CN114829640A - System and method for producing elements from a mixture, storage/generation vessel and storage/generation vessel assembly - Google Patents

Abstract

Systems and/or methods for producing free elements, systems and/or methods for producing element storage/generation vessel assemblies, systems and/or methods for purifying elements and providing progeny generation assemblies are provided.

Description

System and method for producing elements from a mixture, storage/generation vessel and storage/generation vessel assembly

Cross Reference to Related Applications

This application is a continuation-in-part application entitled "system and method for separation of radium from lead, bismuth and thorium" U.S. patent application serial No. 16/894,679 filed on 5.6.2020, claiming priority and benefit of U.S. provisional patent application serial No. 62/857,681 entitled "separation of radium from lead, bismuth and thorium for medical isotope production applications" filed on 5.6.2019. The present application also claims priority and benefit of U.S. provisional patent application serial No. 62,946,592 entitled "fluid system for packing a generation column with a resin containing uniformly distributed isotopes" filed on 2019, 12, 11, each of which is incorporated herein by reference in its entirety.

Statement regarding rights to disclose made under federally sponsored research and development

This disclosure was made with government support under contract DE-AC0576RL01830 awarded by the U.S. department of energy. The government has certain rights in this invention.

Technical Field

The present disclosure relates generally to the separation of metals, e.g., as elements, and assemblies for storage/generation of metals, and, in more specific embodiments, to medical radionuclides, and more particularly to methods for obtaining materials and performing separations to produce such materials.

Background

In the field of medical radionuclides, there are a number of obstacles facing the isolation of materials and the preparation of materials, including in various therapies. Availability, cost, opportunity and limited shelf life coupled with the need to perform many activities in a professional security facility create a number of obstacles. ²¹² Pb/ ²¹² The existing method of Bi generator preparation requires two stepsThe method comprises the following steps: the first step, must be from ²²⁸ Separation in Th stock solution ²²⁴ Ra; in the second step, the process must be carried out ²²⁴ Ra Loading onto cation exchange (CatIX) resin (which becomes ²¹² Pb/ ²¹² Bi generation column) which performs a potential exposure of personnel to high radiation doses. The dosage is mainly less than ²¹² Short-lived progeny (progeny) of Po. In addition, this process is cumbersome and labor intensive, and may require multiple columns and boil-down steps to achieve the desired purpose.

What is needed are more and more improved methods to simplify these processes, increase yields, and address various use barriers. The following description provides numerous examples and developments in this regard.

Disclosure of Invention

A system for separating Ra from a mixture comprising at least Ra, Pb, Bi, and Th is provided. The system may include: a first container containing a first medium and containing Pb or Bi and/or Th; and a second vessel in fluid communication with the first vessel, the second vessel containing a second medium and Ra, wherein the first medium is different from the second medium.

Also provided is a system for separating Ra from a mixture comprising at least Ra, Pb, Bi, and Th, the system may comprise: a first container for containing a first medium and Th and/or Bi; and a second vessel in fluid communication with the first vessel, the second vessel containing a first medium and Pb, wherein the first medium is different from the second medium.

Further systems for separating Ra from a mixture comprising at least Ra, Pb, Bi, and Th may comprise: a first container for containing a first medium and Th or Bi; a second vessel in fluid communication with the first vessel, the second vessel containing a second medium and Pb; and a third vessel in fluid communication with the second vessel, the third vessel containing a third medium and Ra, wherein at least one of the first medium, the second medium, or the third medium is different from the other medium.

A method for separating Ra from Pb, Bi, and Th is provided, which may include: providing a first mixture comprising Ra, Pb, Bi, and/or Th; providing a system comprising: a first container containing a first medium; and a second vessel in fluid communication with the first vessel, the second vessel containing a second medium; exposing the first mixture to the first medium within the first container to separate the Th and Bi from the Ra and Pb; then, the remaining mixture is exposed to the second medium in the second container by fluid communication to associate the Pb or Ra with the second medium.

The method for separating Ra from Pb, Bi, and Th may also include: providing a first mixture comprising Ra, Pb, Bi, and/or Th; providing a system that may include: a first container containing a first medium; a second vessel in fluid communication with the first vessel, the second vessel containing a second medium; and a third vessel in fluid communication with the second vessel, the third vessel containing a third medium; and exposing the first mixture to the first medium within the first container, then exposing a first remaining portion to the second medium in the second container by fluid communication, then exposing a next remaining portion to the third medium in the third container by fluid communication, the exposing separating the Th and Bi from the Ra and Pb and separating the Ra from the Pb.

Methods for separating Ra from association with a medium are also provided. The method may include: exposing the Ra and the medium to a chelating agent to form a mixture comprising Ra complexed with the chelating agent.

Also provided is a method for separating Ra from Pb, Bi, and Th, which may include: providing a first mixture comprising Ra and at least Bi and/or Th; separating one or more of Bi and/or Th from the Ra, the separation associating the Bi and/or Th with a first medium; and dissociating the Bi and/or Th from the first medium to form a mixture comprising the Bi and Th, and transferring the mixture to a vessel containing at least Ra and additional Bi and/or Th.

The system/method may include providing a mixing vessel in fluid communication with both a bound element source and an acid source. The mixing vessel may be operably configured to mix the contents of the mixing vessel. The system can include a first multi-way valve operably engaged with the outlet of the mixing vessel, and a second multi-way valve operably engaged with the first multi-way valve, the acid source, and the collection vessel.

Also provided are methods for producing free elements from bound elements. The method may include: providing a solution comprising an element bound to a complex; exposing the solution to an acid solution to separate the complex from the element; and removing the separated element or the complex from the solution to produce a free element.

Systems and/or methods for producing a metal storage/generation vessel assembly are provided. The system may include: a first mixing vessel in fluid communication with the first and second multi-way valves; a manifold of multi-way valves in fluid communication with the second multi-way valve; a second mixing vessel in fluid communication with at least one of the multi-way valves of the manifold; a third multi-way valve in fluid communication with an outlet of the second mixing vessel; and a metal storage/generation vessel in fluid communication with the third multi-way valve.

The first mixing vessel and the second mixing vessel define different volumes. The first mixing vessel defines a volume that is greater than a volume defined by the second mixing vessel.

A method for producing a metal storage/generation vessel assembly is also provided. The method may include: homogenizing the resin slurry in a first mixing vessel; replenishing free elements to the homogenized resin slurry to form a homogenized bound element resin slurry; and transferring the homogenized binding element resin slurry to a storage/generation vessel assembly. As shown and described, without homogenization, the resin/media of the present disclosure, alone or in combination with free elements, will consolidate or adhere to other portions of the container at the lower portion of the container. Homogenization herein maintains the distribution of the resin/medium alone or in combination with the free elements throughout the solution in the vessel. This distribution may be uniform and/or free of heterointerfaces.

Also provided is a metal storage/generation vessel assembly, which may include: a sidewall extending between the inlet opening and the outlet opening to define a container volume; an inert material adjacent the outlet opening; and a bed of homogenized bound element resin within the vessel, the inert material being between the resin bed and the outlet opening.

Drawings

Embodiments of the present disclosure are described below with reference to the following drawings.

Fig. 1 illustrates an overall scheme for separating, releasing and creating a storage/generator vessel assembly according to one embodiment of the present disclosure.

Fig. 2 depicts a more specific scenario, which also illustrates an exemplary storage/generator assembly and generation of isotopes using a storage/generator container assembly in accordance with an embodiment of the present disclosure.

FIG. 3 shows an exemplary improved three-post ²²⁴ An Ra separation scheme; the green cells indicate the active flow path at each step a through E. (A) Loading and washing "a" to adsorb Th, Pb and Ra on C1-C3, respectively; (B) secondary wash "b" for C2-C3; (C) water washing by C3 to remove H ⁺ Ions; (D) elution of Ra from C3; and (E) elution of Th from C1 for reuse.

FIG. 4 depicts step A: ²²⁸ initial 3 columns of Th stock were loaded + wash "a".

Figure 5 shows the gamma spectrum obtained after a three column loading/washing procedure (see path a in figure 4). Will be provided with ²²⁸ Th/progeny sample Loading (A) and use 6M HNO ₃ Washing (B) through all three columns; no activity was observed to penetrate the three-pillar stack. (C) After loading and washing steps, AnIX _poly (defined below Table 1) media (C1) showed adsorption onto resin beads ²²⁸ Th、 ²¹² Bi and ²⁰⁸ Tl。

FIG. 6 shows that during the wash "a" sequence, the appearance is shown in the fractions collected as soon as they are downstream of C2What is more ²²⁴ Gamma spectrum of Ra emission. It was also observed that adsorption onto C2 is likely ²¹² Trace amount of Pb production ²¹² Bi/ ²⁰⁸ Tl (not retained at C2).

Fig. 7 shows step B: wash "b" C2+ C3.

Fig. 8 shows the resin capacity factor (k') of (a) a group II divalent cation in nitric acid on Sr resin. (B)2M HNO ₃ Not retained in ²¹² Bi and a small amount of Bi remaining ²²⁴ The Sr resin effluent fraction elution profile of Ra.

Fig. 9 shows the gamma spectrum obtained after a two-column loading/washing procedure (see path B in fig. 7). (A) Using 2M HNO ₃ Will be provided with ²¹² Pb and ²²⁴ ra washes through C2/C3; no activity was observed to penetrate the double column stack because ²¹² Pb remained on the Sr resin column (C2), and ²²⁴ ra was retained on the Ra-01 resin column (C3). (B) The spectrum obtained from the Sr resin column (C2) at the end of the "b" washing step shows a pure appearance ²¹² Pb。

FIG. 10 is step C: c3 washing with water.

FIG. 11 shows (A) the use of water from ²²⁴ Ra-loaded C3 elution residue ²¹² And Pb. (B) The decay rate of the water wash fraction indicates that there is little or no decay rate during the water wash step ²²⁴ And Ra is lost.

FIG. 12 is step D: separated from each other ²²⁴ Ra C3 elution.

FIG. 13 shows (A) ²²⁴ Combined radiochromatograms of Ra elution fractions. (B) Monitoring separation with respect to theoretical decay rate as a function of time ²²⁴ The activity of the Ra fraction indicates that it is radionuclide pure.

FIG. 14 is step E: using HCl ²²⁸ C1 elution of Th stock.

FIG. 15 is (A) the reaction of (A) AnIX with 8M HCl _poly (defined below in Table 1) elution of resin M1 ²²⁸ Th、 ²¹² Bi and ²⁰⁸ tl. (B) AnIX after HCl elution cycle _poly (defined below Table 1) the spectrum of resin M1 shows incomplete ²²⁸ Th eluted.

FIG. 16 isAutomated three-column system according to one embodiment of the present disclosure ²²⁴ Schematic fluid layout of Ra purification system.

FIG. 17 shows (A) for ²²⁸ Th a stepper motor driven syringe pump for liquid storage loading operation. (B) For driving a triple column according to an embodiment of the present disclosure ²²⁴ The Ra isolation procedure solenoid is a fluid routing system.

FIG. 18 is a graph of MP-1M resin (M1) in the presence of 1M HCl ²²⁸ Gamma spectrum of the Th elution chromatogram (A). Using 8M HCl on the same resin ²²⁸ Th elution chromatogram (B). The dashed line at 10mL indicates that the EDTA back-extraction (strip) solution was initially applied to remove any residual from the column ²²⁸ Th。

FIG. 19 shows (A) from 6M HNO ₃ 1cc TEVA resin effluent collected loading and washing the "a" fraction. Arrow indicates absence ²²⁸ Location of Th X-ray. Observing the penetration of the medium ²¹² Pb、 ²¹² Bi and ²⁰⁸ tl photon peak ( ²²⁴ With Ra emission hidden at-240 keV ²¹² Below the Pb peak). (B) Analysis of TEVA resin effluent over time showed a correlation with ²²⁴ A decay rate consistent with the decay rate of Ra; this indicates that during the loading/washing "a" step ²²⁸ Th is sufficiently adsorbed on the medium.

FIG. 20 shows the use of 1M HCl on TEVA resin (M1) ²²⁸ Gamma spectrum of the Th elution chromatogram (A). Using 8M HCl on the same resin ²²⁸ Th elution chromatogram (B). The dashed line at 10mL indicates the start of EDTA stripping solution administration.

FIG. 21 shows (A) ²²⁸ Th activity score as a function of 1M HCl elution volume from TEVA resin of different column internal volumes. (B) It accumulates ²²⁸ Yield of Th activity.

Figure 22 shows the observed activity decay rate for the TEVA resin load fraction (combined load) for 1cc (a) versus 0.25cc (b) vessel volume. The dotted line is ²²⁴ Theoretical decay rate of Ra. And ²²⁴ positive deviation of the Ra curve indicates the presence of breakthrough as a TEVA resin column ²²⁸ Th。

FIG. 23 shows TEVA cartridges for 2cc (A), 1cc (B), 0.4cc HML (half ml) (C) and 0.2cc QML (quarter ml) cartridges (D) ²²⁸ Observed rate of activity decay of Th loaded fraction. The dotted lines for black and gray are ²²⁴ Ra and ²²⁸ theoretical decay rate curve of Th. And ²²⁴ positive deviation of the Ra curve indicates the presence ²²⁸ Th。

FIG. 24(A) shows a TEVA column for a 1cc hand-packed TEVA resin Solid Phase Extraction (SPE) column ²²⁸ Observed rate of activity decay of Th loaded fraction. (B) Shows the accumulation as a function of the 1M HCl elution volume of the column ²²⁸ The Th activity score.

FIG. 25 shows the accumulation as a function of 1M HCl elution volume ²²⁸ Th activity score, this 1M HCl elution volume comes from a machine-filled TEVA resin cartridge with a decrease in internal resin volume. The medicine box comprises (A)2cc, (B)1cc, (C) HML and (D) QML.

FIG. 26 is a HML (0.41cc) and QML (0.25cc) kit evaluated at position C2 ²¹² The Pb removal rate.

FIG. 27 is the 6M HNO during the load + Wash "a" step ₃ From C1+ C2 ²²⁸ Th/ ²²⁴ Gamma spectrum of the Ra solution effluent fraction. The volume of C2 varied between 0.41cc (A) and 0.25cc (B) of Sr resin bed. Colored arrows indicate the radionuclides observable in the fractions: blue ═ blue ²²⁸ Th (absent); gray ═ ²¹² Bi; yellow ═ ²¹² Pb; green ═ green ²²⁴ Ra; orange ═ ²⁰⁸ Tl。

FIG. 27C shows a comparison of metal morphology (speciation) along the same pH spectrum i) Pb/Pb-EDTA; ii) Bi/Bi-EDTA; iii) Th/Th-EDTA; and iv) Ra/Ra-EDTA.

FIGS. 27D i and ii show that using a Ra-01 resin column (3X 50mm) will proceed through the protocol listed in Table 6B ²²⁴ Ra and ²¹² bi and ²¹² and (5) separating Pb. The column effluent fraction categories are indicated at the top. The legend is the number of days elapsed between column run and fraction gamma analysis. (right) the time series of the selection passes represent the radionuclide present on the separation protocol.

FIG. 28 shows (A) the load + wash "a" effluent fraction from 0.25cc Ra-01 resin, showing ²²⁸ Th (arrow), some ²¹² Pb and ²¹² Bi/ ²⁰⁸ elution of Tl. (B) Effluent fraction from wash "b" showing no observable ²²⁸ Th X-ray (arrow). Observe that ²¹² Bi/ ²⁰⁸ Tl is washed off the medium.

FIG. 29 is a load/wash "a" column effluent fraction showing passage through C1+ C2 ²²⁴ Ra elution profile, where C2 is (A) an HML cartridge or (B) a QML cartridge filled with Sr resin.

FIG. 30 shows a view from ²²⁴ Water washed fraction of C3 step 3 inserted before Ra elution step. (A) The gamma spectrum of the C3 effluent fraction collected during the water wash showed ²¹² And removing Pb. (B) The rate of decay of activity observed from the water wash effluent; it and ²¹² the decay rates of Pb are matched. The data show that it is possible to identify, ²²⁴ ra remained adsorbed to the media during the water wash.

