A method for pre-enriching of an isotope and a pre-enricher

Abstract

The invention is in the field of a method of pre-enriching isotopes, a pre-enrichment system, an array of such enrichment systems, and a computer program for carrying out the method. It therefore also relates to preparations containing radioactive substances, which may be used in therapy or testing. Typically thereto a further enrichment step is required.

Description

[0001] A METHOD FOR PRE-ENRICHING OF AN ISOTOPE AND A PRE-ENRICHER

[0002] FIELD OF THE INVENTION

[0003] The invention is in the field of a method of pre-enriching isotopes, a pre-enrichment system, an array of such enrichment systems, and a computer program for carrying out the method. It therefore also relates to preparations containing radioactive substances, which may be used in therapy or testing. Typically, thereto a further enrichment step is required.

[0004] RELATED APPLICATIONS

[0005] The present application claims the benefit of priority from Dutch Patent Application NL2038759, filed on October 3, 2024, in the name of Radboud Universiteit Nijmegen, and Rijksuniversiteit Groningen, The Netherlands.

[0006] The entire contents of the above-referenced applications and of all priority documents referenced in the Application Data Sheet filed herewith are hereby incorporated by reference for all purposes.

[0007] BACKGROUND OF THE INVENTION

[0008] Isotopes are distinct nuclear species of the same chemical element, wherein the chemical element is an element of the Periodic System of Elements (periodic table). Isotopes have the same atomic number, relating to the number of protons in their nuclei. And therefore isotopes have the same position in the periodic table. The number of protons is equal to the number of electrons in the neutral atom. The difference between isotopes of the same element lies in the number of neutrons in their nuclei. Typically, isotopes of a given element have similar or the same chemical properties; however, they often have different physical properties. Examples of such isotopes are40Ca,44Ca,46Ca,48Ca,142Nd,143Nd,144Nd,145Nd,146Nd,148Nd,150Nd,156Dy,158Dy,160Dy,161Dy,162Dy,163Dy, and164Dy. Isotopes are also referred to as nuclides. A nuclide is an individual nuclear species of an atom with a specific number of protons and neutrons in the nucleus, as are the isotopes. The nuclide concept emphasizes nuclear properties over chemical properties, whereas the isotope concept emphasizes chemical over nuclear.

[0009] Heavy, stable isotopes of calcium, in particular46Ca and48Ca, have a number of medical and scientific applications. The natural abundance is low, only 0.004% for46Ca and 0.187% for48Ca. Enrichment up to a medium to high purity is possible using electromagnetic isotope separation in a calutron (see below) or by laser separation. However, both methods have a relatively low efficiency, which limits the production quantity, and drives up the costs. For instance, the annual worldwide production of pure48Ca is 10 g and the price is above 400 k€ / g.

[0010] Calcium isotopes are an important target material to produce isotopically pure nuclides for medical purposes. In personalized medicine, patients are treated according to an individually tailored treatment regime. In nuclear medicine, this approach is realized by exploiting diagnostic techniques, such as non- invasive imaging by means of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), together with individualized radi- otherapeutic treatment. The resulting combination became known as the theragnostic approach and uses the same molecular targeting vectors, labelled either with a diagnostic or therapeutic radionuclide

[0011] In addition, ideally, employed radionuclides represent a matched pair, wherein both are radioisotopes of the same chemical element. Only a limited number of matching radionuclides are found suited for radio-theragnostic use. Of those the radionuclides of scandium,44Sc / 43Sc and47Sc, are most promising candidates. The emission of low-energy p--particles from47Sc is particularly interesting for targeted radionuclide therapy of small tumors and cancer metastases. Moreover, the shorter half-life of47Sc (Tl / 2 = 3.35 d) is favorable for certain applications. Availability of high activity47Sc with adequate purity is important for future clinical applications. The current bottleneck lies in the production of pure47Sc samples using enriched isotopes of calcium. The preferred production mode for47Sc is through neutron capture on46Ca:46Ca(n,y)47Ca —47Sc. The low natural abundance of46Ca, even 45x lower than for48Ca, makes this process economically not viable. An alternative production mechanism starts with48Ca and uses the48Ca(p,2n)47Sc process. Using a proton beam with an energy of 17-24 MeV on a CaCO3 target purities of 85% for47Sc have been achieved. Both46Ca and48Ca are used to measure calcium absorption mainly in women and children. In adults, calcium deficiency is strongly related to increasing severity of osteoporosis. In children, calcium deficiency is primarily related to the development of rickets. Finally,44Ca has a natural abundance of 2%. It is used the production of the PET isotope 44Sc in cyclotrons. While there is adequate supply, the cost is 25k€ / g for high purity calcium

