recovery, the extraction and recovery of astatine can be expedited without the need for additional chemical manipulation or evaporation of the dissolution solution. Conventional chromatographic techniques utilize a liquid-liquid extraction process in which two immiscible liquids interact to extract a compound, e.g., astatine, from the dissolution solution. The use of liquids when performing the extraction requires the conversion of the solvent to extract the desired compound, resulting in multiple liquid-liquid extraction steps in the column. For example, if a nitric acid medium is used to form the dissolution solution in conventional chromatography, with the development of phase interface sensors, the nitric acid medium needs to be converted to a hydrochloric acid medium, e.g., hydrochloric acid, before astatine can be extracted. After conversion, the dissolution solution is reacted with hydrochloric acid medium to extract astatine therefrom in a conventional manner. In some embodiments, the liquid-liquid extraction process may further require chemical destruction of the nitrate salts with hydroxylammonium chloride as described above, and / or heating to complete the extraction process. In comparison, the solid-liquid extraction of the present embodiment performs extraction of the compound directly from the nitric acid medium without conversion, resulting in higher conversion efficiency and shorter extraction time. Furthermore, the solid-liquid extraction process using the resin bed of the present embodiment occurs without heating. Still further, in some embodiments, the solid-liquid extraction process can be performed in continuous flow rather than batch flow, which further improves efficiency and shortens the recovery period of astatine from the dissolution solution. For example, under continuous flow, the solution passing through column 320 can contact multiple stages of beads on its way therethrough, thereby repeatedly exposing the solution to the organic solvent impregnated therein and increasing the recovery of the compound of interest.That is, the solution flows continuously from one stage of beads to the next, with extraction of astatine occurring at each stage.

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

[0077] In some embodiments, the frequency of flowing the lysis solution through the QA device 326 can be tapered over time. For example, sampling can be more frequent toward the beginning of the extraction process to ensure that the activity of the lysis solution is within an acceptable range. As the process continues, the flow of fluid through the QA device 326 can be less frequent and eventually stopped, so long as the activity level remains within a desired range. The activity level can be monitored by the control system 200, which is configured to resume sampling and / or increase the frequency of sampling if the activity level of the lysis solution falls outside of the acceptable range.

[0078] The QA device 326 can have a volume ranging from approximately about 20 milliliters to about 80 milliliters, about 30 milliliters to about 70 milliliters, about 40 milliliters to about 60 milliliters, or can have a value of about 50 milliliters. One skilled in the art will recognize that the volume of the QA device can be selected such that sufficient sample is tested to confirm 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 a user. In such an embodiment, an operator can monitor the chemical processes occurring during irradiation, separation, and / or collection without manually interacting with components, thereby reducing the amount of radiation and / or harmful chemical exposure to the operator. Additionally, once the target is placed in the melting box 312, the control system 200 can adjust the system 300 remotely from a user. It will be appreciated that while the system is automated, one or more features or inputs can be performed manually.

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

[0081] Additionally, one skilled in the art will recognize that variations of the system are possible. For example, while a single column is shown in FIG. 4, in some embodiments, the batch of lysis solution flowing from the lysis box 312 can be split into multiple columns. The multiple columns can be of equal size and / or equal geometric shapes, while in some embodiments, the columns can be of different sizes and / or different geometric shapes. Additionally, the columns within the multiple columns can include the same resin / bed therein, while in some embodiments, the columns within the multiple columns can include different resins / beds therein. In some embodiments, the multiple columns can be arranged in series such that a single flow of solution passes through two or more columns. In alternative embodiments, the multiple columns can be arranged in parallel such that the batch of lysis solution is split before flowing through the columns.

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

[0083] 5 illustrates an exemplary method 500 for recovering a compound of interest using the system of the present disclosure. As discussed above, the method includes recovering a compound of interest that has been irradiated with alpha particles. 209Although discussed with respect to the recovery of astatine from a Bi target material, the steps of method 500 of the present disclosure can be used to separate and recover a variety of compounds of interest from solution. Additionally, it will be appreciated that control system 200 can automate and / or remotely control each of the steps of method 500 by signals sent to one or more components of the system, as described in detail above.

