TrisKem International. Development of new extraction chromatographic resins and applications

Transcription

1 TrisKem International Development of new extraction chromatographic resins and applications

2 TrisKem International Based near Rennes (Brittany, France) Independent company since 02/07 Formerly part of Eichrom Europe (Eichrom Technologies LLC) ISO 9001 since 2007 Sales into 70 countries New products world wide, historical Resins : Europe, Africa, Middle-East, Russia and China Staff : 17 in Beijing (China) R&D (& TS) group: 6 incl. 2 radiochemistry PhDs, 1 PhD & 1 PostDoc organic chemistry Currently hiring 2-3 more PhDs (radiochemistry/organic chemistry) November 2015: moved into new facilities

3 TrisKem International Production and trade of selective resins and accessories Mainly extraction chromatographic resins Functionalized polymers and silicates PAN embedded inorganic compounds Applications in various domains Distribution (Europe): LSC consumables PEEK columns Raddec Pyrolyser (H-3 & C-14) Certified ICP standards Accessories

4 Accessories Empty cartridges 12 ml, 4 ml, 2 ml, 1 ml PEEK columns Mass spectrometry Radiopharma

5 TrisKem R&D Development of new resins, separation techniques and applications for all domains of interest Two R&D labs Synthesis (new resins and extractants) Incl. grafted resins (silica or polymers), macrocycles, Application Preparation of extraction chromatographic resins Resin characterisation and method development Equipment: Nexion 350 with TruFAST, IC, TOC, TGA, IR, NMR (43 MHz), production facilites and equipment Customized resins /solutions and contract R&D Very interested in cooperations

6 TrisKem International Member of Isotope4Life / Atlanpole Biotherapies / ID2Santé Member of Nucleopolis Member of Prometia Two projects financed by the BPI Radiopharmacy: CARAT (Orano Med, Pb-212), LU-177 Member of BPI Excellence & FrenchFab

7 Extraction chromatography Combination of liquid-liquid extraction (LLX) and chromatography Liquid-liquid extraction: distribution of an element between 2 non-miscible phases Most general case: organic and aqueous phase Chromatography: distribution of an element between a solid and a liquid phase

8 Extraction chromatography Organic extractant impregnated onto inert support «Supported Solvent Extraction» / «Solvent Impregnated Resins» Distribution between two non-miscible phases High variety of selectivities (crownethers, phosphine oxides, oximes, amines, diglycolamides, hydroxamates ) Pure extractants, synergetic mixtures, solid extractants in diluents

9 Extraction chromatography Selectivity of solvent extraction Wide choice of different extractants/selectivities Acidic extractants (e.g. HDEHP), Amines and ammonium salts (e.g. Aliquat 336), Solvating and chelating extractants, especially P=O group containing (e.g. CMPO, TBP), Crownethers,. Pure extractant or extractant dissolved in diluents (ideally synergetic systems) Non-miscible with water Selectivity adaptable to separation problem Generally high selectivity for product element/no selectivity for target Small columns => small reagent volumes Bleeding => may be adressed with PreFilter Resin

10 Extractant Resin Applications DTCH18C6/octanol SR Sr-82 DTCH18C6/isodecanol PB Tl-201 DTCH18C6/HDEHP TK100 Sr-82 Aliquat 336 TEVA Th, Tc DPPP UTEVA U Dipex Actinide Ra, Ac HDEHP LN Lanthanides (Lu, Tb, Ho, ) DGA (Normal & Branched) DGA DGA Sheets Actinides, Sc, Ac QC Ra-223, Pb-212, Ac-225, Ga-68 TBP TBP Sn-117m, Zr-89 Phosphine sulfide CL Ag-211, Pa, iodine removal Oximes CU Cu Hydroxamate ZR Zr, Ti, Ga, Ge TOPO TK200 Ga-67/8, Zn, Pt, Sc Long-chained alcohol TK400 Pa, Nb, Mo