FIG. 31 shows the self-loading with ²²⁸ Th/ ²²⁴ Initial stage of Ra-01 resin column (C3) of Ra solution ²²⁴ Observed activity decay rate of Ra elution fraction. The dotted line is theory ²²⁴ The rate of Ra decay.

FIG. 32 is a graphical representation of Ra (II) and Ra (II)/EDTA complex in 0.05M EDTA over a range of pH.

FIG. 33 is a diagram showing a method for converting a light beam from a three-column method ²²⁴ Schematic representation of the procedure for Ra loading onto CatIX Generation column (CatI-based Generator column). By adding small volumes of concentrated acids such as HNO ₃ Or HCl may be purified ²²⁴ Acidification of the Ra/EDTA product solution to achieve a pH of 4 allows ²²⁴ Ra from ²²⁴ The Ra/EDTA complex is released or dissociated. The acidified may then be ²²⁴ Ra ²⁺ The solution is incorporated into the storage/generator container assembly.

FIG. 34 shows EDTA dissociation upon acidification of HCl ²²⁴ Ra ²⁺ Data obtained after loading the product onto strong cation exchange media. ²²⁴ Ra Loading fraction (A)) And the wash fraction (B) is plotted against elapsed time. The legend indicates the collected fractions (1 mL each) of the wash solution delivered through the media-containing vessel. The rate of decay indicates that all during the loading/washing step ²²⁴ Ra can be adsorbed onto the media. (C) With respect to elapsed time ²²⁴ Direct counting of Ra-loaded cation exchange media indicates a time of more than-1.6 days ²²⁴ Ra, where daughter equilibrium occurs first.

Fig. 35 is a schematic diagram of a system for producing free isotopes (monomeric isotopes) according to one embodiment of the present disclosure.

Fig. 36 is a schematic view of a system for producing free isotopes according to another embodiment of the present disclosure. a) From an element separation system ²⁴ R binding element elution line; b) an acid distribution line; c) activated carbon ²²⁰ An Rn well; d)5mL Rezorian ^TM Column w/Spin

PTFE stir bars and hydrophobic Polyethylene (PE) sieve plates (frit ); e) a three-way plug valve; f) a servo motor (SvM); g) a cleaning agent container for pipelines; h) a vertical magnetic stirrer; i) an inverted digital Syringe Pump (SP) w/8-way distribution valve; j) a 0.45 μm Polyethersulfone (PES) filter; and k) ²²⁴ R collecting container.

Figure 37 is an image of a portion of the system of figure 36 configured as an EDTA precipitation/filtration device. a) Activated carbon ²²⁰ An Rn well; b) an acid distribution line from an inverted digital SP; c)5mL of Rezorian ^TM A column; d)

a PTFE stirring rod; e) hydrophobic PE sieve plate; f) an assembled servo motor (SvM) with a servo horn attached; g) a vertical magnetic stirrer; h) a three-way plug valve; i) a 3D printed device base; and j) a pipeline that outputs to the inverted digital SP.

FIG. 38 is pre-acidified ²²⁴ Ra-EDTA (a), acidified and stirred ²²⁴ Ra-EDTA (b) and after acidification and stirring ²²⁴ Image of Ra-EDTA solution (c).

Fig. 39 is an image of a series of configurations of a system for producing free isotopes, according to one embodiment of the present disclosure. (a) Acidifying and stirring ²²⁴ A Ra-EDTA solution mixing, precipitating and filtering container; (b) ²²⁴ r is a collection container; (c) precipitation of filtered EDTA; (d) free form ²²⁴ An Ra solution; (e) line cleaner storage tanks (reservoirs); and (f) an in-line membrane filter.

FIG. 40 is a general schematic diagram for preparing a storage/generation vessel assembly according to one embodiment of the present disclosure.

FIG. 41 is a system for producing a metal storage/generation vessel assembly according to one embodiment of the present disclosure. A syringe pump w/8-way distribution valve (SP); 4-way and 6-way selector valves (V4 or V6); an Assembled Generation Column (AGC); holding coils to 4-way and 6-way valves (HC/V4 or HC/V6); excess Supernatant Coil (ESC); a transport pipeline (TL); large scale mixing vessels (LMVs); a Small Mixing Vessel (SMV); 3 Stopcock Manifold (SM); a servomotor block (SVMB) with three servomotors (SVM1, SVM2, and SVM 3); solenoid control isolation valves (SCIV1 and SCIV 2); and N ₂ Gas regulators (R1 and R2).

FIG. 42 is an image of a system for producing a metal storage/generation vessel assembly according to another embodiment of the present disclosure. The labels are identified in FIG. 41.

FIG. 43 is a graph showing the use of N ₂ An image of a mixing vessel (LMV) of the system of fig. 41 and 42 with gas agitation for mixing according to one embodiment of the present disclosure. A) A resin slurry suction line (outlet); B) n is a radical of ₂ A gas discharge (outlet) port; and C) N ₂ Gas (inlet) line. Five milliliters of a settled resin bed in 20mL of deionized water (DI) was seen in the vial.

Fig. 44A and 44B are images of a mixing vessel (LMV) and blender of the system of fig. 41 and 42 using a Multi-stir mixer according to another embodiment of the present disclosure. A) A resin slurry suction line (outlet); B) a rotating magnet base; C) a vertical magnetic rotation device; D) fabrication vane #1 with alternating 7/16 "diameter holes and edges; and E) manufacturing blade #2 with 3/16 "diameter holes alternating at 5/16" intervals.

Fig. 45 is an image of another mixing vessel (SMV) of the system of fig. 41 and 42, according to one embodiment of the present disclosure. A) ESC (inlet/outlet) lines; B) a resin slurry distributor (inlet) line; C) n is a radical of ₂ A gas discharge (outlet) port; and D) N ₂ Gas (inlet) line.

Fig. 46 is an image of a multi-pass manifold (SM) assembly for use with the systems of fig. 41 and 42. A) And (4) resin screening sieve plates.

Fig. 47 is a schematic view of a series of manifold configurations for use with the systems of fig. 41 and 42 according to one embodiment of the present disclosure.

FIG. 48 shows the use of 2 PSIN without agitation (A) ₂ Image of resin slurry in one mixing vessel (LMV) of the system of fig. 41 and 42 with gas sparging (B).

FIG. 49 shows the use of 3 PSIN without agitation (A) ₂ Image of resin slurry in another mixing vessel (SMV) of the system of fig. 41 and 42 with gas sparging agitation (B).

FIG. 50 is an image of the resin slurry in one mixing vessel (LMV) of the system of FIGS. 41 and 42 uniformly mixed using blade #1 at a Multi-Stirus mixer setting of 60 RPM. A) A resin slurry suction line (outlet); B) a rotating magnet base; and C) a vertical magnetic rotation device.

Fig. 51 is an image of resin slurry in one mixing vessel (LMV) of the system of fig. 41 and 42 with insufficient mixing (a), uniform mixing (B), and over mixing (C). D) Gravity settling resin bed; E) n is a radical of ₂ A gas (inlet) line; and F) ejecting droplets of the resin paste.

FIG. 52 shows color contour plots of calculated (left) and empirically determined (right) dry resin mass dispensed as a function of different flow rates and aspiration volumes. The legend is the delivered dry AG MP-50 resin mass (g).

Fig. 53 is a schematic illustration of stages in the preparation of a storage/generator vessel assembly according to one embodiment of the present disclosure.

Fig. 54 is an image of a storage/generator vessel assembly according to one embodiment of the present disclosure.

Fig. 55 is an image of a storage/generator vessel assembly according to another embodiment of the present disclosure.

FIGS. 56A-56B show images of the thorium-228 decay chain (56A) and radium-224 decay and daughter in-growth (ingrowth) curves (56B) over a 1-day interval.

Fig. 57 illustrates a series of duplicate storage/generator vessel assemblies prepared in accordance with an embodiment of the disclosure.

Fig. 58 is a schematic diagram of a system including both free isotope production and storage/generator vessel assembly production in accordance with an embodiment of the present disclosure.

FIG. 59 shows as loaded into ²²⁴ Ra Single (. smallcircle.) and accumulation (□) of 2M HCl volume on column data as a function of total elution Activity ²¹² Recovery rate of Pb fraction.

FIG. 60 shows the representation as ten consecutive ²¹² Some metals from a single storage/generator vessel assembly as a function of Pb squeeze cycle (squeezing cycle) ((ii)) ²²⁴ Ra) data of Breakthrough (BT). Each extrusion cycle was 1.0mL of 2M HCl followed by 1.0mL of deionized water (DI).

FIG. 61 shows a block diagram according to an embodiment of the present disclosure ²²⁴ Ra/ ²¹² Images of Pb storage/generator container assemblies and supplemental trap bed cartridges.

FIG. 62A shows 2M HCl at-20 mL ²¹² In Pb eluent ²²⁴ Progressive penetration of Ra from different reservoir/generator vessel assembly configurations.

FIG. 62B shows the accumulation of components of 61B ²²⁴ Ra penetrates. In this figure, the first squeeze of the victim has been omitted from the cumulative plot.

FIG. 63A shows fractional use of 2M HCl for four storage/generator vessel assemblies ²¹² Pb elution profile.

FIG. 63B shows the accumulation of the components of FIG. 60A ²¹² Pb activity fraction recoveryAnd (4) rate.

Detailed Description

The present disclosure will be described with reference to fig. 1-63B. Referring first to fig. 1, there is shown a general scheme 2 for production storage and/or generator vessel assembly that may begin with an element separation system/module 3 and continue to a free element production system/module 4 and then to a generator vessel production system/module 5. Embodiments of these systems/modules may be used in the order presented above, or in various combinations, to advantage in the desired manner. For example, a single system/module may be used, or they may be used as a combination of paired systems/modules. For example, as indicated in fig. 1, particular embodiments may use system/module 3 in combination with system/module 5, rather than system/module 4. According to exemplary embodiments, for example, embodiments of the present disclosure provide techniques that can be used remotely or hands-free and automated, enabling the safe and efficient production and transfer of valuable elements, such as radioisotopes.

In general, the element separation system/module 3 may produce one element from another element within a container and then separate it via the system/method of the present disclosure. This separate element may be provided to system/module 4 or system/module 5 as shown in fig. 1. Referring to fig. 2, an exemplary overview of element separation in the case of Th and Th descendants is shown. In accordance with the systems and methods of the present disclosure, Ra can be separated from a mixture of Th and Ra.

Referring again to fig. 1, after separation of the elements as described herein, for example, an element may be produced that complexes or binds with another material. Consistent with the scheme of fig. 2, Ra can be isolated as a complex of EDTA. System/module 4 may provide free elements, such as free Ra. This free element may be provided to the system/module 5 according to fig. 1.

The system/module 5 may be configured to prepare a storage/generator vessel assembly. System/module 5 may receive the separated elements from system/module 3 or the free elements from system/module 4. Consistent with the example of fig. 2, free Ra may be provided to system/module 5, and Pb may be producedAnd/or Bi storage/generator vessel assembly 6. The container may be configured to store elements and generate element children on demand. According to an exemplary embodiment, one may put ²²⁴ Ra and ²²⁸ th is separated and then provided as a storage/generation container assembly 6 as shown. According to an exemplary embodiment, this storage/generation container assembly 6 may be "squeezed" so as to function as detailed herein ²²⁴ Ra/ ²¹² Pb/ ²¹² The Bi generation column utilizes radioactive isotope decay to produce lead and/or bismuth isotopes. The scope of the present disclosure is not limited to Th and Th progeny. Other elements that may be processed/provided using one or more of the systems/modules of the present disclosure may include, but are not limited to: ⁹⁹ Mo/ ^99m Tc； ¹¹³ Sn/ ^113m In； ⁴⁴ Ti/ ⁴⁴ Sc； ⁵² Fe/ ^52m Mn； ⁶⁸ Ge/ ⁶⁸ Ga； ⁷² Se/ ⁷² As； ¹¹⁸ Te/ ¹¹⁸ Sb； ⁸² Sr/ ⁸² Rb； ¹³⁴ Ce/ ¹³⁴ La； ¹⁴⁰ Nd/ ¹⁴⁰ Pr； ⁹⁰ Sr/ ⁹⁰ Y； ¹⁸⁸ W/ ¹⁸⁸ Re； ¹⁶⁶ Dy/ ¹⁶⁶ Ho； ¹⁹⁴ Os/ ¹⁹⁴ Ir； ²²⁶ Ra/ ²²² Rn； ²²⁵ Ac/ ²¹³ Bi； ⁸³ Rb/ ^83m Kr： ¹¹³ Sn/ ^113m In： ¹⁰³ Pd/ ^103m Rh； ¹⁶⁷ Tm/ ^167m Er； ¹⁷² Hf/ ¹⁷² Lu； ¹⁴⁰ Ba/ ¹⁴⁰ La； ¹⁴⁴ Ce/ ¹⁴⁴ Pr； ¹⁰⁹ Cd/ ^109m Ag； ¹⁷⁸ W/ ¹⁷⁸ Ta； ¹⁹¹ Os/ ^191m Ir； ⁶² ZN/ ⁶² Cu； ¹¹⁰ Sn/ ^110m In； ¹²² Xe/ ¹²² i; and/or ¹²⁸ Ba/ ¹²⁸ And (c) Cs. Thus, the present disclosure may have particular utility where the elements form a mixture of elements and progeny of the elements. Thus, the generator container component may include elements and element children, e.g., system/module 3 may be configured to separate element children from an element/element children mixture.

Further, the present disclosure will define the column by the media present in the column. This is considered to be the medium within the container. Thus, when an element is retained or bound to a column, it can be considered to be bound or retained to the medium within the column/vessel.

In addition, chelating agents are described as ligands that bind a metal to more than one coordination site, such as EDTA. Organic compounds that coordinate metal ions to a cyclic structure (chelate ring) are considered to be chelating agents. Most chelating agents contain oxygen, nitrogen or sulfur atoms in their molecules. The chelate structure having a five-membered ring or a six-membered ring forms the most stable chelate ring. More typically, the chelating agent has an organic backbone with functional groups that coordinate to the metal. These functional groups include, but are not limited to, phosphonates, phosphinates, phosphines, sulfonates, carboxylates, imines, and amines. In the chelation reaction of typical chelators, including but not limited to ethylenediamine, acetylacetone, and 8-hydroxyquinoline (oxine), a molecule coordinates with one metal ion. Ethylenediaminetetraacetic acid (EDTA), which has many coordinating atoms, forms a very stable chelate between one EDTA molecule and a metal ion. Chelates based on phosphonic acids may also be used.

According to an exemplary embodiment, all or a portion of the above may be performed hands-free, automated, and/or remotely, as the user may be separated from potentially toxic or harmful elemental compounds, including isotopes, by using a mechanical orientation module. According to exemplary embodiments, for example, the systems and methods of the present disclosure may be performed using mechanical servos and/or pumps (including syringe pumps) that may be operatively and operatively coupled to computer processing circuitry that may operatively control the pumps, servos, and valves in a predetermined manner or remotely through a computer interface.

Exemplary systems and/or methods for producing elements are provided below with reference to fig. 3-32.

Exemplary embodiments of systems and methods for free element production are described below with reference to fig. 33-39, for example. An additional step or procedure that may be completed after production of the free elements may be a system or method for producing a storage/generator vessel assembly as shown in fig. 1.

A system and method for producing a storage/generator vessel assembly is described below with reference to fig. 40-58. A storage/generator vessel assembly produced in accordance with an exemplary embodiment of the present disclosure and use thereof is described with reference to fig. 59-63B of the present disclosure.

The present disclosure provides systems and methods for material separation that can be used to obtain targets for alpha radiation in targeted radioimmunotherapy applications. In one example of the above-described method, ²¹² Pb/ ²¹² the Bi isotope pair shows good prospects. Parent isotope ²²⁴ Ra must be periodically separated from ²²⁸ Th were separated. Then purified ²²⁴ Ra can be used for the preparation ²²⁴ Ra/ ²¹² Pb/ ²¹² A Bi generator. The present disclosure provides a ²²⁴ Ra purification methods, which can be safer and more efficient than prior art methods, leading to lower individual doses, lower labor costs, and reduced preparation time; and may be fully, but at least partially, automated using laboratory fluidics.