[0012] Isotope production, specifically isotope enrichment, may further rely on a so-called calutron as mentioned. The calutron is a type of mass spectrometer, which is an instrument in which a sample is ionized and then accelerated by electric fields and deflected by magnetic fields. In the mass spectrometer ions ultimately collide with a plate and produce a measurable electric current. Since the ions of the different isotopes have the same electric charge but different masses, the heavier isotopes are deflected less by the magnetic field, causing the beam of particles to separate into several beams by mass, striking the plate at different locations. The same principle may be used, not only to separate isotopes from one and another, but also to collect separated fractions thereof, with respective higher and lower concentrations of specific isotopes. Therewith enriched isotopes can be produced. Production of these isotopes is however slow and costly. As such the availability of certain isotopes, such as heavy isotopes, e.g. of calcium (48Ca,46Ca and44Ca), which are used in medical applications and scientific research, may form a problem, in particular when a calutron is not or less available. The present invention aims to resolve or at least reduce this availability problem.

[0013] Further, isotopes may be treated with e.g. radiation to produce a desired (further) isotope. Typically, isotopes are separated from one and another in a further process step, and then transported to a location of use.

[0014] Incidentally reference can be made to Jordan et al.(DOI:10.1515 / zna-1966-1007), Lyubimov (D01:10.1070 / RC1972V041N03ABEH002041) and Lantelme (D01:10.5560 / zna.2012-0105). These articles relate to isotope separation by counter-current electromigration, wherein single valence metals are used. Isotope mobilities and their temperature dependence in molten KC1, RbCl and RbBr are investigated. Lyubimov mentions ionic migration for the separation of stable isotopes under laboratory conditions and in large-scale plant are considered. The phenomenological theory of the process, the apparatus, the mode of operation, experimental conditions, and results obtained for twenty elements are discussed in detail. Results obtained by countercurrent and zone electrical migration for the structure of molten salts and the mechanism of the migration of ions in an electric field are examined. Lantelme mentions molten salts and isotope separation performed. Their studies relate to ionic motions in melts, and liquids in general. Some recent results of such simulations - molecular dynamics (MD) and Brownian dynamics (BD) - as well as of related theoretical work are discussed.

[0015] The present invention therefore relates to an improved method for pre-enrichment of isotopes, a system for such enrichment, and further aspects thereof, which overcome one or more of the above disadvantages, without jeopardizing functionality and advantages.

[0016] SUMMARY OF THE INVENTION

[0017] The present invention relates in a first aspect to a method of pre-enriching an isotope, comprising providing a mixture comprising a first salt comprising the to be enriched isotope first cation of a first chemical element, and a first anion, and at least one further isotope cation of said chemical element, and at least one second salt comprising a second anion and a second cation, providing the salt in an enrichment system, the enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), an optional bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment comprising a filter F, a heater for heating the respective compartments, a salt outlet (13) in fluidic contact with the at least one cathode compartment CC, and a salt inlet (12) in fluidic contact with the at least one anode compartment AC, melting the salt, applying a voltage to the cathode and anode during an enrichment time at an enrichment current density, therewith providing flow of the molten salt, providing un-en- riched mixture to the salt inlet, that is, with natural occurring quantities of respective isotopes, and optionally removing an isotope depleted mixture from the salt outlet (13), that is, with less heavier isotope than naturally occurring. In comparative cases likewise lighter isotopes, of interest, may be obtained at higher concentrations or quantities than naturally occurring. The present invention relates amongst others to a device for pre-enriching heavy calcium isotopes by counter current electromigration in a molten salt solution. It is noted that typically molten salts are highly corrosive, so care has to be taken. The present mixture is found to be much less corrosive. Also, by using a mixture with a relatively low melting point, energy costs are much more acceptable. An enrichment factor of five would already reduce the production time and cost by 80%.e.g. for Ca. In an exemplary embodiment a pre-enricher for46Ca and48Ca is developed. By enriching those isotopes by a factor 5-10, further enrichment to a higher purity is less cumbersome. The time required for enrichment and costs would be reduced by a similar factor and in addition would reduce the pressure on enrichment facilities. The present invention would typically start from natural available material, such as Ca comprising46Ca and48Ca isotopes. The present method can performed in a reproducible and consistent manner, e.g. involving filling and extraction. Therewith a target production of 250g / year is easily achievable. In an example the present device also enriches44Ca by about half the amount wherein48Ca is enriched. Such is an additional advantage. It is noted that in the present invention a relative mobility of different species, e.g. cations, and anions, is not the same in the present mixture. “Not the same” implies that the relative mobility [m / sec] of said different species is, relative to another species, at least 1% larger or smaller, typically at least 5% larger or smaller, such as at least 10% larger or smaller. To some extent the present mobility may be compared to electrophoresis. Mobilities are typically rather small, e.g. in the order 1 O'9- 1 O'6m / s, e.g. depending on the cation, applied voltage, charge of the cation, Stokes radius, concentration, etc. A “first” second salt may be referred to as “second” salt, a subsequent “second” salt as “third” salt, and so on. The present first salt is typically present in an amount of 10-70 atom%, in particular 20-50 atom%, more in particular 30-45 atom%, such as 38-42 atom%, the present second salt is typically present in an amount of 10-70 atom%, in particular 20-50 atom%, more in particular 30-45 atom%, such as 38-42 atom%, an optional present third and fourth salt may be typically each individually present in an amount of 2-30 atom%, in particular 5-25 atom%, more in particular 10-20 atom%, such as 15-18 atom%, an optional fifth and subsequent salt may be typically each individually present in an amount of 0.1-20 atom%, in particular 0.5-17 atom%, more in particular 1-15 atom%, even more in particular 3-13 atom%, such as 5-12 atom%.