11 Domains and applications Radiopharmacy/nuclear medicine Radionuclide production Cooperation with cyclotrons & reactors (NL, RN producers, ) Separation of radionuclides from irradiated targets» Diagnostics: Zr-89, Cu-64, Ga-68, Ge-68, Ti-44/5 ZR Resin, CU Resin, TK200 Resin,» Therapy: alpha emitters, Lu-177, Cu-67, Sn-117m, TK400, TBP Resin, CU Resin, ongoing research (Lu, alphas),

12 Domains and applications Radiopharmacy/nuclear medicine Purification of generator eluats Decontamination of contaminated effluents Quality control Generator eluats and QC of produced/received radionuclides» DGA sheets (functionalized TLC, Ra-223, Ga-68, Pb-212)» Presence of long-lived mother nuclides

13 ZR Resin Original scope: Hydroxamate based resin Standard for Zr separation from Y targets Ready to use Facile Zr elution (avoid 1M oxalic acid) Zr-89 production via (p,n) reaction from natural Y (Y-89) targets High Zr/Y selectivity necessary Fast extraction kinetics: > 99% after 1 min Also used for other separations possible (Ti/Sc, Ge/Ga, Ga/Zn) Applications in analytical applications (Zr-93, Nb, )

14 ZR Resin - HCl No selectivity for Y, Sc High Ge/Ga selectivity at elevated HCl High selectivity for Zr, Ti, Nb, W over wide HCl concentration range No selectivity for alcaline and earth alcalines Lanthanides are not retained Strong Fe retention (dip at 2 3M HCl)

15 Zr Resin HNO 3 High selectivity for Zr, Ti, Nb, W over wide HNO 3 concentration range Loss of selectivity at 6M HNO 3 => Resin shows colour change No selectivity for Y, Sc, lanthanides, alcalines and earth alcalines and most transition metals High Ge/Ga selectivity at 3M HNO 3 Strong Fe retention up until 1M HNO 3

16 ZR Resin oxalic acid Low D W for Zr starting 0.03M oxalic acid Low D W for Ti, Nb starting M oxalic acid 0.05M oxalic acid looks promising for Zr/Nb separation

17 Recovery (%) L: 1 ml 2M HCl + NH2OH*HCl Zr separation incl. Fe removal 100% Zr separation on 1 ml ZR Resin column 90% 80% R1: 8 x 1 ml 2M HCl R2: 8 x 1 ml water E: 4 x 1 ml 0.05M oxalic acid 70% 60% 50% 40% 30% Zr Y Fe Ti 20% 10% 0% Volume (BV) Load from 2 6M HCl Rinsing conditions described by Holland et al. can be used - No activation with acetonitrile Quantitative Zr elution in ml 0.05M oxalic acid Facile Fe removal improved under reducing loading conditions (e.g. HONH 2 *HCl)

18 Ge/Ga separation In 2M HCl tested up to 200 mg Ga/50 mg Ni per 100 mg ZR Resin tests on higher Ga amounts on-going, first «hot» tests started Several g Ga/Ni (3M HNO3)

19 Futher elution studies Ga/Ge Loading from 3M HNO3 possible Fe removal with 2M HCl Rinse with HCl also improves Ge elution Better separation when working in 2M HCl

20 Ge separation from H2SO4

21 Ti-Sc Separation 60% 50% 40% Ti/Sc separation, ZR Resin Sc Ti L 1 ml ME 10 M HCl R1 2 ml 10 M HCL R2 2 ml 10 M HCL R3 2 ml 10 M HCL R4 2 ml 10 M HCL R5 2 ml 10 M HCL E1 0.5 ml 0.1 M citric acid E2 0.5 ml 0.1 M citric acid 30% E3 0.5 ml 0.1 M citric acid E4 0.5 ml 0.1 M citric acid 20% E5 0.5 ml 0.1 M citric acid E6 0.5 ml 0.1 M citric acid 10% 0% L R1 R2 R3 R4 R5 E1 E2 E3 E4 E5 E6 In-house tested up to 50 mg Sc (100 mg ZR Resin) Ti retained from 10M HCl, Sc not retained Ti elution with 0.1M citric, 0.2M oxalic acid, 0.1M H 2 O 2