Referring to fig. 3, the present disclosure provides systems and/or methods for separating Ra from a mixture comprising at least Ra, Pb, Bi, and Th. As can be seen in fig. 3, there are three containers (C1, C2, and C3), but there may be two or at least one container. These containers may contain a medium. For example, C1 may accommodate medium M1, C2 may accommodate medium M2, and C3 may accommodate medium M3. For example, one or all three of the containers may be in fluid communication via a conduit. For example, each of the conduits may be controlled by one or more valves. Referring to fig. 4, according to an exemplary embodiment, a mixture of Ra, Pb, Bi, and Th (at HNO) may be provided ₃ Th/Ra + ("+" may have subsequent progeny)) in container C1-C3, and thus M1-M3. The respective media may be different from each other.

Thus, the medium may be (in fluid introduction order, and as shown in Table 1) AnIX-M1(AG MP-1M, Bio-Rad, or TEVA resin, Eichrom); in 1-octanol diluents18-crown-6 ether-M2 (Sr resin, Eichrom); m3(Ra-01 resin, IBC Advanced Technologies). In accordance with an exemplary embodiment of the present invention, ²²⁸ Th/ ²²⁴ Ra/ ²¹² Pb/ ²¹² bi/etc. can be in strong HNO ₃ (. gtoreq.6M, however, low levels of 0.5 to 1M or even 2M HNO may be employed ₃ Concentration of (d) through all three vessels; can deliver 3 columns of detergent (strong HNO) ₃ ) And Th + Bi remains partially in C1; pb remains in C2; ra remains in C3 (the system configuration of which is shown as (a) in fig. 4.

Accordingly, the system of the present disclosure may include: a first container (C1 or C2) containing a first medium and containing Pb or Bi and/or Th; and a second vessel in fluid communication with the first vessel, the second vessel containing a second medium and Ra (C3), wherein the first medium is different from the second medium. Additionally, the system of the present disclosure may include: a first container (C1) containing a first medium and Th and/or Bi; and a second container in fluid communication with the first container, the second container containing a second medium and Pb (C2), wherein the first medium is different from the second medium. Embodiments of the present disclosure may also include a system having: a first container (C1) for containing a first medium and Th or Bi; a second container in fluid communication with the first container, the second container containing a second medium and Pb (C2); and a third vessel in fluid communication with the second vessel, the third vessel containing a third medium and Ra (C3), wherein at least one of the first medium, the second medium, or the third medium is different from the other medium.

There is also provided a method, which may comprise: providing a mixture having Ra, Pb, Bi, and/or Th; providing the described system having a vessel (C1) containing medium (M1) and a vessel (C2 or C3) in fluid communication with vessel (C1), wherein vessel (C2 or C3) contains medium (M2 or M3); exposing the mixture to a medium (M1) within a vessel (C1) to separate Th and Bi from Ra and Pb; the remaining mixture is then exposed to the medium (M2 or M3) in a vessel (C2 or C3) via fluid communication to associate Pb or Ra with the M2 or M3 medium. According to exemplary embodiments, Th (with Bi) of C1 can be eluted from M1 in strong HCl to be dried or stored for reuse as needed.

Additionally, as shown and described, the vessel (C3) may be in fluid communication with the vessel (C2), and the vessel (C3) may contain the medium (M3). The method may include: exposing the mixture to medium (M1) within a vessel (C1), then, by fluid communication, exposing a first remainder (which is through C1 or washed through C1) to medium (M2) in vessel (C2), then, by fluid communication, exposing a next remainder (which is through C2 or washed through C2) to medium (M3) in vessel (C3), said exposing separating Th and Bi from Ra and Pb, and separating Ra from Pb to sequester Th and Bi in one vessel, sequester Pb in another vessel, and sequester Ra in yet another vessel.

In distributing material within the system, referring to configuration B of FIG. 3, less or weaker HNO is used ₃ (< 7M, between 2M and 7M, or < ═ 6M, and in some embodiments, 0.5 to 1M HNO ₃ ) Washing vessels C2 and C3. According to an exemplary embodiment, in configuration C, M3 may then be washed with water to remove H ⁺ Excess Pb. In configuration D, Ra can be eluted from M3 (which associates with Ra) with dilute EDTA solution (pH adjusted to > 7) or chelating solution with a binding constant higher than that of M3 resin in C3. For example, according to FIG. 32, Ra is-100% EDTA-bound at pH-6 and-50% EDTA-bound at pH-5.3. Thus, the methods of the present disclosure provide for separating Ra from association with a medium by exposing the Ra and the medium to a chelating agent to form a mixture comprising the Ra complexed with the chelating agent.

Ra/EDTA product solution and the CatIX series of column loading incompatible. Addition of sufficient HCl to the Ra/EDTA solution to lower the pH to below-2 (Ra is released from EDTA at pH 4 according to FIG. 32. by pH 2, EDTA is insolubilized and precipitated leaving Ra in the supernatant) allows decoupling or dissociation of Ra from EDTA (thereby producing free Ra in solution) ²⁺ Ions). The weakly acidified Ra can then be reacted ²⁺ The solution was adsorbed onto a CatIX lineage generation column.

The systems and methods of the present disclosure can provide for separation and dissociation ²²⁴ Ra product, which can be loaded onto a CatIX generation column. Embodiments of the present disclosure may be performed without a concentration or acid displacement (acid displacement) step. Purified Ra (without) can be purified at low doses ²¹² pb and ²¹² bi progeny) for several hours. This may enable packing of the generating column before the dosage becomes problematic, removing the column from the containment vessel, and packaging it for shipping. Additionally, the present disclosure also provides a fluidic system for performing the method. This may provide a fluidic platform.

TABLE 1 according to ²²⁴ Ra and ²²⁸ commercial resins evaluated by the three column procedure for Th separation.

a. Functional group: quaternary amines on macroporous polystyrene divinylbenzene copolymers.

b. Functional group: aliquat 336, an organic quaternary ammonium salt on Amberchrom CG-71 ("prefilter") polymer support.

c. Functional group: 18-crown-6 and 1-octanol on Amberchrom CG-71 polymer support.

d. Functional group: is proprietary; presumably 21-crown-7 (partially) on a silica support.

An example overall fluid scheme for a modified three column process is shown in tables 2 and 3.

TABLE 2 for ²²⁴ Ra from ²²⁸ Protocol for improved three-column purification in Th. Exemplary resins and column volumes are included. a is

C1 ═ 1cc TEVA resin; c2 ═ 0.25cc Sr resin; c3 ═ 0.25cc Ra-01 resin.

b. ²²⁸ Th and ²²⁴ ra and progeny.

The pH was adjusted to 11.

TABLE 3 description of the steps of the schematic of FIG. 3.

During step A, the prepared ²²⁸ Th/progeny stock solution (at 6M HNO ₃ Middle) through three columns each fluidly interconnected. 6M HNO ₃ The concentration may provide a high affinity of Th on the AnIX medium (1) and a high affinity of Pb on the Sr medium (M2). During the loading step, Th (and Bi/Tl daughter) was adsorbed on M1, Pb on M2, and Ra on M3.

After loading the solution is washed "a", comprising 6M HNO ₃ . This can provide complete fluid transport of the loading solution through three columns in series.

The effect of the step a process is confirmed by the gamma energy spectrum in fig. 5. In this case, M1 is AnIX _poly . The solution can be delivered to three columns at 1 mL/min. Can be combined with ²²⁸ Th/progeny loading (a) and initial "wash a" solution (B) three column effluent fractions were collected in tubes and counted by gamma spectrometer. No activity from fractions passing through all three columns was observed during the loading and washing "a" steps; all activity was adsorbed to the column.

In addition, direct gamma counting of C1 immediately after completion of the load/wash "a" step indicates the presence ²²⁸ Th、 ²¹² Bi and ²⁰⁸ tl (FIG. 5C). Not observed on M1 ²¹² Pb or ²²⁴ Ra gamma peak because these radionuclides have adsorbed onto M2 and M3, respectively.

Confirmation may be made by evaluating the wash "a" effluent fraction split from C3 ²²⁴ Ra flows from C1 and C2. While in FIG. 6, pure in the C2 effluent can be observed ²²⁴ Ra and trace amounts ²¹² Bi and ²⁰⁸ tl. The trace 212Pb peak is visible at channel 80. Is totally absent ²¹² The Pb line indicates good collection efficiency of Pb on Sr resin (C2).C2 combined ²¹² Any new in-growth of Pb ²¹² Bi and ²⁰⁸ the Tl daughter may not remain on M2 during this step, but is carried away from C2 and through C3 to waste.

M2 functions through C1 ²¹² Pb/ ²²⁴ Adsorption of Ra mixtures ²¹² And Pb. HNO at various molar concentrations ₃ The 18-crown-6 ether extractant on Sr resin has a strong affinity for pb (ii) ions and a low affinity for ra (ii) ions and bi (iii) ions (see fig. 7 and 8). Therefore, the temperature of the molten metal is controlled, ²²⁴ ra may pass through Sr resin, thereby being collected on M3. At M2 ²¹² Any generation of Pb ²¹² Bi/ ²⁰⁸ TI does not remain, and will be equal to ²²⁴ Ra flows out together from C2 to C3. Because of the fact that ²¹² Bi/ ²⁰⁸ TI likewise does not remain on M3, so it will reach waste, but ²²⁴ Ra is loaded.

In step B, C1 can be disconnected from the chain of containers and kept static until the end of the process, at which point the adsorbed is recovered by a separate elution step as step E ²²⁸ Th. By breaking, fluid communication is simply cut off, but the conduits associated with C1 and C2 may remain.

Including 2M HNO ₃ Wash "b" of (a) can be passed through C2 and C3 to ensure quantitative transfer of Ra from C2 to C3. Pb strongly binds to M2 and remains there. 2MHNO may be used in this step ₃ This is because it provides a high level of affinity for Pb on Sr resins.

At 2M HNO ₃ Ra has a low level of affinity for Sr resin (M2) (k' ≈ 2, fig. 8). This is evidenced by the slight delay in Ra during the load/wash "B" step shown in fig. 8 (B). Here, the number of the first and second electrodes, ²¹² the Bi trace indicates that the ion not retained (k' < 0.4) is in ²²⁴ Ra was passed through the vessel before passing. Due to this slight Ra/resin affinity, washing "b" may require a volume of-10 mL to ensure Ra passes completely through the Sr resin column.

The wash "b" process data is shown in fig. 9 (a). The C2/C3 effluent fraction is not shown ²¹² Pb or ²²⁴ Evidence of Ra penetration from these columns.Once the washing "B" is completed, FIG. 9(B) shows that pure 21 is observed on the Sr resin column (C2) ² The Pb spectrum.

Referring next to FIG. 10, in step C, C2 may be disconnected from C3 because M3 now contains a split ²²⁴ And (5) Ra fraction. Again, disconnecting does not remove the conduit connecting containers C2 and C3, but simply prevents fluid flow through the conduit.

Water may be flushed through C3 to remove HNO from the system ₃ . During water rinsing, Ra remains strongly bound to M3, since the affinity of Ra for Ra-01 resin generally follows HNO ₃ The concentration decreases and increases. In addition, water washing by C3 may result in removal of water that may have settled on the column ²¹² And Pb. This is achieved by ²¹² Pb may be derived from C2 penetration, or from M3 binding ²²⁴ New ingrowth of Ra production ²¹² And Pb. A series of five 1mL water effluent fractions were collected and analyzed by gamma spectroscopy. Removal from C3 during water washing is shown in FIG. 11(A) ²¹² And Pb. Water-grade freedom was determined by evaluating the rate of water-grade decay deceleration over time ²²⁴ And Ra. Rate of activity loss and ²¹² the Pb decay factors agree (fig. 11 (B)). This indicates that during the water wash ²²⁴ Ra is not in contact with ²¹² And (4) carrying out Pb co-elution.

Because of the fact that ²²⁸ Th、 ²¹² Bi and ²⁰⁸ tl is locked to M1 of the now disconnected C1 container, and ²¹² pb was locked to M2 of C2, now open, and a trace on M3 ²¹² Pb was removed during the water washing, so the separated bound to M3 ²²⁴ Ra has a low associated dose rate. This is temporary, because ²²⁴ Ra progeny in-growth rapidly increased the dose on M3.

Referring next to FIG. 12, in step D, 5mL of 0.05M EDTA (which has been adjusted to pH 11 using NaOH) is used to elute on M3 ²²⁴ And Ra. The column effluent fractions were collected and gamma spectrometry was performed. The resulting radiochromatogram is shown in fig. 13 (a). Therein, the ²²⁴ In Ra elution, four ml contained the majority ²²⁴ Ra Activity (higher concentrations of EDTA or stronger chelators or smaller cartridges are suspectedThe product resulted in a more sharp 224Ra elution peak).

For the series over a period of-35 days ²²⁴ The Ra eluted fractions were counted repeatedly to measure the decay rate and evaluate the separated ²²⁴ Radionuclide purity of Ra. FIG. 13(B) shows that, over several orders of magnitude, the decay rate of activity of C3 eluted product is consistent with theory ²²⁴ The rate of Ra decay. Importantly, the decay rate data showed a drop to at least-0.1% of the initial activity fraction at ²²⁴ Absence in Ra product fraction ²²⁸ Th。

Referring next to FIG. 14, recovery from M1 of C1 may be performed ²²⁸ Th. According to an exemplary embodiment, a method for separating Ra from Pb, Bi, and Th may include separating one or more of Bi and/or Th from Ra. This separation may associate Th and/or some Bi with the medium (M1). The method may further comprise dissociating Bi and/or Th from the first medium (M1) to form a mixture comprising Bi and Th, and transferring the mixture to a vessel containing at least Ra and additional Bi and/or Th. According to some embodiments, this container may be considered as a "cow container" (cow), which generates, by attenuation, a further Ra that may be used to start step a. According to an alternative embodiment, to avoid a large radiation dose to the C1 resin, Th may be eluted and kept separate from the polymer-based AnIX resin of C1.

From AnIX Using 5mL of 8M HCl _poly Medium (M1) elutes Th. (from 1M to 12M, Th may elute). About 8M is sufficient if the concentration is sufficient to elute Bi and/or Th. Fig. 15(a) shows the spectrum obtained from these Th elution fractions. The first and second elutions showed the majority of Th recovered. In addition, it was observed that, in the case of, ²¹² bi and ²⁰⁸ tl and ²²⁸ th co-elute together, mainly in the first elution fraction. In 5mL of 8M HCl transport, it was not possible to remove the compound from AnIX _poly Complete recovery of the medium (M1) ²²⁸ Th. Direct counts after C1 elution indicated that a fraction of Th remained on the column, fig. 15 (B). Therein, the ²²⁸ After Th retention observation, 5mL of 0.05M EDTA (pH 3.5) was passed through C1. This secondary elution process may provide for the removal of Th from M1.

Referring next to fig. 16 and 17, a fluidic system capable of performing the methods of the present disclosure in a fully automated manner is provided. The fluid system configuration is provided as a schematic in fig. 16. The system is designed with eyes for operation remotely or in shielded facilities. Two digital syringe pumps (SP1, SP2) are responsible for reagent delivery to the containers (C1, C2 and C3); these pumps may be located outside the shielded region to eliminate the possibility of radiolytic or chemical degradation.

A third syringe pump (SP3) may be within the shielded area. For example, the pump may include a stepper motor and a disposable plastic syringe. The SP3 has the function of ²²⁸ The Th "cow container" solution (e.g., the first mixture) is extracted into the sample injection loop indicated at the top of fig. 16 and in fig. 17(B) (upper left of the figure). Once the cow containers are loaded into the loop, a digital syringe pump located outside the shielded area can access the cow container solution in the loop and direct it through the column.

