Disposable monolithic column

• US 20050274662A1
• Filed: 08/10/2005
• Published: 12/15/2005
• Est. Priority Date: 06/26/2002
• Status: Active Grant

• Current Assignee: Dionex Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Teledyne Isco, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Xie, Shaofeng
• Granted Patent: US 7,473,367 B2
• Time in Patent Office: Days
• US Class Current: 210/198.200
• CPC Class Codes: B01D 15/20 relating to the conditioning of the sorbent material
• CPC Class Codes: B01D 15/206 Packing or coating
• CPC Class Codes: B01J 19/0013 Controlling the temperature of the process
• CPC Class Codes: B01J 19/18 Stationary reactors having moving elements inside B01J19/08, B01J19/26 take precedence
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/28042 Shaped bodies; Monolithic structures
• CPC Class Codes: B01J 20/28052 Several layers of identical or different sorbents stacked in a housing, e.g. in a column
• CPC Class Codes: B01J 20/283 based on silica
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 2219/00162 controlling the pressure
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/58 Use in a single column
• CPC Class Codes: B01J 2220/82 Shaped bodies, e.g. monoliths, plugs, tubes, continuous beds
• CPC Class Codes: B01J 39/26 Cation exchangers for chromatographic processes
• CPC Class Codes: B01J 41/20 Anion exchangers for chromatographic processes
• CPC Class Codes: B01J 8/0005 Catalytic processes under superatmospheric pressure non-catalytic processes B01J3/00
• CPC Class Codes: G01N 2030/522 pressure
• CPC Class Codes: G01N 2030/525 surface properties, e.g. porosity
• CPC Class Codes: G01N 2030/528 Monolithic sorbent material
• CPC Class Codes: G01N 2030/567 coating
• CPC Class Codes: G01N 30/30 : of temperature
• CPC Class Codes: G01N 30/52 : Physical parameters
• CPC Class Codes: G01N 30/54 : Temperature
• CPC Class Codes: G01N 30/56 : Packing methods or coating methods
• CPC Class Codes: G01N 30/6091 : Cartridges
• CPC Class Codes: Y10T 29/49604 : Filter

Abstract

Permeable polymeric monolithic materials are prepared in a plastic column casing. In one embodiment, the permeable polymeric monolithic materials are polymerized by the application of heat from an external source starting at a low temperature such as 40 degrees centigrade, depending on the mixture and size of the column, and continuing at a higher temperature, such as 60 degrees centigrade. The temperature at the start of the polymerization is low enough so as not to cause exothermal run-away conditions and to avoid high heat of reaction that would prevent a substantially constant temperature across the cross-section of the column. The higher temperature is used after sufficient monomer depletion has occurred and steric interference has increased so the polymerization reaction is sufficiently slow to avoid heat of reaction generation high enough to cause significant reduction in the homogeneousness of the pore sizes.

Claims

1. A disposable chromatographic column comprising:

a disposable chromatographic plastic column casing having internal column walls;

a permeable monolithic polymeric plug in said column walls;

said permeable monolithic polymeric plug being a polymer having separation-effective openings of a controlled size formed in the polymer by a porogen in a polymerization mixture before polymerization and controlled cross sectional uniformity by temperature-time moderation during polymerization.

2. A disposable chromatographic column according to claim 1 wherein sizes of the separation-effective openings are controlled at least partly by pressure during polymerizations.

3. A disposable chromatographic column in accordance with claim 1 in which the permeable monolithic polymeric plug has smooth walls and is size compensated by pressure.

4. A disposable chromatographic column in accordance with claim 1 wherein there are substantially no pores within the permeable monolithic polymeric plug and the permeable monolithic polymeric plug has smooth walls.

5. A disposable chromatographic column in accordance with claim 1 wherein there are substantially no pores within the permeable monolithic polymeric plug.

6. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is free of channeling openings in the walls of the plug.

7. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is formed principally of methacrylate.

8. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is formed principally of methacrylate with hydrophobic surface groups.

9. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is formed principally of urea formaldehyde.

10. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is formed principally of silica.

11. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is principally formed of polymers of glycidyl methacrylate and of ethylene dimethacrylate in a ratio by weight in the range of from 1 to 1 and 2 to 1.

12. A disposable chromatographic column in accordance with claim 1 wherein the permeable monolithic polymeric plug is principally formed of polymers of glycidyl methacrylate and of ethylene dimethacrylate in a ratio by weight of 3 to 2.

13. A disposable chromatographic column in accordance with claim 1 in which the permeable monolithic polymeric plug includes as its principal component a mixture of divinylbenzene and styrene in a ratio in the range of 3 to 1 and 9 to 1.

