Polydadmac and its derivatives for [18f]fluoride concentration and trapping

Abstract

Disclosed herein is an anion exchanger, a method for manufacturing an anion exchanger, anion exchange devices, and a system comprising the anion exchanger, wherein the anion exchanger comprises a polyDADMAC polymer, and wherein the anion exchanger is suitable for purifying and concentrating [18F]fluoride.

Description

[0001] POLYDADMAC AND ITS DERIVATIVES FOR [18F]FLUORIDE CONCENTRATION AND TRAPPING

[0002] TECHNICAL FIELD

[0003] The present disclosure generally relates to radiolabeled radiopharmaceuticals. The disclosure relates particularly, though not exclusively, to radiolabeled radiopharmaceuticals obtained through18F-fluorination with anionic [18F]fluoride, also called18F’.

[0004] BACKGROUND

[0005] This section illustrates useful background information without admission of any technique described herein representative of the state of the art.

[0006] Positron emission tomography (PET) is a powerful diagnostic methodology enabling precise detection and monitoring of various diseases and clinical conditions, such as diagnosis of cancers or neurological diseases, non-invasively. PET imaging utilizes positron emitting diagnostic agents, namely radiotracers or radiopharmaceuticals, that are administered intravenously into the patient prior image acquisition with a PET camera. The most used PET radionuclide is fluorine-18 (18F) due to its wide availability, optimal half-life (ti / 2 = 110 min) and lower emitted positron energy, leading to shorter positron travel range in tissue and subsequently to higher spatial resolution of the PET image, in comparison to other readily available positron emitters.

[0007] Fluorine-18 is produced with a cyclotron in its anionic form (18F_, [18F]fluoride) within a liquid target comprising of oxygen-18 enriched water (H218O, >97% nuclidic purity) by bombardment of the target with high energy protons (MeV scale). This high-energy and harsh event results in activation of materials and leaching of metallic impurities from the target and other material in the way of the proton beam, as well as production of radioactive impurities, that require separation to ensure the purification of the resulting [18F]fluoride. These produced impurities may hamper any subsequent radiofluorination reactions. Additionally, it is widely known that most chemical reactions are concentration dependent leading to higher yields in higher concentrations, therefore concentration of the [18F]fluoride solution is often necessary. The separation of18F_generally takes place by a resin-based solid-phase extraction cartridge using ion-exchange (IEX) chemistry. This method is widely used and robust, resulting in purified18F_that has been concentrated from milliliter scale (2 - 5 mL typically) to hundreds of microliters (500 - 1000 pL), which serves as the gold standard for currently available radiofluorination chemistry. Resin-based cartridge concentration is traditionally used together with crown- ethers and azeotropic distillation to remove residual water from the concentrated [18F]fluoride, providing reactive nucleophilic18F_anions. This process is time-consuming and the [18F]fluoride is unevenly spread out in the reaction vessel leading to alterations in radiochemical yields (RCY) and absorption of18F_on the vessel material, resulting in loss of radioactivity, lower RCY% and lower molar activities (Am).

[0008] As the understanding of the power of PET imaging continuously increases as well as the increase in conditions requiring this diagnostic modality, novel diagnostic PET imaging agents are in high demand, requiring new radiofluorination chemistries for their production in meaningful RCYs. These novel radiofluorination reactions require often even more concentrated18F_in smaller volumes than previously, resulting in the attempt of transferring the traditional milliliter scale radiofluorination synthesis into microfluidic setups and into microliter volumes (< 50 pL). Several resin-based mini-cartridges have been assembled from commercially available IEX resin by various research groups byhand in-house, including us, in the attempt of attaining18F_in microliter volumes. The resin-based mini-cartridges perform often repeatably and are relatively robust and offer a setup compatible with current synthesis platforms but suffer from a concentration limit resulting from the minimum volume attainable for18F_due to the bed volume of the apparatus itself. Furthermore, the benefit of the microliter scale is often lost once the resin-based cartridge is connected with traditional luers and adjacent lines into a reaction vial, leading to “a droplet in a pool” effect. Hence, more streamlined microfluidic apparatus is required to offer a truly microfluidic setup from purification and concentration all the way into microfluidic radiofluorination of the precursor.

[0009] It is an object of the present disclosure to alleviate at least some of the above problems regarding currently available materials, devices and methods that are used for concentration and purification for aqueous18F- for manufacturing of18F-labelled radiopharmaceuticals for PET imaging. It is another object to provide an anion exchanger which can be used to effectively purify and concentrate anions, such as [18F]fluoride, into small volumes for use in PET imaging. SUMMARY

[0010] The present disclosure concerns the inventions defined in the appended independent claims, and their embodiments disclosed below. The appended claims define the scope of protection. Any method, process, product, or apparatus disclosed in the description or drawing which is not covered by a claim is provided as an example which is not an embodiment of the claimed invention, but which is useful for understanding the claimed invention.

[0011] 18F-chemistry for PET imaging requires nucleophilic anhydrous fluoride anions that are activated to actuate the subsequent nucleophilic reactions. Previously, this process has been achieved by solid-phase extraction cartridges and azeotropic distillation or by electrochemical separation of18F_that provides an alkaline solution of18F_in around milliliter scale (ca. 0.5-2 mL).

[0012] Herein is disclosed a novel ion-exchange (IEX) polymer for [18F]fluoride concentration and purification (lEX-polymer, also referred to as lEX-material and an anion exchanger) and a method to coat solid surfaces with the lEX-polymer for the trapping, purification, and concentration of [18F]fluoride. The present method uses polyDADMAC and optionally different crosslinking agents to tailor the IEX polymer suitable for the [18F]fluoride trapping devices. The developed lEX-polymer and apparatus enables microfluidic radiofluorination providing higher incorporation yields and simpler pre-concentration of [18F]fluoride prior radiosynthesis.

[0013] In the present disclosure a method is described for the preparation of novel cross-linked poly(diallyldimethylammonium chloride) (polyDADMAC) networks for [18F]fluoride purification and preconcentration prior to radiolabeling reaction. Furthermore, disclosed are methods enabling anchoring the polyDADMAC-based lEX-material on different solid supports, including porous polyethylene (PE) sterile filters and microfabricated, off- stoichiometric thiol-ene (OSTE) based microfluidic chips. These apparatuses offer efficient18F_concentration for streamlined radiolabeling, which further allows for higher incorporation yields and lower consumption of expensive precursors or reagents. The developed platform is optimally suited for water-tolerant highly concentration dependent radiofluorinations to precursors with e.g. trifluoroborate (BFs) moieties.

[0014] Above limitations of the presently available methods and materials for purifying18F- anions are at least partially alleviated by the present invention. According to a first aspect is provided a method for manufacturing an anion exchanger comprising: providing a reaction mixture comprising diallyldimethylammonium chloride (DADMAC) and an initiator; and heating to provide an anion exchanger comprising a polyDADMAC polymer.

[0015] In an embodiment the initiator is at least one of ethyl(2,4,6-trimethylbenzoyl)- phenylphosphinate (Igracure TPO-L), ammonium persulfate (APS), 2,2’-azobis(2- methylpropionamide) dihydrochloride (V-50), 1 -Hydroxycyclohexyl phenyl ketone, 2,2- Dimethoxy-2-phenylacetophenone, 1 -[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl- 1 -propane-1 -one, and Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0016] In an embodiment the reaction mixture further comprises at least one crosslinker capable of forming crosslinks between polymers of the poly-DADMAC polymer, the crosslinker being preferably a trifunctional allyl (3E), a tetrafunctional allyl (4E), or a combination thereof, and more preferably being selected from 1 ,3,5-triallyl-1 ,3,5-triazine- 2, 4, 6(1 H,3H,5H)-trione (TATATO, 3E), and pentaerythritol tetraacrylate (PETA, 4E), or a combination thereof.

[0017] In an embodiment the crosslinker is a trifunctional allyl (3E) or a tetrafunctional allyl (4E).

[0018] In an embodiment the reaction mixture further comprises a functionalized solid substrate, preferably an allyl-functionalized solid substrate, a thiol-functionalized solid substrate, or a combination thereof.

[0019] In an embodiment the reaction mixture further comprises a solid substrate, preferably an allyl-functionalized solid substrate, a thiol-functionalized solid substrate, or a combination thereof, into which the polyDADMAC polymer is mechanically or chemically anchored. In an embodiment the reaction mixture comprises an allyl-functionalized solid substrate prepared from or functionalized with at least one of 1 ,3,5-triallyl-1 ,3,5-triazine- 2, 4, 6(1 H,3H,5H)-trione (TATATO), pentaerythritol tetraacrylate (PETA), tetraallyl piperazinium dichloride (TAP), methacrylamidopropyl trimethyl ammonium chloride (MAPTAC), acrylamide (AM), methacryloxy-ethyltrimethyl ammonium chloride (DMC), acryloyloxyethyltrimethyl ammonium chloride (DAC), butylacrylate (BA), Tri(ethylene glycol) divinyl ether; Trimethylolpropane diallyl ether, Trimethylolpropane-tri(norborn-2- ene-5-carboxylate; Pentaerythritol-tri(norborn-2-ene-5-carboxylate); Pentaerythritol- tetra(norborn-2-ene-5-carboxylate), di(trimethylolpropane)tetra-(norborn-2-ene-5- carboxylate), 1 ,6-heptadiyne, and 1 ,7-octadiyne. In an embodiment the reaction mixture comprises a thiol-functionalized solid substrate prepared from or functionalized with at least one of pentaerythritol tetrakis(3- mercaptopropionate) (PETMP, trimethylolpropane tris(3-mercaptopropionate) (TMPTMP), 1 ,6-hexanedithiol, 2,5-dimercaptomethyl-1 ,4-dithiane, 2,3-dimercapto-1 - propanol, Benzene-1 ,2-dithiol, 1 ,8-octanedithiol, Ethylene glycol bis(3- mercaptopropionate), Trimethylolpropane tris(3-mercaptoacetate), 2,3- (dimercaptoethylthio)-l -mercaptopropane, and Pentaerythritol tetrakis(2- mercaptoacetate).