Since the stepper motor can drive the syringe pump with a voltage signal from outside the shielded area, and the stepper motor has no integrated circuit inside it, the likelihood of radiolytic degradation of this component is small. For example, 208R/hr may be used in a hot chamber ¹³⁷ The Cs source illuminates two of these stepper motors. The motor received a total dose of 33,700R over a period of 6.75 days. Testing the function of each motor after removing the motor from the hot cell; both remain functional.

Fluids can be routed through a number of paths using, for example, teflon FEP tubing and solenoid actuated valves, for example, characterized by fluoropolymer wetted surfaces (fig. 18 (B)). Because the solenoid is electromagnetically driven by a voltage applied from outside the shielded area, the possibility of radiation-based component failure is low. The fluid system may be used conventionally ²²⁸ Th/ ²²⁴ The Ra spiking solution was used in a radioactive fume hood (or in a glove box or shielded location using multiple mCi levels of 228Th/224 Ra).

Comparison between 1M and 8M HCl at AnIX _poly On resin ²²⁸ Th elution Performance. The results are shown in fig. 18.

As shown, in AnIX _poly On a resin column, 8M HCl showed better than in 1M HCl ²²⁸ Th elution Performance. TEVA resin is an extraction chromatography resin loaded with organic quaternary ammonium salt Aliquat 336. Evaluate ²²⁸ Th loading/wash "a" on 1cc TEVA resin column/elution performance. Reuse of 6M HNO ₃ Load/wash "a" was performed and elution was performed with 1M and 8M HCl.

Relative to C1(1cc TEVA resin) ²²⁸ The Th loading/wash "a" performance is shown in fig. 19(a and B). No discernible identification was observed ²²⁸ Th breakthrough. With respect to the MP-1M resin, ²¹² bi and ²⁰⁸ tl has a low retention; they begin to penetrate the column at the third loading/washing of the "a" fraction.

The subsequent C1 from TEVA resin with 1M (FIG. 20(A) and 8M HCl (FIG. 20(B)) is shown ²²⁸ Th eluted. Here, relative to that obtained from a stronger HCl concentration eluent ²²⁸ Th recovery, reduced HCl concentration resulted in improved ²²⁸ And (4) recovering Th. The use of lower concentrations of HCl is advantageous in a shielded environment because less corrosion of the containment vessel and equipment is expected.

The elution of 1M ((A)/(B)) and 8M ((C)/(D)) HCl from FIGS. 18(MP-1M) and 20(TEVA resin) is provided in Table 4 ²²⁸ Fractions were recovered by elution from a 1cc column of Th. From this table the following conclusions can be drawn: optimum results from TEVA resin column using 1M HCl as the elution solution ²²⁸ And (4) eluting and recovering Th.

TABLE 4. for MP-1M and TEVA resin columns (1cc) in 1M and 8M HCl as a function of-1 mL elution fraction volume ²²⁸ Th column yield (%). The major recovery fractions are indicated in bold face.

a. Cumulative activity fraction from 5mL 0.05M EDTA (pH 3.5) strip applied at the end of HCl elution.

As shown in Table 4, at 6M HNO ₃ In the matrix, the base body is provided with a plurality of grooves,the TEVA resin and MP-1M may have about the same adsorption from the loading solution ²²⁸ The ability of Th. 8M HCl provides better (but not complete) conversion from MP-1M relative to 1M HCl ²²⁸ Th eluted. TEVA resins can provide improvements in both 1M and 8M HCl ²²⁸ Th elution profile. From TEVA resins in 1M HCl relative to 8M HCl ²²⁸ Th elution profile was better.

Other pillar geometries and volumes may also be employed. For example, the above 1cc SPE column geometry (0.56X 4.1cm) and 0.61X 0.865cm (0.25cc volume, QML cartridge).

The evaluation results are shown in FIG. 21(A), in which ²²⁸ Th elution profiles are plotted (fractions aged 32 days to allow for ²²⁸ Th progeny in-growth). The smaller volume of the column results in an earlier ²²⁸ Th is released; after 3mL of the eluate was obtained, ²²⁸ the Th yield reached-96% (FIG. 21 (B)). In contrast, the 1cc column started its elution at the 2 nd 1mL fraction, and after 3mL elution, the recovery reached-94%. These recoveries are within experimental uncertainty of each other.

Using the same ²²⁸ Th Loading solution (6M HNO) ₃ ) Parallel column evaluation was performed through 1cc and 0.25cc TEVA resin columns. Will contain ²²⁴ The loaded effluent of Ra was collected and aged for a period of more than-1 month. Can be used with ²²⁴ The decay rate of the TEVA effluent fraction of Ra is determined relative thereto ²²⁸ Purity of Th. The results are shown in FIG. 22(A) for 1cc and in FIG. 22(B) for 0.25cc TEVA media. Comprises ²²⁴ Ra fraction decay Rate and theory ²²⁴ There are differences in Ra decay rates, over-28 days for a 1cc column and over-12 days for a 0.25cc column. The 0.25cc column showed significantly larger during the loading step compared to the 1cc column ²²⁸ Th breakthrough.

TABLE 5 according to ²²⁸ TEVA resin cartridges and columns for Th adsorption, desorption and breakthrough evaluation. ^a

a. Some of the column chambers are slightly conical cylinders; the reported volumes are based on truncated cones.

b. Normalized values with respect to a 1cc SPE column

c. The passage time of the material in the resin bed is not retained.

Hml ═ half a milliliter "

QML ═ one-quarter milliliter

In both cases, the column effluent fraction was aged for more than 30 days to allow for near completion ²²⁸ Th progeny in-growth. Using the obtained ²²⁸ Quantification of Th + progeny Gamma spectra in fractions ²²⁸ Th activity.

The four TEVA resin cartridges and TEVA resin SPE columns listed in Table 5 received the same in 6M HNO ₃ In (1) ²²⁸ Th admixture solution. The flow rate was 1 mL/min. The C1 effluent was collected and aged for up to two months. During this time, track each packet ²²⁴ TEVA of Ra Loading/washing the decay Rate of the "a" effluent fraction to determine it relative to ²²⁸ Purity of Th. The results for the four machine-filled cartridges are shown in fig. 23, and the results for the hand-filled 1cc SPE tubes are shown in fig. 24 (a).

Thus, in 1M HCl, after 3mL elution volume, 1cc and 0.25cc TEVA resins provided approximately the same ²²⁸ Th elution yield (FIG. 21). 1cc of TEVA resin retains a greater portion during the load/wash "a" step as compared to a 0.25cc column volume ²²⁸ Th, since some were observed ²²⁸ Th penetration (fig. 22). Thus, 1cc of TEVA resin provides higher purity ²²⁴ The Ra fraction was passed into the remaining fluid system.

As the volume of the cartridge bed decreases, the measured activity value of the column-loaded fraction may begin to deviate from the theoretical value at progressively shorter elapsed times ²²⁴ Ra decay curve. These observed decay curves may deviate from the inclusion ²²⁴ In the column-loaded fraction of Ra ²²⁸ An increase in Th levels is associated. Next, one can fit over data points that have passed over 40 days ²²⁸ A Th decay profile. Extrapolating the curve to the y-intercept to provide a solution containing ²²⁴ Present in column-loaded effluents of Ra ²²⁸ Estimation of Th activity score. Observe calculation ²²⁸ The Th activity score increased with decreasing TEVA kit volume (figure 23, grey dashed line also shows this phenomenon).

Of these calculations ²²⁸ Th activity scores are provided in table 6A. From which can be obtained ²²⁴ In TEVA column Loading fraction of Ra ²²⁸ Th purification factor (DF). QML kit (minimum TEVA resin bed volume evaluated) has an unexpectedly high calculation of-1.6% ²²⁸ Th load/wash "a" breakthrough (DF 61). For the maximum bed volume (2mL) kit, this breakthrough fraction can be reduced to 0.018% (DF 548).

Table 6a. observed performance of TEVA resin column/cartridge for resin bed geometry listed in table 5: ²²⁴ in the Ra elution fraction ²²⁸ Th purification factor (DF), and from Loading/washing/elution Process ²²⁸ The yield of Th was found.

a. Based on ²²⁸ Th "load" fraction decay profile values.

b. By ²²⁸ Reciprocal derivation of Th Activity scores

c. Values based on the sum of column load/wash/elution fractions (see cumulative yield traces in fig. 22 and fig. 23).

Hml ═ half a milliliter "

QML ═ one-quarter milliliter "

Notably, four TEVA resin cartridge type load/wash "a" effluent when modeled relative to the resin bed volume of each cartridge (provided in Table 5) ²²⁸ The Th activity score follows a negative power function. The modeling curve is that y is 0.00268x ^-1.1112 (R ² 0.9797) and a 1cc SPE tube activity score does not follow this curve.

It should be noted that the data presented may indicate that the hand-filled 1cc SPE tube provides the highest yield ²²⁸ Th purification factor (evenHigher than 2cc TEVA kit).

Second kit/column Performance evaluation for evaluation ²²⁸ Quality of Th elution profile. After the load/wash "a" solution had been delivered to each TEVA kit shown in Table 6A, elution was performed with 10mL of 1M HCl delivered at 1mL/min ²²⁸ Th. Fractions of approximately 1mL were collected. Illustrating the accumulation of TEVA resin in the four TEVA resin cartridge types in FIG. 25 and the SPE column in FIG. 24(B) ²²⁸ Yield of Th fraction.

²²⁸ The Th elution profile coincides with the expected peak broadening associated with an increase in volume of the TEVA resin bed. However, even for the largest (2mL) TEVA kit, ²²⁸ th recovery is also almost complete after the third fraction. Of 1cc SPE tubes ²²⁸ The cumulative yield of Th is shown in fig. 24 (B); the yield is likewise almost complete after 3mL of eluent. Calculated from the sum of all loading/washing/elution fractions ²²⁸ The Th elution yields are shown in table 6A. 94% to 98% of ²²⁸ Th elution yield, and this range is within experimental uncertainty.

Machine filled/commercially available TEVA kits ²²⁸ Th penetration levels increase with decreasing bed volume. The hand-filled 1cc SPE tubes provided the lowest relative to the kit ²²⁸ The degree of Th penetration. The TEVASPE container and kit appeared to be almost complete after 3mL of 1M HCl eluent had been delivered at 1mL/min ²²⁸ Th eluted. In summary, a hand-packed 1cc SPE TEVA column provides high purity relative to a machine-packed TEVA cartridge ²²⁴ The Ra fraction.

Media M2, in HNO ₃ The 18-crown-6 ether extractant on the Sr resin column has a strong affinity for Pb (II) ions and a low affinity for Ra (II) ions and Bi (III) ions. Therefore, the number of the first and second electrodes is increased, ²²⁴ ra can be collected on C3(Ra-01 resin) through Sr resin column. And ²²⁴ ra together through C2 ²¹² Bi and ²⁰⁸ TI is likewise not retained on column 3, so that the resulting dose of radionuclide pairs is sent to waste, while ²²⁴ Ra is loaded. Through C2 ²¹² Pb removal and after C3 ²¹² Bi/ ²⁰⁸ TI diversion to waste can be reduced by ²²⁴ Ra progeny provides the radioactive dose.

As shown in FIG. 26, HML (0.41cc) and QML (0.25cc) kits, both from Eichrom, can be used for M2. The Sr-resin-containing drug cassette was loaded into the C2 tank in the three-column system, and the C1 tank was configured to have a 1cc TEVA resin column. C3 was not installed. The flow rate was 1 mL/min. Collect C1 → C2 effluent fractions of-1 mL each during the column load + wash "a" step, where the loading solution is at and ²²⁴ with long-term equilibrium of RA and its progeny ²²⁸ Th。

The results for 0.41cc HML and 0.25cc QML cartridge effluents are shown in fig. 27(a) and 27(B), respectively. The gamma spectra (fig. 27) are nearly identical; in both cases of the above-mentioned situation, ²¹² pb is smoothly contained ²²⁴ The stream of Ra is washed away. The volume of the kit is between 0.41cc and 0.25cc, and is in the range of ²²⁴ Ra removal from a charge stream ²¹² At Pb, each of them behaves almost identically.

In accordance with another exemplary embodiment of the present invention, ²²⁸ Th/ ²²⁴ ra can be provided directly as a solution through C3, and the C3 effluent fraction collected throughout the process.

Referring to fig. 27(C) and (D) and table 6B below, according to yet another embodiment, C2 may be removed from the three-column process. In the absence of C2, both Pb and Ra emerging from the AnIX column may bind to the Ra-01 column and separate Ra therefrom. The Pb can be selectively removed from the column using a chelating agent, such as EDTA, which is adjusted to a pH below the value at which the ra (ii)/EDTA complex is formed. According to fig. 32, Ra is not complexed with EDTA at a pH below-4. However, pb (ii) is fully complexed with EDTA at a pH above about 2, with 50% complexing at a pH of about 1.3. Thus, a solution of EDTA at pH 3.5 may be provided through the column, which selectively complexes ²¹² Pb and eluting it from the column while simultaneously eluting it ²²⁴ Ra remained on the column (the Pb/EDTA complex was retained at a much lower pH, so the Pb/EDTA complex was 100% formed at pH 3.5). Next, a solution of EDTA at pH 11 (or at a pH greater than 6) may be provided to C3Liquid to remove Pb-free ²²⁴ Ra。

FIG. 27C shows a comparison of metal morphology along the same pH spectrum i) Pb/Pb-EDTA; ii) Bi/Bi-EDTA; iii) Th/Th-EDTA; and iv) Ra/Ra-EDTA.

FIGS. 27D i and ii show that using a Ra-01 resin column (3X 50mm) the protocol outlined in Table 12 will be followed ²²⁴ Ra and ²¹² bi and ²¹² and (5) separating Pb. Column effluent fraction categories are designated at the top. The legend is the number of days elapsed between column run and fraction gamma analysis. (right) the time series of the selection passes indicates the presence of the radionuclide on the separation protocol.

TABLE 6B. for ²²⁴ Loading Ra solution on Ra-01 resin column, and eluting ²¹² Pb and elution ²²⁴ Scheme Ra. ^a

a. The solution flow rate is 0.5 mL/min; the column size was 3 × 50mm (0.35 cc).

b. The volume consumed is correlated to the subsequent column effluent gamma activity map.

The loading + washing "a" fraction gamma energy spectrum is shown in fig. 28(a), and the washing "B" fraction is shown in fig. 28 (B). Can be eliminated from the Ra-01 column during the washing "a" step ²²⁸ Th. During the washing "b" step, no evidence was evident ²²⁸ Th； ²²⁸ Th has been largely eliminated from C3. This data indicates any that may penetrate C1 and enter the downstream fluid system during the load/wash "a" step ²²⁸ Th would pass through the Ra-01 resin without retention.

The spectra in FIG. 28 also show ²¹² Bi/ ²⁰⁸ The majority of Tl was not retained on Ra-01. Is apparently absent in the Ra-01 effluent fraction ²¹² Pb； ²¹² Pb remained on the Ra-01 resin (which is why C2(Sr resin) was upstream of the Ra-01 resin column to back-extract it).

According to an exemplary embodiment, the water wash may be located at wash "b" and ²²⁴ between Ra elution steps. The water is used at an introduction pH of-11 ²²⁴ Removal of residual H from the column before Ra elution solution ⁺ Ions.

0 it is preferred that the wash "a" volume be sufficient to ensure ²²⁴ Ra passed through C1 and onto C2/C3 (step A), and wash "b" volume was sufficient to ensure ²²⁴ Ra passed through C2 and onto C3 (step B). Thus, the volume of the load/wash "a" shown in fig. 29 is more than sufficient to achieve the goal of step a.

The effect of water washing through the Ra-01 resin is shown in FIG. 30 (A). ²¹² Pb (retained on the Ra-01 column due to the absence of upstream C2 in this experiment) was removed from the vessel in water. Evaluation of the decay rates of these column effluent fractions indicated the absence ²²⁴ Ra (fig. 30B). Thus, it was shown that water washing can be used to eliminate excess H ⁺ Ionic (preventing EDTA precipitation) and further removal from Ra-01 resin ²¹² Pb (thereby lowering ²²⁴ Ra product dose) without affecting ²²⁴ Ra elution yield.