[0084] As shown, the irradiated target material having bismuth and astatine therein can be exposed to a nitric acid solution to form a dissolution solution in which the bismuth and astatine dissolve in the nitric acid (S502). In some embodiments, the exposure of the target material can occur in a dissolution box, where the target material is placed in the dissolution box and the nitric acid solution is directed to it. In some aspects, the control system 200 can direct one or more of the pump 302 and / or the valve 304 to flow the nitric acid solution to the dissolution box 312. In some embodiments, the control system 200 can remotely signal the solution selection valve 322 to flow the nitric acid solution therethrough and can signal the pump 302 to flow the nitric acid solution to the dissolution box 312. The solution can flow to the target material substantially continuously and / or in batches to facilitate dissolution of the target material.

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

[0086] Optionally, in some embodiments, a portion of the lysis solution can flow toward the QA device 326 to measure the activity of the lysis solution (S505). In such embodiments, the QA device 326 can sample the lysis solution to measure the activity level of dissolved astatine in the lysis solution. Once sampled, the lysis solution can be flowed back through the two-way selection valves 326a, 326b to the column 320 for recovery of astatine from the lysis solution.

[0087] After contacting with the solution containing the mixture containing At, the resin may be washed (S506). The washing step may include washing the resin with an aqueous solution. In some embodiments, the aqueous solution includes an acid. In some embodiments, the aqueous washing solution includes 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 6M, the acid concentration in the washing solution may be less than about 6M, e.g., about 2M. In some embodiments, the acid concentration is less than about 10M, less than about 8M, less than about 6M, or less than about 4M. In some embodiments, the acid concentration is up to about 8M, up to about 6M, or up to about 4M. In an exemplary embodiment, 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 can be a different acid. For example, the acid can be HClO 4 , HCl, HBr, or H 2 SO 4 Illustratively, changing the acid used in the washing step can 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 bed volumes. For example, the resin can be washed with a solution having a volume of at least about 2 bed volumes, at least about 3 bed volumes, at least about 4 bed volumes, at least about 5 bed volumes, or at least about 6 bed volumes. In an exemplary embodiment, the resin can be washed sequentially with an aqueous solution containing an acid and an aqueous solution not containing an acid. The washing steps can be adjusted by means known in the art to include additional or fewer washing steps of aqueous solutions.

[0090] In embodiments where the aqueous wash solution includes an acid, a separate wash 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 the column. Once the acid has been washed away, the column can be washed with the extracted 211 It may contain a resin bed having At attached thereto.

[0091] In some embodiments, astatine can be eluted or stripped from the resin (S510). Illustratively, the elution step dissociates At from the resin to allow At to be collected. The elution step can be carried out by contacting the resin with an organic solvent. In some embodiments, the organic solvent is the same solvent that impregnates the resin. In some embodiments, the organic solvent in the elution step is miscible with the solvent that impregnates the resin. In some embodiments, the organic solvent is an optionally substituted C 1 ~C 18 alkyl, where C 1 ~C 18 Each hydrogen atom of an alkyl is optionally replaced by a functional group. 1 ~C 18Optional substitutions on the alkyl are generally known in the art and include halogen, hydroxyl, amine, thiol, oxo, ketone, carboxylate, aldehyde, amide, carbonate, carbamate, combinations thereof, and the like. In some embodiments, the organic solvent comprises an aldehyde, ketone, ester, amide, carbonate, carboxylate, or carbamate. In some embodiments, the organic solvent comprises an aldehyde, ketone, ester, amide, carbonate, carboxylate, or carbamate. 1 ~C 18 , C 1 ~C 12 , or C 1 ~C 6 In some embodiments, the organic solvent comprises a carboxylic acid selected from the group consisting of a carboxylic acid and a carboxylic acid of formula C. 1 ~C 6 Alkyl-C(O)-C 1 ~C 6 In some embodiments, the organic solvent is of formula C 1 ~C 6 Alkyl-C(O)-C 1 ~C 6 alkyl, where C 1 ~C 6 Each hydrogen atom in the 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 C 1 ~C 18 In some embodiments, the solvent comprises ethanol.