[0020] In an embodiment the reaction mixture further comprises at least one chain transfer agent, preferably a reversible addition-fragmentation chain transfer (RAFT) agent selected from at least of 2-(n-butyltrithiocarbonate)-propionic acid (BTPA), 2-((((2- carboxyethyl)thio)carbonothioyl)thio)-2-methylpropanoic acid (CEMP), bis(carboxymethyl) trithiocarbonate (BCMT), S,S’-bis(a,a’-dimethyl-a”-acetic acid)trithiocarbonate (BDMAT).

[0021] In an embodiment the solid substrate is at least one of a microfabricated solid support, microfluidic chip, capillary tube, microcapillary channel, microcapillary array, porous mini filter, centrifugal spin-filter, resin, and adsorbent material.

[0022] In an embodiment a microfluidic chip comprises openings and channels allowing passing fluid through the microfluidic chip.

[0023] In an embodiment the heating step comprises heating around 30-1200 min at around 40- 90 °C, preferably around 60-240 min at around 50-80 °C.

[0024] In an embodiment the heating step comprises heating around 30-300 min at around 40- 90 °C, preferably around 60-240 min at around 50-80 °C.

[0025] In an embodiment the method further comprises a pretreating step comprising irradiating the reaction mixture with UV light before heating, preferably irradiating with UV light at around 67-270 J / cm2.

[0026] In an embodiment the reaction mixture comprises a functionalized solid substrate, the reaction mixture is irradiated with UV light to provide an irradiated reaction mixture, and the irradiated reaction mixture is heated to provide a polyDADMAC polymer chemically anchored to the solid substrate. According to another aspect is provided an anion exchanger for concentrating and purifying anions and manufactured by the present method.

[0027] In an embodiment the anions comprise [18F]fluoride anions.

[0028] According to another aspect is provided an anion exchanger for concentrating and purifying [18F]fluoride and manufactured by the present method.

[0029] In an embodiment the present anion exchanger is characterized by having around 5 - 800 nm size distribution with > 90% of the polymer with size distribution between around 300 - 500 nm when manufactured with using a crosslinker.

[0030] In an embodiment the present anion exchanger is characterized by the polymer having about 5 - 800 nm size distribution. Preferably, more than 90% of the polymer has a size distribution between about 300 - 500 nm when manufactured with using a crosslinker.

[0031] The present anion exchanger has a size distribution, which is narrower than in previous polyDADMAC materials, such as in those used in wastewater treatment. The narrow size distribution makes the present anion exchanger preferable for [18F] purification.

[0032] In an embodiment the present anion exchanger has an operational anion exchange capacity in the range around 1000 - 2000 neq / mg.

[0033] According to another aspect is provided an anion exchange device, wherein the anion exchange device is a purification cartridge comprising at least one inlet configured to receive a fluid comprising [18F]fluoride and impurities; a body housing the present anion exchanger; and at least one outlet configured to elute purified [18F]fluoride.

[0034] In an embodiment in the present anion exchange device the anion exchanger is arranged inside the body housing the anion exchanger as a bed.

[0035] In an embodiment in the present anion exchange device the anion exchanger is positioned between the at least one inlet and the at least one outlet.

[0036] According to another aspect is provided a microfluidic device comprising at least one volume configured to allow passing fluid through the microfluidic device, a linear and / or a crosslinked network of the present anion exchanger inside the volume, and optionally the anion exchanger being covalently attached to at least one surface defining the volume, and optionally filling the volume. In an embodiment the anion exchanger is chemically attached to at least one surface defining the volume. In another embodiment the anion exchanger is mechanically attached to at least one surface defining the volume. According to another aspect is provided a method for purifying anions comprising providing a solution comprising anions in an aqueous medium; contacting the solution with the present anion exchanger, with the present anion exchange device, or with the present microfluidic device, to provide anions bound to the anion exchanger; optionally washing; and subsequently eluting the bound anions to obtain purified anions.

[0037] In an embodiment the anions comprise radioactive anions,18F_anions, cyclotron produced18F_anions, or stable19F_anions.

[0038] In an embodiment the anions comprise cyclotron produced18F_anions.

[0039] In an embodiment in the elution step the precursor is eluted to a volume below 50 pL, preferably to a volume below 40 pl, more preferably to a volume below 30 pl.

[0040] According to another aspect is provided a kit for producing a radiotracer comprising the present anion exchange device, or the present microfluidic device, and further comprising a reaction vial for mixing the purified18F_with a precursor molecule.

[0041] According to another aspect is provided a system comprising the present anion exchange device or the present microfluidic device; pumps and valves configured to control fluid flow through the device; temperature control means configured to monitor and set temperature of device; and control logic configured to control operation of the system and fluid flow through the device.

[0042] The present anion exchanger, as well as devices and systems containing it, allow efficient purification and concentration of anions, such as18F_, into small volumes with high efficiency. Due to the unique properties of the synthesized polyDADMAC polymer, the anion exchanger is suitable for purifying and concentrating anions, such as18F_anions. The present method is able to produce an anion exchanger, which is suitable to purify and / or concentrate18F_anions in purity and in volumes that can be used in manufacturing of radiolabeled radiopharmaceuticals. Additionally, due to the flexible manufacturing method, the present anion exchanger can be chemically and covalently attached to solid substrates during polymerization simultaneously with the polymerization reaction. Alternatively, the polymerized polyDADMAC can be attached on solid substrates after polymerization. BRIEF DESCRIPTION OF THE FIGURES

[0043] Some example embodiments will be described with reference to the accompanying figures, wherein:

[0044] Figure 1 is the structure of 1 ,3,5-Triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (3E) crosslinked poly-DADMAC3E proposed repeating unit.

[0045] Figure 2 is the structure of Pentaerythritol tetraacrylate (PETA, 4E) crosslinked polyDADMAC4E proposed repeating unit.

[0046] Figures 3 and 4 shows1H NMR and13C analysis results demonstrating the characteristic signals of a polyDADMACiinear.

[0047] Figure 5 shows DLS data of commercially available polyDADMACiinear homopolymer used as reference.

[0048] Figure 6 shows DLS data of in-house synthesized polyDADMACiinear homopolymer.

[0049] Figure 7 shows DLS data of in-house synthesized crosslinked polyDADMAC4E copolymer.

[0050] Figure 8 shows ATR-FTIR data of commercially available polyDADMACiinear homopolymer and commercially available DADMAC monomer used as references.

[0051] Figure 9 shows ATR-FTIR data of polyDADMACiinear reference material, synthesized polyDADMACiinear from two samples and synthesized crosslinked polyDADMAC4E.

[0052] Figure 10 shows SEM-EDS of linear polyDADMAC (a reference sample).

[0053] Figure 11 shows SEM-EDS of branched polyDADMAC4E according to the invention.

[0054] DETAILED DESCRIPTION

[0055] In an embodiment the functionalized solid substrate is an allyl-functionalized solid substrate without further functionalization for crosslinking.

[0056] In an embodiment the functionalized solid substrate is a thiol-functionalized solid substrate without further functionalization for crosslinking.

[0057] In an embodiment the allyl-functionalized solid substrate contains an excess of or is functionalized with at least one of 1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO), pentaerythritol tetraacrylate (PETA), tetraallyl piperazinium dichloride (TAP), methacrylamidopropyl trimethyl ammonium chloride (MAPTAC), acrylamide (AM), methacryloxyethyltrimethyl ammonium chloride (DMC), acryloyloxyethyltrimethyl ammonium chloride (DAC), butylacrylate (BA), Tri(ethylene glycol) divinyl ether; Trimethylolpropane diallyl ether, Trimethylolpropane-tri(norborn-2-ene-5-carboxylate; Pentaerythritol-tri(norborn-2-ene-5-carboxylate); Pentaerythritol-tetra(norborn-2-ene-5- carboxylate), di(trimethylolpropane)tetra-(norborn-2-ene-5-carboxylate), 1 ,6-heptadiyne, and 1 ,7-octadiyne. Consequently, after the method the anion exchanger is a cross-linked polyDADMAC functionalized with the above agent.

[0058] In an embodiment in the present method the functionalized solid substrate contains an excess of or is a thiol-functionalized solid substrate functionalized with at least one of but not limited to pentaerythritol tetrakis(3-mercaptopropionate) (PETMP, trimethylolpropane tris(3-mercaptopropionate) (TMPTMP), 1 ,6-hexanedithiol, 2,5-dimercaptomethyl-1 ,4- dithiane, 2, 3-dimercapto-1 -propanol, Benzene-1 ,2-dithiol, 1 ,8-octanedithiol, Ethylene glycol bis(3-mercaptopropionate), Trimethylolpropane tris(3-mercaptoacetate), 2,3- (dimercaptoethylthio)-l -mercaptopropane, and Pentaerythritol tetrakis(2- mercaptoacetate).