14. A disposable chromatographic column in accordance with claim 1 in which the permeable monolithic polymeric plug includes as its principal component a mixture of divinylbenzene and styrene in a ratio in the range of 4 to 1.

15. A disposable chromatographic column in accordance with claim 1 in which the column is in the range of 35 percent and 80 percent by weight divinylbenzene.

16. A disposable chromatographic column in accordance with claim 1 in which the column is 64 percent by weight divinylbenzene.

17. A disposable chromatographic column in accordance with claim 1 in which the column includes a polymeric plug with a temperature measuring device within it.

18. A disposable chromatographic column in accordance with claim 1 having a diameter of over 10 mm.

19. A disposable chromatographic column in accordance with claim 1 in which a volume of pores per square millimeter and mean size of pore openings in the direction of a longitudinal axis of the column per square millimeter does not vary from location to location and does not vary by more than 5 percent.

20. A method of making a disposable chromatographic column comprising the steps of:

putting a polymerization mixture in a plastic column casing;

polymerizing the polymerization mixture in the plastic column casing using a combination of low and high temperature polymerization.

21. A method in accordance with claim 20 in which the step of putting a polymerization mixture in a plastic column casing comprises the step of putting a polymerization mixture in a plastic column casing having a diameter of at least 10 mm.

22. A method of making a disposable chromatographic column comprising the steps of:

putting a polymerization mixture in a plastic column casing wherein the polymerization mixture comprises a functional monomer containing a sulfonic group; and

directly polymerizing the mixture to provide a strong cation exchanger.

23. A method in accordance with claim 22 wherein the step of putting a polymerization mixture in a plastic column casing comprises the steps of hydrolyzing a polymer in the polymerization mixture and modifying a hydroxyl formed in the step of hydrolyzing the polymer with chlorosulfonic acid.

24. A method in accordance with claim 22 wherein the step of putting a polymerization mixture in the plastic column casing comprises the steps of hydrolyzing a polymer in the polymerization mixture and modifying a hydroxyl formed in the step of hydrolyzing the polymer with a pyridine salt solution of chlorosulfonic acid.

25. The method of claim 24 in which the step of putting a polymerization mixture in the plastic column casing includes the step of inserting at least one vinyl monomer, an initiator, and a porogen.

26. A method of making a monolithic disposable chromatographic plastic column comprising the steps of:

adding a polymerization mixture containing a porogen to a closed plastic column casing;

polymerizing the mixture under temperature-time moderation to form a size compensated polymer plug; and

washing the polymer plug to remove the porogen.

27. A method according to claim 26 in which the step of polymerizing the mixture includes the step of polymerizing the mixture under pressure to form a polymer plug, whereby sufficient pressure is applied to prevent voids from being formed caused by vacuum due to shrinkage during polymerization.

28. A method of making a monolithic disposable chromatographic plastic column comprising the steps of:

preparing a polymerization mixture including a porogen within tubular plastic walls with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end;

performing polymerization with temperature-time moderation to form a polymer plug;

washing the polymer plug to remove the porogen, wherein the plug tends to swell; and

applying pressure to prevent swelling of the polymer plug and eliminate voids.

29. A method of making a monolithic disposable weak cation plastic column, comprising steps of:

mixing GMA, MMA, EDMA, an initiator and a porogen to form a polymerization mixture within tubular plastic walls with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end; and

polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug.

30. A method of making a monolithic disposable weak cation column in accordance with claim 29 wherein the step of mixing includes the step of supplying a polymerization mixture comprising 1 part of GMA to between 4 and 6 parts of MMA and 10 and 14 parts of EDMA and an initiator to a plastic column casing with the first plastic end piece formed on the first end and adapted to have the second plastic end piece attached to the second end.

31. A method of making a monolithic disposable weak cation column in accordance with claim 29 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at a low temperature and gradually increasing the temperature to a safe point and curing at a higher temperature wherein temperature run-away is avoided and adequate polymerization and cross linking is obtained.

32. A method of making a monolithic disposable weak cation column in accordance with claim 29 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at a value between 35 and 45°

C. and gradually increasing the temperature to a safe point and curing at a higher temperature.

33. A method of making a monolithic disposable weak cation column in accordance with claim 30 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at and gradually increased to a safe point and curing at a higher temperature.

34. A method in accordance with claim 29 wherein the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug without substantial non-uniform characteristics caused by temperature gradients.

35. A method in accordance with claim 29 wherein the step or polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug with substantial non-uniform characteristics caused by temperature gradients resulting from exotherms.