[0092] Illustratively, 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 comprising At. In some embodiments, the processes recover from about 80% to about 99%, from about 85% to about 99%, or from about 90% to about 99% of At from a composition comprising At.

[0093] Illustratively, the eluted At has a higher purity of At than the composition containing At prior to the chromatographic 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 can 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. Illustratively, the processes are carried out in less time than comparable processes that require dissolving the At / Bi composition in a nitric acid solution, evaporating the nitric acid solution, and reconstituting the residue in hydrochloric acid prior to chromatography, or compared to comparable processes that require destruction of the nitrates prior to chromatography. The processes described herein isolate At at a specific fraction of its half-life. In some embodiments, the process comprises: 211 At less than about 20%, less than about 15%, less than about 10%, or less than about 5% of the half-life of At, such as At.

[0095] The purified glycerol collected by this system 211 It will be appreciated that At isotopes can have a variety of uses. Astatine (At) may be useful as a radioactive label for therapeutic agents. For example, the astatine of the present 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 a therapeutic agent with the eluted At. This may be done directly on the eluted At column fraction, or may include concentrating the At-containing fraction and suspending or dissolving the At in a solution used for the labeling step.

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

[0097] The astatine in the drying column can have a variety of uses. For example, in some embodiments, the drying column can be delivered to a facility for elution of the column to recover the astatine stored in the column. In some aspects, the drying column can be used to label biomolecules. In some embodiments, the astatine can be used to treat cancer by targeting cancer cells. For example, the radioactive decay of astatine can be used to label anti-tenascin monoclonal antibody 81C6 (ch81C6), F(ab') in the column. 2 This can be utilized by adding astatine to biologically relevant molecules, such as astatine, a fragment of the murine IgG1 monoclonal antibody MX35, and / or an anti-CD45 monoclonal antibody, and the astatine and molecule can then be stripped from the column and injected into a patient as a cancer treatment.

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

[0099] 6A-6E show in more detail the sequence of flow through the automated compound recovery system 300 for the steps of the method 500. For example, as shown in FIG. 6A, the solution selection valve 322 can be in fluid communication with a number of vials 324. The vials can contain several fluids, such as acid, water, and / or solvents stored therein, as shown. As discussed above, the solution selection valve 322 can include a number of inlets 306, each connected to one of the vials 324, and a single outlet 308 configured to flow the contents of the vials 324 throughout the system 300. Fluid exiting through the outlet 308 can flow to a two-way selection valve 326a and to the pump 302. From the pump 302, the fluid can flow to a second two-way selection valve 326b and to the dissolution box 312 for dissolving the target material in the dissolution solution. From the dissolution box 312, the dissolution solution can flow, in some embodiments, through a third two-way selection valve 326c to a product vial or QA device 326 for sampling. The dissolution box 312 can also be in fluid communication with a fourth two-way selection valve 326d to pass gaseous substances, e.g., vapors, to a scrubber vat 330 and a charcoal vat 332 to remove astatine vapor. It will be appreciated that in some embodiments, the fourth two-way selection valve is configured to allow gas to flow therethrough instead of liquid. The dissolution box 312 can also be in fluid communication with a column 320 and a fraction collection valve 328, as discussed in more detail below.

[0100] FIG. 6B illustrates a flow sequence for forming a dissolution solution (S502) in the system 300. As illustrated, acid, e.g., nitric acid, from a vial 324 can enter one of a number of inlets 306 of the solution selection valve 322 (A) and exit through an outlet 308 (B) to flow to a two-way selection valve 326a. From the two-way selection valve 326a, the acid flows to the pump 302 (C) and is then pumped through a two-way selection valve 326b (D) to the dissolution box 312 to form a dissolution solution (E). Once sufficiently dissolved, vapors generated by the formation of the dissolution solution can flow out of the dissolution box 312 to a fourth two-way selection valve 326d (F) and into the scrubber vat 330 and charcoal vat 332. The vats 330, 332 can perform a safe scrubbing of the astatine to ensure that vapors do not escape the solution. For example, gas, e.g., vapor, exiting fourth two-way select valve 326d can enter scrubber vat 330 containing sodium hydroxide solution. The sodium hydroxide in scrubber vat 330 can interact with gas produced by the dissolution solution to neutralize astatine vapor emanating from the gas produced by the dissolution solution. The unreacted astatine vapor can then pass to charcoal vat 332, which acts as a filter for any gas from the dissolution solution to prevent escape of unreacted astatine vapor from the gas into the laboratory and / or surrounding environment.