[0059] In an embodiment in the present method reversible addition-fragmentation chain transfer (RAFT) agent is added, the RAFT agent being selected from at least one of but not limited to the 2-(n-butyltrithiocarbonate)-propionic acid (BTPA), 2-((((2-carboxyethyl)thio)- carbonothioyl)thio)-2-methylpropanoic acid (CEMP), bis(carboxymethyl) trithiocarbonate (BCMT), S,S'-bis(a, a'-dimethyl-a"-acetic acid)trithiocarbonate (BDMAT). The RAFT agent may be used to control polymerization.

[0060] In an embodiment in the present method the solid substrate is at least one of a microfluidic solid support, microchip, capillary tube, microcapillary array, porous mini filter, centrifugal spin-filter, resin, and adsorbent material; or at least one surface, filter, or matrix thereof.

[0061] In an embodiment the polyDADMAC polymer is a polyDADMAC polymer gel. In another embodiment, the polyDADMAC polymer is a polyDADMAC polymer gel, in which polyDADMAC polymer chains are at least partially crosslinked with each other. In another embodiment, the polyDADMAC polymer gel is anchored chemically and / or mechanically to the solid support.

[0062] In an embodiment the method comprises immersing a solid support, such as a porous filter or microfluidic chip, with the reaction mixture, optionally exposing to UV irradiation, heating, and washing to remove unreacted material comprising DADMAC monomers. This allows manufacturing an anion exchanger, in which the polyDADMAC polymer or the polyDADMAC polymer gel is manufactured inside solid support, such as the porous filter or chip. Additionally, if a functionalized solid substrate is used, the polyDADMAC can be chemically anchored to the solid substrate.

[0063] In an embodiment the method comprises applying the reaction mixture to a vial comprising a solid support filter, optionally exposing to UV irradiation, heating, and washing to remove unreacted material comprising DADMAC monomers.

[0064] In an embodiment the anion exchange capacity is expressed as X neq / mg, meaning that 1 milligram of the material can adsorb or exchange X nanoequivalents of anions. In an embodiment the anion exchange capacity is expressed as based on dry weight.

[0065] In an embodiment the anion exchanger has an operational anion exchange capacity in the range around 1000 - 2000 neq / mg, or around 1000-1900, 1000-1800, 1000-1700, 1000-1600, 1000-1500, 1000-1400, 1100-1900, 1100-1800, 1100-1700, 1100-1600, 1100-1500, 1100-1400,1200-1900, 1200-1800, 1200-1700, 1200-1600, 1200-1500, 1200-1400, 1300-1900, 1300-1800, 1300-1700, 1300-1600, 1300-1500, or 1300-1400 neq / mg.

[0066] In an embodiment the anion exchanger has a particle size distribution range of around 5-800 nm (hydrodynamic size) and operational anion exchange capacity > 1000 neq / mg (dry).

[0067] In an embodiment the anion exchanger has a particle size distribution range of around 5-800 nm (hydrodynamic size) and operational anion exchange capacity > 1300 neq / mg (dry).

[0068] As used herein, the particle size refers to the particle size of the polymerized DADMAC.

[0069] In an embodiment the present microfluidic device comprises at least one microfluidic chip and / or at least one microchannel, and the present anion exchanger substantially fills at least one microchannel of the microfluidic chip. In another embodiment the microfluidic chip comprises a bed of the anion exchanger, which fills at least partially at least one microchannel. In another embodiment the present anion exchanger is chemically anchored on at least one surface of the microfluidic device, such as on a surface of a microchannel or a reaction chamber. In an embodiment the microfluidic device comprises at least volume which is connected to at least one inlet and at least one outlet configured to allow passing fluid through the microfluidic device, such as a microchannel or a reaction chamber inside the microfluidic device.

[0070] In the microfluidic chip the present anion exchanger may be covalently attached to at least one surface of the microfluidic chip, or a surface defining the volume. The surface may be a surface of a microchannel, or a surface of chamber inside the microfluidic chip, such as a reaction chamber or a mixing chamber. In another embodiment the surface is at least one surface of a micropillar or an array of micropillars inside the microfluidic chip.

[0071] In another embodiment is provided a method for manufacturing a radioactive precursor comprising providing a solution comprising cyclotron produced18F_ions in an aqueous medium; contacting the solution with the present anion exchanger or with the present anion exchange device, to provide18F_bound to the anion exchanger; and subsequently eluting the bound18F_to obtain purified18F_.

[0072] In an embodiment in the present method the purified18F_is eluted with a volume below 50 pL.

[0073] The present methods, materials, and devices are advantageous because they allow efficient purification and concentration of18F_anions. Because of the present anion exchanger material, the purified18F_anions can be eluted in a very small volume, which has been impossible or difficult with previous methods. Notably, the present anion exchanger allows very small elution volumes with high yield, which makes the anion exchanger material suitable for demanding applications such as microfluidic devices.

[0074] As used herein, the term “tracer compound” or “tracer” means a chemical compound that can be traced with radiation detectors. In an embodiment, the tracer compound contains one or more atoms that have been replaced by a radionuclide, preferably fluorine-18.

[0075] As used herein, a crosslinker refers to a reagent which participates in the polymerization and branching of the DADMAC network.

[0076] The selected crosslinker influences the resulting polyDADMAC characteristics (solubility, wettability, particle size distribution, charge density, ion-exchange capacity, rigidness).

[0077] In an embodiment the crosslinker is selected such that the polyDADMAC network is chemically modified to enhance its stabilization and interaction with the18F_. In an embodiment the crosslinker is 1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO, 3E) or pentaerythritol tetraacrylate (PETA, 4E), or a combination thereof.

[0078] As used herein, a solid substrate refers to a solid support onto which the DADMAC polymer is covalently anchored or into which the DADMAC polymer is mechanically trapped / anchored. The solid support may be functionalized such that the DADMAC polymer network is covalently bound to the solid support.

[0079] In one embodiment, the terms mechanically anchored or mechanically trapped to a solid substrate mean use of physical methods such as at least one of interlocking structures, compression, external fasteners, and surface roughening, to secure attachment of the polymer to the solid substrate without chemical bonding.

[0080] As used herein, an initiator herein refers to a chemical that catalyzes crosslinking reactions. The initiator is selected by its water solubility (miscibility), and its activation method (UV irradiation, heat).

[0081] In an embodiment the pretreatment step comprises irradiating at around 320-390 nm wavelength.

[0082] In an embodiment the pretreatment step comprises irradiating at around 320-330 nm, 320-340 nm, 320-350 nm, 320-360 nm, 320-370 nm, 320-380 nm, 320-390 nm, 330-340 nm, 330-350 nm, 330-360 nm, 330-370 nm, 330-380 nm, 330-390 nm, 340-350 nm, 340- 360 nm, 340-370 nm, 340-380 nm, 340-390 nm, 350-360 nm, 350-370 nm, 350-380 nm, 350-390 nm, 360-370 nm, 360-380 nm, 360-390 nm, 370-380 nm, 370-390 nm, or 380- 390 nm.

[0083] In an embodiment the heating step comprises heating at a temperature of at least 30°C.

[0084] In an embodiment the heating step comprises heating at a temperature of not more than 90°C.

[0085] In an embodiment the heating step comprises heating at around 30-40 °C, 30-50 °C, 30- 60 °C, 30-70 °C, 30-80 °C, 30-90 °C, 40-50 °C, 40-60 °C, 40-70 °C, 40-80 °C, 40-90 °C, 50-60 °C, 50-70 °C, 50-80 °C, 50-90 °C, 60-70 °C, 60-80 °C, 60-90 °C, 70-80 °C, 70-90 °C, or 80-90 °C.

[0086] In an embodiment the heating step comprises heating for at least 30min.

[0087] In an embodiment the heating step comprises heating for not more than 1200min. In an embodiment the heating step comprises heating for around 30-60 min, 30-90 min, 30-120 min, 30-150 min, 30-180 min, 30-210 min, 30-240 min, 30-270 min, 30-300 min, 60-90 min, 60-120 min, 60-150 min, 60-180 min, 60-210 min, 60-240 min, 60-270 min, 60-300 min, 90-120 min, 90-150 min, 90-180 min, 90-210 min, 90-240 min, 90-270 min, 90-300 min, 120-150 min, 120-180 min, 120-210 min, 120-240 min, 120-270 min, 120- 300 min, 150-180 min, 150-210 min, 150-240 min, 150-270 min, 150-300 min, 180-210 min, 180-240 min, 180-270 min, 180-300 min, 210-240 min, 210-270 min, 210-300 min, 240-270 min, 240-300 min, or 270-300 min.

[0088] In an embodiment the heating step comprises heating for around 40-60 min, 40-90 min, 40-120 min, 40-150 min, 40-180 min, 40-210 min, 40-240 min, 40-270 min, 40-300 min, 70-90 min, 70-120 min, 70-150 min, 70-180 min, 70-210 min, 70-240 min, 70-270 min, 70-300 min, 100-120 min, 100-150 min, 100-180 min, 100-210 min, 100-240 min, 100- 270 min, 100-300 min, 130-150 min, 130-180 min, 130-210 min, 130-240 min, 130-270 min, 130-300 min, 160-180 min, 160-210 min, 160-240 min, 160-270 min, 160-300 min, 190-210 min, 190-240 min, 190-270 min, 190-300 min, 220-240 min, 220-270 min, 220- 300 min, 250-270 min, 250-300 min, or 280-300 min.