36. A method of making a disposable weak cation plastic column, comprising steps of:

applying a polymerization mixture comprising 1 part of GMA to between 4 and 6 parts of MMA and 10 and 14 parts of EDMA and an initiator into a plastic column casing with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end;

shaking the mixture gently until the mixture becomes a homogeneous solution;

weighing a porogen into the homogeneous solution and shaking until the new mixture is homogeneous to form a polymerization solution;

degassing;

putting the polymerization solution in the column;

polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug; and

washing the plug to remove the porogen.

37. A method in accordance with claim 36, wherein the column includes means for applying pressure to the polymerization solution further comprising the steps of sealing the column and applying pressure to the polymerization mixture.

38. A method in accordance with claim 36 wherein the polymerizing mixture is polymerized at a gradient temperature starting at a control initiation point at a value between 35 and 45°

C. and gradually increased to a safe point in 12 hours and cured at a temperature of between 55 and 65°

C. for 24 hours.

39. A method in accordance with claim 36 wherein the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug without substantial non-uniform characteristics caused by temperature gradients.

40. A method in accordance with claim 36 wherein the step or polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug with substantial non-uniform characteristics caused by temperature gradients resulting from exotherms.

41. A method of making a disposable strong anion plastic column, comprising steps of:

mixing GMA, ATMS, EDMA, an initiator and a porogen to form a polymerization mixture; and

polymerizing the polymerization solution in a plastic column casing with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end under temperature-time moderation conditions to form a plug.

42. A method of making a disposable strong anion plastic column in accordance with claim 41 wherein the step of mixing includes the step of supplying a polymerization mixture comprising between 2 and 4 parts of GMA to between 2 and 4 parts of ATMS to between 7 and 11 parts of EDMA and an initiator to a plastic column casing with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end.

43. A method in accordance with claim 41 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at a low temperature and gradually increasing the temperature to a safe point and curing at a a higher temperature wherein temperature run-away is avoided and adequate polymerization and cross linking is obtained.

44. A method in accordance with claim 41 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at a value between 35 and 45°

C. and gradually increasing the temperature to a safe point and curing at a higher temperature.

45. A method in accordance with claim 41 wherein the step of polymerizing includes the step of polymerizing at a gradient temperature starting at a control initiation point at and gradually increased to a safe point and curing at a higher temperature.

46. A method in accordance with claim 41 wherein the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug without substantial non-uniform characteristics caused by temperature gradients.

47. A method of making a disposable strong anion plastic column, comprising steps of:

applying a polymerization mixture comprising between 2 and 4 parts of GMA to between 2 and 4 parts of ATMS to between 7 and 11 parts of EDMA and an initiator into a plastic column casing with a first plastic end piece formed on a first end and adapted to have a second plastic end piece attached to a second end;

shaking the mixture gently until the mixture becomes a homogeneous solution;

weighing a porogen into the homogeneous solution and shaking until the new mixture is homogeneous to form a polymerization solution;

degassing;

putting the polymerization solution in the column;

polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug; and

washing the plug to remove the porogen.

48. A method in accordance with claim 47, wherein the column includes means for applying pressure to the polymerization solution further comprising the steps of sealing the column and applying pressure to the polymerization mixture.

49. A method in accordance with claim 47 wherein the polymerizing mixture is polymerized at a gradient temperature starting at a control initiation point at a value between 35 and 45°

C. and increasing gradually to a safe-point at between 55 and 65°

C. in 12 hours and cured at a temperature of between 55 and 65°

C. for 24 hours.

50. A method in accordance with claim 47 wherein the polymerizing mixture is polymerized at a temperature of between 35 and 45°

C. for 72 hours and then cured at a temperature of between 55 and 65°

C. for 24 hours.

51. A method in accordance with claim 47 wherein the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug without substantial non-uniform characteristics caused by temperature gradients.

52. A method in accordance with claim 47 wherein the step or polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug includes the step of polymerizing the polymerization solution in the column under temperature-time moderation conditions to form a plug with substantial non-uniform characteristics caused by temperature gradients resulting from exotherms.

53. A method of forming a disposable plastic chromatographic column comprising the steps of:

putting a polymerization mixture in a plastic column casing with a polymerization mixture comprising a functional monomer containing a sulfonic group; and

directly polymerizing the mixture to provide a strong cation exchanger.

54. A method in accordance with claim 53 wherein the step of putting a polymerization mixture in the plastic column casing comprises the steps of hydrolyzing a polymer in the polymerization mixture and modifying a hydroxyl formed in the step of hydrolyzing the polymer with chlorosulfonic acid.

55. A method in accordance with claim 54 wherein the step of putting a polymerization mixture in the column casing comprises the steps of hydrolyzing a polymer in the polymerization mixture and modifying a hydroxyl formed in the step of hydrolyzing the polymer with a pyridine salt solution of chlorosulfonic acid.