After water washing, Ra-01 resin contains ²²⁴ And Ra. Elution with EDTA solution ²²⁴ Ra, and the decay rate of the elution fraction is monitored to assess its radionuclide purity.

The results presented in FIG. 30 indicate that in washing "a" and ²²⁴ addition of water wash between Ra elution for H + ion elimination from the column, which in turn eliminates alkaline EDTA lines ²²⁴ Acidification of the Ra eluent. In addition, water washing was observed to remove from the column ²¹² Pb, and ²²⁴ ra is preserved.

The results presented in FIG. 31 show that in this experiment, Ra-01 resin was used ²²⁴ Ra and ²²⁸ single column (C3) separations of Th can achieve-1000 fold purification factors (purification factor determination is limited by the dynamic range of the assay). In other words, it is expected to ²²⁴ Ra eluate find 0.1% of any that managed to penetrate C1 during the Loading/washing "a" step (two steps in which all three columns were connected to each other) ²²⁸ Th. Consider C1 ²²⁸ The Th retention factor is at least 500. If so, then the wholeIn the three-column method ²²⁸ Th purifying factor is not less than 5 × 10 ⁵ 。

Although it is not limited to ²²⁴ Radionuclide purity of Ra is important in providing robust isotope products, but equally important is that the output of the three-column process is compatible with existing and future ²²⁴ Ra/ ²¹² A Pb generator.

For the existing ²²⁴ Ra/ ²¹² The design of the Pb generator is characterized in that, ²²⁴ the Ra source was loaded onto a CatIX resin column (using AG MP-50 resin beads). Thus, the Ra output of the three-column process should be suitable for direct loading onto CatIX resin. Unfortunately, the purified Ra product delivered in dilute EDTA solution (pH adjusted to > 7) does not bind to CatIX resin as free divalent cations; according to the morphology of the Ra/EDTA mixture (FIG. 32), Ra completely binds EDTA above pH 7. When the pH is raised above 7, the chelated complex may be selected from [ Ra (EDTA)] ^- Development into [ Ra (EDTA)] ^2- . However, at pH values close to 5, the Ra/EDTA complex is-50%, and at pH values ≦ 4, Ra ²⁺ The cation is completely dissociated from the EDTA complex.

Referring to FIG. 1 above and to module 4, free element production, systems and/or methods for producing free elements are provided. The system/method can include providing a mixing vessel in fluid communication with a source of a binding element and a source of an acid. The mixing vessel may be operably configured to mix the contents of the mixing vessel. The system can include a first multi-way valve operably engaged with the outlet of the mixing vessel, and a second multi-way valve operably engaged with the first multi-way valve, the acid source, and the collection vessel.

As detailed below, the element can be Ra, however, as described above, other elements can be processed using these systems and/or methods.

Methods of producing free elements from bound elements are also provided. The method may include: providing a solution comprising an element bound to a complex; exposing the solution to a precipitation solution to precipitate a complex of the bound element and produce a solution of the free element; and transferring the free element solution to a collection vessel.

The system/method may include separating Ra from a solution comprising Ra and Th to form a solution comprising Ra bound to EDTA. The solution of Ra bound with EDTA has a pH greater than 11, and the free element solution may contain Ra and have a pH less than 4 or even less than 2.

As provided herein, will ²²⁴ A reduction in the pH of the Ra/EDTA product solution to 4 or less will result in free Ra in the solution ²⁺ A cation. FIG. 33 is a schematic representation of a process for preparing free Ra ²⁺ And free Ra ²⁺ An on-column approach to binding to AG MP-50 CatIX resin.

21.7. mu.L of concentrated HCl (0.26 mmole of H added) may be used ⁺ ) Separating the separated fractions from the three-column separation ²²⁴ One mL of Ra product (5mL) was acidified. Next, the acidified solution can be delivered to the MP-50 resin at 0.5 mL/min. The data in fig. 36(a) shows the activity observed in the column-loaded effluent fraction (as a function of elapsed days). There was little activity in the column effluent solution. After media loading, the media can be washed with four 1mL portions of dilute HCl solution (fig. 34 (B)). Elution of the short-lived daughter isotope can be observed immediately after collection of the fractions; the isotope may decay away within the first-0.18 days (-4 h) and this indicates that there was no wash period ²²⁴ Ra was exuded. Continuous counting of CatIX media within 7 showed more than-1.6 days ²²⁴ Characteristic decay rate of Ra (fig. 34 (C)).

The results in FIG. 34 show that the product isolated by the three-column method ²²⁴ Acidification of the Ra product fraction may provide ²²⁴ Quantitative loading of Ra onto CatIX media. Thus, the three-column process appears to be well suited for subsequent steps by a solution acidification step ²²⁴ Ra/ ²¹² And preparing a Pb generation column.

As can be seen in fig. 35, free isotope(s) is shown ²²⁴ Ra ²⁺ ) At least one schematic of the preparation of (a). The chemical modification chamber or mixing vessel may receive bound isotopes (D), e.g., directly from the three-column process (step D of fig. 12, above) ²²⁴ Ra/EDTA) eluent. In this chamber, an acid may be injected to mixThe pH of the solution is lowered to a value at which the Ra/EDTA complex is eliminated or decoupled, thereby producing free isotopes in the solution: ( ²²⁴ Ra ²⁺ ) Ions (see fig. 32). The acid may be mixed into using a stirring rod ²²⁴ Ra in the eluent.

If the solution is acidified to a pH of < -2, then not only is the pH adjusted ²²⁴ Ra ²⁺ Disassociated from the Ra/EDTA complex and the EDTA precipitated from solution. Once the EDTA precipitate is completely formed, the supernatant may be removed from the base of the chemical modification chamber or mixing vessel, for example, by passing through a hydrophobic polyethylene sieve plate, thereby removing the EDTA from the base ²²⁴ Ra ²⁺ Removing the EDTA crystals precipitated in the solution.

TABLE 7 syringe pump dispensing valve port and system description shown in FIG. 33.

Port(s)	Port description
		1	Waste (go)
2	DI water (in)
		3	Acids (in)
4	Close off
		5	Air (in)
6	Ra/EDTA acidification pipe line (go)
		7	Ra filtrate line (in)
8	Column packing system pipeline (out)

According to another exemplary configuration, system 100 is shown in FIG. 36. As shown, the system 100 may include a mixing vessel 110 in fluid communication with both a bound isotope source 112 and an acid source 114. According to an exemplary embodiment, for example, the bound isotope source may be a source as described herein with respect to the separation of the element Ra from thorium. According to other exemplary embodiments, for example, the acid source 114 may be a syringe pump that may be mechanically controlled. Mixing vessel 110 may be configured to mix the contents therein using, for example, a magnetic mixer, such as magnetic mixer 116, placed on or below or around the side of the operable configuration of mixing vessel 110 that contains magnetic stirrer 130.

The system 100 can further include a first multi-way valve and a second multi-way valve, wherein the first multi-way valve 118 can be operably connected to the outlet 124 of the mixing vessel 110, and the second multi-way valve 120 can be operably connected to the first multi-way valve 118 and the acid source 114 and collection vessel 126. According to an exemplary configuration, the released element may be Ra, such as ²²⁴ And Ra. The elements may be released from complexing agents such as chelating agents. Exemplary chelating agents may include, but are not limited to, EDTA. As described, the first and second multi-way valves can be configured to be remotely operated, and the system can be coupled in series with an Ra production system such as the system described previously for separating Ra from Th.

According to at least one exemplary embodiment, the mixing vessel 110 may be equipped with a hydrophobic Polyethylene (PE) screen 135(Scientific models inc., Lake Havasu City, AZ), PTFE

Magnetic stir bar 130(SP Scientific ware, Wayne, NJ), one-way stopcock valve 118(Cole-Parmer, Vernon Hills, IL), 0.45 μm PES filter 131(Pall, Port Washington, N.Y.), 12mL disposable polypropylene syringe 114(Thermo Fischer Scientific, Waltham, MA), and "Multi-Stirrus" magnetic stand mixer 116 (V)&P Scientific, San Diego, Calif.) 5mL of Rezorian ^TM Column (Supelco, Bellefonte, Pa.).

According to an exemplary method, 5mL of Rezorian ^TM The tube may be drawn from column 3 of a three-column system (C3) ²²⁴ Receiving an aliquot volume of Ra elution ²²⁴ Ra-EDTA solution. Prevention of occlusion with an embedded hydrophobic screen plate (at the base of the Rezorian tube) and attached one-way stopcock valve (set "closed") ²²⁴ The Ra solution leaks through the bottom port. May be in Rezorian tubes ²²⁴ An aliquot of mineral acid is added to the Ra/EDTA solution to lower the pH, thereby forming insoluble EDTA (which precipitates out of solution). A vertical magnetic mixer can be used to generate a magnetic field to drive a magnetic stir bar to mix the acid/Ra/EDTA solution and increase the precipitation rate. Once EDTA precipitation is complete, the stopcock valve may be opened and the EDTA removed may be passed through the hydrophobic sieve plate ²²⁴ The Ra supernatant was removed from the Rezorian tube and extracted into a syringe barrel. An additional syringe filter may be added in the line between the syringe barrel and the 224Ra collection container to remove any fine EDTA particles that may have passed through the larger-pore hydrophobic sieve plate.

A schematic of an automated in-line EDTA precipitation and filtration system is shown in fig. 36. An automated version of the sedimentation and filtration system may employ an inverted digital syringe pump 114(SP, 48,000 steps, IMI Norgren, Littleton, CO) with an 8-way dispensing valve 120, a three-way stopcock valve 118(Cole-Parmer, Vernon Hills, IL) that may be controlled by a servo motor (SvM, Dsservo, east, China), "Multi-Stirrus" vertical magnetic rotation device 116, and a 0.45 μm PES filter connected to a 224Ra collection vessel. Port assignments, flow directions, and port names for SPs are listed in table 8. Each of the components in the system is described in more detail below. The operation of the SP, vertical magnetic mixer and SvM can be controlled by software via the processing circuitry.

The present disclosure provides systems and/or methods that may be advantageously performed with the aid of processing circuitry. The processing circuitry may include a personal computing system including a computer processing unit that may include one or more microprocessors, one or more supporting circuits, circuits including a power supply, a clock, input/output interfaces, electronic circuitry, and the like. In general, all of the computer processing units described herein may be of the same general type. The computing system may include memory, which may include random access memory, read only memory, removable disk storage, flash memory, and various combinations of these types of memory. The memory may be referred to as main memory and is a cache memory or a portion of a buffer memory. The memory may store various software packages and components, such as an operating system.

The computing system may also include a network server, which may be any type of computing device suitable for distributing data and processing data requests. The web server may be configured to execute system applications such as reminder scheduling software, databases, email, etc. The memory of the network server may include a system application program interface for interacting with a user and one or more third party applications. The computer system of the present disclosure may be standalone or work in conjunction with other servers and other computer systems (which may be used with, for example, larger company systems such as financial institutions, insurance providers, and/or software support providers). The system is not limited to a particular operating system, but may be adapted to run on multiple operating systems, such as, for example, Linux and/or Microsoft Windows. For example, a computing system may be coupled to a server, and the server may be located at the same site as the computer system or at a remote location.

According to an exemplary embodiment, these processes may be used in conjunction with the described processing circuitry. These processes may use the following combinations or types of software and/or hardware. For example, for server-side languages, the electronic circuitry may use, for example, Java, Python, PHP,. NET, Ruby, Javascript, or Dart. Some other types of servers that may be used by the system include Apache/PHP,. NET, Ruby, NodeJS, Java, and/or Python. Databases that may be used are Oracle, MySQL, SQL, nosqlite or sqlite (for mobile). Client side languages that can be used, this would be client side languages, such as ASM, C + +, C #, Java, Objective-C, Swift, Actionscript/Adobe AIR, or Javascript/HTML 5. Communication between a server and a client, for example using a TCP/UDP socket based connection as a third party data network service, may be employed, including GSM, LTE, HSPA, UMTS, CDMA, WiMax, WiFi, Cable and DSL. Hardware platforms that may be employed in the processing circuitry include embedded systems such as (Raspberry PI/Arduino), (Android, iOS, Windows Mobile) -cell phones and/or tablets, or any embedded system using these operating systems, i.e. cars, watches, glasses, headsets, augmented reality wearable devices, etc., or desktop/laptop/hybrid devices (Mac, Windows, Linux). Architectures that may be used for software and hardware interfaces include x86 (including x86-64) or ARM.

According to an exemplary embodiment, the servo system for engaging a one-way or multi-way valve and the mechanical or electrical switch for engaging the valve may be configured according to software and/or hardware to engage/disengage upon reaching and ending a condition such as temperature, time, pressure, volume, etc. Thus, many of the systems and methods of the present disclosure can be executed remotely from the processing circuit interface and/or automatically according to a program.

The system can be laid with 0.02 'or 0.03' or 0.04 'ID × 1/16' OD Fluorinated Ethylene Propylene (FEP) pipe (IDEX Health)&Science, Oak Harbor, WA), which is connected to a pipe with a connecting rod

Union-jointed Polyetheretherketone (PEEK)1/4-28 flangeless nut (IDEX Health)&Science, Oak Harbor, WA) or PEEK 10-32 nuts (Valco) with PEEK taper sockets.

Table 8. description of the 8-position syringe pump dispensing valve port dispense for the automated in-line sedimentation and filtration system shown in fig. 36.

Port allocation	Flow direction of	Port name	Pipe size (ID X OD)
				1	Go out	Waste material	0.02″×1/16″
2	Into	Deionization (DI) H 2 O	0.03″×1/16″
				3	Into	6M HNO 3	0.03″×1/16″
4	N/A	Close off	N/A
				5	Into	Air (a)	0.03″×1/16″
6	Go out	Line out to settling vessel	0.02″×1/16″
				7	Into	Line flowing from settling vessel	0.04″×1/16″
8	Go out	Flows out to 224 R line of collection vessel	0.02″×1/16″

An automated in-line sedimentation and filtration system may employ the same sedimentation vessel as described herein, with the addition of a teflon (teflon) cap fitted with tubing and an activated carbon trap to filter the filtrate from the sediment ²²⁴ Of the air space above the Ra solution ²²⁰ Rn emissions. ²²⁴ Ra-EDTA solution can be dispensed from the three-column purification system through one of these lines, while the other is used to dispense the mineral acid into the column containing ²²⁴ Ra in the eluent. The rate of EDTA precipitation was increased by using a vertical magnetic stirrer.

In an automated filtration process, a three-way stopcock with three ports can connect the containment vessel to a digital syringe pump and add a filter for removing residual content ²²⁴ Line for Ra liquid. The stopcock valve may be connected to a servo motor (SvM) operable between the ports. The supernatant was aspirated using an inverted syringe pump with an 8-way dispensing valve and then dispensed through a 0.45 μm filterAnd enter into ²²⁴ Ra in the collection vessel as shown in fig. 36.

Referring to fig. 37, custom supports may be provided to hold the settling vessel, servo motor, and vertical mixer in close proximity. The part holder was designed with Solidworks2017(Dassault Systems, Waltham, MA) and 3D printed on uPrint SE Plus (Stratasys, Eden Prairie, MN).

Referring to FIG. 38, pre-acidified is shown ²²⁴ Images of Ra-EDTA solution (a), precipitate-forming solution (b), and post-precipitate solution (c).

Referring to FIG. 39, the configuration of a system for automating an online process replicates the described method, with first receiving using two separate pipelines ²²⁴ Ra-EDTA solution, then a small amount of 6MHNO ₃ Adding into a precipitation container. The settling vessel may be configured from a 5mL Rezorian tube kit with an embedded 20 μm pore size hydrophobic polyethylene sieve plate in the base, and a teflon coated magnetic stir bar. Under magnetic mixing, adding into ²²⁴ The acid in the Ra-EDTA solution lowers the pH, thereby causing EDTA to precipitate out of solution and at the same time will precipitate ²²⁴ Ra ²⁺ Left in the supernatant.