[0089] In an embodiment the heating step comprises heating for around 30-1200 min, 40-1200 min, 50-1200 min, 60-1200 min, 70-1200 min, 80-1200 min, 90-1200 min, 100-1200 min, 110-1200 min, 120-12000 min, 150-1200 min, 180-1200 min, 210-1200 min, 240-1200 min, 270-1200 min, 300-1200 min, 330-1200 min, 360-1200 min, 390-1200 min, 420- 1200 min, 450-1200 min, 480-1200 min, 510-1200 min, 540-1200 min, 600-1200 min, 660-1200 min, 720-1200 min, 780-1200 min, 810-1200 min, 840-1200 min, 870-1200 min, 900-1200 min, 930-1200 min, 960-1200 min, 990-1200 min, 1020-1200 min, 1050- 1200 min, 1080-1200 min, 1110-1200 min, 1140-1200 min, or 1170-1200 min.

[0090] In an embodiment the heating step comprises heating for around 30-1200 min at around 40-90 °C.

[0091] In an embodiment the heating step comprises heating for around 30-300 min at around 40-90 °C, preferably for around 60-240 min at around 50-80 °C.

[0092] In an embodiment the functionalized solid substrate is irradiated with UV light to initiate anchoring to the surface of the functionalized solid substrate. According to this embodiment, when a functionalized solid substrate is used, the UV irradiation thus anchors the polymerizing DADMAC monomers to the solid substrate, and the subsequent heating maintains polymerization reaction, because the polymerization reaction is heat- initiated. Alternatively or optionally, it is also possible to first carry out the heating to polymerize monomers, and then irradiate with UV to anchor the polyDADMAC on the surface of the functionalized solid substrate.

[0093] In an embodiment the pretreating step comprises irradiating with UV at least 67, 70, or 80 J / cm2.

[0094] In an embodiment the pretreating step comprises irradiating with UV at not more than 270 J / cm2.

[0095] In an embodiment the pretreating step comprises irradiating with UV at around 67-270 J / cm2.

[0096] In an embodiment the pretreating step comprises irradiating with UV at around 60-80 J / cm2, 60-90 J / cm2, 60-100 J / cm2, 60-110 J / cm2, 60-120 J / cm2, 60-130 J / cm2, 60-140 J / cm2, 60-150 J / cm2, 60-160 J / cm2, 60-170 J / cm2, 60-180 J / cm2, 60-190 J / cm2, 60-200

[0097] J / cm2, 60-210 J / cm2, 60-220 J / cm2, 60-230 J / cm2, 60-240 J / cm2, 60-250 J / cm2, 60-260

[0098] J / cm2, 60-270 J / cm2, 70-90 J / cm2, 70-100 J / cm2, 70-110 J / cm2, 70-120 J / cm2, 70-130 J / cm2, 70-140 J / cm2, 70-150 J / cm2, 70-160 J / cm2, 70-170 J / cm2, 70-180 J / cm2, 70-190

[0099] J / cm2, 70-200 J / cm2, 70-210 J / cm2, 70-220 J / cm2, 70-230 J / cm2, 70-240 J / cm2, 70-250

[0100] J / cm2, 70-260 J / cm2, 70-270 J / cm2, 80-100 J / cm2, 80-110 J / cm2, 80-120 J / cm2, 80-130

[0101] J / cm2, 80-140 J / cm2, 80-150 J / cm2, 80-160 J / cm2, 80-170 J / cm2, 80-180 J / cm2, 80-190

[0102] J / cm2, 80-200 J / cm2, 80-210 J / cm2, 80-220 J / cm2, 80-230 J / cm2, 80-240 J / cm2, 80-250

[0103] J / cm2, 80-260 J / cm2, 80-270 J / cm2, 90-110 J / cm2, 90-120 J / cm2, 90-130 J / cm2, 90-140

[0104] J / cm2, 90-150 J / cm2, 90-160 J / cm2, 90-170 J / cm2, 90-180 J / cm2, 90-190 J / cm2, 90-200

[0105] J / cm2, 90-210 J / cm2, 90-220 J / cm2, 90-230 J / cm2, 90-240 J / cm2, 90-250 J / cm2, 90-260

[0106] J / cm2, 90-270 J / cm2, 100-120 J / cm2, 100-130 J / cm2, 100-140 J / cm2, 100-150 J / cm2, 100- 160 J / cm2, 100-170 J / cm2, 100-180 J / cm2, 100-190 J / cm2, 100-200 J / cm2, 100-210 J / cm2, 100-220 J / cm2, 100-230 J / cm2, 100-240 J / cm2, 100-250 J / cm2, 100-260 J / cm2, 100-270 J / cm2, 110-130 J / cm2, 110-140 J / cm2, 110-150 J / cm2, 110-160 J / cm2, 110-170 J / cm2, 110-180 J / cm2, 110-190 J / cm2, 110-200 J / cm2, 110-210 J / cm2, 110-220 J / cm2, 110-230 J / cm2, 110-240 J / cm2, 110-250 J / cm2, 110-260 J / cm2, 110-270 J / cm2, 120-140 J / cm2, 120-150 J / cm2, 120-160 J / cm2, 120-170 J / cm2, 120-180 J / cm2, 120-190 J / cm2, 120-200 J / cm2, 120-210 J / cm2, 120-220 J / cm2, 120-230 J / cm2, 120-240 J / cm2, 120-250 J / cm2, 120-260 J / cm2, 120-270 J / cm2, 130-150 J / cm2, 130-160 J / cm2, 130-170 J / cm2, 130-180 J / cm2, 130-190 J / cm2, 130-200 J / cm2, 130-210 J / cm2, 130-220 J / cm2, 130-230 J / cm2, 130-240 J / cm2, 130-250 J / cm2, 130-260 J / cm2, 130-270 J / cm2, 140-160 J / cm2, 140-170 J / cm2, 140-180 J / cm2, 140-190 J / cm2, 140-200 J / cm2, 140-210 J / cm2, 140-220 J / cm2, 140-230 J / cm2, 140-240 J / cm2, 140-250 J / cm2, 140-260 J / cm2, 140-270 J / cm2, 150-170 J / cm2, 150-180 J / cm2, 150-190 J / cm2, 150-200 J / cm2, 150-210 J / cm2, 150-220 J / cm2, 150-230 J / cm2, 150-240 J / cm2, 150-250 J / cm2, 150-260 J / cm2, 150-270 J / cm2, 160-180 J / cm2, 160-190 J / cm2, 160-200 J / cm2, 160-210 J / cm2, 160-220 J / cm2, 160-230 J / cm2, 160-240 J / cm2, 160-250 J / cm2, 160-260 J / cm2, 160-270 J / cm2, 170-190 J / cm2, 170-200 J / cm2, 170-210 J / cm2, 170-220 J / cm2, 170-230 J / cm2, 170-240 J / cm2, 170-250 J / cm2, 170-260 J / cm2, 170-270 J / cm2, 180-200 J / cm2, 180-210 J / cm2, 180-220 J / cm2, 180-230 J / cm2, 180-240 J / cm2, 180-250 J / cm2, 180-260 J / cm2, 180-270 J / cm2, 190-210 J / cm2, 190-220 J / cm2, 190-230 J / cm2, 190-240 J / cm2, 190-250 J / cm2, 190-260 J / cm2, 190-270 J / cm2, 200-220 J / cm2, 200-230 J / cm2, 200-240 J / cm2, 200-250 J / cm2, 200-260 J / cm2, 200-270 J / cm2, 210-230 J / cm2, 210-240 J / cm2, 210-250 J / cm2, 210-260 J / cm2, 210-270 J / cm2, 220-240 J / cm2, 220-250 J / cm2, 220-260 J / cm2, 220-270 J / cm2, 230-250 J / cm2, 230-260 J / cm2, 230-270 J / cm2, 240-260 J / cm2, 240-270 J / cm2, or 250-270 J / cm2.

[0107] In an embodiment polymerization reaction of the DADMAC monomers is continued up to 2 h and maximum 20 h. The present method is advantageous in that extended periods typically required for DADMAC polymerization for manufacturing anion exchange materials can be avoided Furthermore, when applying a crosslinker and optionally a longer heating time (max. 20 h), a polymer with more uniform and narrow size range distribution can be produced.

[0108] In an embodiment, when the18F_is eluted, an elution solution, or an elution buffer solution, is used which is compatible with the subsequent synthesis of18F-labeled tracer. This has an advantage of ensuring that the purified18F_is in a form directly usable for PET radiotracer synthesis. Alternatively, the bound18F_can be washed with a compatible solution and eluted with a desired elution solution.

[0109] As used herein, the term “18F” or “Fluorine-18” means a fluorine radioisotope which decays mainly by positron emission. Fluorine-18 can be produced in a cyclotron by bombarding oxygen-18 enriched water with protons.

[0110] As used herein, the term “radioimaging” refers to a method employing radioactive substances to visualize and measure physiological structures and activities inside macro- or micro-organisms. As used herein, the term “comprising” includes the broader meanings of ’’including”, ’’containing”, and ’’comprehending", as well as the narrower expressions “consisting of’ and “consisting only of’.

[0111] The terms “a” and “an” and “the” and similar in the context of describing features, elements, examples, or claims are to be construed to cover both the singular and the plural, unless otherwise indicated or clearly contradicted by context.

[0112] Recitation of ranges of values herein are merely intended to serve as a way of referring individually to each separate value falling within the range, unless otherwise indicated herein. Each separate value is thus disclosed in the specification as if it were individually recited. In an embodiment, and as is understood by the skilled person in the context in which the expression is used, an open-ended range such as “less than 10” is to be construed as a range disclosing values below 10, but above 0. Such a range can be understood to include a lower limit of e.g. 0.0001 , 0.001 , 0.1 , or 1 . If a lower limit is not recited, a lower limit of an open-ended range can be determined by the skilled person such that at least one technical effect is observable or measurable, thereby excluding insignificant trace amounts in the relevant context.