[0101] FIG. 6C shows the flow for the transfer of the lysis solution from the lysis box 312 to the QA device 326 (S505). As shown, the lysis solution exits the lysis box 312 in flow (G) and then passes through the third bidirectional selection valve 326c to pass to the QA device 326 for sampling activities (H). Once sampled, the QA device 326 can be in fluid communication with the third bidirectional selection valve 326c and the bidirectional selection 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 out of the QA device 326 by negative pressure, which draws air rather than liquid out of the QA device via flow (I). Drawing vapor out of the QA device 126 can act as a safety measure to ensure there are no leaks in the system. Pump 302 can create a corresponding pressure within dissolution box 312 via flow (J) passing through two-way selection valve 326b and entering dissolution box 312 to remove air and potentially harmful astatine gas from dissolution box 312. As mentioned above, use of QA device 326 can be optional, although in some embodiments sampling via QA device 326 can be less frequent over time.

[0102] FIG. 6D illustrates the loading of column 320 (S504) in more detail. As shown, the lysis solution can exit the lysis box (K), pass through the third two-way selection valve 326c, and enter the product vial 326 for sampling. Once activity has been measured, the lysis solution can pass through the third two-way selection valve 326c and the two-way selection valve 326a to exit the QA device 326 via flow (L) and flow to the pump 302. From the pump 302, the lysis solution can be pumped (M) through the two-way selection valve 326b to the fraction collection valve 328. As shown, the fraction collection valve 328 can include a single inlet 336 and multiple outlets 338, each connected to a corresponding column 320. The lysis solution 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 lysis solution (M) from pump 302 can enter column 320 before passing through fraction collection valve 328. In such embodiments, the flow of fluid (N) exiting column 320 can pass through outlet 338 of fraction collection valve 328 to be collected in dispense vial 329, as discussed in FIG.

[0103] FIG. 6E illustrates in more detail washing the column 320 (S508) to remove unextracted species from the column. As shown, water can pass through the solution selection valve 322, through one of the inlets 306, and out through the outlet 308 (O). Once the water leaves the solution selection valve 322, it can pass through the two-way selection valve 326a and into the pump 302 (P). From the pump 302, the water can be pumped (Q) through the two-way selection valve 326b to the fraction collection valve 328. From the fraction collection valve, the water can flow to the column 320 to flush the column of unextracted species. Those skilled in the art will recognize that the sequence for washing the column can be similar 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 to dry the column 320.

[0104] As mentioned above, in some embodiments, the system 100, 300 can be coupled and / or otherwise associated with a controller 200 configured to automate and / or remotely control the steps of the 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, as such configurations are understood in light of the present disclosure. FIG. 7 is a block diagram of one exemplary embodiment of a computer system 1500 on which the controller or control system 200 of the present disclosure can be built, executed, trained, etc. For example, any module or system is an example of the system 1500 described herein. The system 1500 can include a processor 1510, a memory 1520, a storage device 1530, and an input / output device 1540. Each of the components 1510, 1520, 1530, and 1540 can be interconnected, for example, using a system bus 1550. The processor 1510 can process instructions for execution within the system 1500. The processor 1510 can be a single-threaded processor, a multi-threaded processor, or a similar device. The processor 1510 can process instructions stored in the memory 1520 or on the storage device 1530. The processor 1510 can perform operations such as starting and stopping fluid flow, controlling fluid paths or pressure, and system configurations that can be automatic, can be responsive to various parameters, and / or can be manually controlled by a user, including in response to signals, parameters, etc., and / or based on observations / preferences, etc., among other features described in connection with this disclosure, by way of non-limiting example. The controller 1500 can optimize operations in response to various conditions of the solutions entering the system, various electricity prices, and other factors that can relate to the energy efficiency, reliability, maintenance, or levelized costs of the solutions used to dissolve the irradiated targets.In some examples, the controller 1500 can optimize operation in response to a desired dissolution solution concentration, type of acidic medium, and / or operating pressure. The controller 1500 can further incorporate machine learning techniques, artificial intelligence, and / or digital twinning, which can assist in improving performance.