[0018] If not mentioned otherwise, characteristics of species are taken at a temperature of 20 °C (293 K) and at 100 kPa, or at the temperature of the respective melt, and pressure thereof. Specific characteristics can easily be found in relevant text books, or on the internet, such as an atomic mass, etc., and can be measured accordingly.

[0019] In an exemplary embodiment in a bath of molten salt, a cathode and an anode are positioned in two sub-reservoirs being connected by a barrier. In operation, the cathode attracts the positive metal ions, with the lighter isotope moving faster than the heavier one. At the anode the negative ions may form a gas (e.g. Cb, B ), which may be fed back to the cathode compartment to react with the metal. This forms a counter-current. In an embodiment, by carefully balancing the currents a net migration to the anode reservoir for the heavier isotopes and to the cathode reservoir for the lighter isotopes is created and after some time the heavier isotopes accumulate in the cathode reservoir.

[0020] In a second aspect the present invention relates to a computer program comprising instructions, the instructions when loaded and running on a computer causing the computer to carry out: providing a mixture comprising a first salt comprising the to be enriched isotope first cation of a first chemical element, and a first anion, and at least one further isotope cation of said chemical element, and at least one second salt comprising a second anion and a second cation, providing the salt in an enrichment system, the enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), a bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment comprising a filter F, a heater for heating the respective compartments, a salt inlet (11) in fluidic contact with the at least one cathode compartment CC, and a salt inlet (12) in fluidic contact with the at least one anode compartment AC, melting the salt, applying a voltage to the cathode and anode during an enrichment time at an enrichment current density, therewith providing flow of the molten salt, providing un-enriched mixture to the salt inlet, and optionally removing an isotope depleted mixture from the salt outlet (13).

[0021] In a third aspect the present invention relates to a system A pre-enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), a bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment comprising a filter F, a heater for heating the respective compartments, a salt inlet (11) in fluidic contact with the at least one cathode compartment CC, and a salt inlet (12) in fluidic contact with the at least one anode compartment AC.

[0022] In a fourth aspect the present invention relates to 27. An array (n*m) of pre-enrichment systems according to any of claims 20-26, wherein in the array an enriched mixture outlet (13) of an ithpre-enrichment system in a row is in fluidic contact with a mixture inlet (11) of an i+lthpre-enrichment system in the same row, wherein ie [l,n-l].

[0023] Thereby the present invention provides a solution to one or more of the above-mentioned problems.

[0024] Advantages of the present invention are detailed throughout the description. DETAILED DESCRIPTION OF THE INVENTION

[0025] The present invention relates in a first aspect to a method according to claim 1.

[0026] In an exemplary embodiment the present method comprises providing un-enriched mixture to the salt inlet (11) at the cathode side.

[0027] In an exemplary embodiment the present method comprises removing an isotope cation depleted mixture from the salt outlet (13) at the cathode side.