[0113] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any example, or exemplary language (e.g., “such as”, “for example”, and “optionally”) provided herein, is intended merely to better illustrate various embodiments and it does not limit the scope of the claims unless otherwise stated. No language in the specification should be construed as indicating that any non-claimed element is an essential feature of the invention. In another embodiment the method steps are carried out in the sequence of steps specified in any embodiment disclosed herein.

[0114] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about” or “around”. Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims may be applied in the present invention as approximations that may vary depending upon the desired properties sought to be obtained by embodiments of the present disclosure. As used herein, “about” and “around” may be understood by persons of ordinary skill in the art and can vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used, “about” and “around” may mean up to plus or minus 10% of the particular term. In another embodiment the recited numerical parameter is employed instead of its approximation.

[0115] Implementation and embodiments of the claimed invention are further disclosed in the following numbered clauses:

[0116] Clause 1 : A method for manufacturing an anion exchanger comprising: providing a reaction mixture comprising diallyldimethylammonium chloride (DADMAC) and an initiator; and heating to provide an anion exchanger comprising a polyDADMAC polymer.

[0117] Clause 2: The method of clause 1 , wherein the initiator is at least one of ethyl(2,4,6- trimethylbenzoyl)-phenylphosphinate (Igracure TPO-L), ammonium persulfate (APS), 2,2’-azobis(2-methylpropionamide) dihydrochloride (V-50), 1 -Hydroxycyclohexyl phenyl ketone, 2,2-Dimethoxy-2-phenylacetophenone, 1 -[4-(2-hydroxyethoxy)-phenyl]-2- hydroxy-2-methyl-1 -propane-1 -one, and Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0118] Clause 3: The method of clause 1 or 2, wherein the reaction mixture further comprises at least one crosslinker capable of forming crosslinks between polymers of the polyDADMAC polymer, the crosslinker being preferably a trifunctional allyl (3E), a tetrafunctional allyl (4E), or a combination thereof, and more preferably being selected from 1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO, 3E), and pentaerythritol tetraacrylate (PETA, 4E), or a combination thereof.

[0119] Clause 4: The method of any one of clauses 1 -3, wherein the reaction mixture further comprises a solid substrate, preferably an allyl-functional ized solid substrate, a thiol- functionalized solid substrate, or a combination thereof, into which the polyDADMAC polymer is mechanically or chemically anchored.

[0120] Clause 5: The method of clause 4, wherein the reaction mixture comprises an allyl- functionalized solid substrate prepared from or functionalized with at least one of 1 ,3,5- triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO), pentaerythritol tetraacrylate (PETA), tetraallyl piperazinium dichloride (TAP), methacrylamidopropyl trimethyl ammonium chloride (MAPTAC), acrylamide (AM), methacryloxyethyltrimethyl ammonium chloride (DMC), acryloyloxyethyltrimethyl ammonium chloride (DAC), butylacrylate (BA), Tri(ethylene glycol) divinyl ether; Trimethylolpropane diallyl ether, Trimethylolpropane- tri(norborn-2-ene-5-carboxylate; Pentaerythritol-tri(norborn-2-ene-5-carboxylate); Pentaerythritol-tetra(norborn-2-ene-5-carboxylate), di(trimethylolpropane)tetra-(norborn- 2-ene-5-carboxylate), 1 ,6-heptadiyne, and 1 ,7-octadiyne.

[0121] Clause 6: The method of clause 4 or 5, wherein the reaction mixture comprises a thiol- functionalized solid substrate prepared from or functionalized with at least one of pentaerythritol tetrakis(3-mercaptopropionate) (PETMP), trimethylolpropane tris(3- mercaptopropionate) (TMPTMP), 1 ,6-hexanedithiol, 2,5-dimercaptomethyl-1 ,4-dithiane, 2, 3-dimercapto-1 -propanol, Benzene-1 ,2-dithiol, 1 ,8-octanedithiol, Ethylene glycol bis(3- mercaptopropionate), Trimethylolpropane tris(3-mercaptoacetate), 2,3-(dimercapto- ethylthio)-1 -mercaptopropane, and Pentaerythritol tetrakis(2-mercaptoacetate).

[0122] Clause 7: The method of any one of clauses 1 -6, wherein the reaction mixture further comprises at least one chain transfer agent, preferably a reversible additionfragmentation chain transfer (RAFT) agent selected from at least of 2-(n- butyltrithiocarbonate)-propionic acid (BTPA), 2-((((2-carboxyethyl)thio)carbono- thioyl)thio)-2-methylpropanoic acid (CEMP), bis(carboxymethyl) trithiocarbonate (BCMT), S,S’-bis(a,a’-dimethyl-a”-acetic acid)trithiocarbonate (BDMAT).

[0123] Clause 8: The method of any one of clauses 1 -7, wherein the solid substrate is at least one of: a microfabricated solid support, microfluidic chip, capillary tube, microcapillary channel, microcapillary array, porous mini filter, centrifugal spin-filter, resin, and adsorbent material.

[0124] Clause 9: The method according to any one of clauses 1 -8, wherein the heating step comprises heating for around 30-300 min at around 40-90 °C, preferably around 60-240 min at around 50-80 °C.

[0125] Clause 10: The method according to any one of clauses 1 -9, wherein the method further comprises a pretreating step comprising irradiating the reaction mixture with UV light before heating, preferably irradiating with UV light at around 67-270 J / cm2.

[0126] Clause 11 : The method of any one of clauses 1 -10, wherein the reaction mixture comprises a functionalized solid substrate, the reaction mixture is irradiated with UV light to provide an irradiated reaction mixture, and the irradiated reaction mixture is heated to provide a polyDADMAC polymer chemically anchored to the solid substrate.

[0127] Clause 12: An anion exchanger for concentrating and purifying anions, and manufactured by the method of any one of the clauses 1 -11. Clause 13: The anion exchanger of clause 12 characterized by having around 5 - 800 nm size distribution with > 90% of the polymer with size distribution between around 300 - 500 nm when manufactured with a crosslinker.

[0128] Clause 14: The anion exchanger of clause 12 or 13 having an operational anion exchange capacity in the range around 1000 - 2000 neq / mg.

[0129] Clause 15: An anion exchange device, wherein the anion exchange device is a purification cartridge comprising at least one inlet configured to receive a fluid comprising [18F]fluoride and impurities; a body housing the anion exchanger of clauses 12-14; and at least one outlet configured to elute purified [18F]fluoride.

[0130] Clause 16: The anion exchange device of clause 15, wherein the anion exchanger is arranged inside the body housing the anion exchanger as a bed.

[0131] Clause 17: A microfluidic device comprising at least one volume configured to allow passing fluid through the microfluidic device, a linear and / or a crosslinked network of the anion exchanger of any one of clauses 12-14 inside the at least one volume, and optionally the anion exchanger being covalently attached to at least one surface defining the volume, and optionally filling the volume.

[0132] Clause 18: A method for purifying anions comprising providing a solution comprising anions in an aqueous medium; contacting the solution with the anion exchanger according to any one of clauses 12-14, with the anion exchange device according to any one of clauses15-16, or with the microfluidic device according to clause 17, to provide anions bound to the anion exchanger; optionally washing; and subsequently eluting the bound anions to obtain purified anions.

[0133] Clause 19: The method of clause 18, wherein the anions comprise cyclotron produced18F’ anions.

[0134] Clause 20: The method of clause 18 or 19, wherein in the elution step the precursor is eluted to a volume below 50 pL.

[0135] Clause 21 : A kit for producing a radiotracer comprising the anion exchange device of clauses 15-16, or the microfluidic device of clause 17, and further comprising a reaction vial for mixing the purified18F_with a precursor molecule.

[0136] Clause 22: A system comprising the anion exchange device of clauses 15-16 or the microfluidic device of clause 17; pumps and valves configured to control fluid flow through the device; temperature control means configured to monitor and set temperature of the device; and control logic configured to control operation of the system and fluid flow through the device.

[0137] EXAMPLES

[0138] The following examples are provided to better illustrate the claimed invention. The examples are not to be interpreted as limiting the scope of the invention, which is determined by the claims. To the extent that specific materials are mentioned, it is merely for purposes of illustration and is not intended to limit the invention. One skilled in the art may develop or purchase equivalent means or products without exercising inventive capacity and without departing from the scope of the invention.

[0139] Materials used in the Examples

[0140] Microfabrication materials

[0141] The silicon wafers were purchased from Siegert Wafer GmbH, Aachen, Germany.

[0142] Sil-8 100 was purchased from Kayaku Advanced Materials (Westborough, MA) and SU- 8 developer, Propylene glycol methyl ether acetate (PGMEA), was purchased from Sigma Aldrich (Steinheim, Germany).

[0143] Sylgard 184 poly(dimethylsiloxane) (PDMS) was purchased from Dow Chemical Company (Midland, Ml)

[0144] 1 ,3,5-Triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione, 98% (triallyl, 3E) was purchased from Sigma-Aldrich and pentaerythritol tetrakis(3-mercaptopropionate) (tetrathiol, 4T) was purchased from Bruno Bock Chemische Fabrik GmbH & Co. KG (Marschacht, Germany).