After the completion of EDTA precipitation, the automated in-line filtration process can be divided into four steps (FIG. 39). In step 1, the servo motor drives the three-way stopcock to 90 ° and will ²²⁴ Ra supernatant was aspirated into an inverted syringe pump at a flow rate of 10 mL/min. During this process, the vast majority of the solid EDTA was captured by the sieve plate. In step 2, the supernatant in the syringe was dispensed through a 0.45 μm syringe filter and into ²²⁴ Ra in the collection vessel (d). An in-line filter is used to remove any small crystals of EDTA that may have migrated through the sieve plate of the Rezorian tube. In step 3, the servo motor drives the three-way stopcock valve to 180 ° to form a single flow path between the cleaning agent container and the SP. A250 μ L aliquot of 0.01M HCl (pH 2) was pumped from the purge vessel through the syringe transfer line and into the SP, thereby removing any residual contents remaining in the tubing ²²⁴ The Ra droplet was carried to the syringe. In step 4, the pH 2 wash solution was dispensed through 0.45μ m filter and enter ²²⁴ Ra in the collection vessel.

According to the system described above, a method for producing free isotopes is provided, which may include providing a solution comprising isotopes bound to a complex. According to exemplary embodiments, the bound isotope may be in a solution having a pH sufficient to bind substantially all of the isotope and/or retain the bound isotope in solution. In addition, the solution may be adjusted to another pH that decomplexes the isotope from the complex and/or precipitates the complex while leaving a substantial amount of the isotope in solution.

For example, these exemplary solutions contain Ra in combination with EDTA. Such a solution may be exposed to a precipitation solution, such as an acidic solution, to precipitate the isotope-bound complex and produce a free isotope solution, as shown and described with respect to the mixing vessel in previous systems. The method may further comprise transferring the free isotope solution to a collection vessel. According to an exemplary embodiment, the solution of the isotope bound to the complex may have a pH greater than 11. Further, the free isotope solution may have a pH of less than 2. According to exemplary embodiments, these solutions may be delivered to and/or from the mixing vessel using, for example, differential pressure techniques, which may include pumping or positive displacement. Further, the method may comprise transferring the free elements or Ra via a filter into a container.

Referring next to fig. 40, a system and method for producing a metal storage/generation vessel assembly is described that includes a particular metal to be stored and/or generated using the vessel. Embodiments of these systems, methods, and components are described with reference to fig. 40-63B.

Systems and/or methods for producing a metal storage/generation vessel assembly are provided. The system may include: a first mixing vessel in fluid communication with the first and second multi-way valves; a manifold of multi-way valves in fluid communication with the second multi-way valve; a second mixing vessel in fluid communication with at least one of the multi-way valves of the manifold; a third multi-way valve in fluid communication with an outlet of the second mixing vessel; and a metal storage/generation vessel in fluid communication with the third multi-way valve.

The first mixing vessel and the second mixing vessel define different volumes. The first mixing vessel defines a volume that is greater than a volume defined by the second mixing vessel.

A method for producing a metal storage/generation vessel assembly is also provided. The method may include: homogenizing the resin slurry in a first mixing vessel; replenishing free elements to the homogenized resin slurry to form a homogenized bound element resin slurry; and transferring the homogenized bonding element resin slurry to a storage/generation vessel assembly. As shown and described, the resin/media of the present disclosure will consolidate or adhere to other portions of the container at the lower portion of the container without homogenization. Homogenization here keeps the resin/medium distributed throughout the solution in the vessel. This distribution may be uniform and/or free of heterointerfaces.

Also provided is a metal storage/generation vessel assembly, which may include: a sidewall extending between the inlet opening and the outlet opening to define a container volume; inert material adjacent to the outlet opening: unbound resin adjacent to the outlet opening (trap bed), with inert material between the unbound resin and the outlet opening; and a bed of homogenized bound elemental resin within the vessel, the inert material and unbound bound resin being between the resin bed and the outlet opening.

Referring first to fig. 40, an exemplary sequence of events may include homogenizing a resin slurry, metering a resin bed volume into another container, then mixing the elements with the slurry mixture, and then delivering the element-loaded slurry to the storage and/or generation assembly 6.

Referring next to fig. 41, a system 200 is provided. Within this system are two mixing vessels, a first mixing vessel 210 and a second mixing vessel 212. The mixing vessel 210 may be in fluid communication with first and second multi-way valves 214 and 216. According to an exemplary embodiment, the system 200 may further include: a manifold 218 of the multi-way valve that may be in fluid communication with the multi-way valve 216. The mixing vessel 212 may be in fluid communication with at least one of the multi-way valves within the manifold 218. The system 200 may also include a third multi-way valve 220 in fluid communication with an outlet of the mixing vessel 212. The system 200 may additionally include a metal storage generation vessel 6 in fluid communication with the multi-way valve 220. FIG. 42 is a diagram of one embodiment of a system 200, according to an exemplary embodiment.

An automated container assembly packaging system is shown in fig. 41, and an image of the system in a fume hood is shown in fig. 42. The system may include a V6 digital syringe pump (SP, 48,000 step, IMI Norgren, Littleton, CO), 4-way and 6-way Cheminert selector valves (V4 and V6, Valco, inc., Houston, TX), stopcock manifold (SM, Cole-Parmer, Vernon Hills, IL), three servomotors (SvM, Dsservo, eastern guang, guangdong, china)), several solution Holding Coils (HC), two gas regulators (R1/R2) (McMaster-car, Los Angeles, CA) and two electromagnetically controlled 3-way isolation valves (SCIV, Bio-Chem, booton, NJ) with an 8-way dispensing valve at its head. The port assignments for the Syringe Pump (SP) are listed in table 9, including flow direction, port name and tubing size. Tables 10 and 11 list the port assignments for the 4-way valve (V4) and the 6-way valve (V6), respectively. Each component in the system and its acronyms will be described in more detail in the following sections. SP, V4, V6, SVMB and SCIV operations using processing circuitry.

Table 9.8 description of port dispense for dispense valve of Syringe Pump (SP).

Port allocation	Flow direction of	Port name	Pipe size (ID X OD)
				1	Go out	Waste material	0.04″×1/16″
2	Into	Deionization (DI) H 2 O	0.04″×1/16″
				3	Into	0.25M HCl	0.04″×1/16″
4	In/out	Excess Supernatant Coil (ESC)	0.04″×1/16″
				5	Into	Air (a)	0.04″×1/16″
6	Go out	Conveying pipeline (TL)	0.04″×1/16″
				7	In/out	Holding coil to V4(HC/V4)	0.063″×1/8″
8	In/out	Holding coil to V6(HC/V6)	0.063″×1/8″

Table 10.4 specification of Cheminert selector valve (V4) port assignment.

Port allocation	Flow direction of	Port name	Pipe size (ID X OD)
				1	Go out	Waste material	0.063″×1/8″
2	Into	Air (a)	0.04″×1/16″
				3	In/out	Large scale mixing container (LMV)	0.063″×1/8″
4	Go out	V4 to 3 Stopcock Manifold (SM)	0.063″×1/8″
				Center of a ship	In/out	Holding coil to V4(HC/V4)	0.063″×1/8″

Table 11.6 description of the Cheminert selector valve (V6) port assignment.

Port allocation	Flow direction of	Port name	Pipe size (ID X OD)
				1	Go out	Waste material	0.063″×1/8″
2	Into	Air (a)	0.04″×1/16″
				3	In/out	Small-sized mixing container (SMV)	N/A
4	Into	224 Ra stock solution	0.04″×1/16″
				5	Into	1M HCl	0.04″×1/16″
6	Go out	Column body	0.063″×1/8″
				Center of a ship	In/out	Holding coil to V6(HC/V6)	0.063″×1/8″

a. The parts are connected without the use of pipes.

According to an exemplary embodiment, the mixing vessels (e.g., LMV and SMV) may define different volumes, where a first mixing vessel may be a larger volume than a second mixing vessel. According to an exemplary embodiment and referring to FIG. 43, a configuration for N is shown ₂ An image of the first mixing vessel being agitated to effect mixing. The mixing vessel of fig. 43 can be considered the first mixing vessel or Large Mixing Vessel (LMV) and contains a known ratio of CatIX resin to water and is capable of forming a homogeneous suspension of these solid/liquid phases.

Two large resin/liquid suspension mixing vessels (LMVs) of the system were evaluated. The first LMV adopts N ₂ Gas or air to form a uniform resin/water slurry (LMV). The vessel was a 50mL polyethylene centrifuge tube containing a reservoir of MP-50 resin and water at a known solid to liquid volume ratio. The LMV has a cover fitted with three holes through which N is fixed ₂ Gas (inlet) line, resin slurry suction line (outlet) and N ₂ A gas discharge (outlet) port. Using N ₂ The air stream or air stream stirs the resin/water mixture to obtain a uniform slurry while a slurry suction line is used to withdraw a metered volume from the LMV. An image of the LMV is shown in fig. 43.

Referring to fig. 44A and 44B, a first mixing vessel configuration is disclosed, which illustrates a mixing vessel that may be mechanically agitated, for example.

Another LMV was evaluated, defining a 50mL centrifuge tube and a resin/water reservoir configured with a plastic blade located in the center thereof (fig. 44A). This LMV is in turn positioned on the base of the oscillating in the reciprocating "washer" mode. The oscillations were driven by a rotating magnetic field using a "Multi-stirling" mixer (V & scientific, San Diego, CA) which caused angular rotation of the blades, thereby agitating the slurry by the action of turbulence. Two blade designs of FIG. 44B were evaluated; they are made with holes along the edges as shown in fig. 44B. The metered volume is withdrawn from the LMV using a slurry suction line.

According to FIG. 45, there is shown a configuration for N ₂ A second mixing vessel for gas or air mixing, for example comprising a gas inlet and an outlet. The second mixing vessel or mini-mixing vessel (SMV) is configured to 1) receive an aliquot volume of MP-50 resin (from LMV) as a slurry, and 2) contain ²²⁴ Contacting the Ra solution with the received resin slurry to obtain adsorption to MP-50 resin ²²⁴ Uniform distribution of Ra. The SMV may be defined by a 10mL polyethylene syringe barrel mounted to a V6 valve via a female luer fitting to an 1/4-28 connector. Tube caps custom made from Teflon FEP fitted with four holes, N ₂ Gas or air (inlet) line, resin slurry distributor (inlet) line, Excess Supernatant Coil (ESC) line (inlet/outlet), and N ₂ Through which passes a gas or air discharge (outlet) portThese holes. An ESC line with an internal volume of 2.00 ± 0.02mL can be used to pump excess supernatant from the dispensed resin slurry. Can be combined with ²²⁴ The Ra solution was introduced into the SMV via the V6 valve; after suction contact from SMV via the same valve ²²⁴ Ra/resin slurry mixture. Using N ₂ Agitating the resin slurry with a stream of air or air ²²⁴ Mixtures of Ra solutions to influence ²²⁴ Ra was uniformly adsorbed onto the resin particles.

According to an exemplary configuration and referring to fig. 46, one configuration of a manifold 218 of the system 200 is shown, including, for example, a configuration of a multi-way valve of the manifold. The Stopcock Manifold (SM) system consists of a set of three 3-way stopcock luer valves (Cole-Parmer). The SM is connected between V4 and the SMV as a transport and metering for eventual use in the SMV ²²⁴ The Ra contacted resin then goes through the path of subsequent column packing. A set volume of slurry can be filled and dispensed into a 0.250mL bed based on the internal volume of the stopcock valves in the manifold system (-0.120 mL) and the connecting cylinder between any pair of stopcock valves (-0.130 mL). A custom-made trimmed high density polyethylene 5mL pipette filter (Eppendorf, Hauppauge, New York, USA) was used as the bottom sieve plate to allow water (but no resin) to pass through the bottom port of the SM. Thus forming a packed resin bed above the sieve plate.

The configuration of the plug valve position in the SM allows the Transfer Line (TL) to push excess resin into the waste while maintaining a set metered volume and subsequently transfer it into the SMV. Adjustment of the position of the stopcock valve may be performed using processing circuitry. An image of the SM is shown in fig. 46, where port names and flow directions are provided in table 12.

Table 12 description of the stopcock manifold System (SM) shown in fig. 46 and 47.

A schematic of the SM resin bed metering and dispensing sequence is shown in fig. 47. Each stopcock valve in the manifold may be operably engaged with the servo block motor. Referring to fig. 47, for the manifold configuration as shown in fig. 47, there is again shown a method for moving the slurry and/or mixing the slurry with elements between preparing the slurry and the generator vessel.

The importance of slurry agitation is illustrated with reference to fig. 48-52, which depict an unstirred slurry and an agitated slurry, for example, in a first mixing vessel.

Two methods were evaluated to promote uniform resin suspension from which to feed into the fluid system. Consistent resin concentration in LMVs is beneficial when pumping large volumes of slurry to deliver sufficient resin mass to the SM for accurate resin bed metering. In LMV, a catalyst containing 5cm ³ Gravity settling of 20mL of resin/water mixture. In SMV, 0.25cm from SM is used ³ The resin composition was gravity settled to 4.25mL of resin/water mixture.

As discussed, the first resin suspension method evaluated employed N controlled via a gas regulator ₂ The air stream or air stream agitates the gravity settled resin bed, causing the resin beads to disperse throughout the water volume until uniform. The gas agitated LMV is referred to as "LMVg". The conditioner was opened at 0.5 pounds Per Square Inch (PSI) increments and then observed for 5 minutes to determine if the entire gravity settled resin bed was suspended and became homogeneous (i.e., indicating that the resin beads did not stratify with liquid depth). This process was repeated until the mixing became excessively vigorous. The minimum and maximum PSI for LMVg and SMV are recorded. Images of these containers in an unagitated and uniformly agitated state are shown in fig. 48(LMVg) and 49 (SMV).

As discussed, the second method employs a magnetic rotating base (Multi-Stir mixer, V & PScientific, San Diego, CA) to cause the oscillatory angular rotation of the LMV. The rotating blade agitating assembly is referred to as "LMVv". The oscillating vessel containing the fixed blades creates turbulent eddies within the vessel, thereby causing mixing. The angular rotation of the system was increased in increments of 10 Revolutions Per Minute (RPM) and then observed for 5 minutes to determine if the entire gravity settled resin bed was suspended and became homogeneous. This process is repeated until 100RPM (maximum) is reached. For each of the two blade designs evaluated, minimum and maximum RPM were recorded. An image of LMVv blended using leaf #1 is shown in figure 50.

Using N ₂ Gas or air agitation evaluated a method for forming a uniform resin suspension in water. The optimum gas regulator pressure range that provides proportional gas flow rates is determined to affect good resin suspension formation. Below this range, a partial suspension (inhomogeneous resin suspension) is formed (fig. 51 (a)). In this range, a uniform suspension was formed (fig. 51 (B)). Beyond this range, the resin slurry may be transferred from an LMV (large mixing vessel (gas used to convey the resin into the system stirs the resin/water mixture) or an SMV (gas used to convey the resin into the system) due to excessive vigorous agitation ²²⁴ Ra adsorbed to a small mixing vessel on the suspension resin mixture) is lost or ejected (fig. 51 (C)). The use of excessive air flow also increases the water evaporation rate, thereby ultimately changing the resin concentration in the suspension.

After having added ²²⁴ After Ra solution, the most significant problems caused by over-mixing occurred in SMV. The resin dispersed above the mixing line (22.5 mL in FIG. 51(B)) may not be re-incorporated into the suspension due to wall cohesion, resulting in loading onto each generation column due to lack of resin mixture transferred to the SMV ²²⁴ Ra combined with loss of resin.

The air regulator pressure ranges of 1.5 to 2.5 PSI and 2 to 4PSI were determined to be optimal for LMVg and SMV, respectively. In subsequent studies, the pressure of the air regulator was set to 2PSI for LMVg and 3PSI for SMV to optimize the degree of resin/water mixing.