[0028] In an exemplary embodiment the present method comprises providing the second salt at the salt inlet at the cathode side, wherein the second salt comprises a more mobile cation than that of the second salt supplemented at the salt inlet at the anode side, such as NH4+salts.

[0029] In an exemplary embodiment of the present method the first cation is selected from Ca, Mg, Ba, Nd, Ni, Zn, Gd, Yb, and Dy, in particular from44Ca,46Ca,48Ca,142Nd,143Nd,144Nd,145Nd,146Nd,148Nd,150Nd,152Gd,168Yb,176Yb,158Dy,160Dy,161Dy,162Dy,163Dy, and164Dy. In principle any suitable heavier or lighter cation isotope can be pre-enriched with the present method, in particular when suitable first and second salts are selected, albeit practical limitations may exist. For enriching isotopes with relative large mass differences, such as40Ca,44Ca and48Ca, enriching is found to be somewhat easier and leading to higher enrichment percentages.

[0030] In an exemplary embodiment of the present method the mixture comprises two or more second salts, in particular 3-12 second salts, in particular wherein the first salt and second salt form one of a binary mixture, ternary mixture, quaternary mixture, etc. It is found that ternary mixtures, quaternary mixtures, and so on, provide a lowering of the melting point of the present mixture. This is in particular when the first salt and second salt form a binary mixture, a ternary mixture, a quaternary mixture, etc.

[0031] In an exemplary embodiment of the present method the at least one second salt comprises at least one second cation of a second chemical element of a lower Group in the periodic table than the first chemical element of the to be enriched isotope first cation. For instance, in case of Ca the second cation may be selected from Na, K, and Li. Atomic masses of chemical elements, and thus of cations thereof, as well as of isotopes, are well known and can be found e.g. in the periodic table of elements (https: / 7en. iklpedia.org / w rkr eriodic table).

[0032] In the present method the second cation has a lower charge than the first cation. The cation charge may also be referred to as oxidation state, or likewise valence. Charges of cations are typically determined by amongst other a position of the chemical element in the above Periodic table; e.g. cations of Group 1 elements typically have a charge of +1, those of Group 2 elements have +2, etc. For each and any chemical element such a charge, and abundance thereof, can typically be found in said Periodic table of elements. A charge of the first cation is typically +1 or +2, whereas a charge of the second cation is typically +2, +3, +4, +5 or +6. The charge of the first cation is in particular +1, whereas a charge of the second cation is typically +2, +3, or +4.

[0033] In an exemplary embodiment of the present method the second cation has a higher (ionic) mobility in the mixture than, relative to, the first cation. It is noted that for cations of Group 2 elements, under all boundary conditions, the relative mobility thereof is smaller than that of (the respective) cations of Group 1 elements. In addition, the higher the atomic mass, the higher the relative mobility, e.g. Mg2+< Ca2+< Sr2+. It is considered that rare earth metal cations, as well as lanthanide cations, and actinide cations, as well as higher charged cations (3+, 4+) behave similar to earth alkali metal cations. Further, e.g. NFL4has a higher mobility under comparable boundary conditions than e.g. Li+, Na+, and K+, respectively.

[0034] In an exemplary embodiment of the present method the voltage is from 50-120 V DC, in particular 70-90 V DC.

[0035] In an exemplary embodiment of the present method the current is from 10-10000 mA, in particular from 20-5000 mA, more in particular 50-3000 mA, such as 100-2000 mA, e.g. 200- 1000 mA. In an exemplary embodiment of the present method the provided electrical charge during enrichment is from 100-3000 kC per unit isotope. With C= 6,241 506 x 1018, and Mol=6, 02214076 x 1023, this is about 107C / mole times charge.

[0036] In an exemplary embodiment of the present method the enrichment time is from 1-50 days, in particular from 3-21 days, such as 5-10 days.

[0037] In an exemplary embodiment of the present method the first and second anion each individually may be selected from nitrate (NO,-), halides, in particular Cl’, Br , and I’, nitrous oxide, oxyanions of halides, such as chlorate, and combinations thereof, in particular wherein the first and second anion are the same.

[0038] In an exemplary embodiment of the present method the second cation is selected from Group I cations, in particular Li+, Na+, and K+, and from ammonia (NH4+).

[0039] In an exemplary embodiment of the present method the first and second cation are se first cation with said second cations. Therewith, typically faster second cations are combined with slower first cation.