[0145] Diallyldimethylammonium chloride (DADMAC, >97.0%) was purchased from Sigma Aldrich. Diallyldimethylammonium chloride (DADMAC, 60 wt-% in H2O) was purchased from Sigma Aldrich. Polymerized DADMAC (polyDADMAC, 20 wt-% in H2O, Mw range 200 000 - 350 000 g / mol) was purchased from Sigma-Aldrich (Steinheim, Germany). Ammonium persulfate was purchased from Sigma-Aldrich. Pentaerythritol tetraacrylate (PETA) was purchased from Sigma-Aldrich. Poly(dimethyl siloxane) (PDMS) used for fabrication of the replication mold was prepared from Sylgard 184 base elastomer and curing agent (Down Corning Corporation, Midland, Ml). Irgacure TPO-L (photoinitiator) was kindly donated by BASF (Ludwigshafen, Germany). Omnirad 184 (1 - Hydroxycyclohexyl) phenyl ketone, Omnirad BDK (2,2-Dimethoxy-2-phenyl- acetophenone), Omnirad 2959 (1 -[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1 - propane-1-one), Omnirad 819 (Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide).

[0146] Monomer solution preparation for coating solid carrier materials with polyDADMAC

[0147] DADMAC (300 mg, 1.9 mol) was dissolved into ultrapure water (600 pL) constituting a 50-weight-% (wt-%) solution. The theoretical polymerization degree and size of polymer network was customized by adding crosslinking agents, such as for example 3E that is also used as the allyl monomer in the microchip fabrication. The DADMAC monomer solution was applied on top of ammonium persulfate (APS, 30 mg, 0.2 nmol). The solution was vortexed to dissolve APS and the solution was placed on top of PETA (40 mg, 0.1 mmol) and vortexed to afford a homogenous solution. From here on, the monomer solution was either applied on the solid surface (A) or optionally the solid support was immersed into the monomer solution (B). After functionalization the solids support systems were washed prior to further use. Wash sequence 1 ; 100% ultrapure water, 2; 20% acetonitrile).

[0148] Polymerization inside the solid support (A)

[0149] The monomer solution was applied inside the solid support (porous filter) and the filter was immersed into the monomer solution in a micro vial for the duration of the reaction. Monomer solution containing the solid support filters was exposed to UV irradiation for a minimum of 10 minutes and heated at 60 °C for minimum of 2 hours (max. 20 h), after which the monomer solution was washed out from the solid support.

[0150] Polymerization in vial coating a filter (B)

[0151] The monomer solution was applied in a vial containing the monomer solution and the reaction vial was closed. Monomer solution containing the solid support filters was exposed to UV irradiation for minimum of 10 minutes and heated at 60 °C for minimum of 2 hours (max. 20 h), after which the monomer solution was washed out from the solid support filters.

[0152] Fabrication and functionalization of the microfluidic solid supports

[0153] The microfluidic chips used as the solid support for the polyDADMAC network comprised an array of ca. 15 000 round-shaped micropillars (d=50 pm; height ca. 200 pm) in a hexagonal lattice (100 pm interpillar spacing from center-to-center) in a microchannel of 30x4x0.2 mm3(lengthxwidthxheight). These pillar arrays were fabricated from off- stoichiometric thiol-ene (OSTE), as described earlier (Tahka, S., Sarfraz, J., llrvas, L. et al. Immobilization of proteolytic enzymes on replica-molded thiol-ene micropillar reactors via thiol-gold interaction. Anal Bioanal Chem 411 , 2339-2349 (2019). https: / / doi.org / 10.1007 / s00216-019-01674-9), following a three-step process: (i) fabrication of the Sll-8 masters using photolithography, (ii) fabrication of the negative molds using PDMS soft lithography, (iii) UV replicamolding and bonding of the OSTE micropillar and cover layers.

[0154] For the fabrication of the Sll-8 masters (step i), Sll-8 100 negative photoresist was spin coated (1150 rpm, 30 s) on a 4-inch silicon wafer to yield ca. 200-pm-thick layer, and soft baked on a hotplate in a stepwise manner, first at 65 °C for 25 min and then at 95 °C for 90 min. Next, the Sll-8 layer was UV exposed through a plastic photomask (Micro Lithography Services Ltd, South Woddham Ferrers, UK) (1.2 J / cm2) using OAI LS 30 / 5 collimated UV light source (OAI, Milpitas, CA), and post exposure baked on a hot plate, first at 65 °C for 10 min and then at 95 °C for 40 min. Finally, the SU-8 microstructures were developed using PGMEA for ca. 30 min with agitation, rinsed with isopropanol, dried with nitrogen, and the wafer was hardbaked at 95 °C for 30 min.

[0155] The PDMS molds (step ii) were made from Sylgard 184 elastomer mixed with the curing agent in a ratio of 10:1 (w / w). The prepolymer mixture was degassed in vacuum, poured on the SU-8 master, and cured in the oven (70 °C, 2-3 h), before detaching them from the SU-8 master.

[0156] The OSTE micropillar and cover layers (step iii) were fabricated using a tetrafunctional thiol (pentaerythritol tetrakis(3-mercaptopropionate), PETMP) and a trifunctional allyl (1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione, TATATO), mixed in a ratio that yielded the desired molar (%) excess of either thiol or allyl functional groups. The mixture of PETMP and TATATO was degassed in vacuum, poured on the PDMS mold to yield ca. 1 -mm-thick OSTE layer, and cured by UV for 5 min using Dymax 5000-EC flood exposure lamp (nominal intensity 225 mW / cm2). After curing, the OSTE replica was gently detached from the PDMS mold. Before bonding, the OSTE based micropillar and cover layers were pre-heated on a hot plate at 70°C and then laminated against each other by applying pressure, and finally exposing them to UV (Dymax 5000-EC) for 2 min.

[0157] To functionalize the micropillar array with polyDADMAC, the bulk OSTE polymer was prepared using two-fold (100%) molar excess of the allyl functional groups to obtain an allyl-rich surface chemistry. These surface functional groups were then functionalized with an allyl-linked DADMAC in the presence of 0.1 % Irgacure® TPO-L (v / v) or ammonium persulfate (ca. 1 / 14 molar ratio to DADMAC) radical initiator via UV or thermally initiated radicalization that triggered concentration- and time-dependent polymerization between the surface allyls and the allyl-linked DADMAC monomers. For this purpose, the micropillar arrays were filled with the chosen composition of the DADMAC monomer solution. Where a crosslinker was used, it was added to the DADMAC solution (1 / 12 molar ratio to DADMAC), and the inlets and outlets were sealed with tape to prevent evaporation, after which the microchips were UV exposed (Dymax 5000-EC) for 10-20 min to initiate polyDADMAC crosslinking. After the initial UV irradiation, the microchips were placed on a hotplate (70 °C) and heated for 1 , 2, or 4h. Finally, the tapes were removed, and the microchips were rinsed with water to ensure complete removal of uncrosslinked DADMAC monomers and unanchored polyDADMAC chains.

[0158] Cyclotron production of [18F]fluoride

[0159] Non-carrier-added [18F]fl uoride was produced via18O(p,n)18F nuclear reaction in a TR-19 cyclotron (Advanced Cyclotron Systems Inc., Richmond, Canada) by proton irradiation of18O-enriched water (> 97%, Rotem Industries, Israel).

[0160] Characterization of synthesized polymers.

[0161] The synthesized polymers were measured with Avance III 400 Nuclear Magnetic Resonance (NMR) spectrometer, using deuterium oxide (D2O) as the solvent.

[0162] The results of NMR experiments are shown in figures 2 and 3.

[0163] The polymer particle size distribution was measured by dynamic light scattering (DLS) using Zetasizer Nano ZS from Malvern Panalytical. A sample (5-10 pL) of the stock solution (prepared from 50 wt-% monomer solution followed by polymerization) was pipetted into 990-995 pL (ca. 2, 5-5,0 mg / mL) of ultrapure water. The diluted sample was vortexed vigorously for 10 sec. The sample was pipetted into a disposable cuvette and measured at 22 °C using 11 scans per sample, each sample measured in triplicate.

[0164] The results of the DLS experiments are shown in figures 5, 6, and 7.

[0165] The functional groups of the polymer were characterized by Fourier transform infrared (FTIR) spectrometry using Nicolet iS50 FTIR Advanced Flex Aluminum Spectrometer with attenuated total internal reflection (ATR) from Thermo Scientific™. The stock solution was pipetted (10-20 pL) as such onto the ATR sample module and measured using measurement range of 400-4000 (cm’1), 64 scans per sample and at absorbance mode.

[0166] The results of the ATR-FTIR experiments are shown in figures 8 and 9.

[0167] SEM-EDS (surface morphology)

[0168] The linear homopolymer polyDADMAC (control) and the crosslinked copolymer polyDADMAC4E samples were applied as a thin layer on top of a TEM grid and the samples were left to dry. The SEM images were taken with a Hitachi S-4800 field emission SEM. The EDS spectra were measured at 20 keV with an Oxford INCA 350 Energy dispersive X-ray spectrometer. The samples were coated with 5 nm of Au-Pd alloy using a Cressington 208HR sputter coater.

[0169] The results of the SEM-EDS experiments are shown in figures 10 and 11 .