22 Ti-44 (LANL) 4g irradiated Sc 65.2 MBq Ti-44 5 ml Zr Resin Ti-44 yield >95% D f (Sc): 10 5 Use of ZR Resin as support in Ti-44/Sc-44 generators Direct (1 ml ZR Resin) and reverse elution (2 ml ZR Resin) tested 65 column volumes tested up until publication High Sc yields, max. Ti-44 breakthrugh: 4.1 E -4% Obtained Sc gave labelling yields > 94%

23 Ga / Zn separation (Ga-67/68) Main application: Ga-68 production from Zn targets (liquid or solid) Ga/Zn separation also at 0.1M HNO 3 possible liquid targets

24 TK200 Resin New resin based on TOPO extractant Extracts U, Th, Pu at ph 2 => preconcetration and purification of selected actinides on same column (mainly U) Extracts Ga from 1.5 2M HCl, elutes Ga in dilute acid/water Typical applications: U separation from water samples Ga-68 production (in combination with ZR Resin) TOPO On-going: Pt/Ir, Zn/Cu (Zn production, Zn removal), Sc production

25 Dw values TK200 HNO3

26 Dw values TK200 HCl

27 Ga conversion using TK200 Resin Clean Ga separation on ZR Resin Elution with 2M or 1.5M HCl possible TK200 load from 1,5 or 2M HCl Elution in 3 4 BV of water No / little additional Zn elimination EANM 17: Presentation Gagnon et al.

28 Zn/Cu separation

29 Sc separation from Ti / Ca Other/better options for elution: oxalic acid, water, Load also from high HCl e.g. 10M

30 CU Resin Oxime based resin (very hydrophobic, preferably use as cartridge) High selectivty for Cu over most other elements Load from ph >2, elution in high acid Not ideal for solid Ni targets (TEVA under evaluation for solid Ni targets), Very suitable for liquid targets and solid Zn targets Typical applications: Cu isotope production from Ni or Zn targets Cu isotope ratio determination by mass spectrometry Geochemistry, Archeometry, Biomedical (Wilsons Disease) (1) C. Dirks, B. Scholten, S. Happel, A. Zulauf, A. Bombard, H. Jungclas: Characterisation of a Cu selective resin and its application to the production of 64Cu. J Radioanal. Nucl. Chem, 286 (2010) , DOI /s , (2010). TrisKem Referenz: T-DC110. (2) C. Dirks, S. Happel: Characterization of a Cu selective resin and its application to the production of Cu-64. Presentation at the TrisKem International users group meeting, 14/09/2010, Chester (UK); available online:

31 CU Resin - selectivity Loading conditions (ph > 2): Good selectivity for Cu over other elements tested, Some selectivity for Fe in HCl at high ph and in H 2 SO 4 Elution: Elevated acid concentrations

32 Cu separation on CU resin Separation of Cu isotopes from Ni or Zn targets liquid targets direct, solid after ph adjustment 350 mg columns (1 ml), load and rinse (8 ml) at ph 2 (HCl), elution with 8M HCl Quantitative recovery of Cu in 1 1,5 ml 8M HCl Cu yield > 90% in 1 ml 8M HCl 97,6% ± 2,3% (k = 1, N=25) in 1.5 ml 8M HCl Pure Cu fraction High D f (ICP-MS) g-spectrometry Obtained Cu suitable for labelling (ARRONAX) Target material recovered in small volume of 8M HCl Further purification for reuse Other application: Ni-64 purification (stable Cu removal)

33 Cu-67 at BNL (DeGraffenreid et al.) Poster presented at the ISRS 2017

34 Cu separation on CU Resin 6M HCl Elution TKI201 can replace AIX => no shrinking/swelling Zn remains retained Optimisation on-going L/R: 6M HCl Elution: 0.5M / 0.05HCl