[0040] In an exemplary embodiment of the present method the mixture melts at a temperature of 50-500 °C (323-773 K), in particular a temperature of 80-300 °C (353-573 K), more in particular a temperature of 100-200 °C (373-473 K), such as 130-180 °C (403-453 K).

[0041] In an exemplary embodiment of the present method the mixture is a eutectic mixture, that is, forming a homogeneous mixture of two or more salts, wherein a melting point of the eutectic mixture is lower than a melt point of each of the contributing salts, in this case, the fist salt, and the at least one second salt.

[0042] In an exemplary embodiment of the present method the first anion is nitrate, and wherein the second anion is nitrate.

[0043] In an exemplary embodiment of the present method the second anion is the same for the at least one second salts.

[0044] In an exemplary embodiment of the present method the mixture is one of a binary mixture, a ternary mixture, and a quaternary mixture.

[0045] In an exemplary embodiment of the present method the second cation is selected from Na+, K+, Li+, and combinations thereof.

[0046] In an exemplary embodiment of the present method the first cation is Ca2+.

[0047] In an exemplary embodiment the present method further comprises adding a formed species at the first cathode, in particular NO2.

[0048] In an exemplary embodiment of the present method the first cathode comprises an element selected from carbon, such as graphite, W, and Ti, and or wherein the first anode comprises a noble metal, in particular Pt.

[0049] In an exemplary embodiment of the present method the first anode comprise a core of Ti. Therewith the life time of the electrode is increased.

[0050] In an exemplary embodiment of the present method the method is repeated, in particular repeated 2-10 times. By repeating, e.g. in a series of subsequently preformed methods according to the invention, the pre-enrichment is improved, almost equal to the number of repetitions.

[0051] In an exemplary embodiment of the present method providing un-enriched mixture to the salt inlet is in a continuous mode, or in a semi-continuous mode. With the un-enriched mixture is significant increase in the level of enrichment is obtained, for instance, for Ca48, typically well above a factor of 2, typically above factor 5.

[0052] In an exemplary embodiment of the present method removing an isotope depleted mixture from the salt outlet (13) is in a continuous mode, or in a semi-continuous mode. Therewith also the level of enrichment is increased, as above. In addition, or as an alternative, un-enriched first salt may be provided at the salt inlet 11 in a continuous mode, or in a semi-continuous mode

[0053] In an exemplary embodiment of the present method an enriched mixture is removed that is, is harvested.

[0054] In an exemplary embodiment of the present method the at least one second salt is provided in a continuous mode, or in a semi-continuous mode.

[0055] In an exemplary embodiment of the present method the mixture forms a gas at the cathode, in particular wherein the gas is selected from halogens, such as Ch, Bn, and I2, from NO2, from O2, and from CO2.

[0056] In an exemplary embodiment of the present method additional at least one second salt is provided to the at least one anode compartment. As a result also the additional at least one second salt is removed from the cathode side, after the salt moved through the present pre-enrichment system.

[0057] In an exemplary embodiment the present computer program further comprises balancing at least two current selected from cation currents and anion currents.

[0058] In an exemplary embodiment the present pre-enrichment system further comprises reservoir (2) in fluid connection with the salt inlet (11) for providing additional mixture to the enrichment system.

[0059] In an exemplary embodiment the present pre-enrichment system further comprises a heater.

[0060] In an exemplary embodiment the present pre-enrichment system further comprises at least one controller, wherein the at least one controller is selected from a temperature controller, a pressure controller, and a flow controller.

[0061] In an exemplary embodiment the present pre-enrichment system provides counter-current electromigration. In an exemplary embodiment of the present pre-enrichment system a volume of the respective cathode compartment and anode compartment each individually is from 10-1000 cm3, in particular from 50-500 cm3.

[0062] In an exemplary embodiment of the present pre-enrichment system a volume of the cathode compartment is 1.1-2 times the volume of the anode compartment. In a case of a bridging compartment in between the anode compartment and the cathode compartment, the volume of the respective compartments is typically less relevant.

[0063] In an exemplary embodiment of the present pre-enrichment system the respective cathode compartment and anode compartment each individually are made from an in view of the mixture chemically inert material, in particular selected from glass, and quartz.

[0064] In an exemplary embodiment of the present pre-enrichment system the bridging compartment, such as a filter, is substantially U-shaped.

[0065] In an exemplary embodiment of the present pre-enrichment system the respective cathode compartment and anode compartment each individually are substantially cylindrical.

[0066] In an exemplary embodiment of the present pre-enrichment system the filter is selected from nanoporous filters, from mesoporous filters, and from microscopic filters.