[0170] Quantitation of quaternary ammonium groups available for18F' exchange (operational anion exchange capacity)

[0171] The synthesized polymer (14 mg, polyDADMAC, 50 wt-% solution in water) with (copolymer) or without a crosslinker (homopolymer), was weighted and dissolved to 1400 pl of Traces ELECT™ water (Honeywell Riedel-de Haen™). The polymer stock (4 x 200 pl) was pipetted into four Amicon (10 kDa MWCO, Millipore) spin filters and physiological saline (0.9% NaCI w / w) was added (4 x 300 pl) to precondition the polymers. Residual of the polymer stock was used for measuring the dry weight of the polymers after lyophilization. The filters were centrifuged for 5 min at 14 000 g. TraceSELECT™ water (500 pl) was added and the samples were centrifuged for 5 min at 14 000 g. The washing step was repeated twice. Carrier free [18F]fluoride was added (500 pl of water) and the samples were centrifuged for 5 min at 14 000 g. TraceSELECT™ water (500 pl) was added and the samples were centrifuged for 5 min at 14 000 g. The filter eluates were pooled and radioactivity of the filter and the pooled eluate were measured. The preconditioned polymer samples on the filters were treated with increasing amount of NaCI (15 nmol, 92 nmol, 169 nmol, 323 nmol, 477 nmol, 862 nmol, 1478 nmol and 2094 nmol) and radioactivity of the filter and the pooled eluates were measured after centrifugation. The results were normalized with the dry mass of the polymer samples and reported as neq / mg.

[0172] Determination of [18F]fluoride trapping efficiency The synthesized IEX polymers on solid supports were pretreated with 0.9% (w / w) NaCI in water and washed with TraceSELECT™ water. Aqueous solution of18F_was passed through the polymer either by using a syringe or by centrifugation, after which the purified18F_was eluted from the polymer by washing with 0.9% (w / w) NaCI in water. Radioactivity of the collected waste, eluted18F_and the residual activity in the polymer were measured by using a dose calibrator and decay corrected to the same timepoint. Trapping efficiency was calculated by dividing sum of the eluted18F_radioactivity and residual activity in the polymer with the total activity. Elution efficiency was calculated by dividing the eluted18F_radioactivity with sum of the eluted18F_radioactivity and residual activity in the polymer.

[0173] Results

[0174] Use of a tetrafunctional allyl (4E) crosslinker was found to affect the polyDADMAC size distribution yielding a narrow size distribution (nm) and thick polymer.

[0175] DLS analysis of polyDADMAC polymers synthesized without a crosslinker, revealed a heterogeneous size distribution (Table 1 ) with variable amount of the polymers falling to the size range of > 204 nm (40.8 - 83%), and presented similarly a heterogenous profile as the commercial homopolymer polyDADMAC (control). Both the in-house synthesized and the commercial control homopolymer polyDADMAC exhibited a larger size distribution range compared to the in-house developed, crosslinked polyDADMAC4E copolymer. By using a crosslinker, more uniform size distribution was obtained with the size of 221-358 nm (91 .3 - 100.0%). The narrower size distribution attained when using a crosslinker in the polymerization guarantees more uniform functionalization of materials while using the polymer for mechanical or chemical functionalization or coating of small devices or filters.

[0176] The polymers' apparent physical characteristics varied based on whether a crosslinker was used. Commercially available 20 wt-% polyDADMAC homopolymer was slightly viscous liquid, as well as the in-house polymerized polyDADMACiinear. Crosslinked polyDADMACsE copolymer, prepared using trifunctional allyl (3E) crosslinker, formed a thick viscous solution with slight gelling during the polymerization reaction, whereas polyDADMAC4E formed a notably thick gel-like material during the polymerization. The results in Table 1 show that when compared to commercially available reference material, the present crosslinked anion exchanger forms a more homogenous and markedly larger polymer (Z=464 - 646 nm, 91 - 100% of 221 - 358 nm size particles). The particle size distribution was postulated to explain the observed difference in viscosity. Broad variation of small and large sized particles in linear polymers resulted in low viscosity, and large particle size with narrow size distribution resulted in thick viscous polymer. Based on the results, it was concluded that using the described polymerization method together with 4E crosslinker yielded a polymer which was superior in homogeneity compared to the commercial or in-house developed linear versions (Figures 5, 6, and 7)

[0177] FTIR characterization of the polymers demonstrated that 4E-crosslinked polymer was the only sample that presented a broad signal at around 1680 cm-1, indicating this polymer has a C=O bond, not present in other polymers. This finding of the carbonyl group corresponds to the addition of 4E crosslinker in the copolymer Commercial polyDADMAC had the simplest spectrum and did not have all the peaks that the in-house synthesized at range of 961-1200-961 cm’1. A strong peak at 1474 cm-1was visible for all polymers which corresponds to the CHs vibrations (bending) of polyDADMAC and was present for all homo- and copolymers but not in the monomer. The presence of quaternary ammonium group is indicated by the C-N stretching in the range of 1200-1300 cm’1and in the spectra it can be detected at 1200-1213 cm’1. Characteristic signals for water, which was used as a solvent in the sample, can be detected with two big and broad signals at ca. 3350 cm’1and 1636 cm’1. A signal at 1047-1099 cm’1indicated the bending signals of C-N-CHs resulting from the quaternary ammonium group (Figures 8 and 9).

[0178] The polymer composition in solution was studied with1H NMR in deuteriumoxide (D2O). In the polyDADMAC structures, the protons (assigned 1 ) at the two methyl groups bound to the quaternary amine presented a characteristic cluster of sharp peaks at 3.04-3.27 ppm, corresponding to 6 protons per repeating unit. The protons (assigned 2-4) bound to the backbone ring structure are detected as broad peaks, which are typical for a long chained polyDADMAC. The signals in both commercial polyDADMAC and in-house synthesized polyDADMACiinear1H NMR corresponded to characteristic polyDADMAC signals. The backbone -CH- protons in 4E crosslinker overlap with -CH- protons of polyDADMAC in the1H NMR and due to the lower molar-% were inseparable from the polyDADMAC -CH- proton signals. Hence, the presence of the crosslinker was verified with SEM-EDS elemental analysis and ATR-FTIR. The polymerization percent for each derivative from starting material was evaluated by integrating product (at 5 3.04-3.27 ppm) and starting material (at 5 3.036 ppm) methyl group (assigned 2) peak areas in1H NMR. The polymerization-% were polyDADMACiinear: 99,7%, polyDADMACsE: 99,3% and T1 polyDADMAC4E: 99,5%. PolyDADMAC (reference, commercial vendor):1H NMR (400 MHz, D2O) 5 3.87 (s, 2H), 3.61 - 3.04 (m, 6H), 2.73 (s, 1 H), 2.31 (s, 1 H), 1 .86 - 0.94 (m, 4H).13C NMR (101 MHz, D2O) 5 70.16, 54.04, 38.24, 26.63. Slightly viscous liquid.

[0179] PolyDADMACiinear homopolymer (no crosslinker, in-house synthesized, Figures 3 and 4):1H NMR (400 MHz, D2O) 5 3.86 (s, 2H), 3.49 - 3.04 (m, 6H), 2.74 (s, 1 H), 2.32, 1 .82 - 0.90 (m, 3H).13C NMR (101 MHz, D2O) 570.36, 54.03, 52.35, 43.36, 38.65, 38.21 , 26.47. Slightly viscous liquid.

[0180] PolyDADMACsE copolymer (with 3E crosslinker):1H NMR (400 MHz, D2O) 5 3.78 (s, 1 H), 3.19 (s, 3H), 3.09 (s, 2H), 1.28 (s, 1 H).1H NMR (400 MHz, D2O) 5 5.92 (3E residue), 5.27-5.23 (3E residue), 4.50 (3E residue), 3.86 (s, 2H), 3.48 - 3.08 (m, 6H), 2.74 (s, 1 H), 2.32, 1.81 - 0.97 (m, 3H), 1 .09.13C NMR (101 MHz, D2O) 5 149.92 (3E residue), 130.94 (3E residue), 117.05 (3E residue), 70.35, 66.12, 54.75, 54.03, 52.34, 45.00, 38.64, 38.22, 26.49. Viscous liquid with gelling. 3E starting material residual peaks; 3E residue.

[0181] PolyDADMAC4E copolymer (with 4E crosslinker):1H NMR (400 MHz, D2O) 5 3.86 (s, 2H), 3.46 - 3.06 (m, 6H), 2.74 (s, 1 H), 2.32, 1.79 - 0.87 (m, 3H).13C NMR (101 MHz, D2O) 5 71.06, 70.35, 54.68, 54.05, 52.35, 43.28, 38.64, 38.21 , 32.89, 26.47. Highly viscous, gel-like substance.

[0182] Table 1. Polymer characteristics measured by dynamic light scattering (DLS) experiments. The crosslinked polyDADMAC4E polymer morphology with semi-quantitative elemental analysis (Figure 11 , right panel) was measured with SEM-EDS and compared to commercially available polyDADMAC (Figure 10). The elemental composition of crosslinked polyDADMAC4E corresponded to four DADMAC units bonded to one 4E from each allyl group per central polymer unit (Table 2). The elements carbon and chlorine were the most abundant in the SEM-EDS analysis, as expected. The crosslinked branched polyDADMAC4E presents higher oxygen content compared to the linear polyDADMAC. The presence of the 4E-crosslinker was verified with the presence of more oxygen in the sample for polyDADMAC4E than for commercially available linear polyDADMAC.

[0183] Table 2. SEM-EDS results (semiquantitative) elemental composition of polyDADMAC4E and control polymer polyDADMAC.

[0184] [18F]Fluoride trapping efficiency of the polymers were tested first with aqueous polymer solutions. Spin-filter tests were executed using molecular weight cut-off (10 kDA MWCO) to separate the polymers from the aqueous solution. The polymer solutions were applied on spin-filters and centrifuged (14 000 x g, rpm) to trap [18F]fluoride and to separate the bigger polymer chains together with18F_from solution. In-house synthesized linear noncrosslinked polyDADMACiinear was compared to commercially available linear polyDADMAC.