35 Zn removal If Zn removal only: TK200 At least up to 4M HCl high Zn over Cu, higher to be testet

36 TBP Resin Based on TBP Typical applications: Determination of long-lived Sn isotopes in rad waste Focus on matrix removal and elimination of isobaric interferences Sn-117m separation for use in nuclear medicine (Auger emitter => therapy) Focus on Sn/Cd/Sb separation NEW: Zr-89 from Y targets (Uni Wisconsin) => Zr elution in HCl Sn separation in geology/archeology Elimination of matrix elements and isobaric interferences TBP (Tributyl Phosphate)

37 Zr-89 from Y targets HCl elution Zr elution with 1M HCl Uni Wisconsin (Graves et al.)

38 Sn from 1g Cd samples Sn-117m production 1g Cd (as chloride) plus multielement solution (ICP-MS) No Sn breakthrough After one column low µg of Cd in Sn fraction (D F ~high 10 5 ) Sn recovery near quantitative in 4 ml 0.1M HCl

39 DGA Sheets Developed at CVUT (Kozempel, Vlk) QC of radionuclides and generator eluents (p.ex. Ra-223, Ac-225/Bi-213, Pb-212, Ge-68/Ga-68 ) with TLC scanner or radiometer after cutting Therapy with mentioned alpha emitters Dignostics e.g. with generator Ga-68 Currently developping new types of sheets in-house (selectivities, geopmetry) Under development (with Subatech) => use in decommissioning (2D TLC)

40 TK400 Resin Long chained alcohol Retention only at high HCl concentration, elution in low HCl, water, Main application: Pa separation (Pa-231 determination by MS) NPL (no selectivity for actinides, Ac, Ra, Pb, => Pa-230 purif.) Also retains Mo, Po, Ga, Nb separation from Zr possible (Nb-90) Knight et al.

41 Mo/Tc separation Ongoing work Two resines under development Tc separation under acidic conditions: TK201 Elution with e.g.: 1M HNO 3 0.1M NH 4 OH Tc separation under alcaline conditions Elution with e.g.: Water

42 CL resin Extractant: Phospine sulfide Main application: Cl-36/radioiodine Ag and Pd methods being tested Selective for PGE, Ag, Au, Halogene selectivity introduced by loading with Ag + Sample loading on Ag + loaded CL resin Acidic, neutral or slightly alkaline conditions Currently in preparation US standard method radioiodine in water Original paper + : water/effluents and leached solid samples (concrete, soil, filter) Leaching: 4h, 70 C, 1M NaOH, Alternative: Raddec Pyrolyser + A. Zulauf, S. Happel, M. B. Mokili, A. Bombard, H.Jungclas: Characterization of an extraction chromatographic resin for the separation and determination of 36Cl and 129I. J. Radanal Nucl Chem, 286(2),

43 Other separations on CL Resin

44 Iodine removal from effluents Decamp et al.: Iodine removal from elevated sample volumes at high flow rates Issues with rad. waste storage Storage as liquid waste challenging Preferably stored as solid waste > 10 L radioactive process effluent (1M HNO 3 ), Flow rate up to 180 ml/min, Mixed-bed columns 3g CL resin (plus 4g XAD-4 resin), iodine uptake: 85 95% C. Decamp (IRE), S. Happel: Utilization of a mixed-bed column for the removal of iodine from radioactive process waste solutions, Journal of Radioanalytical and Nuclear Chemistry, online April 2013, DOI: /s

45 Further ongoing projetcs CARAT (Pb-212 => OranoMed) Ra Resins Lu-177 separation from Yb Mn-52 separation At-211 separation using resins (e.g. TK400) Ac-225 separation SE Resin: Se-72/As-72 Ga purification (Ge-68 generators) Ge removal cartridge Ga purification (Ge, Fe and Zn removal) Grafted resin (polymers/silicates) Removal of radiouclides from effluents (e.g.radioiodine, long-lived impurities, )

46 Thank you for your attention! Questions?