[0105] The memory 1520 can store information within the system 1500. In some implementations, the memory 1520 can be a computer-readable medium. The memory 1520 can be, for example, a volatile or non-volatile memory unit. In some implementations, the memory 1520 can store information related to fluid paths and system components, such as when and / or in response to what conditions the permeate generation and flushing configurations should be implemented, and / or different conditions for various loops allowed by the system, and can store flush times, permeate salinity, and / or operating pressures, among other information, which can enable machine learning optimization of the system.

[0106] The storage device 1530 can provide mass storage for the system 1500. In some implementations, the storage device 1530 can be a non-transitory 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 mass storage device. The storage device 1530 can alternatively be a cloud storage device, for example, a logical storage device including multiple physical storage devices distributed over and accessed using a network. In some implementations, information stored on the memory 1520 can also be stored on the storage device 1530 or can be stored instead on the storage device 1530.

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

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

[0109] Although an exemplary processing system is described above, the implementation of the subject matter and functional operations described above can be implemented in other types of digital electronic circuitry, including the structures disclosed herein and their structural equivalents, or in computer software, firmware, or hardware, or in one or more combinations thereof. The implementation of the subject matter described herein can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible program carrier, such as 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 matter that provides a machine-readable propagated signal, or one or more combinations thereof.

[0110] Various embodiments of the present disclosure may be implemented, at least in part, in any conventional computer programming language. For example, some embodiments may 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 may 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 encompass all apparatus, devices, and machines for processing data, including, by way of non-limiting example, a programmable processor, computer, or multiple processors or computers. In addition to hardware, a processing system may include code that creates an execution environment for the computer program in question, such as code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or one or more combinations thereof.

[0112] A computer program (also known as a program, software, software application, script, 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 a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file 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 in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, subprograms, or portions of code). A computer program can be deployed to run on one computer or to run on multiple computers located at one site or distributed across multiple sites and interconnected by a communication network.

[0113] Such implementations may include a set of computer instructions fixed in any tangible, non-transitory medium such as a computer-readable medium. The set of computer instructions may embody all or part of the functionality previously described herein with respect to the system. Computer-readable media suitable for storing computer program instructions and data include all forms of non-volatile or volatile memory, media, and memory devices, including, by way of example, semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices, magnetic disks, e.g., 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 supplemented by or incorporated in special purpose logic circuitry. The components of the system may be interconnected by any form or medium of digital data communication, e.g., a communications network. Examples of communications networks include local area networks ("LANs") and wide area networks ("WANs"), e.g., the Internet.

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

[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, may be preloaded into a computer system (e.g., on a system ROM or fixed disk), or may be distributed from a server or bulletin board over a network (e.g., the Internet or the World Wide Web). Indeed, some embodiments may be implemented in a Software-as-a-Service model ("SAAS") or cloud computing model. Of course, some embodiments of the present disclosure may be implemented as a combination of both software (e.g., computer program products) and hardware. Still other embodiments of the present disclosure may be implemented entirely as hardware or entirely as software. [Explanation of symbols]