[0185] The spin filter tests (Table 3) revealed that the commercial polyDADMACiinear trapped near 95% of all added18F_whereas the in-house synthesized polyDADMACiinear trapped 79% and the crosslinked polyDADMAC4E 83 %. With all polymers, fluoride-18 was efficiently released (> 85%) by elution with physiological saline (0.9% NaCI, w / w). The trapping capacity of the synthesized polyDADMACiinear and polyDADMAC4E was nearly equal, but the release of18F_was better from the linear polymer.

[0186] Table 3. Spin filter tests (10 kDa MWCO) for [18F]fluoride trapping with polyDADMAC polymers.

[0187] The operational18F_exchange capacity of the synthesized polyDADMAC polymers was determined by spin-filtering (10 kDa MWCO) the18F-treated polymers with an increasing concentration of NaCI and by quantification of the released [18F]fluoride. The operational18F’ exchange capacity for polyDADMACiinear was 1300 neq / mg (dry) and for synthesized polyDADMAC4E with a crosslinker 1400 neq / mg (dry).

[0188] The non-crosslinked polyDADMACiinear functionalized filters resulted only in 3.1 % [18F]fluoride trapping efficiency, whereas the crosslinked polyDADMAC4E polymer functionalized filters were able to trap 77% of [18F]fluoride (Table 4). The trapped [18F]fluoride was efficiently eluted (> 86 %) by using physiological saline. Using a crosslinker had a significant effect on performance of polyDADMAC treated PE filters which were produced by physical functionalization of the filter material with the polymer.

[0189] Table 4. [18F]Fluoride trapping efficiency of the synthesized polyDADMACiinear and crosslinked polyDADMAC4E on porous filter. [18F]Fluoride trapping efficiency, when covalently anchored on OSTE micropillar array (solid substrate), was 42.5 ± 19.9% (N = 33) for polyDADMACiinear and 53.4 ± 11 .3 (N = 22) for crosslinked polyDADMAC4E, and even > 80%18F-trapping efficiencies were observed for some individual chip batches (Table 5). With both surface functionalizations, fluoride-18 was released with high efficiency (> 95%) by elution with physiological saline (0.9% NaCI, w / w, 25 pl).

[0190] Table 5. [18F]Fluoride trapping efficiency of OSTE chips covalently functionalized with polyDADMAC. Elution with 25 pl of physiological saline (0.9% NaCI w / w).

[0191] The foregoing description has provided by way of non-limiting examples and embodiments a full and informative description of the best mode presently contemplated by the inventors for carrying out the invention. It is however clear to a person skilled in the art that the invention is not restricted to details of the embodiments presented in the foregoing, but that it can be implemented in other embodiments using equivalent means or in different combinations of embodiments without deviating from the characteristics of the invention as described in the independent claims.

[0192] Some of the features of the embodiments and examples may be used to advantage without the use of other features. As such, the foregoing description shall be considered as merely illustrative of the principles of the present invention, and not in limitation thereof. Hence, the scope of the invention is only restricted by the appended patent claims.

Claims

CLAIMS1 . A method for manufacturing an anion exchanger comprising: providing a reaction mixture comprising diallyldimethylammonium chloride (DADMAC) and an initiator; and heating to provide an anion exchanger comprising a polyDADMAC polymer.

2. The method of claim 1 , wherein the initiator is at least one of ethyl(2,4,6- trimethylbenzoyl)-phenylphosphinate (Igracure TPO-L), ammonium persulfate (APS), 2,2’-azobis(2-methylpropionamide) dihydrochloride (V-50), 1 -Hydroxy- cyclohexyl phenyl ketone, 2,2-Dimethoxy-2-phenylacetophenone, 1 -[4-(2- hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1 -propane-1 -one, and Phenylbis- (2,4,6-trimethylbenzoyl)phosphine oxide.

3. The method of claim 1 or 2, wherein the reaction mixture further comprises at least one crosslinker capable of forming crosslinks between polymers of the polyDADMAC polymer, the crosslinker being preferably a trifunctional allyl (3E), a tetrafunctional allyl (4E), or a combination thereof, and more preferably being selected from 1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO, 3E), and pentaerythritol tetraacrylate (PETA, 4E), or a combination thereof.

4. The method of any one of claims 1 -3, wherein the reaction mixture further comprises a solid substrate, preferably an allyl-functionalized solid substrate, a thiol-functionalized solid substrate, or a combination thereof, into which the polyDADMAC polymer is mechanically or chemically anchored.

5. The method of claim 4, wherein the reaction mixture comprises an allyl- functionalized solid substrate prepared from, or functionalized with, at least one of 1 ,3,5-triallyl-1 ,3,5-triazine-2,4,6(1 H,3H,5H)-trione (TATATO), pentaerythritol tetraacrylate (PETA), tetraallyl piperazinium dichloride (TAP), methacrylamidopropyl trimethyl ammonium chloride (MAPTAC), acrylamide (AM), methacryloxyethyltrimethyl ammonium chloride (DMC), acryloyloxyethyltrimethyl ammonium chloride (DAC), butylacrylate (BA), Tri(ethylene glycol) divinyl ether; Trimethylolpropane diallyl ether, Trimethylolpropane-tri(norborn-2-ene-5- carboxylate; Pentaerythritol-tri(norborn-2-ene-5-carboxylate); Pentaerythritol- tetra(norborn-2-ene-5-carboxylate), di(trimethylolpropane)tetra-(norborn-2-ene-5- carboxylate), 1 ,6-heptadiyne, and 1 ,7-octadiyne.

6. The method of claim 4 or 5, wherein the reaction mixture comprises a thiol- functionalized solid substrate prepared from, or functionalized with, at least one of pentaerythritol tetrakis(3-mercaptopropionate) (PETMP), trimethylolpropanetris(3-mercaptopropionate) (TMPTMP), 1 ,6-hexanedithiol, 2,5-dimercaptomethyl- 1 ,4-dithiane, 2, 3-dimercapto-1 -propanol, Benzene-1 ,2-dithiol, 1 ,8-octanedithiol, Ethylene glycol bis(3-mercaptopropionate), Trimethylolpropane tris(3- mercaptoacetate), 2,3-(dimercaptoethylthio)-1 -mercaptopropane, andPentaerythritol tetrakis(2-mercaptoacetate).

7. The method of any one of claims 1 -6, wherein the reaction mixture further comprises at least one chain transfer agent, preferably a reversible additionfragmentation chain transfer (RAFT) agent selected from at least of 2-(n- butyltrithiocarbonate)-propionic acid (BTPA), 2-((((2-carboxyethyl)thio)carbono- thioyl)thio)-2-methylpropanoic acid (CEMP), bis(carboxymethyl) trithiocarbonate (BCMT), and S,S’-bis(a,a’-dimethyl-a”-acetic acid)trithiocarbonate (BDMAT).

8. The method of any one of claims 1 -7, wherein the solid substrate is at least one of: a microfabricated solid support, microfluidic chip, capillary tube, microcapillary channel, microcapillary array, porous mini filter, centrifugal spin-filter, resin, and adsorbent material.

9. The method according to any one of claims 1 -8, wherein the heating step comprises heating for around 30-1200 min at around 40-90 °C, preferably around 60-240 min at around 50-80 °C.

10. The method according to any one of claims 1 -9, wherein the method further comprises a pretreating step comprising irradiating the reaction mixture with UV light before heating, preferably irradiating with UV light at around 67-270 J / cm2.11 .The method of any one of claims 1 -10, wherein the reaction mixture comprises a functionalized solid substrate, the reaction mixture is irradiated with UV light to provide an irradiated reaction mixture, and the irradiated reaction mixture is heated to provide a polyDADMAC polymer chemically anchored to the solid substrate.

12. An anion exchanger for concentrating and purifying anions, and manufactured by the method of any one of the claims 1-11.

13. The anion exchanger of claim 12 characterized by having around 5 - 800 nm size distribution with > 90% of the polymer with size distribution between around 300 - 500 nm when manufactured with a crosslinker.

14. The anion exchanger of claim 12 or 13 having an operational anion exchange capacity in the range around 1000 - 2000 neq / mg.

15. An anion exchange device, wherein the anion exchange device is a purification cartridge comprising at least one inlet configured to receive a fluid comprising[18F]fluoride and impurities; a body housing the anion exchanger of claims 12-14; and at least one outlet configured to elute purified [18F]fluoride.

16. The anion exchange device of claim 15, wherein the anion exchanger is arranged inside the body housing the anion exchanger as a bed.

17. A microfluidic device comprising at least one volume configured to allow passing fluid through the microfluidic device, a linear and / or a crosslinked network of the anion exchanger of any one of claims 12-14 inside the at least one volume, and optionally the anion exchanger being covalently attached to at least one surface defining the volume, and optionally filling the volume.

18. A method for purifying anions comprising providing a solution comprising anions in an aqueous medium; contacting the solution with the anion exchanger according to any one of claims 12-14, with the anion exchange device according to any one of claims 15-16, or with the microfluidic device according to claim 17, to provide anions bound to the anion exchanger; optionally washing; and subsequently eluting the bound anions to obtain purified anions.

19. The method of claim 18, wherein the anions comprise cyclotron produced18F_anions.

20. The method of claim 18 or 19, wherein in the elution step the precursor is eluted to a volume below 50 pL.21 . A kit for producing a radiotracer comprising the anion exchange device of claims 15-16, or the microfluidic device of claim 17, and further comprising a reaction vial for mixing the purified18F_with a precursor molecule.

22. A system comprising the anion exchange device of claims 15-16 or the microfluidic device of claim 17; pumps and valves configured to control fluid flow through the device; temperature control means configured to monitor and set temperature of the device; and control logic configured to control operation of the system and fluid flow through the device.

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