An evaluation of resin mass delivery using a gas mixing system was conducted to determine the resin mass of the pumped slurry volume as a factor in the pumping/dispensing flow rate. To ensure reproducibility in column packing systems, the slurry pumped from LMVg requires a consistent resin concentration to deliver sufficient resin quality. Maximizing resin slurry flow rate is important to reduce the overall time of an automated column packing procedure, which will reduce the time during the process ²²⁴ Ra daughter product in-growth. However, excessive flow rates may cause cavitation of the pumped solution and need to be avoided.

Using for 1cm ³ 0.347. + -. 0.009g/cm determined from packed semi-wet bed ³ For a dry resin density of 5cm ³ A uniform 20mL suspension of the gravity settled resin was calculated to be 0.087. + -. 0.002g/cm ³ The theoretical resin concentration of (2). Using this theoretical value, delivered resin mass deviation can be evaluated for aspirated suspension volumes in the range of 5 to 30 mL/min. A contour plot showing the empirically determined and calculated dry resin mass (as a function of suction volume and flow rate) is shown in fig. 52. The comparison of the data sets is shown in table 13.

TABLE 13 comparison of empirically determined and calculated resin masses at different flow rates and suction volumes. Mass deviations of > 10% are shown in bold.

a. The relative deviation is such that,

contour plots of the calculated data and the empirical data show similar mass distributions with increasing delivered resin mass relative to increasing suction volume. Furthermore, for a given flow rate of 0.5 to 3mL, the empirically determined dry resin mass shows a tendency for the deviation to decrease as the suction volume increases. For a draw volume of at least 1mL per flow rate, a minimum loss of resin mass per unit volume (less than 7.5%) was observed. However, based on the determined dry resin density, the filling is 0.250cm ³ The resin bed required a mass of 0.087 grams; therefore, a suction volume of < 1mL will not provide sufficient resin quality at any flow rate.

In the container assembly filling method, excess resin mass can be removed during the SM resin metering process, so a larger suction volume (2mL) can be employed. In addition, due to the heat from ²²⁴ The ingrowth of the short-lived daughter products of Ra, the process must be carried out in a rapid manner. To minimize the elapsed processing time, the system will be such thatWith a higher flow rate. Based on the data, it may be beneficial to pump 2mL at a flow rate of 30mL/min because it is fast and has the lowest relative deviation (less than 0.01%).

For the container assembly filling sequence, 0.25cm based on SM ³ Internal volume, the suction volume of the resin slurry was reduced to 1.85mL (0.161 g). This delivered slurry volume will allow a slight resin excess to be observed without unnecessary overfilling of the SM.

Referring to fig. 53, an exemplary process for preparing a storage/generator vessel assembly is shown, wherein the component designations of the generation columns are set forth in table 14.

TABLE 14 exemplary part details of the generation column.

After the chemically resistant polypropylene felt screen (322) was packed over the capture bed (320), the open column was closed with a barbed (barbed) polycarbonate reducer (314B), which barbed polycarbonate reducer (314B) was connected to a female luer-lock (luer-lok)/barbed tube coupler (326) through a silicone tubing (312B). In automation ²²⁴ Adsorption uniformly distributed in the Ra Loading column packing step ²²⁴ A resin bed (324) of Ra is distributed as a slurry through inlet conduits (326, 312B and 314B) and into the column, thereby filling the bed. In the final assembly, a one-way check valve (328) is used to connect the inlet/outlet silicone lines (312A and 312B) through their luer-lock fittings (310 and 326).

According to another embodiment, the column 300 is enclosed within a polyethylene vial prior to column bed filling to eliminate the risk of contamination and reduce the hand dose caused by previous processes (plugging the top with lint and closing the column after delivery of the bed). In addition, a one-way check valve is installed to provide back pressure, thereby preventing deformation of the uniform resin bed during transportation.

As described above, this system is configured to be hands-free, and remotely and/or automatically operable. As in the systemAs shown, a method for producing a metal storage generating container may include homogenizing a resin slurry in a first mixing container, then replenishing metal to the homogenized resin slurry to form a homogenized metal-bound resin slurry, and transferring the homogenized metal-bound resin slurry to a storage generating container. According to exemplary embodiments, the methods may provide for stable transfer and dispensing of these elements into storage and/or generation containers. In addition, the storage and generation vessel may include a "capture bed" 320, the "capture bed" 320 including an unbound or element-free resin portion adjacent to the vessel outlet. This resin portion may be above the screen or porous material 318 to mitigate resin transfer out of the storage vessel. Another sieve plate 322 placed above the trapping bed 320 enables the trapping bed 320 and adsorption to be carried out ²²⁴ The resin bed 324 of Ra separates.

Accordingly, the metal storage generating vessel assembly is described with reference to fig. 54-61. The vessel 6 may have a metal-free trap bed 320 below the metal and resin distribution bed 324. According to an exemplary embodiment, an elution solution may be provided to the aspiration conduit, and the resulting metal may be provided through the elution conduit. According to an exemplary embodiment, this elution conduit may be a decay product of an element or isotope present or provided to the storage and generation vessel.

Referring next to FIG. 55, a more detailed view of one embodiment of a storage generating vessel is shown, wherein dimensions and materials are described in more detail.

Referring to fig. 56A-56B, decay chain images are provided illustrating Pb production from an Ra storage/generator vessel assembly according to one embodiment of the present disclosure.

Referring next to fig. 57, an exemplary series of storage and generation vessels prepared by the device is shown. This series was used to evaluate the reproducibility of resin bed delivery.

The time during which the column preparation and packing process takes place should be minimized as much as possible in order to allow ²²⁴ Ra progeny in-growth is minimized. Based on elapsed time of up to 15 minutes, relative to the initial ²²⁴ Ra activity, will grow less than 0.1%/min ²¹² Pb and 0.01%/min ²¹² Bi、 ²⁰⁸ Tl and ²¹² and Po. During the execution of the column packing process, the ²²⁴ Ra daughter ingrowth minimization for reduction of radiation dose from high energy photons (from ²⁰⁸ Tl up to 2.6MeV) is necessary.

The process for minimizing the elapsed time of an automated column packing sequence can be divided into four parts: A) maximization of reagent flow rate, B) reduction of tubing path length, C) simplification of sequence code, and D) reduction of software cycle time.

Similar to the resin slurry delivery study, the water delivery study was conducted at increments of 10mL/min up to 50mL/min to determine the upper limit of the internal diameter and SP of each pipe employed. The upper flow rate limit is specified when cavitation and/or incomplete transfer of reagents within the tubing or syringe pump occurs. The optimum flow rates determined from this study are shown in table 15.

TABLE 15 maximum suction and dispense flow rates for column packing systems.

When operating a fluid delivery sequence at elevated flow rates, significant pressure may be generated in the line, thus requiring an additional step to relieve the pressure. This is performed by adjusting the SP dispense valve to the waste port, which ensures that pressure equalization is achieved before the next step is started (e.g., before switching flow paths). Further time minimization is performed by reducing the various tubing lengths to shorten the path required for the reagents to traverse the system.

The additional time delay initially programmed into the code during the troubleshooting activity is reduced or eliminated. Finally, an internal software package is implemented, thereby enabling full automation of the system while providing additional control over each of the electromechanical components in the system.

Using the interface, the idle time associated with the cycling port locations on SP, V4, and V6 is reduced. The elapsed time for the automated column packing sequence is shown in table 16.

The elapsed time for the entire column packing process was reduced from-18 minutes to-12 minutes, with the column packing stage requiring 8.9 minutes. This time can be further reduced by dividing the column packing stage into two sections. Steps 2 to 7 may be carried out ²²⁴ Purification of Ra and delivery to the column packing system is performed before, while steps 8 to 13 may be performed after. Separation of this phase will reduce the endogenous time by 5.2 minutes, thus requiring only-3.7 minutes to dispense/contact ²²⁴ Ra and packed in a bed for transport. It is to be noted that ²²⁴ The adsorption rate of Ra on MP-50 resin, which may increase slightly, may be > -60 seconds.

TABLE 16 elapsed time for automated column packing sequence. Not in bold at ²²⁴ Ra isolation and delivery are performed before or after; in bold face is ²²⁴ Ra delivery was followed.

The occurrence column packing system was evaluated by extensive testing to ensure a reproducible bed with less than 5% change in resin bed volume. This is necessary because each generation column is preassembled, with only enough empty space for the bed, and then a barbed end fitting placed over the bed is added. This requires the generation column inserted into the fluid system to receive a consistent volume of resin in a uniform configuration over the felt screen deck 322 and the capture bed 320.

The packed bed reproducibility test was performed by using gravimetric and volumetric measurements. Based on the optimal conditions described above, gravimetric analysis was used to assess mass loss when 1.85mL of the pumped resin slurry (from LMVg) was delivered through the system.

After consistent resin mass was delivered, the bed packed in each generation column was evaluated using volumetric analysis. This operation is performed to ensure that a uniform bed of columns is packed without disturbing the trap bed and that no air bubbles are trapped within the resin bed. Resin containing embedded bubblesThe bed may significantly alter the flow path of the mobile phase through the resin, resulting in inconsistencies ²¹² Pb elution recovery rate

Automated packing methods were evaluated to quantify the reproducibility of the resin quality delivered to the column delivery line. Five sets of six runs were performed (n-30) in which each bed was dispensed into a tared 20mL LSC vial, then vacuum dried and weighed as described. The results of all 30 runs are shown in table 17.

The system showed that consistent resin quality could be delivered with a Relative Standard Deviation (RSD) of less than 3% over thirty replicates. Furthermore, each batch of separately prepared resin/water suspension can be used for at least six consecutive iterations without refilling or replacing. The small deviations observed in mass delivery may be due to differences in the size distribution of the resin beads pumped or human error in drying the sample.

Table 17. measured mass of dry resin in bed from automated column packing process.

In general, the system demonstrates that consistent quality resin can be delivered to the column. An average AG MP-50 resin mass delivery of 0.0875 ± 0.0026 grams of dry resin was observed (n ═ 30).

In use ²²⁴ Prior to Ra stock solutions, automated filling methods were evaluated to quantify the reproducibility of filling consistent resin bed volumes. Two sets of six runs were performed using a semi-automated filling method (n-12); images of individual packed columns are shown side by side in fig. 57. Two additional six runs (n-12) were performed using a fully automated system using SVMB and SCIV. The packed resin bed volume of each column was calculated using the bed height and the inner diameter of the column tube. The results of these twenty-four runs are shown in table 18. Note that no embedded air pockets were observed in the packed bed.

Table 18 bed volume determined from the automated packed column.

a. The bed volume was determined using the column internal diameter (0.4 cm).

Based on ²²⁴ Ra distributed generation bed volume measurements, the overall average of all twenty-four runs being 0.259. + -. 0.005cm ³ (±2.0％RSD)。

Referring next to fig. 58, an EDTA precipitation/filtration module and a container assembly module in series are depicted and evaluated. The automated precipitation/filtration modules may be coupled in series for the purpose of reducing the number of electronic components and extraneous process time between steps in the process. By coupling the two systems, only one microcontroller and computer are required to operate the two systems. Furthermore, this enables two sets of process steps to be integrated into a single process sequence, which minimizes the number of code lines and system idle time. A schematic of a two module system in series, not included in FIG. 58, is shown ²²⁴ Components of the column packing system prior to Ra delivery. The description of the components is shown in table 19.

Table 19.EDTA precipitation/filtration module and column packing system module are schematically labeled (fig. 58).

In performing the automation process, time minimization is performed to ensure at initialization ²²⁴ After Ra purification ²¹² Pb/ ²¹² Bi/ ²⁰⁸ Minimal ingrowth of Tl. Through the integration of two modules, EDTA is precipitated and filtered, and ²²⁴ the process time required for Ra delivery to the column packing module and packing of the generating column is minimized. An overview of the steps of these processes is shown in table 20.

By in-delivery ²²⁴ System preparation (steps 1 to 5) and repair (steps 14 to 15) before and after Ra can reduce the total elapsed time of the whole process from 16.6 minutes to 8.8 minutesA clock. In contrast to the individual column packing modular process described herein ²²⁴ The elapsed time of the two module sequence steps performed after Ra delivery increased only by 5.0 minutes (from 3.8 to 8.8 minutes).

TABLE 20 elapsed time for automated in-line EDTA precipitation/filtration and column packing sequences. Not in bold at ²²⁴ Ra delivery is performed before or after. In a three-column module ²²⁴ Ra delivery is followed by a bold step.

Evaluation of two module systems in series to evaluate individual processes from an online use of a fully automated system ²²⁴ Ra yield. The automated precipitation and filtration method is connected in-line with the automated column packing process described herein. FIG. 58 shows a partial schematic of a two module system. For this evaluation, 1 minute was used ²²⁴ Ra/resin contact time. A series of six replicates were performed and the results are shown in table 21.

TABLE 21 for use of an automated in-line EDTA precipitation/filtration and column packing system ²²⁴ Evaluation of recovery of Ra fraction. The overall average results are shown in bold.

Each module showed an average recovery within 1% of its previous individual evaluation.

The EDTA precipitation/filtration system and the column packing system were successfully integrated into a series in-line system. Of the precipitation/filtration step ²²⁴ The Ra yield (0.872 ± 0.012) agreed with the previous evaluation (0.867 ± 0.010), and the generator fill yield of 0.982 ± 0.007 agreed with the previous evaluation (0.980 ± 0.010). Overall, a 0.856. + -. 0.012 accumulation was demonstrated ²²⁴ Ra yield. Furthermore, the elapsed time of the process was reduced to 8.8 minutes by the recombination sequence step, so that ²²⁴ Ingrowth of Ra progeny(dosage to the user) is minimized.

By integrating the use of three-column systems and methods ²²⁴ Ra separation module followed by EDTA precipitation/filtration module and column packing system module to perform the process of automation through the entire three modules ²²⁴ Evaluation of Ra yield. In a three-module process, three columns of fluid modules ²²⁴ The Ra elution outlet line was connected directly to the precipitation vessel (label a in fig. 58) so that an evaluation of the entire in-line process could be performed. An overview of the elapsed process time for the entire three-module process is shown in table 22.

TABLE 22 when starting from ²²⁸ Automated three-module process acquisition at the beginning of Th stock solution ²²⁴ Ra packing gives an overview of the elapsed process time of the column.

In the evaluation of an integrated three-module process, the individual segments are recombined in such a way that ²²⁴ Ra separation modules are preceded by all system preparation steps and followed by all system repair steps after assembly of the production column. Based on the described process time, separating ²²⁴ Ra, precipitating/filtering EDTA, ²²⁴ The total elapsed time for Ra/CatIX loading and column assembly was 59.0 minutes, with the entire process (including the preparatory and system repair steps) consuming 1.5 hours.

A series of twenty-one iterations were performed to evaluate when each modular step was completed ²²⁴ Ra yield and determination of accumulation ²²⁴ Ra yield. The results of the evaluation are shown in table 23.

TABLE 23 vs. Slave ²²⁸ Starting of Th stock solution through automated on-line three-module system ²²⁴ Evaluation of Ra yield. The overall average results are shown in bold.

Is automated inThe line three module system showed reproducible average yields of 0.832 ± 0.029. In addition, the EDTA precipitation/filtration and column packing module demonstrated excellent performance consistency, wherein between this system and the previous system (Table 21) where only modules 2 and 3 were employed, ²²⁴ the Ra yield is within 1 sigma uncertainty.

In summary, the integrated three-module process shows that, ²²⁴ ra can be reproducibly isolated, EDTA purified, resin loaded and packed into a generating column assembly with an average yield of 0.832 ± 0.029 in a process that takes less than 1 hour, with only an additional-0.5 hour to set up and repair the system.

Prepared using a three-module fluid system ²²⁴ Ra/ ²¹² Pb generation column, performance parameters were evaluated, including: 1) during squeezing ²¹² Pb elution Profile, and 2) from the column ²²⁴ Ra penetrates.

Using production by a three-module process ²²⁴ Ra generation column to carry out ²¹² Evaluation of Pb elution behavior. A3 mL aliquot of 2M HCl was loaded onto the generation column to measure the change with eluent ²¹² And (4) recovering Pb. After completion, the generation column was rinsed with 1mL of water delivered through the generation column for storage. FIG. 59 shows in 2M HCl ²¹² Pb elution profile.