[0067] In an exemplary embodiment of the present pre-enrichment system the reservoir (2) comprises a second cathode (1) and a second anode (3), wherein the reservoir is configured to provide a gaseous pre-cursor of the at least one second cation to the cathode compartment CC, in particular NO2.

[0068] In an exemplary embodiment of the present array n is from 21-26, in particular n is from 22-24.

[0069] In an exemplary embodiment of the present array m is from 2°-25, in particular m is from 21-24.

[0070] In an exemplary embodiment in the array an enriched mixture outlet (13) of an n111pre- enrichment system of a jthrow m is in fluidic contact with a mixture inlet (11) of a first pre-enrichment system in an j+1111row, wherein j e [l,m-l].

[0071] The invention is further detailed by the accompanying figure and example, which are exemplary and explanatory of nature and are not limiting the scope of the invention. To the person skilled in the art, it may be clear that many variants, being obvious or not, may be conceivable falling within the scope of protection, defined by the present claims.

[0072] SUMMARY OF THE FIGURES

[0073] Figure la-b, 2a-b and 3 show details of the invention.

[0074] DETAILED DESCRIPTION OF THE FIGURES

[0075] In the figures:

[0076] 1 second cathode

[0077] 2 reservoir

[0078] 3 second anode 4 first cathode

[0079] 5 first anode

[0080] 11 salt inlet

[0081] 12 second salt inlet

[0082] 13 excess second salt outlet

[0083] 14 inlet cathode side

[0084] 15 outlet anode side

[0085] AC anode compartment BC bridging compartment CC cathode compartment F Filter H heater

[0086] Hi Heavier cation isotope, e.g.48Ca2+

[0087] Lc Lighter or more mobile cation of second salt, e.g. Na+

[0088] Li Lighter cation isotope, e.g.40Ca2+

[0089] Figure la shows an exemplary embodiment of the present pre-enrichment system, comprising an anode compartment AC in fluid connection with an optional bridging compartment BC which is in fluid connection with a cathode compartment CC. A first cathode 4 is provided in the CC and a first anode 5 in the AC. Optionally a second cathode 1, in a reservoir 2 in fluid connection with the CC, and further comprising a second anode 3. A salt inlet 11 is provided for introducing un-enriched salt; a depleted salt outlet 13 is provided for removing depleted salt, and an enriched salt outlet 13 is provided for removing enriched salt. Also, a Filter F may be present in the bridge compartment. The system is heated with a heater H, such as a spiral of metal wire. The flows of heavier cation isotope, e.g.48Ca2+Hi, and lighter cation isotope, e.g.40Ca2+Li, are shown. Flows of isotope cations, second cations, and so on are shown. Fig. lb further focuses on these flows of anion and cation species. As a result of the present pre-enrichment in the example of Ca, Ca48is enriched at a left side of the U-shaped tube.

[0090] Fig. 2a shows an experimental partition of the present system into sections 1-8. Fig. 2b shows the experimental ratio of48Ca / 44Ca for the respective sections 1-8 after 9 days, at 80 V and 8 mA, and heating the below mixture to 131 °C.. The heavier Ca48isotope is clearly enriched with respect to the lighter Ca isotope. Typically the natural abundance of44Ca is about 2.09 atom%, whereas that of48Ca is about 0.187 atom%; so48Ca / 44Ca is about 0.895.

[0091] Fig. 3 shows flows of ionic species, replenishment of species, relative partition of the species over the various compartments, removal of ionic species, and so on.

[0092] The figures are further detailed in the description and examples below.

[0093] EXAMPLES / EXPERIMENTS

[0094] The below relates to an example of the present invention.

[0095] Inventor enriched48Ca in a table-top experiment. They used a ternary salt consisting of 42wt.% Ca(NC>3)2, 43wt.% KNO3 and 15wt.% NaNCh obtained from Yara with a unique relatively low melting point of 131°C. This allowed to use a simple glass U-shaped tube as a reservoir. The set-up is schematically presented in figure 1. The bottom of the U-tube was filled with quartz sand to act as a barrier. The tube was heated using a resistive wire wrapped around it. The electrodes were made of graphite. To add additional NO2 to the cathode an extra reservoir 2 of salt was added with two electrodes 1,3 and guided the NO2 gas back to the main cathode 4. A voltage of 80 V DC was applied over the electrodes, which resulted in a current of 8 mA. The set-up was left running for 9 days. The total charge through the experiment was 6.2kC, which is 500x less than a comparable prior art one. After the electrolysis, the tube was divided in 8 sectors (fig. 2a) and the ratio of48Ca / 44Ca was measured using a mass spectrometer. Inventors found an enrichment of 1.5%, which corresponds to 3% in the48Ca / 40Ca. The sectors and the ratio plot are shown in figure 2b. A clear enrichment can be observed. This is a validation in the lab of the method in a ternary salt.