[0116] 100 Compound separation and recovery system, system, compound recovery system 102 Pump 104 Valve or selector, valve, selector 104' valve, 6 port valve 104" 4-port valve 106 Entrance, Port 106' entrance 108 Exit, Port 108' Exit 110 Selector stator 110' Rotary Valve 110" Rotary Valve 111 Plate 112 Melting box, melting box or container 114 Peristaltic Pump 116 USB Camera 130 Scrubba 132 Charcoal bat 200 Control system, controller, controller or control system 202 Microcontroller 204 Switch 206 Power supply 300 Automatic compound recovery system, system 302 Pump 304 Valve / Selector 306 Entrance 308 Exit 312 Melting Box 320 Column 322 Solution Selection Valve 324 Vials 326 Quality Assurance (QA) Device or Product Vial, QA Device 326a Two-way selection valve 326b Two-way selection valve, second two-way selection valve 326c Third Two-Way Selector Valve 326d Fourth Two-Way Selector Valve 328 Fraction collection valve, valve 329 Dispensing vials, vials 330 Scrubbabat, Bat 332 Charcoal bat, bat 336 Entrance 338 Exit 1500 Computer system, system 1510 Processor 1520 Memory 1530 Storage Device 1540 Input / Output Devices 1550 System Bus

Claims

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

2. 13. The system of claim 1, further comprising a dissolution vessel in fluid communication with the pump and the column, the dissolution vessel configured to form the dissolution solution by mixing irradiated target material and a medium therein.

3. 3. The system of claim 2, further comprising one or more selectors in fluid communication with the pump and configured to deliver the solvent or dissolution solution therethrough.

4. The system of claim 3 , wherein an orientation of the one or more selectors is determined by the signal from the control system.

5. The system of claim 3 , wherein the control system is configured to communicate with the pump and the one or more selectors substantially simultaneously.

6. The system of claim 3 , wherein the one or more selectors include a single inlet and multiple outlets.

7. The system of claim 3 , wherein the one or more selectors include a single outlet and multiple inlets.

8. 5. The system of claim 4, wherein the one or more selectors are in fluid communication with one or more vials containing a solution therein, and the pump is configured to deliver the medium through the one or more selectors to the dissolution vessel.

9. 9. The system of claim 8, wherein the medium comprises one or more of nitric acid, hydrobromic acid, hydrochloric acid, sulfuric acid, or perchloric acid.

10. 10. The system of claim 1, wherein the extraction medium is a resin bed.

11. 10. The system of claim 1, wherein the solvent can include one or more of octanone, 3-octanone, or 1-octanol.

12. 10. The system of claim 1, wherein the extraction of astatine occurs without heating.

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

14. 10. The system of claim 1, further comprising a second column configured to receive a portion of the lysis solution therethrough.

15. 15. The system of claim 14, wherein the second column is disposed in series with the first column.

16. 15. The system of claim 14, wherein the second column is disposed in parallel with the first column.

17. 1. A method for compound recovery, comprising: exposing the 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 one or more compounds therein; passing the lysis solution through a chromatography column to extract the one or more compounds from the lysis solution, wherein the one or more compounds are extracted into a resin bed disposed within the chromatography column; washing the resin bed to remove unextracted lysis solution from the column; Including, each of the steps of exposing the target material, passing the lysis solution through the chromatography column, and washing the resin bed occurs in response to an automated or remotely located signal; method.

18. 18. The method of claim 17, wherein the resin bed is washed with the acidic medium.

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

20. 20. The method of claim 17, further comprising washing the chromatography column with an aqueous solution to remove the acidic medium from the chromatography column.

21. 20. The method of claim 17, wherein the lysis solution is formed over a period ranging from approximately about 5 minutes to about 30 minutes.

22. 21. The method of claim 20, further comprising eluting the one or more compounds from the resin to collect the one or more compounds.

23. 21. The method of claim 20, further comprising the steps of drying the column to remove excess fluid from the column and sealing the column.

24. 24. The method of claim 23, wherein drying the column further comprises blowing air through the column until excess fluid is substantially removed.

25. 25. The method of claim 24, wherein the column retains the compound after the air is blown through the column.

26. 18. The method of claim 17, wherein the lysis solution is passed through the chromatography column by a pump in fluid communication with one or more selectors disposed between the pump and the column.

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

28. 20. The method of claim 17, further comprising splitting the lysis solution into multiple streams, each stream entering a separate chromatography column.

29. 20. The method of claim 17, wherein the extraction of the one or more compounds occurs without heating.

30. 20. The method of claim 17, further comprising the step of sampling the portion of the lysis solution to determine its activity level prior to passing the portion of the lysis solution to the column.

Images