Method for mixed mode adsorption and mixed mode adsorbents

• US 20040020857A1
• Filed: 06/19/2003
• Published: 02/05/2004
• Est. Priority Date: 12/31/2000
• Status: Active Grant

• Current Assignee: Cytiva Bioprocess R&D AB (Danaher Corporation)
• Original Assignee: Amersham Biosciences (General Electric Company)
• Inventors: Johansson, Bo-Lennart, Maloisel, Jean-Luc, Belew, Makonnen
• Granted Patent: US 7,008,542 B2
• Time in Patent Office: Days
• US Class Current: 210/660
• CPC Class Codes: B01J 20/3285 Coating or impregnation layers comprising different type of functional groups or interactions, e.g. different ligands in various parts of the sorbent, mixed mode, dual zone, bimodal, multimodal, ionic or hydrophobic, cationic or anionic, hydrophilic or hydrophobic
• CPC Class Codes: B01J 39/04 Processes using organic exchangers
• CPC Class Codes: B01J 39/26 Cation exchangers for chromatographic processes
• CPC Class Codes: B01J 41/04 Processes using organic exchangers
• CPC Class Codes: B01J 41/20 Anion exchangers for chromatographic processes
• CPC Class Codes: B01J 43/00 Amphoteric ion-exchange, i.e. using ion-exchangers having cationic and anionic groups; Use of material as amphoteric ion-exchangers; Treatment of material for improving their amphoteric ion-exchange properties ion-exchange chromatography processes B01D15/36

Abstract

Method for the removal of a substance from an aqueous liquid by ion exchange comprising providing a liquid with said substance is present; providing an adsorption matrix which comprises at least two different ligands; contacting the liquid with the matrix under a period of time and conditions sufficient to allow adsorption of the substance to the matrix; and adding an eluent that desorbs the substance from the matrix. Each one of the ligands interacts with the substance during the adsorption step, and at least one of the ligands is charged and capable of ionic interaction with the substance. The method can be run as a cation or anion exchange. The substance desorption can be performed by adding an eluent comprising an increasing ionic strength. The invention also encompasses an adsorbent comprising at least two structurally different ligands, which interact with the same kind of substance when used in a separation procedure.

Claims

1. A method for the removal of a substance from an aqueous liquid by ion exchange, said method comprising the steps of:

providing a liquid wherein said substance is present in a charged state;

providing an adsorption matrix which comprises at least two structurally different ligands, comprising at least one weak ion exchanger or at least one strong ion exchanger;

contacting the liquid with the matrix under a sufficient period of time to allow adsorption of the substance to the matrix; and

adding an eluent that desorbs the substance from the matrix;

wherein each ligand interacts with the substance during the adsorption step and at least one of said ligands is charged and capable of ionic interaction with the substance.

2. A method according to claim 1, wherein one charged ligand is a anion exchanger and the substance to be removed is initially negatively charged, the conditions for adsorption being defined by a pH>

pl of the negatively charged substance and pH<

pKa of the positively charged groups of the ligand.

3. A method according claim 2, wherein the adsorption capacity for the substance is ≧

100%, such as ≧

200%, of the adsorption capacity of the same substance in a corresponding reference ion-exchanger in which essentially all of the charged groups are quaternary ammonium groups (q-groups).

4. A method according to claim 2 or 3, wherein the desorption is performed by adding an eluent comprising an increasing ion-strength gradient.

5. A method according to claim 1I wherein one charged ligand is a cation ion exchanger and the substance to be removed is initially positively charged, the conditions for adsorption being defined by a pH<

pl of the positively charged substance and pH>

pKa of the negatively acid corresponding to the ligand.

6. A method according claim 5, wherein the adsorption capacity for the substance is ≧

100%, such as ≧

200%, of the adsorption capacity of the same substance in a corresponding reference ion-exchanger in which essentially all charged groups are sulfopropyl group.

7. A method according to claim 5 or 6, wherein the desorption is performed by adding an eluent comprising an increasing ionic strength.

8. A method according to any one of the previous claims, wherein the adsorption is performed at an ionic strength higher than or equal to that of a water solution of 0.10 M NaCl, preferably 0.20 M NaCl or 0.30 M NaCl.

9. A method according to any one of the previous claims, wherein the ligands are capable of binding the substance of interest in an aqueous reference liquid at an ionic strength corresponding to 0.25 M NaCl.

10. A method according to any one of the previous claims, wherein at least one ligand interacts with the substance by hydrophobic and/or electron donor-acceptor interaction.

11. A method according to claim 10, wherein said ligand is chargeable and desorption of the substance from the matrix is performed by a pH switch.

12. A method according to any one of the previous claims, wherein the polarity of the eluent is lower than that of the aqueous liquid from which the substance is removed.

13. A method according to any one of the previous claims, wherein at least one ligand is a mixed mode ligand comprising

(c) a first mode site which gives charge-charge attractive interaction with the substance, and

(d) a second mode site which gives charge-charge attractive interaction and/or hydrophobic interaction and/or electron donor-acceptor interaction with the substance.

14. A method according to any one of the previous claims, which is for removal of a biopolymer structure from a liquid, which structure is selected from the group comprised of carbohydrate structures, peptide structures, peptide nucleic acid (PNA) structures and nucleic acid structures.

15. A method according to any one of the previous claims, which is for removal of a biopolymer the charge of which is pH-dependent.

16. A method according to any one of the previous claims, which is for removal of an amphoteric substance.

17. An adsorbent suitable for use in the method according to any one of claims 1-16, which comprises a first and a second ligand comprising at least one functional group that participates in electron donor-acceptor interaction with the substance to be separated, which functional group is selected from the group comprised of:

(i) donor atoms/groups such as;

oxygen with a free pair of electrons, such as in hydroxy, ethers, nitro, carbonyls, such as carboxy, esters (—

O— and

—

CO—

O—

) and amides,

sulphur with a free electron pair, such as in thioethers (—

S—

),

nitrogen with a free pair of electron, such as in amines, amides including sulphone amides],

halo (fluorine, chlorine, bromine and iodine), and

sp- and sp²-hybridised carbons, or

(iii) acceptor atoms/groups, i.e. electron deficient atoms or groups, such as metal ions, cyano, nitrogen in nitro, hydrogen bound to an electronegative atom as for instance in HO—

(hydroxy, carboxy etc), —

NH—

(amides, amines etc), HS—

(thiol etc) etc.

18. An adsorbent according to claim 17, wherein the ratio between the degrees of substitution for any pair of the sets is within 0.02-50.

19. An adsorbent according to claim 17 or 18, wherein the first and the second ligands have been introduced so that they occur essentially at random in relation to each other, at least in a part of the support matrix.