Claims

CLAIMS1. A method of pre-enriching an isotope, comprising providing an un-enriched mixture comprising a first salt comprising the to be enriched first cation isotope of a first chemical element, and a first anion, and at least one further isotope cation of said chemical element, and at least one second salt comprising a second anion and a second cation, wherein the second cation has a lower charge than the first cation, providing the un-enriched mixture in an enrichment system, the enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), a heater for heating the respective compartments, a salt outlet (13) at the cathode side in fluidic contact with the at least one cathode compartment CC, a salt inlet (12) at the anode side in fluidic contact with the at least one anode compartment AC, and optionally a bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment, the bridging compartment comprising a filter F, melting the salt, applying a voltage to the cathode and anode during an enrichment time at an enrichment current, therewith providing flows of the respective ions of the molten salt, and supplementing the at least one second salt to the salt inlet (12) at the anode side and removing the at least one second salt at the salt outlet (13) at the cathode side.

2. The method according to claim 1, comprising providing un-enriched mixture to the salt inlet (11) at the cathode side.

3. The method according to any of claims 1-2, comprising removing an isotope cation depleted mixture from a salt outlet (13) at the cathode side.

4. The method according to any of claims 1-3, comprising providing the second salt at the salt inlet at the cathode side, wherein the second salt comprises a more mobile cation than that of the second salt supplemented at the salt inlet at the anode side, such as NH4+salts.

5. The method according to any of claims 1-4, wherein the first cation is selected from Ca, Mg, Nd, Ni, Zn, Gd, Yb, and Dy.

6. The method according to any of claims 1-5, comprising two or more second salts, in particular 3-12 second salts7. The method according to any of claims 1-6, wherein the at least one second salt comprises at least one second cation of a second chemical element of a lower Group in the periodic table than the first chemical element of the to be enriched isotope first cation, wherein a charge of the first cation is selected from +1 and +2, and wherein a charge of the second cation is selected from +2, +3, +4, +5, and +6, and / or wherein the second cation has a higher mobility in the mixture than the first cation.

8. The method according to any of claims 1-7, wherein the voltage is from 50-120 V DC, in particular 70-90 V DC, and / or wherein the current is from 10-10000 mA, in particular from 20-5000 mA, more in particular 50-2000 mA, such as 100-1000 mA, and / or wherein the provided electrical charge is from 100-3000 kC, and / or wherein the enrichment time is from 1-50 days, in particular from 3-21 days.

9. The method according to any of claims 1-8, wherein the first and second anion each individually may be selected from nitrate (NCh'), halides, in particular CT, Br", and T, nitrous oxides, oxyanions of halides, such as chlorate, and combinations thereof, in particular wherein the first and second anion are the same, and / or wherein the second cation is selected from Group I cations, in particular Li+, Na+, and K+, and from ammonia (NH4+),10. The method according to any of claims 1-9, wherein the mixture melts at a temperature of 50-500 °C (323-773 K), in particular a temperature of 80-300 °C (353-573 K), more in particular a temperature of 100-200 °C (373-473 K), such as 130-180 °C (403-453 K), and / or wherein the mixture is a eutectic mixture.

11. The method according to any of claims 1-10, wherein the first anion is nitrate and wherein the second anion is nitrate, and / or wherein the second anion is the same for the at least one second salts, and / or wherein the mixture is one of a binary mixture, a ternary mixture, and a quaternary mixture, and / or wherein the second cation is selected from Na+, K+, and combinations thereof, and / or wherein the first cation is Ca2+.

12. The method according to any of claims 1-11, further comprising adding a formed species at the first cathode, in particular NO2.

13. The method according to any of claims 1-12, wherein the first cathode comprises an element selected from carbon, such as graphite, W, and Ti, and / or wherein the first anode comprises a noble metal, in particular Pt, and / or wherein the first anode comprise a core of Ti.