The storage/generator container assembly showed that-55% of the in-growth elutable was recovered in the first 0.5mL fraction collected ²¹² Pb, but recovered in the first 1mL to 95%. For the ²²⁴ Ra Generator purge, 1mL is sufficient to recover most of the elutable ²¹² Pb, while each additional 0.25mL fraction will only slightly increase recovery (< 1% gain).

Also identified are generators prepared from an automated three-module process ²²⁴ Ra penetration level.

To confirm being newly filled ²¹² On P-generating column ²²⁴ Ra breakthrough was measured using 1mL 2M HCl load followed by 1mL DIW rinse for 10 squeeze cycles. A comparison in each of these squeeze cycles is shown in FIG. 60 ²²⁴ Graph of fractional loss of Ra. Is determined by gamma counting ²²⁴ Before Ra levels, each fraction was allowed to decay for several days to ensure ²²⁴ Ra and ² pb is in long-term equilibrium.

Observed between the 1 st and 2 nd squeezing cycles ²²⁴ Ra breakthrough was reduced, while stability was noted from cycle 2 to cycle 10 ²²⁴ Ra penetrates. The 1 st squeeze cycle is typically discarded (as it represents the 1 st squeeze cycle after the column reaches the end user facility occurs) as it grows in stable Pb during transport. Excluding this first squeeze cycle, the breakthrough of the system was-0.14%/elution cycle. Based on these observed results, a careful evaluation of the squeeze process was conducted in an attempt to understand and minimize the observation from the self-packed generation column ²²⁴ Ra penetrates.

In 2M HCl ²¹² In the Pb elution matrix, the distribution coefficient (K) of Ba (a chemical analogue close to Ra) on the macroporous CatIX resin was estimated _d ) Only 300 mL/g. In contrast, K of Pb thereon _d Is 5 mL/g. Thus, with respect to Ba (Ra), ²¹² pb eluted from the column with a resin affinity of-1/60. As shown in fig. 59, the low CatIX resin affinity for Pb is evident from the sharp elution from the occurrence column.

For moderate adsorption ²²⁴ Ra, Ra at the base of a distributed CatIX bed ²⁺ The ions had a 50. mu.L resin trapping bed (. about.0.4 mm bed height) to prevent them from interacting with ²¹² And (4) carrying out Pb co-elution. The volume of the trap bed may not be sufficient to ensure a high purity of the squeeze out ²¹² A Pb product.

For better understanding of the columns from distributed bed generation ²²⁴ Loss of R, using an end-to-end fluid system to prepare a generation column without a-50 μ L trapping bed, and three columns each containing a standard trapping bed at the base of the column. A column without a trapping bed would enable the evaluation of the distribution in the absence of a protective trapping bed ²²⁴ Ra elution Rate. Using three columns with trapping beds, the presence and absence of a supplemental trapping bed cartridge was compared ²²⁴ Ra penetrates.The make-up trap bed was prepared from a trimmed SPE column (5.6mm ID) and 20 μm pore size polyethylene sieve plates were used above and below the make-up resin bed. The preparative columns used in this evaluation are shown in fig. 61 and described in table 24.

TABLE 24. shown in FIG. 61 ²²⁴ Ra/ ²¹² Description of the configuration of the Pb generation column.

a. Prepared in a trimmed SPE column (5.6mm diameter)

It is assumed that 2M HCl (. about.1 mL) is used to squeeze from the generation column ²¹² Pb, then use this reagent to deliver-20 ²¹² The Pb squeezes out the equivalent of the cycle. This study was not included in each 1mL ²¹² Water injection between Pb eluent injections. The column effluent is typically collected in 1.0 ± 0.1mL fractions and allowed to decay until any of the effluent fractions ²²⁴ Ra is exuded and ²¹² pb is in long-term equilibrium. Analysis of fractions by automated gamma detector counting provides for loading onto individual generation columns ²²⁴ Of Ra activity ²²⁴ Ra penetration fraction.

Shown in FIG. 62A as ²¹² Step by step of Pb eluent volume function ²²⁴ Ra penetration fraction. As can be seen in FIG. 60, for the column without the trapping bed (column a), eluted from the column in the first-1 mL of 2M HCl ²²⁴ The Ra release was slightly higher. 1mL before ²¹² After the elution of the Pb, the Pb-containing solution, ²²⁴ the extent of Ra penetration is typically reduced to a plateau level of about 0.8%/mL. This platform is significant because ²²⁴ Ra was uniformly distributed in the CatIX resin bed; at the top of the column ²²⁴ Ra is as much as at the bottom most of the column. With following ²²⁴ Ra migrates down the column, with a continuous level of bleed expected. In fig. 61B, the same data is shown, but as an accumulation graph. If the first "sacrificial" elution volume (. about.1 mL) is discarded, 8% of the elution is lost from column a after 10mL ²²⁴ Ra, and a loss of 15% after 20 mL.

With distributed type ²²⁴ The Ra bed and the standard column embedded in the 50. mu.L trapping bed (column b) performed differently. At the beginning of the process, ²²⁴ the Ra penetration was low (reduced to-1/25) because the trap bed was in ²²⁴ With Ra successfully trapping a fraction of the fraction migrating from the distributed CatIX bed ²²⁴ And Ra. However, as the volume of 2M HCl delivered through standard column b increases, ²²⁴ the Ra penetration also increased. This is that ²²⁴ Evidence that Ra did eventually migrate through the trap bed. If sufficient 2M HCl volume is provided, then this is expected ²²⁴ The Ra penetration will increase until it reaches the plateau level obtained by column a. For long-term squeeze, column b achieved-1.4% and-4.0% accumulation after 10mL and 20mL of eluent delivery, respectively ²²⁴ And Ra is lost.

Columns c and d with supplemental 100. mu.L and 200. mu.L resin cartridges attached to the outlet of the generating column, respectively, are shown in ²²⁴ Further reduction in Ra penetration. Column c started with-0.005% penetration and rose to-0.016% penetration per mL at-20 mL. Although slight, the rise in permeation levels indicated some incremental increase from the kit ²²⁴ Ra level. At elution volumes of 10mL and 20mL, accumulation ²²⁴ Ra penetration levels were-0.08% and-0.2%, respectively.

In contrast, bar d shows extremely low ²²⁴ Loss of Ra; data traces plot the Minimum Detectable Activity (MDA) levels above 3 mL. Column d at 10mL and 20mL even with MDA level versus volume buildup ²¹² Pb elution solutions delivered show-0.001% and-0.003%, respectively ²²⁴ And Ra is lost.

In that ²²⁴ After Ra breakthrough studies, the four generation column configurations discussed herein can be stored for more than two weeks. At the end of-20 mL of 2M HCl delivery, the columns were blown with air, capped and stored.

The correspondence of each column configuration was evaluated ²¹² The Pb squeeze curve. Each column (with or without the supplemental column described in Table 24) received 2M HCl at a flow rate of 1.0mL/min to squeeze out the in-grown ²¹² And Pb. For each column elution cycle, fractions of 0.5mL were collected. The results are shown inIn fig. 63A and 63 Bb. Here, it is observed that, in this case, ²¹² the Pb elution volume is almost the same between the column a and the column b; presence of 50 μ L trapping bed ²¹² No observable effect of the Pb elution Profile (this is comparable to that on MP-50 resin ²¹² Low Kd of Pb unity). After 1mL elution volume, of column a and column b ²¹² The Pb yield was 88%.

The two columns with the resin-supplemented cartridge (columns c and d) did show some degree of ²¹² The Pb elution becomes broader. ²¹² The Pb activity is distributed relatively evenly between the first two-0.5 mL fractions; columns c and d had 1mL of 85% and 81%, respectively ²¹² And (4) the Pb yield. In the fraction 3 and beyond, the fraction, ²¹² the Pb tail is consistent with those observed for columns a and b without the supplemented resin cartridge. At 1.5mL elution volume, all columns ²¹² The Pb elution yield is more than 90 percent.

Relative to the standard generation column configuration (column b), at 1.0mL elution volume, immediately adjacent to ²¹² The presence of 100. mu.L and 200. mu.L supplemental resin cartridges placed downstream of the Pb generation column was similar ²¹² And (4) the Pb yield. Therefore, the replenishment of the resin cartridge does not adversely affect ²¹² Pb recovery while providing a Pb-rich fraction containing significantly higher Pb from ²²⁴ Of radionuclide purity of Ra ²¹² A Pb product.

Claims (62)

1. A system for producing free elements, the system comprising:

providing a mixing vessel in fluid communication with both a source of a binding element and a source of an acid, wherein the mixing vessel is operably configured to mix contents within the mixing vessel;

a first multi-way valve operably engaged with an outlet of the mixing vessel; and

a second multi-way valve operably engaged with the first multi-way valve, the acid source, and a collection vessel.

2. The system of claim 1, wherein the element is Ra.

3. The system of claim 1, wherein the element is an isotope.

4. The system of claim 3, wherein the isotope is ²²⁴ Ra。

5. The system of claim 1, wherein the element is bound to a chelator.

6. The system of claim 5, wherein the element is Ra and the chelating agent is EDTA.

7. The system of claim 1, wherein the first and second multi-way valves are configured to be operated remotely.

8. The system of claim 1, further comprising a system for separating Ra from Th to form the source of binding elements.

9. The system of claim 1, further comprising a sorbent vessel coupled to the mixing vessel.

10. The system of claim 9, wherein the sorbent vessel contains activated carbon.

11. The system of claim 1, wherein the mixing vessel is oriented vertically with the outlet at the bottom of the mixing vessel.

12. The system of claim 10, further comprising a porous structure adjacent the outlet.

13. The system of claim 11, wherein the porous structure defines a frit or a filter.

14. A method of producing a free element from a bound element, the method comprising:

providing a solution comprising an element bound to a complex;

exposing the solution to an acid solution to separate the complex from the element; and

removing the separated element or the complex from the solution to produce a free element.

15. The method of claim 14, wherein exposing the solution to an acid solution precipitates the complex to produce a free elemental solution, the method further comprising transferring the free elemental solution into a collection container.

16. The method of claim 14, wherein the solution having an element bound to a complex comprises Ra bound to EDTA.

17. The method of claim 16, further comprising separating the Ra from a solution comprising Ra and Th to form the solution comprising Ra bound to EDTA.

18. The method of claim 16, wherein the solution of Ra bound to EDTA has a pH greater than 11.

19. The method of claim 16, wherein the free element solution comprises Ra and has a pH of less than 4.

20. The method of claim 16, wherein the free element solution comprises Ra and has a pH of less than 2.

21. The method of claim 15, wherein providing a solution comprising an element bound to a complex comprises utilizing a pressure differential to provide the solution into a mixing vessel.

22. The method of claim 21, further comprising stirring the solution within the mixing vessel using a stirring element.

23. The method of claim 15, wherein transferring the free isotope solution comprises using a pressure differential to transfer the solution through a filter into the collection container.

24. A system for producing a metal storage/generation vessel assembly, the system comprising:

a first mixing vessel in fluid communication with the first and second multi-way valves;

a manifold of multi-way valves in fluid communication with the second multi-way valve;

a second mixing vessel in fluid communication with at least one of the manifold's multi-way valves;

a third multi-way valve in fluid communication with an outlet of the second mixing vessel; and

a metal storage/generation vessel in fluid communication with the third multi-way valve.

25. The system of claim 24, wherein the first mixing vessel and second mixing vessel define different volumes.

26. The system of claim 25, wherein the first mixing vessel defines a volume that is greater than a volume defined by the second mixing vessel.

27. The system of claim 24, further comprising a solution delivery assembly in fluid communication with the first multi-way valve.

28. The system of claim 27, wherein the fluid delivery system is a pressure differential system.

29. The system of claim 24, further comprising a resin source in fluid communication with the first mixing vessel.

30. The system of claim 29, further comprising a valve operably engaged between the resin source and the first mixing vessel.

31. The system of claim 30, wherein the valve is remotely operable.

32. The system of claim 24, further comprising a free element source in fluid communication with the second mixing vessel.

33. The system of claim 32, further comprising a valve operably engaged between the free element source and the second mixing vessel.

34. The system of claim 33, wherein the valve is remotely operable.

35. A method for producing a metal storage/generation vessel assembly, the method comprising:

homogenizing the resin slurry in a first mixing vessel;

replenishing free elements to the homogenized resin slurry to form a homogenized bound element resin slurry; and

the homogenized bonding element resin slurry is transferred to a storage/generation vessel assembly.

36. The method of claim 35, further comprising transferring the homogenized resin slurry from the first mixing vessel into a second mixing vessel.

37. The method of claim 36, wherein the homogenized resin slurry is supplemented with the free elements in the second mixing vessel.

38. The method of claim 35, further comprising transferring the homogenized resin slurry from the first mixing vessel into the storage/generation vessel assembly to form a capture bed within the storage/generation vessel assembly.

39. The method of claim 35, further comprising homogenizing the resin slurry within the first mixing vessel with an inert gas.

40. The method of claim 39, wherein the inert gas is N ₂ 。

41. The method of claim 35, further comprising homogenizing the resin slurry within the first mixing vessel with a stirring assembly.

42. The method of claim 35, further comprising mixing the homogenized resin slurry with the free elements using an inert gas.

43. The method of claim 42, wherein the inert gas is N ₂ 。

44. A metal storage/generation vessel assembly, said metal storage/generation vessel assembly comprising:

a sidewall extending between the inlet opening and the outlet opening to define a container volume;

an inert material adjacent the outlet opening; and

a bed of homogenized bound element resin within the vessel, the inert material being between the resin bed and the outlet opening.

45. The metal storage/generation vessel assembly of claim 44 further comprising an unbonded resin adjacent the exit opening, wherein the inert material is between the unbonded resin and the exit opening.

46. The metal storage/generation vessel assembly of claim 44 wherein the element is an isotope.

47. The metal storage/generation vessel assembly of claim 44 wherein the element is Ra.

48. The metal storage/generation vessel assembly of claim 44 wherein the element is ²²⁴ Ra。

49. The metal storage/generation vessel assembly of claim 44 wherein the metal/storage vessel is generated ²¹² Pb and/or ²¹² Bi。

50. The metal storage/generation vessel assembly of claim 44 further comprising an inlet conduit and an outlet conduit operatively coupled to an opening of the vessel.

51. The metal storage/generation vessel assembly of claim 50 further comprising an auxiliary coupling operably secured to each conduit.

52. The metal storage/generation vessel assembly of claim 51 further comprising at least one non-return valve operably engaged with one of the inlet or outlet conduits.

53. A system for preparing free elements and providing a storage/generator vessel assembly, the system comprising:

a free element generation module configured to decouple the complexing elements; and

a storage/generator container assembly production module configured to combine the free elements and media within the container assembly.

54. The system of claim 53, wherein the free elements are predictably unstable, thereby forming progeny that can be removed from the container assembly.

55. The system of claim 53, wherein the free element is Ra.

56. The system of claim 54, wherein the container assembly is operable to produce Pb.

57. The system of claim 53, further comprising an element separation module configured to separate elements from a mixture of elements.

58. The system of claim 57, wherein the element separation module is configured to separate Ra from a mixture comprising at least Ra, Pb, Bi, and Th.

59. A method for providing a free element and providing a storage/generator vessel assembly containing the element, the method comprising:

providing a complexing element into a first mixing vessel;

providing an acid solution to the first mixing vessel to release the complexing element and precipitate the complex while leaving the free element in solution;

separating the free elements from the precipitate;

providing the free elements into a second mixing vessel to mix the free elements with a homogenization medium; and

providing the element-medium mixture into a storage/generator vessel assembly.

60. The method of claim 59, wherein the element is Ra and the complex is EDTA.

61. The method of claim 59, wherein the free Ra is ²²⁴ Ra ²⁺ 。

62. The method of claim 59, further comprising separating Ra from a mixture comprising at least Ra, Pb, Bi, and Th to form complexed Ra.

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