14. The method according to any of claims 1-13, wherein the method is repeated, in particular repeated 2-10 times.

15. The method according to any of claims 1-14, wherein providing un-enriched mixture to the salt inlet is in a continuous mode, or in a semi-continuous mode.

16. The method according to any of claims 1-15, wherein removing an isotope depleted mixture from the salt outlet (13) is in a continuous mode, or in a semi-continuous mode, and / or providing un-enriched first salt at the salt inlet (11) in a continuous mode, or in a semi-continuous mode.

17. The method according to any of claims 1-16, wherein an enriched mixture is removed.

18. The method according to any of claims 1-17, wherein the at least one supplemented second salt is provided in a continuous mode, or in a semi-continuous mode.

19. The method according to any of claims 1-18, wherein the mixture forms a gas at the cathode, in particular wherein the gas is selected from halogens, such as Ch, Bn, and I2, from NO2, fromO2, and from CO2.

20. A computer program comprising instructions, the instructions when loaded and running on a computer causing the computer to carry out: providing an un-enriched mixture comprising a first salt comprising the to be enriched first cation isotope of a first chemical element, and a first anion, and at least one further isotope cation of said chemical element, and at least one second salt comprising a second anion and a second cation, wherein the second cation has a lower charge than the first cation, providing the un-enriched mixture in an enrichment system, the enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), a heater for heating the respective compartments, a salt outlet (13) at the cathode side in fluidic contact with the at least one cathode compartment CC, a salt inlet (12) at the anode side in fluidic contact with the at least one anode compartment AC, and optionally a bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment, the bridging compartment comprising a filter F, melting the salt, applying a voltage to the cathode and anode during an enrichment time at an enrichment current, therewith providing flows of the respective ions of the molten salt, and supplementing the at least one second salt to the salt inlet (12) at the anode side and optionally removing the at least one second salt at the salt outlet (13) at the cathode side.

21. The computer program according to claim 20, further comprising balancing at least two current selected from cation currents and anion currents.

22. A pre-enrichment system comprising at least one cathode compartment CC comprising a cathode (4), at least one anode compartment AC comprising an anode (5), a heater for heating the respective compartments, a salt inlet (11) in fluidic contact with the at least one cathode compartment CC, a salt inlet (12) in fluidic contact with the at least one anode compartment AC, and optionally a bridging compartment BC in fluidic contact with the at least one cathode compartment and the at least one anode compartment, the bridging compartment comprising a filter F23. The pre-enrichment system according to claim 22, further comprising reservoir (2) in fluid connection with the salt inlet (11) for providing additional mixture to the enrichment system.

24. The pre-enrichment system according to claim 22 or 23, further comprising a heater.

25. The pre-enrichment system according to any of claims 22-24, further comprising at least one controller, wherein the at least one controller is selected from a temperature controller, a pressure controller, and a flow controller.

26. The pre-enrichment system according to any of claims 22-25, wherein the pre-enrichment system provides counter-current electromigration.

27. The pre-enrichment system according to any of claims 22-26, wherein a volume of the respective cathode compartment and anode compartment each individually is from 10-1000 cm3and / or, wherein a volume of the cathode compartment is 1.1-2 times the volume of the anode compartment, and / or wherein the respective cathode compartment and anode compartment each individually are made from an in view of the mixture chemically inert material, in particular selected from glass, and quartz, and / or wherein the bridging compartment is substantially U-shaped, and / or wherein the respective cathode compartment and anode compartment each individually are substantially cylindrical, and / or wherein the filter is selected from nanoporous filters, from mesoporous filters, and from microscopic filters.

28. The pre-enrichment system according to any of claims 22-27, wherein the reservoir (2) comprises a second cathode (1) and a second anode (3), wherein the reservoir is configured to provide a gaseous pre-cursor of the at least one second cation to the cathode compartment CC, in particular NO2.

29. An array (n*m) of pre-enrichment systems according to any of claims 22-28, wherein in the array an enriched mixture outlet (13) of an 1thpre-enrichment system in a row is in fluidic contact with a mixture inlet (I I ) of an i+ 1111pre-enrichment system in the same row, wherein ie [l,n-l],30. The array according to claim 29, wherein n is from 21-26, in particular n is from 22-24, and / or wherein m is from 2°-25, in particular m is from 2'-24.

31. The array according to claim 29 or 30, wherein in the array an enriched mixture outlet (13) of an nthpre-enrichment system of a j111row m is in fluidic contact with a mixture inlet (11) of a first pre-enrichment system in an j+ 1111row, wherein j e [l,m-l].

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